Image source @ vision china

Wen Yi Zheng Lun

In the farming era, agriculture is the foundation of the country. Entering industrial civilization, although agriculture accounts for less and less of the total economic output, it is an important foundation of all industries, and agriculture has a multi-layered relationship with modern economic development.

Taking China as an example, China’s economy, especially after the reform and opening up, has experienced sustained high-speed growth for 40 years. In this process, two topics have become the focus of academic circles and public opinion: one is the sustained growth for 40 years (including the high-speed growth in the first 30 years and the medium-high-speed growth in the second 10 years), which has been praised as the "China miracle" by many scholars and given different explanations from different angles.

The second is the trend of slow growth in recent ten years, which is accompanied by the retreat of late-comer advantage, the disappearance of demographic dividend, the slowdown of urbanization and the anti-globalization trend, which makes many people feel anxious.

If we examine the logic behind China’s economic development from the perspective of agriculture, we may be able to reduce our anxiety in the face of slowing economic growth and get a peek at the opportunities for future economic development.

review

Generally speaking, agriculture has two meanings for economic development: the first is the primary industry in economic growth-agriculture, but the proportion of the added value of primary production in the total GDP will become smaller and smaller with the process of national industrialization; Secondly, from the perspective of development economics, the development of agriculture is the foundation of population growth, labor transfer and urbanization.

(Illustration: The increase of agricultural output can bring about the increase of population, and the increase of population leads to the expansion of economic scale; The improvement of agricultural labor productivity can transfer more labor to modern industry and commerce and provide labor capital for economic development; Population growth, industrial and commercial development, and more people moving from rural areas to cities have brought about the development of urbanization. )

On the macro level as a whole

(Statistics of population, grain output, urbanization rate, GDP and growth rate in China from 1949 to 2019-Source: National Bureau of Statistics)

From 1949 to 2019, the annual output of grain in China increased from 113 million tons to 664 million tons; The added value of the primary industry (agriculture, forestry, animal husbandry and fishery, but excluding agriculture, forestry, animal husbandry and fishery services) ranged from 34.3 billion yuan to 7046.7 billion yuan (1952-2019); The population has increased from 540 million to nearly 1.4 billion; Gross national product (GDP) from 67.9 billion yuan to 99,086.5 billion yuan (1952-2019); The urbanization rate ranges from 10.6% to 60.6%. All this is inseparable from the contribution of basic agriculture.

In this process, we have gone from not having enough to supplying by ticket, to solving the problem of food and clothing poverty, and now we have plenty of food and clothing. Great changes have also taken place in our diet structure, from a diet dominated by staple food to a more balanced and scientific diet of grain, fruits and vegetables, meat, eggs and milk.

People’s health status and education level have been greatly improved. The obvious performance is that the average life expectancy has dropped from less than 35 to 77 now, and the illiteracy rate has dropped from 80% to about 5%. Agricultural development not only pushes up the population base, but also provides a high-quality population for economic development, industrial and commercial development and urbanization.

Today, we are the largest agricultural producer in the world, accounting for 20% of the world’s grain output, 39% of the world’s vegetable and fruit output, and 56% of the world’s pigs. We feed 21% of the world’s population with less than 9% of the earth’s arable land, and the food self-sufficiency rate is 82.3%(2017).

The above is the overall view. Since the founding of the People’s Republic of China, China has experienced several different historical periods. The political and economic systems in each period are not only the same, but also the agricultural and economic development have different structural models and logical relationships. Therefore, we need to look at the relationship between agriculture and economic development in stages.

Look at it in stages

Professor Cai Fang once divided China’s economic development into five stages: Malthusian trap, Ghilt’s involution, Lewis’s dual economic development, Lewis’s turning point and Solow’s neoclassical growth. We divide and simplify it into three stages to explain the relationship between agriculture, population and economic development respectively.

I From Malthusian Trap to Involution (1949-1978)

At the beginning of the founding of the People’s Republic of China, we just got out of the war. We are a poor and backward agricultural country, and more than 500 million people are facing the situation of not having enough to eat and not being warm. The population situation is that the high birth rate is accompanied by the high death rate, showing a slow growth, that is to say, it is in the Malthusian trap.

Malthusian trap was put forward by thomas robert malthus, a British political economist, and named after it. It means that the population growth is in accordance with geometric progression, while the survival resources are only in accordance with arithmetic progression. The extra population will always be eliminated in some way, and the population cannot exceed the corresponding level of agricultural development.

We got out of the Malthusian trap on the one hand from the post-war peace, and on the other hand from the food growth brought by agricultural development. After the founding of the People’s Republic of China, although China experienced political movements such as cooperatives, people’s communes, the Great Leap Forward and the Cultural Revolution, our grain output still increased gradually during this period.

During this period, agricultural development was promoted by both agricultural system and agricultural technology.

From the early days of the founding of the People’s Republic of China to 1952, China basically completed the land reform, more than 300 million farmers regained their land, and agricultural production gradually resumed after the war; Subsequently, agricultural production gradually began the movement from mutual aid groups, cooperatives, primary cooperatives, advanced cooperatives to people’s communes. Although from the perspective of system, the influence of system on agricultural development in different periods is both positive and negative, the progress from agricultural technology has obviously promoted agricultural development. Modern agricultural technologies after the industrial revolution: chemical fertilizers, pesticides, improved varieties, irrigation and mechanization (chemical fertilizer industry and mechanization are mainly after the reform and opening up), which have greatly promoted the development of agriculture.

(Illustration: The grain growth brought by agricultural development increases the environmental carrying rate, and with peaceful development, the mortality rate is greatly reduced and the population is growing rapidly. )

The development of agriculture made us get out of the Malthusian trap, and the population increased. However, due to the influence of planned economy, unified purchase and marketing, people’s commune and household registration policy in this period, the increased population did not shift from agriculture to industry and commerce, nor did more people shift from rural areas to cities. The urbanization rate only increased from 10.6% to 17.9% in 30 years.

A large number of surplus labors stay in the countryside, forming an involution society.

Involution was put forward by Ghilt, an American anthropologist, when studying Indonesian agriculture. It refers to the phenomenon that a social or cultural model stagnates or cannot be transformed into another advanced model after reaching a certain form at a certain stage of development.

Huang Zongzhi used the concept of involution in the study of China’s economic development and social changes in "Small Farmers’ Families and Rural Development in the Yangtze River Delta". He called the growth without development "involution" by investing a lot of labor on limited land to obtain the way of total output growth, that is, the way of diminishing marginal benefits.

A large number of surplus labor stranded in rural areas in the involution stage will become an important resource in the following dual development stage.

II Lewis’s dual economic development stage (1978-2004)

In 1978, China began to reform and open up, and changed from a planned economy to a socialist market economy. Since then, China’s economy has embarked on a long-term high-speed growth channel, with high-speed industrial and commercial development and increasing urbanization rate. In this process, a large number of surplus laborers stranded in rural areas during the involution period were released, and they entered cities and towns from rural areas, and entered industry and commerce from agriculture, which became the main driving force of economic development and formed a dual high-speed development model. This model lasted until around 2004, and entered the next stage of development with the arrival of lewis turning point and the disappearance of the demographic dividend.

Dual Economic Model and lewis turning point;

Dual economic model was put forward by British economist Lewis, which means that developing countries coexist with two different economic systems: traditional agricultural economic system and modern industrial system, which is called dual economic structure.

In the dual economic model, the traditional agricultural sector has a large number of surplus labor with zero marginal productivity, and the surplus labor is continuously transferred from the agricultural sector to the industrial sector.

When the surplus labor force is completely transferred, it is the first turning point of Lewis. After the transfer of surplus labor force, the labor force began to be in short supply. However, because the marginal productivity of the industrial sector is still greater than that of the agricultural sector, it will continue to absorb the labor force of the agricultural sector, but the wage level will continue to increase until the marginal productivity of the two sectors is equal, forming a labor market integrating urban and rural areas. At this time, it is Lewis’ second turning point.

The development of agriculture in this period is reflected in two aspects: system reform and technological progress. The landmark event of China’s reform and opening up was the "all-in-one contract" in Xiaogang village in 1978. The household contract responsibility system began to gradually replace the people’s commune, which improved the incentive mechanism and mobilized the enthusiasm of farmers.

The system reform has brought about the improvement of production efficiency and output. Professor Lin Yifu said that 47% of the increase in agricultural product output comes from the improvement of incentive mechanism by household contract system. In terms of system, it also promoted the development of agriculture by abolishing the state monopoly on purchase and marketing (gradually abolished in the mid-1980s), and land circulation (starting in 2002) further increased the mobility of factors.

In terms of technology, industrialized agricultural technologies such as chemical fertilizers, pesticides, improved varieties and mechanization have further promoted agricultural production and income. In this stage of agricultural industrialization and modernization, agricultural development and industrial development promote each other.

According to the production and use of chemical fertilizers, there were only a few chemical fertilizer plants in China before the reform, and the annual chemical fertilizer output was only a few million tons, and now it has reached 40-50 million tons/year. Pesticide, seed industry and mechanization also developed rapidly during this period.

During this period, the industrial structure of agriculture has also undergone important changes. The proportion of agriculture (planting), animal husbandry (breeding) and fishing has changed from planting-oriented industrial structure to about 6:3:1 structure, and in planting, the proportion of fruits and vegetables is increasing.

These can be perceived from our daily life for decades. Our daily diet structure has changed from the traditional 8: 1: 1 food: vegetables: meat structure to the 4: 3: 3 model of the upper class in the city and the richer areas such as Taiwan Province and Hongkong. This change is the "hidden" agricultural revolution put forward by Professor Huang Zongzhi.

On the whole, the development of agriculture in this period is not only reflected in the nearly two-fold increase of grain output, but more importantly, the change of food structure, and the improvement of population quality (reflected in the average life expectancy and education level) while the population increases. In this case, the total population growth and quality improvement, coupled with a large number of surplus labor stranded in rural areas during the involution period, provided a large number of cheap surplus labor for the economic development of this period.

At the same time, China’s working-age population (15-59 years old) increased before 2010, reaching a peak of 940 million in 2010. These constitute a huge demographic dividend of economic development since the reform and opening up and become the main driving force for rapid economic growth. At this stage, China’s economy continued to grow at a high speed, with an average annual growth rate of 10% from 1978 to 2010. The urbanization rate ranges from 17.9% to 49.9%.

III transition period (2004-)

In 2004, the "labor shortage" first appeared in the Pearl River Delta and the Yangtze River Delta, so some scholars regarded 2004 as the lewis turning point of China. After the first turning point of Lewis, the labor supply structure has changed from unlimited labor supply to limited surplus and then to labor shortage.

The arrival of lewis turning point was accompany by that disappearance of the demographic dividend. The disappearance of demographic dividend is divided into two aspects, on the one hand, the disappearance of surplus agricultural labor force, on the other hand, the change of population structure, that is, the aging is intensified and the dependency ratio is improved.

2010 can be said to be the turning point of demographic changes. In 2010, the working-age population reached its peak, and the dependency ratio was close to the trough. After that, the working-age population experienced negative growth, aging intensified and the dependency ratio increased.

Entering the turning point, the labor cost rises, and the marginal income of investment in economic growth begins to decline. We can see the decline of GDP growth rate in 2004, especially after 2010. At the same time, the growth rate of urbanization has slowed down (as shown in the following figures: 1978-2004, 2004-2010, 2010-).

Slow down, trap or endogenous?

After 2010, China’s economic growth slowed down obviously. The arrival of lewis turning point and the disappearance of demographic dividend are one of the important factors, because the variables related to labor force in economic growth have negative growth, and the marginal income of investment has also declined.

In addition to the labor factor, the factors that often lead to the slowdown of economic growth are: the disappearance of late-comer advantage (the change from catch-up growth to cutting-edge growth), the sluggish domestic demand and unsustainable investment-driven growth, the crisis of middle-income trap, and the environmental constraints on future development caused by environmental damage caused by economic development.

However, at this turning point, there are also good factors to maintain the sustained economic growth. Some scholars believe that China’s reform has stepped out of the unique "China model" and can stimulate innovation, so that knowledge and technology can become the driving force for economic progress and enter the endogenous growth model.

So is the future good or bad? Maybe the answer lies in the land under our feet.

Opportunities from the perspective of agriculture

Agricultural development is welcoming two important changes, one is technical and the other is attribute. These two changes will bring new opportunities for economic development from a new perspective.

Technically, post-industrial agricultural technology is changing the petrochemical agricultural model.

Our modern agriculture, namely, Industrial Agriculture, is an important stage of world agricultural development after traditional agriculture. Petrochemical agriculture is characterized by consuming a lot of petroleum-based energy and raw materials, using a lot of fertilizers and pesticides, large-scale single planting or breeding, and a highly mechanized, automated and large-scale agricultural model.

Undeniably, this model has brought about a double increase in agricultural output in China, but at the cost of environmental pollution and degradation (ecological environment degradation, soil degradation, soil organic matter reduction, water pollution, agricultural greenhouse gas emissions and air pollution, etc.) and the unsustainability of high energy input model.

Agricultural technology in the post-industrial era is changing the unsustainability of petrochemical agriculture and the negative externalities of the environment in many ways.

There is no strict definition of agriculture in the post-industrial era. In terms of modes, such as ecological agriculture, biological agriculture, circular agriculture, organic agriculture, permanence agriculture, natural agriculture, forest agriculture and Regenerative agriculture, these are all attempts in this regard.

Although the early organic agriculture and natural agriculture left the impression of low yield and low efficiency, with the development of microbial technology, molecular biotechnology, ecological technology, information technology, complex systems and other technologies, agriculture in the post-industrial era is constantly improving productivity on the premise of sustainable development.

Take the application of microbial technology in soil improvement as an example: the industrialized agricultural model has caused soil fertility degradation, organic matter reduction, soil microbial degradation and other problems. This not only reduces the yield, but also reduces the soil organic matter, which also means increasing the greenhouse gas emissions. Using microbial technology can efficiently return straw to the field, improve soil organic matter, and restore healthy microbial population in the soil, which not only restores soil fertility, but also increases soil carbon sequestration and reduces greenhouse gas emissions.

In addition to the field of soil improvement, the development of microbial technology in anaerobic/aerobic fermentation has also greatly improved the efficiency of agricultural and domestic organic waste recycling, turning the garbage in industrial thinking into energy and fertilizer for agriculture in the post-industrial era.

There are biotechnology, such as biological nitrogen fixation; Ecological technology, such as making more use of biological natural enemies for pest management, treating weeds not with herbicides but with comprehensive management (even utilization); At the same time, modern information technology and artificial intelligence technology can more accurately fertilize and use drugs and reduce the waste of unsustainable resources.

On the whole, agricultural technology in the post-industrial era is constantly improving productivity on the premise of sustainable development.

Attribute: agriculture has changed from a single production attribute to a multi-functional attribute.

As an industry with the closest connection between man and nature, agriculture should have multiple functions, but it was only regarded as the production of agricultural products and means of production (pure production function) during the industrialization period. Agriculture should have social, economic and environmental functions besides production functions.

As early as the 1980s and 1990s, Japan and Europe began to actively promote MFA- Multifunctional Agriculture. UNEP The United Nations Environment Programme (UNEP) described multifunctional agriculture in its "Agriculture at the Crossroads: A Comprehensive Report" in 2009:

(Illustration: Multifunctional Agriculture Multifunctional Agriculture, IAASTD, UNEP)

Social function of agriculture: agriculture provides a healthy environment and food for the whole society, agriculture and rural areas are also the inheritance of social traditions and culture, and agriculture also plays the role of employment buffer and social stability.

The economic function of agriculture: the commercialization of crop output and its processed products, the primary and secondary production of agriculture, and the positive externalities created by agriculture can empower the economy.

The environmental functions of agriculture: soil, water, climate and biodiversity, which are not only the foundation of agriculture, but also the environment on which our human society depends. Agriculture can destroy the environment, and agriculture can also repair it.

China is a country with a large population. In the early days of the founding of the People’s Republic of China and the period of rapid economic development, the issue of grain output and food security has always been the primary issue of agricultural development. However, with the 12-year continuous increase of grain from 2003 to 2015, the self-sufficiency rate of grain reached 80-90%, and the output was no longer the main goal of agricultural development. We gradually began to pay attention to the social, economic and environmental functions of agriculture, and this trend can also be clearly seen from China’s agricultural policies and rural revitalization strategies in recent years.

The transformation of agricultural technology and attributes brings new opportunities for economic development.

Let’s go back to the economic growth function:

Economic growth function: Y=F(A,K,L),

Y stands for total output, which can be understood as GDP；; A stands for innovation, K stands for capital investment, and L stands for human capital. That is to say, economic growth is a function of innovation, capital and labor.

In the period of dual development, agriculture continuously provides human capital (L) for the development of industrial sectors, but after the Lewis turning point, at our present stage, agriculture will promote economic development by promoting social innovation (A) and form an endogenous growth model driven by technological innovation.

How does agriculture promote innovation? Focus on the environmental function of agriculture.

Sustainable agriculture combined with rational planning, rural areas (including suburbs and towns) have healthy soil, high-quality water, biodiversity and beautiful natural landscape.

The first is industries based on beautiful environment, such as rural tourism, pension, health care, natural education and other industries. Beautiful environment is not only the core assets of these industries, but also provides new competitive advantages and stimulates industry innovation.

Secondly, a good environment will attract those enterprises suitable for telecommuting to settle in villages (or towns). Compared with big cities, rural areas have better natural environment, lower living costs, slower pace of life and cheap and fresh ingredients, which makes some R&D departments such as IT enterprises or high-tech enterprises begin to consider or are moving enterprises/departments out of big cities and into villages/towns.

In fact, the headquarters of many high-tech enterprises in Europe and America are located in some humble towns. There is a famous rural Silicon Valley in Japan, which is located in the once-depressed village-Kamiyama-CHO. Now, many places in China have begun to take advantage of the rural environment to develop innovative industries, as well as rural Silicon Valley. This approach not only reduces the costs of enterprises and employees in many aspects, but also brings employees a healthier life. At the same time, a beautiful environment can stimulate the creativity of enterprises and individuals and inject innovative vitality into the whole economic development.

The so-called "Lucid waters and lush mountains are invaluable assets", a good environment is not only an asset in itself, but also can empower more industries and society, stimulate innovation, and form an endogenous growth model driven by innovation.

summary

In the early days of the founding of the People’s Republic of China, the progress of agriculture enabled us to get out of the Malthusian trap and the population doubled. However, due to the social system, a large number of people were stranded in the countryside and then involved.

With the reform and opening up and the activation of the system, a large number of surplus labor in agriculture has become a huge demographic dividend in the dual development model, achieving rapid growth for 30 years; When traveling to lewis turning point, the demographic dividend disappeared, and at the same time, with the retreat of late-comer advantage and environmental degradation, the growth slowed down;

The transformation of technology and attributes of agriculture brings new opportunities to China’s economy in the transition period. Sustainable agricultural technology can repair the environment. On the one hand, the environmental function of agriculture promotes economic growth with environmental capital, on the other hand, it stimulates innovation with environmental empowerment, thus forming an endogenous growth model driven by innovation.

References:

1. The most important thing for Cai Fang and China is to find new sources of growth.

2. Huang Zongzhi, "China’s hidden agricultural revolution"

3. ronald harry coase/Wang Ning, Transforming China: The Road to China in Market Economy.

4. the Central Committee of the Communist Party of China and the State Council, Rural Revitalization Strategic Plan (2018-2022).

5. Liang Jianzhang: Enlightenment of Paul Romer’s Nobel Prize in Economics to China.

6.World Bank and the United Nations Food and Agricultural Organization，《Agriculture at a Crossroads- International Assessment of Agricultural Knowledge,Science and Technology for Development》

[Introduction of titanium media author: Zheng Lun, founder of AgriReview of field observation, please send an email to 19222038@qq.com if you contact the author. 】

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Inquiry method of online banking transaction limit of bank card

In today’s digital financial era, online banking has become an indispensable part of our daily life. However, it is very important to know the online banking transaction limit of bank cards to ensure the safety of funds and smooth transactions. The following will introduce several common methods for you to inquire about the online banking transaction limit of bank cards in detail.

First of all, it is the most direct and convenient way to inquire through the official website of the bank. You just need to open the official website of the bank and log in to your online banking account. Usually, you can find specific information about the transaction limit in the relevant menus such as personal settings, security settings or transaction settings. The website layout of different banks may be different, but there are generally clear guidelines to help you find relevant content.

Secondly, you can also call the customer service phone of the bank to make an inquiry. Customer service staff will accurately inform you of the online banking transaction limit of the bank card according to the identity information and bank card information provided by you. When making a call, please prepare the relevant certificate information so that the customer service staff can verify your identity.

In addition, some banks’ mobile banking applications also provide the function of querying transaction limits. After you log in to your account in mobile banking, you can usually get detailed limit information by searching in the options related to settings or transactions.

In order to give you a clearer understanding of the trading limits of different banks, here are some online banking trading limits of some common banks (the data are for reference only, subject to the latest regulations of each bank):

| Bank Name|| Transfer Limit| Payment Limit|
|—-|—-|—-|
| Bank of China | 500,000 yuan in a single transaction, with a daily accumulative total of 1 million yuan | Depending on different payment scenarios |
| Industrial and Commercial Bank of China | 500,000 yuan in a single transaction, with a daily cumulative amount of 2.5 million yuan | depending on different payment scenarios |
| Construction Bank | 500,000 yuan for a single transaction, and 5 million yuan for a day | Depending on different payment scenarios |

It should be noted that the bank’s online banking transaction limit may change due to many factors, such as your account type, security authentication method, bank policy adjustment, etc. Therefore, it is recommended that you regularly check the latest transaction limit information to ensure that your online banking transactions can proceed smoothly.

In a word, there are many ways to query the online banking transaction limit of bank cards, so you can choose the most convenient and quick way according to your actual situation. Knowing the trading limit in time can help you plan the use of funds better and avoid unnecessary troubles in the trading process.

[Disclaimer] This article only represents the author’s own views and has nothing to do with Hexun. Hexun.com is neutral about the statements and opinions in this article, and does not provide any express or implied guarantee for the accuracy, reliability or completeness of the contents. Readers are requested for reference only, and please take full responsibility. Email: news_center@staff.hexun.com.

　　BEIJING, June 15 (Xinhua) According to South Korea’s "East Asia Daily" report, the investigation on the shipwreck of the South Korean "Shiyue" passenger ship is still in progress. 14th, responsible for investigating "‘ The special inspection team of Shiyue, who was puzzled by the falsification of evidence at the time of the tragedy, seized and searched the server of the comprehensive digital evidence management system of the Grand Prosecutor’s Office, which kept CCTV image data on the day of the tragedy.

　　According to reports, on the same day, Li Xianzhu’s special inspection team dispatched investigators to the Grand Prosecutor’s Office in Seocho District, Seoul, and mastered the investigation teams related to the "Shiyue" incident such as Gwangju District Prosecutor’s Office and Seoul Central District Prosecutor’s Office in 2014. Closed-circuit television images and investigation records collected inside and outside the ship at that time.

　　The special inspection team published a report on the same day, saying: "More than 800 records and 40TB electronic intelligence materials have been obtained from the Special Investigation Committee on Social Tragedy (referred to as the Social Tragedy Committee), and more than 30 boxes of documents and 100TB video have been ensured through the seizure and search of the navy and the marine police, which are being analyzed."

　　According to the report, the special inspection team also investigated the suspicion that the CCTV image data was forged on the day of the sinking of the Shiyue and the video recording device (DVR) that stored the data was replaced before being submitted to the prosecution.

　　The special inspection team has entrusted the National Institute of Scientific Investigation to identify four materials, such as the original DVR hard disk, recovery data, video containing DVR recovery scenes, and video inside the hull of Shiyue. According to the special inspection, 11 people, including the relevant persons of the Social Welfare Committee, have been summoned as witnesses for investigation.

　　The report pointed out that the special inspection team must end the investigation before July 11, and then decide whether to prosecute. If necessary, the special inspection can be approved by the President to extend the investigation period by 30 days.

　　According to previous reports, on April 16, 2014, the "Shiyue" passenger ship carrying 476 people accidentally entered the water and sank in the waters north of Pingfeng Island, Jindo County, Jeollanam-do, South Korea, and the 300-year-old was killed or missing. After the tragedy, the South Korean government promised to rectify and set April 16th as "National Security Day" every year.

　　At the same time, since the "crony intervention" incident broke out, there have been allegations that former South Korean President park geun-hye left his post without directing rescue within seven hours after the shipwreck, and the former chief secretary of Cheongwadae’s civil affairs intervened in the prosecution’s investigation of the "Shiyue" shipwreck and obstructed the search, which cast more shadows on this tragedy. Poor response after the accident was also written in the impeachment bill against park geun-hye.

1905 movie network news　As of press time, the cumulative box office of comedy movies has exceeded 300 million yuan, occupying the champion of single-day box office and film scheduling list for 7 consecutive days, leading the Lunar New Year file.

Today (December 19th), the film exposed the feature footage of "artificial face changing", the special effects of Peng Yuchang’s powerful acting performance, and Qiao Shan’s routine full of jokes, which aroused the enthusiasm of the audience to "brush again". The film Bath Buddy is directed by Xiaoxing Yi, starring Peng Yuchang and Qiao Shan, starring Guanjin Bu and Wei Qing, and starring Jin Shijia in friendship. The film is being shown.

Bath Buddy box office broke the 300 million yuan mark.

Peng Yuchang’s "artificial face change" made the audience laugh.　

Qiao Shan’s "Bathhouse Brothers"

In the "Artificial Face Change" released this time, Zhou Donghai played by Qiao Shan continued to be his younger brother for "Routine" Peng Yuchang, and came up with a video of Xiao Xiang and the family life in the bathhouse by artificial face change. From Guanjin Bu’s large-scale double-bidding scene of Xixi’s "little brother" Xiao Xiang and his brother Zhou Donghai, to Xiao Xiang’s "face-changing" video with consistent body movements and situations, and Zhou Donghai’s "caring for Han Han’s younger brother" eyes, many viewers were deeply impressed and felt "laughing" in succession.

Peng Yuchang watched the face-changing video and was routine by Qiao Shan.

Unexpectedly, the video of Xiao Xiang’s face changing on Xixi’s birthday was not made with special effects, but was performed by Peng Yuchang himself. "When watching the feature film, I thought it was late P, and the whole theater was full of laughter." Peng Yuchang was praised as "hand-changing face", which surprised the audience. Some viewers even entered the magnifying glass viewing mode when they brushed two times and three times, and carefully observed the details of "changing face", which showed the ingenuity and intention of the film’s master.

Peng Yuchang, Qiao Shan, Guanjin Bu and Wei Qing have a happy family.

Bathhouse family warms, heals and transmits strength.　

Bath Buddy Huo Tap Water Crazy Amway

Bath Buddy, a comedy film, tells the laughing story that Xiao Xiang, played by Peng Yuchang, changed from a playboy to a bathing worker after his accidental amnesia, and under the guidance of Zhou Donghai, played by Qiao Shan, practiced his bathing skills hard, hoping to become a generation of "king of bathing". The clip of "Artificial Face Changing" released today is not only another successful case of Zhou Donghai’s "routine" Zhou Jixiang, but also presents the warm picture of the bathhouse family living together in a comedy way. And Zhou Donghai’s video for "Routine" brother is exactly what Zhou Jixiang expects from his family.

Bath Buddy stills

Under the cloak of comedy, movies are the emotional core that makes people feel warm, and the movie-watching experience of "being happy, warm-hearted, and laughing at ease" has gained many audiences’ "tap water" Amway. Hand-painted bathhouse brothers’ Q version image, in-depth interpretation of the details of movie eggs, and bathing enterprises’ group viewing … … The audience’s fancy ways of calling are endless, which helps topics such as "The King of Bath’s box office broke 100 million yuan", "The King of Bath’s box office broke 200 million yuan" and "The King of Bath’s feature film fragment" to get the scores of call’s Eye 8.8 and Taobao Film 8.7, leading the New Year’s Eve file, and setting off an upsurge of punching in the "Brothers Bathroom" this winter.

Bath Buddy stills

The film Bath Buddy is directed by Xiaoxing Yi, starring Peng Yuchang and Qiao Shan, starring Guanjin Bu and Wei Qing, and starring Jin Shijia. The film is being shown all over the country, washing away troubles and welcoming the new year happily.

1905 movie network On the evening of August 28th, the studio issued a document saying that it noticed that a large number of users spread videos, video screenshots and chat records containing insulting and defamatory remarks by using AI face-changing technology through online channels. When the content was maliciously spread in January this year, the studio made clarification and statement, but the rumor still caused a wider spread. In order to safeguard the legitimate rights and interests of Haoran Liu, the studio reported the case to the police today.

It is reported that AI’s face changing technology is increasingly developed, and many stars have suffered greatly. Haoran Liu is just one of them. In recent years, Haoran Liu has been deeply troubled, and some fans have followed suit. The time to find rumors was in 2019, and the source was the external network. Some bloggers used artificial intelligence to change Haoran Liu’s face, and then netizens spread it to major websites, and then rendered the text, and all kinds of gossip followed. In 2020, the picture of Haoran Liu’s face changing spread to domestic forums. At that time, it was recognized as a face changing, but it was still spreading.

Haoran Liu studio statement:

Recently, my studio noticed that a large number of users spread videos, video screenshots and chat records containing insulting and defamatory remarks by using AI face-changing technology through online channels. When the above content was maliciously spread in January, 2021, my studio made a clarification and statement, reminding and advocating the vast number of network users to treat network information rationally, and not to spread rumors or rumors. However, this rumor still caused a wider spread and caused extremely bad influence when some netizens with ulterior motives kept selling videos and screenshots. As the above content is mainly spread through WeChat, QQ and group chat channels in the form of screenshots and forwarding, there are objectively difficulties and obstacles in obtaining the user information involved in the relevant chat records. In order to safeguard the legitimate rights and interests of Mr. Haoran Liu, our studio has reported the case to the police today.　

　　Today, the problem of bacterial drug resistance has launched a major challenge to the global public health field.

　　Every year, 700,000 people worldwide die from drug-resistant infections, and 230,000 newborns die. Studies have shown that bacterial drug resistance mainly comes from the abuse of antibiotics, including both human treatment abuse and excessive use of animals.

　　Antibiotics are "double-edged swords"

　　Antibiotics are a kind of secondary metabolites produced by microorganisms (including bacteria, fungi and actinomycetes) or higher animals and plants in the course of life, which have anti-pathogen or other activities and can interfere with the development function of other biological cells. At present, the commonly used antibiotics in clinic are genetically engineered bacteria, extracts from culture medium and compounds synthesized or semi-synthesized by chemical methods. If used reasonably, antibiotics are the bane of bacteria. If abused, bacteria will "immunize" it and become super bacteria, resulting in the final incurable infected person.

　　Superbacteria are bacteria that can’t be killed by using all antibiotics. This kind of bacteria can show resistance to almost all kinds of antibacterial drugs, even to powerful antibiotics such as carbapenem antibiotics and vancomycin, and some of them also show multiple resistance. Because patients are often unable to produce anti-bacterial antibodies from their own bodies after infection, the mortality rate is greatly increased.

　　Powerful antibiotics are usually regarded as the last line of defense against superbugs. Why is it so vulnerable? This will start with our daily medication habits. Generally speaking, we don’t have to use antibiotics in the face of common germs, but patients often ask doctors to cure them as soon as possible, so doctors will habitually use antibiotics in the face of minor illnesses. However, after taking the medicine, patients usually don’t use up all the drugs in a series of courses, and they will stop taking the medicine when their condition improves slightly, which is the main reason for the drug resistance of bacteria. In addition, excessive use of antibiotics in poultry and livestock feed is also a major cause of the outbreak of superbugs. At present, 80% of antibiotics in the world will flow into animal feed, and superbugs will be excreted with animal excrement, and these bacteria have evolved enough drug resistance in animal gallbladder before being excreted.

　　For example, a salmonella that can hardly be subdued by antibiotics can easily spread between people and animals. At present, we can only passively defend against this superbug, but we can’t actively attack it. The main source of this superbug is almost all the intestines, and we are all likely to come into contact with these bacteria that were originally parasitic in the intestines. The World Health Organization admits that it is a very difficult clinical problem that Enterobacteriaceae is resistant to many commonly used and widely effective antibiotics.

　　The influence affects all walks of life. In fact, bacterial drug resistance is not a problem that only exists in the health field. Statistics show that between 2000 and 2014, the standard dose of antibiotics used worldwide has increased by 50%. A research report published by the World Bank on September 19th, 2016 shows that by 2050, the medical expenses of drug-resistant infections will account for 1.1% ~ 3.8% of the world GDP. According to the current development trend, by 2050, the problem of bacterial drug resistance will kill 10 million people every year, and superbugs will also lead to global economic losses of $6.1 trillion. At the same time, problems such as labor shortage, rising medical costs and shrinking market will follow. At that time, the world economy may face a more serious blow than the 2008 financial crisis, especially for developing countries. By 2050, it is expected that the GDP of these countries will decrease by 5% as a whole.

　　According to the research results of the European Bureau for Disease Control, the development speed of modern medicine is nothing compared with the speed of preventing bacterial drug resistance and bacterial variation. The resistance of human body to antibiotics is increasing, and the tools that human beings can use to deal with drug-resistant bacteria are almost used up. If market forces are allowed to allocate resources by themselves, it is impossible to complete the research and development of a new generation of antibiotics on time, and the candidates for research and development of antibiotics will be basically exhausted.

　　The deadliest superbug.

　　On February 27th, 2017, based on the clinical drug resistance, the mortality caused by drug resistance, the frequency of people’s infections and the burden of these infections on the health care system, the World Health Organization released the list of 12 superbugs with the highest priority for the first time. They are Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacteriaceae, Enterococcus faecalis, Staphylococcus, Helicobacter pylori, Campylobacter, Salmonella, Neisseria gonorrhoeae, and Campylobacter. The researchers classified them into three categories according to their degree of danger: emergency, high priority and medium priority.

　　At present, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacteriaceae have been listed in the emergency level. These highly pathogenic bacteria will not only cause drug-resistant infections, but also bring a heavy burden to the existing medical system and take the lives of patients. Among them, Acinetobacter baumannii is resistant to carbapenem antibiotics, which is easy to cause serious infections in hospitalized patients, such as pneumonia, wound or blood infection. Pseudomonas aeruginosa is resistant to carbapenem antibiotics, which can easily lead to rash and ear infection in healthy people, and also lead to serious blood infection and pneumonia in hospitalized patients. Enterobacteriaceae bacteria inhabit human intestines and are resistant not only to carbapenems but also to cephalosporins. In 2014, among the samples of Escherichia coli (a common intestinal bacteria) collected by the World Health Organization, penicillin was ineffective in 60% of the samples, and about 25% of the samples were resistant to one or two other commonly used antibiotics.

　　Enterococcus faecalis, Staphylococcus, Helicobacter pylori, Campylobacter, Salmonella and Neisseria gonorrhoeae are classified into high priority categories, and their main feature is that they are easy to cause infection in healthy people. At present, there is no particularly effective method to combat this kind of infection. The remaining Streptococcus pneumoniae, Haemophilus influenzae and Shigella are given medium priority. The resistance of these three pathogens to existing antibiotics is still increasing, among which Streptococcus pneumoniae, which is insensitive to penicillin, is easy to cause pneumonia, ear sinus infection, meningitis and blood infection.

　　"Drug-resistant bacterial infections are posing a serious threat to our health care system today," said the head of the drug-resistant infection division of Wellcome Trust, a British medical charity. "The list of superbugs made this time is very important to guide the research and development of antibiotics against drug-resistant bacterial infections. If new antibiotics are not developed, 10 million people will die every year because of drug-resistant bacteria infection. In addition, if we fail to develop new drugs against deadly infections, then some treatments and means that could have saved lives, such as chemotherapy and organ transplantation, may also induce death. "

　　Superbacteria ravage many countries.

　　Recently, the European Bureau for Disease Control issued a warning against the current situation of bacterial drug resistance: a superbug is sweeping across Europe. In a physical examination report on animals and food published by the European Union, the name of bactericidal antibiotic clarithromycin appeared for the first time, which is almost the last line of defense antibiotic for those infected by super bacteria. Inspectors can find traces of them in animals and food, indicating that some people have easily used such drugs for some reasons.

　　The report also pointed out that in the pork tested in Europe this time, the staff have found a very small number of drug-resistant Escherichia coli. If these Escherichia coli or Salmonella are transmitted to humans by pigs or cattle, then we will not have any effective antibiotics to deal with them. The report also shows that people in northern and western European countries are generally less resistant to bacteria than those in southern and eastern Europe, which is probably caused by the abuse of antibiotics.

　　At present, Russia is being invaded by superbugs. Scientists have found three kinds of bacteria on the list of superbugs of the World Health Organization in 15 big cities, including Moscow and St. Petersburg. "Three kinds of superbugs were first discovered in the laboratory of St. Petersburg Institute of Children’s Clinical Infectious Diseases," pointed out Yuri Robzin, an academician of the Russian Academy of Sciences. "They can cause abscess, meningitis and septicemia. If we don’t take action now, in the next 10 to 15 years, human beings may die from the humble acne suppuration. "

　　On May 26, 2016, US health officials reported that the first case of bacterial infection resistant to all known antibiotics had been discovered in the United States. The patient was a 49-year-old woman from Pennsylvania. At that time, she went to the clinic because of urinary tract infection, and the doctor used colistin, an antibiotic specially used to fight "nightmare bacteria", but the condition was not controlled. The journal of American Society for Microbiology, Antimicrobial Agents and Chemotherapy, published a report on this infection case. The report said that this superbug itself was first infected by a small DNA molecule called Plasmid, and the plasmid carried the mcr-1 gene that was resistant to colistin. "This shows that there are truly pan-drug-resistant bacteria," warned Tom Freeden, director of the Centers for Disease Control and Prevention (CDC). "This is the first case of mcr-1 reported in the United States. We face the risk of being in the post-antibiotic world. If this super bacteria is allowed to spread freely, it may’ devour’ everyone in the future. "

　　Real countermeasures

　　However, some medical experts have pointed out that the term "superbugs" has actually existed for many years, and some superbugs have even become very common. But in our environment, superbugs are still a minority after all, so you don’t have to panic too much.

　　Facing the challenge of superbugs, we should change our thinking: instead of investing more powerful antibiotics to "exercise" them, we should let them return to the ecological competition of the original colonies. Among bacterial colonies, if there is no selective pressure of antibiotics, it will not optimize the "particularly powerful role."

　　In addition, we should strictly abide by the guidelines for the use of antibiotics in clinic: try not to use antibiotics for patients with bacteria who have no signs of infection. In fact, without the intervention of antibiotics, drug-resistant bacteria are more likely to be replaced by wild drug-resistant bacteria and then disappear from the human body. Abuse of antibiotics will only "strengthen" the strength of drug-resistant superbugs while killing other bacteria. Therefore, adhering to good hygiene habits and striving to improve physical fitness are the truly effective ways to avoid bacterial infection and combat superbugs. Although the iterative update of antibiotics can control the temporary disease invasion, it also gives birth to more powerful drug-resistant bacteria. I would like to ask, in the long run, when is the head?

　　CCTV News:According to the news released by the Sri Lankan police on April 22, the death toll caused by the explosion attacks in Sri Lanka on April 21 has risen to 290, and another 500 people have been injured. The Sri Lankan security department has arrested 24 suspects involved in the explosion. The Sri Lankan government said that most of these explosions were suicide attacks. After the attack, Sri Lankan President Sirisena issued a statement calling on the people to remain calm and cooperate with the official investigation. Sri Lankan Defense Minister Ruwan Wijewardene said that the attack that day was a "terrorist attack". Colombo reported another suspected explosion on April 22, and the ninth explosion detonated explosives for the police.

　　On the afternoon of April 22nd, the Sri Lankan Cabinet held a press conference on the serial bombing attack in Sri Lanka on the 21st. A spokesman for the Sri Lankan cabinet confirmed at the press conference that the Sri Lankan security department had intercepted relevant information about 10 days before the explosion. The intelligence showed that extremist organizations might launch suicide attacks on many targets in Sri Lanka, including hotels, scenic spots and churches. The Sri Lankan government apologized for failing to take timely measures to avoid this tragedy.

　　Li Wei, an expert on counter-terrorism: In counter-terrorism work, counter-terrorism intelligence is the most important link to prevent terrorist attacks, and it is actually the most difficult aspect to obtain intelligence. Sri Lanka actually had some relevant information ten days before this serial explosion, and we also made some analysis on this information. Personally, I think, as a relatively complete intelligence chain, it lacks unknown factors. This terrorist attack may involve too many areas, and I don’t know which buildings, sensitive buildings or dignitaries or politicians to protect, which puts forward great difficulties. What is it lacking most? Who could carry out such a terrorist attack? Without this, it will be very difficult to prevent, so such a terrorist attack also presents a situation that cannot be prevented.

　　Secondly, this serial bombing attack in Sri Lanka presents one of the biggest characteristics. In the past, it was a decades-long civil war between the LTTE and the Sri Lankan government, including some sporadic violent attacks since then. Its target and the way of committing crimes are very different from this serial bombing. Therefore, it is classified as Sri Lanka. This terrorist bombing is the internationalization of local terrorist attacks. Why is it international? Because of the targets it targets, the targets it attacks, and the way it commits crimes, it can be seen in some hot spots of terrorist activities outside Sri Lanka. A church in Egypt was attacked by terrorists, and so was a church in Surabaya, Indonesia. Attacks on five-star hotels, including Marriott in Pakistan, Marriott in Indonesia, Lisen Hotel in Mali and these high-end hotels in Somalia, are consistent with the extreme ideology advocated by international terrorist forces and the goal of hate conflicts they want to create, which is its most prominent feature.

　　The second feature, just now we heard at the press conference that NTG, an extremist organization in Sri Lanka, was behind this crime. It is certain that NTG is involved, but we should also see that another factor of the internationalization of this terrorist attack should be influenced by extremist organizations in the Middle East. Seeing some suicide bombings, this technique can be seen from outside Sri Lanka. In the process of searching the houses of these people who carried out terrorist attacks and bombings, some propaganda materials and some demagogues associated with extremist organizations in the Middle East were also found. Therefore, from this point of view, the serial terrorist attacks and bombings in Sri Lanka are definitely not only the work of local extremist organizations, but also closely related to extremist organizations abroad, especially in the Middle East. This also reflects that international counter-terrorism, especially the counter-terrorism of a country, is difficult to rely solely on the counter-terrorism of a single country. International counter-terrorism must be United, including opposing local terrorism and international terrorism, so as to curb the threat and harm posed by terrorism to human society from a larger aspect.

Author | Li Beichen

Source | Whale Fall Business Review

As we all know, today’s Chinese music scene is called "Shaking".

At the end of last year, Tencent Music made the top ten hot songs of the year, namely: Cloud and the Sea, Bai Yueguang and Zhu Shazhi, Gossip of the Prodigal Son, Dream that Can’t Wake Up, Treading on the Mountains and Rivers, Qian Qian Never Will Fall, Shepherd of Coco Tuohai, Emptying, and Obsession.

Almost all of them are Tik Tok Divine Comedy.

Yes, the most popular part of Chinese music has become the accompaniment of Tik Tok.

In the face of traffic, QQ Music and Netease Cloud Music also chose to bow their heads, with a special list of popular songs in Tik Tok, and QQ Music regarded "Tik Tok Hot Search" as a recommended option for searching songs.

Whether you like it or not, the subversion and controversy brought by Tik Tok to China’s music industry have become increasingly apparent. Those Tik Tok Divine Comedy haunts your mind, which has made the music market in China undergo an unpredictable evolution.

Obviously, Byte himself realized this, and then suddenly realized: "Why should I give up my own traffic?"

So they left the stage and entered the music market in person, which may completely change the appearance of the music market-and even the whole "music".

Traffic coordination in ByteDance

From the moment of its birth, Tik Tok has a close relationship with music-Tik Tok has a "sound" in his name, and the icon is also a note.

Looking back, Tik Tok’s predecessor, A.me, positioned itself as "short music video", which was quite similar to musical.ly, which was popular among American teenagers at that time, and created short videos by guiding users to lip-synch with music or dance. By the end of 2017, musical.ly had more than 200 million registered users.

Also in 2017, musical.ly was acquired by ByteDance, and then merged into the overseas version of TikTok in TikTok, which brought many active users and creators to TikTok and laid a good foundation for its rapid expansion in the global market.

ByteDance’s "formal" entry into the music market began two years ago.

In March, 2020, Byte officially launched the music playing software Resso in India and Indonesia. You can understand it as "Tik Tok in Music". Once the App is opened, it will be personalized song recommendation. If you don’t like this song, you can swipe the screen up and down like a Tik Tok and quickly cut to the next one.

Resso has been online for half a year, and the download volume has exceeded 15 million times. With this experience, in 2021, a music division was established within Byte, and a key task was to open up the music community of Resso and TikTok.

However, due to various reasons, Resoo has not expanded its territory to more countries and regions. At present, only a few countries such as India, Indonesia and Brazil are open.

In terms of music, perhaps the next force point of Byte is the domestic market.

In the spring of 2022, ByteDance launched an online music app-soda music in China.

The interface of soda music is very similar to Resso, which also uses sliding up and down to cut songs. Compared with the familiar left and right key switching, sliding up and down can greatly improve the speed of cutting songs. Under this interactive logic, people are not so much listening to songs as "brushing songs".

More importantly, according to media reports, most of the data of soda music and Tik Tok are synchronized. Soda music can help people to collect the divine comedy heard in Tik Tok synchronously, and find more similar songs in ByteDance’s proud algorithm recommendation.

Byte’s intention to engage in music is obvious, that is, to cooperate with the flow of Tik Tok and soda music.—— It is foreseeable that the soda concert will be more deeply bound with Tik Tok to form a closed loop of flow: Tik Tok can hatch the Tik Tok Divine Comedy and guide it to soda music; Those minority songs in soda music can also be hatched into "soda divine comedy" with the help of recommendation algorithm, which can be used to feed back short video with vibrato and become Tik Tok divine comedy, thus further consolidating Tik Tok’s position in the field of short video.

It does look wonderful.

In the future, music will eventually become shorter.

As for the penetration of bytes into the music field, what it means to the music market in China is a matter of opinion.

Please note that this article has no intention to talk about the vulgarization tendency of Chinese music. After all, there is no need to argue about the reality. The whole Chinese music presents a dangerous prosperity that will collapse once the coarse gravel foundation is removed. Huang Shujun has a song called "Change 1995", and there is a lyric that won my heart: "Only pop, no music, I think it is a good thing that you are out of sight."

So today, we are out of sight, avoiding "music quality" and talking about "music length".

Have you ever thought about it,When music can be "brushed", people will inevitably leave less and less time for a song, and they will become more and more stingy, so that they will never give you "time for a song" again.

Yes, now is not the era of "slow in the past". In the past, everyone was sincere: a song is a song; Movies, one is another. This is not the case now. People’s interest cycle is getting shorter and shorter, and the content carrier is also getting shorter and shorter, so that they can be embedded in people’s increasingly fragmented nothingness life at any time.

Therefore, just as people have become more and more impatient to watch the whole movie and are used to watching the short video of "watching a movie in X minutes", people have become more and more impatient to listen to the whole song and are used to going straight to the climax and only listening to the chorus (especially for new songs).

I even think,One day in the future, the online music platform will be completely "chorus", that is, every song that people brush will only have a climax.

If this is the case, then this new technology carrier will change the music-the time of a song is bound to become shorter, and the "memory points" such as melody and rhythm are bound to become more accurate-as much as the music was changed when vinyl was born.

You know, nowadays, a song usually lasts only a few minutes, thanks to vinyl. At first, there was no time limit for church music and court music (Beethoven’s Ninth Symphony lasted about 70 minutes), but as music can be stored, copied and distributed by new technology, a piece of music is also "framed" in the poor capacity of 4 minutes when vinyl was born. Musicians can choose not to compromise on technology, but as long as you want to seize the dividend of new technology, you must make the work shorter and make the melody and rhythm more accurate to meet the increasingly impatient attention of the audience.

Well, whether you like it or not, this process is repeating itself. The emergence of new technical media such as bytes makes human attention shorter than before, which also makes the time of a song shorter than before.

Maybe a hundred years later, the new generation of young people will look back at Jay Chou in the 21st century, just as we look back at Beethoven in the 18th century-"It’s just a song, why did you write it so long?"

Author: Li Beichen (WeChat: Whale Fall Business Review)

?　　Foreword　　

In 1993, Belgian scientists discovered a new antibody-nano-antibody (VHHs) in camel serum, which is different from the traditional antibody structure and only consists of heavy chain variable regions. Compared with traditional antibodies, nano-antibodies have the advantages of stable physical and chemical properties, low immunogenicity, strong tissue permeability, and can recognize epitopes that traditional antibodies cannot recognize, which makes them a strong and beneficial supplement to traditional antibodies.

Nano-antibody is only composed of heavy chain variable region, with small molecular weight and simple structure, which enables it to realize stable expression in various expression systems. So far, VHHs has been expressed in many expression systems, from prokaryotic cells, yeast, fungi, insect cells, mammalian cell lines to plants. This paper mainly introduces the expression of nano-antibody in different expression systems, and the present situation and development trend in the field of this system.

Prokaryotic expression system　Prokaryotic expression system is the earliest mature protein expression system studied. Obtaining foreign proteins through prokaryotes can obtain gene expression products in a short time, and the cost required is relatively low. The expression system mainly includes Escherichia coli expression, Bacillus subtilis expression and Streptomyces expression. Among them, Escherichia coli system is the most widely used, and the prokaryotic system generally refers to the expression of Escherichia coli.

Escherichia coli expression system　Escherichia coli expression system is the most important expression platform of recombinant protein in laboratory environment, and the expression is controlled by lactose operon. The host of Escherichia coli system has the advantages of fast growth, simple culture, low price, clear genetic background and high protein expression. However, it can not modify the expression product after translation, and the expression product contains a lot of endotoxin and is easy to form inclusion bodies.

Common host bacteria of Escherichia coli expression system

Periplasmic space, as the only compartment with oxidation environment in Escherichia coli, is the most commonly used expression system of nano-antibodies containing specific disulfide bonds. In addition to aerobic environment, there are many partners and isomerases in the periplasmic space, which can promote the correct formation of disulfide bonds and help protein fold. Nano-antibody protein is first produced in the cytoplasmic space, and then secreted into the periplasmic space through Sec pathway, SPR pathway or Tat pathway. After signal peptide is removed by signal peptidase, the target protein can be obtained [1].

Up to now, many VHHs have been successfully expressed in periplasm, some of which can reach tens of milligrams per liter, but there are still a lot of VHHs with low yield. This is because many fusion proteins can not be effectively secreted in the periplasmic space, and cytoplasmic expression seems to be the only expression mode of such fusion proteins [8].

The cytoplasm is a reduced compartment, so that the proteins expressed through the cytoplasm can not be folded correctly, and most of them are inclusion body proteins. The proteins are protected from the degradation of intracellular enzymes and are easy to be separated in high purity and concentration. However, there are many kinds of proteins in cytoplasm, and it is difficult to purify them. At the same time, nonfunctional inclusion proteins need to be completely denatured and refolded to be recovered from these inclusions, but the recovery of VHHs is usually inefficient [1]. In order to solve the problem of cytoplasmic expression, Xue X and others designed a new dialysis-dilution device in 2016. Using this device, researchers refolded VHHs and achieved a recovery rate of 85%, while the conventional dialysis and dilution methods only reached 13%[9]. Bacterial cytoplasm can be an effective compartment to produce correctly folded nanoparticles when expressed by recombinant vectors with sulfhydryl oxidase and disulfide isomerase activities. Larger volume and wider cytoplasm of chaperone/folding enzyme can achieve high yield of nano-antibody [6]. At the same time, double mutants with defects in thioredoxin and glutathione pathways have been developed. Some of these strains have been sold commercially in recent years, such as Origami (Novagen), Rosetta-gami (Novagen) and SHuffle?T7 (New England Biolabs) [10]. Among them, Shufflet 7 overexpresses a critical periplasmic isomerase DsbC, which can effectively catalyze the isomerization of disulfide bonds. Some studies have found that,The activity of isomerase DsbC can increase the yield of functional recombinant protein in periplasmic research [11].　　

Kavousipour Soudabeh and other modified vectors added four different signal peptide sequences to guide the secretion and expression of nano-antibodies, and found that TrBC signal peptide had the best effect [5]. Jianli Yu et al. used repetitive amino acid sequence motifs (GAGAGS) found in silk fibroin (SFP) as a new fusion tag (SF-tag) to enhance the expression of nanosomes in E.coli.. The transcription level of labeled protein is 2.3-7.0 times that of unlabeled protein, and the yield is increased by 2.5-7.1 times [27]. Xi Xie and others tried to select antifreeze protein AXX, and obtained its reverse transcription protein XXA by synthesizing XXA gene, which was used to develop new soluble fusion tags. It was found that the solubility ratio of fusion protein expressed by XXA fusion tag reached 86%, which was much higher than that of other tags [12].

Other prokaryotic expression systems　Lactic acid bacteria are the most common intestinal probiotics, which are generally considered to be harmless to human body and are very suitable for the production host of therapeutic molecules. However, the existing expression data show that the yield of VHHS produced by lactic acid bacteria is low, about 1-3mg/L, which is much lower than that of Escherichia coli [13,14]. Lactobacillus rhamnosus DSM14870, as a normal flora in human vagina, can express HIV antibody in the form of soluble or cell wall anchor fixation, and is a suitable expression host for HIV antibody [2]. When Bacillus brevis choshinensis was used for 3L fed-batch fermentation, the yield was as high as 3g/L[15]. This system is easy to manipulate genes, has no endotoxin and shows weak protease activity, so it is a very noteworthy system.

Eukaryotic expression system　

Due to the defects of prokaryotic expression system, such as difficult purification of inclusion body protein and incomplete protein modification, people began to use eukaryotic expression system to study genes. At present, eukaryotic expression systems commonly used in genetic engineering research include yeast expression system, insect cell expression system and mammalian cell expression system.

Yeast expression system　Yeast system has clear genetic background, simple operation, easy genetic operation, perfect eukaryotic protein expression control system and advantages of both prokaryotic and eukaryotic expression systems. Yeast eukaryotic protein expression systems include methanol yeast expression system, Saccharomyces cerevisiae expression system, Schizosaccharomyces expression system and Kluyveromyces expression system [17].

Saccharomyces cerevisiae is the first yeast fermented by human beings, which has no specific virus and low cost. At present, it is the largest yeast expression system in shake flask culture, with the output exceeding 100mg/L[16]. Some amino acids in VHHs can participate in the recruitment of molecular chaperones in endoplasmic reticulum, thus narrowing the difference of molecular chaperones between Saccharomyces cerevisiae and mammalian cells, which is beneficial to the folding kinetics of nano-antibodies and improving the yield of nano-antibodies in Saccharomyces cerevisiae [17]. The protein expressed by Saccharomyces cerevisiae is prone to hyperglycosylation, and a large number of endogenous proteins are produced during fermentation, so the secretion efficiency of the target protein is low [1]. Considering the above problems, Saccharomyces cerevisiae is gradually replaced by methanol yeast represented by Pichia pastoris.

Pichia pastoris expression system is an efficient expression system of foreign proteins. This microorganism does not accumulate toxic ethanol, but only secretes a few endogenous proteins, and its glycosylation degree is the same as that of mammalian cells, so its immunogenicity is weak, so it is the most commonly used eukaryotic expression system. Pichia pastoris has a strictly regulated methanol inducible AOX1 promoter, which is suitable for high expression of foreign proteins [1]. But methanol is a highly toxic and dangerous chemical product. The GAP promoter without methanol induction is used instead of AXOI, and the carbon source does not need to be changed during the culture process, so the operation is simpler and the time for foreign proteins to reach the peak level can be shortened. The yield and affinity of nanoparticles produced by this system are similar to those produced by methanol-induced expression. It has been studied that the yield of nano-antibody expressed by this system in shake flask is 51.71mg/L[18] and 16mg/L[19].

Fungal expression system　

Some filamentous fungi, such as Trichoderma and Aspergillus, can secrete a large number of foreign proteins in the culture medium. However, the fungal system not only expresses protein of interest, but also produces many proteases, which affects the yield. Joosten et al. obtained only 1.5 mg/L VHHs in Aspergillus awamori medium. After adding 0.25% BSA, it reached 7 mg/L. It is reported that more than 80% of VHH is degraded or adhered to the cell wall compared with endogenous xylanase secreted efficiently in this system, and researchers believe that the low secretion efficiency of VHHs is the bottleneck of fungal expression [20]. In order to overcome this limitation and protect VHHs from degradation, other researchers fused VHH with the high amylase A signal sequence (sTAA) of Rhizopus oryzae lipase (N28) and the N-terminal 28 amino acid fragment (N28), so that the highest yield of VHHs expressed in Aspergillus oryzae reached 73mg/L, which was 300-800 mg/L lower than that of Escherichia coli [21]. The final yield of GlaB-VHH fusion protein in Aspergillus oryzae can reach 610mg/L, which provides the possibility for high expression of nano-antibody, but its stability needs to be verified [22]. In addition, VHH[23] was expressed by maize head smut in unconventional secretion pathway.

Insect cell expression system　

Insect cells are a widely used eukaryotic expression system, and recombinant baculovirus vectors (such as AcMNPV) can specifically transfect insect cells. Its survival in nature is short, and the strong promoter is inactivated in mammals and cannot infect vertebrates, so the recombinant baculovirus is safe for human beings. Proteins with complex structures under the control of strong promoters may not be able to form correct folding and post-translation modification, which may lead to the aggregation of target proteins and reduce antibody production, so the expression yield of VHHs in this system is much higher than that of other types of antibodies [17].

Gómez-Sebastián and others used the improved baculovirus expression system (IBES? technology) to express VHHs for the first time. The chigger larvae were inoculated with different recombinant baculovirus inoculation methods. The yield of VHH extracted from larvae is 257 mg/L, and the recovery rate after purification is 50%[7]. When expressing anti-endothelial cell selection protein, Drosophila cell SC-2 secreted 12-14mg/L, but the target protein was not detected when expressed in Escherichia coli at the same time, which may be related to the processing and modification ability of insect cells [26].

Mammalian cell expression system　Mammalian cells are the best expression system for therapeutic antibodies, because the produced antibodies have the weakest immunogenicity. At present, the main cell lines include CHO, NS0, Sp2/0, HEK293 and per C6 [17]. Among them, CHO cells grow rapidly and adapt to serum-free suspension culture, which is the most popular host. They can express VHHS up to 100mg/L in shake flask [24]. HEK293 cells are more commonly used in the laboratory because of transient transfection and semi-stable expression, because they require less time and labor. However, monoclonal antibodies approved for the treatment of human diseases are only produced by CHO, NS0 and SP2/0. So far, HEK293 cells have not been used to produce VHHs, and there are few reports about producing antibody fragments by this method [17]. In most literatures, CHO is used to produce antibody fragments. Up to now, 50% of the therapeutic proteins produced in industry are still produced by CHO [1]. The production costs associated with mammalian cell lines are much higher than those associated with any other laboratory research platform.

Common host cells of mammalian expression system

Plant expression system　Compared with other expression systems, plant production platform (stable and transient expression system) is cheap, safe, capable of folding and assembling complex proteins and post-translation modification, easy to expand, and unaffected by human pathogens and diseases. It is an ideal protein expression host and is usually used as an alternative method for mammalian expression systems. In addition, plant expression products can be concentrated in specific organs, such as leaves or seeds, and can be taken orally directly. Tobacco leaves are the most common hosts for expressing VHHs, while the proteins expressed in Arabidopsis and rice seeds have attracted much attention because of their direct oral input of VHHs[1]. The stable transformation methods commonly used in plant system expression have some problems, such as the recombinant gene escaping to nature or the time-consuming transformation. Therefore, some studies have proposed the transient expression system of plant virus expression vector as an alternative method, and the nano-body content with correct conformation reaches 0.45% of the total soluble protein [25].

Present situation and development of nano-antibody expression　

Escherichia coli expression system is the most commonly used expression system of nano-antibody, which has two expression modes: periplasmic expression and cytoplasmic expression, each with its own advantages and disadvantages. Some oxidation engineering strains have been modified, but more experimental support is needed. In addition, various methods of modifying vectors, such as adding labels or signal peptides, have been put forward and have been verified by experiments. Compared with Escherichia coli, Pichia pastoris has excessive glycosylation, which may lead to immunogenicity and ultimately affect its clinical application. The expression systems of fungi, insects, plants and mammals are much more complicated than prokaryotic and eukaryotic expression systems, and are generally not easily adopted after considering the production time, cost and laboratory conditions.

Escherichia coli system is fast, convenient and cheap, and it is the first choice for VHH expression under most laboratory conditions. When some types of VHHs can’t be successfully produced in E.coli, other systems will be used instead.

List of nano-antibody expression

　　When it comes to cancer, our first impression is often a terminal illness, which makes people "talk about cancer." The data shared at the 10th annual meeting of the National Cancer Center shows that the 5-year survival rate of cancer in China has increased from 30.9% to 40.5% in the past decade. Although the incidence of cancer has increased, with the change of public concept and the progress of medical treatment, cancer has become a chronic disease in China. ①②

　　Figure from White Deer Video ②

　　In fact, it may take several years from early cancer to late cancer. And with the development of medical technology, after scientific treatment, the five-year survival rate of many cancers has been above 90%.

　　Cancer has become a chronic disease.

　　The "Core Information and Knowledge Points of Cancer Prevention and Control" issued by the CDC of the National Health and Wellness Commission pointed out: "Cancer is a kind of chronic disease that seriously endangers people’s health." ③

　　It may take several years for cancer from early stage to late stage.

　　The development of most cancers is not so fast, and the pathogenic process of cancer is also very long. It takes quite a long time from normal cells to cancer cells, from continuous division and proliferation into cell clusters to "visible" diagnosable cancer nodules, ranging from a few years, usually taking more than ten to twenty years, or decades. ④

　　It’s just that some symptoms are ignored by us as ordinary physical discomfort, so that once they are discovered, they are in the late stage. Naturally, they feel that the disease is progressing rapidly and it is difficult to treat and recover.

　　Figure from Shanghai CDC ⑤

　　2. Scientifically treat some cancers, and the five-year survival rate is over 90%

　　With the change of people’s concept and the progress of medical level, cancer has changed towards the development direction of chronic diseases in China. In 2021, according to the statistics of the National Cancer Center, the five-year survival rate of malignant tumors has increased from 30.9% ten years ago to 40.5% at present, an increase of nearly 10 percentage points. For some malignant tumors, such as esophageal cancer, the five-year survival rate has been higher than that of developed countries such as the United States. ⑥

　　Yao Zhendan, deputy chief physician of the Fourth Ward of Gastrointestinal Cancer Center of Peking University Cancer Hospital, said in a video interview with Bailu that the treatment effect of early cancer is excellent. According to statistics, the five-year survival rate of early gastric cancer and intestinal cancer is above 90%, the five-year survival rate of middle gastric cancer is about 50%, and the five-year survival rate of middle intestinal cancer is about 70%. Even for patients with advanced cancer, the survival rate becomes better after treatment, and the survival time with cancer is longer. ②

　　Image from White Deer Video

　　Therefore, early detection and treatment of cancer is very necessary.

　　15 small signs of pre-cancer to know!

　　What are the symptoms and signs of early cancer? This is a problem that many people are concerned about. Pan Zhanhe, deputy chief physician of the Department of Oncology, Zhongshan Hospital affiliated to Xiamen University, listed 15 possible symptoms and signs in the early stage of cancer in the "Oncologist" WeChat publication in 2018 for your reference. ⑦

　　1. Masses and nodules

　　Mass nodules are not necessarily cancer, we can make a preliminary judgment on it:

　　Look at the size. The smaller the nodule, the more likely it is to be benign, of course, it is not absolute, so we should pay attention to follow-up and review; Pay attention if the nodule is more than 1 cm. Note that nodules that continue to increase, especially those that increase rapidly, tend to be malignant and should be paid special attention to.

　　Look at the texture. Soft or cystic masses tend to be benign; Hard, fixed or solid masses tend to be malignant, but the swollen lymph nodes of lymphoma are tough to the touch.

　　Third, look at the boundary and activity. Benign tumors usually have clear boundaries and good activity; Most malignant tumors have unclear boundaries, often adhere to or fuse with surrounding tissues, and their activity is poor.

　　Health Times Mao Yuanyuan/photo

　　2. Persistent pain is not traumatic

　　If there is persistent pain in a certain part of the body that is not caused by trauma and has unknown reasons, you should go to the hospital to find out the reason.

　　3. Cough if you don’t cure for a long time

　　For chronic cough or blood in sputum, especially long-term smokers, we should be alert to the possibility of lung cancer.

　　4. Unexplained total fever

　　If the cause of fever is unknown and persists, you should be alert to the possibility of cancer and conduct relevant examinations as soon as possible.

　　5. Inexplicable emaciation and fatigue

　　If you don’t take the initiative to lose weight, you don’t deliberately go on a diet, but you lose weight for unknown reasons, or you are accompanied by anorexia, fatigue, fatigue, etc. To find out the reasons, emaciation and fatigue may also be one of the manifestations of cancer.

　　6. No trauma but bleeding

　　Non-traumatic abnormal bleeding, such as hematochezia or hematemesis, should pay attention to exclude the possibility of intestinal cancer and gastric cancer; Beware of lung cancer when coughing up blood and taking blood in sputum; Irregular vaginal bleeding or menstrual bleeding may be related to gynecological tumors such as endometrial cancer and ovarian cancer. Painless hematuria or dysuria, beware of urinary tumors; Non-traumatic epistaxis should be careful to rule out nasopharyngeal carcinoma.

　　7. Abnormal digestion persists.

　　If indigestion persists, or accompanied by acid reflux, heartburn, abdominal pain and discomfort, we should be alert to the possibility of gastric cancer or esophageal cancer.

　　8. Obstruction of swallowing food

　　If you have a feeling of bloating or burning behind the sternum, pain behind the sternum, or a feeling of foreign body in the esophagus, especially the feeling of swallowing food obstruction, you should be alert to the possibility of esophageal cancer and laryngeal cancer.

　　9. hoarseness persists and is difficult to recover

　　If hoarseness is difficult to recover and lasts for a long time, we should be alert to the possibility of laryngeal cancer, lung cancer and so on invading or oppressing the recurrent laryngeal nerve.

　　10. Changes in stool habits and characteristics

　　If the habit, frequency or character of stool changes (such as thin stool shape, pus in stool, blood and mucus, etc.), or constipation and diarrhea alternate, be alert to colorectal cancer and go to the hospital for examination as soon as possible.

　　11. White spots increase burning and itching

　　Oral leukoplakia, leukoplakia of female vulva or male penis glans rapidly expand with burning itching, and attention should be paid to eliminating canceration.

　　12. Mole enlargement and discoloration

　　If the mole suddenly increases, the edge becomes irregular or the color changes, or there is bleeding or burning pain, and the original hair on the mole falls off, it is suspected that melanoma may be possible.

　　13. Fracture is easy to occur.

　　Fractures that are easy to occur without obvious or slight external force may be pathological fractures, so we should be alert to bone malignant tumors. Teenagers should pay attention to leukemia if they have non-traumatic joint pain and swelling.

　　14. Ulcer wounds persist for a long time

　　If the skin wound or ulcer persists, be alert to the possibility of skin cancer. Oral ulcer is very common, but if it cannot heal for a long time, we should be alert to the possibility of oral cancer.

　　15. Abnormal changes in male breasts

　　Although male breast cancer is rare, if male breast grows abnormally or has other abnormal changes, you should be alert to the possibility of male breast cancer and go to a breast specialist as soon as possible.

　　Of course, these manifestations are not necessarily cancer, but remind you to pay attention to it and go to the hospital for further examination to make a clear diagnosis.

　　Early and timely detection,

　　Kill cancer in the cradle

　　For ordinary people, regular physical examination can keep abreast of their physical health; Especially in the age of high incidence of cancer, timely screening can minimize the risk. Recommendations for screening and prevention of common malignant tumors in residents (2023 edition)
It is suggested that ordinary people with general risks can arrange screening in this way: ⑧

　　Health times chart

　　For high-risk groups, especially those with a family history of cancer, screening and physical examination should be done in advance and regularly according to the doctor’s advice.

　　This article is synthesized from:

　　① On March 29th, 2023, Shanxi Daily held the 10th Annual Academic Conference of National Cancer Center.

　　② 2023-08-14 White Deer Video "# Cancer has become a chronic disease in China #"

　　③ Key Information and Knowledge Points of Cancer Prevention and Control by CDC of National Health and Wellness Commission.

　　④ 2020-09-29 WeChat WeChat official account "Oncologist" "Who is easy to get cancer? Doctors say that people with cancer belong to these five categories! 》

　　⑤ 2020-06-30 Shanghai CDC "Science of Cancer Prevention? Is cancer a chronic disease? 》

　　⑥ Written Record of the Regular Press Conference of the National Health and Wellness Committee on April 27th, 2021.

　　http://www.nhc.gov.cn/xcs/s3574/202104/df811bc1ee8b4c8db0f0561758172ca8.shtml

　　⑦ 2018-10-29 oncologist "The most comprehensive cancer science: cancer prevention, early diagnosis, screening and treatment. The whole article includes "

　　⑧ Recommendations for Screening and Prevention of Common Malignant Tumors among Residents (2023 Edition). Shanghai Anti-Cancer Association, Cancer Hospital Affiliated to Fudan University.