This issue of the "Precision Frontier" column shared by Zhao Haitao’s research team published inGenome Medicine(IF =11.12) [1], a mutation signature was constructed and verified to predict the prognosis of patients receiving immunotherapy, and the potential immune response of different subtypes was studied by using multidimensional data.

Research background

Immunocheckpoint inhibitors (ICI) have changed the treatment of many cancers. However, the beneficiaries of ICI treatment are limited, so it is necessary to screen and predict biomarkers to classify patients. At present, many biomarkers, such as tumor mutation load (TMB), have been used as indicative biomarkers in clinic. However, some high TMB patients with gene mutation related to immunotherapy resistance are not sensitive to ICI treatment. Therefore, it is necessary to go beyond TMB and identify the specific genetic determinants of ICI treatment response.

research design

The study included genome and clinical data of 12,647 patients. There were 1572 cases in the training set (immunotherapy patients with 9 kinds of cancer) and 932 cases in the verification set (immunotherapy patients with 5 kinds of cancer). The training set was sequenced by MSK-IMPACT panel containing 468 genes.

The authors identified a set of 11 genes based on mutation, which can divide patients into high-risk and low-risk groups. The mutation of these 11 genes is related to the better response to ICI treatment, and this gene set has been proved to be an independent prognostic factor after ICI treatment.

research results

1. Identify mutant gene sets that can predict the outcome of immunotherapy.

Firstly, the survival differences of 468 genes in the training set were compared between wild type and mutant type, and 98 genes related to OS (global survival) were obtained. After that, LASSO COX regression analysis was further screened and 11 important genes were finally obtained. Through COX regression analysis, the risk score of each patient was quantified on the basis of 11 mutant gene sets. In the training concentration, the OS of patients in the high-risk group is shorter than that of patients in the low-risk group (Figure 1B). In order to study whether the gene set is limited to a specific population or suitable for different populations, the subgroup analysis regardless of age, drug use type and cancer species shows that the gene set is significantly related to the OS of patients treated with ICI (Figure 1C-E).

Figure 1. Generation and Verification of Gene Set Based on Mutation

2. Verification of predictable immunotherapy results

In order to further confirm the value of mutation-based gene set in predicting the results of immunotherapy, it was found that the OS of low-risk group was higher than that of high-risk group (Figure 1F). The research results of predicting ICI treatment response in gene set show that the DCB(durable clinical benefit) of ICI treatment in low-risk group is significantly increased compared with that in high-risk group (Figure 1G), and low-risk patients are more likely to respond to ICI treatment (Figure 1H). These results get the same results in the verification set (Figure 1I, J).

3. Gene set is an independent prognostic predictor of immunotherapy.

Next, the author verifies whether the gene set based on mutation is an independent predictor of immunotherapy response. In the training and validation set, univariate COX regression analysis showed that the gene set was related to OS. After adjusting for drug type, tumor type and TMB, multivariate COX regression analysis showed that the gene set was still an independent predictor, which confirmed the stability of its independent prediction of ICI prognosis (Figure 2A, B). In order to determine which factor has the best predictive performance, C-index is used to compare the performance of mutation-based gene sets with TMB and drug types. The results of C-index show that the gene set based on mutation can predict the prognosis more accurately than TMB and drug type in both training set and validation set (Figure 2C, D).

Fig. 2. Relationship between mutation-based gene sets and other characteristics

4. The clinical benefit of ICI treatment can be predicted based on the mutant gene set, disease stage, CTL and 6-IFN-g gene signature.

Considering the stage of disease, CTL and 6-gene IFN-g signature have been proved to be highly predictive of the response to ICI treatment, the authors speculate that they may play a synergistic role in predicting the response to immunotherapy. The author combined the gene set based on mutation with disease stage, CTL and 6-gene IFN-g signature through Nomotograph, and provided a method for clinicians to quantitatively predict the OS of patients treated by ICI. Fig. 2E is the nomogram of Riaz cohort construction, and the calibration curve of fig. 2F shows the consistency of actual and predicted results, indicating that these signature should be integrated into the predicted nomogram of ICI treatment.

5. Potential external immune landscape of high and low risk groups

In order to further explore the relationship between immune system and mutation-based gene set, the authors conducted a multi-group analysis of TCGA cohort, and the risk score divided TCGA cohort into high and low risk groups (Figure 3A). At the genome level, the proportion of white blood cells, lymphocytes and TIL in the low-risk group was significantly higher than that in the high-risk group (Figure 3B-D). The H&E staining results of TIL ratio are consistent with the above results (Figure 3E). In addition, the proportion of immunostimulatory cells (such as CD8 T cells) in the low-risk group is also significantly higher than that in the high-risk group (Figure 3F). The above results were further tested by Danaher et al.’ s immune infiltration score (figure 3G) and immune characteristic score (figure 3H), and it was found that the abundance of immune cells in low-risk group was higher. Then unsupervised clustering was used to cluster the immune characteristic scores of patients in TCGA cohort, and the results were clustered into two immune infiltration modes (Figure 3I), and the high immune infiltration was significantly enriched in the low-risk group (Figure 3J).

Fig. 3. Immune status of high and low risk population in TCGA cohort.

In addition, the immune signature in the low-risk group was significantly higher than that in the adjacent cancer tissue; On the contrary, the immune signature in the high-risk group was significantly lower than that in the adjacent tissues (Figure 4A). The correlation of immune activity in low-risk group was significantly higher than that in high-risk group (Figure 4B, C). GSEA results showed that 13 pathways were significantly enriched in the low-risk group, including 6 immune-related pathways, such as "cytotoxicity mediated by natural killer cells" (Figure 4D). Tumors in the low-risk group are associated with significantly higher CYT scores, and the number of fibroblasts in the high-risk group is now increasing (Figure 4E, F). According to these results, the low-risk group is rich in immune cells, which can respond to ICI treatment, and fibroblasts may help the high-risk group escape. The expression of chemokines in the low-risk group is higher (Figure 4G, H), so the author speculates that the enrichment of chemokines in the low-risk group may trigger an immune response.

Figure 4. Potential external immune landscape of high and low risk groups　

6. Potential inherent immune landscape of high and low risk groups

Some potential factors determining tumor immunogenicity between the two groups were compared. Mutation, new antigen load, TCR and BCR diversity in low-risk group were significantly higher than those in high-risk group, but CNV load and aneuploidy in high-risk group were higher than those in low-risk group (Figure 5A). This result is consistent with previous studies, that is, tumor aneuploidy is related to immunotherapy and decreased immune escape marker response. In addition, the heterogeneity of tumor in high-risk group is higher than that in low-risk group, which further supports the view that tumor will promote the development of heterogeneity in the presence of cytolytic activity and less active infiltration of immune cells. In order to further understand the mutation process of high and low risk groups, the mutation characteristics were described according to somatic mutation data, and four different mutation patterns were determined in TCGA cohort (Figure 5B). The frequency of these four mutation signals in the low-risk group is significantly higher than that in the high-risk group (Figure 5C). In addition, it was also found that immune checkpoint molecules (such as PD-1, PD-L1 and CTLA4) and costimulatory molecules were more highly expressed in the low-risk group (Figure 5E).

Figure 5. Potential innate immune response and escape landscape in high and low risk groups.　

7. Copy number characteristics of high and low risk groups

Significant differences in chromosome variation were detected in high and low risk groups (fig. 6A). Local amplification peaks of immune genes with good characteristics, such as PD-L1 (9p24.1) and PD-L2 (9p24.1), were observed in the low-risk group (fig. 6B, C). GO function annotation of the specifically amplified genes showed that the low-risk group was significantly enriched in two immune-related biological processes, while the high-risk group was significantly enriched in the biological process of "positive regulation of fibroblast proliferation", but not in any immune-related biological processes (Figure 6E). At the level of mRNA expression in TCGA cohort, the expression of PD-L1 and PD-L2 mRNA in low-risk group increased significantly (Figure 6G), which was consistent with CNV data. This finding suggests that CNVs in tumor contributes to the observed difference in immune infiltration.

Figure 6. Variation of copy number in high and low risk groups

discuss

This study is the first time to use an independent cohort to study the comprehensive mutant gene sets of different tumor types. Through PSM algorithm, hierarchical analysis and multivariate COX regression analysis, the application performance of mutation-based gene sets in different types of tumors was tested, and the results showed that mutation-based gene sets were reliable.

This study has the following innovation and practical application value. First, different types of tumors (such as NSCLC (non-small cell lung cancer), melanoma and renal cell carcinoma) are used, which represent the most common types of cancer treated with ICI. Secondly, the application of multiple biomarker prediction model needs to understand the factors that affect the accuracy and precision of Qualcomm analysis in clinical practice. The risk score formula and threshold of mRNA expression calculation are not suitable for verification with other types of data. Therefore, this study developed a gene set based on mutation to predict the clinical efficacy of ICI treatment. The composition of the above mutations is neither affected by tissue types nor adjusted by any other biomarkers. The risk score formula and threshold of gene set based on mutation can be verified by other tumor analysis methods, such as DNA sequencing and single nucleotide polymorphism microarray analysis. Therefore, mutation-based gene sets are not affected by technological changes, even when different platforms are used in different centers. Thirdly, in practice, gene sets based on mutations avoid exposing patients to potential immune-related adverse reactions when they are unlikely to respond, and enable patients to match to potentially more effective treatments more quickly. Fourthly, the prediction performance of gene set based on mutation is compared with other factors that can predict immunotherapy, and it is found that the prediction performance of gene set based on mutation is better than all these factors.

Several limitations of this study. First of all, because some mutations may be enriched in some tumor types, the initial goal of this study is to create a panel instead of identifying a single gene (such as BRAF), because the former can contain more genes to predict the prognosis of different types of tumors. Secondly, although the immune landscape of 11 genes in the gene set based on mutation has been explored, it is still necessary to clarify the molecular mechanism of each gene affecting immunotherapy in vivo and in vitro functional experiments. Thirdly, the enrichment scores of carcinogenic pathways and the expression patterns of immune checkpoints should also be detected by immunohistochemistry.

tag

The mutation-based gene set proposed in this study is the first comprehensive genomic marker systematically identified, which can be used to evaluate the ICI treatment effect of pan-cancer species. This study is also the largest prognostic model discovery project for cancer patients receiving ICI treatment (whether single drug treatment or combined treatment of anti-PD-1 and anti-CTLA-4). Nomoto, which combines mutation-based gene set with TMB and drug types, can help clinicians choose patients who may have a strong response to ICI treatment. In addition, it also reveals the different immune conditions of high and low risk groups, and specific genomic changes may drive the formation of these microenvironments. In a word, this work puts forward a new tumor classification method, which may guide the decision-making of ICI treatment.　END　

References:

[1]　Long, J., Wang, D., Wang, A. et al. A mutation-based gene set predicts survival benefit after immunotherapy across multiple cancers and reveals the immune response landscape. G enome Med 14, 20 (2022). https://doi.org/10.1186/s13073-022-01024-y

Write Liu Hua Hua

Editing and typesetting SX

　　What is the most tearful thing these days? Nothing is more than "the head is not bald yet, and the cervical vertebrae are collapsed first." Low-headed people don’t hurry to touch their back necks. Is your cervical vertebra okay? As a "senior" patient with cervical spondylosis, the reporter also groped for a long time on the road to saving cervical vertebrae and tried many methods, but compared with this netizen, the reporter sighed! How hard they have worked to treat cervical spondylosis! Take a quick look at their fancy self-help method.

　　Yangzi Evening News/Zi Niu Journalist Wang Yun

　　Netizens share neck brace, traction and massage … … Evaluation of cervical self-help artifact

　　Artifact 1: Neck Bracket

　　"I think this kind of thing should have one person." Netizen Elly introduced her new good product to her colleagues: neck support. According to the photo, this neck brace looks like an advanced version of the "neck collar". The professional term is an ergonomic curved neck strap, which can adjust the neck circumference according to the thickness of one’s neck and has the effect of supporting decompression.

　　Netizen Elly said that when she first wore it, she felt a little uncomfortable and needed to hold it all the time, but she got used to it after two days of adaptation. "It is very light and small, and the fabric is quite comfortable. Wearing it can play a role of reminding, like holding the back of the head with one hand. I feel that this is also conducive to opening the shoulders, and it will not put any pressure on the cervical vertebrae and shoulders for one day."

　　Artifact 2: Traction Pillow

　　"Torturing my cervical spondylosis and neck pain, it’s much better to use a traction pillow!" A netizen said that his cervical spine was particularly sore because he often played mobile phones, and there was a "rich bag" that affected his posture. After trying the traction pillow, he felt more relaxed and comfortable.

　　The reporter found that the traction pillow is different from the advertised sleeping pillow for repairing cervical vertebrae. It is not used for sleeping, but for going to bed. This kind of product claims that it only takes a few minutes every day to lie down gently and bid farewell to cervical discomfort. It uses the gravity of the head to pull the cervical vertebra and guide the cervical vertebra to return to a healthy curvature. The slightly advanced one also has a heating function.

　　Artifact 3: Cervical Vertebral Instrument

　　"We are bald for a while, overworked for a while, and we have to soak Lycium barbarum in a thermos cup for a while … …” A netizen laughed at himself. It is nothing new to feel that the post-90s generation is full of problems. Now the neck has become a key protection object. The artifact she recommended is a cervical vertebra instrument, which looks like a big crab pliers and is covered with bumps. This kind of product is not electric massage, but self-weight massage.

　　"This massager really pinpoints the sore point on the cervical vertebra. Lying on it for ten minutes every day with arm exercise is really sour and refreshing, especially relaxing the trapezius muscle." Netizens share their own experience and recommend it to cervical vertebra patients with shoulder and neck pain.

　　Artifact 4: Foam Axis

　　"I want to announce that the foam shaft is an artifact of cervical spondylosis, which really saved my cervical discomfort tonight." A netizen shared her newly discovered artifact to save cervical vertebra — — Foam shaft, "can make you really relax in an instant, feel much more comfortable, at least not painful."

　　She also shared the use of foam shaft to relieve cervical pain: the whole body lies flat and relaxes, the foam shaft is placed on the pillow, and the head is slightly twisted left and right. You can feel the pain in the acupoints below the back of your head, and you will relax a lot after rolling.

　　Artifact 5: Cervical traction chair

　　Do you still remember the "hanging" cervical exercise method created by aunts and uncles? On the big trees in the park, they hang their heads on the trees, swing and shake their bodies rhythmically, and some can even keep their feet off the ground. It is precisely because of the strange style of painting that it once occupied the hot search list. However, what I want to talk about here is of course not this kind of "hanging by hanging", but netizens directly buy "cervical traction chair" and treat it by hanging their necks at home. "The advantage is that it is uncomfortable. I can use it at home at any time. I have used it for more than a dozen times in a row and feel that my shoulders and neck are much easier." Some netizens commented on the use experience.

　　The reporter searched on the shopping website and found that there are quite a few hospitals with the same model, and the sales volume is also good. Many of them advertised "solving the fundamental problem of cervical vertebrae". The reporter noticed that these traction chair are even more luxurious than those in hospitals, and many of them are more comfortable to sit for a long time with sofa-class seats; Can adjust the lever by itself, which can be long or short; Even the traction belt is widened and thickened, which can be adjusted according to the face shape.

　　Expert’s opinion, the good habit of "looking up at the sky" may be the best artifact.

　　So many artifacts to save the cervical vertebra, which one is useful? The reporter found an interesting phenomenon. Whenever a netizen shares his "self-help artifact", there are different opposition voices underneath. For example, although the neck brace recommended by the above netizens is good for their own use, some people use their own failure examples to suggest that those people with poor cervical vertebrae can’t wear it for a long time, which will make the neck muscles lose their self-regulation ability.

　　Just like a netizen accidentally revealed the "truth" — — "If there are such artifacts, the topic of cervical spondylosis will not exist!"

　　Tian Jiwei, chief medical officer of Deyu Medical, vice president of Nanjing Jiangbei Hospital and director of the Orthopedic Center, pointed out that cervical spondylosis is a syndrome concept, and most people do not need surgery after suffering from cervical spondylosis. "In clinic, less than 10% of patients really need surgery, which means that 90% of patients can achieve good results through conservative treatment, and even play a preventive role."

　　For a variety of therapeutic artifacts such as cervical pillows on the market, he also reminded that they may not play a therapeutic role.

　　How to prevent cervical spondylosis? It is very simple. First of all, we should reduce the inactivity that lasts for a long time. "If an action lasts for three hours, our cervical vertebrae will degenerate and strain, and long-term degeneration and strain will induce the proliferation, bulging and protrusion of intervertebral discs, and finally induce cervical spondylosis." Tian Jiwei said that for the "low-headed people" who use mobile phones and computers for a long time, they should get into the habit of looking up at the sky and rest for 15 minutes after a continuous action for two hours. "This will restore our physiological curvature without further aggravation."

　　Tian Jiwei believes that in the conservative treatment methods that cervical vertebra patients can try, besides changing posture regularly at work, exercise is also very important. Gentle neck movement and upper limb movement are beneficial to the relaxation of neck and shoulder muscles and improve blood circulation, and mild cervical spondylosis will be improved. "But not all sports are suitable. Swimming and flying kites are the sports that patients with cervical spondylosis can choose. These two exercises are effective for the recovery of cervical physiological curvature, the repair of cervical intervertebral disc and the prevention of the deterioration of cervical spondylosis. "

　　Xinhua Online Hai, August 14th (Reporter He Xinrong, Joline) The home is too messy, please ask someone to help you "break away"; Running at night, there are people who accompany the guidance; I can’t find bike-sharing when I go out, and someone will come and put it in a few days … … Have you ever thought that there are rich new job opportunities behind these increasingly familiar scenes?

　　It’s not that I don’t understand, it’s that the world is changing too fast. The surging new economy makes the definition of "work" richer and more exciting. More and more post-80s and post-90s have started different careers. While showing personality, it also brings more vitality to society.

　　The Magic of New Economy: From 360 Lines to 3600 Lines

　　Bike-sharing operator, shared office housekeeper, credit manager, quantitative trader, fashion blogger, family organizer, food stylist, escort runner, genetic tester, UP owner, drone trainer & HELIP; … The degree of "brain holes" in new occupations is beyond imagination.

　　Rome was not built in a day, and new occupations did not emerge overnight. The booming new economy in recent years is a fertile ground for these new occupations.

　　Although there is no accurate official definition, the coverage of "new economy" is very extensive. It not only refers to internet plus, Internet of Things, cloud computing and other emerging industries and formats in the tertiary industry, but also includes intelligent manufacturing and mass customization production in industry, and also involves family farms in the primary industry, and the integrated development of rural primary, secondary and tertiary industries.

　　In the past two years, the "new economy" has accelerated its growth, showing amazing "magic power": China’s employment indicators (including newly employed population, survey unemployment rate, etc.) rank first among 63 major economies in the world, while the macroeconomic growth rate is slowing down.

　　There is no doubt that the "new occupation" spawned by the "new economy" has absorbed a large number of employed people. The constantly updated list of national vocational qualifications shows that the number of jobs is moving from the original 360 to the new 3600. More and more people are creating new values for society while releasing their individuality.

　　Five rules of new career: see how many you have.

　　It is precisely because it resonates with the new economy at the same frequency that new occupations that look colorful actually have rules to follow. If you don’t want to be bound by the "cubicle", you may wish to refer to the following five rules:

　　[Internet Gene] The sharing economy has created operators, shared office housekeepers and shared house landlords in bike-sharing, while the platform economy has brought car drivers, couriers and take-away workers. Nowadays, most of the hottest entrepreneurial fields have Internet genes. With the Internet "connecting everything", people’s "career map" is being refreshed rapidly.

　　The current Internet applications are mainly concentrated in the fields of consumption and services. With the Internet becoming an infrastructure like hydropower and coal, and expanding to manufacturing and agriculture, new jobs with Internet genes will continue to emerge.

　　Su Hainan, vice president of china association for labour studies, said that the new occupation in the Internet era has some new features. If the task is fragmented, the working hours are not fixed; Diversified labor relations, such as the traditional employment relationship between platform and employees; Products and services are personalized, and labor output is more suitable for the specific needs of consumers.

　　[Subdivide and subdivide] A food can’t be nutritious, but it must be delicious. It’s not good just to eat, but to look good. As a result, the food stylist was born gorgeous. It must be said that the escalating demand of consumers has created new occupations in many seemingly inconspicuous segments.

　　"Professional people do professional things", with the east wind of consumption upgrading, new demands are constantly being stimulated: running and exercising with runners, traveling in personal tailor … … Because of China’s huge domestic demand market, any small demand may contain infinite potential.

　　[People behind "Nobody"] Unmanned driving, unmanned supermarket, drone delivery … … The rapid development of artificial intelligence technology makes the concept of "nobody" hot, and also makes many people worry that they will become a "useless" class. The statement that "50% of jobs will disappear in the next decade" has scared many fragile hearts.

　　In fact, no matter how developed artificial intelligence is and how many "unmanned" technologies are, there are still people behind it who are studying and manipulating it. However, their work changed from being in front of the stage to being behind the scenes. Tommy, Vice Minister of Science and Technology, said that in the long run, the employment brought by science and technology is far greater than unemployment. Take artificial intelligence for example, the algorithm engineer behind it is now in a state of extreme shortage. Instead of worrying about being replaced in the future, it is better to charge it now.

　　[Hobby is work] A few years ago, the old people would say, "Humor can’t be a meal", and no one regarded "telling jokes" as a job. Nowadays, "Duan Zishou" has really appeared. A few years ago, it was just a pastime to like the secondary culture and be good at making barrage videos. Today, the studio of "UP Master" has completed commercial realization in the real world of three dimensions.

　　Turning hobbies into jobs has become a new choice for many post-90s and post-90s. There are not so many instructions, and there is no strict index assessment. I do things with interest and "make money by playing." Therefore, parents who are eager to enroll their children in extracurricular training classes should see how important it is to respect their children’s nature and cultivate their interests!

　　[Rejuvenation of old crafts] It sounds that new occupations are often related to new knowledge and new skills? It’s not exactly like this. People always have some urgent needs, such as eating. From the ancient skilled worker to the modern chef, the professional "vest" is changing, but the core of pursuing delicious food has not changed.

　　Therefore, in the era of vigorous development of the new economy, the story of "rejuvenation of old crafts" has been staged again and again, even more moist than before. Bike-sharing is on fire, which has ruined the manufacturing workshop and the mechanic. There are fewer tailors on the street, but the old masters who come to order are popular. Once regarded as an unpopular veterinary graduate, she is now a pet beautician in MengMeng … … Society will not mistreat people with skills.

　　New employment concept: the boundary between white collar with gold collar and blue collar with gray collar is blurring.

　　The new economy gives birth to new occupations, and new occupations bring new employment concepts. In the past, people habitually divided their occupations into gold collar, white collar, gray collar and blue collar according to the working environment and income. Nowadays, more and more people find that the boundaries between these "collars" are becoming increasingly blurred.

　　"I earn 15,000 yuan a month. Will I lose this job for a gift of 2,000 yuan?" A few years ago, the story of a SF Express courier "getting angry" in a white-collar office was circulated around the Internet. Between words, full of professional pride. According to the traditional concept, the courier is a "blue-collar" position, which can make the courier stand at the scene of the bell ringing ceremony of listed companies due to the rapid growth of social demand and increasing technical content.

　　In the interview, the reporter was also exposed to many touching stories. Han Yien, a 28-year-old lawyer, was a financial company in Lujiazui, Shanghai. When she switched to be a home organizer, her mother cried. Because in the eyes of the older generation, this is a job of "serving people". But after more than two years of accumulation, Han Yien made a name for himself in the circle. Not only on-site service, but also receiving students and giving lectures, the "Qian Jing" is quite impressive. More and more elders gradually understand and recognize her choice of "not doing housework".

　　From farming society, industrial society, information society and intelligent age, the development of new technology has rapidly changed the traditional labor pattern. When mobile payment replaces cashier, artificial intelligence replaces repetitive workers, just as car drivers replaced coachmen.

　　It can be predicted that in the future, the social division of labor will become more and more detailed and the occupations will become more and more diversified. "Tall" jobs, such as investment bank traders, may be replaced by artificial intelligence if they don’t work hard. And more jobs without innate aura can live a wonderful life as long as they are willing to make sincere efforts.

　　The future has come. Embrace the new economy and fall in love with the new occupation. You, are you ready?

　　How do new Chinese immigrants overcome the difficulty of studying?

　　When new Chinese immigrants come to foreign countries and work hard, it is often difficult to take care of their children’s studies. In recent years, some young Chinese immigrants have gone abroad to study, but they are also faced with challenges such as different study environments in foreign countries and family financial difficulties, resulting in some dropouts. Let the children of new immigrants and young new immigrants better integrate into the new learning environment and ensure their academic success, which requires better home-school cooperation and better system design at the social level.

　　It is not common to play truant and work.

　　When new Chinese immigrants first arrive in the United States, they face many difficulties, and the education of their children is one of them.

　　According to the US "World Journal" report, due to the large number of young shop assistants recruited by Chinese restaurants and retail stores in new york, the problem of many new immigrant Chinese students dropping out of school is more serious.

　　According to Zhao Hongfang, a bilingual psychological counselor at Jiangbang High School in Flushing, some Chinese students are in Internet cafes all day and night. When they are familiar with the store, they actually help to watch the store at night. When asked by their parents how they have money to spend, they lie about working after class.

　　Some Chinese students don’t get along well with their parents, so they moved out at the age of 17 and watched the shop at night to earn living expenses. In particular, the owners of new Chinese restaurants in Flushing are looking for young clerks who know English, attracting a large number of dropouts. The school said that they would go to the restaurant to bring these students back.

　　However, the lack of diplomas will only bring more difficulties for new immigrants to seek a living in the United States in the future. According to the report, a survey in new york in 2015 showed that the annual salary of those without a high school diploma was only $21,121, those with a high school diploma was $31,038 and those with a bachelor’s degree was about $60,000.

　　It is worth noting that although new Chinese immigrants have played truant, worked or even dropped out of school, this is not the norm.

　　In an interview with this newspaper, Liang Guanjun, chairman of the American East Asian Association, believes that some students in every school play truant or drop out of school for some reason. "Flushing is so big, and employment opportunities are still limited. We can only say that this phenomenon exists among the new immigrants in new york, but the size of the’ large number’ in the report is debatable."

　　Even so, the difficulty in adapting to new Chinese immigrants still needs attention.

　　Inadvertence in discipline and difficulty in adaptation

　　Different from the "Chinese" born and raised in the United States, behind the new Chinese immigrants who came to the United States to work and play truant is the helplessness of their families’ inability to discipline and adapt to the environment.

　　"This is an old problem, which exists in big cities in the east and west of the United States and is quite difficult to solve." Chinese lawyer Sun Lantao said in an interview with this newspaper that Chinese in the United States often choose school districts to send their children to school. All the above phenomena occur in bad school districts. There, parents are forced to survive, sometimes working hard for 12 hours every day, and have no time to ask about their children’s learning. Children’s own English is not enough, and they are under bilingual pressure, so they are discouraged and unwilling to learn.

　　For new immigrant students, the financial hardship of their families is also a major incentive to play truant and work. "Nowadays, in the United States, it is not easy for restaurants to recruit people, so the salaries are relatively high." Liang Guanjun introduced that the monthly salary of Flushing Restaurant is about 2,800 dollars, which attracts students who can’t go on studying, and there are also cases where individual families have financial difficulties and need their children to make money.

　　The educational environment and allocation of educational resources in American society are also very different from those in China.

　　Sun Lantao introduced that the US Constitution and the constitutions of all states stipulate that any school-age children must receive compulsory education before the age of 18, regardless of whether they or their parents have immigration status. That is to say, even the children of illegal immigrants, as long as they are school-age children, no matter where they live, public schools must accept them and must not refuse them to go to school on the grounds of poor English and insufficient test scores. However, at the implementation level, the imbalance of educational resources has greatly reduced the effect of ensuring the enrollment rate of immigrant children.

　　"American culture is different from that of China, where the whole people attach importance to education. Ordinary public schools often have poor basic education. Psychological counseling and bilingual guidance advocated by the education department cannot be put in place at all because of the lack of human resources. " Sun Taotao introduced.

　　The negligence of family discipline and the difference of social environment bring poor communication between home and school, which eventually leads to inefficiency in the academic management cooperation of new immigrant children. "Chinese immigrants, Chinese new immigrants, survival is a problem, and the language is unreasonable. I don’t know how to start." Sun Lantao said that the communication information between parents and school teachers is seriously poor, which reduces the effectiveness of cooperation between schools and parents.

　　Multi-party cooperation to promote studies together

　　How to help new Chinese immigrants better integrate into the new learning environment and ensure their enrollment rate? Experts said that the joint efforts and effective cooperation of all parties are needed.

　　On the one hand, new immigrant families need to integrate into the new study environment more actively. Cai Wenyao, consultant of the American Chinese Chamber of Commerce, said in an interview with this newspaper: "Children need to get out of the comfort zone and consult more local students. Parents can also make good use of community resources and communicate with other immigrant parents who have experienced difficult stages instead of resting on their laurels."

　　At the same time, home and school also need to better cooperate, psychologically appease their children, and more effectively prevent students who want to skip classes and work from drilling loopholes in the system.

　　In an interview with the World Journal, Zhao Hongfang said that parents can take the initiative to provide contact information to the school and learn to check attendance records and grades online. If parents leave their children completely unattended, the school can report it and ask the Children’s Service Administration to intervene in the investigation.

　　On the other hand, the society can also make efforts in promoting the children of Chinese new immigrants to study.

　　"In a short time, it is still a luxury to solve the problem of young Chinese immigrants going to school." Lawyer Sun Lantao said that despite this, from the legislative point of view, with the increasing proportion of Chinese in politics, this phenomenon will attract the attention of political circles, and the education department will also strengthen investment in this group and training bilingual teachers. With the increase of corresponding educational resources and infrastructure, the current situation may gradually change.

　　Central Meteorological Observatory (in China)At 18: 00 on October 2,continueIssue a cold wave blue warning:Affected by strong cold air, it is estimated that the temperature will generally drop by 8 ~ 12℃ in most parts of central and eastern China from 20: 00 on October 2 to 20: 00 on October 6, and the temperature will drop by 12 ~ 16℃ in central and eastern Inner Mongolia, northeast China, most of Shaanxi, southwestern Shanxi, Huanghuai, Jianghuai, northern Hunan, northwestern Jiangxi, southern Anhui, southern Jiangsu and northern Zhejiang, among which, central Inner Mongolia and southeastern Heilongjiang. On the morning of 6th to 7th, the lowest temperature 0℃ line will be located in the northern part of North China and the central part of Northeast China, and the lowest temperature 10℃ line will be located in the northeastern part of Sichuan, the central part of Hubei, the southern part of Henan and the southern part of Shandong. There will be 4~6 winds in the Yangtze River basin and its north, and gusts in high altitude areas and rivers and lakes can reach 7~8. There will be 7-8 strong winds and 9-10 gusts in the northern and eastern seas of China.

Defense guide：

1, personnel should pay attention to add clothes to keep warm; In production, be prepared for the defense against strong winds and cool weather;

2, doors and windows, hoardings, scaffolding, temporary structures and other structures that are easily blown by strong winds are fastened, and outdoor items that are easily affected by strong winds are properly placed;

3. Take shelter from the wind in sheltered places and notify outdoor workers to pay attention to safety;

4, pay attention to the latest information about the media reports of gale cooling, so as to take further measures;

5, transportation, public security and other departments should do a good job in preparing for road icing in accordance with their duties.

China Fund News reporter Yishan

On July 12th, Zotye Automobile, which has recorded 8 days and 5 boards, was exposed to double negative, which not only officially announced the termination of the 6 billion yuan fixed-income project, but also revealed that the company’s net profit in the first half of the year was expected to be negative.

According to the previous announcement, Zotye Automobile plans to issue no more than 1.521 billion shares (including the number) to specific targets, and raise no more than 6 billion yuan (including the number). The raised funds will be used for new energy intelligent networked automobile development and R&D capacity improvement projects, channel construction projects and supplementary liquidity.

As for the reason for the termination, Zotye Automobile said that it was a decision made after comprehensive consideration of the changes in the external market environment, the actual situation of the company, the controlling shareholder and the actual controller planning to change the actual controller of the company, and full communication with relevant parties such as intermediaries.

8 days and 5 boards! Since July, the share price has risen by over 52%.

On July 12, Zotye Automobile announced the abnormal fluctuation of stock trading. On July 11 and July 12, the deviation of the closing price of the company’s stock for two consecutive trading days was more than 20%, which was an abnormal fluctuation of stock trading according to the relevant regulations of Shenzhen Stock Exchange.

In fact, since July, Zotye Auto’s share price has risen sharply. As of the close of July 12, Zotye Auto reported 3.75 yuan per share, an increase of 9.97%. In the past eight trading days, it has recorded five daily limit boards, with an interval increase of over 52%. Once again, it has become the strongest "monster stock" in the recent new energy automobile sector.

In this abnormal fluctuation announcement, Zotye Automobile disclosed the relevant situation that the company paid attention to and verified.

First of all, after verification, the company found no need to correct or supplement the information disclosed in the previous period; No major undisclosed information that may or has had a great impact on the company’s stock trading price has been reported by the public media recently; Recently, the company’s operation is normal, and the internal and external operating environment has not changed significantly.

Secondly, Zotye Automobile said that the controlling shareholder and actual controller of the company are planning to change the actual controller of the company, and there are still uncertainties about when the planning to change the actual controller will be completed and whether it can be completed in the end. It is understood that at the end of May this year, Huang Jihong, the "white knight" who pulled the company back from the brink of bankruptcy, resigned as chairman for personal reasons. At the end of June, Zotye Automobile announced that the actual controller of the company may change.

Finally, it was in this announcement that Zotye Motor suddenly announced the termination of the 6 billion fixed-income fundraising.

The 6 billion fixed-income project suddenly ended.

According to the announcement previously issued by Zotye Automobile, the company plans to issue no more than 1.521 billion shares (including the number) to specific targets, and raise no more than 6 billion yuan (including the number). The raised funds will be used for the development of new energy intelligent networked vehicles and R&D capacity improvement projects, channel construction projects and supplementary liquidity.

On March 15th, Shenzhen Stock Exchange issued an inquiry letter, pointing out that the net assets attributable to the parent company at the end of the latest period were 3.025 billion yuan, and the total amount of funds raised this time was nearly twice that of the company at the end of the latest period. In addition, Zotye Auto is also required to explain the specific process of the new energy vehicle development project from research and development to official listing, and whether the company has the ability to develop new energy vehicles.

On May 9, the Shenzhen Stock Exchange issued a second round of inquiry letter, but since May 17, Zotye Automobile has disclosed nine delayed reply announcements. In the announcement on July 11, the company said that it would disclose the reply to the second round of audit inquiry letter before July 18.

However, at the fourth interim meeting of the Eighth Board of Directors in 2023, the Board of Directors of Zotye Automobile unanimously reviewed and approved the Proposal on the Company’s Termination of Issuance of A Shares to Specific Objects and Withdrawal of Application Documents. Decided to terminate the issue of A shares to specific targets in 2022, and applied to Shenzhen Stock Exchange to withdraw the application documents.

Regarding the reasons for the termination, Zotye Automobile said that since the company disclosed the plan to issue shares to specific targets, the company and relevant intermediaries have actively promoted related work. After comprehensively considering the changes in the external market environment, the actual situation of the company, the controlling shareholder and the actual controller planning to change the actual controller of the company and other factors, and after fully communicating with relevant parties such as intermediaries, the company decided to terminate the issue of shares to specific targets and withdraw the relevant application documents.

The risk of liquidity shortage remains.

After bankruptcy and reorganization, Zotye Auto successfully took off its hat in November last year, but it is not optimistic in terms of operating performance and asset status.

According to the financial report data, the company’s revenue declined year by year from 2018 to 2022. In 2018, the company’s revenue was still 14.764 billion yuan. By 2022, the company’s revenue was only 783 million yuan, and the company’s revenue shrank by over 94% in four years. In terms of net profit, the company has been losing money since 2019. Although the loss has narrowed, the net loss of the company has exceeded 23.6 billion yuan in the past four years. At the same time, Zotye Auto also revealed in the latest announcement that although the specific figures have not yet been counted, the company initially expects the net profit for the first half of 2023 to be negative.

By the end of 2022, the company’s net assets returned to its mother were 2.437 billion yuan, its total liabilities exceeded 4.6 billion yuan, and its ending cash balance was 116 million yuan. According to the company’s announcement, as of the end of the first quarter of this year, the company’s monetary funds were 922 million yuan, including 867 million yuan of restricted funds, and only 55.1074 million yuan of freely usable funds remained. This is obviously a drop in the bucket for a manufacturer with vehicle production qualification and Zotye Automobile, which will invest a lot of money in vehicle production and manufacturing in the future.

Zotye Auto also bluntly stated in the previous announcement that if the company’s external financing channels are not smooth, or the accounts receivable cannot be recovered on schedule or cannot be recovered, or the supplier fails to restore a reasonable credit period to the company for a long time, the company may face the risk of liquidity shortage, which will adversely affect the normal operation of the company.

In fact, due to the lack of liquidity, Zotye Automobile’s vehicle manufacturing almost came to a standstill in 2020 and 2021. In recent years, the company’s revenue mainly came from the sales of auto parts and door industry. Although the company has announced that it will gradually resume the whole vehicle business in 2022, and has completed the remodeling of core functional departments such as production, sales and research and development, it is not easy for Zotye to transform its new energy vehicles in the new energy vehicle market where the competition among new car-making forces such as Ideal, Weilai and Tucki is becoming increasingly fierce. In addition, as a vehicle manufacturer with an annual sales volume of more than 300,000 vehicles, Zotye Automobile sold only 502 vehicles in 2022.

In the previous increase specification, Zotye Automobile revealed that it will invest 5.037 billion yuan in the new energy intelligent networked vehicle development and research and development capability improvement project, including three parts: new energy intelligent networked vehicle development, common technology research and development and R&D center construction; In addition, 533 million yuan will be invested in channel construction projects. The company plans to build 216 self-operated stores in 100 cities including Beijing, Shanghai and Guangzhou in advance, covering major target markets and helping the company to quickly introduce new energy automobile products into the terminal consumer market.

According to the plan, if the above-mentioned 6 billion yuan fixed-income project finally lands, Zotye Automobile may be able to do a big job in the field of new energy vehicles. But now with the withdrawal of the fixed-income plan, where is the money for the company to build a car? Still a problem.

However, in the latest announcement, Zotye Automobile emphasized that all production and business activities of the company are proceeding normally at present, and the decision to terminate the fixed increase and withdraw the relevant application documents was made through full communication and careful analysis by the company’s management, intermediaries and other relevant parties. It will not have a significant adverse impact on the normal operation and sustained and stable development of the company, and there is no harm to the interests of the company and all shareholders, especially minority shareholders.

Wind data shows that as of July 10th, the total number of shareholders of Zotye Automobile reached 183,000, an increase of 34.56% compared with June 30th.

Editor: Huang Mei

Audit: Muyu

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Authorized Reprinting Cooperation Contact: Yu Xiansheng (Tel: 0755-82468670)

Original title: "Billion car companies suddenly announced: termination! 》

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　　[Learning on the Road] In the first seven months of this year, General Secretary of the Supreme Leader visited and investigated six provinces, covering Chongqing, Jiangxi, Anhui, Heilongjiang, Ningxia and Hebei. In Fengyang, Anhui, when the General Secretary presided over the symposium on rural reform, he emphasized that China must strengthen agriculture, China must be beautiful in rural areas, and China must be rich in farmers. In Guyuan, Ningxia, the General Secretary said with deep affection that the Red Army’s Long March led by our party has written a heroic epic full of lofty sentiments. The new Long March to promote the cause of Socialism with Chinese characteristics should be carried out continuously and for a long time, and every generation of us should take our own long March.

　　On the way to study, I specially combed 12 sentences investigated by the Supreme Leader General Secretary outside Beijing in July this year for readers to read.

　　Chongqing investigation

　　From January 4th to 6th, the Supreme Leader made an investigation in Chongqing. On the afternoon of January 4th, the Supreme Leader had a cordial conversation with the field workers in Orchard Port, Liangjiang New Area, Chongqing. Xinhua News Agency reporter Li Tao photo

　　1. Advocating innovation, paying attention to coordination, advocating green, open planting and promoting sharing.

　　The Supreme Leader pointed out that the development concept of innovation, coordination, green, openness and sharing put forward by the Fifth Plenary Session of the 18th CPC Central Committee is a prescription for China’s economic development to enter a new normal and the world economic recovery to be sluggish. The new development concept is baton, which should be resolutely implemented. The understanding of inadaptability, inappropriateness or even violation of the new development concept should be adjusted immediately, and the behaviors that are unsuitable, unsuitable or even contrary to the new development concept should be resolutely corrected, and the practices that are unsuitable, unsuitable or even contrary to the new development concept should be completely abandoned. At the same time, the five development concepts are an inseparable whole, which are interrelated, interconnected and mutually promoted. They must be adhered to and implemented as a whole, and they cannot be neglected or replaced.

　　2. The success or failure of poverty alleviation and development depends on precision. We must identify the "poor roots" and stick to maturity and pick one.

　　The supreme leader pointed out that the success or failure of poverty alleviation and development depends on precision, and it is necessary to identify the "poor roots", clearly target, tailor-made, and prescribe the right medicine, and truly help the point and help the roots. To get rid of poverty, we should stick to maturity and pick one at a time, which will not only prevent us from not making progress, waiting for what we need, but also prevent us from overextending ourselves and seeking false reputation.

　　Jiangxi investigation

　　From February 1 to 3, the Supreme Leader came to Jiangxi to visit and express condolences to the broad masses of cadres and the troops stationed in Jiangxi. On February 2nd, the Supreme Leader paid a New Year greeting to the villagers in Shenshan Village, Mao Ping Township, Jinggangshan City, wishing them a happy life and a lucky Year of the Monkey. Xinhua News Agency reporter Xie Huanchi photo

　　3. In our country, the people are masters of their own affairs, and all leading cadres are people’s servants.

　　In the poor household Zhang Chengde’s home, the supreme leader visited room by room, sat down with the couple to calculate the income and expenses, and asked what was planted and raised at home, and what difficulties and needs were there. The fellow villagers served steaming rice fruit and asked the general secretary to taste it. The hostess said that the general secretary has done a good job for the people of the whole country and the people feel very happy. The supreme leader responded that our country is the people who are the masters of the country, and all leading cadres, including me, are people’s servants.

　　4. Proceed from reality, concentrate on the construction of inclusive, basic and comprehensive people’s livelihood.

　　The supreme leader pointed out that there is no end to safeguarding and improving people’s livelihood, only a continuous new starting point, and measures with stronger pertinence, wider coverage, more direct effect and more obvious effect should be taken to really help the masses solve problems, increase their welfare and let them enjoy fairness. We should proceed from reality, concentrate our efforts on building an inclusive, basic and comprehensive livelihood, continuously improve the co-construction capacity and sharing level of public services, weave a "safety net" for people’s livelihood, eliminate hidden dangers, and ensure that the people live and work in peace and contentment and the social order is stable and orderly.

　　Anhui investigation

　　From April 24th to 27th, the Supreme Leader made an investigation in Anhui. This is the afternoon of April 24, when the Supreme Leader learned about poverty alleviation from the villagers in Dawan Village, Huashi Township, Jinzhai County, Lu ‘an City. Xinhua News Agency reporter Li Xueren photo

　　5. To deepen reform in an all-round way, it is essential to stimulate motivation and let the people have a sense of gain.

　　The supreme leader stressed that the new round of reform is characterized by more hard bones, more tough battles and more cheese. To deepen the reform in an all-round way, we must first cut the blade inward and dare to make self-revolution. The key point is to break the word and face difficulties. We must fundamentally stimulate motivation and let the people have a sense of gain. Party committees and governments at all levels, as well as leading cadres at all levels, should put themselves into thinking, discussing and grasping reform, and strive to be the pioneers of reform. List reform topics and set reform measures, closely meet the needs of the masses, listen carefully to their opinions, and let the people make contributions and gain more benefits in the reform.

　　6. China must be strong in agriculture, China must be beautiful in rural areas, and China must be rich in farmers.

　　The Supreme Leader emphasized that China must be strong in agriculture, China must be beautiful in rural areas, and China must be rich in farmers. We must persist in taking solving the "three rural issues" as the top priority of the whole party’s work, intensify rural reform under the new situation, strengthen urban and rural planning, fully implement the policy of strengthening agriculture, benefiting farmers and enriching farmers, and promote a solid agricultural foundation, rural harmony and stability, and farmers live and work in peace and contentment.

　　Heilongjiang investigation

　　From May 23rd to 25th, the Supreme Leader made an investigation in Heilongjiang. On the afternoon of May 23rd, the Supreme Leader had a cordial conversation with his family and neighbors at the home of Liu Yangshun (fifth from left), an employee of Xishui Management Office of Shangganling Forestry Bureau in Yichun. Xinhua News Agency reporter Li Tao photo

　　7, food security is an important foundation of national security, protect farmers’ enthusiasm for growing grain.

　　The supreme leader pointed out that farmers’ professional cooperatives are an effective organizational form to drive farmers to increase their income and develop modern agriculture. It is necessary to sum up and popularize advanced experience and further run the cooperatives. The Supreme Leader stressed that food security is an important foundation of national security, and it is necessary to innovate the grain production and operation mode, optimize production technical measures, implement various support policies, protect farmers’ enthusiasm for growing grain, and strive to improve the efficiency of grain production.

　　8. Changing the mode and adjusting the structure is hard work, not hard work.

　　The supreme leader pointed out that at present, China’s economic development is at a critical juncture of changing the mode and adjusting the structure, which is not only a critical period for climbing over the ridge, but also a window period for making great achievements. Only by making a concerted effort to promote the supply-side structural reform in a down-to-earth manner can China’s industrial structure level and social productivity level make a big leap. If you look around in policy and dabble in work, you will delay the opportunity. Changing the mode and adjusting the structure is hard work, not hard work. We must turn policies into actions and make every effort to fight a tough battle.

　　Ningxia investigation

　　From July 18th to 20th, the Supreme Leader made an investigation in Ningxia. On the afternoon of July 18th, the Supreme Leader had a cordial conversation with his family and villagers’ representatives at Mark Jun’s home in Yangling Village, Dawan Township, Jingyuan County, Guyuan City. Xinhua News Agency reporter Li Tao photo

　　9. Every generation of us should take our own long March.

　　The Supreme Leader said with deep affection that the Long March of the Red Army led by our Party wrote a heroic epic full of lofty sentiments. The great Long March spirit is a vivid reflection of the Communist Party of China (CPC) people’s revolutionary style, and we should continue to combine the new reality to inherit and carry forward it. The new Long March to promote the cause of Socialism with Chinese characteristics should be carried out continuously and for a long time, and every generation of us should take our own long March.

　　10. We should adhere to the principle that time is subordinate to quality, scientifically determine the time to get rid of poverty, and do not make layers of overweight.

　　The Supreme Leader pointed out that poverty alleviation and development have reached the stage of conquering the last bastion, and most of them are poor in poverty and trapped in poverty, which requires greater determination, clearer thinking and more precise measures. We must adhere to the principle that time is subordinate to quality, scientifically determine the time to get rid of poverty, and do not engage in layers of overweight. We must really help the poor, help the poor, and get rid of poverty.

　　Hebei investigation

　　On July 28th, the Supreme Leader visited Tangshan City, Hebei Province. This is the supreme leader visiting paraplegic patients in the activity room of Tangshan paraplegic sanatorium and enjoying the erhu accompaniment "Singing a Folk Song for the Party". Xinhua News Agency reporter Xie Huanchi photo

　　11, improve the national awareness of disaster prevention and relief, and comprehensively improve the national comprehensive disaster prevention, mitigation and relief capabilities.

　　The supreme leader emphasized that fighting against natural disasters is an eternal topic for human survival and development. We should handle the relationship between good people and nature more consciously, correctly handle the relationship between disaster prevention, mitigation and relief and economic and social development, constantly sum up experience from the practice of resisting various natural disasters, implement responsibilities, improve the system, integrate resources and make overall efforts, improve the national awareness of disaster prevention and relief, and comprehensively improve the country’s comprehensive disaster prevention, mitigation and relief capabilities. The Supreme Leader emphasized that disaster prevention, mitigation and relief are related to the safety of people’s lives and property, social harmony and stability, and an important aspect of measuring the leadership of the ruling party, testing the government’s execution, judging the national mobilization and embodying national cohesion.

　　12. Let the party’s flag fly high in the minds of the community.

　　The supreme leader pointed out that the community is the "last mile" for the party and the government to contact and serve the residents. It is necessary to improve the community management and service system, integrate various resources, and enhance the public service capacity of the community. Community work should always carry out the Party’s purpose everywhere, let the Party’s banner fly high in the minds of the community masses, and let the party member in the community give full play to its role in serving the masses and show a good image.

　 　 Last year, many people were reminded of their own memories by this film, and they remembered their imperfect youth, but now they seem to feel better.

　 　　On March 10th, another film was released in the memory of campus times — — One day we will fly.

　 　 The slogan on the poster is "You say your dreams are grandiose, I say you are old". From this sentence, we can also see that it is not a twin sister with My Girlhood.

　 　 The original name of the film is "The Root of Love", which originated from this song by Alan Tam. Listen, the feeling it conveys is actually quite similar to this film.

　 　 Female No.1 is Yu Fengzhi, played by Miriam Yeung. She is in her thirties and is an ordinary employee of a travel agency.

　 　 Her husband is Peng Shenghua (Lin Haifeng), a classmate in high school. He is an interior designer who tries his best to cater to customers every day.

　 　 The dull and busy life has made the communication between husband and wife less and less. Not only did the last trip together take place five years ago, but Peng Shenghua, who was busy with work, spent less and less time at home, and even a mistress seemed to appear in this family.

　 　　It is in this kind of life that when the husband and wife attended the reunion of high school classmates, Yu Fengzhi heard the name of "Su Bowen", a close friend of her and Peng Shenghua, and an indelible part of her memories of youth.

　 　 At that time, Yu Fengzhi, a girl, and Su Bowen and Peng Shenghua, teenagers, had the best high school years and shared their secrets and dreams together.

　 　 Peng Shenghua is enthusiastic and outgoing, good at making, nicknamed "Handmade King". He liked Yu Fengzhi from the beginning, and he can also make a whole set of paper-bound rose gardens.

　 　 Su Bowen, who is taciturn, loves flying and is good at physics. He often skips classes to study water rockets and mechanical planes. In fact, he has always had a crush on Yu Fengzhi. His dream is to be an airplane pilot and fly her to the world.

　 　 So, Yu Fengzhi, who wanted to fly in those days but was trapped now, remembered the teenager who dreamed of flying with her at the beginning, and the future and ideal they talked about when they were together.

　 　 In this way, she began to look for where Su Bowen is now and whether he has realized his dream.

　 　 We won’t spoil the next process and ending.

　 　 It’s also a film recalling my lush years. Do you think it is similar to My Girlhood?

　 　 In fact, they do have many similarities. For example, the heroine’s life is dull and trivial now, which is far from her dream. Yu Fengzhi is like this, and Lin Zhenxin is the same.

　 　 They can do "out of line" things when they are young, and they all believe that they will be very different. Yu Fengzhi refused the support of his father who abandoned his family. When he was a student, Lin Zhenxin once stood in front of the teachers and students of the whole school and talked to the director about the rights of his classmates.

　 　 Because they all had the purest feelings at that time, they let the mediocre life have flashing memories to rely on.

　 　 But after that, they all got irreparable regret for losing someone.

　 　 In the process of pursuing the past, Yu Fengzhi recovered her childhood dream, and Lin Zhenxin also decided to change herself now.

　 　 To sum up, although the two films have different times and backgrounds, the protagonist’s situation is also different. "Which day will we fly" is aimed at the middle-aged crisis, and "My girlhood" also focuses on the memory of the first love. However, both Hong Kong’s Yu Fengzhi and Taiwan Province’s Lin Zhenxin rediscover their original heart and discover their original self through recalling the past.

　 　 When it comes to reminiscing about youth, we have to mention the girl we chased together in those years.

　 　 In fact, it’s not just Ke Jingteng. Everyone had a special "Shen Jiayi" when he was a student.

　 　 Sometimes she turns against you, sometimes she says you are wrong, and sometimes you find that she actually cares about you the most.

　 　 You think you will always be together like this, that the world will always be simple.

　 　 But one day, many years later, she finally got married, and the groom was not you. At this time, you might "put on a handsome suit" like Ke Jingteng and watch her become someone else’s bride.

　 　 "Growing up" may mean knowing that some things have passed is the past, and then indulging in them and clinging to them can only show that I am now a very failure.

　 　 All the films of "recalling youth" that successfully resonate with the audience are also the ones in which the protagonists gradually find their lost enthusiasm, confidence and hope for life in the process of reappearing in the past years.

　 　 Just like the hot Korean film Sunshine Sisters Amoy in 2011.

　 　 Nami, who is now a housewife, has a boring life. She recalls the "Sunny" group of seven in those years. During the search and visit of her old friends in those years, Nami remembered the past when several people went to school.

　 　 Not only that, when she reached middle age, she was relieved in such a journey, and even comforted herself face to face.

　 　 In the end, Nami found the happiness of life again in the face of the entrustment of his old friend after his death.

　 　 This is the case with My Girlhood, and so is The One Day We Will Fly, which was just released today.

　 　 Recalling youth is not to indulge in it, but to regain the ability to be happy and hope for life.

　 　 So, do you remember which youth film gave you this feeling?

　　Guangming Daily, Beijing, November 2 (Reporter Yang Shu) A critical developmental period of mammalian fertilized eggs after implantation in uterus is called "gastrula movement". On October 31st, 2019, the international journal Science published a research achievement from China Academy of Sciences online. The research team successfully reproduced the development process of primordial movement of primate embryos for the first time by culturing cynomolgus monkey embryos in vitro.

　　The research results were jointly completed by Institute of Zoology, Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, and Innovation Institute of Stem Cell and Regenerative Medicine, China Academy of Sciences. Many scientists have commented that uncovering the mystery of this critical stage will provide important data for human beings to deeply understand embryo development and optimize assisted reproductive technology.

　　Wang Hongmei, a researcher at the Institute of Zoology, Chinese Academy of Sciences, said that gastrula movement is one of the most important stages in the early development of animal embryos, and abnormality in this process can easily lead to pregnancy failure or organ development defects, and human women of childbearing age often have a risk of spontaneous abortion of 20% ~ 30% at this stage, so gastrula movement has high research value. However, the gastrula movement occurs after the embryo is implanted in the uterus. Due to technical and ethical restrictions, scientists are "invisible and intangible" about this development stage of primate embryos.

　　This time, the research team selected a primate close to human beings — — Crab-eating monkeys as the research object. By establishing a mature embryo culture system in vitro, the researchers successfully cultured the cynomolgus monkey embryos to 20 days after fertilization, thus highly reproducing the development process of embryo gastrulation, and proving for the first time that primate embryos can develop to gastrulation in vitro without maternal support. At the same time, researchers have also obtained the gene expression characteristics of amniotic cells during the early embryonic development of primates, and redefined various cell types of early embryos of primates.

　　Qiao Jie, an academician of China Academy of Engineering, said: "Monkeys are considered as reliable animal models for studying human physiology and pathology. This achievement will greatly improve our understanding of primate and human early embryonic development, especially for the discussion of the causes of adverse pregnancy and fetal malformation."

　　Sha Jiahao, a professor at the State Key Laboratory of Reproductive Medicine of Nanjing Medical University, said that this achievement is an important basic breakthrough in the field of biology, which not only fills the theoretical gap in the mechanism of embryo development in higher animals, but also provides basic theoretical guidance and develops new treatment methods for clinical treatment of infertility and prevention of birth defects. In addition, it is also of great significance to the research of regenerative medicine and will promote the development of human reproductive medicine.

　Today, King of Barbecue released a preview and poster, and the film will be launched on November 12th. The film is directed by Cui Zhijia, co-directed by Zi Wang and starring Cui Zhijia, Sun Yue, Lao Si, Zhang Qi and Guo Xiangpeng. The film vividly depicts that Li Yanxi, a humble migrant worker, was forced to switch to a barbecue shop, presenting the audience with a unique barbecue culture and wine table culture in Northeast China.

Cui Zhijia Sun Yue HappyAssemble,barbecuelarge-scale warbe poised for

In today’s preview, Li Yanxi, played by Cui Zhijia, returned to the company as soon as possible in order to alleviate the contradiction between Zheng Yan and his son, and tried his best to interfere with Zheng Neng’s barbecue restaurant. After frequent failures, he decided to compete fairly, so he and his partner triggered a barbecue war in a series of fancy operations. The bold character of the Northeastern people is perfectly presented in the joyful and funny atmosphere, and the humorous lines with a strong Northeast accent are also in stitches. The overall point of view and laughter are both wonderful.

The fixed poster exposed together with the notice is also very eye-catching. The poster mainly adopts two colors of red and yellow, which is very pyrotechnic with warm lighting. Cui Zhijia at the barbecue table laughed heartily with kebabs in his hand, and the objects in the hands of the other four people also conveyed a lot of information. The dazzling "big gold chain" on Old Four’s body, the barbecue held high by He Yutong, the beer in Sun Yue’s hand and the banner of "Opening for Business" in Zhang Qi’s hand fully showed the lively atmosphere and strong northeast atmosphere of the barbecue shop, and it was really expected that the title of "King of Barbecue" would fall.

The best taste in the world is barbecue, and some people have feelings and stories.

Some people say that if the barbecue has an ID card, then its household registration must be in the northeast, which shows that the status of the northeast in the barbecue industry is really unshakable. "King of Barbecue" takes barbecue as the carrier, and tells the story of Li Yanxi, who accidentally became the owner of barbecue shop, who fought fiercely with her competitor Zheng Neng to become the king of barbecue. In the competition between the two barbecue shops, the fancy "marketing" of Li Yanxie and Zheng Energy shows a strong human fireworks and authentic comedy culture in Northeast China.

Not only that, but there is also a warm core hidden under the humorous shell of the film. Behind Zheng Yanpai’s employee Li Yanxie’s ruining his father’s barbecue shop is his rare filial piety, and his father’s hard persistence is because the barbecue shop carries the memories of him and his son, and Li Yanxie also gains the understanding and support of his close comrades-in-arms and his wife in the process. Can Zheng Yanxie and his son, who lack communication, be reconciled with Li Yanxie’s help? The answer has yet to be revealed by the audience themselves after the film is released. The King of Barbecue, by depicting three main emotional lines, shows the delicate and warm side of the generous and humorous character of the Northeast people, making people feel the deep warmth in the film while enjoying the joy.

Comedians are United, and high-energy laughter never stops.

Through a small barbecue, the film shows people the barbecue culture and wine table culture with Northeast characteristics, and the stories of laughter and tears also let people know the positive and optimistic attitude and warm and generous personality of the Northeast people.