With the progress and development of society and the continuous advancement of curriculum standard reform,society has higher requirements for students’English skills.The junior high school stage is the best time to c...With the progress and development of society and the continuous advancement of curriculum standard reform,society has higher requirements for students’English skills.The junior high school stage is the best time to cultivate students’communication skills,however,junior high school English classes are currently still based on traditional teaching as the main teaching method,which only focuses on cultivating students’reading and writing skills,thus neglecting the training of listening and speaking skills.Despite its evident benefits,the implementation of the task-based language teaching(TBLT)method in junior high school English communication classes is not without challenges.The current state of these classes reveals a significant gap in the integration of communicative tasks into the teaching process.This gap stems from a variety of factors,including the lack of appropriate resources,insufficient teacher training,and the deeply ingrained reliance on traditional teaching methods.This study will briefly explain the definition and characteristics of the task-based language teaching method,analyze the current situation of junior high school English communication classes,the difficulties of using TBLT in junior high school English classrooms,and the application methods of task-based teaching methods.The teaching method makes up for the shortcomings of English communication classes in junior high schools and improves the quality of teaching.展开更多
Perfluorooctanoic acid(PFOA)is a novel type of persistent synthetic organic pollutant,and its exposure on pregnant women can cause some adverse effects,such as pregnancy-induced hypertension,gestational diabetes melli...Perfluorooctanoic acid(PFOA)is a novel type of persistent synthetic organic pollutant,and its exposure on pregnant women can cause some adverse effects,such as pregnancy-induced hypertension,gestational diabetes mellitus,and preeclampsia.Therefore,understanding the metabolic changes caused by PFOA exposure is of great significance to protect pregnant women from its adverse effects.In this study,the metabolomes from the urine samples of pregnant women exposure to PFOA at different degrees were analyzed by GC-MS and LC-MS.The samples in different groups were distinguished and the differential metabolites were screened based on the VIP value,FC,and P-value of each comparison group through multivariate statistical analysis.The pathways related to differential metabolites were searched to reveal the effects of PFOA exposure on metabolic changes in pregnant women at different degrees.Finally,the ROC of differential metabolites was performed,and the differential metabolites with large area under the curve(AUC)values were selected and compared to identify the mutually differential metabolites.Meanwhile,these metabolites were fitted with a multivariable to explore if they could be used to distinguish different groups.The quantitative comparison of mutually differential metabolites revealed that the levels of L-cysteine,glycine,and 5-aminovaleric acid were positively correlated with the degree of PFOA exposure,indicating that different degrees of PFOA exposure could affect the synthesis or degradation of GSH and change the metabolism of oral or intestinal microbiota.Additionally,they may cause oxidative stress and abnormal fat metabolism in pregnant women.展开更多
New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) appear rapidly every few months.They have showed powerful adaptive ability to circumvent the immune system. To further understand SARS-CoV-2...New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) appear rapidly every few months.They have showed powerful adaptive ability to circumvent the immune system. To further understand SARS-CoV-2’s adaptability so as to seek for strategies to mitigate the emergence of new variants, herein we investigated the viral adaptation in the presence of broadly neutralizing antibodies and their combinations. First, we selected four broadly neutralizing antibodies, including pan-sarbecovirus and pan-betacoronavirus neutralizing antibodies that recognize distinct conserved regions on receptor-binding domain(RBD) or conserved stem-helix region on S2 subunit.Through binding competition analysis, we demonstrated that they were capable of simultaneously binding.Thereafter, a replication-competent vesicular stomatitis virus pseudotyped with SARS-CoV-2 spike protein was employed to study the viral adaptation. Twenty consecutive passages of the virus under the selective pressure of individual antibodies or their combinations were performed. It was found that it was not hard for the virus to adapt to broadly neutralizing antibodies, even for pan-sarbecovirus and pan-betacoronavirus antibodies. The virus was more and more difficult to escape the combinations of two/three/four antibodies. In addition, mutations in the viral population revealed by high-throughput sequencing showed that under the selective pressure of three/four combinational antibodies, viral mutations were not prone to present in the highly conserved region across betacoronaviruses(stem-helix region), while this was not true under the selective pressure of single/two antibodies.Importantly, combining neutralizing antibodies targeting RBD conserved regions and stem helix synergistically prevented the emergence of escape mutations. These studies will guide future vaccine and therapeutic development efforts and provide a rationale for the design of RBD-stem helix tandem vaccine, which may help to impede the generation of novel variants.展开更多
文摘With the progress and development of society and the continuous advancement of curriculum standard reform,society has higher requirements for students’English skills.The junior high school stage is the best time to cultivate students’communication skills,however,junior high school English classes are currently still based on traditional teaching as the main teaching method,which only focuses on cultivating students’reading and writing skills,thus neglecting the training of listening and speaking skills.Despite its evident benefits,the implementation of the task-based language teaching(TBLT)method in junior high school English communication classes is not without challenges.The current state of these classes reveals a significant gap in the integration of communicative tasks into the teaching process.This gap stems from a variety of factors,including the lack of appropriate resources,insufficient teacher training,and the deeply ingrained reliance on traditional teaching methods.This study will briefly explain the definition and characteristics of the task-based language teaching method,analyze the current situation of junior high school English communication classes,the difficulties of using TBLT in junior high school English classrooms,and the application methods of task-based teaching methods.The teaching method makes up for the shortcomings of English communication classes in junior high schools and improves the quality of teaching.
基金the National Natural Science Foundation of China(Nos.81874307 and 21874088)the Shanghai Science and Technology Commission Scientific Research Project(Nos.19142203100,20142200400,18490731500,and 19DZ2202200)the National Facility for Translational Medicine,Shanghai(No.TMSK-2020-131).
文摘Perfluorooctanoic acid(PFOA)is a novel type of persistent synthetic organic pollutant,and its exposure on pregnant women can cause some adverse effects,such as pregnancy-induced hypertension,gestational diabetes mellitus,and preeclampsia.Therefore,understanding the metabolic changes caused by PFOA exposure is of great significance to protect pregnant women from its adverse effects.In this study,the metabolomes from the urine samples of pregnant women exposure to PFOA at different degrees were analyzed by GC-MS and LC-MS.The samples in different groups were distinguished and the differential metabolites were screened based on the VIP value,FC,and P-value of each comparison group through multivariate statistical analysis.The pathways related to differential metabolites were searched to reveal the effects of PFOA exposure on metabolic changes in pregnant women at different degrees.Finally,the ROC of differential metabolites was performed,and the differential metabolites with large area under the curve(AUC)values were selected and compared to identify the mutually differential metabolites.Meanwhile,these metabolites were fitted with a multivariable to explore if they could be used to distinguish different groups.The quantitative comparison of mutually differential metabolites revealed that the levels of L-cysteine,glycine,and 5-aminovaleric acid were positively correlated with the degree of PFOA exposure,indicating that different degrees of PFOA exposure could affect the synthesis or degradation of GSH and change the metabolism of oral or intestinal microbiota.Additionally,they may cause oxidative stress and abnormal fat metabolism in pregnant women.
基金funded by the National Natural Science Foundation of China(81773621,82073751 to J.Z.)the National Science and Technology Major Project“Key New Drug Creation and Manufacturing Program”of China(No.2019ZX09732001-019 to J.Z.)+1 种基金the Key R&D Supporting Program(Special Support for Developing Medicine for Infectious Diseases)from the Administration of Chinese and Singapore Tianjin Eco-city to Jecho Biopharmaceuticals Ltd.Co.the Shanghai Jiao Tong University“Crossing Medical and Engineering”grant(20X190020003 to J.Z.)
文摘New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) appear rapidly every few months.They have showed powerful adaptive ability to circumvent the immune system. To further understand SARS-CoV-2’s adaptability so as to seek for strategies to mitigate the emergence of new variants, herein we investigated the viral adaptation in the presence of broadly neutralizing antibodies and their combinations. First, we selected four broadly neutralizing antibodies, including pan-sarbecovirus and pan-betacoronavirus neutralizing antibodies that recognize distinct conserved regions on receptor-binding domain(RBD) or conserved stem-helix region on S2 subunit.Through binding competition analysis, we demonstrated that they were capable of simultaneously binding.Thereafter, a replication-competent vesicular stomatitis virus pseudotyped with SARS-CoV-2 spike protein was employed to study the viral adaptation. Twenty consecutive passages of the virus under the selective pressure of individual antibodies or their combinations were performed. It was found that it was not hard for the virus to adapt to broadly neutralizing antibodies, even for pan-sarbecovirus and pan-betacoronavirus antibodies. The virus was more and more difficult to escape the combinations of two/three/four antibodies. In addition, mutations in the viral population revealed by high-throughput sequencing showed that under the selective pressure of three/four combinational antibodies, viral mutations were not prone to present in the highly conserved region across betacoronaviruses(stem-helix region), while this was not true under the selective pressure of single/two antibodies.Importantly, combining neutralizing antibodies targeting RBD conserved regions and stem helix synergistically prevented the emergence of escape mutations. These studies will guide future vaccine and therapeutic development efforts and provide a rationale for the design of RBD-stem helix tandem vaccine, which may help to impede the generation of novel variants.
