Rapamycin, similar to FKS06, can promote neural regeneration in vitro. We assumed that the mechanisms of action of rapamycin and FK506 in promoting peripheral nerve regeneration were similar. This study compared the e...Rapamycin, similar to FKS06, can promote neural regeneration in vitro. We assumed that the mechanisms of action of rapamycin and FK506 in promoting peripheral nerve regeneration were similar. This study compared the effects of different concentrations of raparnycin and FK506 on Sc hwann cells and investigated effects and mechanisms of rapamycin on improving peripheral nerve regeneration. Results demonstrated that the lowest rapamycin concentration （1.53 nmol/L） more significantly promoted Schwann cell migration than the highest FK506 concentration （100μmol/L）. Rapamycin promoted the secretion of nerve growth factors and upregulated growth-associated protein 43 expression in Schwann cells, but did not significantly affect Schwann cell proliferation. Therefore, rapamycin has potential application in peripheral nerve regeneration therapy.展开更多
Taking the construction of new liberal arts as a background,this paper proposes that the international economy and trade major should optimize the teaching system and personnel training mechanism by adding the new cro...Taking the construction of new liberal arts as a background,this paper proposes that the international economy and trade major should optimize the teaching system and personnel training mechanism by adding the new cross-border e-commerce direction.This paper highlights the development path of high-quality international economy and trade professional training,and further ensures the first-class talent training and first-class professional construction specialty.展开更多
Stalagmite is one kind of secondary carbonates formed in limestone caves(speleothem). After cave water droplets containing Ca2+and HCO3 drip onto floor, carbonate in the water might become supersaturated due to CO2 de...Stalagmite is one kind of secondary carbonates formed in limestone caves(speleothem). After cave water droplets containing Ca2+and HCO3 drip onto floor, carbonate in the water might become supersaturated due to CO2 degassing under certain conditions, resulting in the formation of stalagmite in a process year after year. Stalagmite is one of important geological archives for paleoclimate research. The advantages include wide spatial distribution, suitable for U-Th and U-Pb dating, enriched in climate proxies, continuity, long time span, comparability and lower sampling cost etc. These factors have propelled stalagmite paleoclimate research to the forefront of global paleoclimatology with an irreplaceable role. The stalagmite paleoclimate study started in the western countries, mainly in Europe and America in 1960 s–1970 s, while the relevant research in China was progressively developed in the 1980 s–1990 s after the Reform and Opening up. Although there was a huge gap between the overall research level in China and western countries, a solid research foundation, as well as a number of talent teams were established during the period. In the 21 st century, starting from the publication of stalagmite records from Hulu Cave in Nanjing in 2001, the stalagmite paleoclimate research in China has ushered in a flourishing development and a real leap on the basis of international cooperation, resulting in significant international impacts. The landmark achievements, including establishment of the world’s longest(640000 years) East Asian monsoon stalagmite record, as well as the longest Indian monsoon(280000 years),South American monsoon(250000 years), North American westerly climate(330000 years), Central Asian westerly climate(135000 years), and northwestern China westerly climate(500000 years), have laid a milestone in the paleoclimate study in these climate domains. Importantly, these stalagmite records have revealed the relationship of Asian monsoon variations with solar insolation climate change in polar regions, and the South American monsoon changes on orbital-suborbital timescales, which have provided new geological observations for the development of orbital-suborbital climate theory;elaborated coupling and differentiation relationships between the Asian monsoon and the westerly climate;reconstructed the history of Asian monsoon changes in the Holocene in detail, and thus the hydrological and climate variances behind Chinese and Indian civilizationcultural evolutions. Furthermore, a large number of high-resolution stalagmite records over the past 2000 years have been reconstructed, which are important for understanding short-term climate variability and magnitude, events, cycles, and thus the future climate projection. The achievements have also involved the improvements of a number of important techniques, such as U-Th dating method, the establishments of various hydroclimatic proxies, as well as the contributions to the reconstruction of the atmosphere14C variation history over the past ~54000 years. On the perspective of the future, the Chinese stalagmite community should continue to develop key techniques, further clarify the hydroclimatic significance of stalagmite proxies, impel the integration of related disciplines, and concentrate on key scientific issues in global climate change and major social demands.展开更多
Although considerable progress has been made in identifying the genes regulating accumulation of hormones that are involved in leaf senescence, only a few studies have focused on natural variations in jasmonates conte...Although considerable progress has been made in identifying the genes regulating accumulation of hormones that are involved in leaf senescence, only a few studies have focused on natural variations in jasmonates content and much less on the underlying genetic basis. Moreover, the epigenetic regulation of jasmonate-mediated leaf senescence remains largely unknown, in this study, we carried out metabolic profiling of a worldwide collection of rice accessions and demonstrated that there are substantial variations in jasmonate levels among these accessions. A subsequent metabolite-based genornewide association study identified candidates for two major quantitative genes （QTGs）, OsPME1 and OsTSD2, affecting the content of jasmonates. Further investigations using a series of relevant mutants and transgenic lines revealed the MeOH-jasmonata cascade plays an important role in regulating leaf senescence. Moreover, we showed that OsSRT1, one of the two Sir2 （silent information regugator 2） homologs in rice, negatively regulates leaf senescence by repressing expression of the biosynthetic genes of this metabolic cascade and at least particiaUy through histone H3K9 deacetylation of OsPME1. Taken together, our results indicate that the MeOH-jasmonates cascade and its epigenetic regulation are crucial for controlling leaf senescence process in rice.展开更多
The Asian summer monsoon(ASM) is a vast climate system, whose variability is critical to the livelihoods of billions of people across the Asian continent. During the past half-century, much progress has been made in u...The Asian summer monsoon(ASM) is a vast climate system, whose variability is critical to the livelihoods of billions of people across the Asian continent. During the past half-century, much progress has been made in understanding variations on a wide range of timescales, yet several significant issues remain unresolved. Of note are two long-standing problems concerning orbital-scale variations of the ASM.(1) Chinese loess magnetic susceptibility records show a persistent glacial-interglacial dominated ~100 kyr(thousand years) periodicity, while the cave oxygen-isotope(δ18 O) records reveal periodicity in an almost pure precession band(~20 kyr periodicity)—the "Chinese 100 kyr problem".(2) ASM records from the Arabian Sea and other oceans surrounding the Asian continent show a significant lag of 8–10 kyr to Northern Hemisphere summer insolation(NHSI), whereas the Asian cave δ18 O records follow NHSI without a significant lag—a discrepancy termed the "sea-land precession-phase paradox". How can we reconcile these differences? Recent and more refined model simulations now provide spatial patterns of rainfall and wind across the precession cycle, revealing distinct regional divergences in the ASM domain, which can well explain a large portion of the disparities between the loess, marine, and cave proxy records. Overall, we also find that the loess, marine, and cave records are indeed complementary rather than incompatible, with each record preferentially describing a certain aspect of ASM dynamics. Our study provides new insight into the understanding of different hydroclimatic proxies and largely reconciles the "Chinese 100 kyr problem" and "sea-land precession-phase paradox".展开更多
Ebola virus(EBOV) belongs to the Filoviridae family and causes severe illnesses such as hemorrhagic fever with a high mortality rate up to 90%. Now two antibody drugs termed Inmazeb and Ebanga have been approved for t...Ebola virus(EBOV) belongs to the Filoviridae family and causes severe illnesses such as hemorrhagic fever with a high mortality rate up to 90%. Now two antibody drugs termed Inmazeb and Ebanga have been approved for treating EBOV infection. However, clinical studies have demonstrated that the mortality rate of the patients who received these two antibody drugs remains above 30%. Therefore, novel therapeutics with better efficacy is still desired. The isolated human IgG1 constant domain 2(CH2 domain) has been proposed as a scaffold for the development of C-based single domain antibodies(C-sd Abs) as therapeutic candidates against viral infections and other diseases. Here, we screened and identified a novel C-sd Ab termed M24 that targets EBOV glycoprotein(GP) from a C-sd Ab phage display library. M24 neutralizes the pseudotype EBOV with IC;of 0.8 nmol/L(12 ng/mL) and has modest neutralizing activity against authentic EBOV.Epitope determination, including molecular docking and site mutation analysis, discloses that M24 binds to the internal fusion loop(IFL) within GP2, a transmembrane subunit of GP. Interestingly, we found that the binding of M24 to GP at pH5.5 has dramatically decreased compared to the binding at pH 7.5, which may lead to weak efficacy in the neutralization of authentic EBOV. Since no sd Ab against EBOV infection has been reported to date, our results not only give a proof of concept that sd Abs could be utilized for the development of potential therapeutic candidates against EBOV infection, but also provide useful information for the discovery and improvement of anti-EBOV agents.展开更多
Dear Editor,Mink circovirus (MiCV), which is clustered in the genus Circovirus of the family Circoviridae, was first described in minks from farms in Dalian, China in 2013 (Lian et al.2014). The complete single-strand...Dear Editor,Mink circovirus (MiCV), which is clustered in the genus Circovirus of the family Circoviridae, was first described in minks from farms in Dalian, China in 2013 (Lian et al.2014). The complete single-stranded circular genome of the virus is 1,753 nucleotides long and contains two major open reading frames (ORFs), designated ORF1 (Rep gene)and ORF2 (Cap gene)(Lian et al. 2014;Ge et al. 2018).展开更多
COVID-19 caused by SARS-CoV-2 infection has caused substantial morbidity and mortality worldwide and paralyzed the international economy.Understanding the magnitude and duration of the antibody response to SARS-CoV-2 ...COVID-19 caused by SARS-CoV-2 infection has caused substantial morbidity and mortality worldwide and paralyzed the international economy.Understanding the magnitude and duration of the antibody response to SARS-CoV-2 is important to achieve a balance between curbing the pandemic and minimizing adverse effects on society.1 Although the antibody response to SARS-CoV-2 within 9 months has been extensively studied,2,3,4,5,6 little is known about the magnitude and kinetics of antibody responses for over 9 months.Moreover,with limited observations over 9 months(n<100),2,7,8 several studies have produced inconsistent conclusions about antibody dynamics,suggesting different rates of antiviral antibody positivity at the last follow-up.2,7,8 These studies have been limited by a lack of measurement of neutralizing antibodies(NAbs),7 of inclusion of mild or asymptomatic cases,2,8 and of further exploration of potential predisposing factors for antibody dynamics.2,7 Considering the individual heterogeneity(such as disease severity)8 and time-dependent nature1 of the immune response,in-depth characterization of SARS-CoV-2 antibody kinetics across disease severity groups over a long period is urgently needed.Therefore,we repeatedly tested IgM,IgG,viral spike protein receptor-binding dom(anti-RBD)IgG,and NAb titers in COVID-19 patients during a follow-up period of up to 10 months and explored potential predisposing factors of antibody titers during follow-up.展开更多
Severe influenza infections are often associated with the excessive induction of pro-inflammatory cytokines,which is also referred to as"cytokine storms".Several studies have shown that cytokine storms are d...Severe influenza infections are often associated with the excessive induction of pro-inflammatory cytokines,which is also referred to as"cytokine storms".Several studies have shown that cytokine storms are directly associated with influenzainduced fatal acute lung injury and acute respiratory distress syndrome.Due to the narrow administration window,current antiviral therapies are often inadequate.The efforts to use immunomodulatory agents alone or in combination with antiviral agents in the treatment of influenza in animal models have resulted in the achievement of protective effects accompanied with reduced cytokine production.Currently,there are no immunomodulatory drugs for influenza available for clinical use.Animal models,despite being ideal to study the anti-inflammatory responses to influenza virus infection,are very costly and time-consuming.Therefore,there is an urgent need to establish fast and economical screening methods using cellbased models to screen and develop novel immunomodulatory agents.In this study,we screened seven human cell lines and found that the human monocytic cell U937 supports the replication of different subtypes of influenza viruses as well as the production of the important pro-inflammatory cytokines and was selected to develop the cell-based model.The U937 cell model was validated by testing a panel of known antiviral and immunomodulatory agents and screening a drug library consisting of 1280 compounds comprised mostly of FDA-approved drugs.We demonstrated that the U937 cell model is robust and suitable for the high-throughput screening of immunomodulators and antivirals against influenza infection.展开更多
The widely accepted“Milankovitch theory”explains insolation-induced waxing and waning of the ice sheets and their effect on the global climate on orbital timescales.In the past half century,however,the theory has of...The widely accepted“Milankovitch theory”explains insolation-induced waxing and waning of the ice sheets and their effect on the global climate on orbital timescales.In the past half century,however,the theory has often come under scrutiny,especially regarding its“100-ka problem.”Another drawback,but the one that has received less attention,is the“monsoon problem,”which pertains to the exclusion of monsoon dynamics in classic Milankovitch theory even though the monsoon prevails over the vast low-latitude(30N to30S)region that covers half of the Earth’s surface and receives the bulk of solar radiation.In this review,we discuss the major issues with the current form of Milankovitch theory and the progress made at the research forefront.展开更多
基金supported by the Major State Basic Research Development Program of China(973 Program),No.2011CB606205the National Natural Science Foundation of China,No.51172171 and 51103112+2 种基金the Key Project of Chinese Ministry of Education,No.313041the Natural Science Foundation of Hubei Province,No.2013CFB354the Fundamental Research Funds for the Central Universities,No.WUT:2013-IV-099
文摘Rapamycin, similar to FKS06, can promote neural regeneration in vitro. We assumed that the mechanisms of action of rapamycin and FK506 in promoting peripheral nerve regeneration were similar. This study compared the effects of different concentrations of raparnycin and FK506 on Sc hwann cells and investigated effects and mechanisms of rapamycin on improving peripheral nerve regeneration. Results demonstrated that the lowest rapamycin concentration （1.53 nmol/L） more significantly promoted Schwann cell migration than the highest FK506 concentration （100μmol/L）. Rapamycin promoted the secretion of nerve growth factors and upregulated growth-associated protein 43 expression in Schwann cells, but did not significantly affect Schwann cell proliferation. Therefore, rapamycin has potential application in peripheral nerve regeneration therapy.
基金supported by Laboratory construction project of Shandong University of Technology"Cross border e-commerce B2C platform product operation simulation experiment construction"(2020018).
文摘Taking the construction of new liberal arts as a background,this paper proposes that the international economy and trade major should optimize the teaching system and personnel training mechanism by adding the new cross-border e-commerce direction.This paper highlights the development path of high-quality international economy and trade professional training,and further ensures the first-class talent training and first-class professional construction specialty.
基金supported by the National Natural Science Foundation of China(Grant Nos.41888101&41731174)
文摘Stalagmite is one kind of secondary carbonates formed in limestone caves(speleothem). After cave water droplets containing Ca2+and HCO3 drip onto floor, carbonate in the water might become supersaturated due to CO2 degassing under certain conditions, resulting in the formation of stalagmite in a process year after year. Stalagmite is one of important geological archives for paleoclimate research. The advantages include wide spatial distribution, suitable for U-Th and U-Pb dating, enriched in climate proxies, continuity, long time span, comparability and lower sampling cost etc. These factors have propelled stalagmite paleoclimate research to the forefront of global paleoclimatology with an irreplaceable role. The stalagmite paleoclimate study started in the western countries, mainly in Europe and America in 1960 s–1970 s, while the relevant research in China was progressively developed in the 1980 s–1990 s after the Reform and Opening up. Although there was a huge gap between the overall research level in China and western countries, a solid research foundation, as well as a number of talent teams were established during the period. In the 21 st century, starting from the publication of stalagmite records from Hulu Cave in Nanjing in 2001, the stalagmite paleoclimate research in China has ushered in a flourishing development and a real leap on the basis of international cooperation, resulting in significant international impacts. The landmark achievements, including establishment of the world’s longest(640000 years) East Asian monsoon stalagmite record, as well as the longest Indian monsoon(280000 years),South American monsoon(250000 years), North American westerly climate(330000 years), Central Asian westerly climate(135000 years), and northwestern China westerly climate(500000 years), have laid a milestone in the paleoclimate study in these climate domains. Importantly, these stalagmite records have revealed the relationship of Asian monsoon variations with solar insolation climate change in polar regions, and the South American monsoon changes on orbital-suborbital timescales, which have provided new geological observations for the development of orbital-suborbital climate theory;elaborated coupling and differentiation relationships between the Asian monsoon and the westerly climate;reconstructed the history of Asian monsoon changes in the Holocene in detail, and thus the hydrological and climate variances behind Chinese and Indian civilizationcultural evolutions. Furthermore, a large number of high-resolution stalagmite records over the past 2000 years have been reconstructed, which are important for understanding short-term climate variability and magnitude, events, cycles, and thus the future climate projection. The achievements have also involved the improvements of a number of important techniques, such as U-Th dating method, the establishments of various hydroclimatic proxies, as well as the contributions to the reconstruction of the atmosphere14C variation history over the past ~54000 years. On the perspective of the future, the Chinese stalagmite community should continue to develop key techniques, further clarify the hydroclimatic significance of stalagmite proxies, impel the integration of related disciplines, and concentrate on key scientific issues in global climate change and major social demands.
基金This work was supported by the State Key Program of the National Natural Science Foundation of China （no. 31530052）, the Major State Basic Research Development Program of China （973 Program, no. 2013CB127001）, the National High Technology R＆D Program of China （863 Program, no. 2012AA10A304）, and the Program from Fundamental Research Funds for the Central Universities （no. 2662015PY196）.
文摘Although considerable progress has been made in identifying the genes regulating accumulation of hormones that are involved in leaf senescence, only a few studies have focused on natural variations in jasmonates content and much less on the underlying genetic basis. Moreover, the epigenetic regulation of jasmonate-mediated leaf senescence remains largely unknown, in this study, we carried out metabolic profiling of a worldwide collection of rice accessions and demonstrated that there are substantial variations in jasmonate levels among these accessions. A subsequent metabolite-based genornewide association study identified candidates for two major quantitative genes （QTGs）, OsPME1 and OsTSD2, affecting the content of jasmonates. Further investigations using a series of relevant mutants and transgenic lines revealed the MeOH-jasmonata cascade plays an important role in regulating leaf senescence. Moreover, we showed that OsSRT1, one of the two Sir2 （silent information regugator 2） homologs in rice, negatively regulates leaf senescence by repressing expression of the biosynthetic genes of this metabolic cascade and at least particiaUy through histone H3K9 deacetylation of OsPME1. Taken together, our results indicate that the MeOH-jasmonates cascade and its epigenetic regulation are crucial for controlling leaf senescence process in rice.
基金supported by the National Natural Science Foundation of China(41971110 and 41888101)the Second Tibetan Plateau Scientific Expedition and Research Program(2019QZKK0601)the Early Career Scheme of Research Grants Council of Hong Kong(28300717)。
基金supported by the National Natural Science Foundation of China (Grant Nos. 41888101 & 41731174)。
文摘The Asian summer monsoon(ASM) is a vast climate system, whose variability is critical to the livelihoods of billions of people across the Asian continent. During the past half-century, much progress has been made in understanding variations on a wide range of timescales, yet several significant issues remain unresolved. Of note are two long-standing problems concerning orbital-scale variations of the ASM.(1) Chinese loess magnetic susceptibility records show a persistent glacial-interglacial dominated ~100 kyr(thousand years) periodicity, while the cave oxygen-isotope(δ18 O) records reveal periodicity in an almost pure precession band(~20 kyr periodicity)—the "Chinese 100 kyr problem".(2) ASM records from the Arabian Sea and other oceans surrounding the Asian continent show a significant lag of 8–10 kyr to Northern Hemisphere summer insolation(NHSI), whereas the Asian cave δ18 O records follow NHSI without a significant lag—a discrepancy termed the "sea-land precession-phase paradox". How can we reconcile these differences? Recent and more refined model simulations now provide spatial patterns of rainfall and wind across the precession cycle, revealing distinct regional divergences in the ASM domain, which can well explain a large portion of the disparities between the loess, marine, and cave proxy records. Overall, we also find that the loess, marine, and cave records are indeed complementary rather than incompatible, with each record preferentially describing a certain aspect of ASM dynamics. Our study provides new insight into the understanding of different hydroclimatic proxies and largely reconciles the "Chinese 100 kyr problem" and "sea-land precession-phase paradox".
基金This work was jointly supported by the Advanced Customer Cultivation Project of Wuhan National Biosafety Laboratory,Chinese Academy of Sciences(2021ACCP-MS01,2019ACCP-ZD03)the Natural Science Foundation of Hubei Province of China(2019CFA076)the National Natural Science Foundation of China(31870926)。
文摘Ebola virus(EBOV) belongs to the Filoviridae family and causes severe illnesses such as hemorrhagic fever with a high mortality rate up to 90%. Now two antibody drugs termed Inmazeb and Ebanga have been approved for treating EBOV infection. However, clinical studies have demonstrated that the mortality rate of the patients who received these two antibody drugs remains above 30%. Therefore, novel therapeutics with better efficacy is still desired. The isolated human IgG1 constant domain 2(CH2 domain) has been proposed as a scaffold for the development of C-based single domain antibodies(C-sd Abs) as therapeutic candidates against viral infections and other diseases. Here, we screened and identified a novel C-sd Ab termed M24 that targets EBOV glycoprotein(GP) from a C-sd Ab phage display library. M24 neutralizes the pseudotype EBOV with IC;of 0.8 nmol/L(12 ng/mL) and has modest neutralizing activity against authentic EBOV.Epitope determination, including molecular docking and site mutation analysis, discloses that M24 binds to the internal fusion loop(IFL) within GP2, a transmembrane subunit of GP. Interestingly, we found that the binding of M24 to GP at pH5.5 has dramatically decreased compared to the binding at pH 7.5, which may lead to weak efficacy in the neutralization of authentic EBOV. Since no sd Ab against EBOV infection has been reported to date, our results not only give a proof of concept that sd Abs could be utilized for the development of potential therapeutic candidates against EBOV infection, but also provide useful information for the discovery and improvement of anti-EBOV agents.
基金financially supported by the National Key Research and Development Program of China (No. 2017YFD0500103)the National Natural Science Foundation of China (No. 31772747)+2 种基金the Science and Technology Development Project of Jilin Province (No. 20170623043TC)the Program for JLU Science and Technology Innovative Research Team (JLUSTIRT, No. 2017TD-28)the Fundamental Research Funds for the Central Universities
文摘Dear Editor,Mink circovirus (MiCV), which is clustered in the genus Circovirus of the family Circoviridae, was first described in minks from farms in Dalian, China in 2013 (Lian et al.2014). The complete single-stranded circular genome of the virus is 1,753 nucleotides long and contains two major open reading frames (ORFs), designated ORF1 (Rep gene)and ORF2 (Cap gene)(Lian et al. 2014;Ge et al. 2018).
基金supported by grants from the Fundamental Research Funds for the Central Universities(2019kfyXMBZ015)the 111 Project(Prof.Wu),the Fellowship of China Postdoctoral Science Foundation(2020T130034ZX,and 2020T130035ZX)+2 种基金the National Key Research and Development Plan Program of China(2020YFC0860800)the Revitalization Projects after the COVID-19 Plague of the China Association for Science and Technology(20200608CG111311)the Emergency Research Projects for COVID-19 Prevention and Control of the Wuhan Health Commission(EG20M01).
文摘COVID-19 caused by SARS-CoV-2 infection has caused substantial morbidity and mortality worldwide and paralyzed the international economy.Understanding the magnitude and duration of the antibody response to SARS-CoV-2 is important to achieve a balance between curbing the pandemic and minimizing adverse effects on society.1 Although the antibody response to SARS-CoV-2 within 9 months has been extensively studied,2,3,4,5,6 little is known about the magnitude and kinetics of antibody responses for over 9 months.Moreover,with limited observations over 9 months(n<100),2,7,8 several studies have produced inconsistent conclusions about antibody dynamics,suggesting different rates of antiviral antibody positivity at the last follow-up.2,7,8 These studies have been limited by a lack of measurement of neutralizing antibodies(NAbs),7 of inclusion of mild or asymptomatic cases,2,8 and of further exploration of potential predisposing factors for antibody dynamics.2,7 Considering the individual heterogeneity(such as disease severity)8 and time-dependent nature1 of the immune response,in-depth characterization of SARS-CoV-2 antibody kinetics across disease severity groups over a long period is urgently needed.Therefore,we repeatedly tested IgM,IgG,viral spike protein receptor-binding dom(anti-RBD)IgG,and NAb titers in COVID-19 patients during a follow-up period of up to 10 months and explored potential predisposing factors of antibody titers during follow-up.
基金supported by the National Natural Science Foundation of China(21890753,21988101 to Dehui Deng,91853101 to Fangjun Wang,and 91845106 to Liang Yu)the Strategic PriorityResearch Program of the Chinese Academy of Sciences(XDB36030200 to Dehui Deng)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(Y201936 to Dehui Deng,Y201750 to Yangbo Hu)。
基金supported by the Important Hubei Science and Technology Innovation Plan 2015ACA062 (to Xulin Chen)the Natural Science Foundation of Hubei Province (2018CFB244, to Jungang Chen)
文摘Severe influenza infections are often associated with the excessive induction of pro-inflammatory cytokines,which is also referred to as"cytokine storms".Several studies have shown that cytokine storms are directly associated with influenzainduced fatal acute lung injury and acute respiratory distress syndrome.Due to the narrow administration window,current antiviral therapies are often inadequate.The efforts to use immunomodulatory agents alone or in combination with antiviral agents in the treatment of influenza in animal models have resulted in the achievement of protective effects accompanied with reduced cytokine production.Currently,there are no immunomodulatory drugs for influenza available for clinical use.Animal models,despite being ideal to study the anti-inflammatory responses to influenza virus infection,are very costly and time-consuming.Therefore,there is an urgent need to establish fast and economical screening methods using cellbased models to screen and develop novel immunomodulatory agents.In this study,we screened seven human cell lines and found that the human monocytic cell U937 supports the replication of different subtypes of influenza viruses as well as the production of the important pro-inflammatory cytokines and was selected to develop the cell-based model.The U937 cell model was validated by testing a panel of known antiviral and immunomodulatory agents and screening a drug library consisting of 1280 compounds comprised mostly of FDA-approved drugs.We demonstrated that the U937 cell model is robust and suitable for the high-throughput screening of immunomodulators and antivirals against influenza infection.
基金supported by the NationalNatural Science Foundation ofChina(41888101 and 42150710534).
文摘The widely accepted“Milankovitch theory”explains insolation-induced waxing and waning of the ice sheets and their effect on the global climate on orbital timescales.In the past half century,however,the theory has often come under scrutiny,especially regarding its“100-ka problem.”Another drawback,but the one that has received less attention,is the“monsoon problem,”which pertains to the exclusion of monsoon dynamics in classic Milankovitch theory even though the monsoon prevails over the vast low-latitude(30N to30S)region that covers half of the Earth’s surface and receives the bulk of solar radiation.In this review,we discuss the major issues with the current form of Milankovitch theory and the progress made at the research forefront.
