Objective:The Flower of Lobed Kudzuvine[Pueraria lobata(Willd.)Ohwi;Gehua in Chinese;GH]and Japanese Raisin Tree Seed(Hovenia dulcis Thunnb.;Zhijuzi in Chinese;ZJZ)are herbs that have been used in China for the treatm...Objective:The Flower of Lobed Kudzuvine[Pueraria lobata(Willd.)Ohwi;Gehua in Chinese;GH]and Japanese Raisin Tree Seed(Hovenia dulcis Thunnb.;Zhijuzi in Chinese;ZJZ)are herbs that have been used in China for the treatment of alcohol intoxication and liver diseases.We aimed to evaluate the hepatoprotective potential of a combination of these in mice with acute alcohol-induced liver injury,and to elucidate the mechanisms involved.Methods:Male ICR mice were randomly allocated to six groups:a control group,an alcohol-administered group,and groups that were administered alcohol and one of silibinin,the GH,the ZJZ or a GH-ZJZ combination(at a ratio of 2:1).Animals were orally administered 56%alcohol(Er Guo-tou white spirit,0.12 mL/10 g/d)for 10 days and at the end of this period,hepatic biochemical indicators,antioxidant parameters,alcohol metabolic enzymes,and histopathologic changes were evaluated.Moreover,the expression of the signaling molecules KEAP1,NRF2,and AQP9 were measured by qRT-PCR and western blotting.Results:Compared with the model group,GH-ZJZ(2:1)had lower serum ALT(12.15±0.39,P紏.003),AST(104.07±1.03,P紏.001),and ALP(148.09±2.55,P紏.010)activities,and lower TC(1.97±0.05,P紏.001)and TG(1.54±0.07,P?.002)concentrations.GH-ZJZ(2:1)also significantly increased the hepatic activities of SOD and GSH(4.24±0.25 and 1.57±0.06,respectively;both P<.01),reduced the ROS and MDA concentrations(97.50±3.00 and 2.39±0.19,respectively;both P<.01),and upregulated Nrf2 expression(P<.01).GH-ZJZ(2:1)significantly reduced the expression of KEAP1 and AQP9 in the liver,compared with alcohol-administered mice(P<.01).Importantly,the GH-ZJZ combination caused a more marked improvement in acute liver injury than GH or ZJZ alone.Conclusion:We have demonstrated protective effects of GH-ZJZ(2:1)against acute alcohol-induced hepatic injury,and shown that these effects may be associated with improvements in lipid and alcohol metabolism,antioxidant capacity,and lipid peroxidation.展开更多
This year,the number college graduates in China surpassed tens of millions for the first time.The employment rate of fresh graduates has been concerning.In view of this,network entrepreneurship has become an important...This year,the number college graduates in China surpassed tens of millions for the first time.The employment rate of fresh graduates has been concerning.In view of this,network entrepreneurship has become an important channel and platform to solve the problem of college students’employment.The government,society and universities has been actively encouraging college students'network entrepreneurship as the value of college students'network entrepreneurship is significant.This paper analyzes the current situation of college students'network entrepreneurship and the problems faced through the survey data and thus suggests corresponding countermeasures.展开更多
With the continuous progress of the society,the new media network has proposed new conditions and provided new means for implicit ideological and political education in private colleges and universities.This article d...With the continuous progress of the society,the new media network has proposed new conditions and provided new means for implicit ideological and political education in private colleges and universities.This article discusses the launching of the e-class platform for private college counselors to develop the feasibility of implicit ideological and political education for private colleges.The involved methods of education are deeply explored,in order to improve the implicit ideological and political education work ability of private college counselors.展开更多
Students from private undergraduate universities were included in this study as research subjects.Questionnaires were distributed to the students to collect information in order to keep abreast of students’motivation...Students from private undergraduate universities were included in this study as research subjects.Questionnaires were distributed to the students to collect information in order to keep abreast of students’motivation,preference,preparation and plan,encountered difficulties and adjustments made,demands,as well as other aspects about their postgraduate entrance examination.The results showed that students from private universities have clear motivation for their postgraduate entrance examination,but there are some problems,such as the lack of scientific choices,long preparation time,more challenges,and lack of school support.In view of these problems,this study offers countermeasures and suggestions for these students and relevant schools.展开更多
Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2,which results in blindness in the working-age population,and there is currently no available treatment.Here,we r...Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2,which results in blindness in the working-age population,and there is currently no available treatment.Here,we report the results of the first-in-human clinical trial(NCT04722107)of gene therapy for Bietti crystalline corneoretinal dystrophy,including 12 participants who were followed up for 180-365 days.This open-label,single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein(rAAV2/8-hCYP4V2).Participants received a single unilateral subretinal injection of 7.5×10^(10)vector genomes of rAAV2/8-hCYP4V2.Overall,73 treatment-emergent adverse events were reported,with the majority(98.6%)being of mild or moderate intensity and considered to be procedure-or corticosteroid-related;no treatment-related serious adverse events or local/systemic immune toxicities were observed.Compared with that measured at baseline,77.8%of the treated eyes showed improvement in best-corrected visual acuity(BCVA)on day 180,with a mean±standard deviation increase of 9.0±10.8 letters in the 9 eyes analyzed(p=0.021).By day 365,80%of the treated eyes showed an increase in BCVA,with a mean increase of 11.0±10.6 letters in the 5 eyes assessed(p=0.125).Importantly,the patients’improvement observed using multifocal electroretinogram,microperimetry,and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment.We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2(named ZVS101e).展开更多
Dear Editor,Coronavirus disease 2019(COVID-19)is a highly infectious respiratory disease that continues to pose a serious global public health emergency.The disease shows a high infection rate,long incubation period,a...Dear Editor,Coronavirus disease 2019(COVID-19)is a highly infectious respiratory disease that continues to pose a serious global public health emergency.The disease shows a high infection rate,long incubation period,and rapidly emerging variants,which have led to its rapid spread worldwide(Krammer 2020).Many vaccines have been developed for the control of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the virus responsible for COVID-19,including vaccines based on messenger RNA(mRNA)(Polack et al.2020),viral vectors(Zhu et al.2020),recombinant proteins(Yang et al.2020),and inactivated SARS-CoV-2(Zhang et al.2021).展开更多
MicroRNAs (miRNAs) recruit the RNA-induced silencing complex (RISC) to repress the translation of target mRNAs. While the 5' 7-methylguanosine cap of target mRNAs has been well known to be important for miRNA rep...MicroRNAs (miRNAs) recruit the RNA-induced silencing complex (RISC) to repress the translation of target mRNAs. While the 5' 7-methylguanosine cap of target mRNAs has been well known to be important for miRNA repression, the underlying mechanism is not clear. Here we show that TNRC6A interacts with elF4E2, a homo- Iogue of eIF4E that can bind to the cap but cannot interact with eIF4G to initiate translation, to inhibit the translation of target mRNAs. Downregulation of eIF4E2 relieved miRNA repression of reporter expression. Moreover, eIF4E2 downregulation increased the protein levels of endogenous IMP1, PTEN and PDCD4, whose expression are repressed by endogenous miRNAs. We further provide evidence showing that miRNA enhances elF4E2 association with the target mRNA. We propose that miRNAs recruit eI4E2 to compete with eIF4E to repress mRNA translation.展开更多
What is already known about this topic?Morbidity and prevalence of several major parasitic diseases have been declining in China.To reduce the disease burden of parasitic diseases and protect public health security,co...What is already known about this topic?Morbidity and prevalence of several major parasitic diseases have been declining in China.To reduce the disease burden of parasitic diseases and protect public health security,conducting accurate diagnoses following timely treatment is important.What is added by this report?In the national competition held in 2019.展开更多
Human babesiosis is an infection caused by intraerythrocytic protozoa of the genus Babesia and is a worldwide emerging tick-borne disease(1).Babesia is mainly parasitized in erythrocytes of human or other vertebrates ...Human babesiosis is an infection caused by intraerythrocytic protozoa of the genus Babesia and is a worldwide emerging tick-borne disease(1).Babesia is mainly parasitized in erythrocytes of human or other vertebrates and transmitted by the bite of ticks,blood transfusion,or organ transplantation(1).Humans are generally susceptible to Babesia,especially those who are immunocompromised with conditions such as splenectomy or splenic dysfunction,as well as those of old age,with infirmity,or with other severe diseases.展开更多
During the two-year pandemic of coronavirus disease 2019(COVID-19), its causative agent, severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), has been evolving. SARS-CoV-2 Delta, a variant of concern, has beco...During the two-year pandemic of coronavirus disease 2019(COVID-19), its causative agent, severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), has been evolving. SARS-CoV-2 Delta, a variant of concern, has become the dominant circulating strain worldwide within just a few months. Here, we performed a comprehensive analysis of a new B.1.617.2 Delta strain(Delta630) compared with the early WIV04 strain(WIV04) in vitro and in vivo, in terms of replication, infectivity, pathogenicity, and transmission in hamsters. When inoculated intranasally, Delta630 led to more pronounced weight loss and more severe disease in hamsters. Moreover, 40%mortality occurred about one week after infection with 10^(4)PFU of Delta630, whereas no deaths occurred even after infection with 10^(5)PFU of WIV04 or other strains belonging to the Delta variant. Moreover, Delta630outgrew over WIV04 in the competitive aerosol transmission experiment. Taken together, the Delta630 strain showed increased replication ability, pathogenicity, and transmissibility over WIV04 in hamsters. To our knowledge, this is the first SARS-CoV-2 strain that causes death in a hamster model, which could be an asset for the efficacy evaluation of vaccines and antivirals against infections of SARS-CoV-2 Delta strains. The underlying molecular mechanisms of increased virulence and transmission await further analysis.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is still rapidly spreading worldwide.Many drugs and vaccines have been approved for clinical use show efficacy in the treatment and prevention of SARS-CoV-2 i...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is still rapidly spreading worldwide.Many drugs and vaccines have been approved for clinical use show efficacy in the treatment and prevention of SARS-CoV-2 infections.However,the emergence of SARS-CoV-2 variants of concern(VOCs),such as Delta(B.1.617.2)and the recently emerged Omicron(B.1.1.529),has seriously challenged the application of current therapeutics.Therefore,there is still a pressing need for identification of new broad-spectrum antivirals.Here,we further characterized a human antibody(58G6),which we previously isolated from a patient,with a broadly authentic virus-neutralizing activity that inhibits the Delta and Omicron variants with half-maximal inhibitory concentrations(ICso)of 1.69 ng/ml and 54.31 ng/ml,respectively.58G6 shows prophylactic and therapeutic effcacy in hamsters challenged with the Delta and Omicron variants through nasal delivery.Notably,a very low dosage(2 mg/kg daily)of 58G6 efficiently prevented Omicron variant replication in the lungs.These advantages may overcome the efficacy limitation of currently approved neutralizing antibodies that can be administered only by intravenous injection.In general,58G6 is a promising prophylactic and therapeutic candidate against current circulating VOCs and even future emerging mutants.To the best of our knowledge,58G6 is one of the most potent neutralizing antibodies against Omicron,with a broader spectrum than those approved for clinical use.58G6 could be developed as a nebulized therapy,which would be more cost effective and user friendly and enhance the clinical outcome comparedto thatobtainedwithdirect nasaldelivery.展开更多
基金This work was supported by the National Natural Science Foundation of China(No.81703723).
文摘Objective:The Flower of Lobed Kudzuvine[Pueraria lobata(Willd.)Ohwi;Gehua in Chinese;GH]and Japanese Raisin Tree Seed(Hovenia dulcis Thunnb.;Zhijuzi in Chinese;ZJZ)are herbs that have been used in China for the treatment of alcohol intoxication and liver diseases.We aimed to evaluate the hepatoprotective potential of a combination of these in mice with acute alcohol-induced liver injury,and to elucidate the mechanisms involved.Methods:Male ICR mice were randomly allocated to six groups:a control group,an alcohol-administered group,and groups that were administered alcohol and one of silibinin,the GH,the ZJZ or a GH-ZJZ combination(at a ratio of 2:1).Animals were orally administered 56%alcohol(Er Guo-tou white spirit,0.12 mL/10 g/d)for 10 days and at the end of this period,hepatic biochemical indicators,antioxidant parameters,alcohol metabolic enzymes,and histopathologic changes were evaluated.Moreover,the expression of the signaling molecules KEAP1,NRF2,and AQP9 were measured by qRT-PCR and western blotting.Results:Compared with the model group,GH-ZJZ(2:1)had lower serum ALT(12.15±0.39,P紏.003),AST(104.07±1.03,P紏.001),and ALP(148.09±2.55,P紏.010)activities,and lower TC(1.97±0.05,P紏.001)and TG(1.54±0.07,P?.002)concentrations.GH-ZJZ(2:1)also significantly increased the hepatic activities of SOD and GSH(4.24±0.25 and 1.57±0.06,respectively;both P<.01),reduced the ROS and MDA concentrations(97.50±3.00 and 2.39±0.19,respectively;both P<.01),and upregulated Nrf2 expression(P<.01).GH-ZJZ(2:1)significantly reduced the expression of KEAP1 and AQP9 in the liver,compared with alcohol-administered mice(P<.01).Importantly,the GH-ZJZ combination caused a more marked improvement in acute liver injury than GH or ZJZ alone.Conclusion:We have demonstrated protective effects of GH-ZJZ(2:1)against acute alcohol-induced hepatic injury,and shown that these effects may be associated with improvements in lipid and alcohol metabolism,antioxidant capacity,and lipid peroxidation.
基金Guangzhou Huashang College 2022 Innovation and Entrepreneurship Education Research Project“Research on the Influencing Factors of College Students’Network Entrepreneurship Intention Based on TPB Model”(Project Number:HS2022CXCY04)。
文摘This year,the number college graduates in China surpassed tens of millions for the first time.The employment rate of fresh graduates has been concerning.In view of this,network entrepreneurship has become an important channel and platform to solve the problem of college students’employment.The government,society and universities has been actively encouraging college students'network entrepreneurship as the value of college students'network entrepreneurship is significant.This paper analyzes the current situation of college students'network entrepreneurship and the problems faced through the survey data and thus suggests corresponding countermeasures.
基金phased achievement of the 2020 Guangdong Provincial Ideological and Political Project in Colleges and Universities and the Moral Education Project in Primary and Secondary Schools“Research on the Role of Two-Dimensional Culture on Implicit Ideological and Political Education in Private Colleges and Universities from the Perspective of New Media”(Project No.2020GXSZ108).
文摘With the continuous progress of the society,the new media network has proposed new conditions and provided new means for implicit ideological and political education in private colleges and universities.This article discusses the launching of the e-class platform for private college counselors to develop the feasibility of implicit ideological and political education for private colleges.The involved methods of education are deeply explored,in order to improve the implicit ideological and political education work ability of private college counselors.
文摘Students from private undergraduate universities were included in this study as research subjects.Questionnaires were distributed to the students to collect information in order to keep abreast of students’motivation,preference,preparation and plan,encountered difficulties and adjustments made,demands,as well as other aspects about their postgraduate entrance examination.The results showed that students from private universities have clear motivation for their postgraduate entrance examination,but there are some problems,such as the lack of scientific choices,long preparation time,more challenges,and lack of school support.In view of these problems,this study offers countermeasures and suggestions for these students and relevant schools.
基金This work was supported by the National Key Research and Development Program during the 14th Five-year Plan Period(2023YFC2706304)the National Key R&D Program of China(2023YFC3403300)+4 种基金National Natural Science Foundation of China(82220108017,82141128,82371074)Capital Health Development Research Special Project(2024-1-2052)Beijing Science and Technology Program(Z231100004823021,Z201100005520045)Beijing Natural Science Foundation(J230031)Sanming Project of Medicine in Shenzhen(No.SZSM202311018)and Chigenovo Co.,Ltd.
文摘Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2,which results in blindness in the working-age population,and there is currently no available treatment.Here,we report the results of the first-in-human clinical trial(NCT04722107)of gene therapy for Bietti crystalline corneoretinal dystrophy,including 12 participants who were followed up for 180-365 days.This open-label,single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein(rAAV2/8-hCYP4V2).Participants received a single unilateral subretinal injection of 7.5×10^(10)vector genomes of rAAV2/8-hCYP4V2.Overall,73 treatment-emergent adverse events were reported,with the majority(98.6%)being of mild or moderate intensity and considered to be procedure-or corticosteroid-related;no treatment-related serious adverse events or local/systemic immune toxicities were observed.Compared with that measured at baseline,77.8%of the treated eyes showed improvement in best-corrected visual acuity(BCVA)on day 180,with a mean±standard deviation increase of 9.0±10.8 letters in the 9 eyes analyzed(p=0.021).By day 365,80%of the treated eyes showed an increase in BCVA,with a mean increase of 11.0±10.6 letters in the 5 eyes assessed(p=0.125).Importantly,the patients’improvement observed using multifocal electroretinogram,microperimetry,and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment.We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2(named ZVS101e).
基金supported by Strategic Priority Research Program of the Chinese Academy of Sciences(XDB39000000 to T.X.)National Natural Science Foundation of China(81925009 to T.X.,81790644 to T.X.,81900855 to M.Z.,82000941 to D.T.)+3 种基金Jack Ma Foundation(2019-nCoV)CAS Project for Young Scientists in Basic Research(YSBR-013)Fundamental Research Funds for the Central Universities(WK5290000001 to Y.C.,WK5290000002 to Y.Y.,WK2090050048 to M.Z.,WK2070000174 to M.Z.)supported by the Anhui Provincial Natural Science Foundation(1808085MH289 to M.Z.).Joint Laboratory of Innovation in Life Sciences from the University of Science and Technology of China(USTC)and Changchun Zhuoyi Biological Co.Ltd.
文摘Dear Editor,Coronavirus disease 2019(COVID-19)is a highly infectious respiratory disease that continues to pose a serious global public health emergency.The disease shows a high infection rate,long incubation period,and rapidly emerging variants,which have led to its rapid spread worldwide(Krammer 2020).Many vaccines have been developed for the control of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the virus responsible for COVID-19,including vaccines based on messenger RNA(mRNA)(Polack et al.2020),viral vectors(Zhu et al.2020),recombinant proteins(Yang et al.2020),and inactivated SARS-CoV-2(Zhang et al.2021).
文摘MicroRNAs (miRNAs) recruit the RNA-induced silencing complex (RISC) to repress the translation of target mRNAs. While the 5' 7-methylguanosine cap of target mRNAs has been well known to be important for miRNA repression, the underlying mechanism is not clear. Here we show that TNRC6A interacts with elF4E2, a homo- Iogue of eIF4E that can bind to the cap but cannot interact with eIF4G to initiate translation, to inhibit the translation of target mRNAs. Downregulation of eIF4E2 relieved miRNA repression of reporter expression. Moreover, eIF4E2 downregulation increased the protein levels of endogenous IMP1, PTEN and PDCD4, whose expression are repressed by endogenous miRNAs. We further provide evidence showing that miRNA enhances elF4E2 association with the target mRNA. We propose that miRNAs recruit eI4E2 to compete with eIF4E to repress mRNA translation.
基金National Science Foundation of China(Grant No.82073619).
文摘What is already known about this topic?Morbidity and prevalence of several major parasitic diseases have been declining in China.To reduce the disease burden of parasitic diseases and protect public health security,conducting accurate diagnoses following timely treatment is important.What is added by this report?In the national competition held in 2019.
基金supported by the General Program Shanghai Municipal Commission of Health and Family Planning of China(Grant No.201840286 and 201640278)the Program for the Shanghai Natural Science Foundation of China(Grant No.18ZR1443500)+3 种基金the Youth Science Foundation of Chinese Center for Disease Control and Prevention(Grant No.2018A105)the Shenzhen San-Ming Project for prevention and research on vector-borne diseases(Grant No.SZSM201611064)the National Science and Technology Major Program of China(Grant No.2018ZX10734-404)the National Sharing Service Platform for Parasite Resources(Grant No.NPRC-2019-194-30).
文摘Human babesiosis is an infection caused by intraerythrocytic protozoa of the genus Babesia and is a worldwide emerging tick-borne disease(1).Babesia is mainly parasitized in erythrocytes of human or other vertebrates and transmitted by the bite of ticks,blood transfusion,or organ transplantation(1).Humans are generally susceptible to Babesia,especially those who are immunocompromised with conditions such as splenectomy or splenic dysfunction,as well as those of old age,with infirmity,or with other severe diseases.
基金supported by China Natural Science Foundation (82150201)
文摘During the two-year pandemic of coronavirus disease 2019(COVID-19), its causative agent, severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), has been evolving. SARS-CoV-2 Delta, a variant of concern, has become the dominant circulating strain worldwide within just a few months. Here, we performed a comprehensive analysis of a new B.1.617.2 Delta strain(Delta630) compared with the early WIV04 strain(WIV04) in vitro and in vivo, in terms of replication, infectivity, pathogenicity, and transmission in hamsters. When inoculated intranasally, Delta630 led to more pronounced weight loss and more severe disease in hamsters. Moreover, 40%mortality occurred about one week after infection with 10^(4)PFU of Delta630, whereas no deaths occurred even after infection with 10^(5)PFU of WIV04 or other strains belonging to the Delta variant. Moreover, Delta630outgrew over WIV04 in the competitive aerosol transmission experiment. Taken together, the Delta630 strain showed increased replication ability, pathogenicity, and transmissibility over WIV04 in hamsters. To our knowledge, this is the first SARS-CoV-2 strain that causes death in a hamster model, which could be an asset for the efficacy evaluation of vaccines and antivirals against infections of SARS-CoV-2 Delta strains. The underlying molecular mechanisms of increased virulence and transmission await further analysis.
基金This work was jointly supported by the Natural Science Foundation of Hubei Province of China(2019CFA076)the National Natural Science Foundation of China(32170949).
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is still rapidly spreading worldwide.Many drugs and vaccines have been approved for clinical use show efficacy in the treatment and prevention of SARS-CoV-2 infections.However,the emergence of SARS-CoV-2 variants of concern(VOCs),such as Delta(B.1.617.2)and the recently emerged Omicron(B.1.1.529),has seriously challenged the application of current therapeutics.Therefore,there is still a pressing need for identification of new broad-spectrum antivirals.Here,we further characterized a human antibody(58G6),which we previously isolated from a patient,with a broadly authentic virus-neutralizing activity that inhibits the Delta and Omicron variants with half-maximal inhibitory concentrations(ICso)of 1.69 ng/ml and 54.31 ng/ml,respectively.58G6 shows prophylactic and therapeutic effcacy in hamsters challenged with the Delta and Omicron variants through nasal delivery.Notably,a very low dosage(2 mg/kg daily)of 58G6 efficiently prevented Omicron variant replication in the lungs.These advantages may overcome the efficacy limitation of currently approved neutralizing antibodies that can be administered only by intravenous injection.In general,58G6 is a promising prophylactic and therapeutic candidate against current circulating VOCs and even future emerging mutants.To the best of our knowledge,58G6 is one of the most potent neutralizing antibodies against Omicron,with a broader spectrum than those approved for clinical use.58G6 could be developed as a nebulized therapy,which would be more cost effective and user friendly and enhance the clinical outcome comparedto thatobtainedwithdirect nasaldelivery.