Background:Understanding the global burden of enteric infections is crucial for prioritizing control strategies for foodborne and waterborne diseases.This study aimed to assess the global burden of enteric infections ...Background:Understanding the global burden of enteric infections is crucial for prioritizing control strategies for foodborne and waterborne diseases.This study aimed to assess the global burden of enteric infections in 2021 and identify risk factors from One Health aspects.Methods:Leveraging the Global Burden of Disease(GBD)2021 database,the incidence,disability-adjusted life years(DALYs),and deaths of enteric infections and the subtypes were estimated,including diarrheal diseases,typhoid and paratyphoid fever,invasive non-typhoidal Salmonella(iNTS)infections,and other intestinal infectious diseases.The estimates were quantified by absolute number,age-standardized incidence rate(ASIR),agestandardized mortality rate(ASMR)and age-standardized DALY rate with 95%uncertainty intervals(UIs).Thirteen pathogens and three risk factors associated with diarrheal diseases were analyzed.Results:In 2021,the global age-standardized DALY rate of enteric infections was 1020.15 per 100,000 popultion(95%UI:822.70-1259.39 per 100,000 population)with an estimated annual percentage change(EAPC)of-4.11%(95%confidence interval:-4.31%to-3.90%)in 1990-2021.A larger burden was observed in regions with lower socio-demographic index(SDI)levels.Diarrheal disease was the most serious subtype with Western Sub-Saharan Africa exhibiting the highest age-standardized DALY rate(2769.81 per 100,000 population,95%UI:1976.80-3674.41 per 100,000 population).Children under 5 and adults over 65 years suffered more from diarrheal diseases with the former experiencing the highest global age-standardized DALY rate(9382.46 per 100,000 population,95%UI:6771.76-13,075.12 per 100,000 population).Rotavirus remained the leading cause of diarrheal diseases despite a cross-year decline in the observed age-standardized DALY rate.Unsafe water,sanitation,and handwashing contributed most to the disease burden.Conclusion:The reduced burden of enteric infections suggested the effectiveness of previous control strategies;however,more efforts should be made in vulnerable regions and populations through a One Health approach.展开更多
Objective: Long non-coding RNAs(lnc RNAs) are involved in numerous biological processes in lung cancer cells. In our previous studies, we identified a lnc RNA, ENST00000439577, which is highly expressed in lung carcin...Objective: Long non-coding RNAs(lnc RNAs) are involved in numerous biological processes in lung cancer cells. In our previous studies, we identified a lnc RNA, ENST00000439577, which is highly expressed in lung carcinomas, and termed it lung cancer progression-associated transcript 1(LCPAT1). To characterize the role of LCPAT1 in lung cancer, we conducted the current study.Methods: Expression of LCPAT1 and autophagy-associated markers in tumor tissues and lung cancer cell lines was determined by real-time quantitative polymerase chain reaction(q PCR). Hematoxylin and eosin(HE) staining, q PCR, Western blot, and immunohistochemistry were performed to evaluate xenografted tumor tissues. Autophagy induced by rapamycin was detected by Western blot and immunofluorescence in lung cancer cell lines.Results: Expression of LCPAT1 and microtubule-associated protein 1 light chain 3 beta(LC3B) was positively correlated in lung cancer. Knockdown of LCPAT1 inhibited tumor growth and suppressed cell autophagy in vivo. Moreover, LCPAT1 knockdown in lung cancer cell lines resulted in decreased autophagy-associated gene expression and alleviated the cell autophagy induced by rapamycin.Conclusions: We speculate that LCPAT1 plays a crucial role in regulating autophagy in lung cancer.展开更多
Background:Cell replacement therapy has been envisioned as a promising treatment for neurodegenerative diseases.Due to the ethical concerns of ESCs-derived neural progenitor cells(NPCs)and tumorigenic potential of iPS...Background:Cell replacement therapy has been envisioned as a promising treatment for neurodegenerative diseases.Due to the ethical concerns of ESCs-derived neural progenitor cells(NPCs)and tumorigenic potential of iPSCs,reprogramming of somatic cells directly into multipotent NPCs has emerged as a preferred approach for cell transplantation.Methods:Mouse astrocytes were reprogrammed into NPCs by the overexpression of transcription factors(TFs)Foxg1,Sox2,and Brn2.The generation of subtypes of neurons was directed by the force expression of cell-type specific TFs Lhx8 or Foxa2/Lmx1a.Results:Astrocyte-derived induced NPCs(AiNPCs)share high similarities,including the expression of NPC-specific genes,DNA methylation patterns,the ability to proliferate and differentiate,with the wild type NPCs.The AiNPCs are committed to the forebrain identity and predominantly differentiated into glutamatergic and GABAergic neuronal subtypes.Interestingly,additional overexpression of TFs Lhx8 and Foxa2/Lmx1a in AiNPCs promoted cholinergic and dopaminergic neuronal differentiation,respectively.Conclusions:Our studies suggest that astrocytes can be converted into AiNPCs and lineage-committed AiNPCs can acquire differentiation potential of other lineages through forced expression of specific TFs.Understanding the impact of the TF sets on the reprogramming and differentiation into specific lineages of neurons will provide valuable strategies for astrocyte-based cell therapy in neurodegenerative diseases.展开更多
The outbreak of the coronavirus disease 2019 in China was first reported in Wuhan in December 2019 and gradually spread to other areas in China.After implementation of prevention and control measures,the estimation of...The outbreak of the coronavirus disease 2019 in China was first reported in Wuhan in December 2019 and gradually spread to other areas in China.After implementation of prevention and control measures,the estimation of the epidemic trend is needed.A phase-and region-adjusted SEIR model was applied for modeling and predicting the number of cases in Wuhan,Hubei Province and regions outside Hubei Province in China.The estimated number of infections could reach its peak in late February 2020 in Wuhan and Hubei Province,which is 55303–84520 and 83944–129312,respectively,while the epidemic peaks in regions outside Hubei Province in China could appear on February 13,2020 with the estimated 13035–19108 cases.According to the estimation,the outbreak would abate in March and April all over China.Current estimation provided evidence for planned work resumption under stringent prevention and control in China to further support the fight against the epidemic.Nevertheless,there is still possibility of the second outbreak brought by the work resumption and population migration,especially from Hubei Province and high intensity cities outside Hubei Province.Strict prevention and control measures still need to be considered in the regions with high intensity of epidemic and densely-populated cities.展开更多
The direct reprogramming of somatic cells into induced neural progenitor cells(iNPCs)has been envisioned as a promising approach to overcome ethical and clinical issues of pluripotent stem cell transplantation.We prev...The direct reprogramming of somatic cells into induced neural progenitor cells(iNPCs)has been envisioned as a promising approach to overcome ethical and clinical issues of pluripotent stem cell transplantation.We previously reported that astrocyte-derived induced pluripotent stem cells(iPSCs)have more tendencies for neuronal differentiation than fibroblast-derived iPSCs.However,the differences of neurogenic potential between astrocytederived iNPCs(AiNPCs)and iNPCs from non-neural origins,such as fibroblast-derived iNPCs(FiNPCs),and the underlying mechanisms remain unclear.Our results suggested that AiNPCs exhibited higher differentiation efficiency,mobility and survival capacities,compared to FiNPCs.The whole transcriptome analysis revealed higher activities of TGFβsignaling in AiNPCs,versus FiNPCs,following a similar trend between astrocytes and fibroblasts.The higher neurogenic competence,migration ability,and cell death resistance of AiNPCs could be abrogated using TGFβ signaling inhibitor LY2157299.Hence,our study demonstrates the difference between iNPCs generated from neural and non-neural cells,together with the underlying mechanisms,which,provides valuable information for donor cell selection in the reprogramming approach.展开更多
Background Rare infectious diseases of poverty(rIDPs)involve more than hundreds of tropical diseases,which domi-nantly affect people living in impoverished and marginalized regions and fail to be prioritized in the gl...Background Rare infectious diseases of poverty(rIDPs)involve more than hundreds of tropical diseases,which domi-nantly affect people living in impoverished and marginalized regions and fail to be prioritized in the global health agenda.The neglect of rIDPs could impede the progress toward sustainable development.This study aimed to esti-mate the disease burden of rIDPs in 2021,which would be pivotal for setting intervention priorities and mobilizing resources globally.Methods Leveraging data from the Global Burden of Disease Study 2021,the study reported both numbers and age-standardized rates of prevalence,mortality,disability-adjusted life-years(DALYs),years lived with disability,and years of life lost of rIDPs with corresponding 95%uncertainty intervals(Uls)at global,regional,and national levels.The temporal trends between 1990 and 2021 were assessed by the joinpoint regression analysis.A Bayesian age-period-cohort model was used to project the disease burden for 2050.Results In 2021,there were 103.76 million(95%Ul:102.13,105.44 million)global population suffered from rIDPs with an age-standardized DALY rate of 58.44 per 100,000 population(95%Ul:42.92,77.26 per 100,000 population).From 1990 to 2021,the age-standardized DALY rates showed an average annual percentage change of-0.16%(95%confidence interval:-0.22,-0.11%).Higher age-standardized DALY rates were dominated in sub-Saharan Africa(126.35 per 100,000 population,95%Ul:91.04,161.73 per 100,000 population),South Asia(80.80 per 100,000 popula-tion,95%Ul:57.31,114.10 per 100,000 population),and countries with a low socio-demographic index.There was age heterogeneity in the DALY rates of rIDPs,with the population aged under 15 years being the most predominant.Females aged 15-49 years had four-times higher age-standardized DALY rates of rIDPs than males in the same age.The projections indicated a slight reduction in the disease burden of rIDPs by 2050.Conclusions There has been a slight reduction in the disease burden of rIDPs over the past three decades.Given that rIDPs mainly affect populations in impoverished regions,targeted health strategies and resource allocation are in great demand for these populations to further control rIDPs and end poverty in all its forms everywhere.展开更多
基金supported by Bill&Melinda Gates Foundation[grant number OPP1152504]International Joint Laboratory on Tropical Diseases Control in Greater Mekong Subregion[grant number 21410750200]+3 种基金National Natural Science Foundation of China[grant number 82304102]Natural Science Foundation of Shanghai[grant number 23ZR1436200]Shanghai Science and Technology Development Foundation[grant number 22YF1421100]Shanghai Science and Technology Development Foundation[grant number 23YF1421200].
文摘Background:Understanding the global burden of enteric infections is crucial for prioritizing control strategies for foodborne and waterborne diseases.This study aimed to assess the global burden of enteric infections in 2021 and identify risk factors from One Health aspects.Methods:Leveraging the Global Burden of Disease(GBD)2021 database,the incidence,disability-adjusted life years(DALYs),and deaths of enteric infections and the subtypes were estimated,including diarrheal diseases,typhoid and paratyphoid fever,invasive non-typhoidal Salmonella(iNTS)infections,and other intestinal infectious diseases.The estimates were quantified by absolute number,age-standardized incidence rate(ASIR),agestandardized mortality rate(ASMR)and age-standardized DALY rate with 95%uncertainty intervals(UIs).Thirteen pathogens and three risk factors associated with diarrheal diseases were analyzed.Results:In 2021,the global age-standardized DALY rate of enteric infections was 1020.15 per 100,000 popultion(95%UI:822.70-1259.39 per 100,000 population)with an estimated annual percentage change(EAPC)of-4.11%(95%confidence interval:-4.31%to-3.90%)in 1990-2021.A larger burden was observed in regions with lower socio-demographic index(SDI)levels.Diarrheal disease was the most serious subtype with Western Sub-Saharan Africa exhibiting the highest age-standardized DALY rate(2769.81 per 100,000 population,95%UI:1976.80-3674.41 per 100,000 population).Children under 5 and adults over 65 years suffered more from diarrheal diseases with the former experiencing the highest global age-standardized DALY rate(9382.46 per 100,000 population,95%UI:6771.76-13,075.12 per 100,000 population).Rotavirus remained the leading cause of diarrheal diseases despite a cross-year decline in the observed age-standardized DALY rate.Unsafe water,sanitation,and handwashing contributed most to the disease burden.Conclusion:The reduced burden of enteric infections suggested the effectiveness of previous control strategies;however,more efforts should be made in vulnerable regions and populations through a One Health approach.
基金funded by the National Natural Science Foundation of China (Grant No. 81401046 and No.21777099)Shanghai Jiao Tong University Interdisciplinary Research Key Grant (Grant No. YG2015ZD01)Shanghai Jiao Tong University "New Young Teachers Startup Plan"
文摘Objective: Long non-coding RNAs(lnc RNAs) are involved in numerous biological processes in lung cancer cells. In our previous studies, we identified a lnc RNA, ENST00000439577, which is highly expressed in lung carcinomas, and termed it lung cancer progression-associated transcript 1(LCPAT1). To characterize the role of LCPAT1 in lung cancer, we conducted the current study.Methods: Expression of LCPAT1 and autophagy-associated markers in tumor tissues and lung cancer cell lines was determined by real-time quantitative polymerase chain reaction(q PCR). Hematoxylin and eosin(HE) staining, q PCR, Western blot, and immunohistochemistry were performed to evaluate xenografted tumor tissues. Autophagy induced by rapamycin was detected by Western blot and immunofluorescence in lung cancer cell lines.Results: Expression of LCPAT1 and microtubule-associated protein 1 light chain 3 beta(LC3B) was positively correlated in lung cancer. Knockdown of LCPAT1 inhibited tumor growth and suppressed cell autophagy in vivo. Moreover, LCPAT1 knockdown in lung cancer cell lines resulted in decreased autophagy-associated gene expression and alleviated the cell autophagy induced by rapamycin.Conclusions: We speculate that LCPAT1 plays a crucial role in regulating autophagy in lung cancer.
基金This work was supported in part by research grants from the National Basic Research Program of China(973 ProgramGrant No.2014CB965001 to JZ)Innovative Research Groups of the National Natural Science Foundation of China(#81221001 to JZ)+2 种基金Joint Research Fund for Overseas Chinese,Hong Kong and Macao Young Scientists of the National Natural Science Foundation of China(#81329002 to JZ)the National Institutes of Health:2R56NS041858-15A1(JZ),1R01NS097195-01(JZ),and R03 NS094071-01(YH)the State of Nebraska,DHHS-LB606 Stem Cell 2009-10 to JZ.
文摘Background:Cell replacement therapy has been envisioned as a promising treatment for neurodegenerative diseases.Due to the ethical concerns of ESCs-derived neural progenitor cells(NPCs)and tumorigenic potential of iPSCs,reprogramming of somatic cells directly into multipotent NPCs has emerged as a preferred approach for cell transplantation.Methods:Mouse astrocytes were reprogrammed into NPCs by the overexpression of transcription factors(TFs)Foxg1,Sox2,and Brn2.The generation of subtypes of neurons was directed by the force expression of cell-type specific TFs Lhx8 or Foxa2/Lmx1a.Results:Astrocyte-derived induced NPCs(AiNPCs)share high similarities,including the expression of NPC-specific genes,DNA methylation patterns,the ability to proliferate and differentiate,with the wild type NPCs.The AiNPCs are committed to the forebrain identity and predominantly differentiated into glutamatergic and GABAergic neuronal subtypes.Interestingly,additional overexpression of TFs Lhx8 and Foxa2/Lmx1a in AiNPCs promoted cholinergic and dopaminergic neuronal differentiation,respectively.Conclusions:Our studies suggest that astrocytes can be converted into AiNPCs and lineage-committed AiNPCs can acquire differentiation potential of other lineages through forced expression of specific TFs.Understanding the impact of the TF sets on the reprogramming and differentiation into specific lineages of neurons will provide valuable strategies for astrocyte-based cell therapy in neurodegenerative diseases.
基金This work is funded by Medicine and Engineering Interdisciplinary Research Fund of Shanghai Jiao Tong University(No.YG2020YQ06)the National Key Research and Development Project(Nos.2018YFC1705100,2018YFC1705103,and 2018YFC2000700)+1 种基金the National Natural Science Foundation of China(Nos.71673187 and 81630086)the Key Research Program(No.ZDRW-ZS-2017-1)of the Chinese Academy of Sciences,Innovative research team of high-level local universities in Shanghai.We acknowledge all health-care workers involved in the diagnosis and treatment of patients all around China.We thank National Health Commission of the People’s Republic of China for coordinating data collection for patients with COVID-19.
文摘The outbreak of the coronavirus disease 2019 in China was first reported in Wuhan in December 2019 and gradually spread to other areas in China.After implementation of prevention and control measures,the estimation of the epidemic trend is needed.A phase-and region-adjusted SEIR model was applied for modeling and predicting the number of cases in Wuhan,Hubei Province and regions outside Hubei Province in China.The estimated number of infections could reach its peak in late February 2020 in Wuhan and Hubei Province,which is 55303–84520 and 83944–129312,respectively,while the epidemic peaks in regions outside Hubei Province in China could appear on February 13,2020 with the estimated 13035–19108 cases.According to the estimation,the outbreak would abate in March and April all over China.Current estimation provided evidence for planned work resumption under stringent prevention and control in China to further support the fight against the epidemic.Nevertheless,there is still possibility of the second outbreak brought by the work resumption and population migration,especially from Hubei Province and high intensity cities outside Hubei Province.Strict prevention and control measures still need to be considered in the regions with high intensity of epidemic and densely-populated cities.
基金This work was supported in part by research grants from the State Key Program of the National Natural Science Foundation of China(No.81830037 to J.Z.)the National Basic Research Program of China(973 Program Grant No.2014CB965001 to JZ)+5 种基金Innovative Research Groups of the National Natural Science Foundation of China(No.81221001 to JZ)Joint Research Fund for Overseas Chinese,Hong Kong and Macao Young Scientists of the National Natural Science Foundation of China(No.81329002 to JZ)the National Institutes of Health(No.1R01NS097195–01 to JZ)the National Natural Science Foundation of China(No.81901333 to XX)Shanghai Sailing Program(No.19YF1451700 to XX)China Postdoctoral Science Foundation Grant(No.2018 M642087 to XX).
文摘The direct reprogramming of somatic cells into induced neural progenitor cells(iNPCs)has been envisioned as a promising approach to overcome ethical and clinical issues of pluripotent stem cell transplantation.We previously reported that astrocyte-derived induced pluripotent stem cells(iPSCs)have more tendencies for neuronal differentiation than fibroblast-derived iPSCs.However,the differences of neurogenic potential between astrocytederived iNPCs(AiNPCs)and iNPCs from non-neural origins,such as fibroblast-derived iNPCs(FiNPCs),and the underlying mechanisms remain unclear.Our results suggested that AiNPCs exhibited higher differentiation efficiency,mobility and survival capacities,compared to FiNPCs.The whole transcriptome analysis revealed higher activities of TGFβsignaling in AiNPCs,versus FiNPCs,following a similar trend between astrocytes and fibroblasts.The higher neurogenic competence,migration ability,and cell death resistance of AiNPCs could be abrogated using TGFβ signaling inhibitor LY2157299.Hence,our study demonstrates the difference between iNPCs generated from neural and non-neural cells,together with the underlying mechanisms,which,provides valuable information for donor cell selection in the reprogramming approach.
基金supported by International Joint Laboratory on Tropical Diseases Control in Greater Mekong Subregion(21410750200)National Natural Science Foundation of China(82304102)+2 种基金Natural Science Foundation of Shanghai(23ZR1436200)Shanghai Science and Technology Development Foundation(22YF1421100,23YF1421200)the Bill&Melinda Gates Foundation.The Funders had no role in the study design or in the collection,analysis,and interpretation of the data,writing of the report,or decision to submit the article for publication.
文摘Background Rare infectious diseases of poverty(rIDPs)involve more than hundreds of tropical diseases,which domi-nantly affect people living in impoverished and marginalized regions and fail to be prioritized in the global health agenda.The neglect of rIDPs could impede the progress toward sustainable development.This study aimed to esti-mate the disease burden of rIDPs in 2021,which would be pivotal for setting intervention priorities and mobilizing resources globally.Methods Leveraging data from the Global Burden of Disease Study 2021,the study reported both numbers and age-standardized rates of prevalence,mortality,disability-adjusted life-years(DALYs),years lived with disability,and years of life lost of rIDPs with corresponding 95%uncertainty intervals(Uls)at global,regional,and national levels.The temporal trends between 1990 and 2021 were assessed by the joinpoint regression analysis.A Bayesian age-period-cohort model was used to project the disease burden for 2050.Results In 2021,there were 103.76 million(95%Ul:102.13,105.44 million)global population suffered from rIDPs with an age-standardized DALY rate of 58.44 per 100,000 population(95%Ul:42.92,77.26 per 100,000 population).From 1990 to 2021,the age-standardized DALY rates showed an average annual percentage change of-0.16%(95%confidence interval:-0.22,-0.11%).Higher age-standardized DALY rates were dominated in sub-Saharan Africa(126.35 per 100,000 population,95%Ul:91.04,161.73 per 100,000 population),South Asia(80.80 per 100,000 popula-tion,95%Ul:57.31,114.10 per 100,000 population),and countries with a low socio-demographic index.There was age heterogeneity in the DALY rates of rIDPs,with the population aged under 15 years being the most predominant.Females aged 15-49 years had four-times higher age-standardized DALY rates of rIDPs than males in the same age.The projections indicated a slight reduction in the disease burden of rIDPs by 2050.Conclusions There has been a slight reduction in the disease burden of rIDPs over the past three decades.Given that rIDPs mainly affect populations in impoverished regions,targeted health strategies and resource allocation are in great demand for these populations to further control rIDPs and end poverty in all its forms everywhere.
