Melanoma Differentiation-Associated gene 5(MDA5)serves as a pattern recognition receptor(PRR)that identifies pathogen-associated molecular patterns(PAMPs),making it instrumental in antiviral defense.However,its non-ca...Melanoma Differentiation-Associated gene 5(MDA5)serves as a pattern recognition receptor(PRR)that identifies pathogen-associated molecular patterns(PAMPs),making it instrumental in antiviral defense.However,its non-canonical role in adaptive immunity,particularly in regulating B-cell immune functions,is poorly characterized.Here,we demonstrate that MDA5 is critical for the marginal zone(MZ)B-cell differentiation,B-cell receptor(BCR)signal transduction,and cytoskeletal dynamics.We determined that the MDA5-NF-κB-DNM1 axis governs actin polymerization and that this impairment in Mda5 knockout(KO)B cells can be rescued by the treatment with the dynamin1(DNM1)activator Bis-T-23.Furthermore,MDA5 deficiency induces metabolic perturbations in B cells,characterized by a reduced extracellular acidification rate(ECAR)and oxygen consumption rate(OCR),excessive reactive oxygen species(ROS)accumulation,and increased mitochondrial fission.Notably,taurine levels are decreased in Mda5 KO B cells,and in vitro taurine supplementation rescues impaired BCR signaling.Finally,MDA5-deficient mice exhibit a blunted humoral immune response.Overall,this study reveals the key functions and molecular mechanisms of MDA5 in B-cell differentiation,BCR signaling,and the humoral immune response.展开更多
为合理评价污染场地风险,以我国云南省某铜堆浸场下游农田土为例,测定土壤中Cu、Pb、Cd和As等4种重金属总量,采用改进BCR(Bureau of European Communities Reference)连续提取法测定4种重金属赋存形态,分析4种重金属间的相关性,并使用...为合理评价污染场地风险,以我国云南省某铜堆浸场下游农田土为例,测定土壤中Cu、Pb、Cd和As等4种重金属总量,采用改进BCR(Bureau of European Communities Reference)连续提取法测定4种重金属赋存形态,分析4种重金属间的相关性,并使用地累积指数法、次生相与原生相比值法(RSP)和风险评价编码法(RAC)对场地土壤重金属污染和潜在风险程度进行评价。结果发现,重金属Cu、Pb、Cd和As平均的含量分别为39.50、46.98、0.16、82.67mg⋅kg^(-1),较云南省重金属背景值,4种重金属超标率分别为0、83.33%、33.33%和100.00%,其中As污染需要特别关注;提取重金属赋存形态结果显示,土样中Cu、Pb、Cd和As均以残渣态为主,占比为83.14%~95.62%,表明4种重金属均以稳定形态存在于土体中;对比3种评价方法,评价结果存在明显差异,地累积指数Igeo结果显示土壤仅As存在污染超标现象,其余3种重金属均无污染,次生相与原生相比值法结果显示,4种重金属对环境均无污染,而风险评价编码法结果显示,Cd对土壤环境存在低风险,其余3种重金属则无风险。对比发现,仅以污染场地土壤重金属总量作为评价指标会一定程度夸大污染风险,应综合重金属总量及赋存形态含量进行分析。虽然重金属元素污染总量较高,但活跃性重金属含量非常低,向环境中扩散的风险也非常低。因此,研究区重金属污染程度较轻,潜在生态风险为低风险。展开更多
Prostate cancer is the most common non-cutaneous cancers occurring in American men,and whilemost men with early-stage prostate cancers are cured,up to a third might manifest with biochemical recurrence(BCR)of prostate...Prostate cancer is the most common non-cutaneous cancers occurring in American men,and whilemost men with early-stage prostate cancers are cured,up to a third might manifest with biochemical recurrence(BCR)of prostate cancer.BCR is a disease entitywhich is characterized by a rising prostate-specific antigen(PSA)in the setting of a previously treated localized prostate cancerwith either surgery or radiation therapywith curativeintent.展开更多
There is a need for more focus in understanding the economic benefits of Climate-Smart Agriculture(CSA)interventions,particularly in sub-Saharan Africa,where extreme climate events are significantly affecting agricult...There is a need for more focus in understanding the economic benefits of Climate-Smart Agriculture(CSA)interventions,particularly in sub-Saharan Africa,where extreme climate events are significantly affecting agriculture and rural livelihoods.This study used the Net Present Value(NPV),Internal Rate of Return(IRR),Benefit-Cost Ratio(BCR),and payback period to evaluate the economic viability of the adopted CSA interventions in the three villages(Doggoh,Jeffiri,and Wulling)of the dryland farming systems of northern Ghana,where CSA interventions were mostly practiced.Data were collected from 161 farm households by the questionnaire survey.The results showed that CSA interventions including livestock-crop integration,mixed cropping,crop rotation,nutrient integration,and tie ridging enhanced crop yield and the household income of smallholder farmers.The five CSA interventions selected by smallholders were in the following order of priority:livestock-crop integration(BCR=2.87),mixed cropping(BCR=2.54),crop rotation(BCR=2.24),nutrient integration(BCR=1.98),and tie ridging(BCR=1.42).Results further showed that livestock-crop integration was the most profitable CSA intervention even under a pessimistic assumption with a long payback period of 5.00 a.Moreover,this study indicated that the implementation of CSA interventions,on average,was relatively profitable and had a nominal financial risk for smallholder farmers.Understanding the economic viability of CSA interventions will help in decision-making process toward selecting the right CSA interventions for resilience development.展开更多
基金supported by the National Natural Science Foundation of China(82371784,32311530061)the National Key Research and Development Program of China(2023YFC2507900,2023YFC2706300)+2 种基金R&D Program of Guangzhou Laboratory(SRPG22-006)State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases(2024ZZ10014)the Hubei Provincial Natural Science Foundation of China(Grant number:2024AFB634).
文摘Melanoma Differentiation-Associated gene 5(MDA5)serves as a pattern recognition receptor(PRR)that identifies pathogen-associated molecular patterns(PAMPs),making it instrumental in antiviral defense.However,its non-canonical role in adaptive immunity,particularly in regulating B-cell immune functions,is poorly characterized.Here,we demonstrate that MDA5 is critical for the marginal zone(MZ)B-cell differentiation,B-cell receptor(BCR)signal transduction,and cytoskeletal dynamics.We determined that the MDA5-NF-κB-DNM1 axis governs actin polymerization and that this impairment in Mda5 knockout(KO)B cells can be rescued by the treatment with the dynamin1(DNM1)activator Bis-T-23.Furthermore,MDA5 deficiency induces metabolic perturbations in B cells,characterized by a reduced extracellular acidification rate(ECAR)and oxygen consumption rate(OCR),excessive reactive oxygen species(ROS)accumulation,and increased mitochondrial fission.Notably,taurine levels are decreased in Mda5 KO B cells,and in vitro taurine supplementation rescues impaired BCR signaling.Finally,MDA5-deficient mice exhibit a blunted humoral immune response.Overall,this study reveals the key functions and molecular mechanisms of MDA5 in B-cell differentiation,BCR signaling,and the humoral immune response.
文摘为合理评价污染场地风险,以我国云南省某铜堆浸场下游农田土为例,测定土壤中Cu、Pb、Cd和As等4种重金属总量,采用改进BCR(Bureau of European Communities Reference)连续提取法测定4种重金属赋存形态,分析4种重金属间的相关性,并使用地累积指数法、次生相与原生相比值法(RSP)和风险评价编码法(RAC)对场地土壤重金属污染和潜在风险程度进行评价。结果发现,重金属Cu、Pb、Cd和As平均的含量分别为39.50、46.98、0.16、82.67mg⋅kg^(-1),较云南省重金属背景值,4种重金属超标率分别为0、83.33%、33.33%和100.00%,其中As污染需要特别关注;提取重金属赋存形态结果显示,土样中Cu、Pb、Cd和As均以残渣态为主,占比为83.14%~95.62%,表明4种重金属均以稳定形态存在于土体中;对比3种评价方法,评价结果存在明显差异,地累积指数Igeo结果显示土壤仅As存在污染超标现象,其余3种重金属均无污染,次生相与原生相比值法结果显示,4种重金属对环境均无污染,而风险评价编码法结果显示,Cd对土壤环境存在低风险,其余3种重金属则无风险。对比发现,仅以污染场地土壤重金属总量作为评价指标会一定程度夸大污染风险,应综合重金属总量及赋存形态含量进行分析。虽然重金属元素污染总量较高,但活跃性重金属含量非常低,向环境中扩散的风险也非常低。因此,研究区重金属污染程度较轻,潜在生态风险为低风险。
文摘Prostate cancer is the most common non-cutaneous cancers occurring in American men,and whilemost men with early-stage prostate cancers are cured,up to a third might manifest with biochemical recurrence(BCR)of prostate cancer.BCR is a disease entitywhich is characterized by a rising prostate-specific antigen(PSA)in the setting of a previously treated localized prostate cancerwith either surgery or radiation therapywith curativeintent.
文摘There is a need for more focus in understanding the economic benefits of Climate-Smart Agriculture(CSA)interventions,particularly in sub-Saharan Africa,where extreme climate events are significantly affecting agriculture and rural livelihoods.This study used the Net Present Value(NPV),Internal Rate of Return(IRR),Benefit-Cost Ratio(BCR),and payback period to evaluate the economic viability of the adopted CSA interventions in the three villages(Doggoh,Jeffiri,and Wulling)of the dryland farming systems of northern Ghana,where CSA interventions were mostly practiced.Data were collected from 161 farm households by the questionnaire survey.The results showed that CSA interventions including livestock-crop integration,mixed cropping,crop rotation,nutrient integration,and tie ridging enhanced crop yield and the household income of smallholder farmers.The five CSA interventions selected by smallholders were in the following order of priority:livestock-crop integration(BCR=2.87),mixed cropping(BCR=2.54),crop rotation(BCR=2.24),nutrient integration(BCR=1.98),and tie ridging(BCR=1.42).Results further showed that livestock-crop integration was the most profitable CSA intervention even under a pessimistic assumption with a long payback period of 5.00 a.Moreover,this study indicated that the implementation of CSA interventions,on average,was relatively profitable and had a nominal financial risk for smallholder farmers.Understanding the economic viability of CSA interventions will help in decision-making process toward selecting the right CSA interventions for resilience development.
