The apoptosis of lens epithehal cells has been proposed as the common basis of cataract formation, with oxidative stress as the major cause. This study was performed to investigate the protective effect of the herbal ...The apoptosis of lens epithehal cells has been proposed as the common basis of cataract formation, with oxidative stress as the major cause. This study was performed to investigate the protective effect of the herbal constituent parthenolide against oxidative stress-induced apoptosis of human lens epithelial （HLE） cells and the possible molecular mechanisms involved. HLE cells （SRA01-04） were incubated with 50 μM H2O2 in the absence or presence of different doses of parthenolide （10, 20 and 50 μM）. To study apoptosis, the cells were assessed by morphologic examination and Annexin V-propidium iodide double staining flow cytometry; to investigate the underlying molecular mechanisms, the expression of caspase-3 and caspase-9 were assayed by Western blot and quantitative RT-PCR, and the activities of caspase-3 and caspase-9 were measured by a Chemicon caspase colorimetric activity assay kit. Stimulated with H202 for 18 h, a high fraction of riLE cells underwent apoptosis, while in the presence ofparthenolide of different concentrations, dose-dependent blocking of HLE cell apoptosis was observed. The expression of caspase-3 and caspase-9 induced by H202 in HLE cells was significantly reduced by parthenolide both at the protein and mRNA levels, and the activation ofcaspase-3 and caspase-9 was also suppressed by parthenolide in a dose-dependent manner. In conclusion, parthenolide prevents HLE cells from oxidative stress-induced apoptosis through inhibition of the activation ofcaspase-3 and caspase-9, suggesting a potential protective effect against cataract formation.展开更多
Dear Editor,The coronavirus disease 2019(COVID-19)outbreak,has spread across the world(Wu et al.,2020).The causative agent of COVID-19,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is highly pathogenic a...Dear Editor,The coronavirus disease 2019(COVID-19)outbreak,has spread across the world(Wu et al.,2020).The causative agent of COVID-19,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is highly pathogenic and infectious,which become a major public health hazard that has had a devastating social and economic impact worldwide(Li Q.Q.et al.,2020).Variants of the virus have emerged that behave differently(CDC2021;Gobeil et al.,2020;Leung et al.,2021).Some of them show increased infectivity(Li Q.et al.,2020;Zhang et al.,2020)and may escape from neutralizing antibodies(Weisblum et al.,2020).展开更多
In the mammalian heart,cardiomyocytes undergo a transient window of proliferation that leads to regenerative impairment,limiting cardiomyocyte proliferation and myocardial repair capacity.Cardiac developmental pattern...In the mammalian heart,cardiomyocytes undergo a transient window of proliferation that leads to regenerative impairment,limiting cardiomyocyte proliferation and myocardial repair capacity.Cardiac developmental patterns exacerbate the progression of heart disease characterized by myocardial cell loss,ultimately leading to cardiac dysfunction and heart failure.Myocardial infarction causes the death of partial cardiomyocytes,which triggers an immune response to remove debris and restore tissue integrity.Interestingly,when transient myocardial injury triggers irreversible loss of cardiomyocytes,the subsequent macrophages responsible for proliferation and regeneration have a unique immune phenotype that promotes the formation of pre-existing new cardiomyocytes.During mammalian regeneration,mononuclear-derived macrophages and self-renewing resident cardiac macrophages provide multiple cytokines and molecular signals that create a regenerative environment and cellular plasticity capacity in postnatal cardiomyocytes,a pivotal strategy for achieving myocardial repair.Consistent with other human tissues,cardiac macrophages originating from the embryonic endothelium produce a hierarchy of contributions to monocyte recruitment and fate specification.In this review,we discuss the novel functions of macrophages in triggering cardiac regeneration and repair after myocardial infarction and provide recent advances and prospective insights into the phenotypic transformation and heterogeneous features involving cardiac macrophages.In conclusion,macrophages contribute critically to regeneration,repair,and remodeling,and are challenging targets for cardiovascular therapeutic interventions.展开更多
Recently,monkeypox has become a global concern amid the ongoing COVID-19 pandemic.Monkeypox is an acute rash zoonosis caused by the monkeypox virus,which was previously concentrated in Africa.The re-emergence of this ...Recently,monkeypox has become a global concern amid the ongoing COVID-19 pandemic.Monkeypox is an acute rash zoonosis caused by the monkeypox virus,which was previously concentrated in Africa.The re-emergence of this pathogen seems unusual on account of outbreaks in multiple nonendemic countries and the incline to spread from person to person.We need to revisit this virus to prevent the epidemic from getting worse.In this review,we comprehensively summarize studies on monkeypox,including its epidemiology,biological characteristics,pathogenesis,and clinical characteristics,as well as therapeutics and vaccines,highlighting its unusual outbreak attributed to the transformation of transmission.We also analyze the present situation and put forward countermeasures from both clinical and scientific research to address it.展开更多
Background:Rare earth elements(REE)are a group of trace elements that behave geochemically coherently.REE fractionation patterns normalized to reference materials provide a powerful tool for documenting pedogenesis.In...Background:Rare earth elements(REE)are a group of trace elements that behave geochemically coherently.REE fractionation patterns normalized to reference materials provide a powerful tool for documenting pedogenesis.Insoil processes are particularly difficult to illustrate with respect to contemporary and past climate conditions.In this study,we characterize the rare earth element(REE)contents in bulk soils and respective geochemical fractions(e.g.,exchangeable,carbonate‑bound,reducible,and oxidizable fractions)and to decipher the relationships between REE geochemistry components and climatic factors across a large‑scale northern China transect(NCT).Results:Across the NCT,bulk REE concentrations ranged from 55.2 to 241.1μg g^(−1)with a main portion in the residual fraction(49–79%),followed by oxidizable fraction(2–40%),reducible fraction(3–22%),carbonate‑bound fraction(0.1–16%),and negligible exchangeable fraction.The REE contents of geochemical components(carbonate‑bound,reducible,and oxidizable)in topsoils correlated to climate factors(mean annual precipitation,mean annual temperature,potential evaporation,and aridity index(AI)).The normalized abundances to the upper continental crust(UCC)composition show that the middle REE was generally enriched than the light REE and heavy REE in topsoils along the transect.The overall UCC‑normalized bulk REE patterns in topsoils and subsoils were similar,characterized by weak negative Ce anomalies and positive Eu anomalies.Conclusions:Our data in topsoils and depth profiles collectively suggest that cycling of REE was primarily regulated by abiotic processes in area with AI<0.2,while the biological effect on REE circulation in soil played a more effective role in area with AI>0.3.The similar UCC normalized patterns in topsoils suggest that the REE was originated from a common source with limited influences from other sources(e.g.,atmospheric dusts and anthropogenic contribu‑tions).Our results to some extent provide evidence for climatic influence REE distribution patterns both in topsoils and subsoils across the continental‑scale transect.Our investigation gives insights into future studies on vertical REE mobility and its associated biogeochemical pathways.展开更多
Both HIV infection and antiretroviral therapy(ART)affect the oral microbiome.Whether successful treatment with ART in people living with HIV(PLWH),which leads to a significant decline in viral loads and immune reconst...Both HIV infection and antiretroviral therapy(ART)affect the oral microbiome.Whether successful treatment with ART in people living with HIV(PLWH),which leads to a significant decline in viral loads and immune reconstitution,is associated with changes in or recovery of the oral microbiome remains unknown.Therefore,we performed a cross-sectional study of 118 PLWH receiving regular ART and 40 healthy controls(HCs).Among the 118 PLWH,18 immunological nonresponders(INRs;<200 CD4^(+)T cells/μL)and 30 immunological responders(IRs;≥500 CD4^(+)T cells/μL)were identified.The oral microbiota composition of all participants was analyzed using 16S rRNA gene sequencing of throat swab samples.Relative abundance of bacterial genera was compared between IRs and INRs,and Pearson correlations between bacterial abundance and peripheral blood immune cell counts were evaluated.The INR group showed lower alpha diversity than the IR and HC groups,which displayed similar alpha diversity.The genera Alloprevotella,Prevotella and Neisseria were more abundant in PLWH than in HCs,whereas the genera Rothia,Streptococcus and Fusobacterium were more abundant in HCs than in PLWH.The genus Rothia was more abundant in the INR group,whereas Prevotella,Alloprevotella,Porphyromonas and Haemophilus were more abundant in the IR group.The genera Rothia and Alloprevotella were negatively and positively associated with CD4^(+)T cell counts,respectively.Thus,an increased abundance of Rothia in the oral microbiome is associated with unfavorable outcomes regarding immune reconstitution in PLWH receiving regular ART,whereas Prevotella,Alloprevotella,Porphyromonas and Haemophilus are associated with favorable outcomes.展开更多
Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2.Here we report that nelfinavir,an FDA approved drug for the treatment of HIV infection,is ef...Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2.Here we report that nelfinavir,an FDA approved drug for the treatment of HIV infection,is effective against SARS-CoV-2 and COVID-19.Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2(IC50=8.26μM),while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93μM(EC50).In comparison with vehicle-treated animals,rhesus macaque prophylactically treated with nelfinavir had significantly lower temperature and significantly reduced virus loads in the nasal and anal swabs of the animals.At necropsy,nelfinavir-treated animals had a significant reduction of the viral replication in the lungs by nearly three orders of magnitude.A prospective clinic study with 37 enrolled treatment-naive patients at Shanghai Public Health Clinical Center,which were randomized(1:1)to nelfinavir and control groups,showed that the nelfinavir treatment could shorten the duration of viral shedding by 5.5 days(9.0 vs.14.5 days,P=0.055)and the duration of fever time by 3.8 days(2.8 vs.6.6 days,P=0.014)in mild/moderate COVID-19 patients.The antiviral efficiency and clinical benefits in rhesus macaque model and in COVID-19 patients,together with its well-established good safety profile in almost all ages and during pregnancy,indicated that nelfinavir is a highly promising medication with the potential of preventative effect for the treatment of COVID-19.展开更多
Rheumatoid arthritis(RA)is associated with alterations in the gut bacterial composition,but the contribution of the viral community(virome)to disease pathogenesis remains poorly understood.Here,we employed metagenomic...Rheumatoid arthritis(RA)is associated with alterations in the gut bacterial composition,but the contribution of the viral community(virome)to disease pathogenesis remains poorly understood.Here,we employed metagenomic sequencing to perform a stratified comparative analysis of gut virome profiles across three clinically defined cohorts:healthy controls and patients with mild or severe RA.We constructed a tripartite interaction network that integrates viral operational taxonomic units,bacterial taxa with RA-pathogenic potential,and disease-specific clinical parameters to delineate the mechanistic interplay between virome perturbations and RA progression.Metavirome profiling revealed significant shifts in gut viral diversity among RA patients,including an increased abundance of Peploviricota and a marked depletion of Podoviridae phages.Concurrently,bacteriome analysis revealed that Blautia,Bifidobacterium and Anaerobutyricum were enriched in the gut microbiota of RA patients,whereas Phocaeicola and Bacteroides were markedly depleted.These microbial alterations were significantly correlated with elevated levels of proinflammatory cytokines,Th17/Treg imbalance and clinical scores.Further analysis revealed enhanced viral–bacterial cross-boundary interactions,such as the co-enrichment of Acinetobacter phage with Blautia,which may exacerbate inflammation through lipopolysaccharide release.Together,our findings highlight the critical role of synergistic dysregulation between the gut virome and bacteriome in RA pathology.Longitudinal studies are warranted to establish causal relationships and explore the therapeutic potential of phage therapy or probiotic modulation.展开更多
基金supported by National Natural Science Foundation of China(No.30471538)Traditional Chinese Medicine Foundation of Zhejiang province(No.2005C086).
文摘The apoptosis of lens epithehal cells has been proposed as the common basis of cataract formation, with oxidative stress as the major cause. This study was performed to investigate the protective effect of the herbal constituent parthenolide against oxidative stress-induced apoptosis of human lens epithelial （HLE） cells and the possible molecular mechanisms involved. HLE cells （SRA01-04） were incubated with 50 μM H2O2 in the absence or presence of different doses of parthenolide （10, 20 and 50 μM）. To study apoptosis, the cells were assessed by morphologic examination and Annexin V-propidium iodide double staining flow cytometry; to investigate the underlying molecular mechanisms, the expression of caspase-3 and caspase-9 were assayed by Western blot and quantitative RT-PCR, and the activities of caspase-3 and caspase-9 were measured by a Chemicon caspase colorimetric activity assay kit. Stimulated with H202 for 18 h, a high fraction of riLE cells underwent apoptosis, while in the presence ofparthenolide of different concentrations, dose-dependent blocking of HLE cell apoptosis was observed. The expression of caspase-3 and caspase-9 induced by H202 in HLE cells was significantly reduced by parthenolide both at the protein and mRNA levels, and the activation ofcaspase-3 and caspase-9 was also suppressed by parthenolide in a dose-dependent manner. In conclusion, parthenolide prevents HLE cells from oxidative stress-induced apoptosis through inhibition of the activation ofcaspase-3 and caspase-9, suggesting a potential protective effect against cataract formation.
基金supported by the Zhejiang Provincial Key Research and Development Program(#2021C03043 and#2021C03039)。
文摘Dear Editor,The coronavirus disease 2019(COVID-19)outbreak,has spread across the world(Wu et al.,2020).The causative agent of COVID-19,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is highly pathogenic and infectious,which become a major public health hazard that has had a devastating social and economic impact worldwide(Li Q.Q.et al.,2020).Variants of the virus have emerged that behave differently(CDC2021;Gobeil et al.,2020;Leung et al.,2021).Some of them show increased infectivity(Li Q.et al.,2020;Zhang et al.,2020)and may escape from neutralizing antibodies(Weisblum et al.,2020).
基金supported by the National Key Research and Development Program of China(No.2021YFA1301100,2021YFA1301101)Shandong Provincial Natural Science Foundation of China(No.SYS202202)the Research Project of Jinan Microecological Biomedicine Shandong Laboratory(China)(No.JNL-2023009Q,JNL-2022012B).
文摘In the mammalian heart,cardiomyocytes undergo a transient window of proliferation that leads to regenerative impairment,limiting cardiomyocyte proliferation and myocardial repair capacity.Cardiac developmental patterns exacerbate the progression of heart disease characterized by myocardial cell loss,ultimately leading to cardiac dysfunction and heart failure.Myocardial infarction causes the death of partial cardiomyocytes,which triggers an immune response to remove debris and restore tissue integrity.Interestingly,when transient myocardial injury triggers irreversible loss of cardiomyocytes,the subsequent macrophages responsible for proliferation and regeneration have a unique immune phenotype that promotes the formation of pre-existing new cardiomyocytes.During mammalian regeneration,mononuclear-derived macrophages and self-renewing resident cardiac macrophages provide multiple cytokines and molecular signals that create a regenerative environment and cellular plasticity capacity in postnatal cardiomyocytes,a pivotal strategy for achieving myocardial repair.Consistent with other human tissues,cardiac macrophages originating from the embryonic endothelium produce a hierarchy of contributions to monocyte recruitment and fate specification.In this review,we discuss the novel functions of macrophages in triggering cardiac regeneration and repair after myocardial infarction and provide recent advances and prospective insights into the phenotypic transformation and heterogeneous features involving cardiac macrophages.In conclusion,macrophages contribute critically to regeneration,repair,and remodeling,and are challenging targets for cardiovascular therapeutic interventions.
基金supported by the National Key Research&Development Program of China(No.2021YFC2301204)Zhejiang Provincial Key Research&Development Program of China(No.2021C03043)Research Project of Jinan Microecological Biomedicine Shandong Laboratory.
文摘Recently,monkeypox has become a global concern amid the ongoing COVID-19 pandemic.Monkeypox is an acute rash zoonosis caused by the monkeypox virus,which was previously concentrated in Africa.The re-emergence of this pathogen seems unusual on account of outbreaks in multiple nonendemic countries and the incline to spread from person to person.We need to revisit this virus to prevent the epidemic from getting worse.In this review,we comprehensively summarize studies on monkeypox,including its epidemiology,biological characteristics,pathogenesis,and clinical characteristics,as well as therapeutics and vaccines,highlighting its unusual outbreak attributed to the transformation of transmission.We also analyze the present situation and put forward countermeasures from both clinical and scientific research to address it.
基金supported by Chinese Academy of Sciences(No.E01X0301)National Natural Science Foundation of China(Grant No.41673005)support from China Scholarship Council.Youth Innovation Promotion Association CAS to Chao Wang(2018231).
文摘Background:Rare earth elements(REE)are a group of trace elements that behave geochemically coherently.REE fractionation patterns normalized to reference materials provide a powerful tool for documenting pedogenesis.Insoil processes are particularly difficult to illustrate with respect to contemporary and past climate conditions.In this study,we characterize the rare earth element(REE)contents in bulk soils and respective geochemical fractions(e.g.,exchangeable,carbonate‑bound,reducible,and oxidizable fractions)and to decipher the relationships between REE geochemistry components and climatic factors across a large‑scale northern China transect(NCT).Results:Across the NCT,bulk REE concentrations ranged from 55.2 to 241.1μg g^(−1)with a main portion in the residual fraction(49–79%),followed by oxidizable fraction(2–40%),reducible fraction(3–22%),carbonate‑bound fraction(0.1–16%),and negligible exchangeable fraction.The REE contents of geochemical components(carbonate‑bound,reducible,and oxidizable)in topsoils correlated to climate factors(mean annual precipitation,mean annual temperature,potential evaporation,and aridity index(AI)).The normalized abundances to the upper continental crust(UCC)composition show that the middle REE was generally enriched than the light REE and heavy REE in topsoils along the transect.The overall UCC‑normalized bulk REE patterns in topsoils and subsoils were similar,characterized by weak negative Ce anomalies and positive Eu anomalies.Conclusions:Our data in topsoils and depth profiles collectively suggest that cycling of REE was primarily regulated by abiotic processes in area with AI<0.2,while the biological effect on REE circulation in soil played a more effective role in area with AI>0.3.The similar UCC normalized patterns in topsoils suggest that the REE was originated from a common source with limited influences from other sources(e.g.,atmospheric dusts and anthropogenic contribu‑tions).Our results to some extent provide evidence for climatic influence REE distribution patterns both in topsoils and subsoils across the continental‑scale transect.Our investigation gives insights into future studies on vertical REE mobility and its associated biogeochemical pathways.
基金from Zhejiang Plan for the Special Support for Top-notch Talents in China(2022R52029)Shandong Provincial Laboratory Project(SYS202202)the Fundamental Research Funds for the Central Universities(2022ZFJH003)。
文摘Both HIV infection and antiretroviral therapy(ART)affect the oral microbiome.Whether successful treatment with ART in people living with HIV(PLWH),which leads to a significant decline in viral loads and immune reconstitution,is associated with changes in or recovery of the oral microbiome remains unknown.Therefore,we performed a cross-sectional study of 118 PLWH receiving regular ART and 40 healthy controls(HCs).Among the 118 PLWH,18 immunological nonresponders(INRs;<200 CD4^(+)T cells/μL)and 30 immunological responders(IRs;≥500 CD4^(+)T cells/μL)were identified.The oral microbiota composition of all participants was analyzed using 16S rRNA gene sequencing of throat swab samples.Relative abundance of bacterial genera was compared between IRs and INRs,and Pearson correlations between bacterial abundance and peripheral blood immune cell counts were evaluated.The INR group showed lower alpha diversity than the IR and HC groups,which displayed similar alpha diversity.The genera Alloprevotella,Prevotella and Neisseria were more abundant in PLWH than in HCs,whereas the genera Rothia,Streptococcus and Fusobacterium were more abundant in HCs than in PLWH.The genus Rothia was more abundant in the INR group,whereas Prevotella,Alloprevotella,Porphyromonas and Haemophilus were more abundant in the IR group.The genera Rothia and Alloprevotella were negatively and positively associated with CD4^(+)T cell counts,respectively.Thus,an increased abundance of Rothia in the oral microbiome is associated with unfavorable outcomes regarding immune reconstitution in PLWH receiving regular ART,whereas Prevotella,Alloprevotella,Porphyromonas and Haemophilus are associated with favorable outcomes.
基金supported by the Natural Science Foundation of Shanghai (21ZR1475600)Science and Technology Commission of Shanghai Municipality (20431900100)+4 种基金Shanghai Science and Technology Committee (19430750100)National Key R&D Program of China (2016YFA0502301 and 2021YFC2301204)Drug development for the newly emerging viral infectious diseases (SIMM010107)Fundamental Research Funds for the Central Universities (2022ZFJH003)Zhejiang Provincial Key Research&Development Program of China (2021C03043 and No.2021C03039).
文摘Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2.Here we report that nelfinavir,an FDA approved drug for the treatment of HIV infection,is effective against SARS-CoV-2 and COVID-19.Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2(IC50=8.26μM),while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93μM(EC50).In comparison with vehicle-treated animals,rhesus macaque prophylactically treated with nelfinavir had significantly lower temperature and significantly reduced virus loads in the nasal and anal swabs of the animals.At necropsy,nelfinavir-treated animals had a significant reduction of the viral replication in the lungs by nearly three orders of magnitude.A prospective clinic study with 37 enrolled treatment-naive patients at Shanghai Public Health Clinical Center,which were randomized(1:1)to nelfinavir and control groups,showed that the nelfinavir treatment could shorten the duration of viral shedding by 5.5 days(9.0 vs.14.5 days,P=0.055)and the duration of fever time by 3.8 days(2.8 vs.6.6 days,P=0.014)in mild/moderate COVID-19 patients.The antiviral efficiency and clinical benefits in rhesus macaque model and in COVID-19 patients,together with its well-established good safety profile in almost all ages and during pregnancy,indicated that nelfinavir is a highly promising medication with the potential of preventative effect for the treatment of COVID-19.
基金supported by the National Key Research and Development Program of China(2021YFF0700305)the Research Project of Jinan Microecological Biomedicine Shandong Laboratory(JNL-2023015D)+1 种基金the Department of Science and Technology of Shandong Province(SYS202202)the Research Project of Jinan Microecological Biomedicine Shandong Laboratory(JNL-2025005B).
文摘Rheumatoid arthritis(RA)is associated with alterations in the gut bacterial composition,but the contribution of the viral community(virome)to disease pathogenesis remains poorly understood.Here,we employed metagenomic sequencing to perform a stratified comparative analysis of gut virome profiles across three clinically defined cohorts:healthy controls and patients with mild or severe RA.We constructed a tripartite interaction network that integrates viral operational taxonomic units,bacterial taxa with RA-pathogenic potential,and disease-specific clinical parameters to delineate the mechanistic interplay between virome perturbations and RA progression.Metavirome profiling revealed significant shifts in gut viral diversity among RA patients,including an increased abundance of Peploviricota and a marked depletion of Podoviridae phages.Concurrently,bacteriome analysis revealed that Blautia,Bifidobacterium and Anaerobutyricum were enriched in the gut microbiota of RA patients,whereas Phocaeicola and Bacteroides were markedly depleted.These microbial alterations were significantly correlated with elevated levels of proinflammatory cytokines,Th17/Treg imbalance and clinical scores.Further analysis revealed enhanced viral–bacterial cross-boundary interactions,such as the co-enrichment of Acinetobacter phage with Blautia,which may exacerbate inflammation through lipopolysaccharide release.Together,our findings highlight the critical role of synergistic dysregulation between the gut virome and bacteriome in RA pathology.Longitudinal studies are warranted to establish causal relationships and explore the therapeutic potential of phage therapy or probiotic modulation.
