The association between meteorological factors and infectious diarrhea has been widely studied in many countries.However,investigation among children under 5 years old in Jiangsu,China remains quite limited.Data inclu...The association between meteorological factors and infectious diarrhea has been widely studied in many countries.However,investigation among children under 5 years old in Jiangsu,China remains quite limited.Data including infectious diarrhea cases among children under five years old and daily meteorological indexes in Jiangsu,China from 2015 to 2019 were collected.The lag-effects up to 21 days of daily maximum temperature(Tmax)on infectious diarrhea were explored using a quasi-Poisson regression with a distributed lag non-linear model(DLNM)approach.The cases number of infectious diarrhea was significantly associated with seasonal variation of meteorological factors,and the burden of disease mainly occurred among children aged 0-2 years old.Moreover,when the reference value was set at 16.7°C,Tmax had a significant lag-effect on cases of infectious diarrhea among children under 5 years old in Jiangsu Province,which was increased remarkably in cold weather with the highest risk at 8℃.The results of DLNM analysis implicated that the lag-effect of Tmax varied among the 13 cities in Jiangsu and had significant differences in 8 cities.The highest risk of Tmax was presented at 5 lag days in Huaian with a maximum RR of 1.18(95% CI:1.09,1.29).Suzhou which had the highest number of diarrhea cases(15830 cases),had a maximum RR of 1.04(95%CI:1.03,1.05)on lag 15 days.Tmax is a considerable indicator to predict the epidemic of infectious diarrhea among 13 cities in Jiangsu,which reminds us that in cold seasons,more preventive strategies and measures should be done to prevent infectious diarrhea.展开更多
Background:Mushrooms are a good source of many nutrients which are potentially beneficial for chronic diseases.We speculated that due to its abundant nutrients edible mushrooms might have a beneficial effect on the pr...Background:Mushrooms are a good source of many nutrients which are potentially beneficial for chronic diseases.We speculated that due to its abundant nutrients edible mushrooms might have a beneficial effect on the prevention of subclinical thyroid dysfunction(SCTD).Therefore,we designed a large-scale cohort study to examine whether mushrooms consumption is a protective factor for SCTD in adults.Methods:This prospective cohort study investigated 6631 participants(mean age:(45.0±10.2)years;55.1%men).Edible mushrooms consumption was measured at baseline using a validated food frequency questionnaire.SCTD was defined as abnormal serum thyroid-stimulating hormone levels and normal free thyroxine.Cox proportional hazards regression models were used to examine the association of edible mushrooms consumption with incident SCTD.Results:During follow-up period,a total of 262 new cases of SCTD were identified,the incidence rate of subclinical hypothyroidism was 8.9/1000 person-years and subclinical hyperthyroidism was 7.2/1000 person-years.After adjusting potential confounding factors,the multivariable hazard ratios(95%confidence intervals)for subclinical hypothyroidism were 1.00(reference)for almost never,0.53(0.29,0.97)for 1-3 times/week and 0.30(0.10,0.87)for≥4 times/week(P for trend=0.02).It also showed edible mushrooms consumption was inversely associated with subclinical hypothyroidism in obese individuals but not non-obese individuals,the final hazard ratios(95%confidence intervals)were 0.14(0.03,0.73)(P for trend<0.01).Conclusions:This population-based prospective cohort study has firstly demonstrated that higher edible mushrooms consumption was significantly associated with lower incidence of subclinical hypothyroidism among general adult population,especially in obese individuals.展开更多
to persist into adulthood and be associated with many adverse health outcomes later in adulthood,including cardiovascular diseases and type 2 diabetes.[1]In utero exposure to“undernutrition”or“over-nutrition”plays...to persist into adulthood and be associated with many adverse health outcomes later in adulthood,including cardiovascular diseases and type 2 diabetes.[1]In utero exposure to“undernutrition”or“over-nutrition”plays an important role in obesity in childhood and diseases in adulthood.[2]It is established that high branchedchain amino acids(BCAAs)are associated with insulin resistance and gestational diabetes mellitus(GDM).[3]However,it is largely unknown whether in utero exposure to high BCAAs also plays a role in adverse childhood growth patterns.We used 8-year children follow-up data of a case-control study nested within a population-based prospective cohort of pregnant women in Tianjin,China,to examine associations between maternal BCAAs levels in early pregnancy and obesity-related growth patterns if any,in offspring at 1-8 years of age.展开更多
Fine particulate matter(PM_(2.5))is a significant risk factor for birth defects.As the first and most important organ to develop during embryogenesis,the heart’s potential susceptibility to PM_(2.5)has attracted grow...Fine particulate matter(PM_(2.5))is a significant risk factor for birth defects.As the first and most important organ to develop during embryogenesis,the heart’s potential susceptibility to PM_(2.5)has attracted growing concern.Despite several studies supporting the cardiac developmental toxicity of PM_(2.5),the diverse study types,models,and end points have prevented the integration of mechanisms.In this Review,we present an adverse outcome pathway framework to elucidate the association between PM_(2.5)-induced molecular initiating events and adverse cardiac developmental outcomes.Activation of the aryl hydrocarbon receptor(AhR)and excessive generation of reactive oxygen species(ROS)were considered as molecular initiating events.The excessive production of ROS induced oxidative stress,endoplasmic reticulum stress,DNA damage,and inflammation,resulting in apoptosis.The activation of the AhR inhibited the Wnt/β-catenin pathway and then suppressed cardiomyocyte differentiation.Impaired cardiomyocyte differentiation and persistent apoptosis resulted in abnormalities in the cardiac structure and function.All of the aforementioned events have been identified as key events(KEs).The culmination of these KEs ultimately led to the adverse outcome,an increased morbidity of congenital heart defects(CHDs).This work contributes to understanding the causes of CHDs and promotes the safety evaluation of PM_(2.5).展开更多
The adverse respiratory outcomes motivated by silica nanoparticles(SiNPs)exposure have received increasing attention.Herein,we aim to elucidate the interplay of diverse cell populations in the lungs and key contributo...The adverse respiratory outcomes motivated by silica nanoparticles(SiNPs)exposure have received increasing attention.Herein,we aim to elucidate the interplay of diverse cell populations in the lungs and key contributors in triggering lung injuries caused by SiNPs.We conducted a subchronic respiratory exposure model of SiNPs via intratracheal instillation in Wistar rats,where rats were administered with 1.5,3.0,or 6.0 mg/kg body weight SiNPs once a week for 12 times in total.We revealed that SiNPs caused pulmonary interstitial injury in rats by histopatho-logical examination and pulmonary hydroxyproline determination.Further,a single-cell RNA-Seq via screening 10457 cells in the rat lungs disclosed cell-specific responses to SiNPs and cell-to-cell interactions within the alveolar macrophages,epithelial cells,and fibroblasts from rat lungs.These disturbed responses were principally related to the dysregulation of protein homeostasis(proteostasis),accompanied by an inflammatory response in macrophages,cell death in epithelial,proliferation,and extracellular matrix deposition in fibroblast.These cell-specific responses may serve a synergistic role in the pathogenesis of pulmonary interstitial disease triggered by SiNPs.In particular,the analyses of gene interaction networks and gene−disease associations filtered out heat shock proteins(Hsps)family genes crucial to the observed pulmonary lesions caused by SiNPs.Of note,both GEO database analysis and our experiments’validation indicated that Hsps,especially Hspd1,may be a key contributor to pulmonary interstitial injury,possibly through triggering oxidative stress,immune response,and disrupting protein homeostasis.Taken together,our study provides insights into pulmonary toxic effects and underlying molecular mechanisms of SiNPs from a single-cell perspective.展开更多
Previous studies have shown that exposure to black carbon(BC,a tracer of traffic-related air pollution)and psychosocial stress are both associated with adverse cardiac effects,but whether psychosocial stress could mod...Previous studies have shown that exposure to black carbon(BC,a tracer of traffic-related air pollution)and psychosocial stress are both associated with adverse cardiac effects,but whether psychosocial stress could modify the cardiac effects of BC is unclear.To investigate the potential modifying effect of psychosocial stress on the associations between acute exposure to BC and typical cardiac health variables,real-time personal 24 h measurements were conducted in a repeated-measure study among adults with elevated blood pressure(high-risk group)and a panel study among normal adults(low-risk group)in China.Measured cardiac health variables included ST-segment depression events,heart rate,and heart rate variability(HRV)variables.Perceived Stress Scale,State Anxiety Inventory and Self-rating Depression Scale were used to assess the recent psychosocial stress status of the participants,and a composite stress index was established based on these scales.Generalized linear mixed-effects model was used to analyze the associations between BC exposure and cardiac health variables and potential effect modification by psychosocial stress.A total of 9724 h measurements among 97 participants in the repeated-measure study and 20224 h measurements among 87 participants in the panel study were included in the final analysis.Acute BC exposure was significantly associated with increased ST-segment depression events and heart rate and decreases in HRV in both studies.The marginal effects of acute BC exposure on most cardiac health variables generally tended to be amplified under higher vs low levels of psychosocial stress in both studies,with the composite stress index apparently modifying the associations of BC exposure with most ST-segment depression events and HRV variables.These findings suggest that psychosocial stress may increase the participants’cardiac susceptibility to BC exposure,which could be helpful for the identification of susceptible individuals in the context of traffic-related air pollution.展开更多
Introduction:This study aimed to investigate the correlation between various plasma metabolites and the likelihood of developing diabetic nephropathy(DN)and construct a diagnostic model for DN in Chinese patients with...Introduction:This study aimed to investigate the correlation between various plasma metabolites and the likelihood of developing diabetic nephropathy(DN)and construct a diagnostic model for DN in Chinese patients with type 2 diabetes mellitus(T2DM).Methods:A cross-sectional investigation was conducted in a hospital setting.Based on medical data,a total of 743 patients from a tertiary hospital were selected and categorized into two groups:the diabetic nephropathy group(DN group)and the non-diabetic nephropathy group(non-DN group).Plasma levels of metabolites,including amino acids and acylcarnitines,were determined using a laser counter measurement system(LC-MS).Subsequently,partial least-squares regression was used to assess the significance of these metabolites.Receiver operating characteristic(ROC)curves were generated for factors that ranked highest in terms of relevance.Model performance was assessed using the curve(AUC).Results:Of the 743 patients with T2DM admitted to the hospital,145 had DN.Compared with the non-DN group,the DN group exhibited elevated systolic blood pressure(P=0.001),high-density lipoprotein cholesterol(P=0.01),and low-density lipoprotein cholesterol(P=0.042).Additionally,the DN group had a higher prevalence of stroke patients(P<0.001)and diabetic retinopathy patients(P<0.001).Finally,a risk model that included citrulline,leucine,tyrosine,valine,propionylcarnitine(C3),and palmitoylcarnitine(C16)was developed.This model achieved an AUC of 0.709,with a 95%confidence interval(CI)ranging from 0.626 to 0.793.Conclusions:A diagnostic model consisting of six plasma metabolites to assess the risk of DN in Chinese patients with T2DM may provide clues for future research.展开更多
Emerging infectious diseases, such as COVID-19, continue to pose significant threats to human beings and their surroundings. In addition, biological warfare, bioterrorism, biological accidents, and harmful consequence...Emerging infectious diseases, such as COVID-19, continue to pose significant threats to human beings and their surroundings. In addition, biological warfare, bioterrorism, biological accidents, and harmful consequences arising from dual-use biotechnology also pose a challenge for global biosecurity. Improving the early surveillance capabilities is necessary for building a common biosecurity shield for the global community of health for all. Furthermore, surveillance could provide early warning and situational awareness of biosecurity risks. However, current surveillance systems face enormous challenges, including technical shortages, fragmented management, and limited international cooperation. Detecting emerging biological risks caused by unknown or novel pathogens is of particular concern. Surveillance systems must be enhanced to effectively mitigate biosecurity risks. Thus, a global strategy of meaningful cooperation based on efficient integration of surveillance at all levels, including interdisciplinary integration of techniques and interdepartmental integration for effective management, is urgently needed. In this paper, we review the biosecurity risks by analyzing potential factors at all levels globally. In addition to describing biosecurity risks and their impact on global security, we also focus on analyzing the challenges to traditional surveillance and propose suggestions on how to integrate current technologies and resources to conduct effective global surveillance.展开更多
Insulin-like growth factor-1 receptor(IGF-1R) has been made an attractive anticancer target due to its overexpression in cancers.However,targeting it has often produced the disappointing results as the role played by ...Insulin-like growth factor-1 receptor(IGF-1R) has been made an attractive anticancer target due to its overexpression in cancers.However,targeting it has often produced the disappointing results as the role played by cross talk with numerous downstream signalings.Here,we report a disobliging IGF-1R signaling which promotes growth of cancer through triggering the E3 ubiquitin ligase MEX3A-mediated degradation of RIG-I.The active β-arrestin-2 scaffolds this disobliging signaling to talk with MEX3A.In response to ligands,IGF-1Rβ activated the basal βarr2 into its active state by phosphorylating the interdomain domain on Tyr64 and Tyr250,opening the middle loop(Leu130-Cys141) to the RING domain of MEX3A through the conformational changes of βarr2.The models of βarr2/IGF-1Rβ and βarr2/MEX3A could interpret the mechanism of the activated-IGF-1R in triggering degradation of RIG-I.The assay of the mutants βarr2Y64Aand βarr2Y250Afurther confirmed the role of these two Tyr residues of the interlobe in mediating the talk between IGF-1Rβ and the RING domain of MEX3A.The truncated-βarr2 and the peptide ATQAIRIF,which mimicked the RING domain of MEX3A could prevent the formation of βarr2/IGF-1Rβ and βarr2/MEX3A complexes,thus blocking the IGF-1R-triggered RIG-I degradation.Degradation of RIG-I resulted in the suppression of the IFN-I-associated immune cells in the TME due to the blockade of the RIG-I-MAVS-IFN-I pathway.Poly(I:C) could reverse anti-PD-L1 insensitivity by recovery of RIG-I.In summary,we revealed a disobliging IGF-1R signaling by which IGF-1Rβ promoted cancer growth through triggering the MEX3A-mediated degradation of RIG-I.展开更多
The well-known insulin-like growth factor 1(IGF1)/IGF-1 receptor(IGF-1R)signaling pathway is overexpressed in many tumors,and is thus an attractive target for cancer treatment.However,results have often been disappoin...The well-known insulin-like growth factor 1(IGF1)/IGF-1 receptor(IGF-1R)signaling pathway is overexpressed in many tumors,and is thus an attractive target for cancer treatment.However,results have often been disappointing due to crosstalk with other signals.Here,we report that IGF-1R signaling stimulates the growth of hepatocellular carcinoma(HCC)cells through the translocation of IGF-1R into the ER to enhance sarco-endoplasmic reticulum calcium ATPase 2(SERCA2)activity.In response to ligand binding,IGF-1Rβis translocated into the ER byβ-arrestin2(β-arr2).Mass spectrometry analysis identified SERCA2 as a target of ER IGF-1Rβ.SERCA2 activity is heavily dependent on the increase in ER IGF-1Rβlevels.ER IGF-1Rβphosphorylates SERCA2 on Tyr^(990)to enhance its activity.Mutation of SERCA2-Tyr^(990)disrupted the interaction of ER IGF-1Rβwith SERCA2,and therefore ER IGF-1Rβfailed to promote SERCA2 activity.The enhancement of SERCA2 activity triggered Ca_(ER)^(2+)perturbation,leading to an increase in autophagy.Thapsigargin blocked the interaction between SERCA2and ER IGF-1Rβand therefore SERCA2 activity,resulting in inhibition of HCC growth.In conclusion,the translocation of IGF-1R into the ER triggers Ca_(ER)^(2+)perturbation by enhancing SERCA2 activity through phosphorylating Tyr^(990)in HCC.展开更多
COVID-19 is the most severe pandemic globally since the 1918 influenza pandemic.Effectively responding to this once-in-a-century global pandemic is a worldwide challenge that the international community needs to joint...COVID-19 is the most severe pandemic globally since the 1918 influenza pandemic.Effectively responding to this once-in-a-century global pandemic is a worldwide challenge that the international community needs to jointly face and solve.This study reviews and discusses the key measures taken by major countries in 2020 to fight against COVID-19,such as lockdowns,social distancing,wearing masks,hand hygiene,using Fangcang shelter hospitals,large-scale nucleic acid testing,close-contacts tracking,and pandemic information monitoring,as well as their prevention and control effects.We hope it can help improve the efficiency and effectiveness of pandemic prevention and control in future.展开更多
文摘The association between meteorological factors and infectious diarrhea has been widely studied in many countries.However,investigation among children under 5 years old in Jiangsu,China remains quite limited.Data including infectious diarrhea cases among children under five years old and daily meteorological indexes in Jiangsu,China from 2015 to 2019 were collected.The lag-effects up to 21 days of daily maximum temperature(Tmax)on infectious diarrhea were explored using a quasi-Poisson regression with a distributed lag non-linear model(DLNM)approach.The cases number of infectious diarrhea was significantly associated with seasonal variation of meteorological factors,and the burden of disease mainly occurred among children aged 0-2 years old.Moreover,when the reference value was set at 16.7°C,Tmax had a significant lag-effect on cases of infectious diarrhea among children under 5 years old in Jiangsu Province,which was increased remarkably in cold weather with the highest risk at 8℃.The results of DLNM analysis implicated that the lag-effect of Tmax varied among the 13 cities in Jiangsu and had significant differences in 8 cities.The highest risk of Tmax was presented at 5 lag days in Huaian with a maximum RR of 1.18(95% CI:1.09,1.29).Suzhou which had the highest number of diarrhea cases(15830 cases),had a maximum RR of 1.04(95%CI:1.03,1.05)on lag 15 days.Tmax is a considerable indicator to predict the epidemic of infectious diarrhea among 13 cities in Jiangsu,which reminds us that in cold seasons,more preventive strategies and measures should be done to prevent infectious diarrhea.
基金supported by grants from the National Natural Science Foundation of China (81941024)Tianjin Major Public Health Science and Technology Project (21ZXGWSY00090)+2 种基金National Health Commission of China (SPSYYC 2020015)Food Science and Technology Foundation of Chinese Institute of FoodScience and Technology (2019-12)2014 and 2016 Chinese NutritionSociety (CNS) Nutrition Research Foundation -DSM Research Fund(2016-046, 2014-071 and 2016-023), China
文摘Background:Mushrooms are a good source of many nutrients which are potentially beneficial for chronic diseases.We speculated that due to its abundant nutrients edible mushrooms might have a beneficial effect on the prevention of subclinical thyroid dysfunction(SCTD).Therefore,we designed a large-scale cohort study to examine whether mushrooms consumption is a protective factor for SCTD in adults.Methods:This prospective cohort study investigated 6631 participants(mean age:(45.0±10.2)years;55.1%men).Edible mushrooms consumption was measured at baseline using a validated food frequency questionnaire.SCTD was defined as abnormal serum thyroid-stimulating hormone levels and normal free thyroxine.Cox proportional hazards regression models were used to examine the association of edible mushrooms consumption with incident SCTD.Results:During follow-up period,a total of 262 new cases of SCTD were identified,the incidence rate of subclinical hypothyroidism was 8.9/1000 person-years and subclinical hyperthyroidism was 7.2/1000 person-years.After adjusting potential confounding factors,the multivariable hazard ratios(95%confidence intervals)for subclinical hypothyroidism were 1.00(reference)for almost never,0.53(0.29,0.97)for 1-3 times/week and 0.30(0.10,0.87)for≥4 times/week(P for trend=0.02).It also showed edible mushrooms consumption was inversely associated with subclinical hypothyroidism in obese individuals but not non-obese individuals,the final hazard ratios(95%confidence intervals)were 0.14(0.03,0.73)(P for trend<0.01).Conclusions:This population-based prospective cohort study has firstly demonstrated that higher edible mushrooms consumption was significantly associated with lower incidence of subclinical hypothyroidism among general adult population,especially in obese individuals.
基金supported by grants from the National Natural Science Foundation of China(Nos.81870549 and 82200932)Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-075C).
文摘to persist into adulthood and be associated with many adverse health outcomes later in adulthood,including cardiovascular diseases and type 2 diabetes.[1]In utero exposure to“undernutrition”or“over-nutrition”plays an important role in obesity in childhood and diseases in adulthood.[2]It is established that high branchedchain amino acids(BCAAs)are associated with insulin resistance and gestational diabetes mellitus(GDM).[3]However,it is largely unknown whether in utero exposure to high BCAAs also plays a role in adverse childhood growth patterns.We used 8-year children follow-up data of a case-control study nested within a population-based prospective cohort of pregnant women in Tianjin,China,to examine associations between maternal BCAAs levels in early pregnancy and obesity-related growth patterns if any,in offspring at 1-8 years of age.
基金supported by the National Key R&D Program of China(2022YFA0806900).
文摘Fine particulate matter(PM_(2.5))is a significant risk factor for birth defects.As the first and most important organ to develop during embryogenesis,the heart’s potential susceptibility to PM_(2.5)has attracted growing concern.Despite several studies supporting the cardiac developmental toxicity of PM_(2.5),the diverse study types,models,and end points have prevented the integration of mechanisms.In this Review,we present an adverse outcome pathway framework to elucidate the association between PM_(2.5)-induced molecular initiating events and adverse cardiac developmental outcomes.Activation of the aryl hydrocarbon receptor(AhR)and excessive generation of reactive oxygen species(ROS)were considered as molecular initiating events.The excessive production of ROS induced oxidative stress,endoplasmic reticulum stress,DNA damage,and inflammation,resulting in apoptosis.The activation of the AhR inhibited the Wnt/β-catenin pathway and then suppressed cardiomyocyte differentiation.Impaired cardiomyocyte differentiation and persistent apoptosis resulted in abnormalities in the cardiac structure and function.All of the aforementioned events have been identified as key events(KEs).The culmination of these KEs ultimately led to the adverse outcome,an increased morbidity of congenital heart defects(CHDs).This work contributes to understanding the causes of CHDs and promotes the safety evaluation of PM_(2.5).
基金supported by the National Natural Science Foundation of China(82273658,82173551)Special Funds for the Construction of High-level Public Health Technical Talents(xuekegugan-01-048).
文摘The adverse respiratory outcomes motivated by silica nanoparticles(SiNPs)exposure have received increasing attention.Herein,we aim to elucidate the interplay of diverse cell populations in the lungs and key contributors in triggering lung injuries caused by SiNPs.We conducted a subchronic respiratory exposure model of SiNPs via intratracheal instillation in Wistar rats,where rats were administered with 1.5,3.0,or 6.0 mg/kg body weight SiNPs once a week for 12 times in total.We revealed that SiNPs caused pulmonary interstitial injury in rats by histopatho-logical examination and pulmonary hydroxyproline determination.Further,a single-cell RNA-Seq via screening 10457 cells in the rat lungs disclosed cell-specific responses to SiNPs and cell-to-cell interactions within the alveolar macrophages,epithelial cells,and fibroblasts from rat lungs.These disturbed responses were principally related to the dysregulation of protein homeostasis(proteostasis),accompanied by an inflammatory response in macrophages,cell death in epithelial,proliferation,and extracellular matrix deposition in fibroblast.These cell-specific responses may serve a synergistic role in the pathogenesis of pulmonary interstitial disease triggered by SiNPs.In particular,the analyses of gene interaction networks and gene−disease associations filtered out heat shock proteins(Hsps)family genes crucial to the observed pulmonary lesions caused by SiNPs.Of note,both GEO database analysis and our experiments’validation indicated that Hsps,especially Hspd1,may be a key contributor to pulmonary interstitial injury,possibly through triggering oxidative stress,immune response,and disrupting protein homeostasis.Taken together,our study provides insights into pulmonary toxic effects and underlying molecular mechanisms of SiNPs from a single-cell perspective.
基金supported by the National Natural Science Foundation of China (82073509)the National Key Research and Development Program of China (2017YFC0211600,2017YFC0211601).
文摘Previous studies have shown that exposure to black carbon(BC,a tracer of traffic-related air pollution)and psychosocial stress are both associated with adverse cardiac effects,but whether psychosocial stress could modify the cardiac effects of BC is unclear.To investigate the potential modifying effect of psychosocial stress on the associations between acute exposure to BC and typical cardiac health variables,real-time personal 24 h measurements were conducted in a repeated-measure study among adults with elevated blood pressure(high-risk group)and a panel study among normal adults(low-risk group)in China.Measured cardiac health variables included ST-segment depression events,heart rate,and heart rate variability(HRV)variables.Perceived Stress Scale,State Anxiety Inventory and Self-rating Depression Scale were used to assess the recent psychosocial stress status of the participants,and a composite stress index was established based on these scales.Generalized linear mixed-effects model was used to analyze the associations between BC exposure and cardiac health variables and potential effect modification by psychosocial stress.A total of 9724 h measurements among 97 participants in the repeated-measure study and 20224 h measurements among 87 participants in the panel study were included in the final analysis.Acute BC exposure was significantly associated with increased ST-segment depression events and heart rate and decreases in HRV in both studies.The marginal effects of acute BC exposure on most cardiac health variables generally tended to be amplified under higher vs low levels of psychosocial stress in both studies,with the composite stress index apparently modifying the associations of BC exposure with most ST-segment depression events and HRV variables.These findings suggest that psychosocial stress may increase the participants’cardiac susceptibility to BC exposure,which could be helpful for the identification of susceptible individuals in the context of traffic-related air pollution.
基金Funding for this project was provided by the Project for the National Key Research and Development Program of China(2021YFA1301202)the National Natural Science Foundation of China(82273676)the Liaoning Province Scientific and Technological Project(2021JH2/10300039).
文摘Introduction:This study aimed to investigate the correlation between various plasma metabolites and the likelihood of developing diabetic nephropathy(DN)and construct a diagnostic model for DN in Chinese patients with type 2 diabetes mellitus(T2DM).Methods:A cross-sectional investigation was conducted in a hospital setting.Based on medical data,a total of 743 patients from a tertiary hospital were selected and categorized into two groups:the diabetic nephropathy group(DN group)and the non-diabetic nephropathy group(non-DN group).Plasma levels of metabolites,including amino acids and acylcarnitines,were determined using a laser counter measurement system(LC-MS).Subsequently,partial least-squares regression was used to assess the significance of these metabolites.Receiver operating characteristic(ROC)curves were generated for factors that ranked highest in terms of relevance.Model performance was assessed using the curve(AUC).Results:Of the 743 patients with T2DM admitted to the hospital,145 had DN.Compared with the non-DN group,the DN group exhibited elevated systolic blood pressure(P=0.001),high-density lipoprotein cholesterol(P=0.01),and low-density lipoprotein cholesterol(P=0.042).Additionally,the DN group had a higher prevalence of stroke patients(P<0.001)and diabetic retinopathy patients(P<0.001).Finally,a risk model that included citrulline,leucine,tyrosine,valine,propionylcarnitine(C3),and palmitoylcarnitine(C16)was developed.This model achieved an AUC of 0.709,with a 95%confidence interval(CI)ranging from 0.626 to 0.793.Conclusions:A diagnostic model consisting of six plasma metabolites to assess the risk of DN in Chinese patients with T2DM may provide clues for future research.
文摘Emerging infectious diseases, such as COVID-19, continue to pose significant threats to human beings and their surroundings. In addition, biological warfare, bioterrorism, biological accidents, and harmful consequences arising from dual-use biotechnology also pose a challenge for global biosecurity. Improving the early surveillance capabilities is necessary for building a common biosecurity shield for the global community of health for all. Furthermore, surveillance could provide early warning and situational awareness of biosecurity risks. However, current surveillance systems face enormous challenges, including technical shortages, fragmented management, and limited international cooperation. Detecting emerging biological risks caused by unknown or novel pathogens is of particular concern. Surveillance systems must be enhanced to effectively mitigate biosecurity risks. Thus, a global strategy of meaningful cooperation based on efficient integration of surveillance at all levels, including interdisciplinary integration of techniques and interdepartmental integration for effective management, is urgently needed. In this paper, we review the biosecurity risks by analyzing potential factors at all levels globally. In addition to describing biosecurity risks and their impact on global security, we also focus on analyzing the challenges to traditional surveillance and propose suggestions on how to integrate current technologies and resources to conduct effective global surveillance.
基金supported by Beijing Natural Science Foundation(7222253,China)National Natural Science Foundation of China(81973350/82173841)supported by Beijing Natural Science Foundation(7212149,China)。
文摘Insulin-like growth factor-1 receptor(IGF-1R) has been made an attractive anticancer target due to its overexpression in cancers.However,targeting it has often produced the disappointing results as the role played by cross talk with numerous downstream signalings.Here,we report a disobliging IGF-1R signaling which promotes growth of cancer through triggering the E3 ubiquitin ligase MEX3A-mediated degradation of RIG-I.The active β-arrestin-2 scaffolds this disobliging signaling to talk with MEX3A.In response to ligands,IGF-1Rβ activated the basal βarr2 into its active state by phosphorylating the interdomain domain on Tyr64 and Tyr250,opening the middle loop(Leu130-Cys141) to the RING domain of MEX3A through the conformational changes of βarr2.The models of βarr2/IGF-1Rβ and βarr2/MEX3A could interpret the mechanism of the activated-IGF-1R in triggering degradation of RIG-I.The assay of the mutants βarr2Y64Aand βarr2Y250Afurther confirmed the role of these two Tyr residues of the interlobe in mediating the talk between IGF-1Rβ and the RING domain of MEX3A.The truncated-βarr2 and the peptide ATQAIRIF,which mimicked the RING domain of MEX3A could prevent the formation of βarr2/IGF-1Rβ and βarr2/MEX3A complexes,thus blocking the IGF-1R-triggered RIG-I degradation.Degradation of RIG-I resulted in the suppression of the IFN-I-associated immune cells in the TME due to the blockade of the RIG-I-MAVS-IFN-I pathway.Poly(I:C) could reverse anti-PD-L1 insensitivity by recovery of RIG-I.In summary,we revealed a disobliging IGF-1R signaling by which IGF-1Rβ promoted cancer growth through triggering the MEX3A-mediated degradation of RIG-I.
基金supported by the National Natural Science Foundation of China(81973350,China)supported by the National Natural Science Foundation of China(81872884 and 82173841,China)Beijing Natural Science Foundation(7222253,China)。
文摘The well-known insulin-like growth factor 1(IGF1)/IGF-1 receptor(IGF-1R)signaling pathway is overexpressed in many tumors,and is thus an attractive target for cancer treatment.However,results have often been disappointing due to crosstalk with other signals.Here,we report that IGF-1R signaling stimulates the growth of hepatocellular carcinoma(HCC)cells through the translocation of IGF-1R into the ER to enhance sarco-endoplasmic reticulum calcium ATPase 2(SERCA2)activity.In response to ligand binding,IGF-1Rβis translocated into the ER byβ-arrestin2(β-arr2).Mass spectrometry analysis identified SERCA2 as a target of ER IGF-1Rβ.SERCA2 activity is heavily dependent on the increase in ER IGF-1Rβlevels.ER IGF-1Rβphosphorylates SERCA2 on Tyr^(990)to enhance its activity.Mutation of SERCA2-Tyr^(990)disrupted the interaction of ER IGF-1Rβwith SERCA2,and therefore ER IGF-1Rβfailed to promote SERCA2 activity.The enhancement of SERCA2 activity triggered Ca_(ER)^(2+)perturbation,leading to an increase in autophagy.Thapsigargin blocked the interaction between SERCA2and ER IGF-1Rβand therefore SERCA2 activity,resulting in inhibition of HCC growth.In conclusion,the translocation of IGF-1R into the ER triggers Ca_(ER)^(2+)perturbation by enhancing SERCA2 activity through phosphorylating Tyr^(990)in HCC.
基金funded by the Advisory Research Project of the Chinese Academy of Engineering(No.2020-XZ-37)the National Natural Science Foundation of China(No.81871738)the Mega-projects of Science and Technology Research(No.2018ZX10711001).
文摘COVID-19 is the most severe pandemic globally since the 1918 influenza pandemic.Effectively responding to this once-in-a-century global pandemic is a worldwide challenge that the international community needs to jointly face and solve.This study reviews and discusses the key measures taken by major countries in 2020 to fight against COVID-19,such as lockdowns,social distancing,wearing masks,hand hygiene,using Fangcang shelter hospitals,large-scale nucleic acid testing,close-contacts tracking,and pandemic information monitoring,as well as their prevention and control effects.We hope it can help improve the efficiency and effectiveness of pandemic prevention and control in future.
