Drug optimization, which improves drug potency/specificity by structure-activity relationship(SAR) and drug-like properties, is rigorously performed to select drug candidates for clinical trials. However,the current d...Drug optimization, which improves drug potency/specificity by structure-activity relationship(SAR) and drug-like properties, is rigorously performed to select drug candidates for clinical trials. However,the current drug optimization may overlook the structure-tissue exposure/selectivity-relationship(STR) in disease-targeted tissues vs. normal tissues, which may mislead the drug candidate selection and impact the balance of clinical efficacy/toxicity. In this study, we investigated the STR in correlation with observed clinical efficacy/toxicity using seven selective estrogen receptor modulators(SERMs) that have similar structures, same molecular target, and similar/different pharmacokinetics. The results showed that drug’s plasma exposure was not correlated with drug’s exposures in the target tissues(tumor, fat pad, bone, uterus),while tissue exposure/selectivity of SERMs was correlated with clinical efficacy/safety. Slight structure modifications of four SERMs did not change drug’s plasma exposure but altered drug’s tissue exposure/selectivity.Seven SERMs with high protein binding showed higher accumulation in tumors compared to surrounding normal tissues, which is likely due to tumor EPR effect of protein-bound drugs. These suggest that STR alters drug’s tissue exposure/selectivity in disease-targeted tissues vs. normal tissues impacting clinical efficacy/toxicity. Drug optimization needs to balance the SAR and STR in selecting drug candidate for clinical trial to improve success of clinical drug development.展开更多
China’s coastal regions,characterized by dense populations and industrial agglomeration,face escalating threats from typhoon disasters.Understanding the evolution of socio-economic exposure to future typhoon landfall...China’s coastal regions,characterized by dense populations and industrial agglomeration,face escalating threats from typhoon disasters.Understanding the evolution of socio-economic exposure to future typhoon landfalls under global change is critical for effective disaster risk management.This study utilizes future typhoon track data simulated by the regional climate model version 4(RegCM4),combined with projected population and Gross Domestic Product(GDP)data for China’s coastal regions under three Shared Socioeconomic Pathways(SSPs:SSP1,sustainability;SSP2,middle of the road;SSP5,fossil-fueled development).We analyze typhoon impact zones for future periods(2030s,2050s,and 2090s)under Representative Concentration Pathways(RCPs:RCP2.6,RCP4.5,and RCP8.5,representing low,medium,and high greenhouse gas emission scenarios,respectively).Exposure levels for 2030,2050,and 2100 are calculated based on the annual average frequency of typhoon impacts during these periods,aiming to quantify the distribution characteristics of typhoon-affected population and GDP in China’s coastal regions.Key findings reveal two high-frequency typhoon im-pact zones:the Taiwan Strait region and the northern Qiongzhou Strait region.Furthermore,under RCP2.6,typhoon impacts may ex-tend to Liaoning,while RCP4.5 and RCP8.5 scenarios indicate potential impacts reaching further north to Heilongjiang.Under RCP4.5,Northeast China will experience the largest typhoon-affected area(43.800×10^(4) km^(2))by the 2030s.High population and GDP exposure concentrates in the Yangtze River Delta,the Pearl River Delta,and the Taiwan Strait coastal areas.Notably,Liaoning’s cumulative ex-posed population may exceed 0.100×10^(8) by 2030 and 2050 under RCP4.5 and RCP8.5 due to typhoon track migration.Given China’s location within the Western Pacific typhoon high-incidence region,the northward expansion of impacts will substantially escalate socio-economic exposure in mid-latitude regions previously at lower risk.These findings underscore the imperative for enhanced disaster pre-vention,mitigation strategies and targeted countermeasure research.展开更多
Glyphosate(GLY),a widely used herbicide,has been extensively applied in both the agricultural and non-agricultural sectors worldwide.The rate of GLY use varies considerably depending on the crop type and local farming...Glyphosate(GLY),a widely used herbicide,has been extensively applied in both the agricultural and non-agricultural sectors worldwide.The rate of GLY use varies considerably depending on the crop type and local farming practices,which can be up to approximately 53.5%of agricultural land in certain regions.展开更多
Objective:To assess prenatal Bisphenol A(BPA)exposure levels and explore their preliminary associations with maternal and fetal characteristics in a population from Northeastern Yunnan.Methods:A cross-sectional analys...Objective:To assess prenatal Bisphenol A(BPA)exposure levels and explore their preliminary associations with maternal and fetal characteristics in a population from Northeastern Yunnan.Methods:A cross-sectional analysis was performed using data and urine samples from 70 pregnant women in their third trimester recruited at Qujing Central Hospital.Urinary BPA was measured by HPLC-MS/MS.Participants were stratified into high and low BPA exposure groups based on the median concentration.Results:BPA was detected in all samples(100%)with a median concentration of 2.41μg/L(IQR:0.68-4.96).The high BPA exposure group(≥2.41μg/L)had a significantly higher proportion of gestational diabetes mellitus(GDM)(42.9%vs.17.1%,p=0.021)and a lower median fetal birth weight(3250 g vs.3450 g,p=0.048)compared to the low exposure group.Conclusion:This pilot study reveals ubiquitous BPA exposure in pregnant women from Northeastern Yunnan.The observed preliminary associations with GDM and reduced fetal birth weight warrant further investigation in larger,longitudinal studies.展开更多
Global warming and socioeconomic development are expected to exacerbate human exposure to heat stress,but the extent and inequality of such changes remain unclear.Here,we quantified the future population exposure to h...Global warming and socioeconomic development are expected to exacerbate human exposure to heat stress,but the extent and inequality of such changes remain unclear.Here,we quantified the future population exposure to heat stress(PEHS)under different Shared Socioeconomic Pathways(SSPs)and Representative Concentration Pathways(RCPs)scenarios using a novel decomposition framework that separates the contributions of climate change,population change,and their interaction.Results show that global PEHS will increase substantially during the 21st century,with low-latitude regions experiencing the largest absolute increases,and high-latitude regions facing the largest relative increases.Globally,projected increases in PEHS under SSP3-7.0 are roughly three times those under SSP1-2.6,with low latitudes contributing about 70%-75%of the global total.SSP1-2.6 most effectively limits future heat exposure,with the highest risks in low-latitude developing regions,underscoring the need for low-emission pathways and targeted population and urbanization management.The findings highlight the urgent need for both climate mitigation and population adaptation strategies to address the growing and uneven heat exposure risks worldwide.展开更多
Objective: To investigate the efficacy of multidimensional protective nursing interventions in reducing occupational exposure risks to hydrofluoric acid in dental departments. Methods: The study was conducted between ...Objective: To investigate the efficacy of multidimensional protective nursing interventions in reducing occupational exposure risks to hydrofluoric acid in dental departments. Methods: The study was conducted between January 2024 and January 2025, involving 60 healthcare workers who were randomly assigned to groups. The control group (n = 30) received conventional occupational protective nursing care, while the observation group underwent multidimensional protective nursing interventions. Results: Following intervention, the observation group demonstrated significantly higher scores than the control group in knowledge of hydrofluoric acid occupational exposure, occupational exposure risk perception, and protective skill operation (p < 0.05). Emergency response capability scores and protective behavior implementation scores were also higher in the observation group (p < 0.05). Compared to the control group, the observation group exhibited higher occupational health satisfaction rates and lower occupational exposure incidence rates (p < 0.05). Conclusion: Multidimensional protective nursing interventions effectively enhance dental healthcare personnel’s awareness and protective capabilities regarding hydrofluoric acid occupational exposure, improve compliance with protective measures, and significantly reduce occupational exposure risks. This approach warrants promotion and application in occupational protective nursing interventions within dental departments.展开更多
Urban populations are increasingly exposed to extreme heat due to climate change and rapid urbanization,heightening health risks in cities worldwide.Accurate heat exposure assessment is essential for public health pla...Urban populations are increasingly exposed to extreme heat due to climate change and rapid urbanization,heightening health risks in cities worldwide.Accurate heat exposure assessment is essential for public health planning and risk reduction.Most existing approaches rely on a single threshold temperature(e.g.,35℃of daily max temperature),applied uniformly to the entire population.However,this one-size-fits-all assumption overlooks substantial differences in heat sensitivity across population subgroups.In this study,we address this limitation by quantifying subgroup-specific temperature-mortality relationships and using corresponding minimum mortality temperatures(MMTs)to assess heat exposure.Results show that the population-wide MMT was 27.5℃,but it varied greatly across population subgroups.The elderly population(≥65)had an MMT of 24.6℃,much lower than the 28.6℃observed in younger individuals(<65).Females also exhibited a lower MMT that males(25℃versus 28.2℃).However,educational attainment did not significantly affect MMT.Using a uniform MMT resulted in substantial underestimation of heat exposure,ranging from 25.3%in 1990 to 13.9%in 2020,reflecting demographic shifts over time.Spatially,nearly half of the city experienced underestimated heat risk,especially in central and northeastern regions where heat-vulnerable populations are concentrated.These findings underscore the need for more nuanced heat exposure assessments that account for demographic and spatial variability,paving the way for targeted public health interventions to protect the most vulnerable urban populations.展开更多
Bisphenol F(BPF)and Bisphenol S(BPS)are widely used substitutes for Bisphenol A(BPA).However,growing evidence indicated that BPF and BPS may induce physiological effects similar to those of BPA.Furthermore,chemical ma...Bisphenol F(BPF)and Bisphenol S(BPS)are widely used substitutes for Bisphenol A(BPA).However,growing evidence indicated that BPF and BPS may induce physiological effects similar to those of BPA.Furthermore,chemical management and control is primarily focus on the risk assessment of individual compounds,often overlooking the implications of chemical mixtures.We hypothesize that exposure to a mixture of BPA and its substitutes will enhance their endocrine-disruptive effects,disrupt steroid hormone homeostasis,and further impair reproductive system functionality.In the animal study,both female and male mice were exposed to 333μg/kg of BPA,BPF,BPS,their mixture(333μg/kg(MIXL),and 1 mg/kg(MIXH))via gavage daily for four weeks.The study demonstrated that bisphenols(BPs)affected the expression of genes related to steroid hormone synthesis.The MIXL group of female mice exhibited an increasing trend in estradiol(E2)levels and a decreasing trend in progesterone(Pg)and testosterone(TT)levels.Additionally,follicular development was impacted,resulting in an increased number of atretic follicles.In contrast,a significant increase in E2 concentration and disruption of testicular morphology were observed in the MIXH group of male mice,accompanied by a decline in sperm quality.Importantly,these results were corroborated by a population-based investigation.Collectively,the animal experiments indicate that mixed exposure to BPs disrupts hormone levels and adversely affects reproductive function,while epidemiological evidence further establishes correlative links between bisphenols and hormone levels.These findings underscore the necessity of considering chemical mixtures during testing and risk assessment.展开更多
Foliar uptake of airborne metal(loid)s plays a crucial role in metal(loid)accumulation in plant organs and is influ-enced by the size and emission sources of aerosols.Given the high enrichment of toxic metal(loid)s in...Foliar uptake of airborne metal(loid)s plays a crucial role in metal(loid)accumulation in plant organs and is influ-enced by the size and emission sources of aerosols.Given the high enrichment of toxic metal(loid)s in submicron-scale particulates(PM1),this study established a PM1 exposure system to examine airborne metal(loid)accu-mulation and foliar physiological responses in Oryza sativa L.The results showed that the concentrations of Cu,Zn,As,Pb,and Cd in the leaves and grains were influenced not only by the airborne metal(loid)levels but also by the specific nature of the PM1 particles.The quantitative model for PM1-associated Pb entry into leaf tissue indicated that foliar Pb accumulation was primarily driven by particle adhesion,followed by hydrophilic pene-tration and trans-stomatal liquid film migration,accounting for 87%–89%of the total accumulation.The strong hygroscopicity and high Pb activity of PM1 emitted from waste incineration(WI)increased the Pb absorption coefficient via the hydrophilic and liquid film migration pathway.In contrast,the high hydrophobicity of PM1 from coal burning(CB)led to greater retention of Pb on leaf surfaces.Both foliar reactive oxygen metabolism and photosynthesis indices were sensitive to air pollution.Foliar metal(loid)accumulation and airborne PM1 concentration accounted for the variance in physiological responses in rice leaves.Our results also indicated that Pb was the key element in PM1 emissions from both coal burning(CB)and waste incineration(WI)responsible for significant physiological changes in rice leaves.展开更多
Kiehl and colleagues1 utilized data from the Osteoarthritis Initiative(OAI)to address a clinically significant question:Is lifetime participation in strength training(ST)associated with improved trajectories of pain,f...Kiehl and colleagues1 utilized data from the Osteoarthritis Initiative(OAI)to address a clinically significant question:Is lifetime participation in strength training(ST)associated with improved trajectories of pain,function,and mobility in individuals with knee osteoarthritis(OA)?Among 3192 participants,those classified as“Lifelong ST”(n=142)demonstrated superior 4-year patient-reported outcomes and exhibited the lowest incidence of mobility disability(0.8%vs 2.3%–4.1%).Notably,they also maintained the fastest walking speeds at Year 4.展开更多
Synthetic phenolic antioxidants(SPAs)are widely used in diverse industries due to their exceptional antioxidant characteristics.However,human exposure to SPAs may cause health problems.In this study,226 dust samples w...Synthetic phenolic antioxidants(SPAs)are widely used in diverse industries due to their exceptional antioxidant characteristics.However,human exposure to SPAs may cause health problems.In this study,226 dust samples were collected from 10 provinces in China,and six SPAs(three parent SPAs and their three transformation products)were analyzed.The concentrations of6SPAs(the sum of six target compounds)ranged from 15.4 to 3210 ng/g(geometric mean(GM):169 ng/g).The highest concentration of6SPAswas found in Sichuan Province(GM:349 ng/g),which was approximately 4 times higher than that in Hubei Province(81.6 ng/g)(p<0.05).The concentrations of butylated hydroxytoluene(BHT),2,2'-methylene bis(4-methyl-6–tert-butylphenol)(AO2246),2,6-di–tert–butyl–1,4-benzoquinone(BHT-Q),2,6-di–tert–butyl–4-(hydroxymethyl)phenol(BHT-OH),and ∑_(p)-SPAs were substantially higher in dust from urban areas than rural areas(p<0.05).AO2246 concentration in dust from homes(GM:0.400 ng/g)was about 4 times higher than that in workplaces(0.116 ng/g)(p<0.01).Significantly higherp-SPAs concentrations were found in dust from homes(GM:17.5 ng/g)than workplaces(11.4 ng/g)(p<0.01).The estimated daily intakes(EDIs)of ∑_(6)SPAs exposed through dust ingestion were 0.582,0.342,0.197,0.076,and 0.080 ng/kg bw/day in different age groups,and exposed through dermal contact was 0.358,0.252,0.174,0.167,and 0.177 ng/kg bw/day.EDIs showed that the exposure risks of SPAs decreased with age.This is the first work to determine SPAs in dust from10 provinces in China and investigate the spatial distribution of SPAs in those regions.展开更多
This study investigated environmental distribution and human exposure of polycyclic aromatic hydrocarbons(PAHs)and their derivatives in one Chinese petroleum refinery facility.It was found that,following with high con...This study investigated environmental distribution and human exposure of polycyclic aromatic hydrocarbons(PAHs)and their derivatives in one Chinese petroleum refinery facility.It was found that,following with high concentrations of 16 EPA PAHs(∑Parent-PAHs)in smelting subarea of studied petroleum refinery facility,total derivatives of PAHs[named as XPAHs,including nitro PAHs(NPAHs),chlorinated PAHs(Cl-PAHs),and brominated PAHs(Br-PAHs)]in gas(mean=1.57×10^(4)ng/m^(3)),total suspended particulate(TSP)(mean=4.33×10^(3) ng/m^(3))and soil(mean=4.37×10^(3) ng/g)in this subarea had 1.76-6.19 times higher levels than those from other subareas of this facility,surrounding residential areas and reference areas,indicating that petroleum refining processes would lead apparent derivation of PAHs.Especially,compared with those in residential and reference areas,gas samples in the petrochemical areas had higher∑NPAH/∑PAHs(mean=2.18),but lower∑Cl-PAH/∑PAHs(mean=1.43×10^(-1))and∑Br-PAH/∑PAHs ratios(mean=7.49×10^(-2)),indicating the richer nitrification of PAHs than chlorination during petrochemical process.The occupational exposure to PAHs and XPAHs in this petroleum refinery facility were 24-343 times higher than non-occupational exposure,and the ILCR(1.04×10^(-4))for petrochemical workers was considered to be potential high risk.Furthermore,one expanded high-resolution screening through GC Orbitrap/MS was performed for soils from petrochemical area,and another 35 PAHs were found,including alkyl-PAHs,phenyl-PAHs and other species,indicat-ing that profiles and risks of PAHs analogs in petrochemical areas deserve further expanded investigation.展开更多
To further expand the application of Mg alloys at high temperatures,the oxidation resistance of Mg-0.3Ca and Mg-3.6Ca alloys with protective coating under flame exposure was studied.Results show that the oxidation res...To further expand the application of Mg alloys at high temperatures,the oxidation resistance of Mg-0.3Ca and Mg-3.6Ca alloys with protective coating under flame exposure was studied.Results show that the oxidation resistance of Mg-Ca alloys under flame exposure is significantly improved by the protective coating,and Mg-3.6Ca alloy shows better oxidation resistance performance.The surface temperature of Mg-Ca alloys is reduced by the coating,therefore improving the oxidation resistance under flame exposure.However,the thermal insulation effect of the coating on Mg-3.6Ca alloy is better,which can be attributed to the Ca accumulation on the surface film.In addition,the surface film with Ca accumulation layer plays a crucial role in protecting the alloy.No obvious Ca accumulation layer exists on the Mg-0.3Ca alloy surface,presenting a restricted protective effect.Nevertheless,the surface film containing Ca accumulation layer is formed on Mg-3.6 Ca alloy,which shows an excellent protective effect.展开更多
Epithelial-mesenchymal transition(EMT)plays an irreplaceable role in the development of silicosis.However,molecular mechanisms of EMT induced by silica exposure still remain to be addressed.Herein,metabolic profiles o...Epithelial-mesenchymal transition(EMT)plays an irreplaceable role in the development of silicosis.However,molecular mechanisms of EMT induced by silica exposure still remain to be addressed.Herein,metabolic profiles of human alveolar type II epithelial cells(A549 cells)exposed directly to silica were characterized using non-targeted metabolomic approaches.A total of 84 differential metabolites(DMs)were identified in silica-treated A549 cells undergoing EMT,which were mainly enriched in metabolisms of amino acids(e.g.,glutamate,alanine,aspartate),purine metabolism,glycolysis,etc.The number of DMs identified in the A549 cells obviously increased with the elevated exposure concentration of silica.Remarkably,glutamine catabolism was significantly promoted in the silica-treated A549 cells,and the levels of related metabolites(e.g.,succinate)and enzymes(e.g.,α-ketoglutarate(α-KG)dehydrogenase)were substantially up-regulated,with a preference toα-KG pathway.Supplementation of glutamine into the cell culture could substantially enhance the expression levels of both EMT-related markers and Snail(zinc finger transcription factor).Our results suggest that the EMT of human alveolar epithelial cells directly induced by silica can be essential to the development of silicosis.展开更多
Animal medicines,which boast a lengthy history as treasures of traditional Chinese medicine(TCM),frequently encounter safety challenges stemming from the accumulation of heavy metals and harmful elements,such as arsen...Animal medicines,which boast a lengthy history as treasures of traditional Chinese medicine(TCM),frequently encounter safety challenges stemming from the accumulation of heavy metals and harmful elements,such as arsenic(As)[1].The toxicity of As differs by species,especially inorganic arsenic(iAs),and current methods for assessing herbal risks based on total arsenic(tAs)content are insufficient[2].To address this,studies have focused on As contamination in TCMs,especially leeches.Widely used for anticoagulant and other pharmacological activities,leeches are susceptible to water contamination and high As levels due to immature farming technology[3].The aim of this study was to comprehensively analyze the distribution of tAs and toxic elements in leeches from multiple sources and batches.We used advanced analytical techniques(e.g.,liquid chromatography-inductively coupled plasma mass spectrometry(LC-ICPMS))to accurately identify As forms.This study aims to investigate the biological effects at the exposure point through in vitro experiments(simulating physiological conditions)and assess the potential clinical risks associated with iAs.展开更多
This article discusses the evolving real-world practice using nitazoxanide,nonsteroidal anti-inflammatory drugs(NSAIDs)and/or azithromycin(Kelleni’s protocol)to manage the evolving manifestations of severe acute resp...This article discusses the evolving real-world practice using nitazoxanide,nonsteroidal anti-inflammatory drugs(NSAIDs)and/or azithromycin(Kelleni’s protocol)to manage the evolving manifestations of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron EG.5.1,its descendant HV.1 as well as BA.2.86 and its descendant JN.1 subvariants in Egypt in 2024.These subvariants are well-known for their highly evolved immune-evasive properties and the manifestations include some peculiar manifestations as persistent cough besides high fever in young children as well as high fever,persistent severe cough,change of voice,loss of taste and smell,epigastric pain,nausea,vomiting,diarrhea,generalized malaise and marked bone aches in adults including the high-risk groups.It’s suggested that the ongoing SARS-CoV-2 evolution is continuing to mostly affect the high-risk groups of patients,to some of whom we’ve also successfully prescribed nitazoxanide and/or NSAIDs for post-exposure prophylaxis of all household contacts.We also continue to recommend starting the immune-modulatory antiviral Kelleni’s protocol as soon as possible in the course of infection and adjusting it in a personalized manner to be more aggressive from the beginning for the high risk patients,at least until the currently encountered surge of infections subsides.展开更多
The highly selective catalytic hydrogenation of halogenated nitroaromatics was achieved by employing Pd‑based catalysts that were co‑modified with organic and inorganic ligands.It was demonstrated that the catalysts c...The highly selective catalytic hydrogenation of halogenated nitroaromatics was achieved by employing Pd‑based catalysts that were co‑modified with organic and inorganic ligands.It was demonstrated that the catalysts contained Pd species in mixed valence states,with high valence Pd at the metal‑support interface and zero valence Pd at the metal surface.While the strong coordination of triphenylphosphine(PPh3)to Pd0 on the Pd surface prevents the adsorption of halogenated nitroaromatics and thus dehalogenation,the coordination of sodium metavanadate(NaVO3)to high‑valence Pd sites at the interface helps to activate H2 in a heterolytic pathway for the selective hydrogenation of nitro‑groups.The excellent catalytic performance of the interfacial active sites enables the selective hydrogenation of a wide range of halogenated nitroaromatics.展开更多
Objective Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health.Analysis of these mixture exposures presents several key challenges for environmental epidemio...Objective Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health.Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment,including high dimensionality,correlated exposure,and subtle individual effects.Methods We proposed a novel statistical approach,the generalized functional linear model(GFLM),to analyze the health effects of exposure mixtures.GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation.The robustness and efficiency was evaluated under various scenarios through extensive simulation studies.Results We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey(NHANES).In the first application,we examined the effects of 37 nutrients on BMI(2011–2016 cycles).The GFLM identified a significant mixture effect,with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI,respectively.For the second application,we investigated the association between four pre-and perfluoroalkyl substances(PFAS)and gout risk(2007–2018 cycles).Unlike traditional methods,the GFLM indicated no significant association,demonstrating its robustness to multicollinearity.Conclusion GFLM framework is a powerful tool for mixture exposure analysis,offering improved handling of correlated exposures and interpretable results.It demonstrates robust performance across various scenarios and real-world applications,advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.展开更多
Many studies have shown the negative relationship between long term exposure to PM_(2.5)and cardiac dysfunction.Recently,studies have shown that even a single exposure of PM_(2.5)from air sample in permissible range c...Many studies have shown the negative relationship between long term exposure to PM_(2.5)and cardiac dysfunction.Recently,studies have shown that even a single exposure of PM_(2.5)from air sample in permissible range can induce very mild cardiac pathological changes.In the present study,we revisited the toxic effect of PM_(2.5)on rat heart by adopting single and multiple exposure durations.FemaleWistar ratswere exposed to PM_(2.5)at a concentration of 250μg/m3 daily for 3 hr for single(1 day)and multiple(7,14,21 days)durations.The major pathological changes noted in 21 days exposed myocardium comprised of an elevated ST segment(the segment between the S wave and the T wave),development of cardiac fibrosis,hypertrophy,cardiac injury,tissue inflammation and declined cardiac function.With 14 days exposed heart,the electrocardiograms(ECG),data showed insignificantly declined heart rate and an increased QT(the time from the start of the Q wave to the end of the T wave)interval along with mild fibrosis,hypertrophy and lesser number of TUNEL positive cells.On the other hand,single-and 7-days exposure to PM_(2.5)did not impart any significant changes in the myocardium.To determine the reversibility potential of PM_(2.5)induced cardiotoxicity,a washout period of 24 hours was adopted and all observed changes in the myocardium were reversed till day 7,but not in 14-and 21-days exposed samples.Based on the above findings we concluded that PM_(2.5)associated cardiac dysfunction is the cumulative outcome of ineffective cardiac adaptive and repair process that accumulate additively over the time due to prolonged exposure durations.展开更多
基金partially supported by the funding from Celgene Corporation (USA)。
文摘Drug optimization, which improves drug potency/specificity by structure-activity relationship(SAR) and drug-like properties, is rigorously performed to select drug candidates for clinical trials. However,the current drug optimization may overlook the structure-tissue exposure/selectivity-relationship(STR) in disease-targeted tissues vs. normal tissues, which may mislead the drug candidate selection and impact the balance of clinical efficacy/toxicity. In this study, we investigated the STR in correlation with observed clinical efficacy/toxicity using seven selective estrogen receptor modulators(SERMs) that have similar structures, same molecular target, and similar/different pharmacokinetics. The results showed that drug’s plasma exposure was not correlated with drug’s exposures in the target tissues(tumor, fat pad, bone, uterus),while tissue exposure/selectivity of SERMs was correlated with clinical efficacy/safety. Slight structure modifications of four SERMs did not change drug’s plasma exposure but altered drug’s tissue exposure/selectivity.Seven SERMs with high protein binding showed higher accumulation in tumors compared to surrounding normal tissues, which is likely due to tumor EPR effect of protein-bound drugs. These suggest that STR alters drug’s tissue exposure/selectivity in disease-targeted tissues vs. normal tissues impacting clinical efficacy/toxicity. Drug optimization needs to balance the SAR and STR in selecting drug candidate for clinical trial to improve success of clinical drug development.
基金Under the auspices of National Key Research and Development Program of China(No.2017YFA0604902,2024YFF1306802)Natural Science Foundation of Fujian Province(No.2022J01497)Open Project of the Strait Meteorology Laboratory(No.2025KF03)。
文摘China’s coastal regions,characterized by dense populations and industrial agglomeration,face escalating threats from typhoon disasters.Understanding the evolution of socio-economic exposure to future typhoon landfalls under global change is critical for effective disaster risk management.This study utilizes future typhoon track data simulated by the regional climate model version 4(RegCM4),combined with projected population and Gross Domestic Product(GDP)data for China’s coastal regions under three Shared Socioeconomic Pathways(SSPs:SSP1,sustainability;SSP2,middle of the road;SSP5,fossil-fueled development).We analyze typhoon impact zones for future periods(2030s,2050s,and 2090s)under Representative Concentration Pathways(RCPs:RCP2.6,RCP4.5,and RCP8.5,representing low,medium,and high greenhouse gas emission scenarios,respectively).Exposure levels for 2030,2050,and 2100 are calculated based on the annual average frequency of typhoon impacts during these periods,aiming to quantify the distribution characteristics of typhoon-affected population and GDP in China’s coastal regions.Key findings reveal two high-frequency typhoon im-pact zones:the Taiwan Strait region and the northern Qiongzhou Strait region.Furthermore,under RCP2.6,typhoon impacts may ex-tend to Liaoning,while RCP4.5 and RCP8.5 scenarios indicate potential impacts reaching further north to Heilongjiang.Under RCP4.5,Northeast China will experience the largest typhoon-affected area(43.800×10^(4) km^(2))by the 2030s.High population and GDP exposure concentrates in the Yangtze River Delta,the Pearl River Delta,and the Taiwan Strait coastal areas.Notably,Liaoning’s cumulative ex-posed population may exceed 0.100×10^(8) by 2030 and 2050 under RCP4.5 and RCP8.5 due to typhoon track migration.Given China’s location within the Western Pacific typhoon high-incidence region,the northward expansion of impacts will substantially escalate socio-economic exposure in mid-latitude regions previously at lower risk.These findings underscore the imperative for enhanced disaster pre-vention,mitigation strategies and targeted countermeasure research.
基金supported by grants from the National Key Research and Development Program of China(2023YFC3603100 and 2023YFC3603105)“Leading Goose”R&D Program of Zhejiang(2022C03076-4),China.
文摘Glyphosate(GLY),a widely used herbicide,has been extensively applied in both the agricultural and non-agricultural sectors worldwide.The rate of GLY use varies considerably depending on the crop type and local farming practices,which can be up to approximately 53.5%of agricultural land in certain regions.
文摘Objective:To assess prenatal Bisphenol A(BPA)exposure levels and explore their preliminary associations with maternal and fetal characteristics in a population from Northeastern Yunnan.Methods:A cross-sectional analysis was performed using data and urine samples from 70 pregnant women in their third trimester recruited at Qujing Central Hospital.Urinary BPA was measured by HPLC-MS/MS.Participants were stratified into high and low BPA exposure groups based on the median concentration.Results:BPA was detected in all samples(100%)with a median concentration of 2.41μg/L(IQR:0.68-4.96).The high BPA exposure group(≥2.41μg/L)had a significantly higher proportion of gestational diabetes mellitus(GDM)(42.9%vs.17.1%,p=0.021)and a lower median fetal birth weight(3250 g vs.3450 g,p=0.048)compared to the low exposure group.Conclusion:This pilot study reveals ubiquitous BPA exposure in pregnant women from Northeastern Yunnan.The observed preliminary associations with GDM and reduced fetal birth weight warrant further investigation in larger,longitudinal studies.
基金funded by National Natural Science Foundation of China(Grant No.42271273)Swedish Research Council(VR:2021-02163).
文摘Global warming and socioeconomic development are expected to exacerbate human exposure to heat stress,but the extent and inequality of such changes remain unclear.Here,we quantified the future population exposure to heat stress(PEHS)under different Shared Socioeconomic Pathways(SSPs)and Representative Concentration Pathways(RCPs)scenarios using a novel decomposition framework that separates the contributions of climate change,population change,and their interaction.Results show that global PEHS will increase substantially during the 21st century,with low-latitude regions experiencing the largest absolute increases,and high-latitude regions facing the largest relative increases.Globally,projected increases in PEHS under SSP3-7.0 are roughly three times those under SSP1-2.6,with low latitudes contributing about 70%-75%of the global total.SSP1-2.6 most effectively limits future heat exposure,with the highest risks in low-latitude developing regions,underscoring the need for low-emission pathways and targeted population and urbanization management.The findings highlight the urgent need for both climate mitigation and population adaptation strategies to address the growing and uneven heat exposure risks worldwide.
基金Construction of Standardized Protective Nursing Plan for Hydrofluoric Acid Operations in Dentistry and Research on Injury Prevention Effects(Project No.:FZ2025101)。
文摘Objective: To investigate the efficacy of multidimensional protective nursing interventions in reducing occupational exposure risks to hydrofluoric acid in dental departments. Methods: The study was conducted between January 2024 and January 2025, involving 60 healthcare workers who were randomly assigned to groups. The control group (n = 30) received conventional occupational protective nursing care, while the observation group underwent multidimensional protective nursing interventions. Results: Following intervention, the observation group demonstrated significantly higher scores than the control group in knowledge of hydrofluoric acid occupational exposure, occupational exposure risk perception, and protective skill operation (p < 0.05). Emergency response capability scores and protective behavior implementation scores were also higher in the observation group (p < 0.05). Compared to the control group, the observation group exhibited higher occupational health satisfaction rates and lower occupational exposure incidence rates (p < 0.05). Conclusion: Multidimensional protective nursing interventions effectively enhance dental healthcare personnel’s awareness and protective capabilities regarding hydrofluoric acid occupational exposure, improve compliance with protective measures, and significantly reduce occupational exposure risks. This approach warrants promotion and application in occupational protective nursing interventions within dental departments.
基金supported by the National Natural Science Foundation of China(Grant No.42225104)CAS Project for Young Scientists in Basic Research(Grant No.YSBR-086).
文摘Urban populations are increasingly exposed to extreme heat due to climate change and rapid urbanization,heightening health risks in cities worldwide.Accurate heat exposure assessment is essential for public health planning and risk reduction.Most existing approaches rely on a single threshold temperature(e.g.,35℃of daily max temperature),applied uniformly to the entire population.However,this one-size-fits-all assumption overlooks substantial differences in heat sensitivity across population subgroups.In this study,we address this limitation by quantifying subgroup-specific temperature-mortality relationships and using corresponding minimum mortality temperatures(MMTs)to assess heat exposure.Results show that the population-wide MMT was 27.5℃,but it varied greatly across population subgroups.The elderly population(≥65)had an MMT of 24.6℃,much lower than the 28.6℃observed in younger individuals(<65).Females also exhibited a lower MMT that males(25℃versus 28.2℃).However,educational attainment did not significantly affect MMT.Using a uniform MMT resulted in substantial underestimation of heat exposure,ranging from 25.3%in 1990 to 13.9%in 2020,reflecting demographic shifts over time.Spatially,nearly half of the city experienced underestimated heat risk,especially in central and northeastern regions where heat-vulnerable populations are concentrated.These findings underscore the need for more nuanced heat exposure assessments that account for demographic and spatial variability,paving the way for targeted public health interventions to protect the most vulnerable urban populations.
基金supported by the National Science Foundation of China(Nos.U23A20103,22476120 and 22106098)Shanxi Province Higher Education"Billion Project"Science and Technology Guidance Project,Youth Science and Technology Research Foundation of Shanxi Province(No.20210302124298)+2 种基金the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2020L0174)the Startup Foundation for Doctors of Shanxi Province(No.SD1917)the Startup Foundation for Doctors of Shanxi Medical University(No.XD1917).
文摘Bisphenol F(BPF)and Bisphenol S(BPS)are widely used substitutes for Bisphenol A(BPA).However,growing evidence indicated that BPF and BPS may induce physiological effects similar to those of BPA.Furthermore,chemical management and control is primarily focus on the risk assessment of individual compounds,often overlooking the implications of chemical mixtures.We hypothesize that exposure to a mixture of BPA and its substitutes will enhance their endocrine-disruptive effects,disrupt steroid hormone homeostasis,and further impair reproductive system functionality.In the animal study,both female and male mice were exposed to 333μg/kg of BPA,BPF,BPS,their mixture(333μg/kg(MIXL),and 1 mg/kg(MIXH))via gavage daily for four weeks.The study demonstrated that bisphenols(BPs)affected the expression of genes related to steroid hormone synthesis.The MIXL group of female mice exhibited an increasing trend in estradiol(E2)levels and a decreasing trend in progesterone(Pg)and testosterone(TT)levels.Additionally,follicular development was impacted,resulting in an increased number of atretic follicles.In contrast,a significant increase in E2 concentration and disruption of testicular morphology were observed in the MIXH group of male mice,accompanied by a decline in sperm quality.Importantly,these results were corroborated by a population-based investigation.Collectively,the animal experiments indicate that mixed exposure to BPs disrupts hormone levels and adversely affects reproductive function,while epidemiological evidence further establishes correlative links between bisphenols and hormone levels.These findings underscore the necessity of considering chemical mixtures during testing and risk assessment.
基金supported by the National Natural Science Foundation of China(Nos.42077367 and 21677123).
文摘Foliar uptake of airborne metal(loid)s plays a crucial role in metal(loid)accumulation in plant organs and is influ-enced by the size and emission sources of aerosols.Given the high enrichment of toxic metal(loid)s in submicron-scale particulates(PM1),this study established a PM1 exposure system to examine airborne metal(loid)accu-mulation and foliar physiological responses in Oryza sativa L.The results showed that the concentrations of Cu,Zn,As,Pb,and Cd in the leaves and grains were influenced not only by the airborne metal(loid)levels but also by the specific nature of the PM1 particles.The quantitative model for PM1-associated Pb entry into leaf tissue indicated that foliar Pb accumulation was primarily driven by particle adhesion,followed by hydrophilic pene-tration and trans-stomatal liquid film migration,accounting for 87%–89%of the total accumulation.The strong hygroscopicity and high Pb activity of PM1 emitted from waste incineration(WI)increased the Pb absorption coefficient via the hydrophilic and liquid film migration pathway.In contrast,the high hydrophobicity of PM1 from coal burning(CB)led to greater retention of Pb on leaf surfaces.Both foliar reactive oxygen metabolism and photosynthesis indices were sensitive to air pollution.Foliar metal(loid)accumulation and airborne PM1 concentration accounted for the variance in physiological responses in rice leaves.Our results also indicated that Pb was the key element in PM1 emissions from both coal burning(CB)and waste incineration(WI)responsible for significant physiological changes in rice leaves.
文摘Kiehl and colleagues1 utilized data from the Osteoarthritis Initiative(OAI)to address a clinically significant question:Is lifetime participation in strength training(ST)associated with improved trajectories of pain,function,and mobility in individuals with knee osteoarthritis(OA)?Among 3192 participants,those classified as“Lifelong ST”(n=142)demonstrated superior 4-year patient-reported outcomes and exhibited the lowest incidence of mobility disability(0.8%vs 2.3%–4.1%).Notably,they also maintained the fastest walking speeds at Year 4.
基金supported by the National Key Research and Development Program of China(No.2023YFC3706602)the National Natural Science Foundation of China(Nos.22225605 and 22193051)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB0750200).
文摘Synthetic phenolic antioxidants(SPAs)are widely used in diverse industries due to their exceptional antioxidant characteristics.However,human exposure to SPAs may cause health problems.In this study,226 dust samples were collected from 10 provinces in China,and six SPAs(three parent SPAs and their three transformation products)were analyzed.The concentrations of6SPAs(the sum of six target compounds)ranged from 15.4 to 3210 ng/g(geometric mean(GM):169 ng/g).The highest concentration of6SPAswas found in Sichuan Province(GM:349 ng/g),which was approximately 4 times higher than that in Hubei Province(81.6 ng/g)(p<0.05).The concentrations of butylated hydroxytoluene(BHT),2,2'-methylene bis(4-methyl-6–tert-butylphenol)(AO2246),2,6-di–tert–butyl–1,4-benzoquinone(BHT-Q),2,6-di–tert–butyl–4-(hydroxymethyl)phenol(BHT-OH),and ∑_(p)-SPAs were substantially higher in dust from urban areas than rural areas(p<0.05).AO2246 concentration in dust from homes(GM:0.400 ng/g)was about 4 times higher than that in workplaces(0.116 ng/g)(p<0.01).Significantly higherp-SPAs concentrations were found in dust from homes(GM:17.5 ng/g)than workplaces(11.4 ng/g)(p<0.01).The estimated daily intakes(EDIs)of ∑_(6)SPAs exposed through dust ingestion were 0.582,0.342,0.197,0.076,and 0.080 ng/kg bw/day in different age groups,and exposed through dermal contact was 0.358,0.252,0.174,0.167,and 0.177 ng/kg bw/day.EDIs showed that the exposure risks of SPAs decreased with age.This is the first work to determine SPAs in dust from10 provinces in China and investigate the spatial distribution of SPAs in those regions.
基金supported by the National Key Research and Development Program of China(No.2019YFC1804501)the National Natural Science Foundation of China(Nos.22036007 and 22122611)+1 种基金the Natural Science Foundation of Shandong Province(No.ZR2020ME228)the Introduction and Cultivation Plan for Young Innovative Talents of Colleges and Universities.
文摘This study investigated environmental distribution and human exposure of polycyclic aromatic hydrocarbons(PAHs)and their derivatives in one Chinese petroleum refinery facility.It was found that,following with high concentrations of 16 EPA PAHs(∑Parent-PAHs)in smelting subarea of studied petroleum refinery facility,total derivatives of PAHs[named as XPAHs,including nitro PAHs(NPAHs),chlorinated PAHs(Cl-PAHs),and brominated PAHs(Br-PAHs)]in gas(mean=1.57×10^(4)ng/m^(3)),total suspended particulate(TSP)(mean=4.33×10^(3) ng/m^(3))and soil(mean=4.37×10^(3) ng/g)in this subarea had 1.76-6.19 times higher levels than those from other subareas of this facility,surrounding residential areas and reference areas,indicating that petroleum refining processes would lead apparent derivation of PAHs.Especially,compared with those in residential and reference areas,gas samples in the petrochemical areas had higher∑NPAH/∑PAHs(mean=2.18),but lower∑Cl-PAH/∑PAHs(mean=1.43×10^(-1))and∑Br-PAH/∑PAHs ratios(mean=7.49×10^(-2)),indicating the richer nitrification of PAHs than chlorination during petrochemical process.The occupational exposure to PAHs and XPAHs in this petroleum refinery facility were 24-343 times higher than non-occupational exposure,and the ILCR(1.04×10^(-4))for petrochemical workers was considered to be potential high risk.Furthermore,one expanded high-resolution screening through GC Orbitrap/MS was performed for soils from petrochemical area,and another 35 PAHs were found,including alkyl-PAHs,phenyl-PAHs and other species,indicat-ing that profiles and risks of PAHs analogs in petrochemical areas deserve further expanded investigation.
基金General Project of Natural Science Research in Higher Education Institutions in Jiangsu Province(23KJB430039)Major Natural Science Research Project of Higher Education Institutions in Jiangsu Province(21KJA460007)National Natural Science Foundation of China(51905462)。
文摘To further expand the application of Mg alloys at high temperatures,the oxidation resistance of Mg-0.3Ca and Mg-3.6Ca alloys with protective coating under flame exposure was studied.Results show that the oxidation resistance of Mg-Ca alloys under flame exposure is significantly improved by the protective coating,and Mg-3.6Ca alloy shows better oxidation resistance performance.The surface temperature of Mg-Ca alloys is reduced by the coating,therefore improving the oxidation resistance under flame exposure.However,the thermal insulation effect of the coating on Mg-3.6Ca alloy is better,which can be attributed to the Ca accumulation on the surface film.In addition,the surface film with Ca accumulation layer plays a crucial role in protecting the alloy.No obvious Ca accumulation layer exists on the Mg-0.3Ca alloy surface,presenting a restricted protective effect.Nevertheless,the surface film containing Ca accumulation layer is formed on Mg-3.6 Ca alloy,which shows an excellent protective effect.
基金supported by the National Natural Science Foundation of China(Nos.22206207,22127810,and 22276224)the Natural Science Foundation of Guangdong Province(Nos.2021A1515011546 and 2023A1515010085)the Science and Technology Planning Project of Guangzhou(No.202102080005)。
文摘Epithelial-mesenchymal transition(EMT)plays an irreplaceable role in the development of silicosis.However,molecular mechanisms of EMT induced by silica exposure still remain to be addressed.Herein,metabolic profiles of human alveolar type II epithelial cells(A549 cells)exposed directly to silica were characterized using non-targeted metabolomic approaches.A total of 84 differential metabolites(DMs)were identified in silica-treated A549 cells undergoing EMT,which were mainly enriched in metabolisms of amino acids(e.g.,glutamate,alanine,aspartate),purine metabolism,glycolysis,etc.The number of DMs identified in the A549 cells obviously increased with the elevated exposure concentration of silica.Remarkably,glutamine catabolism was significantly promoted in the silica-treated A549 cells,and the levels of related metabolites(e.g.,succinate)and enzymes(e.g.,α-ketoglutarate(α-KG)dehydrogenase)were substantially up-regulated,with a preference toα-KG pathway.Supplementation of glutamine into the cell culture could substantially enhance the expression levels of both EMT-related markers and Snail(zinc finger transcription factor).Our results suggest that the EMT of human alveolar epithelial cells directly induced by silica can be essential to the development of silicosis.
基金supported by the National Natural Science Foundation of China(Grant No.:82404856)the National Key Research and Development Program of China(Grant No.:2023YFC3504100)the Key projects for Building a Scientific System for Drug Regulation,China(Project No.:RS2024Z006).
文摘Animal medicines,which boast a lengthy history as treasures of traditional Chinese medicine(TCM),frequently encounter safety challenges stemming from the accumulation of heavy metals and harmful elements,such as arsenic(As)[1].The toxicity of As differs by species,especially inorganic arsenic(iAs),and current methods for assessing herbal risks based on total arsenic(tAs)content are insufficient[2].To address this,studies have focused on As contamination in TCMs,especially leeches.Widely used for anticoagulant and other pharmacological activities,leeches are susceptible to water contamination and high As levels due to immature farming technology[3].The aim of this study was to comprehensively analyze the distribution of tAs and toxic elements in leeches from multiple sources and batches.We used advanced analytical techniques(e.g.,liquid chromatography-inductively coupled plasma mass spectrometry(LC-ICPMS))to accurately identify As forms.This study aims to investigate the biological effects at the exposure point through in vitro experiments(simulating physiological conditions)and assess the potential clinical risks associated with iAs.
文摘This article discusses the evolving real-world practice using nitazoxanide,nonsteroidal anti-inflammatory drugs(NSAIDs)and/or azithromycin(Kelleni’s protocol)to manage the evolving manifestations of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron EG.5.1,its descendant HV.1 as well as BA.2.86 and its descendant JN.1 subvariants in Egypt in 2024.These subvariants are well-known for their highly evolved immune-evasive properties and the manifestations include some peculiar manifestations as persistent cough besides high fever in young children as well as high fever,persistent severe cough,change of voice,loss of taste and smell,epigastric pain,nausea,vomiting,diarrhea,generalized malaise and marked bone aches in adults including the high-risk groups.It’s suggested that the ongoing SARS-CoV-2 evolution is continuing to mostly affect the high-risk groups of patients,to some of whom we’ve also successfully prescribed nitazoxanide and/or NSAIDs for post-exposure prophylaxis of all household contacts.We also continue to recommend starting the immune-modulatory antiviral Kelleni’s protocol as soon as possible in the course of infection and adjusting it in a personalized manner to be more aggressive from the beginning for the high risk patients,at least until the currently encountered surge of infections subsides.
文摘The highly selective catalytic hydrogenation of halogenated nitroaromatics was achieved by employing Pd‑based catalysts that were co‑modified with organic and inorganic ligands.It was demonstrated that the catalysts contained Pd species in mixed valence states,with high valence Pd at the metal‑support interface and zero valence Pd at the metal surface.While the strong coordination of triphenylphosphine(PPh3)to Pd0 on the Pd surface prevents the adsorption of halogenated nitroaromatics and thus dehalogenation,the coordination of sodium metavanadate(NaVO3)to high‑valence Pd sites at the interface helps to activate H2 in a heterolytic pathway for the selective hydrogenation of nitro‑groups.The excellent catalytic performance of the interfacial active sites enables the selective hydrogenation of a wide range of halogenated nitroaromatics.
基金supported in part by the Young Scientists Fund of the National Natural Science Foundation of China(Grant Nos.82304253)(and 82273709)the Foundation for Young Talents in Higher Education of Guangdong Province(Grant No.2022KQNCX021)the PhD Starting Project of Guangdong Medical University(Grant No.GDMUB2022054).
文摘Objective Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health.Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment,including high dimensionality,correlated exposure,and subtle individual effects.Methods We proposed a novel statistical approach,the generalized functional linear model(GFLM),to analyze the health effects of exposure mixtures.GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation.The robustness and efficiency was evaluated under various scenarios through extensive simulation studies.Results We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey(NHANES).In the first application,we examined the effects of 37 nutrients on BMI(2011–2016 cycles).The GFLM identified a significant mixture effect,with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI,respectively.For the second application,we investigated the association between four pre-and perfluoroalkyl substances(PFAS)and gout risk(2007–2018 cycles).Unlike traditional methods,the GFLM indicated no significant association,demonstrating its robustness to multicollinearity.Conclusion GFLM framework is a powerful tool for mixture exposure analysis,offering improved handling of correlated exposures and interpretable results.It demonstrates robust performance across various scenarios and real-world applications,advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
基金the Indian Council of Medical Research(No.3/1/2(22)/Env/2021-NCD-II)Department of science and technology,India(CRG/2021/000227)for funding this research.
文摘Many studies have shown the negative relationship between long term exposure to PM_(2.5)and cardiac dysfunction.Recently,studies have shown that even a single exposure of PM_(2.5)from air sample in permissible range can induce very mild cardiac pathological changes.In the present study,we revisited the toxic effect of PM_(2.5)on rat heart by adopting single and multiple exposure durations.FemaleWistar ratswere exposed to PM_(2.5)at a concentration of 250μg/m3 daily for 3 hr for single(1 day)and multiple(7,14,21 days)durations.The major pathological changes noted in 21 days exposed myocardium comprised of an elevated ST segment(the segment between the S wave and the T wave),development of cardiac fibrosis,hypertrophy,cardiac injury,tissue inflammation and declined cardiac function.With 14 days exposed heart,the electrocardiograms(ECG),data showed insignificantly declined heart rate and an increased QT(the time from the start of the Q wave to the end of the T wave)interval along with mild fibrosis,hypertrophy and lesser number of TUNEL positive cells.On the other hand,single-and 7-days exposure to PM_(2.5)did not impart any significant changes in the myocardium.To determine the reversibility potential of PM_(2.5)induced cardiotoxicity,a washout period of 24 hours was adopted and all observed changes in the myocardium were reversed till day 7,but not in 14-and 21-days exposed samples.Based on the above findings we concluded that PM_(2.5)associated cardiac dysfunction is the cumulative outcome of ineffective cardiac adaptive and repair process that accumulate additively over the time due to prolonged exposure durations.
