Non-ferrous metal smelting poses significant risks to public health.Specifically,the copper smelting process releases arsenic,a semi-volatile metalloid,which poses an emerging exposure risk to both workers and nearby ...Non-ferrous metal smelting poses significant risks to public health.Specifically,the copper smelting process releases arsenic,a semi-volatile metalloid,which poses an emerging exposure risk to both workers and nearby residents.To comprehensively understand the internal exposure risks of metal(loid)s from copper smelting,we explored eighteen metal(loid)s and arsenic metabolites in the urine of both occupational and non-occupational populations using inductively coupled plasma mass spectrometry with high-performance liquid chromatography and compared their health risks.Results showed that zinc and copper(485.38 and 14.00μg/L),and arsenic,lead,cadmium,vanadium,tin and antimony(46.80,6.82,2.17,0.40,0.44 and 0.23μg/L,respectively)in workers(n=179)were significantly higher compared to controls(n=168),while Zinc,tin and antimony(412.10,0.51 and 0.15μg/L,respectively)of residents were significantly higher than controls.Additionally,workers had a higher monomethyl arsenic percentage(MMA%),showing lower arsenic methylation capacity.Source appointment analysis identified arsenic,lead,cadmium,antimony,tin and thallium as co-exposure metal(loid)s from copper smelting,positively relating to the age of workers.The hazard index(HI)of workers exceeded 1.0,while residents and control were approximately at 1.0.Besides,all three populations had accumulated cancer risks exceeding 1.0×10^(-4),and arsenite(AsIII)was the main contributor to the variation of workers and residents.Furthermore,residents living closer to the smelting plant had higher health risks.This study reveals arsenic exposure metabolites and multiple metals as emerging contaminants for copper smelting exposure populations,providing valuable insights for pollution control in non-ferrous metal smelting.展开更多
BACKGROUND Numerous epidemiological studies have found that pesticide exposure is associated with the incidence of type 2 diabetes(T2D);however,the underlying mechanisms remain unknown.DNA methylation may play a role ...BACKGROUND Numerous epidemiological studies have found that pesticide exposure is associated with the incidence of type 2 diabetes(T2D);however,the underlying mechanisms remain unknown.DNA methylation may play a role in this process.AIM To identify the genes associated with pesticide exposure and T2D by reviewing the current literature.METHODS We systematically searched PubMed and Embase for relevant studies that examined the association between pesticide exposure and DNA methylation,and studies on DNA methylation and T2D through January 15,2024.RESULTS We identified six genes(Alu,CABLES1,CDH1,PDX1,PTEN,PTPRN2)related to pesticide exposure and T2D.We also suggested future research directions to better define the role of DNA methylation in the association between pesticide exposure and T2D.CONCLUSION DNA methylation of specific genes may play a vital role in the association between pesticide exposure and T2D.展开更多
Evidence on the association of occupational exposure to benzene,toluene,ethylbenzene,and xylene(BTEX)with hematologic and hepatic profiles were equivocal,and few studies have investigated overall effect of BTEX mixtur...Evidence on the association of occupational exposure to benzene,toluene,ethylbenzene,and xylene(BTEX)with hematologic and hepatic profiles were equivocal,and few studies have investigated overall effect of BTEX mixtures.Herein,significant higher concentrations(p<0.05)of hippuric acid,1,2-dihydroxybenzene,mandelic acid,trans,trans-muconic acid and phenylglyoxylic acid were found in petrochemical workers than the controls,in accordance with higher levels of hematologic and hepatic profiles found in petrochemical workers(p<0.05).Occupational exposure to individual BTEX was associated with elevated levels of white blood cell(WBC),lymphocyte(LYMPH),alanine aminotransferase(ALT),and gamma-glutamyl transferase(GGT).Further,the Weighted Quantile Sum Regression model and Bayesian Kernel Machine Regression model consistently identified a positive associa-tion between BTEX mixture exposure and WBC,LYMPH,and GGT.Xylene was the primary contributor to increased WBC,LYMPH,and GGT levels.Furthermore,BTEX exposure resulting in the increased inflammation indices were mainly related to perturbations of sphingolipid metabolism,biosynthesis of unsaturated fatty acids,and primary bile acid biosynthesis.Whereas metabolites mediated the correlation between BTEX exposure and liver function indiceswere related to the perturbations of biosynthesis of unsaturated fatty acids,arachidonic acid metabolism,sphingolipid metabolism,primary bile acid biosynthesis,etc.Our findings revealed potential health risk of occupational exposure to BTEX andmight help one to understand the link between BTEX exposure and hematologic and hepatic profiles.展开更多
Anemia is still prevalent among low and middle-income countries,posing serious family and social burdens.However,scarce studies provided evidence for real-world exposure to polycyclic aromatic hydrocarbons(PAHs)and an...Anemia is still prevalent among low and middle-income countries,posing serious family and social burdens.However,scarce studies provided evidence for real-world exposure to polycyclic aromatic hydrocarbons(PAHs)and anemia among pregnant women,as well as involved biological mechanisms.So,we conducted this study including 1717 late pregnant women fromZunyi Birth Cohort and collected urine samples for PAHs metabolites detection.Logistic regression and restricted cubic spline regression were used to examine exposuredisease risks and dose-response relationships.We conducted Bayesian kernel machine regression,weighted quantile sum regression,and quantile g-computation regression to fit the joint impacts of multiple PAHs in the real-world scenario on hypocalcemia and anemia.Results showed single exposure to 2-OHNap,2-OHFlu,9-OHFlu,1-OHPhe,2-OHPhe,3-OHPhe,and 1-OHPyr(all P-trend<0.05)increased the risks of hypocalcemia and anemia.Moreover,PAHs mixture was significantly related to higher risks of hypocalcemia and anemia,with 3-OHPhe and 1-OHPyr identified as their major drivers,respectively.Importantly,hypocalcemia served as a significant biological mechanism responsible for PAHs and anemia.Our findings suggest that individual and joint exposure to PAHs during late pregnancy elevate the anemia risk,and calcium supplementation might be a low-cost intervention target for reducing the PAHs-related impairment on anemia for pregnant women.展开更多
For much of the world＇s population, food is the major source of exposure to arsenic.Exposure to this non-essential metalloid at relatively low levels may be linked to a wide range of adverse health effects. Thus, eva...For much of the world＇s population, food is the major source of exposure to arsenic.Exposure to this non-essential metalloid at relatively low levels may be linked to a wide range of adverse health effects. Thus, evaluating foods as sources of exposure to arsenic is important in assessing risk and developing strategies that protect public health. Although most emphasis has been placed on inorganic arsenic as human carcinogen and toxicant, an array of arsenic-containing species are found in plants and animals used as foods. Here,we 2evaluate the contribution of complex organic arsenicals（arsenosugars, arsenolipids,and trimethylarsonium compounds） that are found in foods and consider their origins,metabolism, and potential toxicity. Commonalities in the metabolism of arsenosugars and arsenolipids lead to the production of di-methylated arsenicals which are known to exert many toxic effects. Evaluating foods as sources of exposure to these complex organic arsenicals and understanding the formation of reactive metabolites may be critical in assessing their contribution to aggregate exposure to arsenic.展开更多
Pathogenic microbes with antibiotic resistance can thrive on municipal solid waste as nutrients and be aerosolized and transported to vicinities during waste disposal processes.However,the characterization of pathogen...Pathogenic microbes with antibiotic resistance can thrive on municipal solid waste as nutrients and be aerosolized and transported to vicinities during waste disposal processes.However,the characterization of pathogenic bioaerosols and assessment of their exposure risks are lacking.Herein,particle size,concentration,activity,antibiotic resistance,and pathogenicity of airborne microorganisms were assessed in different sectors of a typical landfill.Results showed that active sector in downwind direction has the highest bioaerosol level(1234 CFU/m3),while residential area has the highest activity(14.82 mg/L).Botanical deodorizer from mist cannon can effectively remove bioaerosol.Most bioaerosols can be inhaled into respiratory system till bronchi with sizes ranging from 2.1−3.3 and 3.3−4.7μm.Pathogenic bacteria(Bacilli,Bacillus,and Burkholderia-Paraburkholderia)and allergenic fungi(Aspergillus,Cladosporium,and Curvularia)prevailed in landfill.Although high abundance of microbial volatile organic compounds(mVOCs)producing bioaerosols were detected,these mVOCs contributed little to odor issues in landfill.Notably,surrounding areas have higher levels of antibiotic-resistance genes(ARGs)than inner landfill with tetC,acrB,acrF,mdtF,and bacA as dominant ones.Most ARGs were significantly correlated with bacterial community,while environmental parameters mainly influenced fungal prevalence.These findings can assist in reducing and preventing respiratory allergy or infection risks in occupational environments relating to waste management.展开更多
Low levels (ng/g) of musk ketone (MK),used as a fragrance additive in the formulation of personal care products,are frequently detected in the water and other environment.Thus,aquatic organisms can be continuously exp...Low levels (ng/g) of musk ketone (MK),used as a fragrance additive in the formulation of personal care products,are frequently detected in the water and other environment.Thus,aquatic organisms can be continuously exposed to MK.In this study,kinetics and dose-response assessments of 2-amino-MK (AMK) metabolite,bound to cysteine-hemoglobin (Hb) in rainbow trout,formed by enzymatic nitro-reduction of MK have been demonstrated.Trout were exposed to a single exposure of 0.010,0.030,0.10,and 0.30 mg MK/g fish.Tw...展开更多
Fine particulate matter(PM2.5)is a major contributor to infant mortality.However,the attributable global burden remains unclear due to the absence of a nonlinear exposure-response function that links all-cause infant ...Fine particulate matter(PM2.5)is a major contributor to infant mortality.However,the attributable global burden remains unclear due to the absence of a nonlinear exposure-response function that links all-cause infant mortality to various PM2.5 concentrations.In this study,we systematically reviewed the literature on PM2.5 exposure and under-five child mortality,then conducted multicenter epidemiological analyses using Demographic and Health Survey(DHS)data with fixed-effects logit regression.We integrated literature-derived estimates with local PM2.5-mortality associations across multiple regions.Using meta-regression,we quantified per unit exposure effects to develop a nonlinear exposure-response function,subsequently extrapolated to 189 countries(1998–2019)to estimate the global infant mortality burden attributable to PM2.5 exposure.The results showed that prenatal exposure was more strongly associated with increased infant mortality in both linear and nonlinear analyses.The local effect of prenatal exposure was higher at the low-concentration end(<20μg/m^(3))than at the high-concentration end(>20μg/m^(3)).The attributable deaths declined from 2.22 to 1.44 million,yet the attributable fraction rose from 32.6%to 39.3%,indicating persistent PM2.5 risks despite child health improvements.These findings suggest that,although the improved child health partially mitigated the adverse effects of worsening air quality between 1998 and 2019,prenatal PM2.5 exposure remained a significant risk factor.展开更多
Tetrabromobisphenol A(TBBPA)is a flame retardant that adversely affects the environment and human health.The present study exposed HepG2 cells to low concentrations of TBBPA daily to investigate the changes in gene re...Tetrabromobisphenol A(TBBPA)is a flame retardant that adversely affects the environment and human health.The present study exposed HepG2 cells to low concentrations of TBBPA daily to investigate the changes in gene regulation,mainly related to pathways associated with the endocrine system.The quantitative polymerase chain reaction(qPCR)confirmed that prolonged exposure gradually activated the thyroid hormone and parathyroid hormone signaling pathways.The expression levels of genes related to the thyroid hormone signaling pathway were upregulated(1.15-8.54 times)after five generations of exposure to 1 and 81 nM TBBPA.Furthermore,co-exposure to 81 nM TBBPA and 0.5 nM thyroid hormone receptor antagonist for five generations significantly reduced the expression of thyroid hormone and parathyroid hormone receptors.Meanwhile,81 nM TBBPA inhibited the activation of the Ras pathway and downregulated Ras gene expression level(3.7 times),indicating the association between the toxic effect and thyroid hormone receptors.Additionally,our experiments revealed that the thyroid hormone pathway regulated the induction of the Ras signaling pathway by TBBPA.The study thus proves that daily exposure to TBBPA interferes with the thyroid hormone signaling pathway and subsequently the endocrine system.展开更多
China’s“three-child policy”,implemented in response to population aging,has made the protection of maternal and infant health an urgent priority.In this environmental and medical big-data era,the Zhejiang Environme...China’s“three-child policy”,implemented in response to population aging,has made the protection of maternal and infant health an urgent priority.In this environmental and medical big-data era,the Zhejiang Environmental and Birth Health Research Alliance(ZEBRA)maternity cohort was established with the aim of identifying risk factors for perinatal morbidity and mortality from the perspectives of both observational epidemiology and experimental etiology.Compared with conventional birth cohorts,the inclusion of a maternity cohort allows greater scope for research and places an emphasis on maternal health.In particular,it allows us to focus on pregnant women with a history of pregnancy-related illnesses and those planning to have a second or third child.There are currently many pressing issues in perinatal health,including the risk associations between exogenous together with endogenous factors and the occurrence of perinatal abnormalities,pregnancy complications,and adverse pregnancy outcomes.It is crucial to explore the interaction between environmental exposures and genetic factors affecting perinatal health if we are to improve it.It is also worthwhile to assess the feasibility of the early stage prediction of major perinatal abnormalities.We hope to study this in the ZEBRA cohort and also seek nationwide and international collaborations to establish a multicenter cohort consortium,with the ultimate goal of contributing epidemiological evidence to literature and providing evidence-based insights for global maternal and child healthcare.展开更多
Background:There is limited evidence of the association between long-term exposure to particulate matter with aerodynamic diameter≤2.5μm (fine particulate matter,PM_(2.5)) and gynecologic cancer incidence,particular...Background:There is limited evidence of the association between long-term exposure to particulate matter with aerodynamic diameter≤2.5μm (fine particulate matter,PM_(2.5)) and gynecologic cancer incidence,particularly in developing countries with high air pollution levels.The present study aimed to investigate the associations of long-term exposure to PM_(2.5)and its constituents with the incidence of gynecologic cancer,and to identify the primary constituent.Methods:A total of 85,500 women from the National Urban Cancer Screening Program in Beijing (2013-2019) were included.5-year average concentrations of PM_(2.5)mass and its constituents,namely carbon black (BC),ammonium (NH_(4)^(+)),nitrate (NO_(3)^(-)),organic matter (OM),and sulfate (SO_(4)^(2-)),were obtained from the Tracking Air Pollution in China (TAP) dataset.Cox proportional hazard models were used to analyze the association between long-term exposure to PM_(2.5)and its constituents and gynecologic cancer incidence.Mixture exposure models,including quantile-based gcomputation (Qgcomp) and explanatory machine learning model (SHapley Additive exPlanations,SHAP),were used to assess the effect of each constituent.Results:During a mean follow-up of 6.22 years,524 participants were diagnosed with gynecologic cancer.The adjusted hazard ratios (HRs) for gynecologic cancer incidence associated with 1 standard deviation (SD) increment was 1.10 (95%CI:1.00-1.22) for PM_(2.5),1.12 (95%CI:1.01-1.23) for BC,1.11 (95%CI:1.00-1.23) for NH_(4)^(+),1.12 (95%CI:1.01-1.23) for OM,1.12 (95%CI:1.01-1.23) for SO_(4)^(2-),and1.08 (95%CI:0.98-1.19) for NO_(3)^(-).The Qgcomp model indicated the association between a mixture of PM_(2.5)constituents and gynecologic cancer incidence,with the weights assigned to BC (61.6%),SO_(4)^(2-)(35.9%),and NO_(3)^(-)(2.5%) in the positive direction.The SHAP model showed that SO_(4)^(2-)was the most important constituent,with the mean|SHAP|value of 0.0322,followed by BC (0.0270),OM (0.0232),NO_(3)^(-)(0.0212) and NH_(4)^(+)(0.0190).Conclusions:Long-term exposure to PM_(2.5)was associated with gynecologic cancer incidence,with SO_(4)^(2-)and BC significantly contributing to the association.展开更多
Studies have shown that exposure to phthalates can affect neonatal birth weight.However,epidemiological evidence on the mediating role of maternal thyroid hormones is limited.Therefore,this study,based on the Complian...Studies have shown that exposure to phthalates can affect neonatal birth weight.However,epidemiological evidence on the mediating role of maternal thyroid hormones is limited.Therefore,this study,based on the Compliance Birth Cohort,aimed to reveal the potential mediating function of maternal thyroid hormones during pregnancy between phthalic acid ester(PAE)exposure and neonatal birth weight.The study included 1274 mother−infant pairs.Linear regression analysis revealed a negative association between MIBP and neonatal birth weight(β=−62.236;95%CI:−118.842,−5.631).Bayesian kernel-machine regression(BKMR)indicated a nonlinear negative association between PAE metabolites(PAEs)and birth weight.Linear regression analysis revealed a positive association between neonatal birth weight and FT3(β=41.605;95%CI:2.631,80.380).The BKMR model also found a positive association between thyroid hormones and birth weight but in a nonlinear manner.Additionally,linear regression analyses showed that TSH,TT3,TT4,FT3,and FT4 were associated with PAEs.The BKMR model revealed an inverted U-shaped association of PAEs with TT3 and FT3 and a nonlinear association with TSH,TT4,and FT4.Structural equation modeling revealed that MMP,MIBP,MBP,MEHP,MOP,MBZP,and MEOHP contributed to a net reduction in neonatal birth weight of 32 g through the TT3,FT3,TT4,and FT4 pathways.The findings suggest that exposure to PAEs during pregnancy leads to a reduction in neonatal birth weight,possibly due to the involvement of maternal thyroid hormones as mediators.Controlling maternal thyroid hormone levels during pregnancy may be a viable method to reduce the harmful effects of phthalate exposure on the developing fetus.展开更多
Using Arsenazo Ⅲ as a myoplasmic calcium indicator, we have studied the calcium transients evoked by voltage-clamp depolarizing pulses in frog twitch muscle fibres which had been temporarily depolarized by 80 mmol/LK...Using Arsenazo Ⅲ as a myoplasmic calcium indicator, we have studied the calcium transients evoked by voltage-clamp depolarizing pulses in frog twitch muscle fibres which had been temporarily depolarized by 80 mmol/LK^+ in the absence or presence of myoplasmic Li^+. After the high K^+ exposure, for either a short (15 rain) or long(1 h) time, the post-K^+ calcium transients could gradually be restored to the level of the pre-K^+ ones, if the fibres were not loaded with Li^+.In contrast, the post-K^+ calcium transients of Li^+-loaded fibres could not fully recover,and were depressed in a Li^+ concentration-dependent manner.The mean amplitude of the post-K^+ responses recorded more than 3.5 h after 15 min high K^+ exposure was reduced to 56% of pre-K^+ control in the fibres which had been loaded with Li^+ in 20 mmol/L Li^+ Ringer's solution.This depression could be prevented or partially reversed by exogenous myo-inositol.More depression could be induced by 1 h high K^+ exposure, but the presence of exogenous myo-inositol could not clearly prevent the post-K^+ calcium transients from reduction.Assuming that high K^+ exposure caused a depletion of myo-inositol and probably other changes in the metabolism of inositol phospholipids in Li^+ loaded fibres,we conclude that some metabolites of phosphoinositides may play modulation roles in excitation-contraction coupling in frog twitch muscle fibres.展开更多
Objective:Studies conducted in large metropolitan inner-city communities with high violent crime rates have demonstrated an association between exposure to violence and mental health problems;therefore the purpose of ...Objective:Studies conducted in large metropolitan inner-city communities with high violent crime rates have demonstrated an association between exposure to violence and mental health problems;therefore the purpose of this study was to determine if similar trends exist in smaller inner-city communities with substantially lower violent crime rates.Methods:One hundred twenty-six children and young adults living in inner-city Omaha,Nebraska,were screened for posttraumatic stress disorder(PTSD),depression,and anxiety symptoms and assessed for community violence exposure(CVE).Pearson’s correlation and analysis of variance were used to determine the relationship between PTSD,depression,and anxiety symptoms and CVE.Results:A statistically significant relationship was found between CVE and PTSD and anxiety symptoms among participants despite their having lower rates of exposure to violent events in com-parison with other studies.No association was found between violence and depression symptoms.Additionally,the presence of anxiety and depression,as well as increased age of participants,was associated with higher rates of PTSD symptoms.Conclusion:We recommend that health care providers in smaller cities,where the effects of violent crime may be underestimated or overlooked,be informed of the existence of this pub-lic health problem within their community and that they screen at-risk patients for mental health problems.展开更多
There is substantial public concern about the health risks of proximity to petrochemical industries.In the Haifa Bay Area(HBA),which contains Israel’s densest industrial area,these concerns have been strengthened by ...There is substantial public concern about the health risks of proximity to petrochemical industries.In the Haifa Bay Area(HBA),which contains Israel’s densest industrial area,these concerns have been strengthened by elevated cancer mortality rates since the late 1960s.We studied the association between adolescent exposure to industrial air pollution in the HBA and adult-onset cancer.This is a historical cohort study.The study population comprised 2,187,317 subjects,using the Israeli medical corps data linked to the Israel National Cancer Registry with follow-up of up to 45 years.Exposure assessments were estimated by a spatial kriging interpolation model of SO2,serving as a marker for the dispersion of air pollution emitted from the complex during the study period.We found increased crude(HR=1.23,95%CI=1.17 to 1.29)and adjusted(HR=1.16,95%CI=1.10 to 1.21)risk of cancer with increased exposure to air pollution in HBA.The associations remained robust in analyses stratified by decade and socio-economic status.We found evidence of monotonically increased risk in five of 13 cancer categories(leukemia,melanoma,female breast,central nervous system,and thyroid tumors).Our findings strengthen the hypothesis that this exposure posed a carcinogenic risk during the study period.展开更多
Coking industry is a potential source of heavy metals(HMs)pollution.However,its impacts to the groundwater of surrounding residential areas have not been well understood.This study investigated the pollution character...Coking industry is a potential source of heavy metals(HMs)pollution.However,its impacts to the groundwater of surrounding residential areas have not been well understood.This study investigated the pollution characteristics and health risks of HMs in groundwater nearby a typical coking plant.Nine HMs including Fe,Zn,Mo,As,Cu,Ni,Cr,Pb and Cd were analyzed.The average concentration of total HMswas higher in the nearby area(244.27μg/L)than that of remote area away the coking plant(89.15μg/L).The spatial distribution of pollution indices including heavy metal pollution index(HPI),Nemerow index(NI)and contamination degree(CD),all demonstrated higher values at the nearby residential areas,suggesting coking activity could significantly impact the HMs distribution characteristics.Four sources of HMs were identified by Positive Matrix Factorization(PMF)model,which indicated coal washing and coking emission were the dominant sources,accounted for 40.4%,and 31.0%,respectively.Oral ingestionwas found to be the dominant exposure pathway with higher exposure dose to children than adults.Hazard quotient(HQ)values were below 1.0,suggesting negligible non-carcinogenic health risks,while potential carcinogenic risks were from Pb and Ni with cancer risk(CR)values>10−6.Monte Carlo simulation matched well with the calculated results with HMs concentrations to be the most sensitive parameters.This study provides insights into understanding how the industrial coking activities can impact the HMs pollution characteristics in groundwater,thus facilitating the implement of HMs regulation in coking industries.展开更多
Poly(butylene adipate-terephthalate)(PBAT),as one of the most common and promising biodegradable plastics,has been widely used in agriculture,packaging,and other industries due to its strong biodegradability propertie...Poly(butylene adipate-terephthalate)(PBAT),as one of the most common and promising biodegradable plastics,has been widely used in agriculture,packaging,and other industries due to its strong biodegradability properties.It is well known that PBAT suffers a series of natural weathering,mechanical wear,hydrolysis,photochemical transformation,and other abiotic degradation processes before being biodegraded.Therefore,it is particularly important to understand the role of abiotic degradation in the life cycle of PBAT.Since the abiotic degradation of PBAT has not been systematically summarized,this review aims to summarize the mechanisms and main factors of the three major abiotic degradation pathways(hydrolysis,photochemical transformation,and thermochemical degradation)of PBAT.It was found that all of them preferentially destroy the chemical bonds with higher energy(especially C-O and C=O)of PBAT,which eventually leads to the shortening of the polymer chain and then leads to reduction in molecular weight.The main factors affecting these abiotic degradations are closely related to the energy or PBAT structure.These findings provide important theoretical and practical guidance for identifying effective methods for PBAT waste management and proposing advanced schemes to regulate the degradation rate of PBAT.展开更多
Indoles and their derivatives are an important class of N-heterocycles.In this article,iridium-catalyzed annulation reactions of N-aryl-2-aminopyridines to synthesize indole derivatives are designed and developed,whic...Indoles and their derivatives are an important class of N-heterocycles.In this article,iridium-catalyzed annulation reactions of N-aryl-2-aminopyridines to synthesize indole derivatives are designed and developed,which utilize vinylene carbonate as a new C2 synthon.This protocol is expected to provide a facile and useful access to various indole derivatives.展开更多
Ochratoxin A(OTA),a secondary fungal metabolite known for its nephrotoxic effects,is widespread in various foods and animal feeds.Our recent investigation suggests a correlation between OTA-induced nephrotoxicity and ...Ochratoxin A(OTA),a secondary fungal metabolite known for its nephrotoxic effects,is widespread in various foods and animal feeds.Our recent investigation suggests a correlation between OTA-induced nephrotoxicity and sigma-1 receptor(Sig-1R)-mediated mitochondrial apoptosis in human proximal tubule epithelial-originated kidney-2(HK-2)cells.However,the involvement of Sig-1R in OTA-induced nephrotoxicity,encompassing other forms of regulated cell death like ferroptosis,remains unexplored.In this research,cell viability,apoptotic rate,cholesterol levels,mitochondrial glutathione(mGSH)levels,reactive oxygen species(ROS)levels,and protein expressions in HK-2 cells treated with OTA and/or blarcamesine hydrochloride(Anavex 2-73)were evaluated.The results suggest that OTA induces mitochondrial apoptosis and ferroptosis by inhibiting Sig-1R,subsequently promoting sterol regulatory element-binding protein 2,3-hydroxy-3-methylglutaryl-CoA reductase,GRAM domain-containing protein 1B,steroidogenic acute regulatory protein,mitochondrial,78 kDa glucose-regulated protein,CCAAT/enhancer-binding protein homologous protein,cyclophilin D,cleaved-caspase-3,B-cell lymphoma-2-associated X protein,and long-chain fatty acid-CoA ligase 4,inhibiting tumor necrosis factor receptor-associated protein 1,mitochondrial 2-oxoglutarate/malate carrier protein,B-cell lymphoma-2-like protein 1,and glutathione peroxidase 4,reducing mGSH levels,and increasing total cholesterol,mitochondrial cholesterol,and ROS levels.In conclusion,OTA induces mitochondrial apoptosis and ferroptosis by inhibiting Sig-1R,thereby disrupting redox and cholesterol homeostasis in vitro.The regulation of cholesterol homeostasis by Sig-1R and its involvement in OTA-induced mitochondrial apoptosis and ferroptosis are reported here for the first time.展开更多
Foods and animal feeds frequently become contaminated with the nephrotoxic ochratoxin A(OTA).Our prior research has indicated that ursolic acid(UA),which is widely present in fruits and medicinal plants,has the potent...Foods and animal feeds frequently become contaminated with the nephrotoxic ochratoxin A(OTA).Our prior research has indicated that ursolic acid(UA),which is widely present in fruits and medicinal plants,has the potential to alleviate nephrotoxicity triggered by OTA.Additionally,excessive induction of endoplasmic reticulum(ER)-phagy exacerbates OTA-induced apoptosis.Therefore,further investigation is essential to comprehend whether UA can mitigate OTA-induced apoptosis by influencing ER-phagy.This objective is accomplished through a series of experiments involving assessments of cell viability,apoptosis,fluorescence microscopy,and western blot analysis.The outcomes of these experiments reveal that pre-treatment with 4μmol/L UA for 2 h can markedly reverse the elevated apoptotic rate,the co-localization of ER and lysosomes,and the protein expressions of GRP78,p-eIF2α,Chop,Bax,and Bak,as well as the reduced cell viability and the protein expressions of Lonp1,Trap1,p62,Tex264,FAM134B,Bcl-2,and Bcl-xl,all caused by exposure to 1μmol/L OTA for 24 h in human proximal tubule epithelial-originated kidney-2(HK-2)cells(P<0.05).Interestingly,the increased expression of LC3B-II induced by OTA is further amplified by UA pre-treatment(P<0.05).In conclusion,OTA triggers a harmful feedback loop between ER stress(ERS)and excessive ER-phagy,thereby further promoting ERS-and mitochondrial-mediated apoptosis in vitro.However,this effect is significantly mitigated by UA through the inhibition of autophagosome-lysosome fusion,consequently blocking the excessive ER-phagic flux.展开更多
基金supported by the National Key Research and Development Project(Nos.2019YFC1804503 and 2019YFC1804504)the National Natural Science Foundation of China(No.41731279)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(No.2017BT01Z032).
文摘Non-ferrous metal smelting poses significant risks to public health.Specifically,the copper smelting process releases arsenic,a semi-volatile metalloid,which poses an emerging exposure risk to both workers and nearby residents.To comprehensively understand the internal exposure risks of metal(loid)s from copper smelting,we explored eighteen metal(loid)s and arsenic metabolites in the urine of both occupational and non-occupational populations using inductively coupled plasma mass spectrometry with high-performance liquid chromatography and compared their health risks.Results showed that zinc and copper(485.38 and 14.00μg/L),and arsenic,lead,cadmium,vanadium,tin and antimony(46.80,6.82,2.17,0.40,0.44 and 0.23μg/L,respectively)in workers(n=179)were significantly higher compared to controls(n=168),while Zinc,tin and antimony(412.10,0.51 and 0.15μg/L,respectively)of residents were significantly higher than controls.Additionally,workers had a higher monomethyl arsenic percentage(MMA%),showing lower arsenic methylation capacity.Source appointment analysis identified arsenic,lead,cadmium,antimony,tin and thallium as co-exposure metal(loid)s from copper smelting,positively relating to the age of workers.The hazard index(HI)of workers exceeded 1.0,while residents and control were approximately at 1.0.Besides,all three populations had accumulated cancer risks exceeding 1.0×10^(-4),and arsenite(AsIII)was the main contributor to the variation of workers and residents.Furthermore,residents living closer to the smelting plant had higher health risks.This study reveals arsenic exposure metabolites and multiple metals as emerging contaminants for copper smelting exposure populations,providing valuable insights for pollution control in non-ferrous metal smelting.
文摘BACKGROUND Numerous epidemiological studies have found that pesticide exposure is associated with the incidence of type 2 diabetes(T2D);however,the underlying mechanisms remain unknown.DNA methylation may play a role in this process.AIM To identify the genes associated with pesticide exposure and T2D by reviewing the current literature.METHODS We systematically searched PubMed and Embase for relevant studies that examined the association between pesticide exposure and DNA methylation,and studies on DNA methylation and T2D through January 15,2024.RESULTS We identified six genes(Alu,CABLES1,CDH1,PDX1,PTEN,PTPRN2)related to pesticide exposure and T2D.We also suggested future research directions to better define the role of DNA methylation in the association between pesticide exposure and T2D.CONCLUSION DNA methylation of specific genes may play a vital role in the association between pesticide exposure and T2D.
基金supported by the National Key Research and Development Project(Nos.2019YFC1804503 and 2019YFC1804502)the National Natural Science Foundation of China(Nos.42307477 and 42207485)Guangdong Provincial Key R&D Program(No.2022-GDUT-A0007).
文摘Evidence on the association of occupational exposure to benzene,toluene,ethylbenzene,and xylene(BTEX)with hematologic and hepatic profiles were equivocal,and few studies have investigated overall effect of BTEX mixtures.Herein,significant higher concentrations(p<0.05)of hippuric acid,1,2-dihydroxybenzene,mandelic acid,trans,trans-muconic acid and phenylglyoxylic acid were found in petrochemical workers than the controls,in accordance with higher levels of hematologic and hepatic profiles found in petrochemical workers(p<0.05).Occupational exposure to individual BTEX was associated with elevated levels of white blood cell(WBC),lymphocyte(LYMPH),alanine aminotransferase(ALT),and gamma-glutamyl transferase(GGT).Further,the Weighted Quantile Sum Regression model and Bayesian Kernel Machine Regression model consistently identified a positive associa-tion between BTEX mixture exposure and WBC,LYMPH,and GGT.Xylene was the primary contributor to increased WBC,LYMPH,and GGT levels.Furthermore,BTEX exposure resulting in the increased inflammation indices were mainly related to perturbations of sphingolipid metabolism,biosynthesis of unsaturated fatty acids,and primary bile acid biosynthesis.Whereas metabolites mediated the correlation between BTEX exposure and liver function indiceswere related to the perturbations of biosynthesis of unsaturated fatty acids,arachidonic acid metabolism,sphingolipid metabolism,primary bile acid biosynthesis,etc.Our findings revealed potential health risk of occupational exposure to BTEX andmight help one to understand the link between BTEX exposure and hematologic and hepatic profiles.
基金supported by the Science&Technology Program of Guizhou Province(Nos.QKHPTRC-GCC[2022]039-1,QKHPTRC-CXTD[2022]014,and QKHHBZ[2020]3002)the Scientific Research Programof Guizhou Provincial Department of Education(No.QJJ[2023]019).
文摘Anemia is still prevalent among low and middle-income countries,posing serious family and social burdens.However,scarce studies provided evidence for real-world exposure to polycyclic aromatic hydrocarbons(PAHs)and anemia among pregnant women,as well as involved biological mechanisms.So,we conducted this study including 1717 late pregnant women fromZunyi Birth Cohort and collected urine samples for PAHs metabolites detection.Logistic regression and restricted cubic spline regression were used to examine exposuredisease risks and dose-response relationships.We conducted Bayesian kernel machine regression,weighted quantile sum regression,and quantile g-computation regression to fit the joint impacts of multiple PAHs in the real-world scenario on hypocalcemia and anemia.Results showed single exposure to 2-OHNap,2-OHFlu,9-OHFlu,1-OHPhe,2-OHPhe,3-OHPhe,and 1-OHPyr(all P-trend<0.05)increased the risks of hypocalcemia and anemia.Moreover,PAHs mixture was significantly related to higher risks of hypocalcemia and anemia,with 3-OHPhe and 1-OHPyr identified as their major drivers,respectively.Importantly,hypocalcemia served as a significant biological mechanism responsible for PAHs and anemia.Our findings suggest that individual and joint exposure to PAHs during late pregnancy elevate the anemia risk,and calcium supplementation might be a low-cost intervention target for reducing the PAHs-related impairment on anemia for pregnant women.
文摘For much of the world＇s population, food is the major source of exposure to arsenic.Exposure to this non-essential metalloid at relatively low levels may be linked to a wide range of adverse health effects. Thus, evaluating foods as sources of exposure to arsenic is important in assessing risk and developing strategies that protect public health. Although most emphasis has been placed on inorganic arsenic as human carcinogen and toxicant, an array of arsenic-containing species are found in plants and animals used as foods. Here,we 2evaluate the contribution of complex organic arsenicals（arsenosugars, arsenolipids,and trimethylarsonium compounds） that are found in foods and consider their origins,metabolism, and potential toxicity. Commonalities in the metabolism of arsenosugars and arsenolipids lead to the production of di-methylated arsenicals which are known to exert many toxic effects. Evaluating foods as sources of exposure to these complex organic arsenicals and understanding the formation of reactive metabolites may be critical in assessing their contribution to aggregate exposure to arsenic.
基金This work was supported by the National Natural Science Foundation of China(Nos.U1901210,41877363,42130611,and 42177410)the Science and Technology Project of Guangdong Province,China(No.2021A0505030070)+2 种基金the Natural Science Foundation of Guangdong Province(No.2019A1515010599)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(No.2017BT01Z032)the Young S&T Talent Training Program of Guangdong Provincial Association,China(No.2022QNRC23).
文摘Pathogenic microbes with antibiotic resistance can thrive on municipal solid waste as nutrients and be aerosolized and transported to vicinities during waste disposal processes.However,the characterization of pathogenic bioaerosols and assessment of their exposure risks are lacking.Herein,particle size,concentration,activity,antibiotic resistance,and pathogenicity of airborne microorganisms were assessed in different sectors of a typical landfill.Results showed that active sector in downwind direction has the highest bioaerosol level(1234 CFU/m3),while residential area has the highest activity(14.82 mg/L).Botanical deodorizer from mist cannon can effectively remove bioaerosol.Most bioaerosols can be inhaled into respiratory system till bronchi with sizes ranging from 2.1−3.3 and 3.3−4.7μm.Pathogenic bacteria(Bacilli,Bacillus,and Burkholderia-Paraburkholderia)and allergenic fungi(Aspergillus,Cladosporium,and Curvularia)prevailed in landfill.Although high abundance of microbial volatile organic compounds(mVOCs)producing bioaerosols were detected,these mVOCs contributed little to odor issues in landfill.Notably,surrounding areas have higher levels of antibiotic-resistance genes(ARGs)than inner landfill with tetC,acrB,acrF,mdtF,and bacA as dominant ones.Most ARGs were significantly correlated with bacterial community,while environmental parameters mainly influenced fungal prevalence.These findings can assist in reducing and preventing respiratory allergy or infection risks in occupational environments relating to waste management.
文摘Low levels (ng/g) of musk ketone (MK),used as a fragrance additive in the formulation of personal care products,are frequently detected in the water and other environment.Thus,aquatic organisms can be continuously exposed to MK.In this study,kinetics and dose-response assessments of 2-amino-MK (AMK) metabolite,bound to cysteine-hemoglobin (Hb) in rainbow trout,formed by enzymatic nitro-reduction of MK have been demonstrated.Trout were exposed to a single exposure of 0.010,0.030,0.10,and 0.30 mg MK/g fish.Tw...
基金supported by the National Key R&D Program of China(2023YFC3708304,2022YFC3703000)National Natural Science Foundation of China(42422507,42375179)+1 种基金Beijing Natural Science Foundation(JQ24052)Shanghai Tongji Gao Tingyao Environmental Science&Technology Development Foundation,China.
文摘Fine particulate matter(PM2.5)is a major contributor to infant mortality.However,the attributable global burden remains unclear due to the absence of a nonlinear exposure-response function that links all-cause infant mortality to various PM2.5 concentrations.In this study,we systematically reviewed the literature on PM2.5 exposure and under-five child mortality,then conducted multicenter epidemiological analyses using Demographic and Health Survey(DHS)data with fixed-effects logit regression.We integrated literature-derived estimates with local PM2.5-mortality associations across multiple regions.Using meta-regression,we quantified per unit exposure effects to develop a nonlinear exposure-response function,subsequently extrapolated to 189 countries(1998–2019)to estimate the global infant mortality burden attributable to PM2.5 exposure.The results showed that prenatal exposure was more strongly associated with increased infant mortality in both linear and nonlinear analyses.The local effect of prenatal exposure was higher at the low-concentration end(<20μg/m^(3))than at the high-concentration end(>20μg/m^(3)).The attributable deaths declined from 2.22 to 1.44 million,yet the attributable fraction rose from 32.6%to 39.3%,indicating persistent PM2.5 risks despite child health improvements.These findings suggest that,although the improved child health partially mitigated the adverse effects of worsening air quality between 1998 and 2019,prenatal PM2.5 exposure remained a significant risk factor.
基金supported by the National Key Research and Development Project(2019YFC1804504 and 2019YFC1804503)National Natural Science Foundation of China(41731279)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2017BT01Z032).
文摘Tetrabromobisphenol A(TBBPA)is a flame retardant that adversely affects the environment and human health.The present study exposed HepG2 cells to low concentrations of TBBPA daily to investigate the changes in gene regulation,mainly related to pathways associated with the endocrine system.The quantitative polymerase chain reaction(qPCR)confirmed that prolonged exposure gradually activated the thyroid hormone and parathyroid hormone signaling pathways.The expression levels of genes related to the thyroid hormone signaling pathway were upregulated(1.15-8.54 times)after five generations of exposure to 1 and 81 nM TBBPA.Furthermore,co-exposure to 81 nM TBBPA and 0.5 nM thyroid hormone receptor antagonist for five generations significantly reduced the expression of thyroid hormone and parathyroid hormone receptors.Meanwhile,81 nM TBBPA inhibited the activation of the Ras pathway and downregulated Ras gene expression level(3.7 times),indicating the association between the toxic effect and thyroid hormone receptors.Additionally,our experiments revealed that the thyroid hormone pathway regulated the induction of the Ras signaling pathway by TBBPA.The study thus proves that daily exposure to TBBPA interferes with the thyroid hormone signaling pathway and subsequently the endocrine system.
基金funding from various sources,including the Zhejiang Province Health Innovative Talent Project(A0466)the International Cooperation Seed Program of Women’s Hospital,Zhejiang University(GH2022B008-01 and GH2024005)+3 种基金the Australian Research Council(DP210102076)the Australian National Health and Medical Research Council(APP2000581)the UK Research and Innovation(UKRI)Centre for Application of Artificial Intelligence to the Study of Environmental Risks(AI4ER,EP/S022961/1)the Start-up Grant from Yong Loo Lin School of Medicine,National University of Singapore(NUHSRO/2024/045/Startup/06),and the US-China Fulbright Program.
文摘China’s“three-child policy”,implemented in response to population aging,has made the protection of maternal and infant health an urgent priority.In this environmental and medical big-data era,the Zhejiang Environmental and Birth Health Research Alliance(ZEBRA)maternity cohort was established with the aim of identifying risk factors for perinatal morbidity and mortality from the perspectives of both observational epidemiology and experimental etiology.Compared with conventional birth cohorts,the inclusion of a maternity cohort allows greater scope for research and places an emphasis on maternal health.In particular,it allows us to focus on pregnant women with a history of pregnancy-related illnesses and those planning to have a second or third child.There are currently many pressing issues in perinatal health,including the risk associations between exogenous together with endogenous factors and the occurrence of perinatal abnormalities,pregnancy complications,and adverse pregnancy outcomes.It is crucial to explore the interaction between environmental exposures and genetic factors affecting perinatal health if we are to improve it.It is also worthwhile to assess the feasibility of the early stage prediction of major perinatal abnormalities.We hope to study this in the ZEBRA cohort and also seek nationwide and international collaborations to establish a multicenter cohort consortium,with the ultimate goal of contributing epidemiological evidence to literature and providing evidence-based insights for global maternal and child healthcare.
基金supported by the Science and Technology Program of the Joint Fund of Scientific Research for the Public Hospitals of Inner Mongolia Academy of Medical Sciences (2023GLLH0132)Scientific Research Fund for the Demonstration Project of Public Hospital Reform and Quality Development (Gastrointestinal Tumor) that is approved by Peking University Cancer Hospital (Inner Mongolia Campus)(2023SGGZ068)+1 种基金Beijing Natural Science Foundation (JQ24052)National Natural Science Foundation of China (42175182, 42375179, and 42422507)
文摘Background:There is limited evidence of the association between long-term exposure to particulate matter with aerodynamic diameter≤2.5μm (fine particulate matter,PM_(2.5)) and gynecologic cancer incidence,particularly in developing countries with high air pollution levels.The present study aimed to investigate the associations of long-term exposure to PM_(2.5)and its constituents with the incidence of gynecologic cancer,and to identify the primary constituent.Methods:A total of 85,500 women from the National Urban Cancer Screening Program in Beijing (2013-2019) were included.5-year average concentrations of PM_(2.5)mass and its constituents,namely carbon black (BC),ammonium (NH_(4)^(+)),nitrate (NO_(3)^(-)),organic matter (OM),and sulfate (SO_(4)^(2-)),were obtained from the Tracking Air Pollution in China (TAP) dataset.Cox proportional hazard models were used to analyze the association between long-term exposure to PM_(2.5)and its constituents and gynecologic cancer incidence.Mixture exposure models,including quantile-based gcomputation (Qgcomp) and explanatory machine learning model (SHapley Additive exPlanations,SHAP),were used to assess the effect of each constituent.Results:During a mean follow-up of 6.22 years,524 participants were diagnosed with gynecologic cancer.The adjusted hazard ratios (HRs) for gynecologic cancer incidence associated with 1 standard deviation (SD) increment was 1.10 (95%CI:1.00-1.22) for PM_(2.5),1.12 (95%CI:1.01-1.23) for BC,1.11 (95%CI:1.00-1.23) for NH_(4)^(+),1.12 (95%CI:1.01-1.23) for OM,1.12 (95%CI:1.01-1.23) for SO_(4)^(2-),and1.08 (95%CI:0.98-1.19) for NO_(3)^(-).The Qgcomp model indicated the association between a mixture of PM_(2.5)constituents and gynecologic cancer incidence,with the weights assigned to BC (61.6%),SO_(4)^(2-)(35.9%),and NO_(3)^(-)(2.5%) in the positive direction.The SHAP model showed that SO_(4)^(2-)was the most important constituent,with the mean|SHAP|value of 0.0322,followed by BC (0.0270),OM (0.0232),NO_(3)^(-)(0.0212) and NH_(4)^(+)(0.0190).Conclusions:Long-term exposure to PM_(2.5)was associated with gynecologic cancer incidence,with SO_(4)^(2-)and BC significantly contributing to the association.
基金funded by the National Key Research and Development Program of China(2018YF-C1004300,2018YFC1004302)Science&Technology Program of Guizhou Province(QKHHBZ[2020]3002,QKHPTRC-GCC[2022]039-1,QKHPTRC-CXTD[2022]014)+1 种基金Natural Science Foundation of Guizhou Province(QKH-J[2022]YB614)Science and Technology Plan Project of Zunyi City(ZKH-J(2021)294).
文摘Studies have shown that exposure to phthalates can affect neonatal birth weight.However,epidemiological evidence on the mediating role of maternal thyroid hormones is limited.Therefore,this study,based on the Compliance Birth Cohort,aimed to reveal the potential mediating function of maternal thyroid hormones during pregnancy between phthalic acid ester(PAE)exposure and neonatal birth weight.The study included 1274 mother−infant pairs.Linear regression analysis revealed a negative association between MIBP and neonatal birth weight(β=−62.236;95%CI:−118.842,−5.631).Bayesian kernel-machine regression(BKMR)indicated a nonlinear negative association between PAE metabolites(PAEs)and birth weight.Linear regression analysis revealed a positive association between neonatal birth weight and FT3(β=41.605;95%CI:2.631,80.380).The BKMR model also found a positive association between thyroid hormones and birth weight but in a nonlinear manner.Additionally,linear regression analyses showed that TSH,TT3,TT4,FT3,and FT4 were associated with PAEs.The BKMR model revealed an inverted U-shaped association of PAEs with TT3 and FT3 and a nonlinear association with TSH,TT4,and FT4.Structural equation modeling revealed that MMP,MIBP,MBP,MEHP,MOP,MBZP,and MEOHP contributed to a net reduction in neonatal birth weight of 32 g through the TT3,FT3,TT4,and FT4 pathways.The findings suggest that exposure to PAEs during pregnancy leads to a reduction in neonatal birth weight,possibly due to the involvement of maternal thyroid hormones as mediators.Controlling maternal thyroid hormone levels during pregnancy may be a viable method to reduce the harmful effects of phthalate exposure on the developing fetus.
基金Project supported by the National Natural Science Foundation of China.
文摘Using Arsenazo Ⅲ as a myoplasmic calcium indicator, we have studied the calcium transients evoked by voltage-clamp depolarizing pulses in frog twitch muscle fibres which had been temporarily depolarized by 80 mmol/LK^+ in the absence or presence of myoplasmic Li^+. After the high K^+ exposure, for either a short (15 rain) or long(1 h) time, the post-K^+ calcium transients could gradually be restored to the level of the pre-K^+ ones, if the fibres were not loaded with Li^+.In contrast, the post-K^+ calcium transients of Li^+-loaded fibres could not fully recover,and were depressed in a Li^+ concentration-dependent manner.The mean amplitude of the post-K^+ responses recorded more than 3.5 h after 15 min high K^+ exposure was reduced to 56% of pre-K^+ control in the fibres which had been loaded with Li^+ in 20 mmol/L Li^+ Ringer's solution.This depression could be prevented or partially reversed by exogenous myo-inositol.More depression could be induced by 1 h high K^+ exposure, but the presence of exogenous myo-inositol could not clearly prevent the post-K^+ calcium transients from reduction.Assuming that high K^+ exposure caused a depletion of myo-inositol and probably other changes in the metabolism of inositol phospholipids in Li^+ loaded fibres,we conclude that some metabolites of phosphoinositides may play modulation roles in excitation-contraction coupling in frog twitch muscle fibres.
文摘Objective:Studies conducted in large metropolitan inner-city communities with high violent crime rates have demonstrated an association between exposure to violence and mental health problems;therefore the purpose of this study was to determine if similar trends exist in smaller inner-city communities with substantially lower violent crime rates.Methods:One hundred twenty-six children and young adults living in inner-city Omaha,Nebraska,were screened for posttraumatic stress disorder(PTSD),depression,and anxiety symptoms and assessed for community violence exposure(CVE).Pearson’s correlation and analysis of variance were used to determine the relationship between PTSD,depression,and anxiety symptoms and CVE.Results:A statistically significant relationship was found between CVE and PTSD and anxiety symptoms among participants despite their having lower rates of exposure to violent events in com-parison with other studies.No association was found between violence and depression symptoms.Additionally,the presence of anxiety and depression,as well as increased age of participants,was associated with higher rates of PTSD symptoms.Conclusion:We recommend that health care providers in smaller cities,where the effects of violent crime may be underestimated or overlooked,be informed of the existence of this pub-lic health problem within their community and that they screen at-risk patients for mental health problems.
文摘There is substantial public concern about the health risks of proximity to petrochemical industries.In the Haifa Bay Area(HBA),which contains Israel’s densest industrial area,these concerns have been strengthened by elevated cancer mortality rates since the late 1960s.We studied the association between adolescent exposure to industrial air pollution in the HBA and adult-onset cancer.This is a historical cohort study.The study population comprised 2,187,317 subjects,using the Israeli medical corps data linked to the Israel National Cancer Registry with follow-up of up to 45 years.Exposure assessments were estimated by a spatial kriging interpolation model of SO2,serving as a marker for the dispersion of air pollution emitted from the complex during the study period.We found increased crude(HR=1.23,95%CI=1.17 to 1.29)and adjusted(HR=1.16,95%CI=1.10 to 1.21)risk of cancer with increased exposure to air pollution in HBA.The associations remained robust in analyses stratified by decade and socio-economic status.We found evidence of monotonically increased risk in five of 13 cancer categories(leukemia,melanoma,female breast,central nervous system,and thyroid tumors).Our findings strengthen the hypothesis that this exposure posed a carcinogenic risk during the study period.
基金supported by the National Key Research and Development Program of China(No.2019YFC1804501)the National Natural Science Foundation of China(Nos.42122056 and U1901210)+2 种基金Guangdong Basic and Applied Basic Research Foundation(No.2021B1515020063)the Key Research and Development Program of Guangdong Province(No.2021B1111380003)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(No.2017BT01Z032).
文摘Coking industry is a potential source of heavy metals(HMs)pollution.However,its impacts to the groundwater of surrounding residential areas have not been well understood.This study investigated the pollution characteristics and health risks of HMs in groundwater nearby a typical coking plant.Nine HMs including Fe,Zn,Mo,As,Cu,Ni,Cr,Pb and Cd were analyzed.The average concentration of total HMswas higher in the nearby area(244.27μg/L)than that of remote area away the coking plant(89.15μg/L).The spatial distribution of pollution indices including heavy metal pollution index(HPI),Nemerow index(NI)and contamination degree(CD),all demonstrated higher values at the nearby residential areas,suggesting coking activity could significantly impact the HMs distribution characteristics.Four sources of HMs were identified by Positive Matrix Factorization(PMF)model,which indicated coal washing and coking emission were the dominant sources,accounted for 40.4%,and 31.0%,respectively.Oral ingestionwas found to be the dominant exposure pathway with higher exposure dose to children than adults.Hazard quotient(HQ)values were below 1.0,suggesting negligible non-carcinogenic health risks,while potential carcinogenic risks were from Pb and Ni with cancer risk(CR)values>10−6.Monte Carlo simulation matched well with the calculated results with HMs concentrations to be the most sensitive parameters.This study provides insights into understanding how the industrial coking activities can impact the HMs pollution characteristics in groundwater,thus facilitating the implement of HMs regulation in coking industries.
基金supported by the National Key R&D Program of China(No.2022YFC3901800)the National Natural Science Foundation of China(No.22176041)Guangzhou Science and Technology Planning Project(No.2023A04J0918)。
文摘Poly(butylene adipate-terephthalate)(PBAT),as one of the most common and promising biodegradable plastics,has been widely used in agriculture,packaging,and other industries due to its strong biodegradability properties.It is well known that PBAT suffers a series of natural weathering,mechanical wear,hydrolysis,photochemical transformation,and other abiotic degradation processes before being biodegraded.Therefore,it is particularly important to understand the role of abiotic degradation in the life cycle of PBAT.Since the abiotic degradation of PBAT has not been systematically summarized,this review aims to summarize the mechanisms and main factors of the three major abiotic degradation pathways(hydrolysis,photochemical transformation,and thermochemical degradation)of PBAT.It was found that all of them preferentially destroy the chemical bonds with higher energy(especially C-O and C=O)of PBAT,which eventually leads to the shortening of the polymer chain and then leads to reduction in molecular weight.The main factors affecting these abiotic degradations are closely related to the energy or PBAT structure.These findings provide important theoretical and practical guidance for identifying effective methods for PBAT waste management and proposing advanced schemes to regulate the degradation rate of PBAT.
文摘Indoles and their derivatives are an important class of N-heterocycles.In this article,iridium-catalyzed annulation reactions of N-aryl-2-aminopyridines to synthesize indole derivatives are designed and developed,which utilize vinylene carbonate as a new C2 synthon.This protocol is expected to provide a facile and useful access to various indole derivatives.
基金financially supported by the National Natural Science Foundation of China(3226058782060598)+4 种基金the Scientific Research Program of Guizhou Provincial Department of Education(QJJ[2023]019)the Science&Technology Program of Guizhou Province(QKHPTRC-CXTD[2022]014)the Excellent Youth Talents of Zunyi Medical University(17zy-006)the Innovation and Entrepreneurship Training Program for College Students of China(202210661140)the Innovation and Entrepreneurship Training Program for College Students of Zunyi Medical University(ZYDC2021110).
文摘Ochratoxin A(OTA),a secondary fungal metabolite known for its nephrotoxic effects,is widespread in various foods and animal feeds.Our recent investigation suggests a correlation between OTA-induced nephrotoxicity and sigma-1 receptor(Sig-1R)-mediated mitochondrial apoptosis in human proximal tubule epithelial-originated kidney-2(HK-2)cells.However,the involvement of Sig-1R in OTA-induced nephrotoxicity,encompassing other forms of regulated cell death like ferroptosis,remains unexplored.In this research,cell viability,apoptotic rate,cholesterol levels,mitochondrial glutathione(mGSH)levels,reactive oxygen species(ROS)levels,and protein expressions in HK-2 cells treated with OTA and/or blarcamesine hydrochloride(Anavex 2-73)were evaluated.The results suggest that OTA induces mitochondrial apoptosis and ferroptosis by inhibiting Sig-1R,subsequently promoting sterol regulatory element-binding protein 2,3-hydroxy-3-methylglutaryl-CoA reductase,GRAM domain-containing protein 1B,steroidogenic acute regulatory protein,mitochondrial,78 kDa glucose-regulated protein,CCAAT/enhancer-binding protein homologous protein,cyclophilin D,cleaved-caspase-3,B-cell lymphoma-2-associated X protein,and long-chain fatty acid-CoA ligase 4,inhibiting tumor necrosis factor receptor-associated protein 1,mitochondrial 2-oxoglutarate/malate carrier protein,B-cell lymphoma-2-like protein 1,and glutathione peroxidase 4,reducing mGSH levels,and increasing total cholesterol,mitochondrial cholesterol,and ROS levels.In conclusion,OTA induces mitochondrial apoptosis and ferroptosis by inhibiting Sig-1R,thereby disrupting redox and cholesterol homeostasis in vitro.The regulation of cholesterol homeostasis by Sig-1R and its involvement in OTA-induced mitochondrial apoptosis and ferroptosis are reported here for the first time.
基金financially supported by the National Natural Science Foundation of China(82060598,32260587)the Natural Science Foundation of Guizhou Province(QKH-J-ZK[2021]181)+4 种基金the Scientific Research Program of Guizhou Provincial Department of Education(QJJ[2023]019)the Science&Technology Program of Guizhou Province(QKHPTRC-CXTD[2022]014)the Excellent Youth Talents of Zunyi Medical University(17zy-006)the Innovation and Entrepreneurship Training Program for College Students of Guizhou Province(S202210661138)the Innovation and Entrepreneurship Training Program for College Students of Zunyi Medical University(ZYDC2021108)。
文摘Foods and animal feeds frequently become contaminated with the nephrotoxic ochratoxin A(OTA).Our prior research has indicated that ursolic acid(UA),which is widely present in fruits and medicinal plants,has the potential to alleviate nephrotoxicity triggered by OTA.Additionally,excessive induction of endoplasmic reticulum(ER)-phagy exacerbates OTA-induced apoptosis.Therefore,further investigation is essential to comprehend whether UA can mitigate OTA-induced apoptosis by influencing ER-phagy.This objective is accomplished through a series of experiments involving assessments of cell viability,apoptosis,fluorescence microscopy,and western blot analysis.The outcomes of these experiments reveal that pre-treatment with 4μmol/L UA for 2 h can markedly reverse the elevated apoptotic rate,the co-localization of ER and lysosomes,and the protein expressions of GRP78,p-eIF2α,Chop,Bax,and Bak,as well as the reduced cell viability and the protein expressions of Lonp1,Trap1,p62,Tex264,FAM134B,Bcl-2,and Bcl-xl,all caused by exposure to 1μmol/L OTA for 24 h in human proximal tubule epithelial-originated kidney-2(HK-2)cells(P<0.05).Interestingly,the increased expression of LC3B-II induced by OTA is further amplified by UA pre-treatment(P<0.05).In conclusion,OTA triggers a harmful feedback loop between ER stress(ERS)and excessive ER-phagy,thereby further promoting ERS-and mitochondrial-mediated apoptosis in vitro.However,this effect is significantly mitigated by UA through the inhibition of autophagosome-lysosome fusion,consequently blocking the excessive ER-phagic flux.
