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
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
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
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
The future increased frequency and intensity of heat waves(HWs)across China will exacerbate adverse effects on society and the environment.However,changes in socioeconomic exposure remain underexplored.In this study,c...The future increased frequency and intensity of heat waves(HWs)across China will exacerbate adverse effects on society and the environment.However,changes in socioeconomic exposure remain underexplored.In this study,climate model outputs from the Coupled Model Intercomparison Project Phase 6(CMIP6),together with population and gross domestic product(GDP)projections were used to investigate projected heat stress and socioeconomic exposure across China and its eight subregions under four shared socioeconomic pathway(SSP)scenarios(SSP1–2.6,SSP2–4.5,SSP3–7.0,and SSP5–8.5)over three periods(2021–2040,2051–2070,and 2081–2100).Our results indicate a consistent upward trend in the Universal Thermal Climate Index(UTCI)across all scenarios,with intensifying increases over time,peaking at>6°C.This suggests a continuous increase in the number of extreme heat events(EHEs)in China.Population exposure to EHEs across the four UTCI thresholds(>26°C,>32°C,>38°C,and>46°C)shows an increasing trend.Projections indicate a∼14-fold increase nationwide,500-fold increase in Northwest China(NWC),and a 1000-fold in Southwest China(SWC2)under SSP5–8.5 by2081–2100 compared with current levels.The eastern and southeastern regions,especially the Yangtze River and Pearl River Delta,show significant GDP exposure increases under SSP3–7.0 and SSP5–8.5.Population exposure is mainly driven by climatic effects under severe scenarios,whereas GDP exposure is influenced by interaction effects,particularly under SSP5–8.5 and during the 2090s.This study's findings offer actionable insights for targeted adaptation in China's diverse geographies.展开更多
Rice,a primary food staple for over half of the global population,is susceptible to environmental pollution.The presence of lipophilic halogenated contaminants,including halogenated polycyclic aromatic hydrocarbons(XP...Rice,a primary food staple for over half of the global population,is susceptible to environmental pollution.The presence of lipophilic halogenated contaminants,including halogenated polycyclic aromatic hydrocarbons(XPAHs),polychlorinated biphenyls(PCBs),organochlorine pesticides(OCPs),brominated flame retardants(BFRs),and polyfluoroalkyl substances(PFAS),has become a growing concern due to their potential health risks and environmental impact.This review focused on the research of lipophilic halogenated contaminants in rice.We summarized the physicochemical properties,toxicity profiles,and contamination levels in rice.Moreover,the strategies for reducing lipophilic halogenated contaminant levels in rice were summarized and proposed,such as phytoremediation and improved processing methods.These findings can provide a reference for the understanding and control of lipophilic halogenated contaminants during rice growing and processing,and therefore reduce the associated risks.展开更多
Background:Cold exposure is associated with metabolic alterations.This study aims to investigate the effects and mechanisms of cold exposure on liver metabolism through the integration of transcriptomics and metabolom...Background:Cold exposure is associated with metabolic alterations.This study aims to investigate the effects and mechanisms of cold exposure on liver metabolism through the integration of transcriptomics and metabolomics.Methods:Liver tissues from mice exposed to cold were subjected to RNA sequencing and liquid chromatography-mass spectrometry(LC-MS)for transcriptomic and metabolomic profiling,respectively.Differentially expressed genes(DEGs)and differentially expressed metabolites(DEMs)were identified.mRNA expression levels were validated by real-time polymerase chain reaction(RT-PCR).Gene ontology(GO),Kyoto encyclopedia of genes and genomes(KEGG),and Reactome enrichment analyses were performed.Finally,transcriptomic and metabolomic data were integrated and analyzed.Results:Cold exposure altered the transcriptomic and metabolomic profiles in the liver in cold exposed mice.Enrichment analyses were of DEGs and DEMs.Enrichment analyses of DEGs and DEMs revealed that DEGs were involved in pathways such as the PI3K-Akt signaling pathway,cytokine-cytokine receptor interaction,and cell adhesion molecules.DEMs were enriched in pathways related to membrane transport,nucleotide metabolism,and the metabolism of cofactors and vitamins.The integration of transcriptomic and metabolomic data identified several pathways potentially associated with cold exposure,such as the PI3K-Akt signaling pathway.Conclusion:Cold exposure alters liver transcriptomic and metabolomic profiles in mice.The integrative analysis of transcriptomic and metabolomic data highlights the complexity of the liver's response to cold exposure and identifies potential targets for further investigation.展开更多
Mercury(Hg),especially methylmercury(MeHg),accumulation in rice grain due to rice paddy possessing conditions conducive to Hg methylation has led to human Hg exposure through consumption of rice-based daily meals.In a...Mercury(Hg),especially methylmercury(MeHg),accumulation in rice grain due to rice paddy possessing conditions conducive to Hg methylation has led to human Hg exposure through consumption of rice-based daily meals.In addition to being a food staple,rice is widely used as a raw material to produce a vast variety of processed food products.Little is known about Hg levels in snacking rice-food products and potential Hg exposure from consumption of them,besides previous studies on infant rice cereals.Aiming to provide complementary information for a more complete assessment on Hg exposure risk originated from Hgcontaining rice,this study determined total Hg(THg)and MeHg levels in 195 rice-containing and rice-free processed food products covering all major types of snack foods marketed in China and the estimated daily intake(EDI)of dietary Hg from the consumption of these foods.The results clearly showed THg and MeHg contents in rice-containing foods were significantly higher than rice-free products,suggesting the transfer of Hg and MeHg from the rice to the end products,even after manufacturing processes.Moreover,significant positive correlations were observed between THg,MeHg,or MeHg/THg ratio and rice content for samples containing multiple grains as ingredients,further indicating the deciding role of rice for Hg levels in the end food products.Although the EDI of THg and MeHg via ricebased food products were relatively low compared to the reference dose,it should be considered these snacking food products would contribute additive Hg intake outside of the daily regular meals.展开更多
This study investigates the microstructural evolution of a novel low-cost second-generation Ni-based single crystal superalloy during long-term thermal exposure at different temperatures(982℃,1038℃,1093℃)and its im...This study investigates the microstructural evolution of a novel low-cost second-generation Ni-based single crystal superalloy during long-term thermal exposure at different temperatures(982℃,1038℃,1093℃)and its impact on the stress rupture properties of alloy.The results reveal that theγ′phase undergoes coarsening and rafting at high temperatures,and its growth behavior follows the Ostwald ripening mechanism.With the increase in aging temperature and extension of aging time,the coarsening rate of theγ′phase increases significantly.Particularly at 1093℃,theγ′phase undergoes the most pronounced growth,leading to a remarkable deterioration of its precipitation strengthening effect.Furthermore,under conditions of higher temperature and longer time,minor amounts of topologically close-packed(TCP)phase precipitate.As the aging temperature rises and time elapses,the precipitation tendency of the TCP phase shows a slight increase.The stress rupture testing at 1100℃/120 MPa demonstrates that the stress rupture life decreases significantly with the increase in thermal exposure temperature and time.This is mainly attributed to the diminished precipitation strengthening effect of theγ′phase and the deteriorating effect of the TCP phase.However,under the same conditions,the stress rupture properties of this alloy are comparable to those of the DD5 alloy.This research provides theoretical support for enhancing the service stability and reliability of single crystal turbine blades,and offers a reference for the development of cost-effective and highperformance turbine blade materials.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
Bisphenol A(BPA)is a recognized estrogenic endocrine disruptor that poses a threat to the reproductive health of fish.However,it remains unclear whether and how paternal BPA exposure can lead to developmental toxicity...Bisphenol A(BPA)is a recognized estrogenic endocrine disruptor that poses a threat to the reproductive health of fish.However,it remains unclear whether and how paternal BPA exposure can lead to developmental toxicity in offspring.To explore the potential paternal BPA exposure impacts on craniofacial cartilage growth in offspring,male rare minnows were subjected to BPA and subsequently mated with normal females to produce progeny.Our results demonstrated that paternal BPA exposure resulted in increased malformation and delayed craniofacial cartilage development in the F1 offspring.Furthermore,BPA exposure led to differential expression of 28 miRNAs in paternal sperm in F0 generation(13 upregulated and 15 downregulated),among which 7 miRNAs were involved in the regulation of bone development.BPA also downregulated the expression of bmp2a and Runx1 during F1 embryonic development.The inhibited bmp2a expression might derive from BPA's stimulation of one miRNA,aca-miR-16a-5P,due to bmp2a being one of its target genes.Notably,paternal BPA exposure did not affect craniofacial cartilage development or gonadal development in the F2 generation.Overall,our study sheds light on the molecular mechanisms underlying the impact of paternal BPA exposure on facial chondrogenesis in offspring and provides theoretical support for the ecological protection of fish populations.展开更多
Solid-phase extraction ultrahigh-performance liquid chromatography-tandem mass spectrometry(SPE-UHPLC-MS/MS)was used to evaluate the contamination of ochratoxin A(OTA)and assessed the human exposure risk of OTA in Ras...Solid-phase extraction ultrahigh-performance liquid chromatography-tandem mass spectrometry(SPE-UHPLC-MS/MS)was used to evaluate the contamination of ochratoxin A(OTA)and assessed the human exposure risk of OTA in Rasa roxburghii.A more suitable method for OTA extraction and purification of R.roxburghii was obtained.Treated 25 mL of R.roxburghii juice with enzymatic hydrolysis at a concentration of 0.06 mg/mL,filtered the resulting mixture and concentrated the filtrate to dry,then redissolved with 0.2 mL of methanol and diluted with 0.4 mL of ultra-pure water.Added sample solution to the activated hydrophilic-lipophilic balance(HLB)column,washed with 6 mL of ultra-pure water and purified by eluting with 6 mL of methanol.The eluent was collected and dried using nitrogen at 40℃,then redissolved in 1 mL of methanol and filtered for detection.The hazard quotient(HQ)values of all R.roxburghii fruit and juice,which were storage at room temperature,4 and−20℃from 0 day to 63 days,ranged from 0.077%to 35.792%,which were within the allowable limits for human consumption.From the perspective of OTA contamination,the results indicated that the maximal storage time of R.roxburghii fruit were 14 days at room temperature,35 days at 4℃and 63 days at−20℃.And the maximal storage time of R.roxburghii juice were 7 days for sealed storage and the same day for open storage at room temperature,14 days for sealed storage and 7 days for open storage at 4℃,and 63 days for sealed storage and 56 days for open storage at−20℃during the experiment period.And all thirty samples randomly sampled from the market were OTA negative.The results of this study can lay a foundation for the formulation of OTA limit standards in fruits and juice in the future,and provide a reference for consumers to consume R.roxburghii more healthily.展开更多
Aluminum is the most abundant environmental pollutant.Recent studies suggest that aluminum exposure increases the risk of multiple diseases,including intestinal barrier dysfunction.We investigated whether Pueraria lob...Aluminum is the most abundant environmental pollutant.Recent studies suggest that aluminum exposure increases the risk of multiple diseases,including intestinal barrier dysfunction.We investigated whether Pueraria lobata extract(PLE)is effective in safeguarding against aluminum chloride exposureexacerbated intestinal barrier dysfunction.Using an experimental colitis model of aluminum-exacerbated dextran sulphate sodium(DSS)-treated mice,clinical and pathological evidence suggested that the administration of PLE counteracted aluminum exposure-induced intestinal barrier damage.In addition,we found that aluminum toxicities,including loss of tight junction molecules(TJs),upregulated pro-inflammatory cytokines,and enhanced myeloperoxidase(MPO)activity,were significantly suppressed by PLE administration.Furthermore,PLE administration was identified to inhibit activation of MAPKs and NF-κB signal pathways,which contribute to upregulation of myosin light-chain kinase(MLCK)in inflamed intestine.Taken together,these results suggest that PLE might be a potential candidate for aluminum exposure-related intestinal barrier dysfunction.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.
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.
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.
基金supported by the Third Xinjiang Scientific Expedition Program(Grant No.2023xjkk0101)the National Youth Talent Project(Grant No.E4150103)。
文摘The future increased frequency and intensity of heat waves(HWs)across China will exacerbate adverse effects on society and the environment.However,changes in socioeconomic exposure remain underexplored.In this study,climate model outputs from the Coupled Model Intercomparison Project Phase 6(CMIP6),together with population and gross domestic product(GDP)projections were used to investigate projected heat stress and socioeconomic exposure across China and its eight subregions under four shared socioeconomic pathway(SSP)scenarios(SSP1–2.6,SSP2–4.5,SSP3–7.0,and SSP5–8.5)over three periods(2021–2040,2051–2070,and 2081–2100).Our results indicate a consistent upward trend in the Universal Thermal Climate Index(UTCI)across all scenarios,with intensifying increases over time,peaking at>6°C.This suggests a continuous increase in the number of extreme heat events(EHEs)in China.Population exposure to EHEs across the four UTCI thresholds(>26°C,>32°C,>38°C,and>46°C)shows an increasing trend.Projections indicate a∼14-fold increase nationwide,500-fold increase in Northwest China(NWC),and a 1000-fold in Southwest China(SWC2)under SSP5–8.5 by2081–2100 compared with current levels.The eastern and southeastern regions,especially the Yangtze River and Pearl River Delta,show significant GDP exposure increases under SSP3–7.0 and SSP5–8.5.Population exposure is mainly driven by climatic effects under severe scenarios,whereas GDP exposure is influenced by interaction effects,particularly under SSP5–8.5 and during the 2090s.This study's findings offer actionable insights for targeted adaptation in China's diverse geographies.
基金supported by the National Natural Science Foundation of China(No.32061160476).
文摘Rice,a primary food staple for over half of the global population,is susceptible to environmental pollution.The presence of lipophilic halogenated contaminants,including halogenated polycyclic aromatic hydrocarbons(XPAHs),polychlorinated biphenyls(PCBs),organochlorine pesticides(OCPs),brominated flame retardants(BFRs),and polyfluoroalkyl substances(PFAS),has become a growing concern due to their potential health risks and environmental impact.This review focused on the research of lipophilic halogenated contaminants in rice.We summarized the physicochemical properties,toxicity profiles,and contamination levels in rice.Moreover,the strategies for reducing lipophilic halogenated contaminant levels in rice were summarized and proposed,such as phytoremediation and improved processing methods.These findings can provide a reference for the understanding and control of lipophilic halogenated contaminants during rice growing and processing,and therefore reduce the associated risks.
基金supported by the National Natural Science Foundation of China(82370269)the Heilongjiang Postdoctoral Foundation(LBH-Q21134 and LBH-Z22226)Harbin Medical University Science Foundation(2023).
文摘Background:Cold exposure is associated with metabolic alterations.This study aims to investigate the effects and mechanisms of cold exposure on liver metabolism through the integration of transcriptomics and metabolomics.Methods:Liver tissues from mice exposed to cold were subjected to RNA sequencing and liquid chromatography-mass spectrometry(LC-MS)for transcriptomic and metabolomic profiling,respectively.Differentially expressed genes(DEGs)and differentially expressed metabolites(DEMs)were identified.mRNA expression levels were validated by real-time polymerase chain reaction(RT-PCR).Gene ontology(GO),Kyoto encyclopedia of genes and genomes(KEGG),and Reactome enrichment analyses were performed.Finally,transcriptomic and metabolomic data were integrated and analyzed.Results:Cold exposure altered the transcriptomic and metabolomic profiles in the liver in cold exposed mice.Enrichment analyses were of DEGs and DEMs.Enrichment analyses of DEGs and DEMs revealed that DEGs were involved in pathways such as the PI3K-Akt signaling pathway,cytokine-cytokine receptor interaction,and cell adhesion molecules.DEMs were enriched in pathways related to membrane transport,nucleotide metabolism,and the metabolism of cofactors and vitamins.The integration of transcriptomic and metabolomic data identified several pathways potentially associated with cold exposure,such as the PI3K-Akt signaling pathway.Conclusion:Cold exposure alters liver transcriptomic and metabolomic profiles in mice.The integrative analysis of transcriptomic and metabolomic data highlights the complexity of the liver's response to cold exposure and identifies potential targets for further investigation.
基金supported by the Shandong Provincial Natural Science Foundation (No.ZR2022QB242)the National Natural Science Foundation of China (No.22306111 and 22306108)+1 种基金the Shandong Provincial Natural Science Foundation (No.ZR2020ZD20)the Chinese Postdoctoral Science Foundation (No.2023M732059).
文摘Mercury(Hg),especially methylmercury(MeHg),accumulation in rice grain due to rice paddy possessing conditions conducive to Hg methylation has led to human Hg exposure through consumption of rice-based daily meals.In addition to being a food staple,rice is widely used as a raw material to produce a vast variety of processed food products.Little is known about Hg levels in snacking rice-food products and potential Hg exposure from consumption of them,besides previous studies on infant rice cereals.Aiming to provide complementary information for a more complete assessment on Hg exposure risk originated from Hgcontaining rice,this study determined total Hg(THg)and MeHg levels in 195 rice-containing and rice-free processed food products covering all major types of snack foods marketed in China and the estimated daily intake(EDI)of dietary Hg from the consumption of these foods.The results clearly showed THg and MeHg contents in rice-containing foods were significantly higher than rice-free products,suggesting the transfer of Hg and MeHg from the rice to the end products,even after manufacturing processes.Moreover,significant positive correlations were observed between THg,MeHg,or MeHg/THg ratio and rice content for samples containing multiple grains as ingredients,further indicating the deciding role of rice for Hg levels in the end food products.Although the EDI of THg and MeHg via ricebased food products were relatively low compared to the reference dose,it should be considered these snacking food products would contribute additive Hg intake outside of the daily regular meals.
文摘This study investigates the microstructural evolution of a novel low-cost second-generation Ni-based single crystal superalloy during long-term thermal exposure at different temperatures(982℃,1038℃,1093℃)and its impact on the stress rupture properties of alloy.The results reveal that theγ′phase undergoes coarsening and rafting at high temperatures,and its growth behavior follows the Ostwald ripening mechanism.With the increase in aging temperature and extension of aging time,the coarsening rate of theγ′phase increases significantly.Particularly at 1093℃,theγ′phase undergoes the most pronounced growth,leading to a remarkable deterioration of its precipitation strengthening effect.Furthermore,under conditions of higher temperature and longer time,minor amounts of topologically close-packed(TCP)phase precipitate.As the aging temperature rises and time elapses,the precipitation tendency of the TCP phase shows a slight increase.The stress rupture testing at 1100℃/120 MPa demonstrates that the stress rupture life decreases significantly with the increase in thermal exposure temperature and time.This is mainly attributed to the diminished precipitation strengthening effect of theγ′phase and the deteriorating effect of the TCP phase.However,under the same conditions,the stress rupture properties of this alloy are comparable to those of the DD5 alloy.This research provides theoretical support for enhancing the service stability and reliability of single crystal turbine blades,and offers a reference for the development of cost-effective and highperformance turbine blade materials.
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 Natural Science Foundation of China(No.31670523)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(No.23KJB180005)+1 种基金the Natural Science Foundation of Jiangsu Province(No.BK20230690)Jiangsu Ocean University Graduate Research and Practice Innovation Program Project(No.KYCX2023-105).
文摘Bisphenol A(BPA)is a recognized estrogenic endocrine disruptor that poses a threat to the reproductive health of fish.However,it remains unclear whether and how paternal BPA exposure can lead to developmental toxicity in offspring.To explore the potential paternal BPA exposure impacts on craniofacial cartilage growth in offspring,male rare minnows were subjected to BPA and subsequently mated with normal females to produce progeny.Our results demonstrated that paternal BPA exposure resulted in increased malformation and delayed craniofacial cartilage development in the F1 offspring.Furthermore,BPA exposure led to differential expression of 28 miRNAs in paternal sperm in F0 generation(13 upregulated and 15 downregulated),among which 7 miRNAs were involved in the regulation of bone development.BPA also downregulated the expression of bmp2a and Runx1 during F1 embryonic development.The inhibited bmp2a expression might derive from BPA's stimulation of one miRNA,aca-miR-16a-5P,due to bmp2a being one of its target genes.Notably,paternal BPA exposure did not affect craniofacial cartilage development or gonadal development in the F2 generation.Overall,our study sheds light on the molecular mechanisms underlying the impact of paternal BPA exposure on facial chondrogenesis in offspring and provides theoretical support for the ecological protection of fish populations.
基金supported by the Guizhou Province High-level Innovative Talent Project(Qiankehe Platform Talent-GCC[2022]027-1)the Science and Technology Project of Guizhou Province(Qiankehe Platform Support-[2021]193).
文摘Solid-phase extraction ultrahigh-performance liquid chromatography-tandem mass spectrometry(SPE-UHPLC-MS/MS)was used to evaluate the contamination of ochratoxin A(OTA)and assessed the human exposure risk of OTA in Rasa roxburghii.A more suitable method for OTA extraction and purification of R.roxburghii was obtained.Treated 25 mL of R.roxburghii juice with enzymatic hydrolysis at a concentration of 0.06 mg/mL,filtered the resulting mixture and concentrated the filtrate to dry,then redissolved with 0.2 mL of methanol and diluted with 0.4 mL of ultra-pure water.Added sample solution to the activated hydrophilic-lipophilic balance(HLB)column,washed with 6 mL of ultra-pure water and purified by eluting with 6 mL of methanol.The eluent was collected and dried using nitrogen at 40℃,then redissolved in 1 mL of methanol and filtered for detection.The hazard quotient(HQ)values of all R.roxburghii fruit and juice,which were storage at room temperature,4 and−20℃from 0 day to 63 days,ranged from 0.077%to 35.792%,which were within the allowable limits for human consumption.From the perspective of OTA contamination,the results indicated that the maximal storage time of R.roxburghii fruit were 14 days at room temperature,35 days at 4℃and 63 days at−20℃.And the maximal storage time of R.roxburghii juice were 7 days for sealed storage and the same day for open storage at room temperature,14 days for sealed storage and 7 days for open storage at 4℃,and 63 days for sealed storage and 56 days for open storage at−20℃during the experiment period.And all thirty samples randomly sampled from the market were OTA negative.The results of this study can lay a foundation for the formulation of OTA limit standards in fruits and juice in the future,and provide a reference for consumers to consume R.roxburghii more healthily.
基金supported by the Shangrao Key Research and Development Project(19A005)。
文摘Aluminum is the most abundant environmental pollutant.Recent studies suggest that aluminum exposure increases the risk of multiple diseases,including intestinal barrier dysfunction.We investigated whether Pueraria lobata extract(PLE)is effective in safeguarding against aluminum chloride exposureexacerbated intestinal barrier dysfunction.Using an experimental colitis model of aluminum-exacerbated dextran sulphate sodium(DSS)-treated mice,clinical and pathological evidence suggested that the administration of PLE counteracted aluminum exposure-induced intestinal barrier damage.In addition,we found that aluminum toxicities,including loss of tight junction molecules(TJs),upregulated pro-inflammatory cytokines,and enhanced myeloperoxidase(MPO)activity,were significantly suppressed by PLE administration.Furthermore,PLE administration was identified to inhibit activation of MAPKs and NF-κB signal pathways,which contribute to upregulation of myosin light-chain kinase(MLCK)in inflamed intestine.Taken together,these results suggest that PLE might be a potential candidate for aluminum exposure-related intestinal barrier dysfunction.
