Clean heating policies were implemented in rural areas of Shaanxi Province in 2017 to alleviate severe air pollution. To evaluate their impacts on bioavailability of PM2.5-bound metals, the influence of emission sources and aerosol acidity on PM2.5-bound metal solubility was explored in Xi'an over three policy-defined periods between 2016 and 2021. Results showed that aerosol pH increased progressively from 4.81 ± 1.82 to 5.29 ± 1.79 following policy implementation, closely associated with reductions in SO2 and NO2 concentrations due to emission controls. Metal concentrations decreased significantly over the study period. In contrast, metal solubility exhibited clear source-dependent variations. Solubilities of metals associated with coal combustion, biomass burning, and industrial activities (As, Cd, Pb, K and Zn) decreased by 16.6-50.5% with weakening aerosol acidity. In contrast, solubilities of metals related to vehicle exhaust, oil fuel combustion and dust (Cu, V, Ni, Ti and Fe) increased by 38.3-56.8%, indicating enhanced influence of emission processes. Source apportionment demonstrated that mixed contributions of coal combustion, biomass burning and industrial activities to total and water-soluble metals decreased by 12% and 11.2%, respectively, while contribution from secondary atmospheric processes increased by 4% and 3.8%. These findings highlight that clean heating policies reshape both metal sources and atmospheric chemical environments, thereby altering metal dissolution characteristics and bioavailability.
{"title":"Changes in Metal Solubility in PM<sub>2.5</sub> in Xi'an City Under Clean Heating Policies: Effects of Emission Source and Aerosol Acidity.","authors":"Hongyu Yan, Pingping Liu, Yuhao Dong, Chuchen Li, Zhiwei Xue, Jing Xue, Jian Sun, Hongmei Xu","doi":"10.3390/toxics14020168","DOIUrl":"10.3390/toxics14020168","url":null,"abstract":"<p><p>Clean heating policies were implemented in rural areas of Shaanxi Province in 2017 to alleviate severe air pollution. To evaluate their impacts on bioavailability of PM<sub>2.5</sub>-bound metals, the influence of emission sources and aerosol acidity on PM<sub>2.5</sub>-bound metal solubility was explored in Xi'an over three policy-defined periods between 2016 and 2021. Results showed that aerosol pH increased progressively from 4.81 ± 1.82 to 5.29 ± 1.79 following policy implementation, closely associated with reductions in SO<sub>2</sub> and NO<sub>2</sub> concentrations due to emission controls. Metal concentrations decreased significantly over the study period. In contrast, metal solubility exhibited clear source-dependent variations. Solubilities of metals associated with coal combustion, biomass burning, and industrial activities (As, Cd, Pb, K and Zn) decreased by 16.6-50.5% with weakening aerosol acidity. In contrast, solubilities of metals related to vehicle exhaust, oil fuel combustion and dust (Cu, V, Ni, Ti and Fe) increased by 38.3-56.8%, indicating enhanced influence of emission processes. Source apportionment demonstrated that mixed contributions of coal combustion, biomass burning and industrial activities to total and water-soluble metals decreased by 12% and 11.2%, respectively, while contribution from secondary atmospheric processes increased by 4% and 3.8%. These findings highlight that clean heating policies reshape both metal sources and atmospheric chemical environments, thereby altering metal dissolution characteristics and bioavailability.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12945187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147290784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The objective of this study was to conduct preliminary tests to determine if differing concentrations of atrazine affected locomotion and/or food-seeking behaviors of juvenile (second and third instar) virile crayfish after a 4-day (96 h) exposure period. After exposing crayfish to 0, 5, 10, 20, and 100 parts per billion (ppb) atrazine treatments, crayfish were tested and video-taped individually in a flow-through test arena before and during introduction of a food odor. Walking speeds (pre-odor, post-odor, and pre- to post-ratios), time to locate the food-odor source, and success rates in finding the food odor were compared among atrazine treatments. Pre-odor walking speeds, time to locate the food-odor source, and post-odor walking speeds did not differ among the control and treatment crayfish. Crayfish success rates in locating the food-odor source also did not differ among treatments and controls. Crayfish in controls and all atrazine treatments walked slightly, but not significantly, faster after a food odor was presented than before. Virile crayfish food-seeking behavior and locomotion were not affected after exposures up to 100 ppb atrazine, so these behaviors likely are not useful indicators of crayfish exposure to environmentally relevant (5 ppb or less) atrazine levels like those measured periodically in regional streams. Expanded replication and testing may be helpful in assessing the effects of atrazine (especially concentrations at or above 100 ppb) on the food-seeking behaviors of this species, although simple behavioral studies of crayfish may not be sensitive enough to assess the true effects of atrazine on aquatic organisms and communities.
{"title":"Preliminary Tests on the Effects of Atrazine Exposure on the Food-Seeking Behaviors and Locomotion of Juvenile Virile Crayfish (<i>Faxonius virilis</i>).","authors":"Neal D Mundahl, Darcy E M Keyport","doi":"10.3390/toxics14020164","DOIUrl":"10.3390/toxics14020164","url":null,"abstract":"<p><p>The objective of this study was to conduct preliminary tests to determine if differing concentrations of atrazine affected locomotion and/or food-seeking behaviors of juvenile (second and third instar) virile crayfish after a 4-day (96 h) exposure period. After exposing crayfish to 0, 5, 10, 20, and 100 parts per billion (ppb) atrazine treatments, crayfish were tested and video-taped individually in a flow-through test arena before and during introduction of a food odor. Walking speeds (pre-odor, post-odor, and pre- to post-ratios), time to locate the food-odor source, and success rates in finding the food odor were compared among atrazine treatments. Pre-odor walking speeds, time to locate the food-odor source, and post-odor walking speeds did not differ among the control and treatment crayfish. Crayfish success rates in locating the food-odor source also did not differ among treatments and controls. Crayfish in controls and all atrazine treatments walked slightly, but not significantly, faster after a food odor was presented than before. Virile crayfish food-seeking behavior and locomotion were not affected after exposures up to 100 ppb atrazine, so these behaviors likely are not useful indicators of crayfish exposure to environmentally relevant (5 ppb or less) atrazine levels like those measured periodically in regional streams. Expanded replication and testing may be helpful in assessing the effects of atrazine (especially concentrations at or above 100 ppb) on the food-seeking behaviors of this species, although simple behavioral studies of crayfish may not be sensitive enough to assess the true effects of atrazine on aquatic organisms and communities.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12945112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147290924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drinking water represents a major pathway for human exposure to heavy metals, which are associated with long-term and cumulative health risks. This study investigated eight heavy metals (Ba, V, Cr(VI), Mn, Mo, Ni, Cu, Fe) in three centralized drinking water sources in southwest Guizhou from January 2021 to December 2023. Overall, the measured heavy metal concentrations complied with relevant national standards; however, transient exceedances of the Class I surface water standard were observed for Cu and Cr(VI) in certain months, with the most pronounced deviations occurring in 2022. Significant temporal variations were observed for Mn, Ni, Cu, and Fe, likely influenced by anthropogenic activities such as sewage discharge and agriculture, while Cr(VI), Mo, Ba, and V showed notable spatial differences linked to the region's geological features. Health risk assessments showed that the non-carcinogenic risks for both adults and children remained below the maximum acceptable level of 5.0 × 10-5 a-1, with Cu, Mo, Ba, and V contributing most to the risks. In contrast, the carcinogenic risk associated with Cr(VI) exceeded the ICRP-recommended benchmark of 1.0 × 10-6 a-1, with estimated risks for children approximately 1.6 times higher than those for adults. In 2022, the carcinogenic risk was highest across all sources. Autoregressive integrated moving average (ARIMA) based forecasts suggest that Cr(VI)-related carcinogenic risk is likely to remain above acceptable levels in the near future, with an increasing trend projected for Mulanghe Reservoir, a declining trend for Xingxihu Reservoir, and relatively stable conditions for Weishanhu Reservoir. These findings underscore the need for targeted interventions, particularly in controlling Cr(VI) concentrations and protecting vulnerable populations.
{"title":"ARIMA-Based Prediction of Heavy Metal Health Risks in Drinking Water Sources of Southwest Guizhou, China.","authors":"Haihe Wang, Lin Zhong, Yuanyuan Sun, Qiuhua Li","doi":"10.3390/toxics14020166","DOIUrl":"10.3390/toxics14020166","url":null,"abstract":"<p><p>Drinking water represents a major pathway for human exposure to heavy metals, which are associated with long-term and cumulative health risks. This study investigated eight heavy metals (Ba, V, Cr(VI), Mn, Mo, Ni, Cu, Fe) in three centralized drinking water sources in southwest Guizhou from January 2021 to December 2023. Overall, the measured heavy metal concentrations complied with relevant national standards; however, transient exceedances of the Class I surface water standard were observed for Cu and Cr(VI) in certain months, with the most pronounced deviations occurring in 2022. Significant temporal variations were observed for Mn, Ni, Cu, and Fe, likely influenced by anthropogenic activities such as sewage discharge and agriculture, while Cr(VI), Mo, Ba, and V showed notable spatial differences linked to the region's geological features. Health risk assessments showed that the non-carcinogenic risks for both adults and children remained below the maximum acceptable level of 5.0 × 10<sup>-5</sup> a<sup>-1</sup>, with Cu, Mo, Ba, and V contributing most to the risks. In contrast, the carcinogenic risk associated with Cr(VI) exceeded the ICRP-recommended benchmark of 1.0 × 10<sup>-6</sup> a<sup>-1</sup>, with estimated risks for children approximately 1.6 times higher than those for adults. In 2022, the carcinogenic risk was highest across all sources. Autoregressive integrated moving average (ARIMA) based forecasts suggest that Cr(VI)-related carcinogenic risk is likely to remain above acceptable levels in the near future, with an increasing trend projected for Mulanghe Reservoir, a declining trend for Xingxihu Reservoir, and relatively stable conditions for Weishanhu Reservoir. These findings underscore the need for targeted interventions, particularly in controlling Cr(VI) concentrations and protecting vulnerable populations.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12944652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147290638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sohyeon Choi, Jae-Hyun Kim, Aram Lee, Yong-Jun Jeon, Won Kim, Inja Choi, Jeongim Park
Despite global restrictions like the Minamata Convention, heavy metal contamination in cosmetics remains a critical public health concern, with limited cross-country comparative data on heavy metal concentrations in cosmetics across Asian markets. We measured Hg, Pb, As, Cd, Sb, Cr, and Ni contents in 189 cosmetic products purchased in 2022 in Bangladesh, India, Indonesia, Korea, Malaysia, the Philippines, and Vietnam. Samples were screened by handheld X-ray fluorescence; Hg was quantified by a direct mercury analyzer and As, Cd, Cr, Ni, Pb, and Sb were quantified by ICP-OES. Principal component analysis (PCA) was used to characterize metal co-occurrence patterns, and Monte Carlo simulation was applied to estimate dermal systemic exposure dose, hazard quotients (HQ), and lifetime cancer risk (LCR). Mercury in face creams exhibited extreme heterogeneity (range: ND-67,000 mg/kg), while eye cosmetics contained elevated Arsenic levels (median 4.13 mg/kg). PCA distinctively separated Hg (PC2) from geogenic metals (As/Cr/Ni on PC1), suggesting intentional adulteration. Probabilistic risk estimates indicated upper-tail non-cancer risk for Hg in facial creams (95th percentile HQ 6.32; P[HQ>1] = 24.4%). As produced the highest LCR estimates (facial cream 95th percentile 2.60 × 10-4). These findings indicate product-type-specific metal patterns and highlight a subset of facial products with extreme Hg levels that can drive substantial upper-percentile risk, supporting the need for targeted market surveillance and enforcement.
{"title":"Concentrations and Probabilistic Health Risks of Seven Metals in Face and Eye Cosmetics Across Seven Asian Countries.","authors":"Sohyeon Choi, Jae-Hyun Kim, Aram Lee, Yong-Jun Jeon, Won Kim, Inja Choi, Jeongim Park","doi":"10.3390/toxics14020167","DOIUrl":"10.3390/toxics14020167","url":null,"abstract":"<p><p>Despite global restrictions like the Minamata Convention, heavy metal contamination in cosmetics remains a critical public health concern, with limited cross-country comparative data on heavy metal concentrations in cosmetics across Asian markets. We measured Hg, Pb, As, Cd, Sb, Cr, and Ni contents in 189 cosmetic products purchased in 2022 in Bangladesh, India, Indonesia, Korea, Malaysia, the Philippines, and Vietnam. Samples were screened by handheld X-ray fluorescence; Hg was quantified by a direct mercury analyzer and As, Cd, Cr, Ni, Pb, and Sb were quantified by ICP-OES. Principal component analysis (PCA) was used to characterize metal co-occurrence patterns, and Monte Carlo simulation was applied to estimate dermal systemic exposure dose, hazard quotients (HQ), and lifetime cancer risk (LCR). Mercury in face creams exhibited extreme heterogeneity (range: ND-67,000 mg/kg), while eye cosmetics contained elevated Arsenic levels (median 4.13 mg/kg). PCA distinctively separated Hg (PC2) from geogenic metals (As/Cr/Ni on PC1), suggesting intentional adulteration. Probabilistic risk estimates indicated upper-tail non-cancer risk for Hg in facial creams (95th percentile HQ 6.32; P[HQ>1] = 24.4%). As produced the highest LCR estimates (facial cream 95th percentile 2.60 × 10<sup>-4</sup>). These findings indicate product-type-specific metal patterns and highlight a subset of facial products with extreme Hg levels that can drive substantial upper-percentile risk, supporting the need for targeted market surveillance and enforcement.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12944837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147290796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jan Oltmanns, Christoph Scheibelein, Fabian A Grimm
Consumer exposure to chemicals in the EU is currently assessed separately for different products without aggregating exposure from different sources. A more integrated ap proach represents a promising opportunity to improve comprehensive risk evaluation and transparency across the value chain. This study develops aggregate consumer expo sure and risk assessment methods that involve calculation of exposure and risk for each pathway using the risk characterization ratio (RCR) as a uniform risk metric. Aggregate risk is obtained by adding up pathway-specific RCRs. The developed methodology re presents a new approach by evaluating exposure of seven population groups via all path ways and by using key input values normalized to body weight to reflect population-specific differences. The study demonstrates the practical applicability of the methodol o gy by assessing consumer exposure to the antioxidant ethylene bis[3,3-bis(3-tert-butyl-4-hydroxyphenyl)butyrate] (Hostanox® O 3), resulting from its use in food and drinking water contact materials, textiles and sealants. This case study demonstrates aggregate RCRs well below one for all groups. The highest aggregate RCRs are found for infants and toddlers, reflecting their proportionally higher food consumption and skin surface area. The methodology is transparent and can easily be applied to other substances, e.g., by industry stakeholders and authorities, if the substance concentration in products can be established. This study may inform further development of aggregate exposure and risk methods in EU regulatory frameworks.
{"title":"Aggregate Consumer Exposure and Risk Assessment in the EU-A Case Study.","authors":"Jan Oltmanns, Christoph Scheibelein, Fabian A Grimm","doi":"10.3390/toxics14020165","DOIUrl":"10.3390/toxics14020165","url":null,"abstract":"<p><p>Consumer exposure to chemicals in the EU is currently assessed separately for different products without aggregating exposure from different sources. A more integrated ap proach represents a promising opportunity to improve comprehensive risk evaluation and transparency across the value chain. This study develops aggregate consumer expo sure and risk assessment methods that involve calculation of exposure and risk for each pathway using the risk characterization ratio (RCR) as a uniform risk metric. Aggregate risk is obtained by adding up pathway-specific RCRs. The developed methodology re presents a new approach by evaluating exposure of seven population groups via all path ways and by using key input values normalized to body weight to reflect population-specific differences. The study demonstrates the practical applicability of the methodol o gy by assessing consumer exposure to the antioxidant ethylene bis[3,3-bis(3-tert-butyl-4-hydroxyphenyl)butyrate] (Hostanox<sup>®</sup> O 3), resulting from its use in food and drinking water contact materials, textiles and sealants. This case study demonstrates aggregate RCRs well below one for all groups. The highest aggregate RCRs are found for infants and toddlers, reflecting their proportionally higher food consumption and skin surface area. The methodology is transparent and can easily be applied to other substances, e.g., by industry stakeholders and authorities, if the substance concentration in products can be established. This study may inform further development of aggregate exposure and risk methods in EU regulatory frameworks.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12945028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147291035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Prenatal exposure to essential and toxic metals may influence fetal development and birth outcomes. Meconium represents a valuable biomarker of cumulative intrauterine exposure; however, data linking maternal lifestyle and diet to meconium metal concentrations remain limited. This study included 152 mother-newborn pairs at the University Hospital Center Split. Meconium samples were analyzed for essential metals (Mn, Zn, Fe, Cu) and toxic metals (Hg, Pb, Cd, Ni, Cr) using atomic absorption spectrometry. Maternal and newborn characteristics were collected via questionnaires and medical records. Associations between maternal factors and metal concentrations were assessed using multivariable regression, and inter-metal correlations were evaluated with Spearman's rank correlation. The correlation matrix indicates positive correlations among essential metals, particularly between Fe and Cu (rs = 0.523), whereas toxic metals show mixed correlation patterns. Maternal factors were associated with several metal concentrations: zinc was positively associated with the newborn ponderal index; greater gestational weight gain and longer gestation were associated with lower iron concentrations; frequent fruit or grain consumption was associated with lower copper concentrations; frequent milk/dairy intake was associated with lower mercury; and fish consumption was associated with higher mercury and manganese. Rural residence and lower smoking intensity were associated with lower lead concentrations, while higher pre-pregnancy body mass index and frequent maternal smoking were associated with increased cadmium. No significant associations were observed for nickel or chromium. These findings highlight the influence of maternal diet, lifestyle, and environmental factors on fetal metal exposure, underscoring the need for monitoring, food safety control, and targeted education during pregnancy.
{"title":"Maternal and Newborn Factors Associated with Meconium Metal Concentrations: A Cross-Sectional Study.","authors":"Bianka Mimica, Ajka Pribisalic, Zlatka Knezovic, Nina Knezovic, Davorka Sutlovic","doi":"10.3390/toxics14020163","DOIUrl":"10.3390/toxics14020163","url":null,"abstract":"<p><p>Prenatal exposure to essential and toxic metals may influence fetal development and birth outcomes. Meconium represents a valuable biomarker of cumulative intrauterine exposure; however, data linking maternal lifestyle and diet to meconium metal concentrations remain limited. This study included 152 mother-newborn pairs at the University Hospital Center Split. Meconium samples were analyzed for essential metals (Mn, Zn, Fe, Cu) and toxic metals (Hg, Pb, Cd, Ni, Cr) using atomic absorption spectrometry. Maternal and newborn characteristics were collected via questionnaires and medical records. Associations between maternal factors and metal concentrations were assessed using multivariable regression, and inter-metal correlations were evaluated with Spearman's rank correlation. The correlation matrix indicates positive correlations among essential metals, particularly between Fe and Cu (r<sub>s</sub> = 0.523), whereas toxic metals show mixed correlation patterns. Maternal factors were associated with several metal concentrations: zinc was positively associated with the newborn ponderal index; greater gestational weight gain and longer gestation were associated with lower iron concentrations; frequent fruit or grain consumption was associated with lower copper concentrations; frequent milk/dairy intake was associated with lower mercury; and fish consumption was associated with higher mercury and manganese. Rural residence and lower smoking intensity were associated with lower lead concentrations, while higher pre-pregnancy body mass index and frequent maternal smoking were associated with increased cadmium. No significant associations were observed for nickel or chromium. These findings highlight the influence of maternal diet, lifestyle, and environmental factors on fetal metal exposure, underscoring the need for monitoring, food safety control, and targeted education during pregnancy.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12945197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147290547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stefan M Leonard, Charlotte R Pearson, Wynand P Roos, Robert W Sobol
Ubiquitin-specific protease 1 (USP1) is an emerging target for poly(ADP-ribose) polymerase 1 (PARP1) inhibitor-resistant and BRCA1/BRCA2 mutant tumors. USP1 is a deubiquitylating enzyme responsible for the removal of the mono-ubiquitin mark on FANCD2, PARP1, and the replication factor proliferating cell nuclear antigen (PCNA), among other proteins. USP1 facilitates proper PCNA-mediated polymerase switching from error-prone trans-lesion synthesis DNA polymerases to replicative DNA polymerases. Due to the critical role of USP1 in DNA synthesis and DNA repair, and the discovery that USP1 deubiquitylates PARP1, USP1 inhibitors (USP1i) were found to have a synthetic lethal relationship with PARP1 inhibitors (PARPi), suggesting a mechanistic link between poly(ADP-ribose) (PAR) dynamics and USP1-mediated ubiquitin hydrolysis. However, the relationship between USP1 inhibition and inhibitors of poly(ADP-ribose) glycohydrolase (PARGi), the primary enzyme responsible for PAR hydrolysis, has not been resolved. Using cell cytotoxicity, synergy, PCNA-ubiquitin, and PAR analyses, it is demonstrated herein that PARG inhibition, combined with USP1 inhibition, leads to increased levels of mono-ubiquitinated PCNA, decreased PAR accumulation, and synergistic cytotoxicity between ML323, a potent USP1i, and PDD00017273, a model PARGi. Future studies will focus on the mechanism that contributes to USP1/PARG synthetic lethality, the mechanism of cell death, and the impact of USP1 on PAR/ubiquitin dynamics and replication stress signaling.
{"title":"Synergistic Cellular Toxicity from Inhibition of Poly(ADP-ribose) Glycohydrolase (PARG) and Ubiquitin-Specific Protease 1 (USP1).","authors":"Stefan M Leonard, Charlotte R Pearson, Wynand P Roos, Robert W Sobol","doi":"10.3390/toxics14020162","DOIUrl":"10.3390/toxics14020162","url":null,"abstract":"<p><p>Ubiquitin-specific protease 1 (USP1) is an emerging target for poly(ADP-ribose) polymerase 1 (PARP1) inhibitor-resistant and BRCA1/BRCA2 mutant tumors. USP1 is a deubiquitylating enzyme responsible for the removal of the mono-ubiquitin mark on FANCD2, PARP1, and the replication factor proliferating cell nuclear antigen (PCNA), among other proteins. USP1 facilitates proper PCNA-mediated polymerase switching from error-prone trans-lesion synthesis DNA polymerases to replicative DNA polymerases. Due to the critical role of USP1 in DNA synthesis and DNA repair, and the discovery that USP1 deubiquitylates PARP1, USP1 inhibitors (USP1i) were found to have a synthetic lethal relationship with PARP1 inhibitors (PARPi), suggesting a mechanistic link between poly(ADP-ribose) (PAR) dynamics and USP1-mediated ubiquitin hydrolysis. However, the relationship between USP1 inhibition and inhibitors of poly(ADP-ribose) glycohydrolase (PARGi), the primary enzyme responsible for PAR hydrolysis, has not been resolved. Using cell cytotoxicity, synergy, PCNA-ubiquitin, and PAR analyses, it is demonstrated herein that PARG inhibition, combined with USP1 inhibition, leads to increased levels of mono-ubiquitinated PCNA, decreased PAR accumulation, and synergistic cytotoxicity between ML323, a potent USP1i, and PDD00017273, a model PARGi. Future studies will focus on the mechanism that contributes to USP1/PARG synthetic lethality, the mechanism of cell death, and the impact of USP1 on PAR/ubiquitin dynamics and replication stress signaling.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12944873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147291001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peixuan Li, Yanqin Ren, Fang Bi, Fangyun Long, Junling Li, Haijie Zhang, Zhenhai Wu, Hong Li
The ability of the atmosphere to convert primary pollutants into secondary pollutants through atmospheric oxidants is referred to as the atmospheric oxidizing capacity (AOC). This study systematically reviews the generation mechanisms, influencing factors, and quantitative characterization methods of major oxidants, along with advances in chemical mechanisms and modeling. We provide a comparative analysis of AOCs across diverse environments, including urban, suburban, and rural regions, highlighting the distinct impacts of anthropogenic and biogenic emissions on oxidation regimes. Despite advancements in chemical transport models and machine learning, limitations such as sparse observations, imperfect parameterizations, and unresolved chemical mechanisms lead to significant underestimations of the AOC. Future research must prioritize multi-scale observational networks and the elucidation of key chemical processes to refine model accuracy and improve the effectiveness of pollution control strategies.
{"title":"Advances and Challenges in Understanding Atmospheric Oxidizing Capacity in China: Insights from Chemical Mechanisms and Model Applications.","authors":"Peixuan Li, Yanqin Ren, Fang Bi, Fangyun Long, Junling Li, Haijie Zhang, Zhenhai Wu, Hong Li","doi":"10.3390/toxics14020159","DOIUrl":"10.3390/toxics14020159","url":null,"abstract":"<p><p>The ability of the atmosphere to convert primary pollutants into secondary pollutants through atmospheric oxidants is referred to as the atmospheric oxidizing capacity (AOC). This study systematically reviews the generation mechanisms, influencing factors, and quantitative characterization methods of major oxidants, along with advances in chemical mechanisms and modeling. We provide a comparative analysis of AOCs across diverse environments, including urban, suburban, and rural regions, highlighting the distinct impacts of anthropogenic and biogenic emissions on oxidation regimes. Despite advancements in chemical transport models and machine learning, limitations such as sparse observations, imperfect parameterizations, and unresolved chemical mechanisms lead to significant underestimations of the AOC. Future research must prioritize multi-scale observational networks and the elucidation of key chemical processes to refine model accuracy and improve the effectiveness of pollution control strategies.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12944996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147290987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Microplastics and nanoplastics, as pervasive and persistent environmental pollutants, are raising growing concerns regarding their potential risks to reproductive health, particularly pregnancy outcomes. Although the reproductive toxicity of polystyrene nanoplastics (PS-NPs) has been reported, the specific mechanisms underlying their effects on placental development and offspring health following gestational exposure remain unclear.
Method: This study aimed to investigate the effects of gestational exposure to PS-NPs of different sizes (50 and 200 nm) and concentrations (1, 3, and 10 mg/mL) on placental function and embryonic development in ICR mice. An exposure model was established via tail vein injection, and samples were collected on embryonic Day 14.5 (E14.5).
Results: the exposed groups tended towards increased embryo weight, embryo length, and embryo head circumference. Transcriptomic analysis revealed that PS-NP exposure significantly downregulated the expression of Ndufa5 (a subunit of mitochondrial respiratory chain complex I) and mt-CO1 (a core subunit of complex IV), but upregulated the expression of the genes Cldn1 (tight junction protein) and Erbb3 (receptor tyrosine kinase) in the placenta. Differentially expressed genes were enriched primarily in pathways related to oxidative phosphorylation, the tricarboxylic acid (TCA) cycle, and ErbB signalling.
Conclusions: These changes collectively led to decreased mitochondrial ATP production, increased oxidative stress in the placenta, and potentially altered placental barrier function and trophoblast cell proliferation signalling. This study reveals a novel mechanism by which PS-NPs disrupt placental development and embryonic growth through impairment of placental energy metabolic homeostasis and key signalling pathways, thus providing crucial experimental evidence for assessing the reproductive and developmental toxicity of nanoplastics.
{"title":"Polystyrene Nanoparticles Disrupt Oxidative Phosphorylation and Impair Placental Development in Mice.","authors":"Bingyi Wang, Xinyi Xie, Nairui Fan, Qiqi Deng, Nannan Shi, Denglu Long, Weipeng Huang, Siqi Zhu, Zhi Chen, Xin Cheng, Xuesong Yang, Guang Wang, Qihao Zhang","doi":"10.3390/toxics14020158","DOIUrl":"10.3390/toxics14020158","url":null,"abstract":"<p><strong>Background: </strong>Microplastics and nanoplastics, as pervasive and persistent environmental pollutants, are raising growing concerns regarding their potential risks to reproductive health, particularly pregnancy outcomes. Although the reproductive toxicity of polystyrene nanoplastics (PS-NPs) has been reported, the specific mechanisms underlying their effects on placental development and offspring health following gestational exposure remain unclear.</p><p><strong>Method: </strong>This study aimed to investigate the effects of gestational exposure to PS-NPs of different sizes (50 and 200 nm) and concentrations (1, 3, and 10 mg/mL) on placental function and embryonic development in ICR mice. An exposure model was established via tail vein injection, and samples were collected on embryonic Day 14.5 (E14.5).</p><p><strong>Results: </strong>the exposed groups tended towards increased embryo weight, embryo length, and embryo head circumference. Transcriptomic analysis revealed that PS-NP exposure significantly downregulated the expression of <i>Ndufa5</i> (a subunit of mitochondrial respiratory chain complex I) and <i>mt-CO1</i> (a core subunit of complex IV), but upregulated the expression of the genes <i>Cldn1</i> (tight junction protein) and <i>Erbb3</i> (receptor tyrosine kinase) in the placenta. Differentially expressed genes were enriched primarily in pathways related to oxidative phosphorylation, the tricarboxylic acid (TCA) cycle, and ErbB signalling.</p><p><strong>Conclusions: </strong>These changes collectively led to decreased mitochondrial ATP production, increased oxidative stress in the placenta, and potentially altered placental barrier function and trophoblast cell proliferation signalling. This study reveals a novel mechanism by which PS-NPs disrupt placental development and embryonic growth through impairment of placental energy metabolic homeostasis and key signalling pathways, thus providing crucial experimental evidence for assessing the reproductive and developmental toxicity of nanoplastics.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12945053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147290753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hexavalent chromium (Cr(VI)) is a recognized environmental and occupational hazard with significant implications for immune function. However, the cell-intrinsic mechanisms by which Cr(VI) coordinately reshapes macrophage polarization together with immunometabolic and mitochondrial alterations remain incompletely characterized. This study investigated how Cr(VI) exposure influences macrophage morphology, polarization, energy metabolism, and mitochondrial integrity using an in vitro model. Macrophages exposed to Cr(VI) exhibited morphological changes, including pseudopod growth and fusiform shapes, alongside a shift toward M1-type polarization. Key M1 associated biomarkers, including TNF-α, CD36, and CD80, increased 24 h after Cr(VI) exposure, whereas the M2 associated VEGFb decreased. Cr(VI) exposure also impaired energy metabolism, reducing ATP production and shifting metabolism towards glycolysis, despite increased glucose uptake. Mitochondrial damage, membrane potential collapse, and elevated oxidative stress further highlighted the immunotoxic effects of Cr(VI). Cr(VI) exposure may drive a metabolic shift in macrophages toward less efficient energy production pathways, such as glycolysis. These findings provide critical insights into Cr(VI)-induced macrophage dysfunction and emphasize the environmental risks associated with Cr(VI) pollution, underscoring the need for further mechanistic research and mitigation strategies to safeguard public health.
{"title":"Chromium(VI) Modulates Macrophage Polarization and Metabolic Reprogramming to Impair Immune Function.","authors":"Cheng Li, Ruihang Zhang, Yuhan Zhang, Hongxi Yu, Yu Zheng, Yifei Du, Shiyi Hong, Lihua Hu, Chaoyang Wang, Guang Jia, Guiping Hu","doi":"10.3390/toxics14020160","DOIUrl":"10.3390/toxics14020160","url":null,"abstract":"<p><p>Hexavalent chromium (Cr(VI)) is a recognized environmental and occupational hazard with significant implications for immune function. However, the cell-intrinsic mechanisms by which Cr(VI) coordinately reshapes macrophage polarization together with immunometabolic and mitochondrial alterations remain incompletely characterized. This study investigated how Cr(VI) exposure influences macrophage morphology, polarization, energy metabolism, and mitochondrial integrity using an in vitro model. Macrophages exposed to Cr(VI) exhibited morphological changes, including pseudopod growth and fusiform shapes, alongside a shift toward M1-type polarization. Key M1 associated biomarkers, including TNF-α, CD36, and CD80, increased 24 h after Cr(VI) exposure, whereas the M2 associated VEGFb decreased. Cr(VI) exposure also impaired energy metabolism, reducing ATP production and shifting metabolism towards glycolysis, despite increased glucose uptake. Mitochondrial damage, membrane potential collapse, and elevated oxidative stress further highlighted the immunotoxic effects of Cr(VI). Cr(VI) exposure may drive a metabolic shift in macrophages toward less efficient energy production pathways, such as glycolysis. These findings provide critical insights into Cr(VI)-induced macrophage dysfunction and emphasize the environmental risks associated with Cr(VI) pollution, underscoring the need for further mechanistic research and mitigation strategies to safeguard public health.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12944406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147290775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}