Background Surging production of lithium-ion batteries elevates exposure to NCM cathodes, triggering complex internal metal co-exposure. However, current data are limited to individual metals, the health impacts of this co-exposure remain unclear, directly hindering biomarkers development for risk assessment. Methods Employing a “data-driven to experimentally-validated” strategy, we utilized network toxicology of components to elucidate the health risks and pathogenic characteristics of co-exposure. These were substantiated using an in vivo mouse model and a 402-subject occupational cohort. Guided by these features, we integrated whole-blood transcriptomics with machine learning to identify a plasma protein panel. A predictive risk model was constructed by integrating the measured population protein panel levels with risk stratification. Findings NCM metals share common risks on cardiovascular disease, especially heart injury, with related biomarkers elevated 2.05-fold in highly exposed populations. Furthermore, this risk is characterized by a pathogenic axis featuring IL1B (upregulated 1.70-fold) as a central hub gene activating the NF-κB pathway (2.98-fold) and increase of IL1Bhi macrophages (3.6-fold). Leveraging these characteristics, a five-plasma protein biomarker panel (IL1B, FOS, DUSP1, HSPA5, and RGS2) was identified to develop a machine learning-driven risk model, which showed consistent performance with established heart injury biomarkers (r = 0.80, p < 0.01). Interpretation Our findings define a previously underappreciated IL1B-centric heart injury risk associated with NCM exposure, providing a scalable biomarker panel and risk model for risk assessment.

Lithium-ion batteries (LIBs) stand as a pivotal technology to achieve decarbonization goals amidst the challenges of climate change, and their applications and market size are expanding rapidly. Organophosphorus flame retardants (OPFRs) are crucial components for ensuring the safety performance of LIBs. These chemicals mainly include organophosphates, organophosphites, organophosphonates, and organophosphazenes, with a growing number of new OPFRs continually being synthesized and introduced into the market. OPFRs in LIBs (LIB-OPFRs) can be released into environmental media during battery production, dismantling, and recycling processes, subsequently leading to their occupational and environmental exposure in humans. This review presents the classification, physicochemical properties, environmental behavior, human exposure, and toxicity of LIB-OPFRs. Our analysis reveals that current research predominantly centers on organophosphate flame retardants, while studies on other categories of LIB-OPFRs exhibit a significant research gap. For emerging LIB-OPFRs with a dearth of relevant data, their physicochemical properties and potential toxicity are predicted in this study. Notably, all four categories of LIB-OPFRs show limited but consistent signals of toxicity, and some newly emerging LIB-OPFRs may exhibit higher toxicity compared to traditional ones. Aryl- and halogenated-OPFRs generally exhibit greater bioaccumulative potential and pose higher health risks in comparison to alkyl-OPFRs. Currently, it is imperative to enhance environmental monitoring, toxicological testing, and health risk assessment of new LIB-OPFRs, which are crucial for bridging data gaps and providing guidance for health protective measures as well as policy formulation.

Lithium iron phosphate (LiFePO4, LFP) is a pivotal cathode material in the lithium-ion battery industry. As the LFP market experiences rapid growth, there is an urgent need to assess the potential health hazards associated with occupational exposure to LFP. Herein, this study established the first cohort of LFP production workers and evaluated the effects of LFP exposure on lung function. Additionally, serum metabolic alterations were investigated using a combined untargeted metabolomics and lipidomics approach. Our results indicate that LFP exposure leads to a decline in pulmonary function, accompanied by elevated inflammatory markers. Metabolomics analysis revealed significant alterations in energy and amino acid metabolism, alongside an impairment of endogenous antioxidant systems. Furthermore, lipidomics demonstrated that LFP exposure perturbs sphingolipid and glycerophospholipid metabolism, pathways critically involved in inflammatory signaling and lung function impairment. Using Least Absolute Shrinkage and Selection Operator (LASSO) regression combined with the Boruta algorithm, we identified 12 key metabolites closely associated with lung function indicators. Bi-directional mediation analysis further revealed that five specific lipids significantly mediated the association between the systemic immune-inflammation index (SII) and forced vital capacity (FVC). These findings suggest that disrupted lipid metabolism acts as a crucial mediator in the inflammation-driven decline of lung function among LFP workers, providing a scientific basis for early occupational health risk assessment.

Lithium-ion batteries are indispensable in modern energy storage systems-including portable electronics, electric vehicles, and grid-scale applications-because of their high energy density, long cycle life, and low self-discharge. Among cathode materials, lithium-nickel-cobalt-manganese oxide (LiNiMnCoO2; NCM) is widely used because of its balanced electrochemical performance and strong commercial viability. With the rapid expansion of NCM production and recycling, concerns regarding occupational exposure and related health risks have increased. However, a comprehensive synthesis addressing the toxicological characteristics of NCM as a composite material-rather than its individual metal constituents-remains lacking. This review critically evaluates current evidence on the occupational health effects of NCM materials across their life cycle, with particular emphasis on inhalation exposure to NCM particulates in manufacturing and recycling settings. We integrated epidemiological data, in vivo and in vitro toxicological studies, and mechanistic research to characterize the health risks associated with NCM exposure. Following deposition in the respiratory tract, persistent particles initiate local inflammatory responses, while the gradual release of Ni, Co, and Mn ions within pulmonary and intracellular microenvironments drives sustained molecular and cellular toxicity. Major adverse outcomes include respiratory inflammation and fibrosis, neurotoxicity, hepatic and renal injury, and other systemic effects. We further summarized key toxicity mechanisms, including oxidative stress, inflammatory signaling, DNA damage, and related pathways, and discuss current occupational exposure limits and regulatory considerations for NCM-related metals. By consolidating multidisciplinary evidence, this review aimed to clarify knowledge gaps, inform future research priorities, support evidence-based regulatory decision-making, and promote safer manufacturing practices for next-generation energy storage technologies.

The global transition to electric vehicles hinges on lithium-ion batteries, yet the health risks of their core components, such as nickel-manganese-cobalt (NCM) cathodes, remain a critical and misunderstood gap, threatening a truly sustainable energy transition. Herein, we reveal that inhaled NCM particles undergo sustained lysosomal dissolution, transforming into metal mixtures whose composition mirrors the parent material. Crucially, we decipher the unique toxicological interactions within this biologically generated mixture-antagonism from Ni/Co and synergy from Mn. This fundamental discovery of NCM's biological fate unlocks accurate risk assessment. Building on this mechanistic insight, we identified the Integrated Addition and Interaction (IAI) model as the framework capable of capturing complex interactions. Applying this model to real-world exposure data uncovers moderate yet significant population-level health risks. Our work establishes a transformative, evidence-based paradigm that connects in-body material transformation to real-world health outcomes, providing the scientific foundation to ensure that the clean energy transition is not only green but fundamentally safe for human well-being.

In recent years, interaction, moderation, and mediation analyses have been widely used in occupational health psychology research to explore the relationships among independent variables, dependent variables, and other related variables; however, issues of misuse and abuse still exist. This article introduced the concepts, theoretical foundations, research designs, and data analysis methods of these three analytical approaches, examined their application scenarios, strengths and limitations, as well as common forms of misuse and abuse in occupational health psychology research, proposed recommendations for their scientific application, and discussed prospects for future application.

Multiple studies have shown that exposure to hexavalent chromium Cr(VI) can lead to an imbalance of metal elements in the blood and urine of the body. However, little was known about the distribution of multiple elements in other target tissues after Cr(VI) exposure. We investigated the elemental homeostasis in the lung, thymus, kidney, liver and spleen tissues of rats after Cr(VI) exposure. Forty-eight specific male Sprague-Dawley (SD) rats received intratracheal instillation of Cr(VI) (0.25, 0.125, 0.05 mg/kg) or the same volume (3 ml/kg) of normal saline weekly for 28 days (total of 5 times). After 28 days of exposure, the rats were euthanised and their tissues and organs were collected for research. The contents of different metal elements were determined using an inductively coupled plasma mass spectrometer. The experimental findings demonstrate that following exposure to Cr(VI), chromium accumulates in diverse organs to disparate extents. Notably, the accumulation level of chromium is the highest in the lung tissue. Concurrently, the copper content in the lung tissue exhibits a moderate increase, whereas the zinc content displays a modest decline. In the thymus, the concentrations of elements including manganese, copper, and zinc register an increase. Similarly, the levels of manganese and zinc show an upward trend in the spleen. Furthermore, the homeostasis of various elements in the kidneys and liver is also perturbed, presenting divergent change tendencies. The complex interaction between Cr(VI) and these essential metals highlights the need for further in-depth research to fully understand the underlying mechanisms and develop effective strategies for preventing and treating Cr(VI)-induced toxicity.

Background The widespread environmental contamination by cobalt compounds, coupled with their documented respiratory toxicities, has become a pressing public health concern. Current mechanistic research on the health impacts of these substances lacks coherence and integration, highlighting the need for a comprehensive investigation into the mechanisms of cobalt-induced lung injury. Methods Utilizing CTDbase and NetInfer databases, we obtained target genes of cobalt and its compound and ascertained their associated lung adverse outcomes. Disease-related targets were retrieved from OMIM, DisGeNet, GeneCards, and NCBI databases. A protein-protein interaction (PPI) network was constructed to identify the core targets between compounds and diseases. Based on the DAVID database, enrichment pathways were evaluated by GO and KEGG analyses. Finally, single-cell analysis was conducted to investigate specific cell types implicated in the cobalt-induced lung hazards. Results Pulmonary hypertension (PH) was determined as the most critical lung injury associated with cobalt compounds. In total, we identified 275 compound-related and 3146 PH-related targets, ultimately pinpointing 169 overlapping targets. Among these, 28 pivotal co-targets were implicated in cobalt and its compound-induced PH, including IL6, AKT1, TNF, TP53, NFKB1, HIF1A, etc., which were primarily involved in the IL-17, TNF, and HIF-1 signaling pathways. Moreover, monocytes and macrophages were recognized as effector cells underlying the induction of PH by cobalt exposure, with CXCL8 and HIF1A serving as signature genes. Conclusion Our study not only elucidates pivotal target genes, pathways, and specific cell types involved in cobalt-induced lung hazards, but also establishes a novel approach to clarify the mechanisms underlying metal toxicity.

Diesel exhaust (DE) entering the environment poses a significant risk to public health, but the molecular mechanisms of DE-induced metabolic disorders remain largely unknown. Here we elucidated the impacts of DE exposure on hepatic lipid metabolism using a range of cohort, in vivo, and in vitro approaches. The cohort study revealed altered liver function indices of diesel engine testers (DETs) compared to those of non-DETs and with increasing exposure duration. Mice exposed to DE via whole-body exposure system developed hepatic steatosis, which coincided with an upregulation of the fatty acid transporter CD36, and a marked increase in long-chain fatty acids. Mechanistically, enhanced CD36 expression was predominantly related to the activation of aryl hydrocarbon receptor (AHR). Notably, treatment with organic extract of diesel exhaust particulate (DEP-OE) up-regulated the AHR/CD36 signaling pathway, and led to lipid accumulation in primary mouse hepatocytes. Both effects were markedly diminished by AHR and CD36 knockdown. Finally, we show that targeted inhibition of AHR alleviated DE-induced steatosis in mouse liver. Together, we demonstrate that the organic components of DE cause hepatic steatosis by activating the AHR/CD36 signaling pathway. Our research elucidates DE exposure risks and sheds new insights into the early prevention of diseases in DE-exposed populations.

Ischemic heart disease (IHD) is a major cardiovascular health concern. In addition to metabolic and behavioral risks, diesel particulate matter (DPM), with a widely exposed population, is an important external environmental risk factor for IHD. However, the effect biomarkers used to diagnose DPM-caused IHD and underlying mechanisms remain unknown. We investigated the biomarkers and underlying mechanisms of DPM in relation to myocardial hypoxia injury. This study applied a unique population of diesel engine testers with stable DPM exposure. Electrocardiogram examination, echocardiogram examination, serum levels of myocardial enzymes, and 6-min walking test were used for the myocardial risks assessment. A mouse model exposed to occupational environmental DPM dose and in vitro models of DPM-induced myocardial hypoxia injury were used for assessment of mitochondrial aerobic metabolism via the oxygraph-2k system, western blotting, and kits. Ion fluorescence probes, ion supplements, and mitochondrial RNA splicing protein 2 (Mrs2) overexpression transfection were used in further investigations and verifications of the mechanism of mitochondrial Mg2+ deficiency. We identified compromised myocardial mitochondrial aerobic metabolism as a precursor biomarker for the cardiac risk of myocardial hypertrophy and hypoxia injury in DPM exposure. DPM induce mitochondrial Mg2+ deficiency of cardiomyocytes, which in turn disrupt the mitochondrial aerobic metabolism processes, including the tricarboxylic acid cycle, oxidative phosphorylation, and ATP synthesis. Mg2+ deficiency is mediated by the disruption of Mg2+ transport proteins, such as DPM-enhanced hyperubiquitination and degradation of Mrs2, a protein responsible for mitochondrial Mg2+ uptake. Our findings show that compromised mitochondrial aerobic metabolism, associated with Mg2+ deficiency, serves as a critical biomarker for DPM-induced IHD and represents a promising investigative avenue for intervention.

Liver fibrosis is a global health issue with limited treatments. While apigenin has demonstrated potential in alleviating liver fibrosis, its mechanisms remain unclear. This study employed an integrated proteotranscriptomic approach to elucidate the molecular mechanisms underlying apigenin's protective effects against CCl4-induced liver fibrosis. Liver tissues from mice with CCl4-induced fibrosis treated with different doses of apigenin (10, 20, and 40 mg/kg) were analyzed using transcriptomics and proteomics. Results demonstrated dose-dependent antifibrotic effects of apigenin. Notably, numerous genes and proteins were inversely regulated by CCl4 and apigenin, with generally low and variable mRNA-protein abundance correlations. We identified 82 biological processes or molecular functions that were inversely regulated by CCl4 and high-dose apigenin at both mRNA and protein levels. Among the 48 key proteins (KPs) involved, 11 and 14 KPs correlated with liver fibrosis in mouse and human data sets, respectively. Six KPs maintained consistent correlations with fibrosis severity across both species, highlighting their potential as both biomarkers for fibrosis progression and translational targets. These findings underscore apigenin's therapeutic potential and emphasize the importance of multiomics approaches in understanding complex diseases like liver fibrosis. This study also provides valuable insights for developing improved therapeutic strategies and diagnostic tools for liver fibrosis.

Objective: This study explored the relationship between susceptibility to single-nucleotide polymorphisms (SNP) and noise-induced hearing loss (NIHL) in a population exposed to occupational noise. Methods: Workers exposed to noise in a steel enterprise in Henan Province were included in the study. Workers with a hearing threshold of ≥40 dB (A) for binaural high-frequency (3000, 4000, and 6000 Hz) in the pure tone audiometry were included in the case group (393 workers in total). Individuals whose hearing threshold for any frequency (500, 1000, and 2000 Hz) was ≤25 dB (A) and an average hearing threshold of <35 dB (A) for high frequencies were included in the control group (731 individuals in total). A SNPscan multiple SNP typing kit was used for SNP typing, and PLINK software was used in analyzing the correlation between each gene locus and NIHL susceptibility. Cumulative noise exposure (CNE) was stratified as CNE < 97 dB (A) · year and CNE ≥ 97 dB (A) · year. Results: Regarding rs11204100, compared with subjects with the TT genotype, subjects with the TC+CC genotype were less susceptible to NIHL (odds ratio [OR] [95% CI] = 0.712 [0.554, 0.913], P = 0.009). After CNE stratification, subjects with the TC+CC genotype were less susceptible to NIHL than those with the TT genotype in the CNE ≥97 dB (A) · year group (OR [95% CI] = 0.614 [0.433, 0.871], P = 0.007). As for the rs10503675, subjects with the AG+GG genotype were less susceptible to NIHL than subjects with the AA genotype (OR [95% CI] = 0.797 [0.541, 0.925], P = 0.011) in the general population. Haplotype results showed that CGT (rs11204100-rs10503675-rs17412009) is associated with lowered susceptibility to NIHL. Conclusion: The ATP6V1B2 gene plays an important role in the risk of NIHL, and the C allele of rs11204100 and G allele of rs10503675 are associated with lowered susceptibility to NIHL.

Objective: To investigate the effect of apigenin on carbon tetrachloride (CCl4)-induced liver fibrosis and elucidate the underlying mechanisms. Methods: A mouse model of CCl4-induced liver fibrosis was used to evaluate the effects of apigenin. Liver function was assessed using biochemical tests, and inflammation-associated markers, including interleukin-1 beta (IL-1β), IL-6, IL-10, and tumor necrosis factor- alpha (TNF-α), were determined by enzyme-linked immunosorbent assay (ELISA). H&E staining, Sirius Red staining, and collagen immunohistochemistry were also conducted. In addition, antioxidant enzyme activity and the underlying mechanisms of hepatoprotective effects of apigenin were examined. Results: CCl4 administration induced hepatic stellate cell activation and liver fibrogenesis in mice. Apigenin treatment markedly decreased liver injury markers, inflammation, oxidative stress, and collagen deposition, mitigating CCl4-induced liver fibrosis. Furthermore, it significantly suppressed the activation of the phosphoinositide 3-kinase/protein kinase B/glycogen synthase kinase 3 beta (PI3K/AKT/GSK3β) pathway by reducing the ratios of p-PI3K/PI3K, p-AKT/AKT, and p-GSK3β/GSK3β in liver tissue. Conclusions: Apigenin ameliorates CCl4-induced liver fibrosis in mice, likely through the inhibition of the PI3K/AKT/GSK3β signaling pathway. These findings suggest that apigenin may have therapeutic potential for treating liver fibrosis.

Diesel exhaust (DE) is a significant contributor to the traffic-related air pollution (TRAP) and has been linked to multiple adverse health outcomes. However, research on glycolipid metabolic disturbance associated with human exposure to DE remains scarce. Based on the cohort of diesel engine testers (DETs), this study revealed that DE exposure could disrupt liver function and interfere with the glucose and lipid metabolism in humans. By combining targeted analyses of amino acids and fatty acids with untargeted lipidomics approaches, we comprehensively elucidated the altered plasma metabolic profiles induced by DE exposure. A total of 8 amino acids, 3 fatty acids, and 36 lipids were identified as differential metabolites. These perturbed metabolites further indicate the impaired glycolipid metabolism, and furnish evidence of the adverse health risks resulting from DE exposure, primarily encompassing insulin resistance, cardiovascular diseases (CVDs), liver diseases, and neurotoxicity. A machine learning-based regression algorithm identified metabolites that are likely to mediate changes in the clinical indicators related to glycolipid metabolism. Mediation analysis and validation cohort showed that alanine (Ala), AcCa(21:1), and PC(38:1) potentially serve as early predictive biomarkers for DE-induced alterations in glucose levels. This study offers the first metabolic evidence establishing a link between DE exposure and glycolipid metabolic disturbance, highlighting the potential health risks posed by TRAP.

Little is known about how diesel engine exhaust (DEE) exposure is associated with changes in blood lipid concentrations, as well as the molecular initiating events (MIEs) and mechanisms underlying this association. The aim of this research was to determine the MIEs and key molecular events and thus construct a putative adverse outcome pathway (AOP) from DEE exposure to an increased risk of metabolism-related diseases by integrating occupational epidemiology and metabolomics analyses. We recruited 136 participants with high DEE exposure and 99 healthy controls to investigate the associations between polycyclic aromatic hydrocarbons (PAHs; an exposure biomarker of DEE), blood lipids (high-density lipoprotein cholesterol (HDL-C) and lowdensity lipoprotein cholesterol), and plasma metabolites. Our results revealed that the concentrations of six OH-PAHs were increased significantly in urine samples from participants with high DEE exposure (P <= 0.001), and that 9-hydroxyphenanthrene (9-OHPh) is uniquely associated with decreased HDL-C concentrations (P = 0.034). Each 10% increase in the 9-OHPh concentration corresponded to a 0.225% decrease in the HDL-C concentration. Targeted metabolomics analysis revealed key pathways associated with both 9-OHPh and HDL-C, including alanine and glutamine metabolism, glutathione biosynthesis, sirtuin, and TP53 pathway. Additionally, nine metabolites (e.g. glutamate, glutamine, and glutathione) were enriched in pathways associated with both 9OHPh and HDL-C. Bioinformatic analyses of these metabolites identified potential MIEs (e.g. CPT1B, LDHB, and SIX1) and adverse outcomes (liver damage, renal necrosis, and cardiac damage). Based on these findings, we propose for the first time a putative AOP connecting DEE exposure with metabolism-related disease risks, which is driven by alterations in MIEs, subsequent metabolic disturbances, and reduced HDL-C levels, thus providing crucial insights into environmental contributors to metabolic disorders.

BackgroundAt present, high level of depression is a serious problem in medical staff and may affect their immune function. The role of psychological resilience between depression and immunity cannot be ignored. However, it is still lack of research report in this area. ObjectiveTo explore the mediating effect of psychological resilience on the association between depression and humoral immunological biomarkers in medical staff. MethodsA total of 108 medical staff from a tertiary hospital in Henan Province were selected using stratified cluster sampling from September 2022 to December 2022. The Connor-Davidson Resilience Scale and Patient Health Questionnaire-9 were used to evaluate their psychological resilience and depression. Serum immunoglobulin (Ig) M (IgM), IgG, IgA, complement 3 (C3), and complement 4 (C4) were detected in fasting venous blood samples. Mann-Whitney U test, Kruskal-Wallis H test, independent-samples t-test, and One-way ANOVA were used for comparisons among different demographic groups. Spearman correlation was used to evaluate correlations among measured variables. PROCESS plug-in was used to verify potential mediating effect of psychological resilience on the relationship between depression and humoral immunological biomarkers. ResultsThe M (P25, P75) score of psychological resilience was 65.50 (53.25, 75.00) in the participating medical staff. The ratios of low, medium, and high levels of psychological resilience were 2.78% (3/108), 51.85% (56/108), and 45.37% (49/108), respectively. The M (P25, P75) score of depression was 6.00 (2.00, 8.00). The positive rate of depression was 61.11% (66/108). The correlation analysis results showed that psychological resilience was negatively correlated with depression and serum complement C3 (r=−0.416 and −0.309, P＜0.01), positively correlated with serum IgG and serum IgA (r=0.302 and 0.517, P＜0.01); optimism, self-improvement, and resilience were negatively correlated with depression (r=−0.387, −0.446, and −0.312, P<0.01), positively correlated with IgG (r=0.194, 0.284, and 0.239, P<0.05), and positively correlated with IgA (r=0.377, 0.378, and 0.444, P<0.01), respectively; resilience was negatively correlated with C3 (r=−0.304, P<0.01), and depression was negatively correlated with serum IgG and serum IgA (r=−0.516 and −0.522, P＜0.01), positively correlated with serum complement C3 (r=0.195, P＜0.05). The mediating effect test showed that psychological resilience showed mediating effects on the relationship between depression and serum IgA and serum complement C3, with mediating effect values of −0.148 (95%CI: −0.051, −0.012) and 0.111 (95%CI: 0.001, 0.010), and their mediating effect ratios were 28.30% and 56.92%. ConclusionThe mental health status of the target medical staff is not optimistic. Depression is associated with changes in some humoral immunological biomarkers. Psychological resilience can mediate the correlations between depression and humoral immunological biomarkers. The managers should take measures to improve the levels of psychological resilience and promote the physical and mental health of medical staff.

Cellular senescence may predominantly drive the progression of early subclinical injury under conditions of low-dose, long-term occupational exposure. However, previous research has largely overlooked the cellular senescence induced by hexavalent chromium [Cr(VI)]. To bridge the gap, 304 workers from a chromate facility were enrolled, and a mouse model was used to confirm the effects of Cr(VI) on cellular senescence. A 2.7-fold increase in blood Cr was related to the changes of p53 [23.19 (13.06, 34.23)%], serum α-Klotho [11.45 (6.13, 17.04)%], adipsin [-14.11(-22.16, -5.24)%], leptin [-4.32(-6.99, -1.58)%] and resistin [-3.29(-5.54, -0.98)%]. There were significant correlations of blood Cr with DNA methylation of ELOVL2 and hTERT genes. Furthermore, methylation at hTERT Pos1, Pos2, Pos6, and Pos8 significantly mediated the relationship between blood Cr and p53. In the mouse model, we observed significantly higher mRNA expression levels of key genes in the p53/p21 and Rb/p16 pathways and senescence-associated β-galactosidase positive cell ratio in the exposed group. In conclusion, we found that p53 in human peripheral blood cells serves as a Cr(VI)-induced senescence biomarker, with α-Klotho upregulation and adipokines (adipsin, leptin, and resistin) downregulation indicating compensatory responses, as well as hTERT methylation partially mediating Cr(VI)-senescence association.

Exposure to hexavalent chromium damages genetic materials like DNA and chromosomes, further elevating cancer risk, yet research rarely focuses on related immunological mechanisms, which play an important role in the occurrence and development of cancer. We investigated the association between blood chromium (Cr) levels and genetic damage biomarkers as well as the immune regulatory mechanism involved, such as costimulatory molecules, in 120 workers exposed to chromates. Higher blood Cr levels were linearly correlated with higher genetic damage, reflected by urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and blood micronucleus frequency (MNF). Exploratory factor analysis revealed that both positive and negative immune regulation patterns were positively associated with blood Cr. Specifically, higher levels of programmed cell death protein 1 (PD-1; mediated proportion: 4.12%), programmed cell death ligand 1 (PD-L1; 5.22%), lymphocyte activation gene 3 (LAG-3; 2.11%), and their constitutive positive immune regulation pattern (5.86%) indirectly positively influenced the relationship between blood Cr and urinary 8-OHdG. NOD-like receptor family pyrin domain containing 3 (NLRP3) positively affected the association between blood Cr levels and inflammatory immunity. This study, using machine learning, investigated immune regulation and its potential role in chromate-induced genetic damage, providing insights into complex relationships and emphasizing the need for further research.

Background:The relationship between CDH23 gene variants and NIHL is unclear. This study investigates the association between cadherin 23 (CDH23) gene variants and noise-induced hearing loss (NIHL).Methods:This is a case-control study. Workers who were exposed to noise from a steel factory in North China were recruited and divided into two groups: the case group (both ears' high-frequency threshold average [BHFTA] ≥40dB) and the control group (BHFTA ≤25 dB). This study used the generalised multifactor dimensionality reduction method to analyse the association among 18 single-nucleotide polymorphisms (SNPs) in CDH23 and NIHL. Logistic regression was performed to investigate the main effects of SNPs and the interactions between cumulative noise exposure (CNE) and SNPs. Furthermore, CNE was adjusted for age, gender, smoking, drinking, physical exercise and hypertension.Results:This study recruited 1,117 participants. The results showed that for rs11592462, participants who carried the GG genotype showed an association with NIHL greater than that of those who carried the CC genotype. Accordingly, genetic variation in the CDH23 gene could play an essential role in determining individual susceptibility to NIHL.Conclusion:Genetic variations in the CDH23 gene may play an important role in determining individual susceptibility to NIHL. These results provide new insight into the pathogenesis and early prevention of NIHL.

Hexavalent chromium (Cr(VI)) has been identified as a Class I human carcinogen, but its carcinogenic mechanism is currently unclear. There is still a lack of understanding of its associations with early pulmonary inflammatory damages. Inflammation is an important stage before the occurrence of tumors, and under the long-term stimulation of inflammation, it can promote the development of tumors. In this study, the aim is to explore the effect of Cr(VI) exposure on pulmonary inflammation and its relationship with the mechanism of inflammation cancer transformation. We established a Cr(VI) exposure model in SD rats using tracheal instillation of potassium dichromate solution, and collected samples at the time of cessation of exposure and 14 days after cessation of exposure. Analyzing the experimental results, it was found that the lung index increased after exposure to Cr(VI), promoting the occurrence of apoptosis in lung tissue cells and exacerbating lung tissue damage. The damage situation improved after exposure termination; Inductively coupled plasma mass (ICPRQ) spectrometer detection found that the exposed group had significantly increased levels of blood chromium, blood manganese, blood copper, blood arsenic, urine chromium, urine copper, and urine lead; After two weeks of repair, blood chromium and blood manganese levels were significantly lower than those in the same dose group of the exposure group, while blood copper levels were significantly higher than those in the same dose group of the exposure group. There was no significant difference in blood arsenic levels between the exposure group and the exposure group. Urine chromium and urine lead levels were significantly lower than those in the same dose group of the exposure group, while urine copper levels only increased. At the same time, it was found that Cr(VI) exposure caused disruption of oxidative stress levels in rat lung tissues. After 14-day exposure, Cr(VI) significantly decreased and oxidative stress levels significantly decreased. Further investigation revealed that Cr(VI) induces activation of inflammasomes NLRP3, AIM2, and their signaling pathways in lung inflammatory injuries, but this condition persists even after cessation of exposure. The study suggested that in hexavalent chromium induced lung tissue injuries in rats, NLRP3 and AIM2 inflammasomes and their signaling pathways activation. Furthermore, the characteristic of sustained activation after cessation of exposure was also indicated. These results provide new ideas and references for further elucidating the mechanisms of Cr(VI), lung inflammation and inflammation cancer transformation.