Corrigendum: Extracellular HSP90α interacts with ER stress to promote fibroblasts activation through PI3K/AKT pathway in pulmonary fibrosis.

[This corrects the article DOI: 10.3389/fphar.2021.708462.].

Nontarget Analysis of Legacy and Emerging PFAS in a Lithium-Ion Power Battery Recycling Park and Their Possible Toxicity Measured Using High-Throughput Phenotype Screening.

Driven by the global popularity of electric vehicles and the shortage of critical raw materials for batteries, the spent lithium-ion power battery (LIPB) recycling industry has exhibited explosive growth in both quantity and scale. However, relatively little information is known about the environmental risks posed by LIPB recycling, in particular with regards to perfluoroalkyl and polyfluoroalkyl substances (PFAS). In this work, suspect screening and nontarget analysis were carried out to characterize PFAS in soil, dust, water and sediment from a LIPB recycling area. Twenty-five PFAS from nine classes were identified at confidence level 3 or above, including 13 legacy and 12 emerging PFAS, as well as two ultrashort-chain PFAS. Based on the target analysis of 16 PFAS, at least nine were detected in each environmental sample, indicating their widespread presence in a LIPB recycling area. Perfluorodecanoic acid, perfluorooctanesulfonic acid and trifluoromethanesulfonamide showed significant differences in the four phenotypic parameters (growth, movement, survival and fecundity) of Caenorhabditis elegans and were the most toxic substances in all target PFAS at an exposure concentration of 200 µM. Our project provides first-hand information on the existence and environmental risk of PFAS, facilitating the formulation of regulations and green development of the LIPB recycling industry.

Sex-specific associations of urinary mixed-metal concentrations with femoral bone mineral density among older people: an NHANES (2017-2020) analysis.

Background: Heavy metal exposure is an important cause of reduced bone mineral density (BMD). Epidemiological studies focusing on the effects of mixed heavy metal exposure on BMD in middle-aged and older people are scarce. In single-metal studies, men and women have shown distinct responses of BMD to environmental metal exposure. This study therefore aimed to elucidate the association between mixed heavy metal exposure and BMD and to investigate whether it is sex-specific. Methods: Data from the 2017-2020 National Health and Nutrition Examination Survey were selected for this cross-sectional study. The study used three statistical methods, i.e., linear regression, Bayesian kernel machine regression (BKMR) modeling, and weighted quartiles (WQS) regression, to explore the association between the urinary concentrations of 11 metals (barium, cadmium, cobalt, cesium, manganese, molybdenum, lead, antimony, tin, thallium, and Tungsten), either individually or as a mixture, and total femoral BMD. Results: A total of 1,031 participants were included in this study. Femoral BMD was found to be higher in men than women. A significant negative correlation between the urinary concentrations of the 10 metals and femoral BMD was found in the overall cohort. Further gender sub-stratified analyses showed that in men, urinary metal concentrations were negatively correlated with femoral BMD, with cobalt and barium playing a significant and non-linear role in this effect. In women, although urinary metal concentrations negatively modulated femoral BMD, none of the correlations was statistically significant. Antimony showed sex-specific differences in its effect. Conclusion: The urinary concentrations of 10 mixed heavy metals were negatively correlated with femoral BMD in middle-aged and older participants, and this effect showed gender differences. These findings emphasize the differing role of mixed metal exposure in the process of BMD reduction between the sexes but require further validation by prospective studies.

1G6-D7 Inhibits Homologous Recombination Repair by Targeting Extracellular HSP90α to Promote Apoptosis in Non-Small Cell Lung Cancer.

Despite recent advances in treatment, non-small cell lung cancer (NSCLC) continues to have a high mortality rate. Currently, NSCLC pathogenesis requires further investigation, and therapeutic drugs are still under development. Homologous recombination repair (HRR) repairs severe DNA double-strand breaks. Homologous recombination repair deficiency (HRD) occurs when HRR is impaired and causes irreparable double-strand DNA damage, leading to genomic instability and increasing the risk of cancer development. Poly(ADP-ribose) polymerase (PARP) inhibitors can effectively treat HRD-positive tumors. Extracellular heat shock protein 90α (eHSP90α) is highly expressed in hypoxic environments and inhibits apoptosis, thereby increasing cellular tolerance. Here, we investigated the relationship between eHSP90α and HRR in NSCLC. DNA damage models were established in NSCLC cell lines (A549 and H1299). The activation of DNA damage and HRR markers, apoptosis, proliferation, and migration were investigated. In vivo tumor models were established using BALB/c nude mice and A549 cells. We found that human recombinant HSP90α stimulation further activated HRR and reduced DNA damage extent; however, eHSP90α monoclonal antibody, 1G6-D7, effectively inhibited HRR. HRR inhibition and increased apoptosis were observed after LRP1 knockdown; this effect could not be reversed with hrHSP90α addition. The combined use of 1G6-D7 and olaparib caused significant apoptosis and HRR inhibition in vitro and demonstrated promising anti-tumor effects in vivo. Extracellular HSP90α may be involved in HRR in NSCLC through LRP1. The combined use of 1G6-D7 and PARP inhibitors may exert anti-tumor effects by inhibiting DNA repair and further inducing apoptosis of NSCLC cells.

ADHD classification with cross-dataset feature selection for biomarker consistency detection.

Objective.Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder in children. While numerous intelligent methods are applied for its subjective diagnosis, they seldom consider the consistency problem of ADHD biomarkers. In practice, these data-driven approaches lead to varying learned features for ADHD classification across diverse ADHD datasets. This phenomenon significantly undermines the reliability of identified biomarkers and hampers the interpretability of these methods.Approach.In this study, we propose a cross-dataset feature selection (FS) module using a grouped SVM-based recursive feature elimination approach (G-SVM-RFE) to enhance biomarker consistency across multiple datasets. Additionally, we employ connectome gradient data for ADHD classification. In details, we introduce the G-SVM-RFE method to effectively concentrate gradient components within a few brain regions, thereby increasing the likelihood of identifying these regions as ADHD biomarkers. The cross-dataset FS module is integrated into an existing binary hypothesis testing (BHT) framework. This module utilizes external datasets to identify global regions that yield stable biomarkers. Meanwhile, given a dataset which waits for implementing the classification task as local dataset, we learn its own specific regions to further improve the performance of accuracy on this dataset.Main results.By employing this module, our experiments achieve an average accuracy of 96.7% on diverse datasets. Importantly, the discriminative gradient components primarily originate from the global regions, providing evidence for the significance of these regions. We further identify regions with the high appearance frequencies as biomarkers, where all the used global regions and one local region are recognized.Significance.These biomarkers align with existing research on impaired brain regions in children with ADHD. Thus, our method demonstrates its validity by providing enhanced biological explanations derived from ADHD mechanisms.

Polystyrene microplastics induce pulmonary fibrosis by promoting alveolar epithelial cell ferroptosis through cGAS/STING signaling.

Polystyrene microplastics (PS-MPs) are new types of environmental pollutant that have garnered significant attention in recent years since they were found to cause damage to the human respiratory system when they are inhaled. The pulmonary fibrosis is one of the serious consequences of PS-MPs inhalation. However, the impact and underlying mechanisms of PS-MPs on pulmonary fibrosis are not clear. In this study, we studied the potential lung toxicity and PS-MPs-developed pulmonary fibrosis by long-term intranasal inhalation of PS-MPs. The results showed that after exposing to the PS-MPs, the lungs of model mouse had different levels of damage and fibrosis. Meanwhile, exposing to the PS-MPs resulted in a markedly decrease in glutathione (GSH), an increase in malondialdehyde (MDA), and iron overload in the lung tissue of mice and alveolar epithelial cells (AECs). These findings suggested the occurrence of PS-MP-induced ferroptosis. Inhibitor of ferroptosis (Fer-1) had alleviated the PS-MPs-induced ferroptosis. Mechanically, PS-MPs triggered cell ferroptosis and promoted the development of pulmonary fibrosis via activating the cGAS/STING signaling pathway. Inhibition of cGAS/STING with G150/H151 attenuated pulmonary fibrosis after PS-MPs exposure. Together, these data provided novel mechanistic insights of PS-MPs-induced pulmonary fibrosis and a potential therapeutic paradigm.

Bile acid metabolism is altered in learning and memory impairment induced by chronic lead exposure.

Lead is a neurotoxic contaminant that exists widely in the environment. Although lead neurotoxicity has been found to be tightly linked to gut microbiota disturbance, the effect of host metabolic disorders caused by gut microbiota disturbance on lead neurotoxicity has not been investigated. In this work, the results of new object recognition tests and Morris water maze tests showed that chronic low-dose lead exposure caused learning and memory dysfunction in mice. The results of 16 S rRNA sequencing of cecal contents and fecal microbiota transplantation showed that the neurotoxicity of lead could be transmitted through gut microbiota. The results of untargeted metabolomics and bile acid targeted metabolism analysis showed that the serum bile acid metabolism profile of lead-exposed mice was significantly changed. In addition, supplementation with TUDCA or INT-777 significantly alleviated chronic lead exposure-induced learning and memory impairment, primarily through inhibition of the NLRP3 inflammasome in the hippocampus to relieve neuroinflammation. In conclusion, our findings suggested that dysregulation of host bile acid metabolism may be one of the mechanisms of lead-induced neurotoxicity, and supplementation of specific bile acids may be a possible therapeutic strategy for lead-induced neurotoxicity.

Tetrandrine alleviates pulmonary fibrosis by inhibiting alveolar epithelial cell senescence through PINK1/Parkin-mediated mitophagy.

Idiopathic pulmonary fibrosis (IPF) is a fatal and insidious interstitial lung disease. So far, there are no effective drugs for preventing the disease process. Cellular senescence plays a critical role in the development of IPF, with the senescence and insufficient mitophagy of alveolar epithelial cells being implicated in its pathogenesis. Tetrandrine is a natural alkaloid which is now produced synthetically. It was known that the tetrandrine has anti-fibrotic effects, but the efficacy and mechanisms are still not well evaluated. Here, we reveal the roles of tetrandrine on AECs senescence and the antifibrotic effects by using a bleomycin challenged mouse model of pulmonary fibrosis and a bleomycin-stimulated mouse alveolar epithelial cell line (MLE-12). We performed the ß-galactosidase staining, immunohistochemistry and fluorescence to assess senescence in MLE-12 cells. The mitophagy levels were detected by co-localization of LC3 and COVIX. Our findings indicate that tetrandrine suppressed bleomycin-induced fibroblast activation and ultimately blocked the increase of collagen deposition in mouse model lung tissue. It has significantly inhibited the bleomycin-induced senescence and senescence-associated secretory phenotype (SASP) in alveolar epithelial cells (AECs). Mechanistically, tetrandrine suppressed the decrease of mitochondrial autophagy-related protein expression to rescue the bleomycin-stimulated impaired mitophagy in MLE-12 cells. We revealed that knockdown the putative kinase 1 (PINK1) gene by a short interfering RNA (siRNA) could abolish the ability of tetrandrine and reverse the MLE-12 cells senescence, which indicated the mitophagy of MLE-12 cells is PINK1 dependent. Our data suggest the tetrandrine could be a novel and effective drug candidate for lung fibrosis and senescence-related fibrotic diseases.

Up-regulation of HSP90α in HDM-induced asthma causes pyroptosis of airway epithelial cells by activating the cGAS-STING-ER stress pathway.

Heat Shock protein 90 α (HSP90α), an main subtype of chaperone protein HSP90, involves important biological functions such as DNA damage repair, protein modification, innate immunity. However, the potential role of HSP90α in asthma occurrence and development is still unclear. This study aimed to elucidate the underlying mechanism of HSP90α in asthma by focusing on the cGAS-STING-Endoplasmic Reticulum stress pathway in inflammatory airway epithelial cell death (i.e., pyroptosis; inflammatory cell death). To accomplish that, we modeled allergen exposure in C57/6BL mice and bronchial epithelial cells with house dust mite. Protein technologies and immunofluorescence utilized to study the expression of HSP90α, activation of cGAS-STING pathway and pyroptosis. The effect of inhibitors on HDM-exposed mice detected by histological techniques and examination of bronchoalveolar lavage fluid. Results showed that HSP90α promotes asthma inflammation via pyroptosis and activation of the cGAS-STING-ER stress pathway. Treatment with the HSP90 inhibitor tanespimycin (17-AAG) significantly relieved airway inflammation and abrogated the effect of HSP90α on pyroptosis and cGAS-STING-ER stress in vitro and in vivo models of HDM. Further data indicated that up-regulation of HSP90α stabilized STING through interaction, which increased localization of STING on the ER. Activation of STING triggered ER stress and leaded to pyroptosis-related airway inflammation. The finding showed the potential role of pyroptosis caused by dysregulation of HSP90α on airway epithelial cells in allergic inflammation, suggested that targeting HSP90α in airway epithelial cells might prove to be a potential additional treatment strategy for asthma.

Association of blood metals with anxiety among adults: A nationally representative cross-sectional study.

BACKGROUND: Previous evidence demonstrated the inconsistent associations between metals and anxiety. The purpose of this study was to evaluate the individual and joint effects of blood lead (Pb), cadmium (Cd), mercury (Hg), selenium (Se) and manganese (Mn) on anxiety in the general population. METHODS: Data of 4000 participants (aged≥20 years) in the study were retrieved from the National Health and Nutrition Examination Survey (NHANES) 2011-2012. Multiple logistic regression, restricted cubic splines (RCS) logistic analysis, and weighted quantile sum (WQS) regression were fitted to explore the possible effects of single and mixed metal exposures on anxiety. Moreover, this association was assessed by smoking group. RESULTS: In the study, 24.60 % of participants were in an anxiety state. In logistic regression, blood Pb, Cd, Hg, Se and Mn were not significantly associated with anxiety in all participants. After stratified by smoking group, blood Cd was positively associated with anxiety in the current smoking group [P = 0.029, OR (95 %): 1.708(1.063, 3.040)], whereas not in other groups. In RCS regression, we observed a linear dose-response effect of blood Cd on anxiety stratified by smoking group. In WQS analysis, mixed metal exposures were positively associated with anxiety [P = 0.033, OR (95 %): 1.437(1.031, 2.003)], with Cd (33.69 %) contributing the largest weight to the index. CONCLUSIONS: Our study showed that excessive exposure to Cd is a significant risk factor for anxiety, and the co-exposures to Pb, Cd, Hg, Se and Mn were positively related with the risk of anxiety in current smokers.

Sodium butyrate alleviates lead-induced neuroinflammation and improves cognitive and memory impairment through the ACSS2/H3K9ac/BDNF pathway.

Lead is an environmentally widespread neurotoxic pollutant. Although the neurotoxicity of lead has been found to be closely associated with metabolic disorders, the effects of short-chain fatty acids on the neurotoxicity of lead and its mechanisms have not yet been explored. In this study, the results of open field tests and Morris water maze tests demonstrated that chronic lead exposure caused learning and memory deficits and anxiety-like symptoms in mice. The serum butyric acid content of lead-treated mice decreased in a dose-dependent manner, and oral administration of butyrate significantly improved cognitive memory impairment and anxiety symptoms in lead-exposed mice. Moreover, butyrate alleviated neuroinflammation caused by lead exposure by inhibiting the STAT3 signaling in microglia. Butyrate also promoted the expression of acetyl-CoA synthetase ACSS2 in hippocampal neurons, thereby increasing the content of acetyl-CoA and restoring the expression of both histone H3K9ac and the downstream BDNF. We also found that the median butyric acid concentration in high-lead exposure humans was remarkably lower than that in the low-lead exposure humans (45.16 µg/L vs. 60.92 µg/L, P < 0.01), and that butyric acid significantly mediated the relationship of lead exposure with the Montreal cognitive assessment scores, with a contribution rate of 27.57 %. In conclusion, our results suggest that butyrate supplementation is a possible therapeutic strategy for lead-induced neurotoxicity.

Lead inhibits microglial cell migration via suppression of store-operated calcium entry.

Lead (Pb) is a non-biodegradable environmental pollutant that can lead to neurotoxicity by inducing neuroinflammation. Microglial activation plays a key role in neuroinflammation, and microglial migration is one of its main features. However, whether Pb affects microglial migration has not yet been elucidated. Herein, the effect of Pb on microglial migration was investigated using BV-2 microglial cells and primary microglial cells. The results showed that cell activation markers (TNF-α and CD206) in BV-2 cells were increased after Pb treatment. The migration ability of microglia was inhibited by Pb. Both store-operated calcium entry (SOCE) and the Ca2+ release-activated Ca2+ (CRAC) current were downregulated by microglia treatment with Pb in a dose-dependent manner. However, there was no statistical difference in the protein levels of stromal interaction molecule (STIM) 1, STIM2, or Ca2+ release-activated Ca2+ channel protein (Orai) 1 in microglia. The external Ca2+ influx and cell migration ability were restored to a certain extent after overexpression of either STIM1 or its CRAC activation domain in microglia. These results indicated that Pb inhibits microglial migration by downregulation of SOCE and impairment of the function of STIM1.

Decline in Working Memory in Stable Schizophrenia May Be Related to Attentional Impairment: Mediating Effects of Negative Symptoms, a Cross-Sectional Study.

Background: Schizophrenia (SCZ) is a severe mental illness, Cognitive deficits and negative symptoms (NS) are prevalent in individuals with SCZ and are crucial indicators of functional recovery. It is well known that cognitive symptoms and negative symptoms are interrelated and that negative symptoms can affect the ability to take cognitive tests. However, the specific relationship between attention, working memory (WM), and NS in stable SCZ remains unclear. This study aims to explore these associations and provide valuable insights for the subsequent treatment of SCZ. Methods: We conducted a comprehensive assessment of 145 patients with stable SCZ using the Chinese Brief Neurocognitive Suite of Tests (C-BCT) and the Positive and Negative Symptom Scale (PANSS). Results: Patients with abnormal cognition exhibited significantly higher PANSS total scores, cognitive symptom scores, and NS than those with normal cognition (P<0.05). Pearson's correlation analysis revealed significant positive correlations between digital breadth(DB) and continuous operation(CO) (r=0.389, P<0.001), as well as a significant negative correlation between DB and NS (r=-0.291, P<0.001). Moreover, CO showed a negative correlation with NS (r=-0.173, P<0.05). However, no significant correlations were found between the digital breadth-anterograde score and CO or NS (r=0.148, P>0.05; r=-0.068, P>0.05). Notably, NS were identified as a mediator in the relationship between attention and WM (effect size=0.024). Conclusion: Our findings highlight significant associations between WM, attention, and NS in individuals with stable SCZ. Moreover, attention not only directly impacts WM but also indirectly influences it through NS. Addressing cognitive deficits and NS in the treatment of SCZ may lead to improved overall outcomes for affected individuals.

The Synergistic Impact of Crystal Seed and Fluoride Ion in the Synthesis of Silicalite-1 Zeolite in Low-Template Systems.

Silicalite-1 zeolites are widely applied in gas adsorption, catalysis, and separation due to their excellent hydrothermal stability and unique pore structure. However, traditional preparation methods have inherent drawbacks such as high pollution, high cost, etc. Therefore, this work proposed a green and efficient route for preparing Silicalite-1 zeolite by adding NH4F (F/Si = 0.1) and seeds (10 wt%) in a much shorter time (8 h) in a low-template system (TPA+/Si = 0.007). It was found that NH4F is beneficial for inhibiting the formation of SiO2. The S-1 seeds could drastically induce the formation of the zeolite skeleton structure. Noteworthy, the morphology of zeolites was determined by the relative content of NH4F and seeds. The crystal morphology is determined by the higher content of the two substances; however, when the content is similar, the crystal morphology is determined by NH4F. The results showed that simultaneous control of NH4F and seeds can suppress SiO2 formation, can improve the relative crystallinity of products, and can be precisely regulated via the synergistic effect of both in zeolite morphology. This work not only provides new ideas for regulating the morphology of silicate-1 crystals but also offers a new path for industrial large-scale production of low-cost and efficient zeolites.

Dynamic alterations of locomotor activity and the microbiota in zebrafish larvae with low concentrations of lead exposure.

Lead (Pb) is a ubiquitous heavy metal associated with developmental and behavioral disorders. The establishment of pioneer microbiota overlaps with the development of the brain during early life, and Pb-induced developmental neurotoxicity may be partially caused by early-life microbiota dysbiosis. This study investigated the locomotor activity and the microbiota in developing zebrafish at multiple developmental time points (five days post fertilization [5 dpf], 6 dpf, and 7 dpf) under exposure to low concentrations of lead (0.05 mg/L). Time-dependent reductions in the number of activities and the average movement distance of larvae compared to the control were observed following Pb exposure. Furthermore, Pb exposure significantly altered the composition of the gut microbiota of zebrafish larvae. At the phylum level, the abundance of Proteobacteria decreased from 5 to 7 dpf, while that of Actinobacteria increased in the control groups. At the class level, the proportion of Alphaproteobacteria decreased, while that of Actinobacteria increased in the control groups. Notably, all showed the opposite trend in Pb groups. A correlation analysis between indices of locomotor activity and microbial communities revealed genus-level features that were clearly linked to the neurobehavioral performance of zebrafish. Seven genera were significantly correlated with the two performance indicators of the locomotion analysis, namely Rhodococcus, Deinococcus, Bacillus, Bosea, Bradyrhizobium, Staphylococcus, and Rhizobium. Rhizobium was dominant in zebrafish and increased in the Pb groups in a time-dependent manner. In addition, the expression levels of bdnf, trkb1, trkb2, and p75ntr changed in zebrafish from 5 to 7 dpf under Pb exposure. Collectively, these results suggest that Pb-induced neurotoxicity could potentially be treated by targeting the gut microbiota.

Nicotinamide mononucleotide attenuates airway epithelial barrier dysfunction via inhibiting SIRT3 SUMOylation in asthma.

Nicotinamide adenine dinucleotide (NAD+) is an essential element in cellular metabolism that regulates fundamental biological processes. Growing evidence suggests that a decline in NAD+ is a common pathological factor in various diseases and aging. However, its role in airway epithelial barrier function in response to asthma remains underexplored. The current study aims to explore the efficacy of restoring cellular NAD+ concentration through supplementation with the NAD+ precursor, nicotinamide mononucleotide (NMN), in the treatment of allergic asthma and to investigate the role of SIRT3 in mediating the effects of NAD+ precursors. In this research, NMN alleviated airway inflammation and reduced mucus secretion in house dust mite (HDM)-induced asthmatic mice. It also mitigated airway epithelial barrier disruption in HDM-induced asthma in vitro and in vivo. But inhibition of SIRT3 expression abolished the effects of NMN. Mechanistically, HDM induced SIRT3 SUMOylation and proteasomal degradation. Mutation of these two SIRT3 SUMO modification sites enhanced the stability of SIRT3. Additionally, SIRT3 was targeted by SENP1 which acted to de-conjugate SUMO. And down-regulation of SENP1 expression in HDM-induced models was reversed by NMN. Collectively, these findings suggest that NMN attenuates airway epithelial barrier dysfunction via inhibiting SIRT3 SUMOylation in asthma. Blockage of SIRT3 SUMOylation emerges as for the treatment of allergic asthma.

Lead aggravates Alzheimer's disease pathology via mitochondrial copper accumulation regulated by COX17.

Alzheimer's disease (AD) is a common neurodegenerative disease that is associated with multiple environmental risk factors, including heavy metals. Lead (Pb) is a heavy metal contaminant, which is closely related to the incidence of AD. However, the research on the role of microglia in Pb-induced AD-like pathology is limited. To determine the mechanism by which Pb exposure aggravates AD progression and the role of microglial activation, we exposed APP/PS1 mice and Aß1-42-treated BV-2 cells to Pb. Our results suggested that chronic Pb exposure exacerbated learning and memory impairments in APP/PS1 mice. Pb exposure increased the activation of microglia in the hippocampus of APP/PS1 mice, which was associated with increased deposition of Aß1-42, and induced hippocampal neuron damage. Pb exposure upregulated copper transporter 1 (CTR1) and downregulated copper P-type ATPase transporter (ATP7A) in the hippocampus of APP/PS1 mice and Aß1-42-treated BV-2 cells. Moreover, Pb enhanced mitochondrial translocation of the mitochondrial copper transporter COX17, leading to an increase in mitochondrial copper concentration and mitochondrial damage. This could be reversed by copper-chelating agents or by inhibiting the mitochondrial translocation of COX17. The increased mitochondrial copper concentration caused by increased mitochondrial translocation of COX17 after Pb exposure may be related to the enhanced mitochondrial import pathway of AIF/CHCHD4. These results indicate that Pb induces the activation of microglia by increasing the concentration of copper in the mitochondria of microglia, and microglia release inflammatory factors to promote neuroinflammation, thus aggravating the pathology of AD. The present study provides new ideas for the prevention of Pb-induced AD.

Association of Serum Concentrations of Copper, Selenium, and Zinc with Grip Strength Based on NHANES 2013-2014.

Increasing evidence has found metals to be strongly associated with muscle strength, but the correlations between serum copper (Cu), selenium (Se), and zinc (Zn) with grip strength in adult populations have not yet been established. We examined the linear and non-linear associations between these three metals and grip strength via multiple linear regression and restricted cubic spline (RCS) regression using data from the National Health and Nutrition Examination Survey (NHANES) 2013-2014. A higher concentration of serum Cu was monotonically linked with lower grip strength [ß = - 0.004 m2 (95% CI: - 0.005, - 0.002)], and serum Zn was positively associated with grip strength [ß = 0.004 m2 (95% CI: 0.002, 0.006)]. We observed a positive association between serum Se and grip strength in the unadjusted model but not in covariate-adjusted models. Interestingly, the results of RCS regression showed that serum Cu had an L-shaped non-linear association with grip strength in all participants and subgroups. We further found a linear-increased trend between serum Zn and the grip strength in all participants. There were also non-linear associations that varied across different subgroups. Taken together, serum Cu and Zn were significantly associated with grip strength, while Se was not. This study offers new evidence to help formulate a reference concentration range for serum Cu and Zn.

Intricate role of intestinal microbe and metabolite in schizophrenia.

BACKGROUND: The brain-gut axis has gained increasing attention due to its contribution to the etiology of various central nervous system disorders. This study aims to elucidate the hypothesis that schizophrenia is associated with disturbances in intestinal microflora and imbalance in intestinal metabolites. By exploring the intricate relationship between the gut and the brain, with the goal of offering fresh perspectives and valuable insights into the potential contribution of intestinal microbial and metabolites dysbiosis to the etiology of schizophrenia. METHODS: In this study, we used a 16S ribosomal RNA (16S rRNA) gene sequence-based approach and an untargeted liquid chromatography-mass spectrometry-based metabolic profiling approach to measure the gut microbiome and microbial metabolites from 44 healthy controls, 41 acute patients, and 39 remission patients, to evaluate whether microbial dysbiosis and microbial metabolite biomarkers were linked with the severity of schizophrenic symptoms. RESULTS: Here, we identified 20 dominant disturbances in the gut microbial composition of patients compared with healthy controls, with 3 orders, 4 families, 9 genera, and 4 species. Several unique bacterial taxa associated with schizophrenia severity. Compared with healthy controls, 145 unusual microflora metabolites were detected in the acute and remission groups, which were mainly involved in environmental information processing, metabolism, organismal systems, and human diseases in the Kyoto encyclopedia of genes and genomes pathway. The Sankey diagram showed that 4 abnormal intestinal and 4 anomalous intestinal microbial metabolites were associated with psychiatric clinical symptoms. CONCLUSIONS: These findings suggest a possible interactive influence of the gut microbiota and their metabolites on the pathophysiology of schizophrenia.

Molecular mechanisms of 1,2-dichloroethane-induced neurotoxicity.

The production of industrial solvents and adhesives often utilizes 1,2-dichloroethane (1,2-DCE), a highly toxic halogenated hydrocarbon compound. Occupational 1,2-DCE poisoning occurs frequently and is a public health concern. Exposure to 1,2-DCE can damage the brain, liver, and kidneys. The main and most severe damage caused by exposure to 1,2-DCE is to the nervous system, especially the central nervous system. Current research on 1,2-DCE mainly focuses on the mechanism of brain edema. Several possible mechanisms of 1,2-DCE neurotoxicity have been proposed, including oxidative stress, calcium overload, blood-brain barrier damage, and neurotransmitter changes. This article reviews the research progress on 1,2-DCE neurotoxicity and the mechanism behind it to provide a scientific basis for the prevention and treatment of 1,2-DCE poisoning.