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Water pollution remains a major environmental concern, with increased toxic by-products being released into water bodies. Many of these chemical contaminants persist in the environment and bio-accumulate in aquatic organisms. At present, toxicological tests are mostly based on laboratory tests, and effective methods for monitoring wild aquatic environments remain lacking. In the present study, we used a well-characterized toxic chemical, 3,3′,4,4′,5-polychlorinated biphenyl (PCB126), as an example to try to identify common biomarker genes to be used for predictive toxicity of this toxic substance. First, we used two laboratory fish models, the zebrafish (Danio rerio) and medaka (Oryzias latipes), to expose PCB126 to obtain liver transcriptomic data by RNA-seq. Comparative transcriptomic analyses indicated generally conserved and concerted changes from the two species, thus validating the transcriptomic data for biomarker gene selection. Based on the common up- and downregulated genes in the two species, we selected nine biomarker genes to further test in other fish species. The first validation experiment was carried out using the third fish species, Mozambique tilapia (Oreochromis mossambicus), and essentially, all these biomarker genes were validated for consistent responses with the two laboratory fish models. Finally, to develop universal PCR primers suitable for potentially all teleost fish species, we designed degenerate primers and tested them in the three fish species as well as in another fish species without a genomic sequence available: guppy (Poecilia reticulata). We found all the biomarker genes showed consistent response to PCB126 exposure in at least 50% of the species. Thus, our study provides a promising strategy to identify common biomarker genes to be used for teleost fish analyses. By using degenerate PCR primers and analyzing multiple biomarker genes, it is possible to develop diagnostic PCR arrays to predict water contamination from any wild fish species sampled in different water bodies.

BackgroundExposure to occupational metallic mixtures has a potential impact on olfactory function. However, research evidence is limited on the potential impact of exposure to metallic mixtures and olfactory dysfunction. Furthermore, the coal dust generated contains multiple various metals during coal mining, and no study yet has focus on the olfactory dysfunction of coal miners.ObjectivesIn this study, we evaluate the association between urinary metallic mixtures and olfactory function in coal miners, while also exploring the potential applicability of plasma olfactory marker protein (OMP) as a biomarker for assessing olfaction.MethodsFrom July to October 2023, coal workers from seven different coal mining enterprises were recruited for the survey when they come for the employee health checkup. Ultimately, 376 participants were met the inclusion criteria and, respectively, determined with the concentrations of urine (16 metals) and plasma (OMP). Meanwhile, applying UPSIT to access their olfactory function. Binary logistic regression and restricted cubic spline (RCS) model were used to estimate the association of individual metals with olfactory function. Bayesian kernel machine regression (BKMR) and Quantile g-computation (QG-C) regression were employed to assess the overall association between metal mixtures and olfactory function and identify the major contributing elements.ResultsIn a single-metal model, two metals in urine were found to be significantly associated with olfactory function. RCS analysis further revealed that the association between Iron (Fe) and olfactory function was linear, while Lead (Pb) exhibited a non-linear. The BKMR model demonstrated a significant positive association between metal mixture concentration and olfactory function. Combined QG-C regression analysis suggested that metals Cr, Fe, Se, Sb, and Pb could impact the performance of the olfactory test (UPSIT), with Pb being identified as the most influential contributor. The correlation between plasma OMP protein levels and urinary metal concentrations was weak.ConclusionMultiple metals are associated with olfactory function in the coal miners. A significant positive association was observed between metal mixture concentrations and olfactory function, with Pb being the most important contributor. In this study, plasma OMP has not been demonstrated to serve as a biomarker for olfactory function.

Lewy body disease (LBD), one of the most common neurodegenerative diseases (NDDs), is characterized by excessive accumulation of α-synuclein (α-syn) in neurons. In recent years, environmental factors such as exposure to herbicides and pesticides have been attributed to the development of this condition. While majority of the studies on neurotoxic effects of paraquat (PQ) have focused on α-syn-mediated neuronal damage in the early stages of α-syn accumulation in neurons, efforts to explore the key target for α-syn degradation are limited. Recent research has suggested that histone deacetylase 6 (HDAC6) might possibly regulate amyloid clearance, and that the metabolism of compounds in neurons is also directly affected by axonal transport in neurons. Dynein predominantly mediates reverse transportation of metabolites and uptake of signal molecules and other compounds at the end of axons, which is conducive to the reuse of cell components. However, the role of interaction of dynein with HDAC6 in metabolites transport is still unclear. Therefore, this study aimed to investigate the role of HDAC6 in α-syn accumulation/clearance in neurons and the associated possible influencing factors. The results revealed that HDAC6 could transport ubiquitinated α-syn, bind to dynein, form an aggresome, and relocate to the center of the microtubule tissue, ultimately reducing abnormal accumulation of α-syn. However, PQ treatment resulted in HDAC6 upregulation, causing abnormal aggregation of α-syn. Taken together, these findings indicated that PQ exposure caused abnormal accumulation of α-syn and decreased effective degradation of α-syn by HDAC6-mediated aggresome-autophagy-lysosome pathway.

PurposeTo explore white matter network topological properties changes in middle-aged and elderly patients with functional constipation (Functional Constipation, FC) by diffusion tensor imaging (DTI), and to evaluate the correlation between the abnormal changes and clinical data.Methods29 FC patients and 31 age- and sex-matched healthy controls (HC) were recruited. Magnetic resonance imaging and clinical data were collected. The white matter network changes in FC patients were analyzed using deterministic fiber tracking methods, graph theory algorithms, and partial correlation analysis with clinical data.ResultsThe nodal clustering coefficient and nodal local efficiency of FC patients in the right orbital inferior frontal gyrus, right medial superior frontal gyrus, right rectus muscle, right hippocampus, left paracentral lobule and left temporal pole, and the nodal clustering coefficient in right orbital superior frontal gyrus, left cuneus lobe and right superior occipital gyrus, the nodal local efficiency in the right medial and paracingulate gyrus, right precuneus and right dorsolateral superior frontal gyrus of FC patients are lower than that of HC. The nodal local efficiency and clustering coefficient of FC patients in left hippocampus, left amygdala, right parietal inferior limbic angular gyrus and right angular gyrus, the nodal local efficiency in the right fusiform gyrus, left supplementary motor cortex and the nodal efficiency in the left lateral temporal gyrus and right orbital middle frontal gyrus (ORBmid.R) of FC patients are higher than that of HC. The nodal efficiency of ORBmid.R in FC was positively correlated with the Patient Assessment of Constipation quality of life questionnaire (PAC-QoL).ConclusionMiddle-aged and elderly FC patients have differences in the nodal level properties in the limbic system, supplementary motor cortex, and default mode network brain regions, and the nodal efficiency of ORBmid.R was positively correlated with the PAC-QoL score, revealing that FC may be related to the abnormal processing of visceral sensorimotor in ORBmid.R and providing potential imaging diagnostic markers and therapeutic targets for middle-aged and elderly FC patients.

Asymmetric base-isolated structures subjected to severe torsion may suffer further aggravation of their torsional and translational responses under pulse-type earthquakes. To counteract these detrimental impacts, this study introduces a two-stage optimal design method. The first stage involved the application of the NSGA-II algorithm for determining an optimal isolator arrangement—namely, position and category—with the objective of reducing both the maximum interstory rotation of the superstructure and the isolation layer. In the second stage, the inclusion of viscous dampers served to minimize the excessive translational response triggered by pulse-type earthquakes. The influence of these dampers’ positions on the structural response was carefully evaluated. The final application of this optimal design method was demonstrated on an asymmetric base-isolated structure. The results indicated a significant reduction in the translational and torsional responses of the asymmetric base-isolated structure when the two-stage optimal design method was utilized, compared to those of structures designed using traditional conceptual methods. It was found that by installing viscous dampers in the isolation layer along both the x and the y directions—specifically, underneath the mass center of the superstructure (CMS)—the effectiveness of the torsional resistance from the first stage could be effectively maintained.

Abstract Purpose Our previous studies have suggested that the first trimester fasting plasma glucose (FPG) level is associated with gestational diabetes mellitus (GDM) and is a predictor of GDM. The aim of the present study was to provide valuable insights into the accuracy of the first trimester FPG level in the screening and diagnosis of GDM in southern China. Methods This retrospective study included pregnant women who had their first trimester FPG level recorded at 9–13+6 weeks and underwent screening for GDM using the 2-h 75 g oral glucose tolerance test (OGTT) between the 24th and 28th gestational weeks. Differences between the GDM and non-GDM groups were assessed by Student’s t test and the chi-squared test according to the nature of the variables. A restricted cubic spine was used to explore the relationship between the first trimester FPG level and the odds ratio (OR) of GDM in pregnant women. Cut-off values of first trimester FPG were determined using receiver operating characteristic (ROC) curves and the area under the curve (AUC), and 95% confidence intervals (CIs), the positive predictive value (PPV) and the negative predictive value (NPV) were calculated. Results The medical records of 28,030 pregnant women were analysed, and 4,669 (16.66%) of them were diagnosed with GDM. The average first trimester FPG level was 4.62 ± 0.37 mmol/L. The OR of GDM increased with increasing first trimester FPG levels and with a value of first trimester FPG of approximately 4.6 mmol/L, which was equal to 1 (Chi-Square = 665.79, P