A rapid and simple non-radioactive assay for measuring uptake by solute carrier transporters.

Introduction: Solute carrier (SLC) transport proteins play a crucial role in maintaining cellular nutrient and metabolite homeostasis and are implicated in various human diseases, making them potential targets for therapeutic interventions. However, the study of SLCs has been limited due to the lack of suitable tools, particularly cell-based substrate uptake assays, necessary for understanding their biological functions and for drug discovery purposes. Methods: In this study, a cell-based uptake assay was developed using a stable isotope-labeled compound as the substrate for SLCs, with detection facilitated by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This assay aimed to address the limitations of existing assays, such as reliance on hazardous radiolabeled substrates and limited availability of fluorescent biosensors. Results: The developed assay was successfully applied to detect substrate uptakes by two specific SLCs: L-type amino acid transporter 1 (LAT1) and sodium taurocholate co-transporting polypeptide (NTCP). Importantly, the assay demonstrated comparable results to the radioactive method, indicating its reliability and accuracy. Furthermore, the assay was utilized to screen for novel inhibitors of NTCP, leading to the identification of a potential NTCP inhibitor compound. Discussion: The findings highlight the utility of the developed cell-based uptake assay as a rapid, simple, and environmentally friendly tool for investigating SLCs' biological roles and for drug discovery purposes. This assay offers a safer alternative to traditional methods and has the potential to contribute significantly to advancing our understanding of SLC function and identifying therapeutic agents targeting SLC-mediated pathways.

Simultaneous Reconstruction of Multiple Time-Varying Thermal Properties Based on Translucent Materials.

In the realm of high-tech materials and energy applications, accurately measuring the transient heat flow at media boundaries and the internal thermal conductivity of materials in harsh heat exchange environments poses a significant challenge when using conventional direct measurement methods. Consequently, the study of photothermal parameter reconstruction in translucent media, which relies on indirect measurement techniques, has crucial practical value. Current research on reconstructing photothermal properties within participating media typically focuses on single-objective or time-invariant properties. There is a pressing need to develop effective methods for the simultaneous reconstruction of time-varying thermal flow fields and internal thermal conductivity at the boundaries of participating media. This paper introduces a computational model based on the numerical simulation theory of internal heat transfer systems in participating media, stochastic particle swarm optimization algorithms, and Kalman filter technology. The model aims to enable the simultaneous reconstruction of various thermal parameters within the target medium. Our results demonstrate that under varying levels of measurement noise, the inversion results for different target parameters exhibit slight oscillations around the true values, leading to a reduction in reconstruction accuracy. However, overall, the model demonstrates robustness and accuracy in ideal conditions, validating its effectiveness.

Edaravone Dexborneol ameliorates the cognitive deficits of APP/PS1 mice by inhibiting TLR4/MAPK signaling pathway via upregulating TREM2.

Currently, there are no effective therapeutic agents available to treat Alzheimer's disease (AD). However, edaravone dexborneol (EDB), a novel composite agent used to treat acute ischemic stroke, has recently been shown to exert efficacious neuroprotective effects. However, whether EDB can ameliorate cognitive deficits in AD currently remains unclear. To this end, we explored the effects of EDB on AD and its potential mechanisms using an AD animal model (male APP/PS1 mice) treated with EDB for 10 weeks starting at 6 months of age. Subsequent analyses revealed that EDB-treated APP/PS1 mice exhibited improved cognitive abilities compared to untreated APP/PS1 mice. Administration of EDB in APP/PS1 mice further alleviated neuropathological alterations of the hippocampus, including Aß deposition, pyramidal cell karyopyknosis, and oxidative damage, and significantly decreased the levels of inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and COX-2 in the hippocampus of APP/PS1 mice. Transcriptome sequencing analysis demonstrated the critical role of the inflammatory reaction in EDB treatment in APP/PS1 mice, indicating that the alleviation of the inflammatory reaction by EDB in the hippocampus of APP/PS1 mice was linked to the action of the TREM2/TLR4/MAPK signaling pathway. Further in vitro investigations showed that EDB suppressed neuroinflammation in LPS-stimulated BV2 cells by inhibiting the TLR4/MAPK signaling pathway and upregulating TREM2 expression. Thus, the findings of the present study demonstrate that EDB is a promising therapeutic agent for AD-related cognitive dysfunction.

Strictosamide promotes wound healing through activation of the PI3K/AKT pathway.

Nauclea officinalis, as a Chinese medicine in Hainan province, had the effect of treating lower limb ulcers, burn infections. In this paper, we studied the effect of Strictosamide (STR), the main bioactive compound in Nauclea officinals, on wound healing and explored its internal mechanism. Firstly, the wound healing potential of STR was evaluated in a rat model, demonstrating its ability to expedite wound healing, mitigate inflammatory infiltration, and enhance collagen deposition. Additionally, immunofluorescence analysis revealed that STR up-regulated the expression of CD31 and PCNA. Subsequently, target prediction, protein-protein interaction (PPI), gene ontology (GO), and pathway enrichment analyses were used to obtain potential targets, specific biological processes, and molecular mechanisms of STR for the potential treatment of wound healing. Furthermore, molecular docking was conducted to predict the binding affinity between STR and its associated targets. Additionally, in vivo and in vitro experiments confirmed that STR could increase the expression of P-PI3K, P-AKT and P-mTOR by activating the PI3K/AKT signaling pathway. In summary, this study provided a new explanation for the mechanism by which STR promotes wound healing through network pharmacology, suggesting that STR may be a new candidate for treating wound.

Differential alteration in Lactiplantibacillus plantarum subsp. plantarum quorum-sensing systems and reduced Candida albicans yeast survival and virulence gene expression in dual-species interaction.

Candida albicans (C. albicans) and Lactiplantibacillus plantarum subsp. plantarum (L. plantarum) are frequently identified in various niches, but their dual-species interaction, especially with C. albicans in yeast form, remains unclear. This study aimed to investigate the dual-species interaction of L. plantarum and C. albicans, including proliferation, morphology, and transcriptomes examined by selective agar plate counting, microscopy, and polymicrobial RNA-seq, respectively. Maintaining a stable and unchanged growth rate, L. plantarum inhibited C. albicans yeast cell proliferation but not hyphal growth. Combining optical microscopy and atomic force microscopy, cell-to-cell direct contact and co-aggregation with L. plantarum cells surrounding C. albicans yeast cells were observed during dual-species interaction. Reduced C. albicans yeast cell proliferation in mixed culture was partially due to L. plantarum cell-free culture supernatant but not the acidic environment. Upon polymicrobial transcriptomics analysis, interesting changes were identified in both L. plantarum and C. albicans gene expression. First, two L. plantarum quorum-sensing systems showed contrary changes, with the activation of lamBDCA and repression of luxS. Second, the upregulation of stress response-related genes and downregulation of cell cycle, cell survival, and cell integrity-related pathways were identified in C. albicans, possibly connected to the stress posed by L. plantarum and the reduced yeast cell proliferation. Third, a large scale of pathogenesis and virulence factors were downregulated in C. albicans, indicating the potential interruption of pathogenic activities by L. plantarum. Fourth, partial metabolism and transport pathways were changed in L. plantarum and C. albicans. The information in this study might aid in understanding the behavior of L. plantarum and C. albicans in dual-species interaction.IMPORTANCEThe anti-Candida albicans activity of Lactiplantibacillus plantarum has been explored in the past decades. However, the importance of C. albicans yeast form and the effect of C. albicans on L. plantarum had also been omitted. In this study, the dual-species interaction of L. plantarum and C. albicans was investigated with a focus on the transcriptomes. Cell-to-cell direct contact and co-aggregation with L. plantarum cells surrounding C. albicans yeast cells were observed. Upon polymicrobial transcriptomics analysis, interesting changes were identified, including contrary changes in two L. plantarum quorum-sensing systems and reduced cell survival-related pathways and pathogenesis determinants in C. albicans.

Deep learning empowers photothermal microscopy with super-resolution capabilities.

In the past two decades, photothermal microscopy (PTM) has achieved sensitivity at the level of a single particle or molecule and has found applications in the fields of material science and biology. PTM is a far-field imaging method; its resolution is restricted by the diffraction limits. In our previous work, the modulated difference PTM (MDPTM) was proposed to improve the lateral resolution, but its resolution improvement was seriously constrained by information loss and artifacts. In this Letter, a deep learning approach of the cycle generative adversarial network (Cycle GAN) is employed for further improving the resolution of PTM, called DMDPTM. The point spread functions (PSFs) of both PTM and MDPTM are optimized and act as the second generator of Cycle GAN. Besides, the relationship between the sample's volume and the photothermal signal is utilized during dataset construction. The images of both PTM and MDPTM are utilized as the inputs of the Cycle GAN to incorporate more information. In the simulation, DMDPTM quantitatively distinguishes a distance of 60 nm between two nanoparticles (each with a diameter of 60 nm), demonstrating a 4.4-fold resolution enhancement over the conventional PTM. Experimentally, the super-resolution capability of DMDPTM is verified by restored images of Au nanoparticles, achieving the resolution of 114 nm. Finally, the DMDPTM is successfully employed for the imaging of carbon nanotubes. Therefore, the DMDPTM will serve as a powerful tool to improve the lateral resolution of PTM.

A complementary method with PFBBr-derivatization based on a GC-EI-MS platform for the simultaneous quantitation of short-, medium- and long-chain fatty acids in murine plasma and feces samples.

Fatty acids (FAs) are essential molecules in all organisms and are involved in various physiological and pathophysiological processes. Pentafluorobenzyl bromide (PFBBr) is commonly used for FA derivatization for gas chromatography-mass spectrometry (GC-MS) quantification by chemical ionization (CI). While CI is the conventional ionization mode for PFBBr derivatization, the electron ionization (EI) source has also demonstrated efficacy in achieving satisfactory analytical performance for the analysis of PFB esters. In this study, we present a novel approach utilizing PFBBr-derivatization on a GC-EI-MS platform to quantitatively analyze a comprehensive range of 44 fatty acids (FAs) spanning from C2 to C24. The method's sensitivity, precision, accuracy, linearity, recovery, and matrix effect were rigorously validated against predetermined acceptance criteria. In comparison to the conventional CI ionization mode, the utilization of PFBBr-derivatization in GC-EI-MS exhibits a wider range of applications and achieves comparable sensitivity levels to the conventional CI platform. By using this method, we successfully quantified 44 FAs in plasma and feces samples from the mice with deoxynivalenol (DON)-induced kidney injury. Among these, the levels of most FA species were increased in the DON-exposure group compared with the control group. The orthogonal partial least squares discriminant analysis (OPLS-DA) of all the tested FAs showed a visual separation of the two groups, indicating DON exposure resulted in a disturbance of the FA profile in mice. These results indicate that the established method by integration of GC-MS with PFBBr derivatization is an efficient approach to quantify the comprehensive FA profile, which includes short-, medium- and long-chain FAs. In addition, our study provides new insights into the mechanism underlying DON exposure-induced kidney injury.

Frizzled receptors (FZDs) in Wnt signaling: potential therapeutic targets for human cancers.

Frizzled receptors (FZDs) are key contributors intrinsic to the Wnt signaling pathway, activation of FZDs triggering the Wnt signaling cascade is frequently observed in human tumors and intimately associated with an aggressive carcinoma phenotype. It has been shown that the abnormal expression of FZD receptors contributes to the manifestation of malignant characteristics in human tumors such as enhanced cell proliferation, metastasis, chemotherapy resistance as well as the acquisition of cancer stemness. Given the essential roles of FZD receptors in the Wnt signaling in human tumors, this review aims to consolidate the prevailing knowledge on the specific status of FZD receptors (FZD1-10) and elucidate their respective functions in tumor progression. Furthermore, we delineate the structural basis for binding of FZD and its co-receptors to Wnt, and provide a better theoretical foundation for subsequent studies on related mechanisms. Finally, we describe the existing biological classes of small molecule-based FZD inhibitors in detail in the hope that they can provide useful assistance for design and development of novel drug candidates targeted FZDs.

DPP Inhibition Enhances the Efficacy of PD-1 Blockade by Remodeling the Tumor Microenvironment in Lewis Lung Carcinoma Model.

The remarkable efficacy of cancer immunotherapy has been established in several tumor types. Of the various immunotherapies, PD-1/PD-L1 inhibitors are most extensively used in the treatment of many cancers in clinics. These inhibitors restore the suppressed antitumor immune response and inhibit tumor progression by blocking the PD-1/PD-L1 signaling. However, the low response rate is a major limitation in the clinical application of PD-1/PD-L1 inhibitors. Therefore, combination strategies that enhance the response rate are the need of the hour. In this investigation, PT-100 (also referred to as Talabostat, Val-boroPro, and BXCL701), an orally administered and nonselective dipeptidyl peptidase inhibitor, not only augmented the effectiveness of anti-PD-1 therapy but also significantly improved T immune cell infiltration and reversed the immunosuppressive tumor microenvironment. The combination of PT-100 and anti-PD-1 antibody increased the number of CD4+ and CD8+ T cells. Moreover, the mRNA expression of T cell-associated molecules was elevated in the tumor microenvironment. The results further suggested that PT-100 dramatically reduced the ratio of tumor-associated macrophages. These findings provide a promising combination strategy for immunotherapy in lung cancer.

The grasp reflex in patients with idiopathic normal pressure hydrocephalus.

OBJECTIVE: To investigate the prevalence and intensity of grasp reflexes and to examine changes in these reflexes after shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS: We enrolled 147 patients with probable iNPH. A standard procedure was used to determine the presence of grasp reflexes, and the intensity of these reflexes was assessed using a four-category classification. Clinical rating scales and their correlation with grasp reflexes were also evaluated. Grasp reflexes were reassessed in 72 patients 1 year after surgery. RESULTS: We found that approximately 50.3% of patients with iNPH exhibited a positive grasp reflex. Among these patients, 69% exhibited bilateral positivity, while the remaining patients showed unilateral positivity. Furthermore, the intensity of the grasp reflex was significantly correlated with the severity of gait and with cognitive, urinary, motor, and behavioural symptoms. Surgical interventions led to a reduction (41.7%) or maintenance (30.6%) of the reflex intensity in 72.3% of iNPH patients. The changes in reflex intensity showed significant positive correlations with changes in the number of steps of the Timed Up and Go test and Trail Making Test-A scores but not with changes in total scores on the iNPH Grading Scale. CONCLUSION: This retrospective study identified grasp reflexes as a highly prevalent phenomenon in patients with iNPH. These reflexes can assist in evaluating the severity of various symptoms, including cognitive, gait, urinary, motor and emotional symptoms.

Changes in the Biology and Susceptibility of Weevil (Cylas formicarius) to the Insecticide Spinetoram as a Response to Cadmium Contamination.

The sweet potato weevil Cylas formicarius is a notorious underground pest in sweet potato (Ipomoea batatas L.). However, little is known about the effects of cadmium (Cd) stress on weevil biology and resistance to pesticides and biotic agents. Therefore, we fed sweet potato weevils with Cd-contaminated sweet potato and assessed adult food intake and survival and larval developmental duration and mortality rates, as well as resistance to the insecticide spinetoram and susceptibility to the entomopathogenic fungus Beauveria bassiana. With increasing Cd concentration, the number of adult weevil feeding holes, adult survival and life span, and larval developmental duration decreased significantly, whereas larval mortality rates increased significantly. However, at the lowest Cd concentration (30 mg/L), adult feeding was stimulated. Resistance of adult sweet potato weevils to spinetoram increased at low Cd concentration, whereas Cd contamination did not affect sensitivity to B. bassiana. Thus, Cd contamination affected sweet potato weevil biology and resistance, and further studies will investigate weevil Cd accumulation and detoxification mechanisms.

Saikosaponin D mitigate pilocarpine-induced astrocyte injury by regulating the NLRP3/caspase-1 signaling pathway.

Studies have shown that saikosaponin D (SSD) has favorable neurotherapeutic effects. Therefore, the objective of this study was to explore the efficacy and possible molecular mechanisms of SSD on pilocarpine (PP)-induced astrocyte injury. Primary astrocytes were isolated from juvenile rats and identified using immunofluorescence. The cells were treated with PP and/or SSD for 6 h and 12 h, respectively, followed by measurement of their viability through 3-(4,5-dimethylthiazol)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Next, quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression levels of Glial fibrillary acidic protein (GFAP), C3, S100 calcium binding protein A10 (S100a10), pentraxin 3 (Ptx3), toll-like receptor 4 (TLR4), and RAG in astrocytes after different treatments. Enzyme-linked immunosorbent assay and biochemical tests were utilized to evaluate the level of inflammatory factors [interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha (TNF-α)] secreted by cells and the content of oxidative stress-related factors (malondialdehyde [MDA] and glutathione [GSH]) or enzyme activity (catalase [CAT] and glutathione peroxidase [GPX]) in cells. The JC-1 mitochondrial membrane potential (MMP) fluorescence probe was used to measure the MMP in astrocytes. Additionally, western blot was applied to test the expression of proteins related to the nod-like receptor protein 3 (NLRP3)/caspase-1 signaling pathway. PP treatment (1 mM) induced cell injury by significantly reducing the viability of astrocytes and expression of cellular markers. SSD treatment (4 µM) had no toxicity to astrocytes. Besides, SSD (4 µM) treatment could significantly up-regulate the cell viability and marker expression of PP-induced astrocytes. Furthermore, SSD could be employed to inhibit inflammation (reduce IL-1ß, IL-6, and TNF-α levels) and oxidative stress (decrease MDA level, elevate GSH level, the activity of CAT and GPX), and ameliorate mitochondrial dysfunction (upregulate JC-1 ratio) in PP-induced astrocytes. Moreover, further mechanism exploration revealed that SSD treatment significantly reduced the activity of the NLRP3/caspase-1 signaling pathway activated by PP induction. SSD increased cell viability, inhibited inflammation and oxidative stress response, and ameliorated mitochondrial dysfunction in PP-induced astrocyte injury model, thus playing a neuroprotective role. The mechanism of SSD may be related to the inhibition of the NLRP3/caspase-1 inflammasome.

Analysis of factors influencing the energy efficiency in Chinese wastewater treatment plants through machine learning and SHapley Additive exPlanations.

Wastewater treatment plants (WWTPs) contribute significantly to the control of pollution in water. However, they are significant energy consumers. Identifying the factors influencing energy consumption is crucial for enhancing the energy efficiency of WWTPs. To address this, the unit energy consumption (UEC) of WWTPs was predicted using machine learning models. In order to accurately evaluate WWTPs' energy utilization efficiency, a comprehensive energy evaluation indicator, UEC (kWh/kg TODremoved) was utilized in this study. Among the prediction models, the eXtreme Gradient Boosting (XGBoost) achieves the highest prediction accuracy. SHapley Additive exPlanations (SHAP) was adopted as the model explanation system, and the results revealed that UEC was negatively affected by TN concentration, which was the most influential factor. The stoichiometry-based model calculation result indicates that the nitrification consumes average 77 % of the overall oxygen demand. SHAP analysis illustrated that the UEC of main technologies decreases with increasing influential factors. Partial dependence plot (PDP) compared average UEC of these technologies and SBR consumed the least amount of energy. The research also indicated that low influent TN concentration is the main problem in China. Consequently, it is imperative to exert efforts in ensuring the influent TN concentration while simultaneously making appropriate adjustments to the treatment process. This study provides valuable implications and methods for retrofitting and upgrading WWTPs.

Investigating the clinical role and prognostic value of genes related to insulin-like growth factor signaling pathway in thyroid cancer.

BACKGROUND: Thyroid cancer (THCA) is the most common endocrine malignancy having a female predominance. The insulin-like growth factor (IGF) pathway contributed to the unregulated cell proliferation in multiple malignancies. We aimed to explore the IGF-related signature for THCA prognosis. METHOD: The TCGA-THCA dataset was collected from the Cancer Genome Atlas (TCGA) for screening of key prognostic genes. The limma R package was applied for differentially expressed genes (DEGs) and the clusterProfiler R package was used for the Gene Ontology (GO) and KEGG analysis of DEGs. Then, the un/multivariate and least absolute shrinkage and selection operator (Lasso) Cox regression analysis was used for the establishment of RiskScore model. Receiver Operating Characteristic (ROC) analysis was used to verify the model's predictive performance. CIBERSORT and MCP-counter algorithms were applied for immune infiltration analysis. Finally, we analyzed the mutation features and the correlation between the RiskScore and cancer hallmark pathway by using the GSEA. RESULT: We obtained 5 key RiskScore model genes for patient's risk stratification from the 721 DEGs. ROC analysis indicated that our model is an ideal classifier, the high-risk patients are associated with the poor prognosis, immune infiltration, high tumor mutation burden (TMB), stronger cancer stemness and stronger correlation with the typical cancer-activation pathways. A nomogram combined with multiple clinical features was developed and exhibited excellent performance upon long-term survival quantitative prediction. CONCLUSIONS: We constructed an excellent prognostic model RiskScore based on IGF-related signature and concluded that the IGF signal pathway may become a reliable prognostic phenotype in THCA intervention.

Metabolomics study reveals blood biomarkers for early diagnosis of chronic kidney disease and IgA nephropathy: A retrospective cross-sectional study.

BACKGROUND AND AIMS: Chronic kidney disease (CKD) causes low quality of life and alarming morbidity and mortality. The crucial to retard CKD progression is to diagnose early for timely treatment. IgA nephropathy (IgAN) is a typical CKD and the most common glomerulonephritis. Both CKD and IgAN lack accurate and sensitive blood biomarkers for early diagnosis. Here we report the potential of plasma biomarkers for early diagnosis of CKD and IgAN. MATERIALS AND METHODS: Plasma levels of metabolites derived from tryptophan were quantified with an LC-MS/MS-based metabolomics for two cohorts. Based on the predictive probability of each metabolite, multivariate models including logistic regression and random forest were used to establish the early diagnostic biomarkers for CKD and IgAN. RESULTS: The plasma melatonin diagnosed early CKD (stages Ⅰ-Ⅱ) with an accuracy exceeding 95%, and a panel of melatonin and tryptophan achieved a remarkable 100% accuracy in diagnosing early CKD. Furthermore, indole-3-lactic acid had an excellent ability to distinguish IgAN among CKD patients. Based on the CKD screening and IgAN diagnosis primarily contributed by melatonin and indole-3-lactic acid, early IgAN could be diagnosed with an accuracy of over 85%. CONCLUSIONS: This study provides promising plasma biomarkers for early diagnosis of CKD and IgAN.

Pathological and pharmacological functions of the metabolites of polyunsaturated fatty acids mediated by cyclooxygenases, lipoxygenases, and cytochrome P450s in cancers.

Oxylipins have garnered increasing attention because they were consistently shown to play pathological and/or pharmacological roles in the development of multiple cancers. Oxylipins are the metabolites of polyunsaturated fatty acids via both enzymatic and nonenzymatic pathways. The enzymes mediating the metabolism of PUFAs include but not limited to lipoxygenases (LOXs), cyclooxygenases (COXs), and cytochrome P450s (CYPs) pathways, as well as the down-stream enzymes. Here, we systematically summarized the pleiotropic effects of oxylipins in different cancers through pathological and pharmacological aspects, with specific reference to the enzyme-mediated oxylipins. We discussed the specific roles of oxylipins on cancer onset, growth, invasion, and metastasis, as well as the expression changes in the associated metabolic enzymes and the associated underlying mechanisms. In addition, we also discussed the clinical application and potential of oxylipins and related metabolic enzymes as the targets for cancer prevention and treatment. We found the specific function of most oxylipins in cancers, especially the underlying mechanisms and clinic applications, deserves and needs further investigation. We believe that research on oxylipins will provide not only more therapeutic targets for various cancers but also dietary guidance for both cancer patients and healthy humans.

Association between PM2.5 and hypertension among the floating population in China: a cross-sectional study.

Few studies have investigated the association between PM2.5 and hypertension among floating populations. We therefore examined the relationship using binary logistic regression. Each grade of increment in the annual average PM2.5 (grade one: ≤15 µg/m3; grade two: 15-25 µg/m3; grade three: 25-35 µg/m3 [Excluding 25]; grade four: ≥35 µg/m3) was associated with an increased risk of hypertension (odds ratio [OR] = 1.081, 95% confidence interval (CI): 1.034-1.129). Among the female floating population (OR = 1.114, 95% CI: 1.030-1.204), those with education level of primary school and below (OR = 1.140, 95% CI: 1.058-1.229), construction workers (OR = 1.228, 95% CI: 1.058-1.426), and those living in the eastern region of China (OR = 1.241, 95% CI: 1.145-1.346) were more vulnerable to PM2.5. These results indicate that PM2.5 is positively associated with hypertension in floating populations. Floating populations who are female, less educated, construction workers, and living in the eastern region of China are more vulnerable to the adverse impacts of PM2.5.

Associations between short-term exposure to ambient PM2.5 and incident cases of cardiovascular disease in Yantai, China.

There are limited studies investigating the association between short-term exposure to PM2.5 and incident cardiovascular disease (CVD) cases in China. This study aims to examine the short-term effects of PM2.5 on the incidence of cardiovascular diseases. A combination of Poisson-distribution generalized linear model and distributed lag non-linear model was used to examine the association between short-term exposure to PM2.5 and incident cases of CVD. The results revealed that per 10 µg/m3 increment of PM2.5 would increase the incident CVD cases by 0.147% (Relative Risk: 1.00147, 95% Confidence Interval: 1.00008-1.00286) at a lag of 2 days. The stratified analyses showed higher effects risk in females, older residents (aged 60-75 years), and acute myocardial infarction group (p-value for difference <0.05). This study indicates that short-term exposure to PM2.5 may increase the risk of CVD and highlights the necessity for a higher air quality standard in Yantai, China.

Metabolomics study reveals increased deoxycholic acid contributes to deoxynivalenol-mediated intestinal barrier injury.

AIMS: Deoxynivalenol (DON), namely vomitoxin, is one of the most prevalent fungal toxins in cereal crops worldwide. However, the underlying toxic mechanisms of DON remain largely unknown. MAIN METHODS: DON exposure-caused changes in the murine plasma metabolome and gut microbiome were investigated by an LC-MS/MS-based nontargeted metabolomics approach and sequencing of 16S rRNA in fecal samples, respectively. Cellular models were then used to validate the findings from the metabolomics study. KEY FINDINGS: DON exposure increased intestinal barrier permeability evidenced by its-mediated decrease in colonic Claudin 5 and E-cadherin, as well as increases in colonic Ifn-γ, Cxcl9, Cxcl10, and Cxcr3. Furthermore, DON exposure resulted in a significant increase in murine plasma levels of deoxycholic acid (DCA). Also, DON exposure led to gut microbiota dysbiosis, which was associated with DON exposure-caused increase in plasma DCA. In addition, we found not only DON but also DCA dose-dependently caused a significant increase in the levels of IFN-γ, CXCL9, CXCL10, and/or CXCR3, as well as a significant decrease in the expression levels of Claudin 5 and/or E-cadherin in the human colonic epithelial cells (NCM460). SIGNIFICANCE: DON-mediated increase in DCA contributes to DON-caused intestinal injury. DCA may be a potential therapeutic target for DON enterotoxicity.