Close Intimacy between PtIn Clusters and Zeolite Channels for Ultrastability toward Propane Dehydrogenation.

Propane dehydrogenation (PDH) serves as a pivotal intentional technique to produce propylene. The stability of PDH catalysts is generally restricted by the readsorption of propylene which can subsequently undergo side reactions for coke formation. Herein, we demonstrate an ultrastable PDH catalyst by encapsulating PtIn clusters within silicalite-1 which serves as an efficient promoter for olefin desorption. The mean lifetime of PtIn@S-1 (S-1, silicalite-1) was calculated as 37317 h with high propylene selectivity of >97% at 580 °C with a weight hourly space velocity (WHSV) of 4.7 h-1. With an ultrahigh WHSV of 1128 h-1, which pushed the catalyst away from the equilibrium conversion to 13.3%, PtIn@S-1 substantially outperformed other reported PDH catalysts in terms of mean lifetime (32058 h), reaction rates (3.42 molpropylene gcat-1 h-1 and 341.90 molpropylene gPt-1 h-1), and total turnover number (14387.30 kgpropylene gcat-1). The developed catalyst is likely to lead the way to scalable PDH applications.

Exploring consumer responses to official endorsement: roles of credibility and attractiveness attributes in live streaming.

Introduction: Official endorsement, distinct from celebrity, expertise, and peer endorsement, introduces a new paradigm where local government officials use online platforms, particularly live streaming, to promote local products and brands. Methods: This study examines the influence of official endorsement on consumer responses using the source credibility and source attractiveness models. We developed a framework that considers official credibility and attractiveness attributes as antecedents, and consumer perceived security and enjoyment as mediators, affecting purchase intention and local brand awareness. The study also incorporates variables such as consumer region and power distance belief. Results: Data from 594 responses obtained through an online survey were analyzed using structural equation modeling. The results indicate that official credibility attributes (expertise, trustworthiness, government credibility) enhances consumer perceived security, while official attractiveness attributes (physical attractiveness, interaction friendliness, and similarity with consumers) increases consumer enjoyment. Both perceived security and enjoyment positively influence purchase intention and local brand awareness. These relationships are partially moderated by consumer region and power distance belief. Discussion: This research pioneers the study of official endorsements, expanding the endorsement literature. It also provides practical insights for marketing professionals and government officials on leveraging official endorsements to enhance the value of local products and brands..

Swirl sign score system: a novel and practical tool for predicting hematoma expansion risk after spontaneous intracerebral hemorrhage.

OBJECTIVE: To methodically analyze the swirl sign and construct a scoring system to predict the risk of hematoma expansion (HE) after spontaneous intracerebral hemorrhage (sICH). METHODS: We analysed 231 of 683 sICH patients with swirl signs on baseline noncontrast computed tomography (NCCT) images. The characteristics of the swirl sign were analyzed, including the number, maximum diameter, shape, boundary, minimum CT value of the swirl sign and the minimum distance from the swirl sign to the edge of the hematoma. In the development cohort, univariate and multivariate analyses were used to identify independent predictors of HE, and logistic regression analysis was used to construct the swirl sign score system. The swirl sign score system was verified in the validation cohort. RESULTS: The number and the minimum CT value of the swirl sign were independent predictors of HE. The swirl sign score system was constructed (2 points for the number of swirl signs > 1 and 1 point for the minimum CT value ≤ 41 Hounsfield units). The area under the curve of the swirl sign score system in predicting HE was 0.773 and 0.770 in the development and validation groups, respectively. CONCLUSIONS: The swirl sign score system is an easy-to-use radiological grading scale that requires only baseline NCCT images to effectively identify subjects at high risk of HE. ADVANCES IN KNOWLEDGE: Our newly developed semi-quantitative swirl sign score system greatly improves the ability of swirl sign to predict HE.

Toxicity burden patterns of MET-selective tyrosine kinase inhibitors: evidence from real-world pharmacovigilance.

MET exon 14 skipping alterations and MET amplifications are recognized as oncogenic and targetable genetic changes in cancer patients. The treatment of MET-selective tyrosine kinase inhibitors (TKIs) in this specific population has shown encouraging therapeutic results. However, a comprehensive understanding of the potential toxicities linked to these agents is still lacking. The present pharmacovigilance analysis was carried out using the FDA Adverse Event Reporting System database to assess notable adverse events associated with MET-selective TKIs. Gastrointestinal disorders, respiratory toxicity, hepatotoxicity, and disturbances in metabolism and nutrition demonstrated a substantial prevalence and significance among the adverse event (AE) categories. Particularly notable were the occurrences of peripheral oedema, nausea, dysphagia, fatigue, and dyspnoea, which emerged as the foremost five reported AEs. The majority of these AEs were observed within the initial months of initiating treatment with MET-selective TKIs and persistently thereafter. Notably, our investigation unveiled a significant correlation between the usage of capmatinib and the incidence of hearing loss and difficulty in swallowing. Diligent monitoring and the implementation of supportive care strategies are essential in managing the toxicities associated with MET-selective TKIs, particularly those related to gastrointestinal disorders, respiratory toxicity, hepatotoxicity, and ototoxicity.

Revealing the Causal Impact of Obstructive Sleep Apnea on Cancer Risk: Insights from Mendelian randomization analysis.

BACKGROUND: Observational studies have suggested that obstructive sleep apnea (OSA) may have a potential carcinogenic role. However, the results of these studies were inconsistent and the underlying genetic mechanisms have yet to be fully understood. METHODS: We conducted a Mendelian randomization (MR) analysis using large-scale genome-wide association studies summary statistics to explore the possible causal effect of OSA on the risk of 16 specific-site cancers in the European population. RESULTS: The MR analysis revealed a significantly negative correlation between OSA and the susceptibility to prostate cancer (OR: 0.87, 95%CI 0.79-0.95, p = 0.002) and a causal increase in the vulnerability to pancreatic malignancies (OR: 2.02, 95%CI 1.1-3.7, p = 0.02). However, no causal effects of OSA on other specific-site cancers were found. Sensitivity analyses demonstrated no significant heterogeneity or horizontal pleiotropy, thus validating the robustness of the original results. CONCLUSION: Our MR provided important insights into the causal associations between OSA and cancer risk, highlighting both protective and potentially harmful effects of OSA on different cancer types.

Enhancement of Frozen-Thawed Human Sperm Quality with Zinc as a Cryoprotective Additive.

BACKGROUND Cryopreservation preserves male fertility, crucial in oncology, advanced age, and infertility. However, it damages sperm motility, membrane, and DNA. Zinc (Zn), an antioxidant, shows promise in improving sperm quality after thawing, highlighting its potential as a cryoprotectant in reproductive medicine. MATERIAL AND METHODS Gradient concentration of ZnSO4 (0, 12.5, 25, 50, and 100 µM) was added in the Glycerol-egg yolk-citrate (GEYC) cryopreservative medium as an extender. Alterations in sperm viability and motility parameters after cryopreservation were detected in each group. Sperm plasma membrane integrity (PMI), acrosome integrity (ACR), DNA fragment index (DFI), and changes in sperm mitochondrial function were examined, including: mitochondrial potential (MMP), sperm reactive oxygen species (ROS), and sperm ATP. RESULTS We found that 50 µM ZnSO4 was the most effective for the curvilinear velocity (VCL) and the average path velocity (VAP) of sperm after cryo-resuscitation. Compared to the Zn-free group, sperm plasma membrane integrity (PMI) was increased, DNA fragmentation index (DFI) was decreased, reactive oxygen species (ROS) was reduced, and mitochondrial membrane potential (MMP) was increased after cryorevival in the presence of 50 µM ZnSO4. CONCLUSIONS Zn ion is one of the antioxidants in the cell. The results of our current clinical study are sufficient to demonstrate that Zn can improve preserves sperm quality during cryopreservation when added to GEYC. The addition of 50 µM ZnSO4 increased curve velocity, mean path velocity, sperm survival (or plasma membrane integrity), and mitochondrial membrane potential while reducing ROS production and DNA breaks compared to GEYC thawed without ZnSO4.

Visible Light-Gating Responsive Nanochannel for Controlled Release of the Fungicide.

Fungicides have been widely used to protect crops from the disease of pythium aphanidermatum (PA). However, excessive use of synthetic fungicides can lead to fungal pathogens developing microbicide resistance. Recently, biomimetic nano-delivery systems have been used for controlled release, reducing the overuse of fungicides, and thereby protecting the environment. In this paper, inspired by chloroplast membranes, visible light biomimetic channels are constructed by using retinal, the main component of green pigment on chloroplasts in plants, which can achieve the precise controlled release of the model fungicide methylene blue (MB). The experimental results show that the biomimetic channels have good circularity after and before light conditions. In addition, it is also found that the release of MB in visible light by the retinal-modified channels is 8.78 µmol·m-2·h-1, which is four times higher than that in the before light conditions. Furthermore, MB, a bactericide drug model released under visible light, can effectively inhibit the growth of PA, reaching a 97% inhibition effect. The biomimetic nanochannels can realize the controlled release of the fungicide MB, which provides a new way for the treatment of PA on the leaves surface of cucumber, further expanding the application field of biomimetic nanomembrane carrier materials.

Association of systemic inflammation markers in cancer mortality with diabetes: evidence from National Health and Nutrition Examination Survey.

AIMS: Inflammation plays a crucial role in the interconnection between diabetes and cancer. Our study seeks to investigate the predictive value of inflammatory indices concerning overall survival (OS) among diabetic cancer patients. METHODS: We analyzed data from the National Health and Nutrition Examination Survey between 1999 and 2020. Using four immune-related markers, we employed the log-rank method, multivariate Cox regression, and subgroup analysis to explore the predictive capacity of these markers for OS among adult individuals with diabetes and cancer. RESULTS: Our study identified four systemic immune-inflammatory indices that demonstrated significant predictive potential for OS among diabetic cancer patients, namely systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio (all p values < 0.05). Notably, these inflammatory biomarkers still maintain their predictive value after adjusting potential confounding factors. The analysis using restrictive cubic splines revealed significant non-linear relationships between inflammatory biomarkers and OS. CONCLUSION: The findings presented in this study underscore the potential of inflammatory markers as prognostic indicators and their crucial role in enhancing risk assessment for diabetic patients with cancer.

Complanatuside A ameliorates 2,4,6-trinitrobenzene sulfonic acid-induced colitis in mice by regulating the Th17/Treg balance via the JAK2/STAT3 signaling pathway.

Immunity imbalance of T helper 17 (Th17)/regulatory T (Treg) cells is involved in the pathogenesis of Crohn's disease (CD). Complanatuside A (CA), a flavonol glycoside, exerts anti-inflammatory activities and our study aimed to identify its effect on TNBS-induced colitis and the possible mechanisms. We found that CA alleviated the symptoms of colitis in TNBS mice, as demonstrated by prevented weight loss and colon length shortening, as well as decreased disease activity index scores, inflammatory scores, and levels of proinflammatory factors. Flow cytometry analysis showed that CA markedly reduced the percentage of Th17 cells while increasing the percentage of Treg cells in TNBS mice. Under Th17 cell polarizing conditions, CA inhibited the differentiation of Th17 cells while the Treg cell differentiation was elevated under Treg cell polarizing conditions. Furthermore, it was observed that JAK2 interacted with CA through six hydrogen bonds via molecular docking. The phosphorylation of JAK2/STAT3 was reduced by CA, which might be correlated with the protective effect of CA on colitis. In conclusion, CA reduced the imbalance of Th17/Treg cells by inhibiting the JAK2/STAT3 signaling pathway in TNBS-induced colitis, which may provide novel strategies for CD treatment.

Identification and validation of microbial biomarkers from cross-cohort datasets using xMarkerFinder.

Microbial signatures have emerged as promising biomarkers for disease diagnostics and prognostics, yet their variability across different studies calls for a standardized approach to biomarker research. Therefore, we introduce xMarkerFinder, a four-stage computational framework for microbial biomarker identification with comprehensive validations from cross-cohort datasets, including differential signature identification, model construction, model validation and biomarker interpretation. xMarkerFinder enables the identification and validation of reproducible biomarkers for cross-cohort studies, along with the establishment of classification models and potential microbiome-induced mechanisms. Originally developed for gut microbiome research, xMarkerFinder's adaptable design makes it applicable to various microbial habitats and data types. Distinct from existing biomarker research tools that typically concentrate on a singular aspect, xMarkerFinder uniquely incorporates a sophisticated feature selection process, specifically designed to address the heterogeneity between different cohorts, extensive internal and external validations, and detailed specificity assessments. Execution time varies depending on the sample size, selected algorithm and computational resource. Accessible via GitHub ( https://github.com/tjcadd2020/xMarkerFinder ), xMarkerFinder supports users with diverse expertise levels through different execution options, including step-to-step scripts with detailed tutorials and frequently asked questions, a single-command execution script, a ready-to-use Docker image and a user-friendly web server ( https://www.biosino.org/xmarkerfinder ).

Heterografting enhances chrysanthemums resistance to Alternaria alternata via jasmonate-mediated increases in trichomes and terpenoids.

Trichomes, specialized hair-like structures in the epidermal cells of the aboveground parts of plants, protect plants from pests and pathogens and produce valuable metabolites. Chrysanthemum morifolium, used in tea products, has ornamental and medicinal value. However, it is susceptible to Alternaria alternata fungal infection, posing a threat to its production and use, resulting in substantial economic losses. Increasing the density of glandular trichomes enhances disease resistance and improves the production of medicinal metabolites in chrysanthemums. Jasmonate (JA), promotes the formation of glandular trichomes in various plants. However, it remains unclear whether glandular trichome in chrysanthemums are regulated by JA. Grafting, a technique to improve plant resistance to biotic stresses, has been insufficiently explored in its impact on glandular trichomes, terpenoids, and disease resistance. In this study, we demonstrated that grafting with Artemisia vulgaris rootstocks improves the resistance of chrysanthemum scions to A. alternata. Heterografted chrysanthemums exhibited higher trichome density and terpenoid content compared to self-grafted counterparts. Transcriptome analysis highlighted the significant role of CmJAZ1-like in disease resistance in heterografted chrysanthemums. Overexpressing CmJAZ1-like lines exhibited sensitivity to A. alternate, characterized by reduced glandular trichome density and limited terpenoids. Conversely, silencing lines exhibited resistance to A. alternata showcasing increased glandular trichome density and abundant terpenoids. Higher JA content was confirmed in heterografted chrysanthemum scions compared to self-grafted ones. Furthermore, we established that JA promotes the development of glandular trichomes and the synthesis of terpenoids while inducing the degradation of CmJAZ1-like proteins in chrysanthemums. These findings suggest that higher JA increases trichome density and terpenoid content, enhancing resistance to A. alternata by regulating CmJAZ1-like in heterografted chrysanthemums.

Nonlinear association of triglyceride-glucose index with hyperuricemia in US adults: a cross-sectional study.

BACKGROUND: Despite abundant evidence on the epidemiological risk factors of metabolic diseases related to hyperuricemia, there is still insufficient evidence regarding the nonlinear relationship between triglyceride-glucose (TyG) index and hyperuricemia. Thus, the purpose of this research is to clarify the nonlinear connection between TyG and hyperuricemia. METHODS: From 2011 to 2018, a cross-sectional study was carried out using data from the National Health and Nutrition Examination Survey (NHANES). This study had 8572 participants in all. TyG was computed as Ln [triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The outcome variable was hyperuricemia. The association between TyG and hyperuricemia was examined using weighted multiple logistic regression, subgroup analysis, generalized additive models, smooth fitting curves, and two-piecewise linear regression models. RESULTS: In the regression model adjusting for all confounding variables, the OR (95% CI) for the association between TyG and hyperuricemia was 2.34 (1.70, 3.21). There is a nonlinear and reverse U-shaped association between TyG and hyperuricemia, with a inflection point of 9.69. The OR (95% CI) before the inflection point was 2.64 (2.12, 3.28), and after the inflection point was 0.32 (0.11, 0.98). The interaction in gender, BMI, hypertension, and diabetes analysis was statistically significant. CONCLUSION: Additional prospective studies are required to corroborate the current findings, which indicate a strong positive connection between TyG and hyperuricemia among adults in the United States.

Association between blood pressure variability and risk of kidney function decline in hypertensive patients without chronic kidney disease: a post hoc analysis of Systolic Blood Pressure Intervention Trial study.

BACKGROUND: Blood pressure variability (BPV) is a risk factor for poor kidney function independent of blood pressure (BP) in chronic kidney disease (CKD). Little is known about the association between kidney function decline and BPV in hypertensive patients without CKD. METHODS: A post-hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) was performed. BPV was measured as standard deviation (SD) and average real variability (ARV). Cox proportional hazard models were employed to explore the relationship between BPV and incident CKD and albuminuria. RESULTS: A total of 5700 patients were included, with a mean age of 66.4 years old. During a median of 3.29 years follow-up, 150 (2.6%) patients developed CKD and 222 (7.2%) patients developed albuminuria. Patients were divided into four groups according to the quartiles of BPV. Compared with SBPV Q1, the incidence of CKD was higher in SBPV Q2-Q4; hazard ratios and 95% confidence interval were 1.81 (1.07-3.04), 1.85 (1.10-3.12) and 1.90 (1.13-3.19), respectively. The association between incident CKD and albuminuria with DBPV was less significant than SBPV. Similar results were found when measuring BPV as ARV and SD. No interaction was detected in BP-lowering strategy and SBPV on incident CKD and albuminuria ( P  > 0.05). CONCLUSION: This study found that BPV was a risk factor for incident CKD and albuminuria in patients without CKD, especially SBPV. Although intensive BP control increased the risk of CKD, the association between SBPV and kidney function decline did not differ between the two treatment groups. REGISTRATION: URL: https://clinicaltrials.gov/ , Unique identifier: NCT01206062.

Strong Covalent Coupling in Vertically Layered SnSe2/PTAA Heterojunctions Enabled High Performance Inorganic-Organic Hybrid Photodetectors.

Controllable large-scale integration of two-dimensional (2D) materials with organic semiconductors and the realization of strong coupling between them still remain challenging. Herein, we demonstrate a wafer-scale, vertically layered SnSe2/PTAA heterojunction array with high light-trapping ability via a low-temperature molecular beam epitaxy method and a facile spin-coating process. Conductive probe atomic force microscopy (CP-AFM) measurements reveal strong rectification and photoresponse behavior in the individual SnSe2 nanosheet/PTAA heterojunction. Theoretical analysis demonstrates that vertically layered SnSe2/PTAA heterojunctions exhibit stronger C-Se covalent coupling than that of the conventional tiled type, which could facilitate more efficient charge transfer. Benefiting from these advantages, the SnSe2/PTAA heterojunction photodetectors with an optimized PTAA concentration show high performance, including a responsivity of 41.02 A/W, an external quantum efficiency of 1.31 × 104%, and high uniformity. The proposed approach for constructing large-scale 2D inorganic-organic heterostructures represents an effective route to fabricate high-performance broadband photodetectors for integrated optoelectronic systems.

The potential therapeutic roles of dental pulp stem cells in spinal cord injury.

Spinal cord injury (SCI) can lead to serious functional disorders, which have serious impacts on patients and society. The current traditional treatments of SCI are not effective the injured spinal cord is difficult to repair and regenerate. In recent years, stem cell transplantation for the treatment of SCI has been a hot research topic. Dental pulp stem cells have strong abilities of self-renewal and multi-directional differentiation, and have been applied for tissue engineering and regenerative medicine. And dental pulp stem cells have certain advantages in neuro-regenetation, bringing new hope to biotherapy for SCI. This article reviews the characteristics of dental pulp stem cells and their research progress in the treatment of SCI.

Association Between Artificial Intelligence Based Chest Computed Tomography and Clinical/Laboratory Characteristics with Severity and Mortality in COVID-19 Hospitalized Patients.

Background: Some patients with COVID-19 rapidly develop respiratory failure or mortality, underscoring the necessity for early identification of those prone to severe illness. Numerous studies focus on clinical and lab traits, but only few attend to chest computed tomography. The current study seeks to numerically quantify pulmonary lesions using early-phase CT scans calculated through artificial intelligence algorithms in conjunction with clinical and laboratory helps clinicians to early identify the development of severe illness and death in a group of COVID-19 patients. Methods: From December 15, 2022, to January 30, 2023, 191 confirmed COVID-19 patients admitted to Xinhua Hospital Affiliated with Shanghai Jiao Tong University School of Medicine were consecutively enrolled. All patients underwent chest CT scans and serum tests within 48 hours prior to admission. Variables significantly linked to critical illness or mortality in univariate analysis were subjected to multivariate logistic regression models post collinearity assessment. Adjusted odds ratio, 95% confidence intervals, sensitivity, specificity, Youden index, receiver-operator-characteristics (ROC) curves, and area under the curve (AUC) were computed for predicting severity and in-hospital mortality. Results: Multivariate logistic analysis revealed that myoglobin (OR = 1.003, 95% CI 1.001-1.005), APACHE II score (OR = 1.387, 95% CI 1.216-1.583), and the infected CT region percentage (OR = 113.897, 95% CI 4.939-2626.496) independently correlated with in-hospital COVID-19 mortality. Prealbumin stood as an independent safeguarding factor (OR = 0.965, 95% CI 0.947-0.984). Neutrophil counts (OR = 1.529, 95% CI 1.131-2.068), urea nitrogen (OR = 1.587, 95% CI 1.222-2.062), SOFA score(OR = 3.333, 95% CI 1.476-7.522), qSOFA score(OR = 15.197, 95% CI 3.281-70.384), PSI score(OR = 1.053, 95% CI 1.018-1.090), and the infected CT region percentage (OR = 548.221, 95% CI 2.615-114,953.586) independently linked to COVID-19 patient severity.

Focus on pemphigus treatment publications: A bibliometric and visual analysis (1992-2022).

Pemphigus is a chronic recurrent disease in dermatology. Although it is not very common, its treatment has been an increasing concern in recent years because it is difficult and long-lasting. At present, there are many papers on pemphigus treatment, and to better understand the research trends and research frontiers of pemphigus treatment, it is necessary to conduct a comprehensive systematic review and analysis. We combined bibliometric and visualization methods to analyze 1365 papers published in the Web of Science database from 1992 to 2022, including basic information about countries, institutions and authors, to gain a general understanding of the treatment of pemphigus. Among them, the United States is the country with the most output, Iran's Tehran University of Medical Sciences is the institution with the most published works, and Ahmed, A. Razzaque of Tufts University is the most influential scholar. In addition, we also learned about the research hotspots and frontiers of pemphigus treatment through a series of analyses on the frequency, clustering, keywords bursts and cited literature, and we briefly reviewed the highly cited literature. We found that the current research focuses in the study of pemphigus treatment are the types, pathogenesis, and treatment of pemphigus, including glucocorticoids, immunosuppressants and many other major treatment methods. Hailey-Hailey disease, genetic susceptibility, and traditional Chinese medicine are potential research hotspots. Rituximab is a research frontier. In conclusion, we hope to provide new research ideas for promoting the development of pemphigus treatment.

Self-supervised contrastive learning for EEG-based cross-subject motor imagery recognition.

Objective. The extensive application of electroencephalography (EEG) in brain-computer interfaces (BCIs) can be attributed to its non-invasive nature and capability to offer high-resolution data. The acquisition of EEG signals is a straightforward process, but the datasets associated with these signals frequently exhibit data scarcity and require substantial resources for proper labeling. Furthermore, there is a significant limitation in the generalization performance of EEG models due to the substantial inter-individual variability observed in EEG signals.Approach. To address these issues, we propose a novel self-supervised contrastive learning framework for decoding motor imagery (MI) signals in cross-subject scenarios. Specifically, we design an encoder combining convolutional neural network and attention mechanism. In the contrastive learning training stage, the network undergoes training with the pretext task of data augmentation to minimize the distance between pairs of homologous transformations while simultaneously maximizing the distance between pairs of heterologous transformations. It enhances the amount of data utilized for training and improves the network's ability to extract deep features from original signals without relying on the true labels of the data.Main results. To evaluate our framework's efficacy, we conduct extensive experiments on three public MI datasets: BCI IV IIa, BCI IV IIb, and HGD datasets. The proposed method achieves cross-subject classification accuracies of 67.32%, 82.34%, and 81.13%on the three datasets, demonstrating superior performance compared to existing methods.Significance. Therefore, this method has great promise for improving the performance of cross-subject transfer learning in MI-based BCI systems.

Vitamin D inhibits ferroptosis and mitigates the kidney injury of prediabetic mice by activating the Klotho/p53 signaling pathway.

Diabetic nephropathy (DN) is a serious public health problem worldwide, and ferroptosis is deeply involved in the pathogenesis of DN. Prediabetes is a critical period in the prevention and control of diabetes and its complications, in which kidney injury occurs. This study aimed to explore whether ferroptosis would induce kidney injury in prediabetic mice, and whether vitamin D (VD) supplementation is capable of preventing kidney injury by inhibiting ferroptosis, while discussing the potential mechanisms. High-fat diet (HFD) fed KKAy mice and high glucose (HG) treated HK-2 cells were used as experimental subjects in the current study. Our results revealed that serious injury and ferroptosis take place in the kidney tissue of prediabetic mice; furthermore, VD intervention significantly improved the kidney structure and function in prediabetic mice and inhibited ferroptosis, showing ameliorated iron deposition, enhanced antioxidant capability, reduced reactive oxygen species (ROS) and lipid peroxidation accumulation. Meanwhile, VD up-regulated Klotho, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression, and down-regulated p53, transferrin receptor 1 (TFR1) and Acyl-Coenzyme A synthetase long-chain family member 4 (ACSL4) expression. Moreover, we demonstrated that HG-induced ferroptosis is antagonized by treatment of VD and knockdown of Klotho attenuates the protective effect of VD on ferroptosis in vitro. In conclusion, ferroptosis occurs in the kidney of prediabetic mice and VD owns a protective effect on prediabetic kidney injury, possibly by via the Klotho/p53 pathway, thus inhibiting hyperglycemia-induced ferroptosis.

Spexin ameliorated obesity-related metabolic disorders through promoting white adipose browning mediated by JAK2-STAT3 pathway.

BACKGROUND: Spexin, a 14 amino acid peptide, has been reported to regulate obesity and its associated complications. However, little is known about the underlying molecular mechanism. Therefore, this study aimed to investigate the effects of spexin on obesity and explore the detailed molecular mechanisms in vivo and in vitro. METHODS: Male C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks to induce obesity, and mice fed a standard fat diet were used as controls. Then, these mice were treated with SPX or Vehicle by intraperitoneal injection for an additional 12 weeks, respectively. The metabolic profile, fat-browning specific markers and mitochondrial contents were detected. In vitro, 3T3-L1 cells were used to investigate the molecular mechanisms. RESULTS: After 12 weeks of treatment, SPX significantly decreased body weight, serum lipid levels, and improved insulin sensitivity in HFD-induced obese mice. Moreover, SPX was found to promote oxygen consumption in HFD mice, and it increased mitochondrial content as well as the expression of brown-specific markers in white adipose tissue (WAT) of HFD mice. These results were consistent with the increase in mitochondrial content and the expression of brown-specific markers in 3T3-L1 mature adipocytes. Of note, the spexin-mediated beneficial pro-browning actions were abolished by the JAK2/STAT3 pathway antagonists in mature 3T3-L1 cells. CONCLUSIONS: These data indicate that spexin ameliorates obesity-induced metabolic disorders by improving WAT browning via activation of the JAK2/STAT3 signaling pathway. Therefore, SPX may serve as a new therapeutic candidate for treating obesity.