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Abstract Aims/Introduction The association between serum angiopoietin‐like 4 (ANGPTL4) levels and the severity of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus remains unclear. Methods A total of 1,115 type 2 diabetes mellitus patients were analyzed in this cross‐sectional study. DKD index included DKD stages defined by estimated glomerular filtration rate, the albuminuria grades and DKD risk management grades. Serum levels of ANGPTL4 and other biomarkers were detected. Multivariable‐adjusted linear and logistic analyses were used to study the association between ANGPTL4 and DKD. The protein levels of ANGPTL4 were assessed in the kidney. Renal tubular cells were stimulated with glucose to study ANGPTL4 expression. Results Compared with the participants in the third or fourth quantile of ANGPTL4, those in the first or second quantile of ANGPTL4 were younger, with lower glycated hemoglobin, triglycerides and urinary albumin creatinine ratio (all P

The study aims to investigate the differences in protein expressions in Xizang's (Tibetan) middle-to-long distance runners after the transition from high altitude to low altitude and reveal the molecular mechanisms underlying their enhanced middle-to-long distance running performance. In the study, eleven subjects were selected from native Tibetan middle-to-long distance runners to participate in an 8-week pre-competition exercise training program consisting of a 6-week training stage in Kangding City at an altitude of 2 560 meters (m) and a subsequent 2-week training stage in Leshan City at an altitude of 360 ​m. Blood samples were collected twice from the runners before beginning altitude exercise training in Kangding and after going to sea level - Leshan City. Using a label-free quantitative method, peptides in the samples were analyzed by mass spectrometry. Proteomic analysis was performed to identify differentially expressed proteins and predict their biological functions. A total of 846 proteins were identified in the 21 samples, including 719 quantified proteins. In total, 49 significantly differentially expressed proteins (p ​

Abstract Background Postoperative delirium is a common neurological complication, especially in older patients undergoing surgery, which is closely related to the poor prognosis of patients. The objective was to investigate the effects of esketamine on postoperative delirium in patients with general anesthesia. Methods The databases of PubMed, Embase, Cochrane Library and the Chinese National Knowledge Infrastructure were searched for all available randomised controlled trials on the effects of esketamine induction on postoperative delirium in patients undergoing elective general anesthesia from inception until April 21, 2024. We used RevMan5.4 software for data analysis. Dichotomous data was analyzed by risk ratios(RR) with a 95% confidence interval(CI), and continuous data by mean differences(MD). We also evaluated the risk of literature bias using the Cochrane Bias Risk Assessment tool. Results We included a total of 17 randomized controlled trials, including 1286 patients undergoing elective general anesthesia. In 17 studies, esketamine significantly reduced the incidence of postoperative delirium (RR: 0.43; 95%CI: 0.33 ~ 0.57; p

Abstract Background Endophytes play an important role in promoting plant growth. To date, although many reports provided insight into the function of endophytes in their hosts, few reports focus on their impact on nearby plants. Intraspecific allelopathy in plant community is common and presents a notable challenge to medicinal plant yield and productivity. Atractylodes lancea is a perennial herb that has relatively low yields due to intraspecific allelopathy. The bacterial endophyte Pseudomonas fluorescens ALEB7B has previously been found to increase essential oil content of A. lancea, but the role of ALEB7B in A. lancea allelopathy is still unknown. Results Noninoculated A. lancea exhibited growth retardation when it was grown in a community, which was related to ethylene-induced intraspecific allelopathy. Further experiment showed that exposing A. lancea to volatile from noninoculated A. lancea or same concentration of ethylene reduced growth of A. lancea. P. fluorescens-inoculated plants showed reduced ethylene emission and relieved growth retardation on neighboring noninoculated A. lancea. Moreover, P. fluorescens inoculation had little allelopathic effect when receivers were treated with ethylene receptor inhibitor or when emitters were treated with ethylene production inhibitor. Transcriptomic analysis revealed that endophyte ALEB7B altered transcriptional response associated with ethylene response and essential oil production in neighboring A. lancea. Conclusions Our results demonstrated that the bacterial endophyte ALEB7B provides fitness benefits for both hosts and neighbors. The allelopathic effect on nearby plants can be alleviated by altering airborne signals, such as ethylene, in endophytic bacteria.

Abstract Studies on the correlation of exposure to metals with diabetic kidney disease (DKD) is scarce, especially concerning the impact of mixed metals on DKD. This study aimed to explore the association of blood heavy metals with DKD risk among type 2 diabetes mellitus (T2DM) patients. This cross-sectional study enrolled patients with T2DM in NHANES 2011–2020. ICP‒MS was applied to detect five metals, namely, Pb, Cd, Hg, Se and Mn, in blood. At the same time, the impacts of exposure to single and mixed metals on DKD were assessed using multivariable logistic regression, WQS, and BKMR models. The relationship was examined based on age, sex, BMI, hypertension, smoking status and PIR. Totally 2362 participants were enrolled for final analysis. Among them, 634 (26.84%) patients undergoing T2DM had DKD. Logistic regression indicated that, Pb (Q4: OR [95% CI]: 1.557 [1.175, 2.064]) was related to DKD when all covariates were adjusted. The WQS analysis, which was set in a positive directional mode, suggested that Pb was correlated positively with a higher incidence of DKD. In BKMR analysis, linear dose‒response curves were generated for Pb when fixing the other metals in the 50th percentile. In addition, exposure to mixed metals was significantly positively related to DKD. Subgroup analysis during logistic regression demonstrated that Pb was significantly and positively related to DKD in females, over 50 years, those with over 25 kg/m2, no hypertension, no smoking status and under PIR. Serum albumin (ALB) did not regulate the indirect impact of blood Pb on DKD risk. The results showed that the increased mixed metal concentration may lead to an increased DKD risk among patients with T2DM. Blood Pb is positively related to the DKD risk in diabetic patients, especially, in females, over 50 years, those with over 25 kg/m2, no hypertension, no smoking status and under PIR in T2DM patients. According to our observations, Pb absorption at least slightly influences DKD occurrence and progression. More studies are needed to validate the results in this work and illustrate the relevant biological mechanism.

Abstract Glioblastoma is one of the most common and aggressive primary brain tumors. The aberration of metabolism is the important character of GBM cells and is tightly related to the malignancy of GBM. We mainly verified the regulatory effects of KHDRBS1, SNORD51 and ZBED6 on pentose phosphate pathway and malignant biological behavior in glioblastoma cells, such as proliferation, migration and invasion. KHDRBS1 and SNORD51 were upregulated in GBM tissues and cells. But ZBED6 had opposite tendency in GBM tissues and cells. KHDRBS1 may improve the stability of SNORD51 by binding to SNORD51, thus elevating the expression of SNORD51. More importantly, SNORD51 can competitively bind to WDR33 with 3’UTR of ZBED6 pre-mRNA which can inhibit the 3’ end processing of ZBED6 pre-mRNA, thereby inhibiting the expression of ZBED6 mRNA. ZBED6 inhibited the transcription of G6PD by binding to the promoter region of G6PD. Therefore, the KHDRBS1/SNORD51/ZBED6 pathway performs an important part in regulating the pentose phosphate pathway to influence malignant biological behavior of GBM cells, providing new insights and potential targets for the treatment of GBM.

Abstract Ice core oxygen isotope (δ18O) records from low-latitude regions preserve high-resolution climate records in the past, yet the interpretation of these ice core δ18O records is still facing difficulty due to the uncertainty of ice core dating. Here we present a new established δ18O time series from Qiangtang (QT) No. 1 ice core retrieved from the central Tibetan Plateau. Due to the vague seasonal signals in the QT ice core, we investigated the spectral properties of δ18O record with depth and discussed the implications of significant spectral power peaks in the QT ice core. We employed a variational mode decomposition (VMD) analysis for the upper part of the QT ice core to decompose the δ18O depth series in order to separate the El Niño Southern Oscillation (ENSO) mode, a signal strongly preserved in the QT ice core δ18O record. With this approach, we established a time series of 335 years (1677–2011 CE) for the upper 50 m of the QT ice core. Subsequently, we examined the frequency of the new established δ18O time series and detected strong signals of the bidecadal and multidecadal modes of Pacific Decadal Oscillation (PDO). The PDO consists of two modes with periods of approximately 25–35 years and 50–70 years, and we found that the 50–70 years periodicity has persisted since 1700 CE, succeeded by dominance of the 25–75 years periodicity after 1900 CE. Additionally, we analyzed the δ18O series of the QT ice core during the past century and determined that the increasing frequency of El Niño events is an important factor contributing to the increase in recent ice core δ18O.

Theoretical research on betavoltaic batteries require calculating characteristic parameters of the radiation-voltage conversion device，in order to predict the output characteristics under irradiation. Through the calculated output characteristics，important theoretical references for the design of betavoltaic batteries are provided. Our algorithm calculates the characteristic parameters of the radiation-voltage conversion device based on the tested dark current-voltage curve and evaluates the quality of the characteristic parameters by statistical methods. To prove the effectiveness of the algorithm，the current-voltage curves under irradiation were predicted，and compared with those obtained by exposing to a real radioactive source. Calculation results achieved good results in both curve fitting and output characteristic prediction of the radiation-voltage conversion device. The results show our algorithm can predict the output of betavoltaic battery through the dark current-voltage curve without irradiation and provide guidance for the design of batavoltaic batteries.

Abstract Triptolide (TP), a major active component of the herb Tripterygium wilfordii Hook F, has been shown excellent pharmacological effects on rheumatoid arthritis. However, TP is prone to causing severe organ toxicity, which limits its clinical application. In recent years, microneedle technology has provided a new option for the treatment of arthritis due to its advantages of efficient local transdermal drug delivery. In this study, we constructed a microneedle platform to deliver TP locally to the joints, thereby enhancing TP penetration and reducing systemic toxicity. Additionally, we investigated whether acupoint drug delivery can produce a synergistic effect of needles and drugs. First, TP was loaded into microneedles using polyvinylpyrrolidone and hyaluronic acid as matrix materials. Next, we established a rat adjuvant-induced arthritis (AIA) model to evaluate the therapeutic effect of TP-loaded microneedles. The experiments showed that TP-loaded microneedles alleviated the AIA rats’ inflammatory response, joint swelling, and bone erosion. However, there was no significant difference in the therapeutic effect observed in the acupoint and non-acupoint administration groups. In conclusion, TP-loaded microneedles have the advantages of safety, convenience, and high efficacy over conventional administration routes, laying a foundation for the transdermal drug delivery system-based treatment of rheumatoid arthritis.

Abstract Isospin symmetry is the most precise flavor symmetry. The effective Hamiltonian of charm quark weak decay is zero under the isospin lowering operators $$I_-^n$$ I - n , which permits us to generate isospin sum rules through several master formulas. In this work, we derive the master formulas of isospin sum rules for the two- and three-body non-leptonic decays of singly and doubly charmed baryons. Hundreds of isospin sum rules are derived to test of isospin symmetry and provide hints for the new decay modes. The isospin sum rules for multi-body decays are not broken by the intermediate resonances and hence can be used to study the isospin partners of exotic hadrons.

Abstract The study explores the dynamic and complex nexus between ICTs and economic performance by applying a meta-analysis with data from 65 typical studies at the country level. The overwhelmingly significant positive effects of ICTs on economic performance are confirmed through the vote count, funnel plot, precision-effect test, and meta-regression analysis. Additionally, differential influences of ICTs on developed and developing countries are investigated. Overall, developed countries gain more benefits from ICTs, while mobile technology tends to have more potential for economic growth. Moreover, the sample size and time period the data covered affect the ICTs—economic performance effect. In contrast, the type of data does not appear to significantly influence this effect. To better understand the impacts of ICTs, the continued skepticism and periodical revisit of this topic are required. The survey provides an updated and comprehensive examination of the state of the literature and also points out that although the generally favorable influences of ICTs are emphasized, the detrimental effects of ICTs on economic performance, especially for developing countries, cannot be ignored. With insights from this review, the study suggests directions for future research.

In recent years, deep learning technology has made significant progress in the field of target detection and recognition in synthetic aperture radar (SAR) images, yet its application still faces complex challenges. Despite deep neural network models achieving recognition rates exceeding 99% under standard operating conditions on the moving and stationary target acquisition and recognition dataset, the unique imaging mechanisms of SAR, its background dependency, variations in imaging parameters, and diversity in preprocessing lead to highly variable image statistical characteristics, thereby affecting the performance of deep learning models. Dataset bias, particularly the bias induced by different SAR image quantization methods, is one of the key factors impacting the generalization capability of models. This article delves into the impact of quantization methods on neural network performance and analyzes strategies to overcome dataset bias to enhance the stability and generalization capability of SAR image recognition. Experimental results indicate that models trained with adaptive quantization can learn more general features; linear quantization exhibits poor generalization when not enhanced, but this can be improved through data augmentation. Furthermore, pretraining and data augmentation techniques significantly enhance the classification performance of models under different quantization strategies, providing scientific evidence for optimizing SAR imaging system design and constructing reasonable datasets.

Abstract Fueled by the rapid advancement of nanofabrication, metasurface has provided unprecedented opportunities for 3D holography. Large depth 3D meta-holography not only greatly increases information storage capacity, but also enables distinguishing of the relative spatial relationship of 3D objects, which has important applications in fields like optical information storage and medical diagnosis. Although the methods based on Fresnel diffraction theory can reconstruct the real depth information of 3D objects, the maximum depth is only 2 mm. Here, we develop a 3D meta-holography based on angular spectrum diffraction theory to break through the depth limit. By developing the angular spectrum diffraction theory into meta-holography, the metasurface structure with independent polarization control is used to create a polarization multiplexing 3D meta-hologram. The fabricated amorphous silicon metasurface increases the depth range by 47.5 times and realizes 0.95 dm depth reconstruction for polarization independent and different color 3D meta-hologram in visible. Such polarization controlled large-depth color meta-holography is expected to open avenue for data storage, display, information security and virtual reality.

Abstract Isospin symmetry, as the most precise flavor symmetry, can be used to extract information about hadronic dynamics. The effective Hamiltonian for bottom quark weak decay is zero under the isospin lowering operators $$I_-^n$$ I - n , which allows us to generate isospin sum rules through several master formulas. In this work, we derive the master formulas of isospin sum rules for the two- and three-body non-leptonic decays of B mesons. Numerous new isospin sum rules, especially those involving three or more decay channels, are proposed. The isospin sum rules can be used to test isospin symmetry and provide hints the isospin partners of exotic hadrons in B decays. It is found ten percent isospin breaking only in decay modes involving two vector mesons, indicating the complex dynamics of vector mesons. Besides, the isospin analysis suggests the charm tetraquark resonances might be observed in the $$ B^- \rightarrow J/\Psi \pi ^-\overline{K}^0$$ B - → J / Ψ π - K ¯ 0 , $$\overline{B}^0 \rightarrow J/\Psi \overline{K}^0\phi $$ B ¯ 0 → J / Ψ K ¯ 0 ϕ , and $$\overline{B}^0\rightarrow D^0\overline{D}^0\overline{K}^0$$ B ¯ 0 → D 0 D ¯ 0 K ¯ 0 modes.

Abstract Circular RNAs (circRNAs) are a type of regulatory RNA that feature covalently closed single-stranded loops. Evidence suggested that circRNAs play important roles in the progression and development of various cancers. However, the impact of circRNA on autophagy-mediated progression of colorectal cancer (CRC) remains unclear. The objective of this project was to investigate the influence of circSEC24B on autophagy and its underlying mechanisms in CRC. To validate the presence and circular structure of circSEC24B in CRC cells and tissues, PCR and Sanger sequencing techniques were employed. Drug resistance and invasive phenotype of CRC cells were evaluated using CCK8, transwell, and Edu assays. Gain- and loss-of-function experiments were conducted to assess the effects of circSEC24B and its protein partner on the growth, invasion, and metastasis of CRC cells in vitro and in vivo. Interactions between circSEC24B, OTUB1, and SRPX2 were analyzed through immunofluorescence, RNA-pulldown, and RIP assays. Mass spectrometry analysis was used to identify potential binding proteins of circRNA in CRC cells. Vectors were constructed to investigate the specific structural domain of the deubiquitinating enzyme OTUB1 that binds to circSEC24B. Results showed that circSEC24B expression was increased in CRC tissues and cell lines, and it enhanced CRC cell proliferation and autophagy levels. Mechanistically, circSEC24B promoted CRC cell proliferation by regulating the protein stability of SRPX2. Specifically, circSEC24B acted as a scaffold, facilitating the binding of OTUB1 to SRPX2 and thereby enhancing its protein stability. Additionally, evidence suggested that OTUB1 regulated SRPX2 expression through an acetylation-dependent mechanism. In conclusion, this study demonstrated that circSEC24B activated autophagy and induced chemoresistance in CRC by promoting the deubiquitination of SRPX2, mediated by the deubiquitinating enzyme OTUB1.

Abstract This study defines the concept of major and minor countries and establishes a multidimensional and dynamic assessment system to evaluate the influence of countries participating in global climate governance. We systematically calculate 45 indicators for 53 countries across 9 global climate negotiation interest groups over the seven years. Our findings indicate a significant difference in influence between major and minor countries. This gap is particularly significant regarding losses incurred from climate disasters, with a more than fourfold difference between the top 25% and the bottom 25% in the influence rankings. The influence-climate disaster Index Gini coefficient further indicates that climate governance is characterized by extreme inequality. We argue that this phenomenon arises because those with more decisive influence in global climate governance do not bear losses from climate disasters commensurate with their influence. Therefore, their willingness to participate in climate governance is lower than those who suffer greater consequences.

Abstract To assess the efficacy of a novel 3D biomimetic hydrogel scaffold with immunomodulatory properties in promoting fracture healing. Immunomodulatory scaffolds were used in cell experiments, osteotomy mice treatment, and single-cell transcriptomic sequencing. In vitro, fluorescence tracing examined macrophage mitochondrial transfer and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Scaffold efficacy was assessed through alkaline phosphatase (ALP), Alizarin Red S (ARS) staining, and in vivo experiments. The scaffold demonstrated excellent biocompatibility and antioxidant-immune regulation. Single-cell sequencing revealed a shift in macrophage distribution towards the M2 phenotype. In vitro experiments showed that macrophage mitochondria promoted BMSCs’ osteogenic differentiation. In vivo experiments confirmed accelerated fracture healing. The GAD/Ag-pIO scaffold enhances osteogenic differentiation and fracture healing through immunomodulation and promotion of macrophage mitochondrial transfer.

Climate change has led to an increasing frequency and intensity of extreme climate events such as heat and drought extremes with considerable global public health burden. This systematic review collected 87 domestic and international studies from 2000 to 2023, considering the impacts of heat extremes, drought extremes, and compound hot-dry events on infectious diseases attributable to various transmission pathways such as waterborne, foodborne, insect-borne, airborne, and contact-transmitted diseases. Our results showed that high temperature was associated with increased transmission risks of waterborne and foodborne diseases including infectious diarrheal diseases (cholera, dysentery, typhoid, and paratyphoid) and infectious gastroenteritis; vector-borne diseases including dengue fever, Zika virus (ZIKV) disease, chikungunya fever, malaria, West Nile fever, and Rift Valley fever; airborne diseases including influenza-like diseases, influenza A, measles, and mumps; and contact-transmitted diseases including HIV/AIDS, schistosomiasis, and leptospirosis. Additionally, drought conditions also amplified the transmission risks of waterborne and foodborne diseases including cholera, Escherichia coli infection, rotavirus infection, and hepatitis E; vector-borne diseases such as scrub typhus, schistosomiasis, hemorrhagic fever with renal syndrome, and West Nile fever; airborne diseases including meningococcal meningitis, pertussis, measles, and upper respiratory infections; and contact-transmitted diseases such as HIV/AIDS. Along with global warming, the frequency of compound high temperature and drought events shows a considerably increasing trend, causing more adverse health effects than heat or drought alone. However, there is limited research quantifying their effects on infectious diseases. These associations may be mediated through temperature and precipitation on infectious disease pathogens, transmission vectors, population susceptibility, public health services, and behaviors. In the context of climate change, the increasing occurrence of compound events of high temperatures and droughts raises health concerns, and further studies are needed to enhance our understanding of the impacts of climate change on infectious diseases and improve human adaption to climate change.

Abstract To date, the types of fuels used in pottery kilns during the Western Zhou Dynasty have not been adequately addressed. Samples from updraft kilns and semi-downdraft kilns at the Fengjing site, the capital in the late Western Zhou period, were selected for analysis. Through phytolith and wood charcoal analysis, various grasses mainly Panicoideae, Pooideae, and Eragrostidoideae, as well as millet, rice, and wheat crops were identified. Additionally, wood primarily from trees of the Quercus, Ulmus, and Liquidambar taxa was found. These findings suggest that different pottery kilns used similar fuels, demonstrating a broad-spectrum rather than specialized fuel utilization during the Zhou period.

Abstract Qarhan Salt Lake, located in the Qaidam Basin on the Qinghai-Tibet Plateau in northwestern China, is the largest potash production base in China. The main potash deposit in Qarhan Salt Lake is a comprehensive deposit in which the liquid potassium resources dominated by potassium-rich and lithium-rich brine coexist with the low-grade solid potassium salt deposit composed of solid potash minerals (polyhalite, carnallite, sylvite). Polyhalite is one of the representative potassium minerals, widely distributed in the Bieletan area of Qarhan Salt Lake, coexisting with halite, and its deposition indicates that the paleo-temperature of brine in this area once fluctuated obviously. Twenty core samples from two boreholes in the Bieletan area of the Qarhan Salt Lake were subjected to fluid inclusions thermometry, and homogenization temperatures reflecting the brine temperatures during the precipitation of evaporite minerals in the Salt Lake were obtained, ranging from 12.4 to 28.9 °C and 9.2 to 19.8 °C, respectively. By scanning electron microscopy, acicular polyhalite and pompom-like aggregate of polyhalite have been identified in the sampling layer, indicating that evaporite deposition have reached the stage of potassium salt deposition. The temperature fluctuations of the fluid inclusions and the elemental chemical data are compared vertically, and the sections with significant temperature fluctuations are close to the layers where polyhalite were deposited. It shows that the paleo-temperature fluctuation impact the sedimentary environment of brine, and then affected the polyhalite deposition of Qarhan Salt Lake.

Abstract Electrocatalytic CO2 reduction to multi-carbon products is a promising approach for achieving carbon-neutral economies. However, the energy efficiency of these processes remains low, particularly at high current densities. Herein, we demonstrate that the low energy efficiencies are, in part, sometimes significantly, attributed to the high concentration overpotential resulting from the instability (i.e., flooding) of catalyst-layer during electrolysis. To tackle this challenge, we develop copper/gallium bimetallic catalysts with reduced activation energies for the formation of multi-carbon products. Consequently, the reduced activation overpotential allows us to achieve practical-relevant current densities for CO2 reduction at low cathodic potentials, ensuring good stability of the catalyst-layer and thereby minimizing the undesired concentration overpotential. The optimized bimetallic catalyst achieves over 50% cathodic energy efficiency for multi-carbon production at a high current density of over $$1.0 \, {{\rm{A}}} \, {{\rm{cm}}}^{-2}$$ 1.0 A cm − 2 . Furthermore, we achieve current densities exceeding $$2.0 \, {{\rm{A}}} \, {{\rm{cm}}}^{-2}$$ 2.0 A cm − 2 in a zero-gap membrane-electrode-assembly reactor, with a full-cell energy efficiency surpassing 30%.

Ribonucleic acid for injection II is a clinical adjuvant cancer therapy treatment based on immunotherapy, which exerts its effects by enhancing immune function and suppressing tumor growth. However, the mechanism underlying the ameliorative effect on immunosuppressed hematopoietic dysfunction remains unclear. This study confirmed the immune-boosting and hematopoietic-promoting effects of ribonucleic acid for injection II, which has a wide distribution of molecular weights and is rich in amino acids and nucleotides. Ribonucleic acid for injection II influences the gut microbiota and serum metabolites to enhance immunity in immunosuppressed mice induced by CTX, while also mitigating bone marrow injury and increasing hematopoietic cells through mediating macrophage M1 differentiation, thereby improving hematopoietic dysfunction in mice.

Abstract Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is an epigenetic regulator that plays critical roles in tumours. However, the DNA methylation alteration patterns driven by UHRF1 and the related differentially expressed tumour-related genes remain unclear. In this study, a UHRF1-shRNA MCF-7 cell line was constructed, and whole-genome bisulfite sequencing and RNA sequencing were performed. The DNA methylation alteration landscape was elucidated, and DNA methylation-altered regions (DMRs) were found to be distributed in both gene bodies and adjacent regions. The DMRs were annotated and categorized into 488 hypermethylated/1696 hypomethylated promoters and 1149 hypermethylated/5501 hypomethylated gene bodies. Through an integrated analysis with the RNA sequencing data, 217 methylation-regulated upregulated genes and 288 downregulated genes were identified, and these genes were primarily enriched in nervous system development and cancer signalling pathways. Further analysis revealed 21 downregulated oncogenes and 15 upregulated TSGs. We also showed that UHRF1 silencing inhibited cell proliferation and migration and suppressed tumour growth in vivo. Our study suggested that UHRF1 and the oncogenes or TSGs it regulates might serve as biomarkers and targets for breast cancer treatment.

Abstract Background Cell subsets differentially modulate host immune responses to Mycobacterium tuberculosis (MTB) infection. However, the nature and functions of these subsets against osteoarticular tuberculosis (OTB) are unclear. Here, we aimed to understand the phenotypes and functions of immune cell subsets in patients with OTB using single-cell RNA sequencing (scRNA-Seq). Methods Pathological and healthy adjacent tissues were isolated from patients with OTB and subjected to scRNA-Seq. Unsupervised clustering of cells was performed based on gene expression profiles, and uniform manifold approximation and projection was used for clustering visualization. Results Thirteen cell subsets were identified in OTB tissues. scRNA-seq datasets of patients and healthy controls (HCs) showed that infection changed the frequency of immune cell subsets in OTB tissues. Myeloid cell examination revealed nine subsets. The frequency of macrophage-RGS1high subsets decreased in OTB tissues; this increased MTB susceptibility in an SLC7A11/ferroptosis-dependent manner. Immunohistochemistry assays and flow cytometry for patients with OTB and osteoarticular bacterial infection (OBI) and HCs verified that the frequency of macrophage-RGS1high subset decreased in OTB tissues and blood samples, thereby distinguishing patients with OTB from HCs and patients with OBI. Conclusion The macrophage-RGS1high subset levels were decreased in patients with OTB, and would be up-regulated after effective treatment. Therefore, the clinical significance of this study is to discover that macrophage-RGS1high subset may serve as a potential biomarker for OTB diagnosis and treatment efficacy monitoring.

Abstract Background Despite centuries of traditional use of silymarin for hepatoprotection, current randomized controlled trial (RCT) studies on the effectiveness of silymarin in managing metabolic dysfunction-associated steatotic liver disease (MASLD) are limited and inconclusive, particularly when it is administered alone. The low bioavailability of silymarin highlights the possible influence of gut microbiota on the effectiveness of silymarin; however, no human studies have investigated this aspect. Objective To determine the potential efficacy of silymarin in improving MASLD indicators and to investigate the underlying mechanisms related to gut microbiota. Method In this 24-week randomized, double-blind, placebo-controlled trial, 83 patients with MASLD were randomized to either placebo (n = 41) or silymarin (103.2 mg/d, n = 42). At 0, 12, and 24 weeks, liver stiffness and hepatic steatosis were assessed using FibroScan, and blood samples were gathered for biochemical detection, while faecal samples were collected at 0 and 24 weeks for 16S rRNA sequencing. Results Silymarin supplementation significantly reduced liver stiffness (LSM, -0.21 ± 0.17 vs. 0.41 ± 0.17, P = 0.015) and serum levels of γ-glutamyl transpeptidase (GGT, -8.21 ± 3.01 vs. 1.23 ± 3.16, P = 0.042) and ApoB (-0.02 ± 0.03 vs. 0.07 ± 0.03, P = 0.023) but had no significant effect on the controlled attenuation parameter (CAP), other biochemical indicators (aminotransferases, total bilirubin, glucose and lipid parameters, hsCRP, SOD, and UA), physical measurements (DBP, SBP, BMI, WHR, BF%, and BMR), or APRI and FIB-4 indices. Gut microbiota analysis revealed increased species diversity and enrichment of Oscillospiraceae in the silymarin group. Conclusion These findings suggest that silymarin supplementation could improve liver stiffness in MASLD patients, possibly by modulating the gut microbiota. Trial registration The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2200059043).

Abstract Glioma is the most common primary brain tumor, and targeting glioma stem cells (GSCs) has become a key aspect of glioma treatment. In this study, we discovered a molecular network in which circRNA forms an R-loop structure with its parental gene to regulate the biological behavior of GSCs. Genes with abnormal expression in GSCs were screened using RNA-seq and circRNA microarray analyses. The study results showed that high expression of YTHDC1 in GSCs promoted the transportation of N6-methyladenosine (m6A)-modified circPOLR2B from the nucleus to the cytoplasm. Decreased circPOLR2B levels in the nucleus resulted in fewer R-loop structures formed with its parental gene POLR2B. This reduction in R-loop structures relieved the inhibitory effect on POLR2B transcription and upregulated PBX1 expression through alternative polyadenylation (APA) action, thereby promoting the malignant biological behavior of GSCs. Knockdown of YTHDC1, POLR2B, and PBX1 reduced xenograft tumor volume and prolonged the survival of nude mice. The YTHDC1/circPOLR2B/POLR2B/PBX1 axis plays a regulatory role in the biological behavior of GSCs, offering potential targets and novel strategies for the treatment of glioma.

ObjectivePhotoelectric volumetric tracing (PPG) exhibits high sensitivity and specificity in flap monitoring. Deep learning (DL) is capable of automatically and robustly extracting features from raw data. In this study, we propose combining PPG with 1D convolutional neural networks (1D-CNN) to preliminarily explore the method’s ability to distinguish the degree of embolism and to localize the embolic site in skin flap arteries. MethodsData were collected under normal conditions and various embolic scenarios by creating vascular emboli in a dermatome artery model and a rabbit dermatome model. These datasets were then trained, validated, and tested using 1D-CNN. ResultsAs the degree of arterial embolization increased, the PPG amplitude upstream of the embolization site progressively increased, while the downstream amplitude progressively decreased, and the gap between the upstream and downstream amplitudes at the embolization site progressively widened. 1D-CNN was evaluated in the skin flap arterial model and rabbit skin flap model, achieving average accuracies of 98.36% and 95.90%, respectively. ConclusionThe combined monitoring approach of DL and PPG can effectively identify the degree of embolism and locate the embolic site within the skin flap artery.

Given the side effects associated with synthetic antihypertensive drugs, there is a growing need among researchers to investigate angiotensin-converting enzyme (ACE) inhibitory peptides derived from food protein as safer therapeutic alternatives. This study used seabuckthorn (Hippophae rhamnoides L.) seed meal as the raw material, and the protein was extracted by alkaline extraction and acid precipitation. After enzymatic digestion, peptides with molecular weight less than 3 kDa were selected for study. The screened peptide had an IC50 value of 4.358 mg/mL on ACE with a non-competitive inhibition mechanism and good inhibition stability. By employing infrared (IR) analysis, exclusively β-fold and β-helix structures were identified in the hydrolysate, while no other structural motifs were detected. X-ray diffraction revealed that it had an irregular amorphous structure. The peptide contains 17 amino acids that are both highly acidic and hydrophobic, with glutamic acid ranking first in terms of the number of individual amino acids. Compared with the database (NCBI, Uniport), ten peptides with ACE inhibitory activity were detected, and molecular docking showed the mechanism of each peptide inhibiting ACE, FRVAWTEKNDGQRAPLANN, LIISVAYARVAKKLWLCNMIGDVT-TEQY, VIRSRASDGCLEVKEFEDIPP, AGGGG-GGGGGGSRRL, LQPREGPAGGTT-ALREELSLGPEAALDTPPAGP, DDEARINQLFL, FAVSTLTSYDWSDRDDATQGR-KL, RQLSLEGSGLGVEDLKDN, GGGGGGGGGGGGGGGIGGGGGGGGGGGAR, and KEALGEGCFGNRIDRIGD. According to the results, AGGGGGG-GGGGSRRL is more stable in binding to ACE and may have better inhibitory activity. It has been shown that seabuckthorn protein can be an alternative source of ACE inhibitory peptides.

Abstract Inherited non-hemolytic anemia is a group of rare bone marrow disorders characterized by erythroid defects. Although concerted efforts have been made to explore the underlying pathogenetic mechanisms of these diseases, the understanding of the causative mutations are still incomplete. Here we identify in a diseased pedigree that a gain-of-function mutation in toll-like receptor 8 (TLR8) is implicated in inherited non-hemolytic anemia. TLR8 is expressed in erythroid lineage and erythropoiesis is impaired by TLR8 activation whereas enhanced by TLR8 inhibition from erythroid progenitor stage. Mechanistically, TLR8 activation blocks annexin A2 (ANXA2)-mediated plasma membrane localization of STAT5 and disrupts EPO signaling in HuDEP2 cells. TLR8 inhibition improves erythropoiesis in RPS19 +/− HuDEP2 cells and CD34+ cells from healthy donors and inherited non-hemolytic anemic patients. Collectively, we identify a gene implicated in inherited anemia and a previously undescribed role for TLR8 in erythropoiesis, which could potentially be explored for therapeutic benefit in inherited anemia.

Background: Postoperative delirium (POD) is common postoperative complications in non-cardiac surgery. While delirium prophylaxis has not yielded unequivocal support. The clinical effects of glucocorticoids on POD remains unclear. Objective: To evaluate the effects of glucocorticoids on postoperative delirium (POD) in patients undergoing non-cardiac surgery. Design: Systematic review with meta-analysis. Methods: In strict accordance with the PRISMA statement, a systematic literature search was undertaken across PubMed, EMBASE, Web of Science and Cochrane Library databases in May 2023. We updated the search results on June 28, 2024. We used the Grading of the Recommendation Assessment, Development, and Evaluation (GRADE) system to evaluate the quality of evidence. Results: This meta-analysis included twelve randomized controlled trials involving 1044 participants undergoing non-cardiac surgery. Compared with the control group, glucocorticoids significantly reduced the incidence of POD in patients undergoing non-cardiac surgery (RR:0.50, 95%CI:0.41 to 0.60, P

Metabolic abnormalities are an important feature of tumours. The glutamine-arginine-proline axis is an important node of cancer metabolism and plays a major role in amino acid metabolism. This axis also acts as a scaffold for the synthesis of other nonessential amino acids and essential metabolites. In this paper, we briefly review (1) the glutamine addiction exhibited by tumour cells with accelerated glutamine transport and metabolism; (2) the methods regulating extracellular glutamine entry, intracellular glutamine synthesis and the fate of intracellular glutamine; (3) the glutamine, proline and arginine metabolic pathways and their interaction; and (4) the research progress in tumour therapy targeting the glutamine-arginine-proline metabolic system, with a focus on summarising the therapeutic research progress of strategies targeting of one of the key enzymes of this metabolic system, P5CS (ALDH18A1). This review provides a new basis for treatments targeting the metabolic characteristics of tumours.

Enhanced understanding of flow structure in braided rivers is essential for river regulation, flood control, and infrastructure safety across the river. It has been revealed that the basic morphological element of braided rivers is confluence-bifurcation units. However, flow structure in these units has so far remained poorly understood with previous studies having focused mainly on single confluences/bifurcations. Here, the flow structure in a laboratory-scale confluence-bifurcation unit is numerically investigated based on the FLOW-3D® software platform. Two discharges are considered, with the central bars submerged or exposed respectively when the discharge is high or low. The results show that flow convergence and divergence in the confluence-bifurcation unit are relatively weak when the central bars are submerged. Based on comparisons with a single confluence/bifurcation, it is found that the effects of the upstream central bar on the flow structure in the confluence-bifurcation unit reign over those of the downstream central bar. Concurrently, the high-velocity zone in the confluence-bifurcation unit is less concentrated than that in a single confluence while being more concentrated than that observed in a single bifurcation. The present work unravels the flow structure in a confluence-bifurcation unit and provides a unique basis for further investigating morphodynamics in braided rivers.Highlights 3D flow structure in a confluence-bifurcation unit (CBU) is numerically investigated.Flow convergence/divergence in CBU is relatively weak when central bars are submerged.Effects of the upstream central bar on CBU flow reign over those of the downstream central bar.The high-velocity zone is less/more concentrated in the CBU than in a single confluence/bifurcation when the central bars are exposed.

Epithelial ovarian cancer (EOC) is a common estrogen-sensitive tumor that poses a serious threat to women 's health, and the mortality rate of EOC ranks first among malignant tumors in females. Studies have indicated a strong link between estrogen abnormality and EOC progression. We accidently found that 3-phosphoinositide-dependent protein kinase-1 (PDPK1) is highly expressed in EOC tissues. Further, estrogen also up-regulates the expression of PDPK1 in EOC cells. Notably, the expression of PDPK1 is controlled strictly, and its expression can determine the fate of cells. However, to date, the molecular mechanism by which estrogen elicits PDPK1 expression in EOC cells, and the role of PDPK1 in estrogen-driven EOC cells are not well defined. In this research, we found that a high expression of PDPK1 was associated with poor prognosis in patients with ovarian cancer. Further, estrogen stimulated the increase of PDPK1 protein expression through estrogen receptor ESR1. The depletion or overexpression of PDPK1 affected the inhibition or amplification of estrogen-driven EOC cell proliferation, and the knockdown of PDPK1 suppressed the migration of EOC cells by estrogen while promoting cell apoptosis. This suggests a critical functional association between estrogen and PDPK1 in the process of EOC. The expression of messenger RNA for cyclin A1, cyclin-dependent kinase 2 (CDK2), matrix metallopeptidase 2 (MMP2), and bcl-2 associated x protein (Bax) is regulated by PDPK1 under estrogen treatment. Our results indicated that PDPK1 plays a role as an oncogene in the development of EOC; hence, elucidating the mechanism by which estrogen promotes EOC progression by regulating PDPK1 expression.

PurposeImpairment in perception and sensory reweighting could predispose older adults to falls. This exploratory study aimed to investigate the differences in sensory reweighting and self-motion perception for postural control under single-sensory and multisensory perturbations between older Tai Chi (TC) practitioners and healthy active older controls.MethodsTwenty-four TC practitioners and 23 age-matched non-practitioners were recruited in this observational study. Participants stood on a force plate with or without a foam surface (baseline), followed by 36 s of visual rotation stimuli, vestibular rotation stimuli, or reduced somatosensory input (adaptation), and then continued standing for 44 s (reintegration). The center-of-pressure (COP) trajectories and self-motion perception were recorded. COP signals were analyzed using traditional sway, multiscale entropy, and wavelet analysis methods and the time-window-of-integration model to examine the postural balance performance and the flexibility and speed of sensory reweighting.ResultsSignificant interaction effects of group with sensory perturbation and group with time window on COP parameters were observed (p

Prostate cancer (PCa) currently ranks second in male tumor mortality. Targeting immune checkpoint in tumor as immunotherapy is a new direction for tumor treatment. However, targeting PD-1/PD-L1 and CTLA4 to treat PCa has poor immunotherapeutic efficacy because PCa is known as a cold tumor. Understanding the mechanism of immunosuppression in PCa can promote the use of immunotherapy to treat PCa. ELAVL1 is highly expressed in many tumors, participates in almost all tumor biological activities and is an oncogene. ELAVL1 is also involved in the development and differentiation of T and B lymphocytes. However, the relationship between ELAVL1 and tumor immunity has not yet been reported. In recent years, ELAVL1 has been shown to regulate downstream targets in an m6A -dependent manner. PD-L1 has been shown to have m6A sites in multiple tumors that are regulated by m6A. In this study, ELAVL1 was highly expressed in PCa, and PCa with high ELAVL1 expression is immunosuppressive. Knocking down ELAVL1 reduced PD-L1 expression in PCa. Moreover, PD-L1 was shown to have an m6A site, and its m6A level was upregulated in PCa. ELAVL1 interacts with PD-L1 mRNA and promotes PD-L1 RNA stability via m6A, ultimately inhibiting the infiltration of CD4-positive T cells. In addition, androgen receptor (AR) was shown to be regulated with ELAVL1, and knocking down AR could also affect the expression of PD-L1. Therefore, ELAVL1 can directly or indirectly regulate the expression of PD-L1, thereby affecting the infiltration of CD4-positive T cells in PCa and ultimately leading to immune suppression.

Urban–rural interlaced zones are characterized by the interpenetration of urban and rural elements, drastic changes in construction, relatively weak planning and management, and anthropogenic activities that constantly impact the ecological background. However, the ecological barriers and hinterland spaces of the city center provide important ecological functions. In this study, we selected forest birds as indicator species of the urban ecological environment and explored the spatial stratification and heterogeneity effects of environmental substrates and anthropogenic activities on bird diversity (species richness, abundance, Shannon–Wiener index, and Simpson index) in urban–rural interlaced zones using the optimal parameter geographic detector model to characterize the changes in ecological functions in these zones. The results of this study are as follows:(1) The bird diversity index in Minhang District, Shanghai, showed an obvious urban-rural gradient divergence with the transition of urban zone- rural-urban interface - rural zone.An agglomerative spatial differentiation pattern was observed more in the southeast but less in the northwest, with a high degree of spatial distribution concentrations and evident imbalance characteristics.(2) The spatially stratified heterogeneity in bird diversity in urban–rural interlaced zones was because of the combined action of multiple driving factors under the three dimensions of habitat environment, degree of urbanization, and anthropogenic interference. Most of the interactions between any two factors showed non-linear or bifactorial enhancement effects. Furthermore, the one-factor explanatory power of urbanization and anthropogenic interference factors on bird diversity was significantly higher than that of the habitat environment factor.(3) Population heat distribution (PD), distance to the center of Shanghai (DC), and nighttime lighting index(NTL) were the main drivers of spatially stratified heterogeneity in bird diversity and the key indicators of urban–rural gradient changes. The interaction between PD and DC had the strongest explanatory power for the spatial differentiation of bird diversity.

Objective In this study, we investigated the cause of the AngII dose elevation in aqueous humor of primary open-angle glaucoma (POAG) patients. Methods Enzyme-linked immunosorbent assay (ELISA), western blotting were used to detect concentration of Angiotensin Converting Enzyme 2 (ACE2) and Prolylcarboxypeptidase (PRCP). AngII and AngII + Recombinant PRCP were injected into anterior chamber of mouse eye. Mouse Intraocular pressure (IOP) was measured every week, mouse eye sections were conducted Hematoxylin-and-Eosin (H&E) staining, Masson’ staining and Immunofluorescence staining. Western blotting and Immunofluorescence staining assays to detected fibrosis of trabecular meshwork cells. Mass spectrometry was used to identify proteins of aqueous humor. Results PRCP dose are decreased in aqueous humor of POAG patients. There is a negative correlation between PRCP and AngII levels in aqueous humor and between PRCP levels and the IOP. PRCP treatment reverses fibrosis of trabecular meshwork (TM) and prevents IOP elevation induced by AngII. Exogenous PRCP rescues fibrosis induced by AngII in HTMCs. Proteome profiling detected 502 differentially expressed proteins. Conclusion Our study found PRCP dose was decreased in POAG patients’ aqueous humor, and it might cause high level of AngII. Restoration of PRCP rescued fibrosis of TM cells and ameliorated IOP in AngII treatment mouse.

BackgroundOsteoarthritis (OA) is the most common joint disease, which mainly damages articular cartilage and involves the whole joint tissue. It has the characteristics of long course, repeated symptoms and high disability rate, and the incidence trend is gradually increasing. Tetramethylpyrazine (TMP) is the main alkaloid active substance in Ligusticum wallichii, a traditional Chinese medicine, which has the effect of promoting blood circulation and dredging collaterals, and has a good effect on the treatment of early OA, but its molecular mechanism has not been fully clarified so far. Based on network pharmacology, molecular docking simulation and animal experiments, this study explored the target and molecular mechanism of TMP in the treatment of OA.MethodsWe used PubChem, SwissTargetPrediction, and PharmMapper databases to predict the molecular structure and potential targets of TMP. GeneCards and DisGeNET databases were used to predict the relevant targets of OA. Apply UniProt database to convert targets into unified gene names, and proofread and remove duplicate gene names. The intersection targets of TMP and OA obtained on venny2.1.0 website were submitted to the STRING database to construct a PPI network. CytoScape 3.8.2 software was used to analyze the PPI network and obtain the sub-network modules and 10 key targets. The intersection targets of TMP and OA were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment using DAVID 6.8 database. The intersecting targets of TMP and OA, the biological process of GO enrichment, and KEGG signaling pathway were imported into Cytoscape 3.8.2 software to construct the TMP-target-pathway network diagram. Use molecular docking technology to simulate the interaction between TMP molecules and key targets, and predict the binding mode and binding ability. Animal models of rabbit knee osteoarthritis were prepared, and magnetic resonance imager (MRI) and fluorescence quantitative PCR (RT-qPCR) were used to observe the effect of TMP in treating OA as well as the expression of key target genes.Results585 potential targets of TMP, 3,857 potential targets of OA, and 49 intersecting targets of TMP and OA were obtained. The top 10 key target genes were obtained, in order of ranking: ALB, ESR1, IL10, CAT, F2, MPO, C3, CYP3A4, CYP2C9, ANXA1. GO and KEGG analysis implied that the key targets might act on OA by affecting endothelial cell permeability, peri-articular microcirculatory status, NETs production, activation of complement system and coagulation pathway, regulation of immune function of macrophages and T cells, and substance metabolism pathway in vivo, etc. The molecular mechanism might involve the formation of neutrophil extracellular trap, regulation of the actin cytoskeleton, complement and coagulation cascades, and T cell receptor signaling pathways, etc. Molecular docking simulations showed that the binding energy of IL10 and ANXA1 to TMP was greater than -5Kal/mol, but the other key target proteins showed better binding to TMP, and the binding energy was less than -5 kcal/mol. Animal experiments showed that TMP had a significant therapeutic effect on OA. The TMP group had significantly reduced knee joint effusion and bone marrow damage compared to the OA group (p < 0.05). The qRT-PCR results showed that compared with the OA group, the mRNA expression of ESR1, CAT, C3, CYP3A4, CYP2C9, and ANXA1 in the TMP group increased (p < 0.05), while there was no significant difference in mRNA expression of ALB, IL-10, F2, MPO, etc. (p > 0.05).ConclusionTMP is effective in the treatment of OA, with multi-target and multi-pathway interactions. ESR1, CAT, C3, CYP3A4, CYP2C9, and ANXA1 may be potential targets for TMP treatment of OA. The molecular mechanism mainly involves the formation of neutrophil extracellular trap, regulation of the actin cytoskeleton, complement and coagulation cascades, and T cell receptor signaling pathways, etc.

In 2009, severe fever with thrombocytopenia syndrome virus (SFTSV), also known as the Dabie bandavirus (DBV), was first discovered in Henan, China. It is a tick-borne zoonotic virus with a fatality rate ranging from 6% to 30%. Currently, we lack safe and effective vaccines or antiviral drugs to treat SFTSV infection. Therefore, the development of a specific, sensitive, and cost-effective detection method is crucial. Using inactivated SFTSV and recombinant SFTSV nucleocapsid protein (SFTSV-NP), we repeatedly immunized mice with different adjuvants and obtained two monoclonal antibodies against SFTSV-NP, which were used to develop a colloidal gold immunochromatographic assay (ICA) rapid test kit for SFTSV. Compared with nucleic acid testing (gold standard), the ICA test strips are 97.67% accurate in testing clinical serum samples (36 cases of clinical serum samples and seven cases of whole blood samples). The test kit was 100% accurate in detecting different SFTSV strains. No false-positive results were generated when detecting other arboviruses. Therefore, our developed SFTSV test kit conveniently, rapidly, and effectively detects SFTSV.

AimThe Triglyceride-Glucose (TyG) index, an indicator of insulin resistance, has been proposed as a predictor of cardiovascular diseases. However, its role in predicting stroke risk, particularly in low-income populations, is not well understood. This study aimed to investigate the predictive value of the TyG index for stroke incidence in a low-income Chinese population, with a focus on gender and age-specific differences.MethodsThis 10-year prospective cohort study included 3,534 participants aged ≥45 years from rural areas in northern China. Baseline data on demographic characteristics, lifestyle factors, and clinical measurements were collected. Participants were followed for stroke incidence, categorized into ischemic and hemorrhagic stroke. Multivariate logistic regression models were used to assess the association between the TyG index and stroke incidence, adjusting for potential confounders.ResultsDuring the follow-up period, 368 participants (10.4%) experienced a stroke, with 327 ischemic and 31 hemorrhagic strokes. TyG index was significantly associated with total and ischemic stroke incidence but not hemorrhagic stroke. After adjusting for confounding factors, for every one standard deviation increase in TyG index, the risk of stroke increased by 32% for overall stroke (RR: 1.32; 95% CI: 1.08-1.61; P=0.006) and 39% for ischemic stroke (RR: 1.39; 95% CI: 1.12-1.73; P=0.003). The risk of stroke in the highest TyG tertile levels (tertile 3) increased by 49% (RR: 1.49; 95% CI 1.11-1.99; P=0.007) for overall stroke, compared to those in the lowest tertile levels (tertile 1). For ischemic stroke, the risk of stroke increased by 53% (RR: 1.53; 95% CI 1.12-2.11; P=0.008) in the highest TyG tertile levels (tertile 3) compared to those in the lowest tertile levels (tertile 1).ConclusionThis 10-year prospective cohort study has established the TyG index as an independent predictor of both total and ischemic stroke incidence in a low-income Chinese population. The findings indicate that the TyG index is particularly effective in predicting stroke risk among women and older adults (≥60 years), but not for hemorrhagic stroke. These insights are crucial for improving clinical practice and stroke prevention strategies.

IntroductionPike perch (Sander Lucioperca) is a predatory freshwater fish, which is highly popular amongst consumers, owing to its white flesh with a delicate structure and mild flavor. Compared to wild pike perch, the diet of farmed ones has shifted from natural food to artificial feeds. These changes would affect the gut flora of the pike perch. Endogenous metabolites of the intestinal flora are transferred through the gut-liver axis, which affects the physiological functions of the host. By studying wild and farmed individuals of the pike perch, novel insights into the stability of the intestinal flora can be provided.Methods and resultsIn this study, we measured various immune parameters in the blood, liver and intestine of wild and farmed pike perch using enzyme activity assays and real-time fluorescence quantitative PCR. Gut microbes were also collected for 16S rRNA gene sequencing. Our results showed that the serum low-density lipoprotein cholesterol (LDL-C) levels were twice as high in the wild group as in the farmed group. Furthermore, the activities of glutamate pyruvate transaminase (GPT) and glutamate oxaloacetate transaminase (GOT) in the intestinal tissues of the wild group were 733.91 U/g and 375.35 U/g, which were significantly higher than those of the farmed group. Expression of IL10 in the liver of farmed pike perch was also 4-fold higher than that of wild pike perch. The expression of genes related to the p53-BAX/Bcl2 signaling pathway was higher in both intestinal and liver tissues of wild pike perch compared with farmed. 16S rRNA gene analysis of the gut microflora showed a high relative abundance of Cetobacterium in the gut of farmed pike perch.ConclusionAs a result, our study indicates that dietary differences affect the diversity, composition and relative abundance of the gut flora of the pike perch. Meanwhile, it affects the glycolipid metabolism and immunomodulation of pike perch.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder distinguished by gradual depletion of motor neurons. RNA binding motif protein 5 (RBM5), an abundantly expressed RNA-binding protein, plays a critical role in the process of cellular death. However, little is known about the role of RBM5 in the pathogenesis of ALS. Here, we found that RBM5 was upregulated in ALS hSOD1G93A-NSC34 cell models and hSOD1G93A mice due to a reduction of miR-141–5p. The upregulation of RBM5 increased the apoptosis of motor neurons by inhibiting Rac1-mediated neuroprotection. In contrast, genetic knockdown of RBM5 rescued motor neurons from hSOD1G93A-induced degeneration by activating Rac1 signaling. The neuroprotective effect of RBM5-knockdown was significantly inhibited by the Rac1 inhibitor, NSC23766. These findings suggest that RBM5 could potentially serve as a therapeutic target in ALS by activating the Rac1 signalling.

In this study, tea polyphenol oxidase (PPO) was purified via three-phase partitioning (TPP) using a deep eutectic solvent (DES) instead of t-butanol. First, the properties of 13 types of synthesized DESs were characterized, and DES-7 (thymol/dodecanoic acid) was selected as the best alternative solvent. The process parameters were optimized using response surface methodology. The experimental results revealed that when the (NH4)2SO4 concentration, DES to crude extract ratio, extraction time, and pH were 41%, 0.5:1, 75 min, and 5.6, respectively, the recovery and purification fold of tea PPO were 78.44% and 8.26, respectively. SDS-PAGE and native-PAGE were used to analyze the PPO before and after purification of the TTP system, and the molecular weight and purification effect of PPO were detected. Moreover, the DES could be recovered and recycled. The results indicate an environmentally friendly and stable DES, and provide a reference for the large-scale application of TPP to extract PPO.

Abstract Sulfate‐reducing microorganisms extensively contribute to the corrosion of ferrous metal infrastructure. There is substantial debate over their corrosion mechanisms. We investigated Fe0 corrosion with Desulfovibrio vulgaris, the sulfate reducer most often employed in corrosion studies. Cultures were grown with both lactate and Fe0 as potential electron donors to replicate the common environmental condition in which organic substrates help fuel the growth of corrosive microbes. Fe0 was corroded in cultures of a D. vulgaris hydrogenase‐deficient mutant with the 1:1 correspondence between Fe0 loss and H2 accumulation expected for Fe0 oxidation coupled to H+ reduction to H2. This result and the extent of sulfate reduction indicated that D. vulgaris was not capable of direct Fe0‐to‐microbe electron transfer even though it was provided with a supplementary energy source in the presence of abundant ferrous sulfide. Corrosion in the hydrogenase‐deficient mutant cultures was greater than in sterile controls, demonstrating that H2 removal was not necessary for the enhanced corrosion observed in the presence of microbes. The parental H2‐consuming strain corroded more Fe0 than the mutant strain, which could be attributed to H2 oxidation coupled to sulfate reduction, producing sulfide that further stimulated Fe0 oxidation. The results suggest that H2 consumption is not necessary for microbially enhanced corrosion, but H2 oxidation can indirectly promote corrosion by increasing sulfide generation from sulfate reduction. The finding that D. vulgaris was incapable of direct electron uptake from Fe0 reaffirms that direct metal‐to‐microbe electron transfer has yet to be rigorously described in sulfate‐reducing microbes.

Chip seal is widely used for preventive maintenance to mitigate pavement deterioration, but it is prone to aggregate loss during pavement service. To further promote the development and application of chip seals in road engineering in China, the research progress of the adhesion behavior of aggregate and binder in chip seals was reviewed in this paper, focusing on the adhesion mechanism of emulsified asphalt and alkaline aggregate. The Influencing factors and evaluation methodology of chip seals' aggregate adhesion behavior were also discussed. The results demonstrate that the adhesion process between emulsified asphalt and alkaline aggregate is divided into three processes including infiltration, demulsification, and cluster, which is more complicated when compared to hot asphalt. When designing a chip seal, not only the characteristics of single material should be paid attention to, but also the combination of binder and aggregate matters a lot. To form good adhesion between aggregate and asphalt binder, various influencing factors such as material selection, design method, and construction technical index should be considered comprehensively in the whole design, construction, and operation process. Three methods for evaluating adhesion behavior are summarized, including macroscopic adhesion performance tests, image analysis technology, and model prediction. It is not objective to evaluate the aggregate adhesion behavior of chip seal only by a single evaluation method. A comprehensive evaluation based on the micro-macro multi-scale method should be considered in the future.

Abstract Background Extracellular adenosine triphosphate (ATP) is an important signal molecule. In previous studies, intensive research had revealed the crucial roles of family with sequence similarity 3 member A (FAM3A) in controlling hepatic glucolipid metabolism, islet β cell function, adipocyte differentiation, blood pressure, and other biological and pathophysiological processes. Although mitochondrial protein FAM3A plays crucial roles in the regulation of glucolipid metabolism via stimulating ATP release to activate P2 receptor pathways, its mechanism in promoting ATP release in hepatocytes remains unrevealed. Methods db/db, high-fat diet (HFD)-fed, and global pannexin 1 (PANX1) knockout mice, as well as liver sections of individuals, were used in this study. Adenoviruses and adeno-associated viruses were utilized for in vivo gene overexpression or inhibition. To evaluate the metabolic status in mice, oral glucose tolerance test (OGTT), pyruvate tolerance test (PTT), insulin tolerance test (ITT), and magnetic resonance imaging (MRI) were conducted. Protein–protein interactions were determined by coimmunoprecipitation with mass spectrometry (MS) assays. Results In livers of individuals and mice with steatosis, the expression of ATP-permeable channel PANX1 was increased (P

Abstract The reconstruction of Cu catalysts during electrochemical reduction of CO2 is a widely known but poorly understood phenomenon. Herein, we examine the structural evolution of Cu nanocubes under CO2 reduction reaction and its relevant reaction conditions using identical location transmission electron microscopy, cyclic voltammetry, in situ X-ray absorption fine structure spectroscopy and ab initio molecular dynamics simulation. Our results suggest that Cu catalysts reconstruct via a hitherto unexplored yet critical pathway - alkali cation-induced cathodic corrosion, when the electrode potential is more negative than an onset value (e.g., −0.4 VRHE when using 0.1 M KHCO3). Having alkali cations in the electrolyte is critical for such a process. Consequently, Cu catalysts will inevitably undergo surface reconstructions during a typical process of CO2 reduction reaction, resulting in dynamic catalyst morphologies. While having these reconstructions does not necessarily preclude stable electrocatalytic reactions, they will indeed prohibit long-term selectivity and activity enhancement by controlling the morphology of Cu pre-catalysts. Alternatively, by operating Cu catalysts at less negative potentials in the CO electrochemical reduction, we show that Cu nanocubes can provide a much more stable selectivity advantage over spherical Cu nanoparticles.

Abstract Comprehending the catalyst structural evolution during the electrocatalytic process is crucial for establishing robust structure/performance correlations for future catalysts design. Herein, we interrogate the structural evolution of a promising Cu-Ag oxide catalyst precursor during electrochemical carbon monoxide reduction. By using extensive in situ and ex situ characterization techniques, we reveal that the homogenous oxide precursors undergo a transformation to a bimetallic composite consisting of small Ag nanoparticles enveloped by thin layers of amorphous Cu. We believe that the amorphous Cu layer with undercoordinated nature is responsible for the enhanced catalytic performance of the current catalyst composite. By tuning the Cu/Ag ratio in the oxide precursor, we find that increasing the Ag concentration greatly promotes liquid products formation while suppressing the byproduct hydrogen. CO2/CO co-feeding electrolysis and isotopic labelling experiments suggest that high CO concentrations in the feed favor the formation of multi-carbon products. Overall, we anticipate the insights obtained for Cu-Ag bimetallic systems for CO electroreduction in this study may guide future catalyst design with improved performance.

Abstract We report a breakthrough in the hardware implementation of energy-efficient all-spin synapse and neuron devices for highly scalable integrated neuromorphic circuits. Our work demonstrates the successful execution of all-spin synapse and activation function generator using domain wall-magnetic tunnel junctions. By harnessing the synergistic effects of spin-orbit torque and interfacial Dzyaloshinskii-Moriya interaction in selectively etched spin-orbit coupling layers, we achieve a programmable multi-state synaptic device with high reliability. Our first-principles calculations confirm that the reduced atomic distance between 5d and 3d atoms enhances Dzyaloshinskii-Moriya interaction, leading to stable domain wall pinning. Our experimental results, supported by visualizing energy landscapes and theoretical simulations, validate the proposed mechanism. Furthermore, we demonstrate a spin-neuron with a sigmoidal activation function, enabling high operation frequency up to 20 MHz and low energy consumption of 508 fJ/operation. A neuron circuit design with a compact sigmoidal cell area and low power consumption is also presented, along with corroborated experimental implementation. Our findings highlight the great potential of domain wall-magnetic tunnel junctions in the development of all-spin neuromorphic computing hardware, offering exciting possibilities for energy-efficient and scalable neural network architectures.

Abstract Background Diabetic retinopathy (DR) is the leading cause of blinding eye disease among working adults and is primarily attributed to the excessive proliferation of microvessels, which leads to vitreous hemorrhage and retinal traction, thereby significantly impairing patient vision. NSUN2-mediated RNA m5C methylation is implicated in various diseases, and in this investigation, we focused on elucidating the impact of NSUN2 on the regulation of the expression of the downstream gene MUC1, specifically through RNA m5C methylation, on the progression of DR. Method Utilizing Microarray analysis, we examined patient vitreous fluid to pinpoint potential therapeutic targets for DR. Differential expression of NSUN2 was validated through qRT-PCR, Western blot, and immunofluorescence in human tissue, animal tissue, and cell model of DR. The relationship between NSUN2 and DR was explored in vitro and in vivo through gene knockdown and overexpression. Various techniques, such as MeRIP-qPCR and dot blot, were applied to reveal the downstream targets and mechanism of action of NSUN2. Results The levels of both NSUN2 and RNA m5C methylation were significantly elevated in the DR model. Knockdown of NSUN2 mitigated DR lesion formation both in vitro and in vivo. Mechanistically, NSUN2 promoted MUC1 expression by binding to the RNA m5C reader ALYREF. Knockdown of ALYREF resulted in DR lesion alterations similar to those observed with NSUN2 knockdown. Moreover, MUC1 overexpression successfully reversed a series of DR alterations induced by NSUN2 silencing. Conclusions NSUN2 regulates the expression of MUC1 through ALYREF-mediated RNA m5C methylation, thereby regulating the progression of DR and providing a new option for the treatment of DR in the future.