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Abstract Background The Vesical Imaging-Reporting and Data System (VI-RADS) has demonstrated effectiveness in predicting muscle invasion in bladder cancer before treatment. The urgent need currently is to evaluate the muscle invasion status after neoadjuvant chemotherapy (NAC) for bladder cancer. This study aims to ascertain the accuracy of VI-RADS in detecting muscle invasion post-NAC treatment and assess its diagnostic performance across readers with varying experience levels. Methods In this retrospective study, patients with muscle-invasive bladder cancer who underwent magnetic resonance imaging (MRI) after NAC from September 2015 to September 2018 were included. VI-RADS scores were independently assessed by five radiologists, consisting of three experienced in bladder MRI and two inexperienced radiologists. Comparison of VI-RADS scores was made with postoperative histopathological diagnosis. Receiver operating characteristic curve analysis (ROC) was used for evaluating diagnostic performance, calculating sensitivity, specificity, and area under ROC (AUC)). Interobserver agreement was assessed using the weighted kappa statistic. Results The final analysis included 46 patients (mean age: 61 years ± 9 [standard deviation]; age range: 39–70 years; 42 men). The pooled AUC for predicting muscle invasion was 0.945 (95% confidence interval (CI): 0.893–0.977) for experienced readers, and 0.910 (95% CI: 0.831–0.959) for inexperienced readers, and 0.932 (95% CI: 0.892–0.961) for all readers. At an optimal cut-off value ≥ 4, pooled sensitivity and specificity were 74.1% (range: 66.0–80.9%) and 94.1% (range: 88.6–97.7%) for experienced readers, and 63.9% (range: 59.6–68.1%) and 86.4% (range: 84.1–88.6%) for inexperienced readers. Interobserver agreement ranged from substantial to excellent between all readers (k = 0.79–0.92). Conclusions VI-RADS accurately assesses muscle invasion in bladder cancer patients after NAC and exhibits good diagnostic performance across readers with different experience levels.

Abstract This research aimed to investigate effects of different yeast culture (YC) levels on in vitro fermentation characteristics and bacterial and fungal community under high concentrate diet. A total of 5 groups were included in the experiment: control group without YC (CON), YC1 (0.5% YC proportion of substrate dry matter), YC2 (1%), YC3 (1.5%) and YC4 (2%). After 48 h of fermentation, the incubation fluids and residues were collected to analyze the ruminal fermentation parameters and bacterial and fungal community. Results showed that the ruminal fluid pH of YC2 and YC4 groups was higher (P

Abstract Secondary lung injury after SCI is a major cause of patient mortality, with apoptosis playing a key role. This study aimed to explore the impact of treadmill training and miR145-5p on the MAPK/Erk signaling pathway and apoptosis in rats with complete SCI. SD rats were used to establish T10 segmental complete SCI models and underwent treadmill training 3, 7, or 14 days postinjury. Various techniques including arterial blood gas analysis, lung wet/dry weight ratio, HE staining, immunofluorescence staining, immunohistochemical staining, qRT-PCR, and Western blotting were employed to assess alterations in lung function and the expression levels of crucial apoptosis-related factors. In order to elucidate the specific mechanism, the impact of miR145-5p on the MAPK/Erk pathway and its role in apoptosis in lung cells were confirmed through miR145-5p overexpression and knockdown experiments. Following spinal cord injury (SCI), an increase in apoptosis, activation of the MAPK/Erk pathway, and impairment of lung function were observed in SCI rats. Conversely, treadmill training resulted in a reduction in alveolar cell apoptosis, suppression of the MAPK/Erk pathway, and enhancement of lung function. The gene MAP3K3 was identified as a target of miR145-5p. The influence of miR145-5p on the MAPK/Erk pathway and its impact on apoptosis in alveolar cells were confirmed through the manipulation of miR145-5p expression levels. The upregulation of miR145-5p in spinal cord injury (SCI) rats led to a reduction in MAP3K3 protein expression within lung tissues, thereby inhibiting the MAPK/Erk signaling pathway and decreasing apoptosis. Contrarily, rats with miR145-5p knockdown undergoing treadmill training exhibited an increase in miR145-5p expression levels, resulting in the inhibition of MAP3K3 protein expression in lung tissues, suppression of the MAPK/Erk pathway, and mitigation of lung cell apoptosis. Ultimately, the findings suggest that treadmill training may attenuate apoptosis in lung cells post-spinal cord injury by modulating the MAP3K3 protein through miR145-5p to regulate the MAPK/Erk signaling pathway.

Abstract Biological nitrogen fixation by free-living bacteria and rhizobial symbiosis with legumes plays a key role in sustainable crop production. Here, we study how different crop combinations influence the interaction between peanut plants and their rhizosphere microbiota via metabolite deposition and functional responses of free-living and symbiotic nitrogen-fixing bacteria. Based on a long-term (8 year) diversified cropping field experiment, we find that peanut co-cultured with maize and oilseed rape lead to specific changes in peanut rhizosphere metabolite profiles and bacterial functions and nodulation. Flavonoids and coumarins accumulate due to the activation of phenylpropanoid biosynthesis pathways in peanuts. These changes enhance the growth and nitrogen fixation activity of free-living bacterial isolates, and root nodulation by symbiotic Bradyrhizobium isolates. Peanut plant root metabolites interact with Bradyrhizobium isolates contributing to initiate nodulation. Our findings demonstrate that tailored intercropping could be used to improve soil nitrogen availability through changes in the rhizosphere microbiome and its functions.

Abstract Background Laminin subunit gamma-1 (LAMC1) is a major extracellular matrix molecule involved in the tumor microenvironment. Knowledge of the biological features and clinical relevance of LAMC1 in cancers remains limited. Methods We conducted comprehensive bioinformatics analysis of LAMC1 gene expression and clinical relevance in pan-cancer datasets of public databases and validated LAMC1 expression in glioma tissues and cell lines. The association and regulatory mechanism between hypoxia inducible factor-1α (HIF-1α) and LAMC1 expression were explored. Results LAMC1 expression in most cancers in The Cancer Genome Atlas (TCGA) including glioma was significantly higher than that in normal tissues, which had a poor prognosis and were related to various clinicopathological features. Data from the Chinese Glioma Genome Atlas also showed high expression of LAMC1 in glioma associated with poor prognoses. In clinical glioma tissues, LAMC1 protein was highly expressed and correlated to poor overall survival. LAMC1 knockdown in Hs683 glioma cells attenuated cell proliferation, migration, and invasion, while overexpression of LAMC1 in U251 cells leads to the opposite trend. Most TCGA solid cancers including glioma showed enhancement of HIF-1α expression. High HIF-1α expression leads to adverse prognosis in gliomas, besides, HIF-1α expression was positively related to LAMC1. Mechanistically, HIF-1α directly upregulated LAMC1 promotor activity. Hypoxia (2% O2)-treated Hs683 and U251 cells exhibited upregulated HIF-1α and LAMC1 expression, which was significantly attenuated by HIF-1α inhibitor YC-1 and accompanied by attenuated cell proliferation and invasion. Conclusions High expression of LAMC1 in some solid tumors including gliomas suggests a poor prognosis. The hypoxic microenvironment in gliomas activates the HIF-1α/LAMC1 signaling, thereby promoting tumor progression. Targeted intervention on the HIF-1α/LAMC1 signaling attenuates cell growth and invasion, suggesting a new strategy for glioma treatment.

Abstract The insufficient abundance and weak activity of tumour-infiltrating lymphocytes (TILs) are two important reasons for the poor efficacy of PD-1 inhibitors in hepatocellular carcinoma (HCC) treatment. The combined administration of tanshinone IIA (TSA) and astragaloside IV (As) can up-regulate the abundance and activity of TILs by normalising tumour blood vessels and reducing the levels of immunosuppressive factors respectively. For enhancing the efficacy of PD-1 antibody, a magnetic metal–organic framework (MOF) with a homologous tumour cell membrane (Hm) coating (Hm@TSA/As-MOF) is established to co-deliver TSA&As into the HCC microenvironment. Hm@TSA/As-MOF is a spherical nanoparticle and has a high total drug-loading capacity of 16.13 wt%. The Hm coating and magnetic responsiveness of Hm@TSA/As-MOF provide a homologous-magnetic dual-targeting, which enable Hm@TSA/As-MOF to counteract the interference posed by ascites tumour cells and enhance the precision of targeting solid tumours. Hm coating also enable Hm@TSA/As-MOF to evade immune clearance by macrophages. The release of TSA&As from Hm@TSA/As-MOF can be accelerated by HCC microenvironment, thereby up-regulating the abundance and activity of TILs to synergistic PD-1 antibody against HCC. This study presents a nanoplatform to improve the efficacy of PD-1 inhibitors in HCC, providing a novel approach for anti-tumour immunotherapy in clinical practice.

To explore the dynamic behavior of magnetic abrasive particles in the grinding process of pipe fittings, the grinding process of magnetic abrasive particles was simulated using discrete elements. The changes in motion trajectory and grinding force with the speed of pipe fittings and the processing gap were analyzed. Single abrasive particle ball motion and magnetic particle grinding test were conducted to verify the accuracy of the magnetic field force model and the feasibility of visualizing the particle kinematic behavior. The results show that as the speed of the pipe fittings increases, the magnetic abrasive particles move outside the processing area due to centrifugal force, and the larger the processing gap, the easier they are "thrown away". Before reaching the critical rotation speed, the grinding force decreases, and material removal efficiency increases with the increase in pipe rotation speed. When the pipe rotation speed increases from 400 r/min to the critical rotation speed and the machining gaps are 2 mm and 4 mm, the grinding forces decrease by 5.4 μN and 2.3 μN respectively, leading to a significant improvement in material removal efficiency. However, with a machining gap of 6 mm, the grinding force changes little, and when the rotation speed exceeds the critical rotation speed of 650 r/min, material removal efficiency decreases. Additionally, the material removal amount increases with the increase in pipe rotation speed before reaching the critical rotation speed, but increasing the processing gap reduces the critical rotation speed. The change in material removal amount aligns with the simulation results, validating the reliability of the simulation analysis.

Introduction Apoptosis and chronic inflammation are the main phenotypes in chronic obstructive pulmonary disease (COPD) pathogenesis. Cigarette smoke exposure is the leading risk factor for COPD, which causes aberrant airway epithelial structure and function. As a non-classical calpain, the molecular function of calpain5 (CAPN5) in COPD remains unclear. This study investigated the role of CAPN5 in mediating cigarette smoke extract (CSE)-induced apoptosis and inflammation. Methods Immunohistochemistry (IHC) and Western blotting (WB) were performed to detect the location and expression of CAPN5. In vitro, BEAS-2B cells were transfected with CAPN5 siRNA or CAPN5 plasmid, followed by phosphatebuffered saline (PBS) or cigarette smoke extract (CSE) treatment. The protein expression levels of CAPN5, NF-κB p65, p-p65, IκBα, p-IκBα and apoptosis proteins (BCL-2, BAX) were measured by WB. Flow cytometry (FCM) was performed to analyze the cell apoptosis index. Results CAPN5 was mainly expressed in the airway epithelium and significantly decreased in the COPD-smoker and emphysema-mouse groups. Silencing CAPN5 significantly decreased the protein expression of BCL-2, IκBα, and increased p-p65 and BAX protein expression. Additionally, an increased apoptosis index was detected after silencing CAPN5. Moreover, overexpression of CAPN5 partly inhibited IκBα degradation and p65 activation, and reduced CSE-induced inflammation and apoptosis. Conclusions These combined results indicate that CAPN5 could protect against CSEinduced apoptosis and inflammation, which may provide a potential therapeutic target for smoking-related COPD.

Caffeine contamination in water sources raises concerns about its transfer to agricultural products and potential risks to human health through the food chain. Despite these concerns, limited research has focused on the accumulation and distribution of exogenous caffeine in tea plants. This study explored the uptake, translocation, targeted accumulation, subcellular distribution, and preliminary metabolism of 14C-labeled caffeine in a hydroponic tea seedling system. After 192 h of cultivation, more than 83.8% of the caffeine had been removed from the nutrient solution. Within the plants, 14C-caffeine and its metabolites predominantly accumulated in the roots. Subcellular analysis indicates that in root cells, 14C was mainly distributed in the soluble fraction, cell walls, and plastids, while in shoot cells, it was concentrated in the soluble fraction and cell walls. Metabolic profiling reveals distinct varietal differences: in Longjing 43 tea seedlings, 14C was predominantly present as the caffeine parent compound, whereas in Jiaming No. 1 tea seedlings, 14C was found both as the parent compound and as its metabolite, xanthine. This study revealed differences in the uptake, translocation, and metabolism of exogenous caffeine among different tea plant varieties, providing broader insights into the impact of caffeine pollution on agricultural ecosystems.

Low-orbit satellite communication networks have gradually become the research focus of fifth-generation (5G) beyond and sixth generation (6G) networks due to their advantages of wide coverage, large communication capacity, and low terrain influence. However, the low earth orbit mega satellite network (LEO-MSN) also has difficulty in constructing stable traffic transmission paths, network load imbalance and congestion due to the large scale of network nodes, a highly complex topology, and uneven distribution of traffic flow in time and space. In the service-based architecture proposed by 3GPP, the introduction of service function chain (SFC) constraints exacerbates these challenges. Therefore, in this paper, we propose GDRL-SFCR, an end-to-end routing decision method based on graph neural network (GNN) and deep reinforcement learning (DRL) which jointly optimize the end-to-end transmission delay and network load balancing under SFC constraints. Specifically, this method constructs the system model based on the latest NTN low-orbit satellite network end-to-end transmission architecture, taking into account the SFC constraints, transmission delays, and network node loads in the end-to-end traffic transmission, uses a GNN to extract node attributes and dynamic topology features, and uses the DRL method to design specific reward functions to train the model to learn routing policies that satisfy the SFC constraints. The simulation results demonstrate that, compared with graph theory-based methods and reinforcement learning-based methods, GDRL-SFCR can reduce the end-to-end traffic transmission delay by more than 11.3%, reduce the average network load by more than 14.1%, and increase the traffic access success rate and network capacity by more than 19.1% and two times, respectively.

Long-term geographic isolation and breeding programs both influence population characteristics. Leiqiong cattle, a native breed from the southernmost region of China, are renowned for disease and heat resistance, with two subgroups on Hainan Island and the Leizhou Peninsula. However, the genomic differences between them remain unexplored. In this study, we conducted genomic comparisons using whole-genome sequencing data from the two subgroups of Leiqiong cattle and three commercial breeds to assess their population structures. Leiqiong cattle in Hainan exhibited lower genetic diversity and a pure ancestral content due to their isolation from the mainland. In contrast, the subgroup in Guangdong displayed higher genetic diversity and mixed ancestry, influenced by the intrusion of commercial breeds. The genetic divergence between them was evaluated by estimating a genetic distance of 0.08 and a split time of 3400 to 4250 years ago, highlighting the role of geographical barriers in speciation. Notably, two candidate genes were identified through selection sweeps, including PIP4K2A, potentially related to immunity, and TNFSF4, possibly involved in hair follicle development. Our findings reveal the different genetic structures and genomic characteristics in the two subgroups of Leiqiong cattle, providing valuable insights into their evolutionary history and establishing a foundation for future breeding strategies.

Accurate wind power forecasting is crucial for optimizing grid scheduling and improving wind power utilization. However, real-world wind power time series exhibit dynamic statistical properties, such as changing mean and variance over time, which make it difficult for models to apply observed patterns from the past to the future. Additionally, the execution speed and high computational resource demands of complex prediction models make them difficult to deploy on edge computing nodes such as wind farms. To address these issues, this paper explores the potential of linear models for wind power forecasting and constructs NFLM, a linear, lightweight, short-term wind power forecasting model that is more adapted to the characteristics of wind power data. The model captures both short-term and long-term sequence variations through continuous and interval sampling. To mitigate the interference of dynamic features, we propose a normalization feature learning block (NFLBlock) as the core component of NFLM for processing sequences. This module normalizes input data and uses a stacked multilayer perceptron to extract cross-temporal and cross-dimensional dependencies. Experiments with data from two real wind farms in Guangxi, China, showed that compared with other advanced wind power forecasting methods, the MSE of NFLM in the 24-step ahead forecasting of the two wind farms is respectively reduced by 23.88% and 21.03%, and the floating-point operations (FLOPs) and parameter count only require 36.366 M and 0.59 M, respectively. The results show that NFLM can achieve good prediction accuracy with fewer computing resources.

The treatment of black tea fermentation with different exogenous tannases was investigated, and processing parameters during black tea fermentation, including fermentation time, fermentation temperature, and exoenzyme amounts, were optimized, while the consumption and transformation pathways of catechins were analyzed. The results showed that tannase from Aspergillus niger was ultimately selected as the optimal enzyme to effectively increase the content of theaflavins by promoting the hydrolysis reaction and benzoylation reaction of catechins, resulting in a greater theaflavin (TF) content of 1.41%. The optimal processing conditions were found to be a fermentation time of 3 h, a fermentation temperature of 20 °C, and 1 g of tannase for 300 g of rolled tea leaves. Processing with the exogenous tannase could provide an ideal choice for the efficient utilization of summer and autumn fresh tea leaves, and could be used to develop summer and autumn black tea and to improve the content of theaflavins. It could also be used to develop deep processing of tea products with theaflavin extracts in the future.

Endophytic bacteria are an important source for developing antimicrobial substances. With the aim to find eco-friendly antimicrobial agents from natural sources, Streptomyces sp. R6 was isolated from Azadirachta indica. After that, a new spirotetronate natural product, lobophorin S (compound 2), together with lobophorin H8 (compound 1) and a known macrolide compound divergolide C (compound 3) were isolated from the cultural solution of strain R6. These compounds mark the first isolation of marine-derived microbial natural products known as lobophorins (LOBs) from endophytic bacteria. The structures of these three compounds were identified by extensive NMR and HRMS analyses. The antimicrobial activities of these three compounds against eight fungal and four bacterial phytopathogens were separately evaluated. Compound 1 demonstrated better antibacterial activity against Erwinia carotovora, Pseudomonas syringae pv. tomato, and P. syringae pv. lachrymans with MIC values of 3.91, 7.81, and 15.63 μg/mL, respectively. Additionally, compounds 1–3 all showed antifungal activity against Botrytis cinerea, with the MIC values of 1.95, 7.81, and 15.63 μg/mL, respectively. Notably, the in vivo antifungal effect of 1 against B. cinerea was up to 78.51 ± 3.80% at 1.95 µg/mL, significantly surpassing polyoxin B (70.70 ± 3.81%). These results highlight the potential of lobophorins as promising lead compounds for the development of new, sustainable agents to control plant diseases.

The spectral vegetation indices derived from remote sensing data provide a detailed spectral analysis for assessing vegetation characteristics. This study investigated the relationship between cotton yield and canopy spectral indices to develop yield estimation models. Spectral reflectance data were collected at various growth stages using an ASD FieldSpec Pro VNIR 2500 spectrometer. Six prediction models were developed using spectral vegetation indices, including the Normalized Difference Vegetation Index (NDVI) and Ratio Vegetation Index (RVI), to estimate the Leaf Area Index (LAI) and above-ground biomass. For LAI estimation using the NDVI, the power function model (y = 10.083x11.298) demonstrated higher precision, with a multiple correlation coefficient of R2 = 0.8184 and the smallest root mean square error (RMSE = 0.3613). These results confirm the strong predictive capacity of NDVI for LAI, with the power function model offering the best estimation accuracy. In estimating above-ground biomass using RVI, the power function model of y = 6.5218x1.33917 achieved the higher correlation (R2 = 0.8851) for fresh biomass with an RMSE of 0.1033, making it the most accurate. For dry biomass, the exponential function model (y = 9.1565 × 10−5∙exp(1.1146x)) was the most precise, achieving an R2 value of 0.8456 and the lowest RMSE value of 0.0076. These findings highlight the potential of spectral remote sensing for accurately predicting cotton canopy structural parameters and biomass weights. By integrating spectral analysis techniques with remote sensing, this research offers valuable insights for precision cotton planting and field management, enabling optimized agricultural practices and enhanced vegetation health monitoring.

Over the past decade, return freight insurance (RFI) and return pickup services (RPSs) have emerged as dominant return service strategies in e-commerce, particularly in China’s competitive online retail market. Despite their prominence, the strategic dynamics guiding e-sellers’ choice between these services remain underexplored. This study develops a game-theoretic model to analyze the equilibrium return strategies of two horizontally competing e-sellers with varying misfit probabilities. By examining four subgames, we identify the conditions under which e-sellers converge on either RFI or RPSs. Our findings revealed that highly similar or highly differentiated products typically favor RFI due to intense price competition or reduced need for service-based competition, while moderately differentiated products lead to RPS adoption as service quality becomes a key competitive lever. Additionally, competitive pressure often drives e-sellers to adopt homogenized return strategies, particularly RPSs, to maintain market position. The equilibrium outcomes are shaped by misfit probability differences, consumer hassle costs, and cost structures, offering actionable insights into optimizing return strategies in competitive e-commerce environments. These findings provide actionable insights into optimizing return service strategies in competitive e-commerce environments and contribute to the growing literature on return policies as a competitive lever in online retail markets.

ε-poly-l-lysine (ε-PL), a natural food preservative, has garnered widespread attention. It is mainly produced by Streptomyces albulus, but the production by wild-type strains fails to meet the demands of industrialization. To address this issue, adaptive laboratory evolution (ALE) was successfully employed in this study, subjecting S. albulus CICC 11022 to environmental stresses such as acidic pH and antibiotics (rifampicin, gentamicin, and streptomycin). As a result of ALE, an evolutionary strain S. albulus C214 was obtained, exhibiting an increase in ε-PL production and cell growth by 153.23% and 234.51%, respectively, as compared with the original strain. Genomic and metabolic analyses revealed that mutations occurred in genes responsible for transcriptional regulation, transporter, cell envelope, energy metabolism, and secondary metabolite synthesis, as well as the enrichment of metabolites involved in the biosynthesis of ε-PL. These findings hold great significance for elucidating the mechanism underlying ε-PL synthesis.

To enhance emergency management and public opinion governance, improve the accuracy of forecasting group emotional responses, and elucidate the complex pathways of multi-factor coupling in the formation of group emotions, this study constructs a theoretical framework grounded in the social combustion theory. Through web scraping and text sentiment analysis, group emotional tendencies were measured in 40 public emergency cases from the past five years. Using the fuzzy-set qualitative comparative analysis (fsQCA) method, the study explored the coupling, configuration effect, and formation pathways of factors such as “burning substance”, “accelerant”, and “ignition” in the emergence of group emotions. The results reveal significant differences in the generation pathways of positive versus negative group emotion. Inter-group threat as a “burning substance” is more likely to trigger negative group emotion, while “accelerant” plays a pivotal role in shaping and guiding emotional responses. Notably, the government’s response speed is critical for fostering positive emotions, whereas the emergence of rumors significantly contributes to the spread of negative group emotions. Additionally, the occurrence of stimulating events markedly increases the generation of negative group emotions. This study provides an important theoretical foundation and practical insights for the management and regulation of group emotions.

Background: With distal transradial access (dTRA), the postoperative compression time remains significantly longer than the recommended range via in practice. This study investigated whether intravenous protamine sulfate might shorten the postoperative compression time and increase safety after coronary angiography via dTRA. Methods: In this retrospective study, patients who underwent coronary angiography were enrolled and divided into two groups. The study group received a slow intravenous injection of 15–20 mg protamine sulfate before sheath retraction. The primary endpoint was the puncture compression time after coronary angiography. Results: A total of 97 patients in the protamine group and 293 in the control group were enrolled. Intraoperative heparin use, contrast dose, angiography duration, and radiation dose did not differ significantly between groups. The mean compression time in the control group was 2.9 ± 0.5 hours, whereas that in the protamine group was 1.6 ± 0.9 hours (P < 0.001). No significant difference was observed in postoperative minor or major hemorrhage or hematoma between groups. Ultrasound 24 hours after angiography indicated an incidence of radial artery thrombosis of 1.1% in the control group and 4.3% in the protamine treatment group, with no statistically significant difference between groups (P = 0.209), and no radial artery occlusion in either group. Logistic regression suggested that radial artery thrombosis was associated with intraoperative heparin dose and a history of chronic kidney disease. Conclusion: Intravenous application of protamine after coronary angiography via dTRA can significantly shorten the time of postoperative compression hemostasis and has good performance in terms of safety.

Significal challenges exist to bacterial infection wound healing. The bacterial infection and inflammation generated by oxidative stress inevitably hinder the process of wound healing. Ag6Cu2 nanoclusters in this study were successfully prepared and displayed excellent physiological stability. Noticeably, Ag6Cu2 nanoclusters exhibited efficient therapeutic potentials for accelerating the process of wound healing, which had good biosafety under the appropriate concentration. The treatment of Ag6Cu2 was able to suppress the bacterial proliferation by destructing the bacterial, resulting in the secondary release of bacterial contents and to exert anti-inflammatory properties via scavenging the overproduction of reactive oxygen species and upregulating the expression of Nrf2 as well as its downstream genes including HO-1 and NQO1. In-vivo studies further validated the efficient therapeutic effects of Ag6Cu2 nanoclusters by inhibiting the activation of the cascade of inflammatory factors and the proliferation of bacteria as a novel agent in a nano scale for accelerating the process of wound healing.

ObjectiveCopy number changes at Chromosomal 16p13.11 have been implicated in a variety of human diseases including congenital cardiac abnormalities. The clinical correlation of copy number variants (CNVs) in this region with developmental abnormalities remains controversial as most of the patients inherit the duplication from an unaffected parent.MethodsWe performed CNV analysis on 164 patients with defective left-right (LR) patterning based on whole genome-exome sequencing (WG-ES) followed by multiplex ligation-dependent probe amplification (MLPA) validation. Most cases were accompanied with complex congenital heart disease (CHD).ResultsCNVs at 16p13.11 were identified in a total of 21 cases, accounting for 12.80% (21/164) evaluated cases. We observed a marked overrepresentation of chromosome 16p13.11 duplications in cases when compared with healthy controls according to literature reports (15/164, 9.14% versus 0.09% in controls). Notably, in two independent family trios, de novo 16p13.11 micro-duplications were identified in two patients with laterality defects and CHD. Moreover, 16p13.11 micro-duplication was segregated with the disease in a family trio containing 2 affected individuals. Notably, five coding genes, NOMO1, PKD1P3, NPIPA1, PDXDC1, and NTAN1, were potentially affected by micro-CNV at 16p13.11 in these patients.ConclusionOur study provides new family-trio based evidences to support 16p13.11 micro-duplications predispose individuals to defective cardiac left-right patterning and laterality disorder.

In this study, the storm surge processes and characteristics of Tide-Surge Interactions (TSI) induced by the sequential tropical cyclones (TCs) BARIJAT and MANGKHUT (2018) in the Northern South China Sea (NSCS) are investigated using the numerical model. By comparing the impacts of the two TCs, we find that storm surges are significantly influenced by multiple factors. Notably, bays situated on the western side of the cyclone’s landfall point exhibit a double peak pattern in storm surge. In addition, TSI exhibits a pronounced impact across bays affected by the two TCs, with amplitude fluctuations ranging from -0.3 to 0.3 meters and contributing approximately -5% to -20% to the peaks of storm surge. Comparative analysis of TSI variations reveals that tides act as the primary determinant, significantly influencing both the magnitude and period of TSI. Dynamic analysis further highlights that variations in TSI are dominated by barotropic pressure gradient and bottom friction stress. Moreover, TSI affects the frequency of storm surges, introducing high-frequency tidal signals to storm surges and reducing the frequency of storm surges.

BackgroundThe global status of chronic kidney disease (CKD) is underestimated, particularly the burden on adolescents and young adults (early-onset, aged 15–39).ObjectiveWe aim to investigate the pattern and trend of early-onset CKD from 1990 to 2019.MethodsWe analyzed age-specific rates of early-onset CKD incidence, death, and disability-adjusted life years (DALY) using Global Burden of Disease Study 2019 data. We examined the global, regional, national, gender-based, age group-based, and temporal changes of early-onset CKD burden from 1990 to 2019, as well as proportional DALY attributions of various risk factors.ResultsFrom 1990 to 2019, the global age-specific incidence rate (per 100,000 population) significantly increased from 25.04 (95% confidence interval 18.51, 31.65) to 32.21 (23.73, 40.81) for early-onset CKD. However, the global age-specific death rate significantly decreased from 2.96 (2.76, 3.15) to 2.86 (2.61, 3.11), and the age-specific DALY rate remained stable. Regarding sociodemographic indexes (SDI), countries with middle SDI had the highest incidence rates and the fastest increasing trends, while those with low and low-middle SDI experienced the highest death and DALY rates. Women had a generally higher age-specific incidence rate than men, whereas men showed higher age-specific death and DALY rates. In addition, the burdens of CKD increased with age among adolescents and young adults. Moreover, the main attributable risk factors for DALY of early-onset CKD were high systolic blood pressure (SBP), fasting plasma glucose (FPG), and body mass index (BMI).ConclusionThe age-specific incidence rate of early-onset CKD increased significantly from 1990 to 2019, and the age-specific DALY rate remained stable. High SBP, high FPG, and high BMI were the primary risk factors. Targeted prevention and healthcare measures should be developed considering age, gender, and region.

Abstract Statins, the first‐line medication for dyslipidemia, are linked to an increased risk of type 2 diabetes. But exactly how statins cause diabetes is yet unknown. In this study, a developed short‐term statin therapy on hyperlipidemia mice show that hepatic insulin resistance is a cause of statin‐induced diabetes. Statin medication raises the expression of progesterone and adiponectin receptor 9 (PAQR9) in liver, which inhibits insulin signaling through degradation of protein phosphatase, Mg2+/Mn2+ dependent 1 (PPM1α) to activate ERK pathway. STIP1 homology and U‐box containing protein 1 (STUB1) is found to mediate ubiquitination of PPM1α promoted by PAQR9. On the other hand, decreased activity of hepatocyte nuclear factor 4 alpha (HNF4α) seems to be the cause of PAQR9 expression under statin therapy. The interventions on PAQR9, including deletion of PAQR9, caloric restriction and HNF4α activation, are all effective treatments for statin‐induced diabetes, while liver specific over‐expression of PPM1α is another possible tactic. The results reveal the importance of HNF4α‐PAQR9‐STUB1‐PPM1α axis in controlling the statin‐induced hepatic insulin resistance, offering a fresh insight into the molecular mechanisms underlying statin therapy.

Anti-tubular basement membrane (anti-TBM) antibody nephritis is a rare type of tubulointerstitial nephritis associated with progressive decline in kidney function. It is characterized histopathologically by tubular atrophy and dilation, interstitial fibrosis, lymphocyte and macrophage-predominant cellular infiltration, and linear deposition of IgG and complement along the tubular basement membrane. We herein present a case of a 69-year-old male who was recently diagnosed with chronic lymphocytic leukemia (CLL) and was referred for evaluation of kidney failure, ultimately diagnosed as anti-TBM antibody nephritis progressing into end-stage kidney disease (ESKD). This case report highlights the management challenges of anti-TBM antibody nephritis as a rare kidney disorder.

Metagenomic shotgun sequencing data can identify microbes and their proportions. But metagenomic shotgun data profiling results obtained from multiple projects using different reference databases are difficult to compare and apply meta-analysis. Our work aims to create a novel collection of human gut prokaryotic genomes, named Microbiome Collection Navigator (MBCN). 2379 human gut metagenomic samples are screened, and 16,785 metagenome-assembled genomes (MAGs) are assembled using a standardized pipeline. In addition, MAGs are combined with the representative genomes from public prokaryotic genomes collections to cluster, and pan-genomes for each cluster's genomes are constructed to build Kraken2 and Bracken databases. The databases built by MBCN are more comprehensive and accurate for profiling metagenomic reads comparing with other collections on simulated reads and virtual bio-projects. We profile 1082 human gut metagenomic samples with MBCN database and organize profiles and metadata on the web program. Meanwhile, using MBCN as a reference database, we also develop a unified, standardized, and systematic metagenomic analysis pipeline and platform, named MicrobiotaCN (http://www.microbiota.cn) and common statistical and visualization tools for microbiome research are integrated into the web program. Taken together, MBCN and MicrobiotaCN can be a valuable resource and a powerful tool that allows researchers to perform metagenomic analysis by a unified pipeline efficiently.

Background: Premature ovarian insufficiency (POI), a modifiable cause of infertility with substantial implications for women's well-being, prompts the exploration of efficacious adjunctive treatments. Acupuncture emerges as a promising therapeutic avenue; however, the nuanced effects of acupuncture in POI warrant more comprehensive investigation. The intricate mechanisms dictating individualized responses remain elusive. This trial seeks to assess the effectiveness of acupuncture as an adjunctive treatment for POI, concurrently delving into the impact of transcriptome analysis on peripheral blood to unravel the underpinnings of these individual variations. The overarching objective is to enrich our comprehension of acupuncture's therapeutic potential in the context of POI, with a view to advancing holistic patient care. Methods/design: Constituting an open-label, nested case-control study, this research endeavors to enroll 108 women diagnosed with POI. Participants will be randomly assigned in a 1:1 ratio to either the study group or the control group, each comprising 54 subjects. Ten patients from each group meeting specific criteria will partake in transcriptome analysis. An additional 10 subjects meeting the study criteria will form a healthy control group. The study group will exclusively undergo acupuncture treatment, while the control group will solely receive Fenmutong. Acupuncture sessions, administered thrice weekly across three menstrual cycles from the fifth day of menstruation, constitute the intervention. Primary outcome measurement rests on Follicle-Stimulating Hormone (FSH) levels, supplemented by secondary assessments encompassing biometric features, hormone biomarkers, anxiety and depression scores, and transcriptome analysis. Baseline measurements precede intervention, with post-intervention evaluations following. The study endeavors to discern specific genes linked to individualized responses to acupuncture. Data analysis, employing SPSS 25.0 software, incorporates a meticulous examination of peripheral blood samples for transcriptome analysis. The investigation aspires to shed light on genetic determinants influencing the effects of acupuncture on women with POI, thereby fostering elevated standards in patient care and management. Discussion: This study pivots on the principal objective of scrutinizing the efficacy of acupuncture as an adjunctive treatment for POI. Beyond effectiveness, it undertakes an exploration of the intricate mechanisms underlying the diverse responses exhibited by individuals in the context of acupuncture, augmenting the depth of understanding in this therapeutic domain.

Hippophae tibetana, belonging to the Elaeagnaceae family, is an endemic plant species of the Qinghai–Tibet Plateau, valued for its remarkable ecological restoration capabilities, as well as medicinal and edible properties. Despite being acknowledged as a useful species, its mitochondrial genome data and those of other species of the Elaeagnaceae family are lacking to date. In this study, we, for the first time, successfully assembled the mitochondrial genome of H. tibetana, which is 464,208 bp long and comprises 31 tRNA genes, 3 rRNA genes, 37 protein-coding genes, and 3 pseudogenes. Analysis of the genome revealed a high copy number of the trnM-CAT gene and a high prevalence of repetitive sequences, both of which likely contribute to genome rearrangement and adaptive evolution. Through nucleotide diversity and codon usage bias analyses, we identified specific genes that are crucial for adaptation to high-altitude conditions. Notably, genes such as atp6, ccmB, nad4L, and nad7 exhibited signs of positive selection, indicating the presence of unique adaptive traits for survival in extreme environments. Phylogenetic analysis confirmed the close relationship between the Elaeagnaceae family and other related families, whereas intergenomic sequence transfer analysis revealed a substantial presence of homologous fragments among the mitochondrial, chloroplast, and whole genomes, which may be linked to the high-altitude adaptation mechanisms of H. tibetana. The findings of this study not only enrich our knowledge of H. tibetana molecular biology but also advance our understanding of the adaptive evolution of plants on the Qinghai–Tibet Plateau. This study provides a solid scientific foundation for the molecular breeding, conservation, and utilization of H. tibetana genetic resources.

ObjectiveThis systematic review and meta-analysis aimed to investigate the association between circulating irisin levels and osteoporosis in women, exploring irisin’s potential role in the pathophysiology and management of osteoporosis.MethodWe searched PubMed, Embase, Web of Science, Cochrane Library, CNKI, WanFang, and VIP databases up to January 2023. The inclusion criteria were observational studies reporting on circulating irisin levels in women. The standardized mean difference (SMD) and correlation coefficients with a 95% confidence interval (CI) were used as the main effect measures under a random-effects model. Heterogeneity was evaluated using the Cochrane Q statistic and the I2 statistics. Subgroup analysis and univariate meta-regression analysis were performed to identify the sources of heterogeneity. The quality of the included study was assessed by the Newcastle-Ottawa Score. The quality of evidence was evaluated using the GRADE system. Publication bias was assessed using Begg’s and Egger’s test, and the trim-and-fill method. Sensitivity analysis was performed to assess the stability of the results.ResultsFifteen studies with a total of 2856 participants met the criteria. The analysis showed significantly lower irisin levels in postmenopausal osteoporotic women compared to non-osteoporotic controls (SMD = -1.66, 95% CI: -2.43 to -0.89, P < 0.0001; I2 = 98%, P < 0.00001) and in postmenopausal individuals with osteoporotic fractures than in non-fractures controls (SMD = -1.25, 95% CI: -2.15 to -0.34, P = 0.007; I2 = 97%, P < 0.00001). Correlation analysis revealed that irisin levels positively correlated with lumbar spine BMD (r = 0.37, 95% CI: 0.18 to 0.54), femoral BMD (r = 0.30, 95% CI: 0.18 to 0.42), and femoral neck BMD (r = 0.31, 95% CI: 0.14 to 0.47) in women. Despite significant heterogeneity, the robustness of the results was supported by using the random effects model and sensitivity analysis.ConclusionThe current evidence suggests that lower irisin levels are significantly associated with osteoporosis and fracture in postmenopausal women, suggesting its utility as a potential biomarker for early detection of osteoporosis and therapeutic target. However, further high-quality prospective research controlling for confounding factors is needed to clarify the relationship between irisin levels and osteoporotic outcomes.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42023410264.

For patients with disorders of consciousness (DoC), accurate assessment of residual consciousness levels and cognitive abilities is critical for developing appropriate rehabilitation interventions. In this study, we investigated the potential of electrooculography (EOG) in assessing language processing abilities and consciousness levels. Patients’ EOG data and related electrophysiological data were analysed before and after explicit language learning. The results showed distinct differences in vocabulary learning patterns among patients with varying levels of consciousness. While minimally conscious patients showed significant neural tracking of artificial words and notable learning effects similar to those observed in healthy controls, whereas patients with unresponsive wakefulness syndrome did not show such effects. Correlation analysis further indicated that EOG detected vocabulary learning effects with comparable validity to electroencephalography, reinforcing the credibility of EOG indicator as a diagnostic tool. Critically, EOG also revealed significant correlations between individual patients’ linguistic learning performance and their Oromotor/verbal function as assessed through behavioural scales. In conclusion, this study explored the differences in language processing abilities among patients with varying consciousness levels. By demonstrating the utility of EOG in evaluating consciousness and detecting vocabulary learning effects, as well as its potential to guide personalised rehabilitation, our findings indicate that EOG indicators show promise as a rapid, accurate and effective additional tool for diagnosing and managing patients with DoC.

Neurodegenerative disorders are chronic conditions that progressively damage and destroy parts of the nervous system, and are currently considered permanent and incurable. Alternative strategies capable of effectively healing neuronal damage have been actively pursued. Here, we report the neuroprotective effects of baicalin (BA) combined with plasma-activated medium (PAM) against glutamate-induced excitotoxicity in SH-SY5Y cells. Through in vitro assays, the cell viability, inflammation, apoptosis, and oxidative stress were evaluated. The co-application of BA and PAM significantly enhanced cell viability, reduced pro-inflammatory markers (TNF-α and NF-κB), decreased apoptotic proteins (Bax and Caspase-3) and boosted antioxidative defenses (increased SOD activity and lowered ROS levels). This study confirms the potential of combining BA with PAM as an effective therapeutic strategy for mitigating the effects of excitotoxicity. PAM is a promising adjunct and potential drug delivery method in neuroprotective therapy, providing a new avenue for developing treatments for diseases characterized by neuronal damage.

Introduction: Esophageal cancer is increasingly recognized as a significant global malignancy. The main pathological subtype of this cancer is esophageal squamous cell carcinoma (ESCC), which displays a higher degree of malignancy and a poorer prognosis. Reactive oxygen species (ROS) play a critical role in modulating the immune response to tumors, and understanding the regulation of ROS in ESCC could lead to novel and improved therapeutic strategies for ESCC patients. Methods: A consensus matrix derived from genes involved in the ROS pathway revealed two subtypes of ROS. These subtypes were categorized as ROS-active or ROS-suppressive based on their level of ROS activity. The heterogeneity among the different ROS subtypes was then explored from various perspectives, including gene function, immune response, genomic stability, and immunotherapy. In order to assess the prognosis and the potential benefits of immunotherapy, a ROS activity score (RAS) was developed using the identified ROS subtypes. In vitro experiments were performed to confirm the impact of core RAS genes on the proliferative activity of esophageal cancer cell lines. Results: Two distinctive subtypes of ROS were identified. The first subtype, referred to as ROS-active, exhibited elevated ROS activity, enhanced involvement in cancer-associated immune pathways, and increased infiltration of effector immune cells. The second subtype, named ROS-suppressive, demonstrated weaker ROS activity but displayed more pronounced dysregulation in the cell cycle and a denser extracellular matrix, indicating malignant characteristics. Genomic stability, particularly in terms of copy number variation (CNV) events, differed between the two ROS subtypes. By developing a RAS model, reliable risk assessment for overall survival (OS) in patients with ESCC was achieved, and the model demonstrated strong predictive capabilities in real-world immunotherapy cohorts. Moreover, the core gene LDLRAD1 within the RAS model was found to enhance proliferative activity in esophageal cancer cell lines. Conclusion: Based on the ROS pathway, we successfully identified two distinct subtypes in ESCC: the ROS-active subtype and the ROS-suppressive subtype. These subtypes were utilized to evaluate prognosis and the sensitivity to immunotherapy.

Abstract Background The triglyceride–glucose (TyG) index and high‐sensitivity C‐reactive protein (hsCRP) are the commonly used biomarkers for insulin resistance and systemic inflammation, respectively. We aimed to investigate the combined association of TyG and hsCRP with the major adverse cardiovascular events (MACE) in patients with chronic coronary syndrome (CCS). Methods A total of 9421 patients with CCS were included in this study. The primary endpoint was defined as a composite of MACE covering all‐cause death, nonfatal myocardial infarction, and revascularization. Results During the 2‐year follow‐up period, 660 (7.0%) cases of MACE were recorded. Participants were divided equally into three groups according to TyG levels. Compared with the TyG T1 group, the risk of MACE was significantly higher in the TyG T3 group. It is noteworthy that among patients in the highest tertile of TyG, hsCRP >3 mg/L was significantly associated with an increased risk of MACE, whereas the results were not significant in the medium to low TyG groups. When patients were divided into six groups according to hsCRP and TyG, the Cox regression analysis showed that patients in the TyG T3 and hsCRP >3 mg/L group had a significantly higher risk of MACE than those in the TyG T1 and hsCRP ≤3 mg/L group. However, no significant interaction was found between TyG and hsCRP on the risk of MACE. Conclusion Our study suggests that the concurrent assessment of TyG and hsCRP may be valuable in identifying high‐risk populations and guiding management strategies among CCS patients.

Objective: To investigate whether an early comprehensive pulmonary rehabilitation intervention initiated during hospital admission is safe and effective for patients with acute exacerbation of chronic obstructive pulmonary disease. Design: Prospective randomized controlled study. Subjects/Patients: Patients with acute exacerbation of chronic obstructive pulmonary disease. Methods: In total, 108 patients were randomized to the early comprehensive pulmonary rehabilitation and usual care groups within 48 hours. The 6-min walking distance, quality of life, breathlessness, and inspiratory muscle strength were measured on admission and discharge. Any adverse events of pulmonary rehabilitation were recorded. Results: On discharge, the patients in the early comprehensive pulmonary rehabilitation group had a more significant improvement in the 6-min walking distance (47.5 vs 23.0, p = 0.04). There was no significant difference in quality of life and breathlessness between the 2 groups. In the early comprehensive pulmonary rehabilitation group, inspiratory muscle strength and peak inspiratory flow were significantly improved, and the changes were much more pronounced than in the usual care group. There were no adverse events. Conclusion: Early comprehensive pulmonary rehabilitation is safe and effective for hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease, and should be performed during the early stage of hospitalization.

Abstract The physiological interactions between the peripheral and central auditory systems are crucial for auditory information transmission and perception, while reliable models for auditory neural circuits are currently lacking. To address this issue, mouse and human neural pathways are generated by utilizing a carbon nanotube nanofiber system. The super‐aligned pattern of the scaffold renders the axons of the bipolar and multipolar neurons extending in a parallel direction. In addition, the electrical conductivity of the scaffold maintains the electrophysiological activity of the primary mouse auditory neurons. The mouse and human primary neurons from peripheral and central auditory units in the system are then co‐cultured and showed that the two kinds of neurons form synaptic connections. Moreover, neural progenitor cells of the cochlea and auditory cortex are derived from human embryos to generate region‐specific organoids and these organoids are assembled in the nanofiber‐combined 3D system. Using optogenetic stimulation, calcium imaging, and electrophysiological recording, it is revealed that functional synaptic connections are formed between peripheral neurons and central neurons, as evidenced by calcium spiking and postsynaptic currents. The auditory circuit model will enable the study of the auditory neural pathway and advance the search for treatment strategies for disorders of neuronal connectivity in sensorineural hearing loss.

Background: This study aimed to explore the longitudinal associations of rumination with suicidal ideation and suicide attempts in individuals with major depressive disorder (MDD). Methods: Participants were derived from the Depression Cohort in China study (DCC). Those who completed at least one follow-up visit during the 12 months were included in the analysis. Dimensions of rumination including brooding and reflection were each measured using five items of the Ruminative Responses Scale. Suicidal ideation was assessed using the Beck Scale for Suicide Ideation. Suicide attempts were also assessed and all were analyzed with generalized estimating equations. Results: Our final sample included 532 participants aged 18 to 59 years (mean [SD], 26.91 [6.94] years) consisting of 148 (27.8%) males and 384 (72.2%) females. After adjusting for temporal trend and potential confounders, individuals with higher levels of reflection were more likely to report suicidal ideation (AOR =1.11, 95% CI:1.01–1.22). However, no statistically significant association was found between brooding and suicidal ideation (AOR =1.06, 95% CI:0.96–1.17). Conversely, individuals with higher levels of brooding were more likely to report suicide attempts (AOR =1.13, 95% CI:1.02–1.24), while no statistically significant association was observed between reflection and suicide attempts (AOR =0.91, 95% CI:0.82–1.01). Conclusion: Rumination reflects a disturbance in cognitive emotional processing and manifests in different dimensions. Our findings suggest that high levels of reflection and brooding may be associated with a higher likelihood of having suicidal ideation and suicide attempts, respectively. However, it should be interpreted with caution, given that effect sizes are small.

In order to investigate the shear behavior of coral aggregate reinforced concrete beam (CARCB), the different concrete strength, steel types affect the shear behavior of CARCB was studied, the calculation formula of shear capacity (Vcs) and numerical analysis model of CARCB was proposed. The results show that: All kinds of CARCB have inclined section suitable reinforcement failure, the failure law of CARCB and ordinary aggregate reinforced concrete beam (OARCB) was basically the same. Considering stirrups corrosion and nonlinear mechanical properties characteristic of coral aggregate concrete (CAC), the Vcs calculation formula of CARCB was proposed, and its applicability in C25 ∼ C60 CARCB was verified, its accuracy was 26% and 34% higher than GB50010–2020 and JGJ/T 12–2019, respectively. A numerical analysis model suitable for describing the shear behavior of CARCB was proposed based on K&C (Karagozian & Case) theory, and its applicability in C25 ∼ C60 CARCB was verified, it was found that this model can well describe the whole process of CARCB inclined section failure, and the errors between simulated and measured values of Vcr, Vcs and midspan deflection are 0∼18%. In addition, the Vcs obtained by the numerical model is 3% more accurate than the calculation formula, indicating that the numerical model can effectively distinguish the variation law of shear behavior of CARCB.

Decabromodiphenyl ether (BDE-209) is an organic compound that is widely used in rubber, textile, electronics, plastics and other industries. It has been found that BDE-209 has a destructive effect on the reproductive system of mammals. However, the effect of BDE-209 exposure on oocyte quality and whether there is a viable salvage strategy have not been reported. Here, we report that murine oocytes exposed to BDE-209 produce a series of meiostic defects, including increased fragmentation rates and decreased PBE. Furthermore, exposure of oocytes to BDE-209 hinders mitochondrial function and disrupts mitochondrial integrity. Our observations show that supplementation with NMN successfully alleviated the meiosis impairment caused by BDE-209 and averted oocyte apoptosis by suppressing ROS generation. In conclusion, our findings suggest that NMN supplementation may be able to alleviate the oocyte quality impairment induced by BDE-209 exposure, providing a potential strategy for protecting oocytes from environmental pollutant exposure.

BackgroundInflammatory scores are known to reflect the systemic inflammatory burden. Despite this, the association between the inflammatory score and the risk of all-cause and cardiovascular mortality in patients with metabolic syndrome (MetS) remains poorly understood. To address this gap in the literature, this study investigated this potential association between these two factors.MethodsA total of 3401 patients with MetS from the National Health and Nutrition Examination Survey (1999–2010) were enrolled. Survival status and cause of death were obtained by linking data from the National Death Index (NDI). The inflammatory score was calculated based on the sum of the Z-scores for white blood cell (WBC) count and C-reactive protein (CRP) at baseline. The patients were divided into inflammatory score quartiles. Cox proportional hazards regression was used to determine the association between inflammatory score and mortality. Restricted cubic splines (RCS) were used to explore the dose-response relationship between inflammatory score and mortality. Stratified analyses and interaction tests were conducted according to sex, age, body mass index (BMI), alcohol consumption, smoking status, hypertension, diabetes, and stroke status.ResultsAfter a mean follow-up of 145.9 months, 1039 all-cause deaths and 295 cardiovascular deaths were recorded. The results of multivariate Cox regression analysis showed that compared to the lowest quartile (Q1), patients in the highest quartile (Q4) had a 1.74-fold increased risk of all-cause mortality (Model 3: HR = 1.74, 95%CI 1.30–2.32, P < 0.001) and a 1.87-fold increased risk of cardiovascular mortality (Model 3: HR = 1.87, 95%CI 1.12–3.13, P = 0.020). There was a ‘J’-shaped nonlinear relationship between the inflammatory score and all-cause mortality (P for nonlinearity = 0.001), and a marginally significant ‘J’-shaped relationship with cardiovascular mortality (P for nonlinearity = 0.057). The threshold points of the inflammatory score for adverse outcomes were - 0.643 and - 0.621, respectively.ConclusionThe inflammatory score is independently associated with increased all-cause and cardiovascular mortality in patients with MetS, and risk stratification of these patients using inflammatory scores may provide specific therapeutic strategies to improve their prognosis.

All-trans retinoic acid (ATRA) plays a role in tissue development, neural function, reproduction, vision, cell growth and differentiation, tumor immunity, and apoptosis. ATRA can act by inducing autophagic signaling, angiogenesis, cell differentiation, apoptosis, and immune function. In the blood system ATRA was first used with great success in acute promyelocytic leukemia (APL), where ATRA differentiated leukemia cells into mature granulocytes. ATRA can play a role not only in APL, but may also play a role in other hematologic diseases such as immune thrombocytopenia (ITP), myelodysplastic syndromes (MDS), non-APL acute myeloid leukemia (AML), aplastic anemia (AA), multiple myeloma (MM), etc., especially by regulating mesenchymal stem cells and regulatory T cells for the treatment of ITP. ATRA can also increase the expression of CD38 expressed by tumor cells, thus improving the efficacy of daratumumab and CD38-CART. In this review, we focus on the mechanism of action of ATRA, its role in various hematologic diseases, drug combinations, and ongoing clinical trials.

Background: Patient-ventilator asynchrony (PVA) frequently occurs in mechanically ventilated patients within the ICU and has the potential for harm. Depending solely on the health care team cannot accurately and promptly identify PVA. To address this issue, our team has developed a cloud-based platform for monitoring mechanical ventilation (MV), comprising the PVA-RemoteMonitor system and the 24-h MV analysis report. We conducted a survey to evaluate physicians' satisfaction and acceptance of the platform in 14 ICUs. Methods: Data from medical records, clinical information systems, and ventilators were uploaded to the cloud platform and underwent data processing. The data were analyzed to monitor PVA and displayed in the front-end. The 24-h analysis report for MV was generated for clinical reference. Critical care physicians in 14 hospitals' ICUs that involved in the platform participated in a questionnaire survey, among whom 10 physicians were interviewed to investigate physicians’ acceptance and opinions of this system. Results: The PVA-RemoteMonitor system exhibited a high level of specificity in detecting flow insufficiency, premature cycle, delayed cycle, reverse trigger, auto trigger, and overshoot, with sensitivities of 90.31 %, 98.76 %, 99.75 %, 99.97 %, 100 %, and 99.69 %, respectively. The 24-h analysis report supplied essential data about PVA and respiratory mechanics. 86.2 % (75/87) of physicians supported the application of this platform. Conclusions: The PVA-RemoteMonitor system accurately identified PVA, and the MV analysis report provided guidance in controlling PVA. Our platform can effectively assist ICU physicians in the management of ventilated patients.

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours, arising mainly from the interstitial cells of Cajal (ICCs) of the gastrointestinal tract. As radiotherapy and chemotherapy are generally ineffective for GISTs, the current primary treatment is surgical resection. However, surgical resection is not choice for most patients. Therefore, new therapeutic strategies are urgently needed. Targeted therapy, represented by tyrosine kinase inhibitors (TKIs), and immunotherapy, represented by immune checkpoint inhibitor therapies and chimeric antigen receptor T-cell immunotherapy (CAR-T), offer new therapeutic options in GISTs and have shown promising treatment responses. In this review, we summarize the molecular classification and immune microenvironment of GISTs and discuss the corresponding targeted therapy and immunotherapy options. This updated knowledge may provide more options for future therapeutic strategies and applications in GISTs.

BackgroundThe gut microbiota plays a pivotal role in the development of diabetes and kidney disease. However, it is not clear how the intestinal microecological imbalance is involved in the context of diabetic kidney disease (DKD), the leading cause of renal failure.ObjectivesTo elucidate the gut microbial signatures associated with DKD progression towards end-stage renal disease (ESRD) and explore whether they could reflect renal dysfunction and psychological distress.MethodsA cross-sectional study was conducted to explore the gut microbial signatures of 29 DKD non-ESRD patients and 19 DKD ESRD patients compared to 20 healthy controls. Differential analysis was performed to detect distinct gut microbial alterations in diversities and taxon abundance of DKD with and without ESRD. Renal dysfunction was estimated by urea, creatinine, and estimated glomerular filtration rate. Psychological distress was assessed using the Self-Rating Anxiety Scale, Self-Rating Depression Scale, Hamilton Anxiety Rating Scale, and Hamilton Depression Rating Scale.ResultsAlpha diversity indexes were reduced in DKD patients, particularly those with ESRD. Beta diversity analysis revealed that the gut microbial compositions of DKD patients were different with healthy individuals whereas similar compositions were observed in DKD patients. Taxon differential analysis showed that when compared with the controls, DKD patients exhibit distinct microbial profiles including reduced abundances of butyrate-produced, anti-inflammatory bacteria Faecalibacterium, Lachnospira, Roseburia Lachnoclostridium, and increased abundances of pro-inflammatory bacteria Collinsella, Streptococcus etc. These distinctive genera presented consistent associations with renal dysfunction, as well as psychological distress, especially in DKD patients.ConclusionsDKD patients, especially those who have progressed to ESRD, exhibit unique characteristics in their gut microbiota that are associated with both renal dysfunction and psychological distress. The gut microbiota may be a significant factor in the deterioration of DKD and its eventual progression to ESRD.

Intestinal microbiota community is an important factor affecting the nutritional and health status of poultry, and its balance is crucial for improving the overall health of poultry. The study aimed to investigate the effect of dietary supplementation with Glycyrrhiza uralensis extract (GUE), Lactobacillus acidophilus (Lac) and their combination (GL) on growth performance and intestinal health in broilers in an 84-day feeding experiment. Supplementary 0.1% GUE and 4.5×107 CFU/g Lac significantly increased average daily gain (ADG), and GL (0.1% GUE and 4.5×107 CFU/g Lac) increased ADG and average daily feed intake (ADFI), and decreased feed conversion rate (FCR) in broilers aged 29 to 84 d and 1 to 84 d. Dietary GUE, Lac and GL increased the superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity and decreased Malondialdehyde (MDA) content in the jejunum mucosa of broilers, and increased secretory IgA (sIgA) content in broilers at 84 d. Moreover, GUE, Lac and GL increased cecal microbial richness and diversity, and modulated microbial community composition. Both GUE and Lac reduced the harmful bacteria Epsilonbacteraeota, Helicobacter, and H. pullorum at 28 d and Proteobacteria, Escherichia, and E. coli at 84 d, while Lac and GL increased beneficial bacteria Lactobacillus and L. gallinarum at 28 d. Compared with individual supplementation, GL markedly increased the SOD activity and the sIgA content, and reduced Helicobacter and Helicobacter pullorum. In conclusion, GUE and Lactobacillus acidophilus as feed additives benefit growth performance and intestinal health, and their combined use shows an even more positive effect in broilers.

IntroductionScreening excellent bacterial strains for fermentation is the key to improving the nutritional value and bioavailability of soybean meal (SBM). This study investigated the application of Bacillus subtilis-fermented soybean meal (FSBM) on the feed of Pacific white shrimp (Litopenaeus vannamei).MethodsFSBM was used to replace 0%, 25%, 50%, 75%, and 100% fish meal, and the feeding trial was lasted for 8 weeks (initial weight: 0.9 g). Results and discussionThe amino acid profile in the whole shrimp body was tested. FSBM substitution only significantly reduced the content lysine in whole shrimp body, but increased the content of arginine. Fatty acid data showed that the content of n-6 PUFAs in whole shrimp was significantly increased by FSBM substitution. In muscle, FSBM substitution significantly reduced the content of MUFAs, but increased the content of PUFAs including C18:3n-3, C18:2n-6 and C20:4n-6. No hepatopancreas structure modifications appeared in the 25% group compared with the control group. Subsequently, we investigated the response patterns of different organs to FSBM substitution from antioxidant, endoplasmic reticulum stress and immunity. A high proportion of FSBM significantly reduced the content of GSH in hemolymph and hepatopancreas, while increased the mRNA expression of cat. FSBM substitution did not affect the activities of antioxidant enzymes in the intestine. However, the mRNA expression level of hsp70 in the intestine was significantly reduced by FSBM. In terms of immunity, the mRNA expression levels of lgbp and penaeidin in the hepatopancreas showed a significant linear increase trend. In muscle, high proportion of FSBM significantly increased the mRNA expression of imd. FSBM substitution did not significantly affect the expression of immune genes in the intestine. In terms of endoplasmic reticulum stress, FSBM substitution significantly increased the mRNA expression of eif2α in the hepatopancreas. In muscle, FSBM substitution inhibited the mRNA expression of bip. In the intestine, FSBM replacing 75% of fish meal significantly increased the mRNA expression of bip and ire1. In summary, this study indicated that when the fish meal content account for 40% in diets (dry weight), the screened Bacillus subtilis-FSBM can replace 25% of fish meal protein without reducing the antioxidant and immune abilities of shrimp.

ObjectiveTo investigate the difference in the effectiveness and refraction of the foldable capsular buckle (FCB) in rhegmatogenous retinal detachment (RRD).MethodsSix patients with simple RRD were treated for FCB scleral buckling at Xiamen Eye Center of Xiamen University from October 2023 to February 2024. The parameters assessed included demographic data, clinical data such as preoperative ocular axis, corneal endothelial count, macular foveal thickness, operative time, preoperative and final follow-up intro ocular pressure (IOP), retinal attachment status, and postoperative complications. Refractive change before and after surgery, including sphere, cylinder degree, spherical equivalent, and absolute spherical equivalent difference were compared.ResultsAll six patients with sound retinal reattachment after FCB scleral buckling, including two men and four women, mean age 41.33 ± 12.40 years old, duration before surgery onset to 7.17 ± 7.16 days, FCB mean operation time 36.67 ± 13.07 min, Preoperative IOP mean 13.35 ± 2.64 mmHg and mean 21.12 ± 8.09 mmHg of final follow-up IOP; there was no significant difference between preoperative IOP and follow-up IOP (p = 0.050). The preoperative sphere range was −6.25 to +2.50 D, and the cylinder range was −2.50 to +1.00 D; the absolute spherical equivalent difference before and after was 1.60 ± 1.69 degrees.ConclusionFCB can achieve retinal reattachment and restore visual function in cases of RRD. The shorter duration of external scleral buckle compression with FCB suggests that FCB scleral buckling holds greater promise in the clinical treatment of RRD caused by retinal tears.

It has been reported that long non-coding RNAs (lncRNAs) are involved in sepsis-induced liver injury, while the role of cancer susceptibility candidate 7 (CASC7) in liver injury induced by sepsis remains elusive. In our study, 62 patients and 55 healthy controls were enrolled from our hospital, from whom CASC7 and microRNA-217 (miR-217) in serum samples were detected by quantitative real-time PCR (qRT-PCR). Then the sepsis-induced liver injury mice model was established by lipopolysaccharide (LPS). The effect of CASC7 on liver injury induced by sepsis was confirmed by hematoxylin and eosin (HE) staining, ELISA assay, TUNEL assay, Annexin V-FITC apoptosis assay and cell counting kit-8 (CCK-8) assay, respectively. Besides, RNA pull-down, luciferase reporter gene assay, qRT-PCR, and western blot were used to evaluate the underlying mechanisms. In this study, lncRNA CASC7 was significantly increased while miR-217 was significantly decreased in patients with sepsis-induced liver injury compared with that in healthy controls. There was a negative association of CASC7 and miR-217 in serum samples from patients with sepsis-induced liver injury and healthy controls. CASC7 was upregulated in a time-dependent manner in liver tissues of LPS-treated mice. It was found that knockdown of CASC7 reduced the liver injury induced by LPS in mice. In vitro, LPS treatment enhanced cell apoptosis, while knockdown of CASC7 inhibited the role of LPS in cell apoptosis. Moreover, knockdown of CASC7 suppressed the LPS-enhanced tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) expression. In addition, miR-217 was found to be a target of CASC7, and miR-217 mimic could reverse CASC7-promoted liver injury. Furthermore, toll-like receptor 4 (TLR4) was identified as the target of miR-217, and both CASC7 and miR-217 could downregulate the mRNA and protein level of TLR4. Additionally, TLR4 overexpression could reverse miR-217-inhibited or CASC7-promoted liver injury. Taken together, CASC7 contributes to the progression of LPS-induced liver injury via the miR-217/TLR4 axis.

Background Inhaler concordance and the peak inspiratory flow rate (PIFR) are important determinants of treatment effects in patients with chronic airway diseases. Adequate PIFR is required for driving aerosol medication into the lower respiratory tract. However, the relationship between them has not been discussed previously. This study aimed to describe the characteristics of inhaler concordance and PIFR in Chinese patients with chronic airway diseases and discuss the associated variables and the relationship between them.Methods In this single-centre, observational study, a total of 680 patients with chronic airway diseases were enrolled from July 2021 to April 2023. We collected data on the socio-demographic and clinical variables of inhaler concordance using the test of adherence to inhalers (TAI) and PIFR. Multivariate logistic regression was conducted to examine variables related to inhaler concordance and PIFR.Results A total of 49.4% of patients had low concordance. Patients with chronic obstructive pulmonary disease (COPD) were more concordant than patients with asthma (mean TAI score: 43.60 vs 41.20; p

Electric vehicle (EV) charging station (CS) congestion is highly dependent on the EV owner’s behavior and their selected CS as charging choice. A fixed pricing strategy causes some CSs to be congested with EVs waiting in line to charge, while there are some other CSs with available electric plugs, which adversely affects both charging station operator (CSO) revenue and EV users’ welfare. To solve this problem, this paper presents a dynamic pricing strategy aimed at conducting EVs from congested CSs to the uncongested ones through controlling the charging prices of CSs at different times. The problem is formulated as a scenario-based stochastic optimization with the objective of maximizing overall revenue of the CSO. Moreover, an attraction function model is developed to quantify the charging choice of the EV owners by considering the effective parameters of CSs in EV charging choice decisions. QGIS software is used in this work to formulate a realistic modeling for CS locations and EV routes to calculate the distances from EVs to CSs. Three scenarios are designed to evaluate the performance of the proposed framework and to compare the results with the fixed pricing approach. The results indicate that the proposed dynamic pricing strategy mitigates the congestion of CSs while facilitating an increased number of charged EVs up to 48% as well as increasing the overall revenue of the CSO.