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Abstract Introduction Sepsis is a life-threatening condition that poses a globally high mortality rate. Identifying risk factors is crucial. Insulin resistance and the TYG index, associated with metabolic disorders, may play a role. This study explores their correlation with mortality in non-diabetic septic patients. Methods This retrospective cohort study used data from the MIMIC-IV (version 2.1) database, which includes over 50,000 ICU admissions from 2008 to 2019 at Beth Israel Deaconess Medical Center in Boston. We included adult patients with sepsis who were admitted to the intensive care unit in the study. The primary outcome was to evaluate the ability of TYG to predict death at 28-day of hospital admission in patients with sepsis. Results The study included 2213 patients with sepsis, among whom 549 (24.8%) died within 28 days of hospital admission. We observed a non-linear association between TYG and the risk of mortality. Compared to the reference group (lower TYG subgroup), the 28-day mortality increased in the higher TYG subgroup, with a fully adjusted hazard ratio of 2.68 (95% CI: 2.14 to 3.36). The area under the curve (AUC) for TYG was 67.7%, higher than for triglycerides alone (AUC = 64.1%), blood glucose (AUC = 62.4%), and GCS (AUC = 63.6%), and comparable to SOFA (AUC = 69.3%). The final subgroup analysis showed no significant interaction between TYG and each subgroup except for the COPD subgroup (interaction P-values: 0.076–0.548). Conclusion In our study, TYG can be used as an independent predictor for all-cause mortality due to sepsis within 28 days of hospitalization.

Abstract For the polarization multiplexing requirements in all-optical networks, this work presents a compact all-fiber polarization beam splitter (PBS) based on dual-core photonic crystal fiber (PCF) and an elliptical gold layer. Numerical analysis using the finite element method (FEM) demonstrates that the mode modulation effect of the central gold layer effectively reduces the dimensions of the proposed PBS. By determining reasonable structural parameters of the proposed PCF, the coupling length ratio (CLR) between X- and Y-polarized super-modes can approach 2, achieving a minimal device length of 0.122 mm. The PBS exhibits a maximum extinction ratio (ER) of − 65 dB at 1.55 μm, with an operating bandwidth spanning 100 nm (1.5–1.6 μm) and a stable insertion loss (IL) of ~ 1.5 dB at 1.55 μm. Furthermore, the manufacture feasibility and performance verification scheme are also investigated. It is widely anticipated that the designed PBS will play a crucial role in the ongoing development process of miniaturization and integration of photonic devices.

Tunnelling has increasingly become an essential tool in the exploration of underground space. A typical construction problem is the face instability during tunnelling, posing a great threat to associated infrastructures. Tunnel face instability often occurs with the soil arching collapse. This study investigates the combined effect of cutterhead opening ratio and soil non-uniformity on soil arching effect and face stability, via conducting random finite-element analysis coupled with Monte–Carlo simulations. The results underscore that the face stability is strongly associated with the evolution of stress arch. The obtained stability factors in the uniform soils can serve as a reference for the design of support pressure in practical tunnelling engineering. In addition, non-uniform soils exhibit a lower stability factor than uniform soils, which implies that the latter likely yields an underestimated probability of face failure. The tunnel face is found to have a probability of failure more than 50% if the spatial non-uniformity of soil is ignored. In the end, a practical framework is established to determine factor of safety (FOS) corresponding to different levels of probability of face failure considering various opening ratios in non-uniform soils. The required FOS is 1.70 to limit the probability of face instability no more than 0.1%. Our findings can facilitate the prediction of probability of instability in the conventionally deterministic design of face pressure.

ABSTRACT: An effective and facile method of generating nitrogen-doped carbon dots (N-CD) by microwave irradiation is presented in this study. A precursor, succinic acid (SA), and a nitrogen source, bis-(3-aminopropyl)-amine (BAPA), were used to obtain N-CD. A precious quantum yield (QY) of 49.0% was obtained from the preparation of N-CD, which was well-soluble in water. The N-CD material was highly selective and sensitive for the detection of nickel ion (Ni2+), with a detection limit of 0.26 μM and a linear concentration range of 5-175 μM. The quenching of the N-CD by the presence of Ni2+ was referred to formation of complexes because of the interaction of Ni2+ on the N-CD. Hence, the proposed study has great promise regarding Ni2+ detection in broad applications. Keywords: Microwave, Ni2+, nitrogen-doped carbon dots.

"Objective To investigate the correlation between serum pancreatic regenerating (Reg) protein Ⅰα and chronic kidney disease (CKD) in diabetic patients, to develop a risk prediction model for diabetes combined with CKD. Methods The clinical data of 500 diabetic patients admitted to the Zhongda Hospital Southeast University from September 2021 to September 2023 were collected for a retrospective study, including general data, medical history, and laboratory indexes［blood routine tests, fasting plasma glucose (FPG), blood urea nitrogen (BUN), serum creatinine (Scr), serum uric acid (UA), and urinary albumin/creatinine ratio (UACR)］. Additionally, the estimated glomerular〖LM〗 filtration rate (eGFR) was calculated. Serum Reg Ⅰα level was measured by enzyme-linked immunosorbent assay, and patients were classified into groups R1 (Reg Ⅰα≤38.60 ng/mL,n=98), R2 (38.60＜Reg Ⅰα≤82.17ng/mL,n=97), R3 (82.17＜Reg Ⅰα≤196.15 ng/mL,n=97) and R4 (Reg Ⅰα＞196.15 ng/mL,n=97), according to quartile levels. Patients were randomly divided into a training set (234 cases) and a validation set (155 cases) using a random number table method in a ratio of 6∶4. Multivariate logistic stepwise regression was utilized to identify model variables and create a nomogram model for predicting the risk of diabetes combined with CKD, and evaluate its efficiency. Results (1) A total of 389 diabetic patients with complete data were included, and 210 (53.98%) patients with CKD. Patients in the R4 group exhibited significantly higher levels of FPG, BUN, Scr, and UA, increased rates of hypertension, coronary heart disease, and CKD, as well as lower levels of red blood cell count, hemoglobin(HGB), and eGFR compared to those in the R1 group (P＜0.05). (2) The indicators in the training and validation sets were found to be well-balanced (P＞0.05). In the training set, the CKD group showed higher levels of Reg Ⅰα, white blood cell count, BUN, Scr, and UA, higher prevalences of hypertension and coronary artery disease, and lower levels of erythrocyte count, HGB, and eGFR compared to the NCKD group (P＜0.05). Binary logistic regression analysis was performed on the basis of collinearity diagnosis,and the results showed that history of hypertension (OR=2.901), Reg Ⅰα＞82.17 ng/mL, decreased HGB (OR=0.965) and increased UA (OR=1.005) were the risk factors of diabetes complicated with CKD (P＜0.05). (3) The areas under the ROC of the training set and validation set were 0.846(95%CI: 0.796-0.896) and 0.920(95%CI： 0.875-0.965), respectively. The calibration curves and the Hosmer-Lemeshow test indicated good agreement of the predicted and observed outcomes (P＞0.05). Conclusion Hypertension, elevated Reg Ⅰα levels, decreased HGB and elevated UA are risk factors for CKD in diabetic patients, and the nomogram model constructed in this study has good predictive power and clinical value."

Brachial plexus injury (BPI) with motor neurons (MNs) damage still remain poor recovery in preclinical research and clinical therapy, while cell-based therapy approaches emerged as novel strategies. Previous work of rat skin precursor-derived Schwann cells (SKP–SCs) provided substantial foundation for repairing peripheral nerve injury (PNI). Given that, our present work focused on exploring the repair efficacy and possible mechanisms of SKP-SCs implantation on rat BPI combined with neurorrhaphy post-neurotomy. Results indicated the significant locomotive and sensory function recovery, with improved morphological remodeling of regenerated nerves and angiogenesis, as well as amelioration of target muscles atrophy and motor endplate degeneration. Besides, MNs could restore from oxygen-glucose-deprivation (OGD) injury upon SKP-SCs-sourced secretome treatment, implying the underlying paracrine mechanisms. Moreover, rat cytokine array assay detected 67 cytokines from SKP-SC-secretome, and bioinformatic analyses of screened 32 cytokines presented multiple functional clusters covering diverse cell types, including inflammatory cells, Schwann cells, vascular endothelial cells (VECs), neurons, and SKP-SCs themselves, relating distinct biological processes to nerve regeneration. Especially, a panel of hypoxia-responsive cytokines (HRCK), can participate into multicellular biological process regulation for permissive regeneration milieu, which underscored the benefits of SKP-SCs and sourced secretome, facilitating the chorus of nerve regenerative microenvironment. Furthermore, platelet-derived growth factor-AA (PDGF-AA) and vascular endothelial growth factor-A (VEGF-A) were outstanding cytokines involved with nerve regenerative microenvironment regulating, with significantly elevated mRNA expression level in hypoxia-responsive SKP-SCs. Altogether, through recapitulating the implanted SKP-SCs and derived secretome as niche sensor and paracrine transmitters respectively, HRCK would be further excavated as molecular underpinning of the neural recuperative mechanizations for efficient cell therapy; meanwhile, the analysis paradigm in this study validated and anticipated the actions and mechanisms of SKP-SCs on traumatic BPI repair, and was beneficial to identify promising bioactive molecule cocktail and signaling targets for cell-free therapy strategy on neural repair and regeneration.

In an era marked by rapid digitalization and the convergence of media platforms, gender equality, particularly within journalism, has gained prominence. However, gender discrimination remains a challenge for female journalists. This research collected 387 valid responses from Spanish media professionals through digital and other channels. Data analysis, including statistical methods like frequency analysis and chi-square tests, aims to uncover factors affecting the careers of Spanish female journalists. The goal is to provide empirically supported recommendations for gender equality in the dynamic Spanish media landscape.

Abstract The amount of actively cultivated land in China is increasingly threatened by rapid urbanization and rural population aging. Quantifying the extent and changes of active cropland and cropping intensity is crucial to global food security. However, national-scale datasets for smallholder agriculture are limited in spatiotemporal continuity, resolution, and precision. In this paper, we present updated annual Cropland Use Intensity maps in China (China-CUI10m) with descriptions of the extent of fallow/abandoned, actively cropped fields and cropping intensity at a 10-m resolution in recent six years (2018–2023). The dataset is produced by robust algorithms with no requirements for regional adjustments or intensive training samples, which take full advantage of the Sentinel-1 (S1) SAR and Sentinel-2 (S2) MSI time series. The China-CUI10m maps have achieved high accuracy when compared to ground truth data (Overall accuracy = 90.88%) and statistical data (R2 > 0.94). This paper provides the recent trends in cropland abandonment and agricultural intensification in China, which contributes to facilitating geographic-targeted cropland use control policies towards sustainable intensification of smallholder agricultural systems in developing countries.

Abstract Background Peritoneal dialysis (PD) and conventional in‐center hemodialysis (HD) are treatment options for patients with end‐stage kidney disease (ESKD). However, their impact on all‐cause mortality is unclear. Methods We conducted a multicenter, open‐label, randomized, non‐inferiority trial to determine the effect of dialysis modality on mortality in patients with ESKD. Eligible patients were recruited from 30 sites across China and assigned to receive either PD or HD in a ratio of 1:1. The primary outcome was all‐cause mortality. Non‐inferiority was defined as the upper bound of the one‐sided 95% confidence interval (CI) for the hazard ratio (HR) being ≤1.25. Results A total of 414 patients with incident ESKD were randomly assigned to PD (n = 213) or HD (n = 201). During a median follow‐up of 1.7 years, 37 patients in the PD group and 31 in the HD group died, giving respective event rates per patient‐year of 0.061 and 0.071. The HR for mortality on PD in comparison with HD was 0.76 (95% CI 0.47–1.24) after adjustment for age, sex, and diabetes status, achieving the limit for non‐inferiority. There were more adverse events (p = 0.003), serious adverse events (p = 0.009), and adverse events leading to hospitalization (p = 0.003) in the PD group than in the HD group; however, there was no significant between‐group difference in adverse events leading to death or discontinuation of treatment. Conclusions PD was non‐inferior to conventional in‐center HD in terms of survival in patients with ESKD. Our findings underscore the need for shared decision‐making between physicians and patients regarding the selection of dialysis modality. Trial registration Registered at ClinicalTrials.gov (NCT01413074).

Abstract Background Investigating the unexplored territory of lncRNA m6A modification in colorectal cancer (CRC) vasculature, this study focuses on LINC01106 and YTHDF1. Methods Clinical assessments reveal upregulated LINC01106 promoting vascular generation via the miR-449b-5p-VEGFA pathway. Results YTHDF1, elevated in CRC tissues, emerges as an adverse prognostic factor. Functional experiments showcase YTHDF1’s inhibitory effects on CRC cell dynamics. Mechanistically, Me-CLIP identifies m6A-modified LINC01106, validated as a YTHDF1 target through Me-RIP. Conclusions This study sheds light on the YTHDF1-mediated m6A modification of LINC01106, presenting it as a key player in suppressing CRC vascular generation.

In this study, rambutan (Nephelium Lappaceum L.) seeds were used to fabricate green carbon dots (gCDs) by employing a hydrothermal process. The synthesized CDs were evaluated using Fourier transform infrared (FT-IR) and X-ray photoelectron spectroscopy (XPS) for the structural properties as well as UV-Vis and fluorescence spectrophotometry for the optical properties. UV-Vis examination revealed that the produced gCDs showed emission-dependent photoluminescence excitation, with two absorption peaks at 265 nm and 330 nm. The presence of functional groups and chemical composition such as C=C, C=O, -COOH, and -OH on the surface of gCDs was confirmed by the results of FTIR and XPS spectra. Consequently, gCDs present several opportunities for exploration in a range of applications.

Steel containers used for geological disposal of high-level radioactive waste will be gradually thinned or even perforated due to corrosion, which will lead to radiolysis of nuclides when they contact with infiltrated groundwater and produce H2O2. This work focused on investigating the influence of H2O2 concentration (0%, 0.001%, 0.01%, 0.1% and 1% by volume) on the corrosion behavior of NiCu low alloy steel as the candidate material for containers was comparatively studied by combining corrosion weight loss test, corrosion product analysis, morphology characterization, thermodynamic analysis and electrochemical measurements. As [H2O2] = 0.001%, H2O2 inhibited the formation of γ-FeOOH and enhanced the compactness of rust layer, which effectively blocked the migration of aggressive ions and slowed down the cathodic reduction reaction of rust, thus improving the corrosion resistance of NiCu steel. With the increase of [H2O2] (0.01%→1%), the cathodic process of NiCu steel corrosion was promoted by the increase of dissolved oxygen involved in cathodic depolarization. Meanwhile, the relative content of Fe3O4 in the rust increased, while Fe6(OH)12SO4 and Fe6(OH)12CO3 decreased obviously, which led to the loose and porous rust layer, thus accelerating the corrosion of NiCu steel.

Abstract Chemotherapeutic agents can inhibit the proliferation of malignant cells due to their cytotoxicity, which is limited by collateral damage. Dihydroartemisinin (DHA), has a selective anti-cancer effect, whose target and mechanism remain uncovered. The present work aims to examine the selective inhibitory effect of DHA as well as the mechanisms involved. The findings revealed that the Lewis cell line (LLC) and A549 cell line (A549) had an extremely rapid proliferation rate compared with the 16HBE cell line (16HBE). LLC and A549 showed an increased expression of NRAS compared with 16HBE. Interestingly, DHA was found to inhibit the proliferation and facilitate the apoptosis of LLC and A549 with significant anti-cancer efficacy and down-regulation of NRAS. Results from molecular docking and cellular thermal shift assay revealed that DHA could bind to epidermal growth factor receptor (EGFR) molecules, attenuating the EGF binding and thus driving the suppressive effect. LLC and A549 also exhibited obvious DNA damage in response to DHA. Further results demonstrated that over-expression of NRAS abated DHA-induced blockage of NRAS. Moreover, not only the DNA damage was impaired, but the proliferation of lung cancer cells was also revitalized while NRAS was over-expression. Taken together, DHA could induce selective anti-lung cancer efficacy through binding to EGFR and thereby abolishing the NRAS signaling pathway, thus leading to DNA damage, which provides a novel theoretical basis for phytomedicine molecular therapy of malignant tumors.

Abstract The Australian culturally and linguistically diverse (CALD) communities may be at higher risk of salt intake than recommended given the use of a combination of discretionary sources and exposure to processed foods within a western country. This survey aimed to understand the knowledge, attitudes, and behaviors toward dietary salt and the acceptability of salt substitutes in the CALD communities. An online cross‐sectional survey was conducted among adults who self‐reported being a part of a CALD community, which was defined as non‐Indigenous cultural groups in Australia having cultural or linguistic connections with their overseas place of birth, ancestry or ethnic origin, religion, preferred language or language spoken at home. A total of 218 respondents opened the survey link. A total of 196 completed the entire survey. The majority of respondents (162, 83%) were aware that high salt intake causes serious health problems. Altogether 134 (69%) respondents were aware that there is a recommended amount for daily salt consumption although only 59 (44%) knew precise recommendations as

Abstract Cardiovascular function and adipose metabolism were markedly influenced under high altitudes. However, the interplay between adipokines and heart under hypoxia remains to be elucidated. We aim to explore alterations of adipokines and underlying mechanisms in regulating cardiac function under high altitudes. We investigated the cardiopulmonary function and five adipokines in Antarctic expeditioners at Kunlun Station (4,087 m) for 20 days and established rats exposed to hypobaric hypoxia (5,000 m), simulating Kunlun Station. Antarctic expeditioners exhibited elevated heart rate, blood pressure, systemic vascular resistance, and decreased cardiac pumping function. Plasma creatine phosphokinase-MB (CK-MB) and platelet-endothelial cell adhesion molecule-1 (sPecam-1) increased, and leptin, resistin, and lipocalin-2 decreased. Plasma leptin significantly correlated with altered cardiac function indicators. Additionally, hypoxic rats manifested impaired left ventricular systolic and diastolic function, elevated plasma CK-MB and sPecam-1, and decreased plasma leptin. Chronic hypoxia for 14 days led to increased myocyte hypertrophy, fibrosis, apoptosis, and mitochondrial dysfunction, coupled with reduced protein levels of leptin signaling pathways in myocardial tissues. Cardiac transcriptome analysis revealed leptin was associated with downregulated genes involved in rhythm, Na+/K+ transport, and cell skeleton. In conclusion, chronic hypoxia significantly reduced leptin signaling pathways in cardiac tissues along with significant pathological changes, thus highlighting the pivotal role of leptin in regulation of cardiac function under high altitudes.

Objective To estimate adolescents and children age using stepwise regression and machine learning methods based on the pulp and tooth volumes of the left maxillary central incisor and cuspid on cone beam computed tomography （CBCT） images, and to compare and analyze the estimation results. Methods A total of 498 Shanghai Han adolescents and children CBCT images of the oral and maxillofacial regions were collected. The pulp and tooth volumes of the left maxillary central incisor and cuspid were measured and calculated. Three machine learning algorithms （K-nearest neighbor, ridge regression, and decision tree） and stepwise regression were used to establish four age estimation models. The coefficient of determination, mean error, root mean square error, mean square error and mean absolute error were computed and compared. A correlation heatmap was drawn to visualize and the monotonic relationship between parameters was visually analyzed. Results The K-nearest neighbor model （R2=0.779） and the ridge regression model （R2=0.729） outperformed stepwise regression （R2=0.617）, while the decision tree model （R2=0.494） showed poor fitting. The correlation heatmap demonstrated a monotonically negative correlation between age and the parameters including pulp volume, the ratio of pulp volume to hard tissue volume, and the ratio of pulp volume to tooth volume. Conclusion Pulp volume and pulp volume proportion are closely related to age. The application of CBCT-based machine learning methods can provide more accurate age estimation results, which lays a foundation for further CBCT-based deep learning dental age estimation research.

Water hammer protection is one of the key factors for the safe operation of the long-distance water delivery systems, which has lots of useful results. However, the protection experiences for bidirectional water delivery systems using the same pipeline are lacking. In this study, the protection method with one-way surge tanks in the bidirectional water delivery system is investigated. The theoretical formula for one-way surge tank setting is derived based on the theory of water hammer propagation, and the pump head and bidirectional water hammer protection constraints. Subsequently, the pump trip transient processes in an actual system are simulated. Finally, different kinds of one-way surge tank protection schemes are compared. The results show that the pressure along the pipeline after the pump trip can meet the standard when using the one-way surge tank protection scheme calculated by the theoretical formula. The proposed method can provide the effective protection strategy for the bidirectional water delivery systems. HIGHLIGHTS Negative pressure protection for the bidirectional water delivery systems in the same pipeline is studied.; The theoretical formula for one-way surge tank setting in bidirectional water delivery system is presented.; The proposed one-way surge tank setting strategy can provide effective water hammer protection for the system.;

Abstract Apple moldy core is a fungus-infested disease that is extremely insidious, usually occurring inside the fruit, making it very difficult to distinguish from the exterior with the naked eye. Using VIS/NIR transmission spectroscopy, this study successfully detected moldy core apples. By combining four wavelength selection algorithms (CARS, CARS-SPA, MC-UVE, and MC-UVE-SPA) with four classifiers (SVM, ELM, KNN, and LDA-KNN), discrimination models were established for two-class and three-class classifications. MC-UVE-SPA-LDA-KNN achieved an AUC of 0.99 and an accuracy of 98.82% for two-class classification, while MC-UVE-SPA achieved an AUC of 0.99 and an accuracy of 97.64% for three-class classification. This confirms MC-UVE-SPA as an effective tool for selecting wavelengths specific to moldy core apples, facilitating precise identification and differentiation of apple states. This study advances dynamic online detection of early-stage moldy core conditions in apples, reducing post-harvest disease occurrence and preserving fruit quality effectively. Graphical Abstract

Abstract Background Numerous previous reports have demonstrated the efficacy of Lactic acid bacteria (LAB) in promoting growth and preventing disease in animals. In this study, Enterococcus faecium ZJUIDS-R1 and Ligilactobaciiius animalis ZJUIDS-R2 were isolated from the feces of healthy rabbits, and both strains showed good probiotic properties in vitro. Two strains (108CFU/ml/kg/day) were fed to weaned rabbits for 21 days, after which specific bacterial infection was induced to investigate the effects of the strains on bacterial diarrhea in the rabbits. Results Our data showed that Enterococcus faecium ZJUIDS-R1 and Ligilactobaciiius animalis ZJUIDS-R2 interventions reduced the incidence of diarrhea and systemic inflammatory response, alleviated intestinal damage and increased antibody levels in animals. In addition, Enterococcus faecium ZJUIDS-R1 restored the flora abundance of Ruminococcaceae1. Ligilactobaciiius animalis ZJUIDS-R2 up-regulated the flora abundance of Adlercreutzia and Candidatus Saccharimonas. Both down-regulated the flora abundance of Shuttleworthia and Barnesiella to restore intestinal flora balance, thereby increasing intestinal short-chain fatty acid content. Conclusions These findings suggest that Enterococcus faecium ZJUIDS-R1 and Ligilactobaciiius animalis ZJUIDS-R2 were able to improve intestinal immunity, produce organic acids and regulate the balance of intestinal flora to enhance disease resistance and alleviate diarrhea-related diseases in weanling rabbits.

ObjectiveThis study explores the relationship between social support and sporting activities of Muslim women and constructs a mediation model through role of psychological adjustment.MethodsUsing stratified cluster sampling, 301 Muslim women were measured in group psychology using the Social Support Scale and the Sports Activities and Psychological Adjustment Scale. The statistical software SPSS 24.0 and SPSS PROCESS 3.3 were used for statistical processing. The common-method variation test was carried out using the Harman single-factor control test. Finally, the Bootstrap sampling test method and process plug-in were used to test the significance of the intermediary effect.Results(1) Social support has a significant predictive effect on sports activities (β = 0.32, p

Summary: Optogenetic manipulation has proven a powerful tool for investigating the mechanisms underlying the function of neuronal networks, but implementing the technique on mammals during early development remains challenging. Here, we present a comprehensive workflow to specifically manipulate mitral/tufted cells (M/TCs), the output neurons in the olfactory circuit, mediated by adeno-associated virus (AAV) transduction and light stimulation in neonatal mice and monitor neuronal and network activity with in vivo electrophysiology. This method represents an efficient approach to elucidate functional brain development.For complete details on the use and execution of this protocol, please refer to Chen et al.1,2,3 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Background: Low muscle mass and obesity are associated with mobility disability, cardiometabolic diseases, and loss of independence. Three skeletal muscle indices (SMIs) are proposed to adjust the body size of individuals. However, it is unknown which index is better correlated with mobility. Additionally, it remains unclear whether low muscle mass or abdominal obesity has a greater impact on the mobility and cardiometabolic health of older adults. Objectives: This study explored the association between different SMIs {appendicular skeletal muscle mass [ASM] adjusted by body height [Ht], body weight [Wt], or body mass index [BMI (kg/m2)]} and mobility/cardiometabolic health. The roles of low muscle mass and abdominal obesity in the mobility and cardiometabolic health of individuals were also identified. Methods: Four-hundred and twenty-seven community-dwelling middle-aged and older adults underwent body composition assessments [dual-energy x-ray absorptiometry and waist circumference (WC)], grip strength, and mobility (timed up-and-go test and chair stand test). Spearman’s rank correlation coefficient and regression models were used to examine research questions. This study was registered in the Thai Clinical Trials Registry (registration number: TCTR20210521007). Results: All SMIs were positively correlated with the grip strength (ASM/Ht2: r = 0.392; ASM/Wt: r = 0.439; ASM/BMI: r = 0.569). Regarding mobility, only ASM/Ht2 wasn’t relevant. After adjusting for age, sex, and WC, ASM/BMI was the only SMI associated with grip strength (β = 0.274). When age and sex were controlled, WC, but not SMI, was associated with mobility and cardiometabolic health. Conclusions: ASM/Ht2 did not correlate with mobility in middle-aged and older adults, whereas ASM/Wt and ASM/BMI did. Abdominal obesity has a greater impact on mobility and cardiometabolic health than low muscle mass in middle-aged and older adults. We recommend using ASM/BMI to identify the low muscle mass of individuals. In addition, clinicians should note the important role of abdominal obesity when considering mobility in middle-aged and older adults.

Abstract Previous studies have shown a bidirectional communication between human gut microbiota and the brain, known as the microbiota–gut–brain axis (MGBA). The MGBA influences the host's nervous system development, emotional regulation, and cognitive function through neurotransmitters, immune modulation, and metabolic pathways. Factors like diet, lifestyle, genetics, and environment shape the gut microbiota composition together. Most research have explored how gut microbiota regulates host physiology and its potential in preventing and treating neurological disorders. However, the individual heterogeneity of gut microbiota, strains playing a dominant role in neurological diseases, and the interactions of these microbial metabolites with the central/peripheral nervous systems still need exploration. This review summarizes the potential role of gut microbiota in driving neurodevelopmental disorders (autism spectrum disorder and attention deficit/hyperactivity disorder), neurodegenerative diseases (Alzheimer's and Parkinson's disease), and mood disorders (anxiety and depression) in recent years and discusses the current clinical and preclinical gut microbe‐based interventions, including dietary intervention, probiotics, prebiotics, and fecal microbiota transplantation. It also puts forward the current insufficient research on gut microbiota in neurological disorders and provides a framework for further research on neurological disorders.

Abstract Immunosuppression is a major hallmark of tumor progression in non‐small cell lung cancer (NSCLC). Cluster of differentiation 147 (CD147), an important pro‐tumorigenic factor, is closely linked to NSCLC immunosuppression. However, the role of CD147 di‐methylation in the immunosuppressive tumor microenvironment (TME) remains unclear. Here, di‐methylation of CD147 at Lys148 (CD147‐K148me2) is identified as a common post‐translational modification (PTM) in NSCLC that is significantly associated with unsatisfying survival outcomes among NSCLC sufferers, especially those in the advanced stages of the disease. The methyltransferase NSD2 catalyzes CD147 to generate CD147‐K148me2. Further analysis demonstrates that CD147‐K148me2 reestablishes the immunosuppressive TME and promotes NSCLC progression. Mechanistically, this modification promotes the interaction between cyclophilin A (CyPA) and CD147, and in turn, increases CCL5 gene transcription by activating p38‐ZBTB32 signaling, leading to increased NSCLC cell‐derived CCL5 secretion. Subsequently, CD147‐K148me2‐mediated CCL5 upregulation facilitates M2‐like tumor‐associated macrophage (TAM) infiltration in NSCLC tissues via CCL5/CCR5 axis‐dependent intercellular crosstalk between tumor cells and macrophages, which is inhibited by blocking CD147‐K148me2 with the targeted antibody 12C8. Overall, this study reveals the role of CD147‐K148me2‐driven intercellular crosstalk in the development of NSCLC immunosuppression, and provides a potential interventional strategy for PTM‐targeted NSCLC therapy.

ABSTRACT From May to July of 2023, one pig farm in Heyuan city, Guangdong Province of China, suffered severe piglet death and sow reproductive disorders. The common pig viruses and bacteria tested negative. To uncover the possible cause of the disease, a metagenomic analysis was performed in the pooled small intestine samples from three 8-day-old diseased piglets. The results showed that Getah virus (GETV), an RNA virus, might be the potential pathogen that affects pig health. Subsequently, GETV nucleotide was detected in all of the 15 samples collected from three diseased piglets using quantitative reverse transcription PCR, suggesting GETV as the main pathogen of the disease. A GETV strain, designated as GDHYLC23, was successfully isolated using the swine testicle cell line. Sequence analysis showed that the epidemic strain had a unique 32-nucleotide repeat insertion in the 3′ noncoding region. Phylogenetic analysis showed that GDHYLC23 belonged to the pandemic group III. The identification of GETV with new variations implies the continuous evolution of the virus, which poses potential threats to the swine industry.IMPORTANCEPig farms are faced with emerging and re-emerging viruses that may cause substantial economic loss. The identification of potentially pathogenic viruses helps to prevent and control the spread of diseases. In this study, by using metagenomic analysis, we found that a neglected virus, GETV with a unique insertion in the genome, was the main pathogen in one pig farm that suffered severe piglet death and sow reproductive disorders. Although the potential impact of such an insertion on viral pathogenicity is unknown, the surveillance of the continuing evolution of GETV in pig farms cannot be ignored.

PurposeTo evaluate and compare the diagnostic value of contrast-enhanced transcranial Doppler (c-TCD) and contrast-enhanced transthoracic echocardiography (c-TTE) for right to left shunt (RLS) in patent foramen ovale (PFO) by meta-analysis.MethodsThe literature included in the Cochrane Library, PubMed, and Embase were searched by using “contrast-enhanced transcranial Doppler (c-TCD), contrast-enhanced transthoracic echocardiography (c-TTE), patent foramen ovale (PFO), and right to left shunt (RLS)” as the keywords from inception through April 30, 2024. The diagnostic accuracy research quality assessment tool (QUADAS-2) was used to evaluate the quality of the included literature. The combined sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and Diagnostic odds ratio (DOR) were pooled, and a comprehensive ROC curve analysis was performed. Statistical software StataSE 12.0 and Meta-Disc 1.4 were used for data analysis.ResultsA total of 8,536 articles were retrieved, and 9 articles that met all inclusion criteria were included in this meta-analysis. The meta-analysis results show that the combined sensitivity, specificity, PLR, NLR, DOR, and area under the SROC curve of c-TCD for the diagnose of PFO-RLS were 0.91 (95% CI, 0.88–0.93), 0.87 (95% CI: 0.84–0.91), 6.0 (95% CI, 2.78–12.96), 0.10 (95% CI, 0.06–0.18), 91.61 (95% CI, 26.55–316.10), and 0.9681, respectively; the corresponding values of c-TTE were 0.86 (95% CI, 0.84–0.89), 0.88 (95% CI, 0.84–0.91), 5.21 (95% CI, 2.55–10.63), 0.16 (95% CI, 0.09–0.31), 71.43 (95% CI, 22.85–223.23), and 0.9532. The ROC curve shows that c-TCD has slightly higher diagnostic value for PFO than c-TTE, but there is no significant statistical difference (Z = 0.622, p > 0.05). Deek funnel pattern showed no significant publication bias.ConclusionBoth c-TCD and c-TTE have high diagnostic values for PFO-RLS. However, c-TCD has slightly higher sensitivity and lower specificity in diagnosing PFO-RLS compared to c-TTE.Systematic review registration: identifier [CRD42024544169].

Common cancer complications include bone cancer pain (BCP), which was not sufficiently alleviated by traditional analgesics. More safe and effective therapy was urgent needed. Metformin relieved osteoarthritis pain, but the analgesia of Metformin in BCP was not well studied. The study aimed to explore the Metformin-mediated analgesic effect and its molecular mechanisms in BCP rats. We demonstrated that Walker 256 cell transplantation into the medullary cavity of the tibia worsened mechanical allodynia in BCP rats, increased the expression of TGFβ1 in the metastatic bone tissue, and raised the expression of TGFβRI and TRPV1 in the L4-6 dorsal root ganglion (DRG) of BCP rats. While, selectively blockade of TGFβRI by SD208 could obviously elevated the paw withdraw threshold (PWT) of BCP rats, together with decreased TRPV1 expression in L4-6 DRG. Notably, continuous Metformin treatment reduced TGFβ1, TGFβRI and TRPV1 expression, and relieved mechanical allodynia of BCP rats in a long-term effect. In conclusion, these results illustrated that Metformin ameliorated bone cancer pain, and the downregulation of TGFβ1-TGFβRI-TRPV1 might be a potential mechanism of Metformin-mediated analgesia in BCP.

Breast cancer (BRCA) is the most common cancer among women. Adriamycin (ADR), also known as doxorubicin (Dox), is a commonly used chemotherapeutic agent for BRCA patients, however, the susceptibility of tumor cells to develop resistance to Dox has severely limited its clinical use. One new promising therapeutic target for breast cancer patients is exosomes. The objective of this study was to investigate the role of exosomes in regulating Dox resistance in BRCA.In this study, the exosomes from both types of cells were extracted by differential centrifugation. The effect of exosomes on drug resistance was assessed by laser confocal microscopy, MTT assay, and qRT-PCR. The miRNA was transfected into cells using Lipofectamine 2000, which was then evaluated for downstream genes and changes in drug resistance.Exosomes from MCF-7 cells (MCF-7/exo) and MCF-7/ADR cells (ADR/exo) were effectively extracted in this study. The ADR/exo was able to endocytose MCF-7 cells and make them considerably more resistant to Dox. Moreover, we observed a significant difference in miR-34a-5p expression in MCF-7/ADR and ADR/exo compared to MCF-7 and MCF-7/exo. Among the miR-34a-5p target genes, NOTCH1 displayed a clear change with a negative correlation. In addition, when miR-34a-5p expression was elevated in MCF-7/ADR cells, the expression of miR-34a-5p in ADR/exo was also enhanced alongside NOTCH1, implying that exosomes may carry miRNA into and out of cells and perform their function.In conclusion, exosomes can influence Dox resistance in breast cancer cells by regulating miR-34a-5p/NOTCH1. These findings provide novel insights for research into the causes of tumor resistance and the enhancement of chemotherapy efficacy in breast cancer.

Introduction: Previous studies have shown that rituximab (RTX) and cyclic oral corticosteroid-cyclophosphamide (CTX) regimens have similar effects on Primary Membranous Nephropathy. However, no studies have compared RTX with an intravenous CTX regimen, which is more commonly used in China and requires fewer cumulative CTX doses. Methods: We prospectively assigned 141 PMN patients with baseline proteinuria ≥ 4 g/24 h, serum albumin < 30 g/L, and eGFR ≥ 30 mL/min × 1.73 m2 despite at least 3 months of treatment with ACEI and/or ARB to the RTX group (375 mg/m2 per injection per week × 4 injections) or to the CTX group (prednisone 0.8 mg/kg/d and intravenous CTX 500 mg/m2 per month until the total dose reached 6–8 g). The primary endpoint was defined as a combination of partial remission or complete remission at 12 months. Results: By the end of 12 months, 43 of 70 patients (61.43%) in the RTX group and 54 of 71 patients (76.06%) in the CTX group reached the primary endpoint(P=0.06). Significantly fewer patients in the RTX group achieved complete remission than the CTX group (14.29% vs. 33.80%, P=0.01). The adverse events rate was similar between the RTX group and the CTX group (28.57% vs. 40.85%, P=0.13). In subgroup analysis, we found that fewer patients from the RTX group achieved the primary endpoint than the CTX group (48.65% vs. 74.29%, P=0.03) among patients with massive proteinuria (urine protein ≥ 8 g/24 h). During the observational phase, 61 patients in the RTX group and 58 in the CTX group completed 24 months of follow-up, exhibiting similar remission rates (RTX vs. CTX: 75.41% vs. 68.97%, P=0.54). Conclusions: Our results show that the intravenous CTX regimen has similar safety and efficacy with higher rates of early complete remission than RTX in the treatment of PMN patients.

ABSTRACT Hypermucoviscosity (HMV) is a phenotype that is commonly associated with hypervirulence in Klebsiella pneumoniae. The factors that contribute to the emergence of HMV subpopulations remain unclear. In this study, eight K. pneumoniae strains were recovered from an inpatient who had been hospitalized for 20 days. Three of the isolates exhibited a non-HMV phenotype, which was concomitant with higher biofilm formation than the other five HMV isolates. All eight isolates were highly susceptible to serum killing, albeit HMV strains were remarkably more infective than non-HMV counterparts in a mouse model of infection. Whole genome sequencing (WGS) showed that the eight isolates belonged to the K57-ST412 lineage. Average nucleotide identity (FastANIb) analysis indicated that eight isolates share 99.96% to 99.99% similarity and were confirmed to be the same clone. Through comparative genomics analysis, 12 non-synonymous mutations were found among these isolates, eight of which in the non-HMV variants, including rmpA (c.285delG) and wbaP (c.1305T > A), which are assumed to be associated with the non-HMV phenotype. Mutations in manB (c.1318G > A), dmsB (c.577C > T) and tkt (c.1928C > A) occurred in HMV isolates only. RNA-Seq revealed transcripts of genes involved in energy metabolism, carbohydrate metabolism and membrane transport, including cysP, cydA, narK, tktA, pduQ, aceB, metN, and lsrA, to be significantly dysregulated in the non-HMV strains, suggesting a contribution to HMV phenotype development. This study suggests that co-occurrence of HMV and non-HMV phenotypes in the same clonal population may be mediated by mutational mechanisms as well as by certain genes involved in membrane transport and central metabolism.IMPORTANCEK. pneumoniae with a hypermucoviscosity (HMV) phenotype is a community-acquired pathogen that is associated with increased invasiveness and pathogenicity, and underlying diseases are the most common comorbid risk factors inducing metastatic complications. HMV was earlier attributed to the overproduction of capsular polysaccharide, and more data point to the possibility of several causes contributing to this bacterial phenotype. Here, we describe a unique event in which the same clonal population showed both HMV and non-HMV characteristics. Studies have demonstrated that this process is influenced by mutational processes and genes related to transport and central metabolism. These findings provide fresh insight into the mechanisms behind co-occurrence of HMV and non-HMV phenotypes in monoclonal populations as well as potentially being critical in developing strategies to control the further spread of HMV K. pneumoniae.

Abstract Skeletal muscle is an important motor organ with multinucleated myofibers as its smallest cellular units. Myofibers are formed after undergoing cell differentiation, cell–cell fusion, myonuclei migration, and myofibril crosslinking among other processes and undergo morphological and functional changes or lesions after being stimulated by internal or external factors. The above processes are collectively referred to as myogenesis. After myofibers mature, the function and behavior of skeletal muscle are closely related to the voluntary movement of the body. In this review, we systematically and comprehensively discuss the physiological and pathological processes associated with skeletal muscles from five perspectives: molecule basis, myogenesis, biological function, adaptive changes, and myopathy. In the molecular structure and myogenesis sections, we gave a brief overview, focusing on skeletal muscle‐specific fusogens and nuclei‐related behaviors including cell–cell fusion and myonuclei localization. Subsequently, we discussed the three biological functions of skeletal muscle (muscle contraction, thermogenesis, and myokines secretion) and its response to stimulation (atrophy, hypertrophy, and regeneration), and finally settled on myopathy. In general, the integration of these contents provides a holistic perspective, which helps to further elucidate the structure, characteristics, and functions of skeletal muscle.

Summary: Pyrrolidine (PyD) has an important impact on the environment and human health. However, there is currently no method for trace detection of PyD. Here, we successfully designed diaminomethylene-4H-pyran (1) as the first specific fluorescent probe for PyD. Only by adding PyD to probe 1, there is blue fluorescence at 455 nm, and the color of the solution changes from colorless to yellow. The detection limit is 1.12 × 10−6 M, and the response time is less than 5 min. Meanwhile, probe 1 can also sense the gaseous PyD and detect PyD in actual water samples. Moreover, due to the low biological toxicity, probe 1 can detect the exogenous PyD in zebrafish. The preliminary mechanism shows that probe 1 and PyD undergo a combination-type chemical reaction to generate a new substance 1-PyD. Therefore, the 100% atom utilization reaction enables probe 1 to exhibit specific adsorption and removal of PyD.