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Abstract Directly solving sophisticated partial differential equation constrained optimization problems is not only extremely time-consuming, but also very hard to find unique optimal solutions. Here, we propose stable and efficient surrogate models for seawater reverse osmosis desalination processes that enable thorough quantitative description of hydrodynamics and local transport characteristics in narrow flow channels. Without iteratively solving complex multi-physics simulation problem taking several hours, the proposed multi-scale design optimization framework significantly reduces the problem complexity by computing the surrogate models in seconds. Moreover, a fast-converging active subspace particle swarm optimization framework is proposed to address the optimal design problem. Compared to the standard particle swarm optimization algorithm, the proposed method enhances the average optimum by 14% and the standard deviation of optimum results for multiple runs is reduced by no less than ten times. The optimized desalination system achieves 9% reduction on energy consumption and 30% improvement on water production efficiency.

Abstract Purpose The advantages of en bloc resection of bladder tumors (ERBT) over transurethral resection of bladder tumors (TURBT) in terms of patient prognosis are not yet clear, and there are some technical limitations. We aimed to compare the tumor recurrence in non-muscle invasive bladder cancer (NMIBC) patients with tumor diameter ≥ 3 cm undergoing either TURBT or thulium laser ERBT. Methods The patients included were those diagnosed with NMIBC based on pathological confirmation and underwent TURBT or modified thulium laser ERBT in the Department of Urology at Tongji Hospital from 2019 to 2024. The patients’ medical records were meticulously collected and postoperative follow-up was diligently conducted by trained personnel. Recurrence-free survival curves were generated utilizing the Kaplan–Meier method, and group comparisons were performed using the log-rank trend test. To minimize biases, we employed stratified survival analysis, alongside univariate and multivariate Cox regression analysis. Results This study included a total of 396 patients with NMIBC, with 214 undergoing TURBT and 182 undergoing ERBT. For all patients, there was no significant difference (P = 0.180) in RFS between the TURBT and ERBT groups. For patients with tumor diameter ≥ 3 cm, stratified analysis revealed that the RFS of the ERBT group was significantly better than that of the TURBT group (P = 0.033). However, in patients with tumor diameter

Abstract Background Aging of the male prostate is an inevitable process in which the prostate undergoes hyperplasia, and this growth may lead to compression of the urethra, resulting in voiding dysfunction and associated symptoms, and an increased risk of prostate cancer. Despite the significance of prostate aging, the molecular mechanisms involved are still not fully understood. Methods Prostate split by lobes from young (2 months) and aged (24 months) mice were collected for single-cell RNA sequencing (scRNA-seq) analysis. Tissues from both anterior prostate (AP) and ventral/dorsal/lateral prostate (VDLP) were included in the study. Data analysis included unsupervised clustering using the uniform manifold approximation and projection (UMAP) algorithm to identify distinct cell types based on marker gene expression. Differential gene expression analysis was performed to identify age-related changes in gene expression across different cell types. Functional enrichment analysis was conducted to elucidate biological pathways associated with differentially expressed genes. Additionally, cellular interactions and developmental trajectories were analyzed to characterize cellular dynamics during prostate aging. Results The single-cell transcriptome analysis of the mouse prostate during aging revealed heterogeneity across various cell types and their changes during the aging process. We found a significant increase in the proportion of mesenchymal and immune cells in aged mice. Our study unveiled alterations in genes and pathways associated with cellular senescence, oxidative stress, and regeneration in epithelial cells. Furthermore, we observed that basal cells may undergo epithelial-mesenchymal transition (EMT) to become mesenchymal cells, particularly prominent in aged mice. Additionally, immune cells, notably macrophages and T cells, exhibited a heightened inflammatory response in aged mice. Conclusion In summary, our study provides a comparative analysis of the single-cell transcriptome of the aged and young mice prostates, elucidating cellular and molecular changes between the aged and young mice prostates.

Abstract Background Currently, the indications for pulpectomy of primary molars performed under dental general anesthesia vary across countries. Therefore, we retrospectively investigated the five-year survival rate of primary molars following pulpectomy performed under dental general anesthesia and the impact of this treatment on permanent successors, assessed the risk factors related to overall survival and clarified the indications for pulpectomy. Methods The medical records of children receiving pulpectomy of primary molars under dental general anesthesia from August 1, 2013, to November 30, 2023, were reviewed. Potential risk factors, including gender, age, general health, tooth type, tooth location, endodontic diagnosis and quality of root filling, were assessed via univariate and multivariate Cox proportional hazards regression models, and the survival rate was examined via the Kaplan‒Meier technique. Moreover, the rate of resorption of the root canal filling materials, degree of resorption of the overfilled/over-extended root canal filling materials and development of permanent successors were assessed by clinical and radiographic examination. Results The study included 320 teeth from 161 children (86 boys and 75 girls). The overall five-year survival rate was 38.2%, and the mean overall survival time was 54.2 months. Endodontic diagnosis was considered a significant risk factor (P

Failure of oocyte activation, including polyspermy and defects in pronuclear (PN) formation, triggers early embryonic developmental arrest. Many studies have shown that phospholipase C zeta 1 (PLCZ1) mutations cause failure of PN formation following intracytoplasmic sperm injection (ICSI); however, whether PLCZ1 mutation is associated with polyspermy during in vitro fertilization (IVF) remains unknown. Whole-exome sequencing (WES) was performed to identify candidate mutations in couples with primary infertility. Sanger sequencing was used to validate the mutations. Multiple PLCZ1-mutated sperm were injected into human and mouse oocytes to explore whether PN formation was induced. Assisted oocyte activation (AOA) after ICSI was performed to overcome the failure of oocyte activation. We identified three PLCZ1 mutations in three patients who experienced polyspermy during IVF cycles, including a novel missense mutation c.1154C>T, p.R385Q. PN formation failure was observed during the ICSI cycle. However, injection of multiple PLCZ1-mutated sperm induced PN formation, suggesting that the Ca2+ oscillations induced by the sperm exceeded the necessary threshold for PN formation. AOA after ICSI enabled normal fertilization, and all patients achieved successful pregnancies. These findings expand the mutational spectrum of PLCZ1 and suggest an important role for PLCZ1 in terms of blocking polyspermy. Furthermore, this study may benefit genetic diagnoses in cases of abnormal fertilization and provide potential appropriate therapeutic measures for these patients with sperm-derived polyspermy.

Abstract Background Permanent left bundle branch area pacing (LBBAP) has been established as an effective means to correct left bundle branch block. Right bundle branch block (RBBB), emerge as a distinct form of cardiac conduction abnormality, can be seen in the context of LBBAP procedure. However, the correction potential of LBBAP in patients with RBBB remains largely unexplored. Objective The objective of this study was to evaluate the efficacy and safety of permanent LBBAP in patients with RBBB. Methods Ninety-two consecutive patients who underwent successful permanent LBBAP were recruited from May. 2019 to Dec. 2022 in Fuwai Central China Cardiovascular Hospital. Among them, 20 patients with RBBB were included in our analysis. These patients were followed up at 1, 3, 6 and 12 months post-LBBAP. The QRS duration (QRSd) on the V1 lead of the 12-lead elctrocardiogram was measured and compared before and after the LBBAP procedure. Additionally, mitral regurgitation, tricuspid regurgitation and cardiac function were assessed using transthoracic echocardiography, specifically focusing on left ventricular ejection fraction (LVEF) and mitral regurgitation severity. The acute pitfills and delayed complications associated with the LBBAP procedure were recorded to evaluate its safety. SPSS 23.0 was used to perform statistical analysis with Student’s t test or one way ANOVA or nonparametric tests (paired Wilcoxon test). A p value less than 0.05 was defined as significant. Results The demographic breakdown of the RBBB cohort revealed a mean age of 66.35 ± 11.55 years, 60% being male. Comorbidities were prevalent, including severe atrioventricular block (AVB) in 75%, sick sinus syndrome (SSS) in 20%, heart failure in 25%, atrial fibrillation in 30%, coronary heart diseases in 45%, hypertension in 35%, and diabetes mellitus in 15%. Regarding the LBBAP procedure, the average operation time was 106.53 ± 2.72 min, with 45% of patients (9 individuals) requiring temporary cardiac pacing during the surgery. Notably, the LBBAP procedure significantly narrow the QRS duration in RBBB patients, from 132.60 ± 31.49ms to 119.55 ± 18.58 ms (P = 0.046). Additionally, at the 12-month follow-up, we observed a marked improvement in LVEF, which increased significantly from 55.15 ± 10.84% to 58.5 ± 10.55% (P = 0.018). Furthermore, mitral regurgitation severity improved, with a median reduction from 4.46 (0.9, 7.3) to 2.29 (0, 3.49) cm2 (P = 0.033). Importantly, no cases of ventricular septum perforation or pericardial effusion were reported during the LBBAP procedure or during the follow-up period. Conclusion LBBAP provides an immediate reduction in QRS duration for patients suffering from RBBB, accompanied by improvements in mitral regurgitation and cardiac function as evident in the 12-month follow-up period.

Abstract Recently emerged SAM-Med2D represents a state-of-the-art advancement in medical image segmentation. Through fine-tuning the Large Visual Model, Segment Anything Model (SAM), on extensive medical datasets, it has achieved impressive results in cross-modal medical image segmentation. However, its reliance on interactive prompts may restrict its applicability under specific conditions. To address this limitation, we introduce SAM-AutoMed, which achieves automatic segmentation of medical images by replacing the original prompt encoder with an improved MobileNet v3 backbone. The performance on multiple datasets surpasses both SAM and SAM-Med2D. Current enhancements on the Large Visual Model SAM lack applications in the field of medical image classification. Therefore, we introduce SAM-MedCls, which combines the encoder of SAM-Med2D with our designed attention modules to construct an end-to-end medical image classification model. It performs well on datasets of various modalities, even achieving state-of-the-art results, indicating its potential to become a universal model for medical image classification.

Abstract Strain engineering plays an important role in tuning electronic structure and improving catalytic capability of biocatalyst, but it is still challenging to modify the atomic-scale strain for specific enzyme-like reactions. Here, we systematically design Pt single atom (Pt1), several Pt atoms (Ptn) and atomically-resolved Pt clusters (Ptc) on PdAu biocatalysts to investigate the correlation between atomic strain and enzyme-like catalytic activity by experimental technology and in-depth Density Functional Theory calculations. It is found that Ptc on PdAu (Ptc-PA) with reasonable atomic strain upshifts the d-band center and exposes high potential surface, indicating the sufficient active sites to achieve superior biocatalytic performances. Besides, the Pd shell and Au core serve as storage layers providing abundant energetic charge carriers. The Ptc-PA exhibits a prominent peroxidase (POD)-like activity with the catalytic efficiency (K cat/K m) of 1.50 × 109 mM−1 min−1, about four orders of magnitude higher than natural horseradish peroxidase (HRP), while catalase (CAT)-like and superoxide dismutase (SOD)-like activities of Ptc-PA are also comparable to those of natural enzymes. Biological experiments demonstrate that the detection limit of the Ptc-PA-based catalytic detection system exceeds that of visual inspection by 132-fold in clinical cancer diagnosis. Besides, Ptc-PA can reduce multi-organ acute inflammatory damage and mitigate oxidative stress disorder.

Abstract Background An association has been observed between primary biliary cholangitis (PBC) and systemic rheumatic diseases (SRDs) in observational studies, however the exact causal link remains unclear. We aimed to evaluate the causal effects of PBC on SRDs through Mendelian randomization (MR) analysis. Methods The genome-wide association study (GWAS) summary data were obtained from MRC IEU OpenGWAS and FinnGen databases. Independent genetic variants for PBC were selected as instrumental variables. Inverse variance weighted was used as the main approach to evaluate the causal effects of PBC on Sjögren syndrome (SS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), mixed connective tissue disease (MCTD) and polymyositis (PM). Horizontal pleiotropy and heterogeneity were measured by MR‒Egger intercept test and Cochran’s Q value, respectively. Results PBC had causal effects on SS (OR = 1.177, P = 8.02e-09), RA (OR = 1.071, P = 9.80e-04), SLE (OR = 1.447, P = 1.04e-09), SSc (OR = 1.399, P = 2.52e-04), MCTD (OR = 1.306, P = 4.92e-14), and PM (OR = 1.416, P = 1.16e-04). Based on the MR‒Egger intercept tests, horizontal pleiotropy was absent (all P values > 0.05). The robustness of our results was further enhanced by the leave-one-out method. Conclusions Our research has provided new insights into PBC and SRDs, indicating casual effects on various SRDs.

Abstract High-entropy materials have been proposed for applications in nuclear systems recently due to their outstanding properties in extreme environments. Chemical complexity in these materials plays an important role in irradiation tolerance since it significantly affects energy dissipation and defect behaviors under particle bombardment. Indeed, better resistance to irradiation-induced amorphization was observed in the high-entropy MAX (HE-MAX) phase (Ti, M)2SnC (M = V, Nb, Zr, Hf). However, in this work, we report an opposite trend in another series of HE-MAX phases (Ti, M)2AlC (M = Nb, Ta, V, Zr). It is demonstrated that the amorphization resistance is sequentially reduced as the number of components increases from single-component Ti2AlC to (TiNbTa)2AlC and (TiNbTaVZr)2AlC. These phenomena are verified through AIMD simulations and interpreted by analyzing the underlying properties combining lattice distortion and bonding characteristics through the first-principle calculation. By developing a machine-learning (ML) model, we can directly predict lattice distortion to screen HE-MAX phases with excellent resistance to irradiation-induced amorphization. We highlight that the elemental species plays a more crucial role in the irradiation tolerance of these MAX phases than the number of constituent elements. Knowledge gained from this study will enable an improved understanding of the irradiation tolerance in HE-MAX phases and other multi-elemental ceramics.

Abstract Sulfenylation is a reversible oxidative posttranslational modification (PTM) of proteins on cysteine residues. Despite the dissection of various biological functions of cysteine sulfenylation, its roles in hepatic fibrosis remain elusive. Here, we report that EphB2, a receptor tyrosine kinase previously implicated in liver fibrosis, is regulated by cysteine sulfenylation during the fibrotic progression of liver. Specifically, EphB2 is sulfenylated at the residues of Cys636 and Cys862 in activated hepatic stellate cells (HSCs), leading to the elevation of tyrosine kinase activity and protein stability of EphB2 and stronger interactions with focal adhesion kinase for the activation of downstream mitogen-activated protein kinase signaling. The inhibitions of both EphB2 kinase activity and cysteine sulfenylation by idebenone (IDE), a marketed drug with potent antioxidant activity, can markedly suppress the activation of HSCs and ameliorate hepatic injury in two well-recognized mouse models of liver fibrosis. Collectively, this study reveals cysteine sulfenylation as a new type of PTM for EphB2 and sheds a light on the therapeutic potential of IDE for the treatment of liver fibrosis.

Abstract The dielectric performance of the pristine and the electrothermal‐aged metallised polypropylene capacitors are investigated under different magnetic fields. The energy storage capacity decreases under the magnetic field. At 12 T, the capacitance value of the pristine capacitors decreases by 8.4%–17% and that of the aged capacitors declines by 15%–20%. The dielectric loss is reduced by 2.6%–6.3%, but the equivalent series resistance shows an 8.3%–23.1% growth. The leakage conductivity increases to 202%–354%, which leads to a weakened voltage holding capacity. In addition to the effects of the magnetic fields, the impacts of ageing have also been investigated. The effects of the magnetic field and ageing on the electrical parameters of the capacitors are discussed separately. The molecular chains of the dielectric are oxidised and decomposed during the ageing process, which reduces the insulating properties of the dielectric. The magnetic field inhibits polarisation by changing the polarisation behaviour through Lorentz force and excites the electrons to enhance charge transmission.

Abstract Background The causal relationship between daytime napping and the risk of Parkinson’s disease (PD) remains unclear, with prospective studies providing limited evidence. This study investigated the association between daytime napping frequency and duration and PD incidence and explored the causality relationship between this association by conducting Mendelian randomization (MR) analysis. Methods This prospective cohort study included 393,302 participants, and accelerometer-measured daytime napping data were available only for 78,141 individuals. Cox proportional hazards regression was used to estimate the association between the daytime napping frequency and duration and the PD risk. The role of the systemic immune-inflammation index (SII) in the association between daytime napping frequency and PD risk was assessed through mediation analyses. Moreover, the causal association between the daytime napping frequency and the PD risk was preliminarily explored by conducting two-sample MR analyses. Results The median follow-up duration was 12.18 years. The participants who reported napping sometimes or usually exhibited a significantly higher PD risk than those who never/rarely napped during the day [sometimes: hazard ratio (HR), 1.13; 95% confidence interval (CI), 1.03–1.23; usually: HR, 1.33; 95% CI, 1.14–1.55], and SII played a mediating role in this association. However, the MR analyses did not indicate that the daytime napping frequency and PD risk were significantly associated. The participants napping for over 1 h exhibited a significantly elevated PD risk (HR, 1.54; 95% CI, 1.11–2.16). Moreover, no significant interaction was identified between napping frequency or duration and genetic susceptibility to PD (P for interaction > 0.05). Conclusions In this study, increased daytime napping frequency and duration were associated with an increased PD risk, but no causal relationship was observed between napping frequency and PD risk in the MR analysis. Larger GWAS-based cohort studies and MR studies are warranted to explore potential causal relationships.

Abstract Mammalian TIP60 is a multi-functional enzyme with histone acetylation and histone dimer exchange activities. It plays roles in diverse cellular processes including transcription, DNA repair, cell cycle control, and embryonic development. Here we report the cryo-electron microscopy structures of the human TIP60 complex with the core subcomplex and TRRAP module refined to 3.2-Å resolution. The structures show that EP400 acts as a backbone integrating the motor module, the ARP module, and the TRRAP module. The RUVBL1-RUVBL2 hexamer serves as a rigid core for the assembly of EP400 ATPase and YL1 in the motor module. In the ARP module, an ACTL6A-ACTB heterodimer and an extra ACTL6A make hydrophobic contacts with EP400 HSA helix, buttressed by network interactions among DMAP1, EPC1, and EP400. The ARP module stably associates with the motor module but is flexibly tethered to the TRRAP module, exhibiting a unique feature of human TIP60. The architecture of the nucleosome-bound human TIP60 reveals an unengaged nucleosome that is located between the core subcomplex and the TRRAP module. Our work illustrates the molecular architecture of human TIP60 and provides architectural insights into how this complex is bound by the nucleosome.

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

Abstract MXene materials have emerged as promising candidates for solving sustainable energy storage solutions due to their unique properties and versatility. MXene materials can not only be used directly as electrode materials but can also be used as functional materials to solve problems such as poor conductivity of electrode materials, severe volume expansion, dendrites, and dissolution of electrode materials. This perspective paper explores the potential applications of MXene materials for sustainable energy storage solutions, emphasizing their distinct characteristics and applications across various domains.

Abstract Background Computed tomography (CT) is the usual modality for diagnosing stroke, but conventional CT angiography reconstructions have limitations. Methods A phantom with tubes of known diameters and wall thickness was scanned for wall detectability, wall thickness, and contrast-to-noise ratio (CNR) on conventional and spectral black-blood (SBB) images. The clinical study included 34 stroke patients. Diagnostic certainty and conspicuity of normal/abnormal intracranial vessels using SBB were compared to conventional. Sensitivity/specificity/accuracy of SBB and conventional were compared for plaque detectability. CNR of the wall/lumen and quantitative comparison of remodeling index, plaque burden, and eccentricity were obtained for SBB imaging and high-resolution magnetic resonance imaging (hrMRI). Results The phantom study showed improved detectability of tube walls using SBB (108/108, 100% versus conventional 81/108, 75%, p

Thread of pin has been proved beneficial to increasing shear action of tool and material intermixing, which however induces abundant formation of intermetallic compounds (IMCs) in Mg/Al dissimilar friction stir welding (FSW) leading to deteriorating the performance of joints. In this work, Mg alloy and Al alloy were well joined by threaded pin and unthreaded pin under the same welding parameters. For threaded pin joints, cracks occured in the banded structure (BS) region and bottom interface, then the main crack propagated along the Mg/Al interface, resulting in low strength and elongation. For unthreaded pin joints, necking and fracture occurred at the softened Al alloy to the retreating side (SAA-RS), and the fracture mode changed from brittle fracture (Mode I) to ductile fracture (Mode III). The tensile strength and strain of unthreaded pin joints are 201 MPa and 7.14 % respectively, significantly higher than those of threaded pin joints (i.e. 140 MPa and 1.15 %), and is the highest combination of strength and strain reported up until now. An unthreaded pin could reduce the local micro-intermixing between Mg and Al to suppress the formation of IMCs, which reduced the hardness in the BS region, preventing the formation and propagation of cracks.

This study investigates the impact of inflation rate fluctuations on economic growth in China, with a particular focus on potential non-linear characteristics. The global economic impact of the COVID-19 pandemic notably heightens the study's relevance. The research that the unidirectional causal relationship from inflation to economic growth in China first strengthens and then weakens over time. Furthermore, there is an inflation rate threshold effect on economic growth, identified at 2%. Below this threshold, inflation positively influences economic growth, whereas above it, the impact turns negative. This finding underscores the importance of balancing economic growth with inflation control in the formulation of monetary policy.

BackgroundThe relationship between vegetarianism and mental well-being remains a debated topic in traditional observational studies. Recent studies have revealed the genetic factors in vegetarianism. We aimed to use genetic variations to explore the potential causal relationships between vegetarianism and mental well-being, offering insights from a new perspective.MethodsWe conducted the inverse variance weighted approach as the primary analysis to explore the bidirectional genetic associations between vegetarianism (N = 442,589) and depressive symptoms (N = 180,866), neuroticism (N = 170,910), and subjective well-being (N = 298,420). The analysis used the summary data from the largest genome-wide association studies (GWAS). We also performed sensitivity analyses to ensure the robustness of the findings, accounting for potential heterogeneity and pleiotropy.ResultsGenetically predicted vegetarianism showed positive causal relationships with depressive symptoms (odds ratio [OR], 3.26; 95% confidence interval [CI], 1.03–10.31; p = 0.044) and neuroticism (OR, 6.72; 95% CI, 2.29–19.74; p = 5.31 × 10−4), as well as a negative causal relationship with subjective well-being (OR, 0.20; 95% CI, 0.05–0.77; p = 0.019). Additionally, depressive symptoms were found to have a causal influence on vegetarianism (OR, 1.01; 95% CI, 1.00–1.02; p = 6.87 × 10−3). No significant heterogeneity or pleiotropy was detected.ConclusionVegetarianism is causally correlated with negative mental well-being, reflected in an increased risk of depressive symptoms and neuroticism, as well as lower subjective well-being. Further research should explore the underlying mechanisms in broader populations.

ObjectivesThis study aims to develop a novel diagnostic approach using the recombinase aided amplification-lateral flow dipstick(RAA-LFD) assay for the distinction of Mycobacterium tuberculosis (MTB) and Mycobacterium avium complex (MAC), enabling rapid and convenient as well as accurate identification of them in clinical samplesMethodsOur study established a duplex RAA-LFD assay capable of discriminating between MTB and MAC. Based on the principles of RAA primer and probe design, specific primers and probes were developed targeting the MTB IS6110 and the MAC DT1 separately. Optimization of reaction time points and temperatures was conducted, followed by an evaluation of specificity, sensitivity, and reproducibility. The established detection method was then applied to clinical samples and compared with smear microscopy, liquid culture, LAMP, and Xpert/MTB RIF in terms of diagnostic performanceResultsThe complete workflow allows for the effective amplification of the MTB IS6110 and MAC DT1 target sequences at constant 37°C within 20min, and the amplification products can be visually observed on the LFD test strip. This method exhibits high specificity, showing no cross-reactivity with nucleic acids from M. kansassi, M. abscessus, M. gordonae, M. chelonae, M. fortuitum, M. scrofulaceum, M. malmoense, M. chimaera, M. szulgai and common respiratory pathogens. It also demonstrates high sensitivity, with a detection limit as low as 102 CFU/mL. Additionally, the method’s Coefficient of Variation (CV) is less than 5%, ensuring excellent repeatability and reliability. Furthermore, clinical performance evaluations, using Xpert/MTB RIF as the gold standard, demonstrated that the duplex RAA-LFD assay achieves a sensitivity of 92.86% and a specificity of 93.75%. It is also noteworthy that the assay exhibits considerable diagnostic efficacy in smear-negative patientsConclusionsOur study introduces a rapid, specific, and sensitive duplex RAA-LFD assay for the discriminatory diagnosis of MTB and MAC. This method represents a significant advancement in the field of infectious disease diagnostics, offering a valuable tool for rapid detection and management of MTB and MAC infections. The implementation of this approach in point-of-care settings could greatly enhance TB control and prevention efforts, especially in resource-limited environments.

The repair of bone defects in the elderly individuals is significantly delayed due to cellular senescence and dysfunction, which presents a challenge in clinical settings. Furthermore, there are limited effective methods available to promote bone repair in older individuals. Herein, melatonin-loaded mesoporous bioactive glasses microspheres (MTBG) were successfully prepared based on their mesoporous properties. The repair of bone defects in aged rats was significantly accelerated by enhancing mitochondrial function through the sustained release of melatonin and bioactive ions. MTBG effectively rejuvenated senescent bone marrow mesenchymal stem cells (BMSCs) by scavenging excessive reactive oxygen species (ROS), stabilizing the mitochondrial membrane potential (ΔΨm), and increasing ATP synthesis. Analysis of the underlying mechanism revealed that the formation of tunneling nanotubes (TNTs) facilitated the intercellular transfer of mitochondria, thereby resulting in the recovery of mitochondrial function. This study provides critical insights into the design of new biomaterials for the elderly individuals and the biological mechanism involved in aged bone regeneration.

Unsafe hoisting operations have been consistently associated with numerous safety incidents involving tower cranes. Currently, the predominant measures to mitigate these operations center around comprehensive training and education, emphasizing standardized protocols prior to hoisting activities. Despite concerted efforts in this direction, a conspicuous research gap persists in early-warning mechanisms during the construction phase. This paper aims to address this gap by proposing an innovative early-warning methodology, inspired by the principles of digital twin and knowledge graph. We firstly introduce a digital twin framework designed to mirror the real-time operational status of the tower crane. This framework enables the immediate detection of deviations or infractions as they occur. Subsequently, we develop a knowledge graph capable of promptly identifying unsafe hoisting operations by leveraging real-time data obtained from the digital twin. To validate the efficacy of our proposed methodology, we construct a scaled-down replica of a tower crane and establish a tailored digital twin system. The findings of a series of experimental trials prominently underscore the system's capability to generate timely alerts in response to unsafe hoisting operations while maintaining an impressively low rate of false alarms.

Janus metasurfaces emerge as a promising platform for implementing multiple wave functionalities by fully exploiting the inherent propagation direction of electromagnetic waves. Their out‐of‐plane asymmetric structures enable different wave functions depending on the propagation direction. Herein, a multiplexed Janus metasurface is proposed, which operates in the microwave region to flexibly manipulate the transmission and reflection wavefronts for same linearly polarized (LP) incidence propagating along the two opposite directions. A meta‐lens is constructed to validate the concept of full‐space shared‐aperture transmission‐reflection‐independent focusing of electromagnetic (EM) waves, exhibiting four distinct focusing performances. Experiments are conducted in the microwave region that agree well with the simulation results. The proposed full‐space Janus metasurface may provide a platform for asymmetric imaging, multichannel information processing, and encrypted communication.

Edge computing, a key technology in the Internet of Things, can help integrate real-time fault diagnosis into industrial applications. Lightweight and compression technologies are essential for deploying high-precision deep learning methods on resource-constrained edge computing systems. However, modeling accuracy is severely compromised by existing methods. To overcome this limitation, a new multi-stage pruning and distillation architecture was proposed in this study to compress a depthwise separable convolutional network for intelligent fault diagnosis of bearings in edge computing systems. The model was implemented on an NVIDIA Jetson Nano and verified using two bearing fault datasets. The results show that the proposed method can significantly reduce the calculation and reasoning time of the model and maintain high accuracy. The proposed method exhibits remarkable effectiveness, requires minimal memory, provides fast inference speeds, and is suitable for use in edge devices with less configuration.

Abstract The “shuttle effect” issue severely hinders the practical application of lithium–sulfur (Li–S) batteries, which is primarily caused by the significant accumulation of lithium polysulfides in the electrolyte. Designing effective catalysts is highly desired for enhancing polysulfide conversion to address the above issue. Here, the one‐step flash‐Joule‐heating route is employed to synthesize a W‐W2C heterostructure on the graphene substrate (W‐W2C/G) as a catalytic interlayer for this purpose. Theoretical calculations reveal that the work function difference between W (5.08 eV) and W2C (6.31 eV) induces an internal electric field at the heterostructure interface, accelerating the movement of electrons and ions, thus promoting the sulfur reduction reaction (SRR) process. The high catalytic activity is also confirmed by the reduced activation energy and suppressed polysulfide shuttling by in situ Raman analyses. With the W‐W2C/G interlayer, the Li–S batteries exhibit an outstanding rate performance (665 mAh g−1 at 5.0 C) and cycle steadily with a low decay rate of 0.06% over 1000 cycles at a high rate of 3.0 C. Moreover, a high areal capacity of 10.9 mAh cm−2 (1381.4 mAh g−1) is obtained with a high area sulfur loading of 7.9 mg cm−2 but a low electrolyte/sulfur ratio of 9.0 µL mg−1.

This study explored the mechanism by which forkhead box O-1 (FoxO1) modulates the biological behaviors of bone mesenchymal stem cell (BMSC). Human BMSCs were cultured for 7 days in DMEM containing bone morphogenetic protein-2 (BMP-2) and treated with a short hairpin-FoxO1 plasmid. The study assessed cell proliferation, migration, apoptosis, adenosine triphosphate (ATP) levels, mitochondrial DNA levels, membrane potential, autophagy, and the levels of FoxO1, apoptosis-associated proteins, osteogenic differentiation-associated proteins, mitochondrial fusion and fission proteins and mitochondrial autophagy-related proteins. The cells were also treated with the mitochondrial fusion activator MASM7 and the mitochondrial autophagy activator carbonyl cyanide 3-chlorophenylhydrazone. The study evaluated whether mitochondrial dynamics and autophagy activation could rescue the FoxO1 knockdown-induced changes in BMSC biological behaviors, mitochondrial dynamics, and mitochondrial autophagy. BMP-2-induced BMSCs exhibited up-regulated FoxO1 expression, enhanced proliferation and migration, and induced osteogenic differentiation, while FoxO1 knockdown inhibited BMP-2-induced BMSC proliferation, migration and osteogenic differentiation, increased apoptosis, and affected mitochondrial dynamics and autophagy. Promoting mitochondrial fusion partially reversed the regulatory effects of FoxO1 downregulation on mitochondrial autophagy and the inhibitory effects of FoxO1 silencing on BMP-2-induced BMSC biological behaviors. Activated mitochondrial autophagy facilitated the homeostasis of mitochondrial dynamics and partially counteracted the inhibitory effects of FoxO1 knockdown on BMP-2-induced BMSC biological behaviors. In conclusion, FoxO1 regulates mitochondrial dynamics and autophagy to modulate the osteogenic differentiation of BMP-2-induced human BMSCs.

Indoor environments can pose a substantial respiratory infection risk, especially in densely populated areas. It is therefore vital to evaluate and predict infection risks for mobile individuals engaging in indoor activities. However, previous studies have primarily focused on assessing viral transmission probabilities between relatively stationary individuals, disregarding the dynamic features of pedestrian trajectories. To address this issue, we propose an approach that uses precise trajectory data and digital twin technology to evaluate and forecast indoor infection risks for mobile individuals. Our approach involves the utilization of high-precision trajectory data to develop a time-varying virus density field map (VDFM), forming the basis for infection risk assessment. Additionally, we present a deep-learning model that employs the transformer method to predict future time-varying VDFMs and associated infection risks. Furthermore, we introduce digital twin to comprehend real-time interactions between the physical and digital realms within the structure. To validate our approach, we conducted a case study at the Wuhan International Exposition Center, serving as the control room. We performed a sensitivity analysis on various preventive measures, including mask-wearing, social distancing, and indoor infection control. The results highlighted the significant impact of these measures on individual infection risks associated with indoor activities. Our research contributes to the development of tailored prevention and control strategies, which play a critical role in mitigating the spread of respiratory infections. Thus, this study holds significant implications for technology-facilitated public health services.

Understanding the recovery mechanism associated with the dislocation cell structure in 316L austenitic stainless steel produced by selective laser melting (SLM), as well as the role played by the accompanying segregation network, is crucial for tailoring the microstructures and mechanical properties of SLM-prepared components. In the present work, the evolution of the dislocation cells was investigated during isothermal annealing, and a recovery mechanism for the dislocation cell structure was proposed based on a combination of microstructural observations and recovery kinetics analysis. The results show that the high-density dislocations at the cell boundaries annihilate during prolonged annealing at 800 °C, resulting in the decomposition of the dislocation cells. The recovery kinetics analysis reveals that SLM-prepared 316L exhibits a lower recovery rate and requires significantly higher apparent activation energy during annealing compared to conventional 316L deformed by cold rolling. The segregation network plays an important role during the dislocation recovery process, which limits the dislocation reaction occurring within the cell boundaries at the early stage of recovery, impedes the dislocation motion after the decomposition of dislocation cells, and leads to a strong temperature dependence of recovery kinetics in SLM-prepared 316L.

Abstract The identification of genes involved in salinity tolerance has primarily focused on model plants and crops. However, plants naturally adapted to highly saline environments offer valuable insights into tolerance to extreme salinity. Salicornia plants grow in coastal salt marshes, stimulated by NaCl. To understand this tolerance, we generated genome sequences of two Salicornia species and analyzed the transcriptomic and proteomic responses of Salicornia bigelovii to NaCl. Subcellular membrane proteomes reveal that SbiSOS1, a homolog of the well-known SALT-OVERLY-SENSITIVE 1 (SOS1) protein, appears to localize to the tonoplast, consistent with subcellular localization assays in tobacco. This neo-localized protein can pump Na+ into the vacuole, preventing toxicity in the cytosol. We further identify 11 proteins of interest, of which SbiSALTY, substantially improves yeast growth on saline media. Structural characterization using NMR identified it as an intrinsically disordered protein, localizing to the endoplasmic reticulum in planta, where it can interact with ribosomes and RNA, stabilizing or protecting them during salt stress.

Abstract Pneumonia is a common comorbidity in patients with severe traumatic brain injury (TBI), and is associated with increased morbidity and mortality. In this study, we established a model of intratracheal Klebsiella pneumoniae administration in young adult male and female mice, at 4 days following an experimental TBI, to investigate how K. pneumoniae infection influences acute post-TBI outcomes. A dose-response curve determined the optimal dose of K. pneumoniae for inoculation (1 x 10^6 colony forming units), and administration at 4 days post-TBI resulted in transient body weight loss and sickness behaviors (hypoactivity and acute dyspnea). K. pneumoniae infection led to an increase in pro-inflammatory cytokines in serum and bronchoalveolar lavage fluid at 24 h post-infection, in both TBI and sham (uninjured) mice. By 7 days, when myeloperoxidase + neutrophil numbers had returned to baseline in all groups, lung histopathology was observed with an increase in airspace size in TBI + K. pneumoniae mice compared to TBI + vehicle mice. In the brain, increased neuroinflammatory gene expression was observed acutely in response to TBI, with an exacerbated increase in Ccl2 and Hmox1 in TBI + K. pneumoniae mice compared to either TBI or K. pneumoniae alone. However, the presence of neuroinflammatory immune cells in the injured brain, and the extent of damage to cortical and hippocampal brain tissue, was comparable between K. pneumoniae and vehicle-treated mice by 7 days. Examination of the fecal microbiome across a time course did not reveal any pronounced effects of either injury or K. pneumoniae on bacterial diversity or abundance. Together, these findings demonstrate that K. pneumoniae lung infection after TBI induces an acute and transient inflammatory response, primarily localized to the lungs with some systemic effects. However, this infection had minimal impact on secondary injury processes in the brain following TBI. Future studies are needed to evaluate the potential longer-term consequences of this dual-hit insult.

Skeleton-based action recognition is an important but challenging task in the study of video understanding and human-computer interaction. However, existing methods suffer from two deficiencies. On the one hand, most methods usually involve manually designed convolution kernel which cannot capture spatial-temporal joint dependencies of complex regions. On the other hand, some methods just use the self-attention mechanism, ignoring its theoretical explanation. In this paper, we proposed a unified spatio-temporal graph convolutional network with a self-attention mechanism (SA-GCN) for low-quality motion video data with fixed viewing angle. SA-GCN can extract features efficiently by learning weights between joint points of different scales. Specifically, the proposed self-attention mechanism is end-to-end with mapping strategy for different nodes, which not only characterizes the multi-scale dependencies of joints, but also integrates the structural features of the graph and an ability of self-learning fusion features. Moreover, the attention mechanism proposed in this paper can be theoretically explained by GCN to some extent, which is usually not considered in most existing models. Extensive experiments on two widely used datasets, NTU-60 RGB+D and NTU-120 RGB+D, demonstrated that SA-GCN significantly outperforms a series of existing mainstream approaches in terms of accuracy.

【Objective】Drought is one of the main abiotic factors that affect rice productivity. Rice yield can be ensured by screening drought-resistant rice.【Method】Ninety-three single-segment substitution lines (SSSLs) constructed from Oryza. meridionalis and O. glumaepatula and their recipient parents 'Huajingxian 74'(HJX74) were used as the test materials. And 20% PEG-6000 was adopted to simulate drought conditions to perform drought tolerance tests at the seedling stage. Besides, four growth and development traits (relative seedling height, relative seedling dry weight, relative root dry weight and relative root length) were used as evaluation indicators. The membership function method was utilized to sort SSSLs and screen SSSLs with relevant traits significantly different from HJX74. Based on the QTL identification and additive effect analysis, QTL related to drought tolerance traits at the seedling stage was preliminarily identified.【Result】The analysis of correlation between the four growth and development traits and the average membership function value revealed that they were all extremely significantly positively correlated, and could be used as indicators for identifying and evaluating the drought tolerance in the seedling stage of SSSLs. According to the analysis result of the membership function method, the average membership function value of the tested SSSLs ranged from 0.20 to 0.71, and the average membership function value of HJX74 was 0.54. The average membership function value of 29 SSSLs was greater than that of HJX74. Among them, M124 had the largest membership function value, indicating strong drought tolerance of M124. Through single factor analysis of variance, 7 relative seedling height QTLs (qRSH1-1, qRSH1-2, qRSH2-1, qRSH3-1, qRSH3-2, qRSH5-1, and qRSH6-1) were identified from 8 SSSLs (M78-1, M78-2, M124, M107, M151, M103, M130, M115), which were distributed on Chromosomes 1, 2, 3, 5, and 6. Their additive effect was 0.05-0.06, and the phenotypic contribution rate was 6.97%-9.01%. Three relative root dry weight QTLs (qRRDW10-1, qRRDW11-1, and qRRDW11-2) were identified from three SSSLs (M79, M145, M148), which were distributed on chromosomes 10 and 11. The additive effect was 0.12-0.20, and the phenotypic contribution rate was 12.51%-19.95%. A relative seedling dry weight QTL (qRSDW5-1) was identified from 2 drought-tolerant SSSLs (M80, X149), and distributed on chromosome 5, with the additive effect of 0.07 and the phenotypic contribution rate of 10.5%.【Conclusion】A total of 13 SSSLs with drought-tolerant QTLs at the seedling stage are screened, laying a solid foundation for further study on fine mapping and cloning.

Vertebrate neurons are highly dynamic cells that undergo several alterations in their functioning and physiologies in adaptation to various external stimuli. In particular, how these neurons respond to physical exercise has long been an area of active research. Studies of the vertebrate locomotor system's adaptability suggest multiple mechanisms are involved in the regulation of neuronal activity and properties during exercise. In this brief review, we highlight recent results and insights from the field with a focus on the following mechanisms: (a) alterations in neuronal excitability during acute exercise; (b) alterations in neuronal excitability after chronic exercise; (c) exercise-induced changes in neuronal membrane properties via modulation of ion channel activity; (d) exercise-enhanced dendritic plasticity; and (e) exercise-induced alterations in neuronal gene expression and protein synthesis. Our hope is to update the community with a cellular and molecular understanding of the recent mechanisms underlying the adaptability of the vertebrate locomotor system in response to both acute and chronic physical exercise.

Abstract The disruption of circadian rhythms caused by long-term shift work can cause metabolic diseases such as obesity. Early growth response 3 (EGR3) is a member of early growth response (EGR) family, which is involved in several cellular responses, had been reported as a circadian rhythm gene in suprachiasmatic nucleus. In this research, EGR3 was found to be widely expressed in the different tissue of human and mice, and downregulated in adipose tissue of obese subjects and high-fat diet mice. Moreover, EGR3 was found negatively regulated by cortisol. In addition, EGR3 is a key negative modulator of hADSCs and 3T3-L1 adipogenesis via regulating HDAC6, which is a downstream target gene of EGR3 and a negative regulator of adipogenesis and lipogenesis. These findings may explain how circadian rhythm disorder induced by shift works can cause obesity. Our study revealed a potential therapeutic target to alleviate metabolic disorders in shift workers and may provide better health guidance to shift workers.

Abstract Background Ultrasound three-dimensional visualization, a cutting-edge technology in medical imaging, enhances diagnostic accuracy by providing a more comprehensive and readable portrayal of anatomical structures compared to traditional two-dimensional ultrasound. Crucial to this visualization is the segmentation of multiple targets. However, challenges like noise interference, inaccurate boundaries, and difficulties in segmenting small structures exist in the multi-target segmentation of ultrasound images. This study, using neck ultrasound images, concentrates on researching multi-target segmentation methods for the thyroid and surrounding tissues. Method We improved the Unet++ to propose PA-Unet++ to enhance the multi-target segmentation accuracy of the thyroid and its surrounding tissues by addressing ultrasound noise interference. This involves integrating multi-scale feature information using a pyramid pooling module to facilitate segmentation of structures of various sizes. Additionally, an attention gate mechanism is applied to each decoding layer to progressively highlight target tissues and suppress the impact of background pixels. Results Video data obtained from 2D ultrasound thyroid serial scans served as the dataset for this paper.4600 images containing 23,000 annotated regions were divided into training and test sets at a ratio of 9:1, the results showed that: compared with the results of U-net++, the Dice of our model increased from 78.78% to 81.88% (+ 3.10%), the mIOU increased from 73.44% to 80.35% (+ 6.91%), and the PA index increased from 92.95% to 94.79% (+ 1.84%). Conclusions Accurate segmentation is fundamental for various clinical applications, including disease diagnosis, treatment planning, and monitoring. This study will have a positive impact on the improvement of 3D visualization capabilities and clinical decision-making and research in the context of ultrasound image.

Whilst automated analysis of immunostains in pathology research has focused predominantly on the epithelial compartment, automated analysis of stains in the stromal compartment is challenging and therefore requires time-consuming pathological input and guidance to adjust to tissue morphometry as perceived by pathologists. This study aimed to develop a robust method to automate stromal stain analyses using 2 of the commonest stromal stains (SMA and desmin) employed in clinical pathology practice as examples. An effective computational method capable of automatically assessing and quantifying tumour-associated stromal stains was developed and applied on cores of colorectal cancer tissue microarrays. The methodology combines both mathematical models and deep learning techniques with the former requiring no training data and the latter as many inputs as possible. The novel mathematical model was used to produce a digital double marker overlay allowing for fast automated digital multiplex analysis of stromal stains. The results show that deep learning methodologies in combination with mathematical modelling allow for an accurate means of quantifying stromal stains whilst also opening up new possibilities of digital multiplex analyses.

BackgroundMyelofibrosis (MF) is a myeloproliferative neoplasm characterized by bone marrow fibrosis associated with substantial morbidity and mortality. The therapeutic landscape for MF has advanced with the development of Janus kinase inhibitors (JAKis) like ruxolitinib (RUX), fedratinib (FED), pacritinib (PAC), and momelotinib (MMB), aiming to alleviate symptoms and enhance patient comfort.MethodsA network meta-analysis was conducted to assess the efficacy and safety of eleven JAKi treatment regimens across nine randomized controlled trials (RCTs) with a total of 2340 participants. Outcomes were evaluated in terms of spleen volume reduction (SVR), total symptom score reduction (TSSR), hematological safety profiles, and overall survival (OS).ResultsRUX and MMB were superior in achieving SVR and TSSR, with significant dose-response relationships observed. PAC and MMB were associated with a decreased risk of grade 3/4 anemia and thrombocytopenia compared to other JAKis. However, no substantial benefits in OS were observed with newer JAKis compared to RUX. The poorer OS outcomes with certain PAC dosages were likely influenced by baseline patient characteristics, particularly severe cytopenias.ConclusionThe introduction of JAKis significantly changed the treatment of MF. This meta-analysis reaffirms the core role of RUX and positions MMB as a potentially powerful alternative for treating symptoms and reducing spleen size. Meanwhile, MMB and PAC have a positive effect on anemia in MF while FED is more tolerable for patients with thrombocytopenia. However, it should be noted that these results are influenced by baseline patient characteristics, particularly cytopenias, which affects both management and overall survival. Therefore, there is an urgent need for personalized dosing strategies to optimize the balance between efficacy and safety, with careful consideration of patient-specific factors.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023424179.

In this paper, using the data collected from phasor measurement units (PMUs), two methods based on Fisher random matrix are proposed to detect faults in power grids. Firstly, the fault detection matrix is constructed and the event detection problem is reformatted as a testing problem for two-sample covariance matrices, which is related with the so-called Fisher matrix. To save computing resources, the screening step of fault interval based on the test statistic is designed to check the existence of faults. Then two point-by-point methods are proposed to determine the time of the fault in the selected interval. One method detects faults by the limiting spectral distribution of the standard Fisher matrix, which can detect the faults with higher accuracy. The other method tests the faults based on the proposed test statistic , which has a faster detection speed. Compared with existing works, the simulation results illustrate that two methods proposed in this paper cost less computational time and provide a higher degree of accuracy and sensitivity.

BackgroundMalnutrition has emerged as main side effects of inflammatory bowel disease (IBD) which might also affect the prognosis of IBD. However, whether these associations are causal remains unclear. We aimed to identify the causality of IBD on malnutrition and explore the causal relationship of malnutrition and nutrients intake on IBD by using Mendelian randomization (MR).MethodsSingle nucleotide polymorphisms associated with IBD, malnutrition and nutrients intake were obtained from previous researches of genome-wide association studies (GWAS) (p 0.05). Further analysis showed similar results that nutrients intake had no direct effect on IBD, neither CD or UC.ConclusionOur results indicated that IBD increases the risk of malnutrition, however, malnutrition and nutrients intake might not directly affect the progression of IBD.

ABSTRACT Polycystic ovary syndrome (PCOS) is a common disease associated with high androgen and infertility. The gut microbiota plays an important role in metabolic diseases including obesity, hyperglycemia, and fatty liver. Although the gut microbiota has been associated with PCOS, little is known about the gut microbial structure and function in individuals with PCOS from Northeast China. In this study, 17 PCOS individuals and 17 age-matched healthy individuals were recruited for community structure and function analysis of the gut microbiota. The results showed that PCOS individuals have reduced diversity and richness of the gut microbiota compared with healthy individuals. Beta diversity analysis showed that the community structure of the gut microbiota of individuals with PCOS was significantly separated from healthy individuals. At the phylum level, PCOS individuals have reduced Firmicutes and Bacteroidota and increased Actinobacteriota and Proteobacteria compared with healthy individuals. At the family and genus levels, the composition of the gut microbiota between PCOS patients and healthy individuals was also significantly different. In addition, PICRUSt2 showed that individuals with PCOS have different microbial functions in the gut compared with healthy individuals. We finally confirmed that Bifidobacterium was enriched in the fecal samples of PCOS patients, while other 11 genera including Bacteroides, UCG_002, Eubacterium__coprostanoligenes_group_unclassified, Dialister, Firmicutes_unclassified, Ruminococcus, Alistipes, Christensenellaceae_R_7_group, Clostridia_UCG_014_unclassified, Roseburia, and Lachnospiraceae_unclassified were depleted compared with healthy individuals. These results indicate that individuals with PCOS have altered community structure and functions of the gut microbiota, which suggests that targeting the gut microbiota might be a potential strategy for PCOS intervention.IMPORTANCEGut microbiota plays a critical role in the development of PCOS. There is a complex and close interaction between PCOS and gut microbiota. The relationship between the pathogenesis and pathophysiological processes of PCOS and the structure and function of the gut microbiota needs further investigation.

Joint stiffness and fibrosis are common complications that affect mobility and quality of life, necessitating effective therapeutic strategies to alleviate these issues. The study aimed to observe the therapeutic effect of static progressive stretching (SPS) combined with botulinum toxin type A (BTX-A) on knee joint stiffness in rats and its effect on the transforming growth factor beta 1 (TGF-β1)/small mother against decapentaplegic (Smad) pathway in the development of joint capsule fibrosis. Forty Sprague Dawley rats were randomly divided into the blank control group, model control group, SPS intervention group, BTX-A intervention group, and SPS combined with BTX-A intervention group. Except for the blank control group, the right knee joints of the other rats were surgically fixed with Kirschner wire internal immobilization in full flexion for four weeks to form joint flexion contracture and cause fibrotic stiffness of the joint. The therapeutic effect of each intervention was assessed by the range of motion (ROM) of the knee joint, joint stiffness, the number of total cells, and collagen deposition in the posterior joint capsule, as well as the protein level expressions of TGF-β1, Smad2, Smad3, Smad4, p-Smad2/3, collagen I and III, and alpha smooth muscle actin (α-SMA) in the posterior joint capsule in the TGF-β1/Smad pathway. SPS combined with BTX-A was more effective in relieving joint fibrosis stiffness, improving the histopathological changes in the posterior joint capsule, and suppressing the high expression of target proteins and the overactivated TGF-β1/Smad pathway. The overactivated TGF-β1/Smad pathway was involved in the formation of knee joint fibrosis stiffness in rats. SPS combined with BTX-A was effective in relieving joint flexion contracture and fibrosis of the joint capsule. Moreover, the inhibition of the overactivated TGF-β1/Smad pathway may be the potential molecular mechanism for its therapeutic effect.

Background Tumor deposits (TD) was a significant risk factor impacting the prognosis of patients diagnosed with gastric cancer (GC), yet it was not currently incorporated into TNM staging systems. The objective of this research was to develop a predictive model for assessing the prognosis of patients with TD-positive GC. Methods Retrospective analysis was performed on the data of 4,972 patients treated for GC with D2 radical gastrectomy at Wannan Medical College’s Yijishan Hospital between January 2012 and December 2021. The patients were categorized based on the number of TD (L1: 1, L2: 2–3, L3: ≥4) and the anatomical location of TD (Q1: single area, Q2: multiple areas). In a 3:1 ratio, patients were randomly assigned to one of two groups: training or validation. Results The study included a total of 575 patients who were divided into the training group (n = 432) and validation group (n = 143). Survival analysis showed that the number and anatomical location of TD had a significant impact on the prognosis of patients with TD-positive GC. Univariate analysis of the training group data revealed that tumor size, T-stage, N-stage, histological grade, number and distribution of TD, neural invasion, and postoperative chemotherapy were associated with prognosis. Multivariate Cox regression analysis identified poor histological grade, T4 stage, N3 stage, number of TD, neural invasion, and postoperative chemotherapy as independent prognostic factors for GC patients with TD. A nomogram was developed using these variables, demonstrating well predictive ability for 1, 3, and 5-year overall survival (OS) in the validation set. The DCA curve shows that the constructed model shows a large positive net gain compared to the eighth edition Tumour, Node, Metastasis (TNM) staging system. Conclusion The prognostic model developed for patients with TD-positive GC has a higher clinical utility compared to the eighth edition of TNM staging.

The non-fullerene acceptor (NFA) chromophores have sparked scientific and economic interest, due to their rapid advancements in power conversion efficiencies. Therefore, a series of new chlorothiazole based compounds (STM1-STM6) with A1–π–A2–π–A1 configuration was designed using reference chromophore (STMR). Structural modifications were made via incorporating selenophene and extended acceptor units, to enhance photovoltaic response in the designed materials. Density functional theory/time dependent-density functional theory (DFT/TD-DFT) calculations were executed at M06/6-311G (d,p) level to investigate key electronic and photovoltaic properties of STM1-STM6. So, various analyses such as UV–Visible, frontier molecular orbitals (FMOs), transition density matrix (TDM), density of states (DOS), open circuit voltage (Voc) and binding energy (Eb) were conducted to comprehend the photovoltaic properties. The designing in structural aspects with terminal acceptors and π-linker induced a reduction in energy gaps (ΔE = 2.078–2.237 eV) with an enhancement in the bathochromic shift (λmax = 744.650–798.250 nm in chloroform) than reference compound. A higher exciton dissociation rate was observed in all the compounds due to lower binding energy values (Eb = 0.525–0.572 eV). Additionally, TDM and DOS findings further endorsed the effective charge delocalization from HOMO to LUMO. Among all the examined compounds, STM3 exhibited the smallest band gap (2.078 eV), highest absorption maxima (798.250 nm), and the lowest exciton binding energy (0.525 eV), indicating significant electronic properties. Moreover, Voc analysis was conducted with respect to HOMOPBDBT-LUMOacceptor for all the designed chromophores; consequently, STM2 demonstrated a substantial Voc value of 1.647 V. Similarly, electron hole analysis was also conducted and significant electron and hole density was observed in all the investigated compounds, especially in STM2. The entitled compounds with photovoltaic potential would be considered as promising materials for the development of solar energy devices.

Currently, there is evidence to suggest the benefits of drinking fermented tea for people with osteoporosis, and based on this, many studies have been conducted on the dosage, exact ingredients, mechanisms, and industrial applications of fermented tea for protecting against osteoporosis. A summary and analysis of studies on the regulation of bone mass by oolong tea, black tea, and their active ingredients (including 39 known catechin compounds) was conducted. It was found that the regulation of bone mass by fermented tea is backed by evidence from epidemiology, animal experiments, and cell experiments. The main active components of fermented tea are tea polyphenols, tea pigments, and trace amino acids. The specific mechanisms involved include regulating bone marrow mesenchymal stem cell osteogenesis, inhibiting osteoclast activity, promoting calcium and phosphorus absorption, reducing inflammation levels, regulating gut microbiota, regulating endocrine function, and inhibiting oxidative stress. In terms of its application, extraction, precipitation, biosynthesis and membrane separation method are mainly used to separate the active ingredients of anti osteoporosis from fermented tea. In conclusion, fermented tea has sufficient theoretical and practical support for regulating bone mass and preventing osteoporosis, and is suitable for development as a health supplement. At the same time, a large amount of epidemiological evidence is needed to prove the specific dosage of tea consumption.

In the current study, a series of A1–π–A2–π–A1 type bisisoindigo-based organic compounds (BTIND1–BTIND9) were designed via the structural tailoring of the reference compound (BTINR) at terminal acceptors for the organic solar cells (OSCs). Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) approaches were utilized to estimate the influence of end-capped engineering over their photovoltaic properties of BTIND1–BTIND9. After their structural optimization, various analyses like, open circuit voltage (Voc), absorption spectra (λmax), frontier molecular orbitals (FMOs), density of states (DOS), binding energy (Eb) and transition density matrix (TDM) were performed at the B3LYP/6-311G(d,p) level. The band gaps range of the engineered molecules was observed as 1.776–1.649 eV, lesser than the BTINR reference (1.812 eV). Their TDM and DOS details further revealed electronic charge transfer in the designed derivatives. The higher λmax values were found in the visible and near-infrared regions i.e., 666.904–701.149 nm in the chloroform solvent and 661.778–895.581 nm in the gaseous phase. Furthermore, their open-circuit voltage (Voc) was determined with PTB7 donor polymer and showed significant values. Among all, BTIND5, BTIND7 and BTIND8 compounds were investigated with remarkable photovoltaic properties. These chromophores possessed least energy gaps (1.649, 1.668 and 1.664 eV) and bathochromic shifts (698.070, 699.646 and 701.149 nm) with least binding energies and prominent Voc results. The above-mentioned outcomes demonstrate that the end-capped modification of bisisoindigo-based molecule is an effective strategy to obtain highly efficient OSCs.

Public open space is an essential component of support for active ageing in place, whilst in a high-density, high-rise housing context, it plays a more crucial role. The public health field has provided much research on the association between public open spaces and active ageing. However, changes to public open spaces during the Covid-19 crisis, including movement restriction, lockdown, social distancing and isolation, have a severe impact on the quality of life among the older group. This study examined the quality of life among older people living in densely populated districts during the COVID-19 pandemic by evaluating how changes to public open spaces due to pandemic prevention impeded active ageing, and further explored pandemic-resilient urban strategies. Macau, a densely populated ageing city, was selected for case study. Forty-five in-depth interviews were conducted in two high-density districts of Macau with the aim of understanding the perceptions and uses of public open spaces among older people during pandemic conditions. The results indicate that the active ageing process has been impacted to a large degree by prevention measures, particularly in regard to movement and accessibility, everyday activities, social interaction, and emotional health. It is difficult for denser urban spaces to effectively guarantee an active life for older people during the emergent crisis. However, older people’ adaptive responses to pandemic conditions have reduced the negative impact on active ageing. Moreover, the active ageing principle is not applicable to all, since subjective well-being can be perceived and defined differently, and people have unique aging principles as they age. It is important to pay more attention to the well-being of older people by exploring pandemic-resilient strategies which would take into account both the target of active ageing and pandemic prevention.

BackgroundClear cell renal cell carcinoma (ccRCC) is a metabolic disorder characterized by abnormal lipid accumulation in the cytoplasm. Lipid metabolism-related genes may have important clinical significance for prognosis prediction and individualized treatment.MethodsWe collected bulk and single-cell transcriptomic data of ccRCC and normal samples to identify key lipid metabolism-related prognostic signatures. qPCR was used to confirm the expression of signatures in cancer cell lines. Based on the identified signatures, we developed a lipid metabolism risk score (LMRS) as a risk index. We explored the potential application value of prognostic signatures and LMRS in precise treatment from multiple perspectives.ResultsThrough comprehensive analysis, we identified five lipid metabolism-related prognostic signatures (ACADM, ACAT1, ECHS1, HPGD, DGKZ). We developed a risk index LMRS, which was significantly associated with poor prognosis in patients. There was a significant correlation between LMRS and the infiltration levels of multiple immune cells. Patients with high LMRS may be more likely to respond to immunotherapy. The different LMRS groups were suitable for different anticancer drug treatment regimens.ConclusionPrognostic signatures and LMRS we developed may be applied to the risk assessment of ccRCC patients, which may have potential guiding significance in the diagnosis and precise treatment of ccRCC patients.

BackgroundMultiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system. While previous studies have indicated that albumin, the primary protein in human plasma, may exert influence on the inflammatory process and confer beneficial effects in neurodegenerative disorders, its role in the context of MS has been underexplored. Here, we aimed to explore the link between albumin and the risk of MS.MethodsEmploying data from the UK Biobank, we investigated the association between baseline levels of serum and urine albumin and the risk of MS using Cox proportional hazards regression analysis.ResultsA higher baseline level of serum albumin was associated with a lower risk of incident MS (HR=0.94, 95% CI: 0.91–0.98, P=7.66E-04). Subgroup analysis revealed a more pronounced effect in females, as well as participants with younger ages, less smoking and deficient levels of vitamin D. Conversely, no association was identified between baseline microalbuminuria level and risk of incident MS.ConclusionHigher serum albumin level at baseline is linked to a reduced risk of MS. These results contribute to an enhanced understanding of albumin’s role in MS, propose the potential use of albumin as a biomarker for MS, and have implications for the design of therapeutic interventions targeting albumin in clinical trials.