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Abstract The tumour microenvironment represents a novel frontier in oncological research. Over the past decade, accumulating evidence has underscored the importance of the tumour microenvironment (TME), including tumour cells, stromal cells, immune cells, and various secreted factors, which collectively influence tumour growth, invasion, and responses to therapeutic agents. Immune cells within the TME are now widely acknowledged to play pivotal roles in tumour development and treatment. While some perspectives have posited that immune cells within the TME facilitate tumour progression and confer resistance to therapeutic interventions, contrasting conclusions also exist. Affirmative and negative conclusions appear to be context dependent, and a unified consensus has yet to be reached. The burgeoning body of research on the relationship between the gut microbiota and tumours in recent years has led to a growing understanding. Most studies have indicated that specific components of the gut microbiota, such as unique bacterial communities or specific secretory factors, play diverse roles in regulating immune cells within the TME, thereby influencing the prognosis and outcomes of cancer treatments. A detailed understanding of these factors could provide novel insights into the TME and cancer therapy. In this study, we aimed to synthesise information on the interactions between the gut microbiota and immune cells within the TME, providing an in-depth exploration of the potential guiding implications for future cancer therapies.

Abstract To assess the safety and efficacy of fecal microbiota transplantation (FMT) as an adjunctive therapeutic intervention for IgA nephropathy (IgAN). Fifteen patients with IgA nephropathy were recruited based on inclusion and exclusion criteria and underwent FMT using enteric microbial capsules. Clinical indicators, intestinal microbiota and metabolomic profiles, as well as changes in serum immune cells and cytokines, were monitored before and after FMT. No severe adverse reactions were observed in the subjects. After FMT, there was a reduction in the 24-h urinary protein quantification in subjects. The relative abundances of Phocaeicola_vulgatus, Bacteroides_uniformis, Prevotella_copri, Phocaeicola_dorei, Bacteroides_ovatus, Bacteroides_xylanisolvens, Parabacteroides _distasonis, Bifidobacterium_pseudocatenulatum, Bacteroides_sp._HF-162, and Bifidobacterium_longum changed after FMT. In terms of intestinal metabolites, the levels of acylcarnitine18:0 (ACar.18:0), cotinine, N-arachidonoyl-L-serine, phosphatidylcholine (PC. (18:3e/22:6)), serotonin, and fumagillin showed significant changes. Flow cytometry analysis showed the absolute count of plasma B cells decreased in subjects, and this change correlated with alterations in the intestinal microbiota and metabolites. This study preliminarily evaluates the safety and efficacy of FMT in patients with IgAN. No significant adverse reactions were observed, and the administration of FMT alongside ACEI/ARB therapy was effective in reducing urinary protein levels in patients with IgAN, a process that may be associated with B-cell immunity.

Abstract CD5 antigen-like (CD5L), also known as Spα or AIM (Apoptosis inhibitor of macrophage), emerges as an integral component of serum immunoglobulin M (IgM). However, the molecular mechanism underlying the interaction between IgM and CD5L has remained elusive. In this study, we present a cryo-electron microscopy structure of the human IgM pentamer core in complex with CD5L. Our findings reveal that CD5L binds to the joining chain (J chain) in a Ca2+-dependent manner and further links to IgM via a disulfide bond. We further corroborate recently published data that CD5L reduces IgM binding to the mucosal transport receptor pIgR, but does not impact the binding of the IgM-specific receptor FcμR. Additionally, CD5L does not interfere with IgM-mediated complement activation. These results offer a more comprehensive understanding of IgM and shed light on the function of the J chain in the immune system.

Abstract Background Glaesserella parasuis (G. parasuis) is the causative agent of Glässer’s disease, which causes significant economic losses in the swine industry. However, research on the pathogenesis of G. parasuis has been hampered by the lack of a simple and efficient marker-free knockout system. Results In this study, a marker-free knockout system was developed for G. parasuis using a temperature-sensitive vector. By alternating the incubation of transformants at 30°C and 37°C, we optimized the screening process for this system. The system was successfully applied to knockout the Kan R cassette from JS0135ΔnanH::Kan R , achieving a knockout efficiency of 90% in the final round of screening. To confirm that temperature variation was a key factor, we proceeded with knocking out the nanH and apd genes in the CF7066 strain. The knockout efficiency reached up to 100%, with the shortest screening time being only four days. The knockout of the nanH gene resulted in a significant reduction in the growth vitality of the strains, while the knockout of the apd gene led to an approximate 56% improvement in the adhesion rate. Additionally, we observed that the expression of recombinant genes in transformants was higher at 30℃ than at 37℃, with the recC gene being upregulated approximately 7-fold. In contrast, there was almost no difference in the expression of recombinant genes between 30℃ and 37℃ in the wild-type strains. This discrepancy was likely due to an elevated copy number of target plasmids at 30℃, which may have resulted in the enhanced expression of recombinant genes. Conclusions In conclusion, this newly developed gene knockout system for G. parasuis presents a valuable tool for advancing research on this organism.

The interface morphology significantly impact the service life of wet clutches friction components in heavy tracked vehicle transmission systems. This paper designs a sliding test and utilizes a recurrent neural network (RNN) model to construct the three-dimensional morphology of the wet clutch friction interface under specific operating conditions. It also explores the relationship between these factors and clutch performance. The interface morphology characteristics are analyzed by the RNN inversion model to assess the effects of three working condition parameters including rotational speed, pressure, and sliding time. This research provides important primary data for engineering studies and applications aimed at optimizing the design of wet clutches and improving transmission system reliability.

High‐producing dairy cows are susceptible to altered redox balance owing to their high secretion and strong metabolism during transition to lactation. Previously reports demonstrated that pterostilbene (PTE) alleviate hydrogen peroxide (H2O2)-induced oxidative damage. However, molecular mechanism underlying protective role of PTE in H2O2-elicited oxidative stress in bovine mammary epithelial cells (MAC-T cells) remains unclear. The aims of our research is to clarify the potential molecular mechanisms of PTE in H2O2-triggered oxidative damage. MAC-T cells were pre-treated with PTE (0, 10, 25 and 50 μM) for 12 h and then cultured with H2O2 (0, 100, 200, 400, 600, 800 and 1000 μM) for another 24 h. The results were interpreted by CCK8, western blot, and immunofluorescence assay. Results showed that PTE significantly attenuated H2O2-mediated reduction in T-AOC, SOD and GSH-Px activity. Mechanistic studies found that PTE restricted the H2O2-induced protein expression of HO-1, GPX4 and SOD1, and PTE reversed intracellular MDA and ROS generation and decreased the MMP in MAC-T cells. Moreover, H2O2 exposure markedly inhibited mitophagy, whereas PTE pre-treatment activated PINK1/Parkin-mediated mitophagy pathway, which further limited ROS production. Overall, PTE can be used to improve oxidative stress and as a novel antioxidant agent in dairy cows. Highlights PTE restored the levels of H2O2-induced oxidative stress markers (T-AOC, SOD, GSH-Px and MDA) in MAC-T cells. PTE effectively blocked the increase of protein expression (HO-1, SOD1 and GPX4) in H2O2-induced MAC-T cells. PTE remarkably decreased the accumulation of ROS and improved MMP in H2O2-induced MAC-T cells. PTE exerted a significant protective effect against oxidative stress injury by reducing the inhibition of H2O2 on mitophagy.

BackgroundPer- and polyfluoroalkyl substances (PFAS) are a class of persistent organic pollu-tants. Industrial production and consumer use of PFAS are the primary sources of exposure in urban areas. E-waste recycling activities are also a significant source of environmental PFAS exposure. ObjectiveTo compare exposure profiles between traditional and emerging PFAS in neonatal cord blood collected from an e-waste recycling area and a general exposure area characterized by modern economic development (hereafter referred to as general exposure area). MethodsBased on a birth cohort study conducted in 2018, 85 pregnant women were recruited (36 participants from an e-waste recycling area and 49 participants from a general exposure area). Neonatal cord blood was collected at delivery. Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to detect 28 common PFAS in the blood. A structured questionnaire was used to gather sociodemographic characteristics of the pregnant women. Mann-Whitney U tests were used to compare PFAS exposure levels in neonatal cord blood between the e-waste recycling area and the general exposure area. Multiple linear regression models were used to explore the influence of residing in the e-waste recycling area on neonatal PFAS exposure, with area as the independent variable and the natural logarithm of PFAS exposure levels as the dependent variable. ResultsA total of 22 PFAS were positive in neonatal cord blood, of which 13 congeners were 100% detectable in the samples from both areas. The median ∑PFAS exposure levels in neonatal cord blood were 14.19 ng·mL−1 and 14.02 ng·mL−1 for the e-waste recycling area and the general exposure area, respectively, with linear perfluorooctanoic acid (L-PFOA) showing the highest median concentration (5.49 ng·mL−1 and 6.39 ng·mL−1, respectively). The results of Mann-Whitney U tests showed that the median exposure levels of long-chain perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), and perfluorotridecanoic acid (PFTrDA), as well as emerging alternatives 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) and 8:2 chlorinated polyfluorinated ether sulfonate (8:2 Cl-PFESA), were higher in the e-waste recycling area than in the general exposure area. In contrast, the median exposure levels of short-chain perfluoropentanoic acid (PFPeA) and perfluorohexanoic acid (PFHxA), as well as perfluorooctanoic acid (PFOA) branched isomers, including perfluoro-6-methylheptanoic acid (iso-PFOA), perfluoro-5-methylheptanoic acid (5m-PFOA), and perfluoro-4-methylheptanoic acid (4m-PFOA), were lower in the e-waste recycling area than in the general exposure area (P

Abstract Background The global prevalence of obesity has escalated into a formidable health challenge intricately linked with the risk of developing cardiac diastolic disfunction and heart failure with preserved ejection fraction (HFpEF). Abnormal fat distribution is potentially strongly associated with an increased risk of cardiac diastolic dysfunction, and we aimed to scrutinize and elucidate the correlation between them. Methods Following the Cochrane Handbook and PRISMA 2020 guidelines, we systematically reviewed the literature from PubMed, Embase, and Web of Science. We focused on studies reporting the mean and standard deviation (SD) of abnormal fat in HFpEF or cardiac diastolic dysfunction patients and the Pearson/Spearman correlation coefficients for the relationship between abnormal fat distribution and the risk of developing cardiac diastolic dysfunction. Data were standardized to the standard mean difference (SMD) and Fisher’s z value for meta-analysis. Results After progressive filtering and selection, 63 studies (43,113 participants) were included in the quantitative analyses. Abnormal fat distribution was significantly greater in participants with cardiac diastolic dysfunction than in controls [SMD 0.88 (0.69, 1.08)], especially in epicardial adipose tissue [SMD 0.99 (0.73, 1.25)]. Abnormal fat distribution was significantly correlated with the risk of developing cardiac diastolic dysfunction [E/E’: 0.23 (0.18, 0.27), global longitudinal strain: r=-0.11 (-0.24, 0.02)]. Meta-regression revealed sample size as a potential heterogeneous source, and subgroup analyses revealed a stronger association between abnormal fat distribution and the risk of developing cardiac diastolic dysfunction in the overweight and obese population. Conclusion Abnormal fat distribution was significantly associated with the risk of developing cardiac diastolic dysfunction. Trial registration CRD42024543774.

Abstract Macrophages may acquire a reparative phenotype that supports tissue repair and remodeling in response to tissue injury. However, the metabolic requirements underpinning this process are incompletely understood. Here, we show that posttranslational modification (PTM) of PPARγ regulates lipid synthesis in response to wound microenvironmental cues and that metabolic rewiring orchestrates function of reparative macrophages. In injured tissues, repair signaling leads to decreased macrophage PPARγ threonine 166 (T166) phosphorylation, which results in a partially active PPARγ transcriptional program comprised of increased binding activity to the regulator regions of lipid synthesis-associated genes, thereby increased lipogenesis. The accumulated lipids serve as signaling molecules, triggering STAT3-mediated growth factor expression, and supporting the synthesis of phospholipids for the expansion of the endoplasmic reticulum (ER), which is required for protein secretion. Genetic or pharmacological inhibition of PPARγ T166 phosphorylation promotes the reparative function of macrophages and facilitates tissue regeneration. In summary, our work identifies PPARγ T166-regulated lipid biosynthesis as an essential pathway for meeting the anabolic demands of the activation and function of macrophages and provides a rationale for potential therapeutic targeting of tissue repair.

In January 2024, Cancer Statistics, 2024 was published in CA: A Cancer Journal for Clinicians. This report estimated cancer cases and deaths in 2024 and described the secular trends of major cancers over recent decades. We summarized the report and integrated the latest data on the cancer burden in China to compare the prevalence cancer between two countries. We also comprehensively interpreted the underlying reasons for these trends to provide insights for cancer prevention and control strategies in China.

Abstract Background Streptococcus suis is an important zoonotic pathogen. Biofilm formation largely explains the difficulty in preventing and controlling S. suis. However, little is known about the molecular mechanism of S. suis biofilm formation. Results In this study, transcriptomic and metabolomic analyses of S. suis in biofilm and planktonic states were performed to identify key genes and metabolites involved in biofilm formation. A total of 789 differential genes and 365 differential metabolites were identified. By integrating transcriptomics and metabolomics, five main metabolic pathways were identified, including amino acid pathway, nucleotide metabolism pathway, carbon metabolism pathway, vitamin and cofactor metabolism pathway, and aminoacyl-tRNA biosynthesis metabolic pathway. Conclusions These results provide new insights for exploring the molecular mechanism of S. suis biofilm formation.

Abstract Background The turnover of newly graduated nurses is a severe challenge for healthcare systems, and so it is essential to identify its predictive factors. This study investigates whether professional commitment, career adaptability, career self-efficacy, anxiety, and depression levels before and after internship can predict the turnover intention of newly graduated nurses after one year of employment. Methods In a longitudinal study, 271 undergraduate nursing students recruited by convenience sampling were surveyed before internship (T1), after internship (T2), and after one year of employment (T3), with all surveys conducted on the Wenjuanxing survey platform ( www.wjx.cn ). Generalized linear models and restricted cubic spline models were used to explore possible linear and nonlinear relationships between turnover intention and the variables of interest. Results Professional commitment both pre-internship (β = −0.060, p = 0.007, 95% CI [− 0.104, − 0.016]) and post-internship (β = −0.053, p = 0.015, 95% CI [− 0.096, − 0.010]) can negatively predict turnover intention. There is also a negative linear relationship between post-internship career self-efficacy and turnover intention (β = −0.308, p

Abstract Saline-sodic stress restricts the absorption of zinc by rice, consequently impacting the photosynthesis process of rice plants. In this experiment, Landrace 9 was selected as the test material and the potting method was employed to investigate the influence of ZnO nanoparticles (ZnO NPs) on zinc absorption and chlorophyll fluorescence in rice grown in saline-sodic land. The research findings demonstrate that the application of ZnO NPs proves to be more advantageous for the growth of rice in saline-sodic soil. Notably, the application of ZnO NPs significantly decreases the levels of Na+ and MDA in rice leaves in saline-sodic soil, while increasing the levels of K+ and Zn2+. Additionally, ZnO NPs enhances the content of chloroplast pigments, specific energy flux, quantum yield, and the performance of active PSII reaction center (PI ABS) in rice leaves under saline-sodic stress. Furthermore, the relative variable fluorescence (W K and V J) and quantum energy dissipation rate (φ Do) of rice are also reduced. Therefore, the addition of ZnO NPs enhances the transfer of electrons and energy within the rice photosystem when subjected to saline-sodic stress. This promotes photosynthesis in rice plants growing in saline-sodic land, increasing their resistance to saline-sodic stress and ultimately facilitating their growth and development.

Abstract Background This study aimed to explore discrepancies in adolescents with chronic illness and their parents’ perceptions of family resilience, as well as the relationship between these differences and the psychological adjustment of adolescents with chronic illness. Methods A cross-sectional study was conducted. A total of 264 dyads of parents (77.7% mothers, mean age 41.60 years, SD = 6.17) and adolescents (48.5% girls, mean age 12.68 years, SD = 2.11) with chronic illness were recruited through convenience sampling from three children’s hospitals in Wenzhou, Hangzhou, and Shanghai, China between June 2022 and May 2023. The Chinese version of the Family Resilience Scale and the Psychological Adjustment Scale, which are commonly used measures with good reliability and validity, were employed to assess family resilience and psychological adaption, respectively. The data were analyzed using polynomial regression and response surface analysis. Results Adolescents with chronic illness reported higher family resilience than their parents (t=-2.80, p

Abstract Background Analyzing distance-dependent functional connectivity density (FCD) yields valuable insights into patterns of brain activity. Nevertheless, whether alterations of FCD in non-acute stroke patients are associated with the anatomical distance between brain regions remains unclear. This study aimed to explore the distance-related functional reorganization in non-acute stroke patients following left and right hemisphere subcortical lesions, and its relationship with clinical assessments. Methods In this study, we used resting-state fMRI to calculate distance-dependent (i.e., short- and long-range) FCD in 25 left subcortical stroke (LSS) patients, 22 right subcortical stroke (RSS) patients, and 39 well-matched healthy controls (HCs). Then, we compared FCD differences among the three groups and assessed the correlation between FCD alterations and paralyzed motor function using linear regression analysis. Results Our findings demonstrated that the left inferior frontal gyrus displayed distance-independent FCD changes, while the bilateral supplementary motor area, cerebellum, and left middle occipital gyrus exhibited distance-dependent FCD alterations in two patient subgroups compared with HCs. Furthermore, we observed a positive correlation between increased FCD in the bilateral supplementary motor area and the motor function of lower limbs, and a negative correlation between increased FCD in the left inferior frontal gyrus and the motor function of both upper and lower limbs across all stroke patients. These associations were validated by using a longitudinal dataset. Conclusions The FCD in the cerebral and cerebellar cortices shows distance-related changes in non-acute stroke patients with motor dysfunction, which may serve as potential biomarkers for predicting motor outcomes after stroke. These findings enhance our comprehension of the neurobiological mechanisms driving non-acute stroke. Trial registration All data used in the present study were obtained from a research trial registered with the ClinicalTrials.gov database (NCT05648552, registered 05 December 2022, starting from 01 January 2022).

Abstract Bacteria utilize intercellular communication to orchestrate essential cellular processes, adapt to environmental changes, develop antibiotic tolerance, and enhance virulence. This communication, known as quorum sensing (QS), is mediated by the exchange of small signalling molecules called autoinducers. AI-2 QS, regulated by the metabolic enzyme LuxS (S-ribosylhomocysteine lyase), acts as a universal intercellular communication mechanism across gram-positive and gram-negative bacteria and is crucial for diverse bacterial processes. In this study, we demonstrated that in Streptococcus suis (S. suis), a notable zoonotic pathogen, AI-2 QS enhances galactose utilization, upregulates the Leloir pathway for capsular polysaccharide (CPS) precursor production, and boosts CPS synthesis, leading to increased resistance to macrophage phagocytosis. Additionally, our molecular docking and dynamics simulations suggest that, similar to S. pneumoniae, FruA, a fructose-specific phosphoenolpyruvate phosphotransferase system prevalent in gram-positive pathogens, may also function as an AI-2 membrane surface receptor in S. suis. In conclusion, our study demonstrated the significance of AI-2 in the synthesis of galactose metabolism-dependent CPS in S. suis. Additionally, we conducted a preliminary analysis of the potential role of FruA as a membrane surface receptor for S. suis AI-2.

Abstract Bacteriophage are sophisticated cellular parasites that can not only parasitize bacteria but are increasingly recognized for their direct interactions with mammalian hosts. Phage adherence to mucus is known to mediate enhanced antimicrobial effects in vitro. However, little is known about the therapeutic efficacy of mucus-adherent phages in vivo. Here, using a combination of in vitro gastrointestinal cell lines, a gut-on-a-chip microfluidic model, and an in vivo murine gut model, we demonstrated that a E. coli phage, øPNJ-6, provided enhanced gastrointestinal persistence and antimicrobial effects. øPNJ-6 bound fucose residues, of the gut secreted glycoprotein MUC2, through domain 1 of its Hoc protein, which led to increased intestinal mucus production that was suggestive of a positive feedback loop mediated by the mucus-adherent phage. These findings extend the Bacteriophage Adherence to Mucus model into phage therapy, demonstrating that øPNJ-6 displays enhanced persistence within the murine gut, leading to targeted depletion of intestinal pathogenic bacteria.

Transformer requires a fixed number of layers and heads which makes them inflexible to the complexity of individual samples and expensive in training and inference. To address this, we propose a sample-based Dynamic Hierarchical Transformer (DHT) model whose layers and heads can be dynamically configured with single data samples via solving contextual bandit problems. To determine the number of layers and heads, we use the Uniform Confidence Bound algorithm while we deploy combinatorial Thompson Sampling in order to select specific head combinations given their number. Different from previous work that focuses on compressing trained networks for inference only, DHT is not only advantageous for adaptively optimizing the underlying network architecture during training but also has a flexible network for efficient inference. To the best of our knowledge, this is the first comprehensive data-driven dynamic transformer without any additional auxiliary neural networks that implement the dynamic system. According to the experiment results, we achieve up to 74% computational savings for both training and inference with a minimal loss of accuracy.

Federated learning (FL) is an emerging paradigm for decentralized training of machine learning models on distributed clients, without revealing the data to the central server. The learning scheme may be horizontal, vertical or hybrid (both vertical and horizontal). Most existing research work with deep neural network (DNN) modeling is focused on horizontal data distributions, while vertical and hybrid schemes are much less studied. In this paper, we propose a generalized algorithm FedEmb, for modeling vertical and hybrid DNN-based learning. The idea of our algorithm is characterized by higher inference accuracy, stronger privacy-preserving properties, and lower client-server communication bandwidth demands as compared with existing work. The experimental results show that FedEmb is an effective method to tackle both split feature & subject space decentralized problems. To be specific, there are 0.3% to 4.2% improvement on inference accuracy and 88.9 % time complexity reduction over baseline method.

As a direct object of ecological environment perception, public satisfaction with ecological environment is an important indicator to judge the status of regional ecological environment. Based on this, this study collected data on public perceptions of environmental issues in seven Chinese cities. On the one hand, we analyzed public satisfaction with ecological environment in China, and on the other hand, we used structural equation modeling (SEM) to analyze the influence paths of public perception of ecological environment and government ecological environment management on public satisfaction with ecological environment. The results of the study indicate that the Chinese public’s satisfaction with the ecological environment is currently low, and they still lack confidence in the future improvement of the ecological environment in China. The Chinese public believes that the biggest environmental problem in China is air pollution, and the degree of improvement of relevant government environmental policies still needs to be improved. The results of structural equation modeling (SEM) show that public perceptions of ecological environment and governmental ecological environmental governance have a significant direct positive effect on ecological environment satisfaction; governmental ecological environmental governance and ecological environmental perceptions also have a mutual positive effect. Environmental governance is a long-term and complex dynamic process. In the future, research can be enriched by expanding the sample data and refining the study of factors influencing ecological environmental satisfaction.

BackgroundCytokines play a pivotal role in the progression of heart failure (HF) by modulating inflammatory responses, promoting vasoconstriction, and facilitating endothelial injury. However, it is now difficult to distinguish the causal relationship between HF and cytokines in observational studies. Mendelian randomization (MR) analyses of cytokines probably could enhance our comprehension to the underlying biological processes of HF.MethodsThis study was to explore the correlation between 41 cytokines with HF at the genetic level by MR analysis. We selected a HF dataset from the Heart Failure Molecular Epidemiology for Therapeutic Targets (HERMES) 2018 and a cytokine dataset from a meta-analysis of cytokine levels in Finns. Two-sample, bidirectional MR analyses were performed using Inverse Variance Weighted (IVW), Weighted Median and MR- egger, and the results were tested for heterogeneity and pleiotropy, followed by sensitivity analysis.ResultsGenetic prediction of high levels of circulating Macrophage inflammatory pro-tein-1β(MIP-1β) (P = 0.0389), Interferon gamma induced protein 10(IP-10) (P = 0.0029), and Regu-lated on activation, normal T cell expressed and secreted(RANTES) (P = 0.0120) expression was associated with an elevated risk of HF. HF was associated with the increased levels of circulating Interleukin-2 receptor, alpha subunit(IL-2ra) (P = 0.0296), Beta nerve growth fac-tor(β-NGF) (P = 0.0446), Interleukin-17(IL-17) (P = 0.0360), Basic fibroblast growth factor(FGF-basic) (P = 0.0220), Platelet derived growth factor BB(PDGF-BB) (P = 0.0466), and Interferon-gamma(IFN-γ) (P = 0.0222); and with decreased levels of Eotaxin (P = 0.0133). The heterogeneity and pleiotropy of the cytokines were acceptable, except for minor heterogeneity of FGF-basic and IL-17.ConclusionThese findings provide compelling evidence for a genetically predictive relationship between cytokines and HF, emphasizing a great potential of targeted modulation of cytokines in slowing the progression of HF. This study draws further conclusions at the genetic level, providing a basis for future large-scale clinical trials.

Background: The association between frailty and sex hormone-binding globulin (SHBG) or insulin-like growth factor-1(IGF-1) levels demonstrates sex differences with inconsistent conclusions. This study aims to explore the causal relationship between frailty and SHBG or IGF-1 levels through bidirectional Mendelian randomization (MR). Methods: We conducted two-sample bidirectional sex-stratified MR analyses using summary-level data from genome-wide association studies (GWASs) to examine the causal relationship between frailty and IGF-1 or SHBG levels, as measured by frailty index (FI) and frailty phenotype (FP). We use the random-effects inverse-variance weighted (IVW), weighted median, MR-Egger, MR-Egger intercept, and leave-one-out approaches. Result: The relationship between frailty and SHBG or IGF-1 levels is inversely related, with a significant decrease in SHBG levels in females. Specifically, SHBG levels significantly decrease with FI (β = −5.49; 95 % CI: −9.67 to −1.32; FDR = 0.02) and more pronounced with FP (β = −10.14; 95 % CI: −16.16 to −4.13; FDR = 0.01), as determined by the IVW approach. However, reverse analysis shows no significant effect of IGF-1 or SHBG levels on either FI or FP (p > 0.05). Conclusion: Our study indicates a negative correlation between frailty and the levels of SHBG and IGF-1. It is suggested that further research is required to establish cut-off values for SHBG and IGF-1 levels in the frailty population. This is particularly important for females at higher risk, such as those undergoing menopause, to enable comprehensive assessment and early prevention efforts. While the findings imply that reduced IGF-1 and SHBG levels may not directly contribute to frailty, it is important not to overlook the underlying mechanisms through which they may indirectly influence frailty.

Label-free three-dimensional imaging plays a crucial role in unraveling the complexities of cellular functions and interactions in biomedical research. Conventional single-cell optical tomography techniques offer affordability and the convenience of bypassing laborious cell labelling protocols. However, these methods are encumbered by restricted illumination scanning ranges on abaxial plane, resulting in the loss of intricate cellular imaging details. The ability to fully control cellular rotation across all angles has emerged as an optimal solution for capturing comprehensive structural details of cells. Here, we introduce a label-free, cost-effective, and readily fabricated contactless acoustic-induced vibration system, specifically designed to enable multi-degree-of-freedom rotation of cells, ultimately attaining stable in-situ rotation. Furthermore, by integrating this system with advanced deep learning technologies, we perform 3D reconstruction and morphological analysis on diverse cell types, thus validating groups of high-precision cell identification. Notably, long-term observation of cells reveals distinct features associated with drug-induced apoptosis in both cancerous and normal cells populations. This methodology, based on deep learning-enabled cell 3D reconstruction, charts a novel trajectory for groups of real-time cellular visualization, offering promising advancements in the realms of drug screening and post-single-cell analysis, thereby addressing potential clinical requisites.

One-step transesterification between ethylene carbonate (EC) and ethanol (EtOH) can effectively prevent the formation of azeotropes in the synthesis of diethyl carbonate (DEC) / ethyl methyl carbonate (EMC). However, owing to the influence of volume and electronic effects of EtOH molecules, the catalytic activity is insufficient. In this study, we propose an on-line synthesis technique for catalysts and prepare a unique heterogeneous alkali catalyst, PS-(NR3OH)EG. This technique simplifies the catalyst preparation process and protects it from exposure to water and carbon dioxide in the air. The active sites of PS-(NR3OH)EG are derived from the product ethylene glycol (EG). PS-(NR3OH)EG exhibits excellent catalytic performance in promoting EC and EtOH transesterification. The physicochemical properties of PS-(NR3OH)EG are analysed, and the reaction conditions are optimized. The results indicate that PS-(NR3OH)EG has superior catalytic activity and stability compared to the similar previously reported catalysts. Notably, after continuous reaction in a fixed-bed reactor for 500 h, PS-(NR3OH)EG maintain its initial catalytic activity. This study provides theoretical and experimental guidance for catalyst preparation and transesterification reaction process design.

Abstract Bio‐waste is a side product of biomedical research containing carbon, which can be utilized for developing carbon dots (CDs). CDs are known to be useful for a variety of applications because of their unique photoluminescence, low toxicity, and straightforward synthesis. In this paper, we employed a one‐step hydrothermal method to prepare CDs from bio‐waste as the only reactant. The as‐synthesized Cell‐CDs were found to be chemically stable and biocompatible. In addition, the spectra of Cell‐CDs’ emissions covered the visible light, which is ideal for super‐resolution imaging. Particularly, dual‐color imaging can be achieved, for example, by staining the plasma membrane with Cell‐CDs emitting one color and staining cytosolic organelles with Cell‐CDs emitting a different color of fluorescence. Here, we demonstrate such applications by studying the subcellular dynamics of live cells.

IntroductionCurrent treatments for bacterial keratitis fail to address the sight-threatening inflammatory host response. Our recent work elucidating the therapeutic mechanisms of adjunctive thymosin beta-4 (Tβ4) in resolving inflammation and infection in bacterial keratitis revealed modulation of effector cell function and enhanced bacterial killing. The current study builds upon the observed effects on effector cell function by investigating the impact of Tβ4 on specialized pro-resolving lipid mediator (SPM) pathways as they play a significant role in inflammation resolution.MethodsUsing a well-established in vivo model of Pseudomonas aeruginosa-induced bacterial keratitis, we assessed key enzymes (5-LOX and 12/15-LOX) involved in SPM pathway activation, SPM end products (lipoxins, resolvins), and receptor levels for these mediators. In vitro validation using LPS-stimulated murine monocyte/MΦ-like RAW 264.7 cells and siRNA to inhibit Tβ4 and LOX enzymes was carried out to complement our in vivo findings.ResultsFindings from our in vivo and in vitro investigations demonstrated that adjunctive Tβ4 treatment significantly influences enzymes and receptors involved in SPM pathways. Further, Tβ4 alone enhances the generation of SPM end products in the cornea. Our in vitro assessments confirmed that Tβ4-enhanced phagocytosis is directly mediated by SPM pathway activation. Whereas Tβ4-enhanced efferocytosis appeared to be indirect.ConclusionCollectively, these findings suggest that the therapeutic effect of Tβ4 resolves inflammation through the activation of SPM pathways, thereby enhancing host defense and tissue repair. Our research contributes to understanding the potential mechanisms behind Tβ4 immunoregulatory function, pointing to its promising ability as a comprehensive adjunctive treatment for bacterial keratitis.

BackgroundAlthough the Chufeng Qingpi Decoction (CQD) has demonstrated clinical effectiveness in the treatment of schistosomiasis, the precise active components and the underlying mechanisms of its therapeutic action remain elusive. To achieve a profound comprehension, we incorporate network pharmacology, bioinformatics analysis, molecular docking, and molecular dynamics simulations as investigative methodologies within our research framework.MethodUtilizing TCMSP and UniProt, we identified formula components and targets. Cytoscape 3.10.0 was used to construct an herb–target interaction network. Genecards, DisGeNET, and OMIM databases were examined for disease-related objectives. A Venn diagram identified the intersection of compound and disease targets. Using Draw Venn, overlapping targets populated STRING for PPI network. CytoNCA identified schistosomiasis treatment targets. GO & KEGG enrichment analysis followed High-scoring genes in PPI were analyzed by LASSO, RF, SVM-RFE. Molecular docking & simulations investigated target-compound interactions.ResultThe component’s target network encompassed 379 nodes, 1629 edges, highlighting compounds such as wogonin, kaempferol, luteolin, and quercetin. Amongst the proteins within the PPI network, PTGS2, TNF, TGFB1, BCL2, TP53, IL10, JUN, MMP2, IL1B, and MYC stood out as the most prevalent entities. GO and KEGG revealed that mainly involved the responses to UV, positive regulation of cell migration and motility. The signal pathways encompassed Pathways in cancer, Lipid and atherosclerosis, Fluid shear stress and atherosclerosis, as well as the AGE-RAGE. Bioinformatics analysis indicated TP53 was the core gene. Ultimately, the molecular docking revealed that wogonin, kaempferol, luteolin, and quercetin each exhibited significant affinity in their respective interactions with TP53. Notably, kaempferol exhibited the lowest binding energy, indicating a highly stable interaction with TP53. Lastly, we validated the stability of the binding interaction between the four small molecules and the TP53 through molecular dynamics simulations. The molecular dynamics simulation further validated the strongest binding between TP53 and kaempferol. In essence, our research groundbreaking in its nature elucidates for the first time the underlying molecular mechanism of CQD in the therapeutic management of schistosomiasis, thereby providing valuable insights and guidance for the treatment of this disease.ConclusionThis study uncovered the efficacious components and underlying molecular mechanisms of the Chufeng Qingpi Decoction in the management of schistosomiasis, thereby offering valuable insights for future fundamental research endeavors.

One-third of patients with autoimmune hepatitis (AIH) have cirrhosis at the time of diagnosis. The relevance of these variables, although unknown, is believed to be critical in AIH because of suspected interactions between the gut microbiome and genetic factors. Dysbiosis of the gut flora and elevated polymeric immunoglobulin receptor (pIgR) levels have been observed in both patients and mouse models. Moreover, there is a direct relationship between pIgR expression and transaminase levels in patients with AIH. In this study, we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta (Reg3b) and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of AIH. Reg3b expression was reduced in pIgR gene (Pigr)-knockout mice compared to that in wild-type mice, leading to increased microbiota disruption. Conversely, exogenous pIgR supplementation increased Reg3b expression and maintained microbiota homeostasis. RNA sequencing revealed the participation of the interleukin (IL)-17 signaling pathway in the regulation of Reg3b through pIgR. Furthermore, the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH, and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3 (STAT3). In this study, pIgR facilitated the upregulation of Reg3b via the STAT3 pathway, which plays a crucial role in preserving the balance of the intestinal microbiota in AIH. Through this research, we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.

Abstract The study of phosphorylase kinase (PhK)-regulated glycogen metabolism has contributed to the fundamental understanding of protein phosphorylation; however, the molecular mechanism of PhK remains poorly understood. Here we present the high-resolution cryo-electron microscopy structures of human muscle PhK. The 1.3-megadalton PhK α4β4γ4δ4 hexadecamer consists of a tetramer of tetramer, wherein four αβγδ modules are connected by the central β4 scaffold. The α- and β-subunits possess glucoamylase-like domains, but exhibit no detectable enzyme activities. The α-subunit serves as a bridge between the β-subunit and the γδ subcomplex, and facilitates the γ-subunit to adopt an autoinhibited state. Ca2+-free calmodulin (δ-subunit) binds to the γ-subunit in a compact conformation. Upon binding of Ca2+, a conformational change occurs, allowing for the de-inhibition of the γ-subunit through a spring-loaded mechanism. We also reveal an ADP-binding pocket in the β-subunit, which plays a role in allosterically enhancing PhK activity. These results provide molecular insights of this important kinase complex.

Abstract In environments characterized by extended multi-stress conditions, pathogens develop a variety of immune escape mechanisms to enhance their ability to infect the host. The capsules, polymers that bacteria secrete near their cell wall, participates in numerous bacterial life processes and plays a crucial role in resisting host immune attacks and adapting to their niche. Here, we discuss the relationship between capsules and bacterial virulence, summarizing the molecular mechanisms of capsular regulation and pathogenesis to provide new insights into the research on the pathogenesis of pathogenic bacteria.

Abstract Background Currently, limited research is available on the comparative analysis of chronic kidney disease (CKD) incidence and mortality rates between China and the United States. This study aimed to explore the trends in CKD incidence and mortality rates in both countries, as well as make some future predictions. Methods The data on CKD incidence and mortality in China and the US from 1990 to 2019 were derived from the 2019 Global Burden of Disease database. A Joinpoint regression model was used to analyze temporal trends in CKD incidence and mortality. An age-period-cohort model was used to assess the effects of age, period, and birth cohort on CKD risk and forecast the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of CKD in China and the US over the next 15 years. Results CKD incidence in China and the US showed an upward trend. Its mortality rate showed a downward trend in China but an upward one in the US. The relative risk (RR) of CKD incidence and mortality increases with age. The RR of CKD incidence in the 0–5 age group exceeds that in the 5–55 age group, and the RR for mortality surpasses that in the 5–35 age group. Over time, the RR of CKD incidence has gradually increased in China and the US. Individuals born in later birth cohorts had a lower RR of CKD incidence and mortality. The ASIR of CKD may increase in both China and the US, whereas its ASMR may decline over the next 15 years. Conclusion Screening measures should be strengthened among populations at high risk of CKD; prenatal examinations of pregnant women should be emphasized to reduce CKD incidence in newborns. It is imperative to increase health education and encourage individuals to adopt healthy lifestyles.

It is well known that calcium oxide (CaO) has better catalytic efficiency than most heterogeneous catalysts in many transesterification reactions. However, the gradual deactivation problem prevents its large-scale application in industry. In this paper, the deactivation mechanism of CaO in a fixed-bed reactor is investigated based on the transesterification reaction of propylene carbonate and methanol. The leaching amount of CaO during the reaction was estimated by the concentration of Ca in the products. The pretreated and recovered catalysts were characterized by FT-IR, XRD, TG-MS and SEM-EDS. It is evident from experiments and characterization that the deactivation process of CaO is accompanied by the leaching of calcium species and the generation of CaCO3, which are also verified by DFT calculations. At high temperature and high weight hourly space velocity, the deactivation was attributed to the formation of dense CaCO3 shell, which prevents the contact between the feedstock and the active species inside.

This study utilized meta-analysis and Mendelian randomization (MR) to identify risk factors for endocrine-related immune-related adverse events (EirAEs) and to ascertain whether EirAEs confer better prognosis of immunotherapy. The meta-analysis identified several risk factors for EirAEs, including elevated baseline TSH (OR = 1.30, 95% CI 1.10–1.53), positive TgAb (OR = 14.23, p

Background The clinical efficacy of cancer treatment protocols remains unsatisfactory; however, the emergence of ferroptosis-driven therapy strategies has renewed hope for tumor treatment, owing to their remarkable tumor suppression effects. Biologically based small-molecule inducers are used in conventional method to induce ferroptosis. Nevertheless, some molecular drugs have limited solubility, poor ability to target cells, and fast metabolism, which hinder their ability to induce ferroptosis over a prolonged period. Fortunately, further investigations of ferroptosis and the development of nanotechnology have demonstrated that nanoparticles (NPs) are more efficient in inducing ferroptosis than drugs alone, which opens up new perspectives for cancer therapy.Objective In order to organize a profile of recent advance in NPs for inducing ferroptosis in cancer therapy, and NPs were comprehensively classified in a new light.Materials and methods: We comprehensively searched the databases such as PubMed and Embase. The time limit for searching was from the establishment of the database to 2023.11. All literatures were related to “ferroptosis”, “nanoparticles”, “nanodelivery systems”, “tumors”, “cancer”.Results We summarized and classified the available NPs from a new perspective. The NPs were classified into six categories based on their properties: (1) iron oxide NPs (2) iron - based conversion NPs (3) core-shell structure (4) organic framework (5) silica NPs (6) lipoprotein NPs. According to the therapeutic types of NPs, they can be divided into categories: (1) NPs induced ferroptosis-related immunotherapy (2) NPs loaded with drugs (3) targeted therapy of NPs (4) multidrug resistance therapy (5) gene therapy with NPs (6) energy conversion therapy.Conclusions The insights gained from this review can provide ideas for the development of original NPs and nanodelivery systems, pave the way for related nanomaterials application in clinical cancer therapy, and advance the application and development of nanotechnology in the medical field.

The pathogenesis of membranous nephropathy (MN) involves podocyte injury that is attributed to inflammatory responses induced by local immune deposits. Astragaloside IV (AS-IV) is known for its robust anti-inflammatory properties. Here, we investigated the effects of AS-IV on passive Heymann nephritis (PHN) rats and TNF-α-induced podocytes to determine the underlying molecular mechanisms of MN. Serum biochemical parameters, 24-h urine protein excretion and renal histopathology were evaluated in PHN and control rats. The expression of tumor necrosis factor receptor associated factor 6 (TRAF6), the phosphorylation of nuclear factor kappa B (p-NF-κB), the expression of associated proinflammatory cytokines (TNF-α, IL-6 and IL-1β) and the ubiquitination of TRAF6 were measured in PHN rats and TNF-α-induced podocytes. We detected a marked increase in mRNA expression of TNF-α, IL-6 and IL-1β and in the protein abundance of p-NF-κB and TRAF6 within the renal tissues of PHN rats and TNF-α-induced podocytes. Conversely, there was a reduction in the K48-linked ubiquitination of TRAF6. Additionally, AS-IV was effective in ameliorating serum creatinine, proteinuria, and renal histopathology in PHN rats. This effect was concomitant with the suppression of NF-κB pathway activation and decreased expression of TNF-α, IL-6, IL-1β and TRAF6. AS-IV decreased TRAF6 levels by promoting K48-linked ubiquitin conjugation to TRAF6, which triggered ubiquitin-mediated degradation. In summary, AS-IV averted renal impairment in PHN rats and TNF-α-induced podocytes, likely by modulating the inflammatory response through the TRAF6/NF-κB axis. Targeting TRAF6 holds therapeutic promise for managing MN.

Graveoline exhibits various biological activities. However, only limited studies have focused on its hepatoprotective properties. This study evaluated the anti-inflammatory and hepatoprotective activities of graveoline, a minor 2-phenylquinolin-4-one alkaloid isolated from Ruta graveolens L., in a liver injury model in vitro and in vivo. A network pharmacology approach was used to investigate the potential signaling pathway associated with the hepatoprotective activity of graveoline. Subsequently, biological experiments were conducted to validate the findings. Topological analysis of the KEGG pathway enrichment revealed that graveoline mediates its hepatoprotective activity through genes associated with the hepatitis B viral infection pathway. Biological experiments demonstrated that graveoline effectively reduced the levels of alanine transaminase and aspartate transaminase in lipopolysaccharide (LPS)-induced HepG2 cells. Graveoline exerted antihepatitic activity by inhibiting the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and elevated the anti-inflammatory cytokines interleukin-4 (IL-4) and interleukin-10 (IL-10) in vitro and in vivo. Additionally, graveoline exerted its hepatoprotective activity by inhibiting JAK1 and STAT3 phosphorylation both in vitro and in vivo. In summary, graveoline can attenuate acute liver injury by inhibiting the TNF-α inflammasome, activating IL-4 and IL-10, and suppressing the JAK1/STAT3 signaling pathway. This study sheds light on the potential of graveoline as a promising therapeutic agent for treating liver injury.

Objectives: The prevalence of respiratory infectious diseases has changed in the post-COVID-19 epidemic era, and mycoplasma pneumoniae (MP) infection in children has attracted wide attention. Methods: Children hospitalized for pneumonia in Wuhan, China, in 2023 were enrolled. Respiratory secretions were obtained for the targeted next-generation sequencing (tNGS) including mutation of MP. Pulmonary inflammation was divided into bronchopneumonia and pulmonary consolidation/atelectasis according to lung computed tomography imaging. Results: Of the 667 pediatric pneumonia, 478 were MP positive (72%). The positive rate of MP detected by tNGS increased from April, and MP had become the primary pathogen of pneumonia in children in 2023. The 23S rRNA mutations were all A2063G, accounting for 85% of detected MP. The clinical symptoms of the mutant and wild-type strains were similar, with half of them experiencing atelectasis and lung consolidation. Early bronchoscopic lavage combined with azithromycin in pediatric pulmonary consolidation was an effective therapy strategy, which could be an alternative selection to MP pneumonia treatment. Conclusions: A2063G mutant strain MP was the primary pathogen of mycoplasma pneumoniae in children recently, which was often complicated by extra-pulmonary symptoms and complications.

Background: In the context of climate change and urbanization, the temporal variation of the adverse health effect of extreme temperature has attracted increasing attention. Methods: The meteorological data and the daily death records of mortality from respiratory diseases of 136 Chinese cities were from 2006 to 2019. Heat wave and cold spell were selected as the indicator events of extreme high temperature and extreme low temperature, respectively. The generalized linear model and time-varying distributed lag model were used to perform a two-stage time-series analysis to evaluate the temporal variation of the mortality risk associated with extreme temperature in the total population, sub-populations (sex- and age- specific) and different regions (climatic zone and relative humidity level). Results: During the study period, relative risk (RR) of respiratory mortality associated with heat wave decreased from 1.22 (95 %CI: 1.07–1.39) to 1.13 (95 %CI: 1.01–1.26) in the total population, and RR of respiratory mortality associated with cold spell decreased from 1.30 (95 %CI: 1.14–1.49) to 1.17 (95 %CI: 1.08–1.26). The impact of heat wave reduced in the males (P = 0.044) and in the females as with cold spell (P

We investigated the potential of ferric iron-modified biochar to lessen autotrophic nitrification and lower nitrous oxide (N2O) emissions in paddy soils. A 15N tracing incubation was conducted to investigate the changes in soil gross nitrogen (N) transformations under various biochar amendments (control, unmodified biochar, and Fe-modified biochar). Acetylene and 1-octyne were used to assess the relative contributions of ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) to N2O emission from paddy soil. The Fe-modified biochar increased the rate of NH4+ immobilization by 26 % and 383 % compared to the control and unmodified biochar treatments, respectively. The gross rate of autotrophic nitrification was reduced to 5.43 μg N g−1 d−1 in the Fe-modified biochar treatment, compared to 6.74 μg N g−1 d−1 in the control treatment and 9.38 μg N g−1 d−1 in the unmodified biochar treatment. Soil pH had varying effects on N2O emissions involving AOB and AOA. The N2O yields of AOA were more sensitive to Fe-modified biochar applications. AOB, specifically the Nitrosopira-AOB genus, dominated N2O production in all treatments. Overall, this study suggests that Fe-modified biochar holds greater potential than unmodified biochar in reducing N2O emissions from paddy soils by stimulating NH4+ adsorption, restraining autotrophic nitrification rates, and AOB-dominant N2O production pathways.

A meaningful and practical phenomenon was observed and investigated, about which a synthesized (2-hydroxyethyl) triethylammonium bromide (NEt3(HE)Br) was used for catalytic cycloaddition of PO (propylene oxide) and CO2 (carbon dioxide) in a homogeneous state, and then separated from the reaction system in a heterogeneous state. The target products were first reported as additives to regulate the distribution of reactants and carbon dioxide (CO2) in the gas-liquid phase, as well as to facilitate the dissolution of NEt3(HE)Br. Under the optimal conditions of 0.2 mol% NEt3(HE)Br dosage, the PC yield (98.71 %) and TOF value (22.54 h−1) reached are significantly higher than the case of without PC addition. Besides, NEt3(HE)Br exhibited impressive stability after five catalytic cycles. The catalytic performances of different additives (i.e., alcohols, cyclic carbonate, amides, sulfones, petroleum ether, straight-chain carbonate and oxalate) were investigated, and their promotional effects and mechanisms were systematically elucidated. The transition behavior of dissolution-catalysis-precipitation process and intrinsic promoting mechanism of NEt3(HE)Br gave an efficient idea for a homogeneous catalytic reaction and heterogeneous separation of the catalyst. Meanwhile, this work provides an important theoretical and practical basis for efficient and facile catalyst synthesis and the corresponding reaction system design.

IntroductionAssociations between parental anxiety and adolescent internet addiction have been documented in the literature; however, few studies have analyzed the role of the family environment in this relationship. This study aims to explore the relationship between parental anxiety and adolescent internet addiction while also investigating the indirect relationships involving multiple dimensions of the family environment and child emotional behavior issues.MethodsSurveys were conducted among 6,296 parent-child pairs. We administered SDQ, CIAS-R, and FES-CV to assess adolescents’ issues and internet addiction, and evaluate family environment. Additionally, parents completed GAD-7 to assess parental anxiety levels.Results: Correlation analysis revealed that the family environment and adolescent emotional behavior issues played an indirect relationship in the link between parental anxiety and internet addiction.DiscussionThe findings emphasize the importance of addressing parental anxiety and fostering a positive family environment as effective measures to alleviate adolescent emotional behavior problems and reduce the risk of internet addiction.

Kokusaginine is an active ingredient alkaloid that has been isolated and extracted from Ruta graveolens L. Some researches have indicated that alkaloids possess anti-inflammatory and antioxidant effects. Nevertheless, the potential nephroprotective effects of kokusaginine on renal fibrosis remain undetermined. This study was conducted to examine the protective effect of kokusaginine on renal fibrosis and to explore the underlying mechanisms using both in vivo and in vitro models. Renal fibrosis was induced in male C57BL/6 J mice by feeding with 0.2% adenine-containing food and UUO surgery. Kokusaginine was administered orally simultaneously after the establishment of renal fibrosis. Renal function was measured by serum levels of creatinine and urea nitrogen. Renal pathological changes were assessed by HE staining and Masson staining. Western blotting was employed to detect the expression levels of fibrosis-related proteins in mice and cells. Additionally, network pharmacology analysis and RNA-seq were utilized to predict the pathways through which kokusaginine could exert its anti-fibrotic effects. The treatment with kokusaginine enhanced renal function, alleviated renal histoarchitectural lesions, and mitigated renal fibrosis in the renal fibrosis models. The network pharmacology and RNA-seq enrichment analysis of the KEGG pathway demonstrated that kokusaginine could exert anti-renal fibrosis activity via the PI3K/AKT signaling pathway. And the results were verified in both in vitro and in vivo experiments. In conclusion, our data implied that kokusaginine inhibited the activation of the PI3K/AKT signaling pathway both in vitro and in vivo, and suppressed the formation of renal fibrosis. Thus, the kokusaginine-mediated PI3K/AKT signaling pathway may represent a novel approach for the treatment of renal fibrosis.

Abstract Fixed frequency beam-scanning leaky-wave antennas have been a focus of attention for many scholars in recent years, and numerous related results have been obtained. However, these antennas suffer from several issues such as small beam-scanning range, low gain, and unsatisfactory impedance matching. To address these problems, this paper proposes a microstrip line (ML) antenna unit based on liquid crystal (LC) materials etched Complementary Split Ring Resonator (CSRR). In a first-of-its-kind approach, the substrate integrated waveguide (SIW) structure and the ML transmission structure are combined to present the SIW-ML transmission structure. The antenna operates in the Ka-band with excellent resonance characteristics at 34.7 GHz, and the S11 parameters are below − 13 dB in the frequency range of 30–40 GHz, indicating outstanding impedance matching. By arranging 56 antenna units, a periodic leaky-wave antenna is created, enabling fixed-frequency beam-scanning at 34.7 GHz. Experimental results show that the antenna can achieve scanning of angles between − 53° and + 60° with a gain of up to 12.63 dB. Once single-beam scanning is achieved, a method combining LC and discrete amplitude weighting technique, as well as multi-beam theory, is proposed for multi-beam study. Experimental results reveal that the designed 56-unit beam-scanning antenna can effectively realize beam scanning in two directions.

Abstract Objectives Emerging evidence suggests a potential relationship between body composition and short-term prognosis of ulcerative colitis (UC). Early and accurate assessment of rapid remission based on conventional therapy via abdominal computed tomography (CT) images has rarely been investigated. This study aimed to build a prediction model using CT-based body composition parameters for UC risk stratification. Methods In total, 138 patients with abdominal CT images were enrolled. Eleven quantitative parameters related to body composition involving skeletal muscle mass, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were measured and calculated using a semi-automated segmentation method. A prediction model was established with significant parameters using a multivariable logistic regression. The receiver operating characteristic (ROC) curve was plotted to evaluate prediction performance. Subgroup analyses were implemented to evaluate the diagnostic efficiency of the prediction model between different disease locations, centers, and CT scanners. The Delong test was used for statistical comparison of ROC curves. Results VAT density, SAT density, gender, and visceral obesity were significantly statistically different between remission and invalidation groups (all p 0.05). Conclusions The predicting model constructed with CT-based body composition parameters is a potential non-invasive approach for short-term prognosis identification and risk stratification. Additionally, VAT density was an independent predictor for escalating therapeutic regimens in UC cohorts. Critical relevance statement The CT images were used for evaluating body composition and risk stratification of ulcerative colitis patients, and a potential non-invasive prediction model was constructed to identify non-responders with conventional therapy for making therapeutic regimens timely and accurately. Key points • CT-based prediction models help divide patients into invalidation and remission groups in UC. • Results of the subgroup analysis confirmed the stability of the prediction model with a high AUC (all > 0.820). • The visceral adipose tissue density was an independent predictor of bad short-term prognosis in UC. Graphical Abstract

Abstract Background The recruitment of thermogenic adipocytes in human fat depots markedly improves metabolic disorders such as type 2 diabetes mellitus (T2DM). However, identification and quantification of thermogenic cells in human fats, especially in metabolic disorders patients, remains a major challenge. Here, we aim to provide a stringent validation of human thermogenic adipocyte signature genes, and construct transcriptome-based models to quantify the browning degree of human fats. Methods Evidence from RNA-seq, microarray analyses and experimental approaches were integrated to isolate robust human brown-like fat signature genes. Meta-analysis was employed to validate the performance of known human brown-like fat marker genes. Autoencoder was used to reveal the browning levels of human adipose samples for supervised machine learning. Ensemble machine learning was applied to devised molecular metrics for quantifying browning degree of human fats. Obesity and T2DM datasets were used to validate the performance of the molecular metrics in adipose-related metabolic disorders. Results Human brown-like adipocytes were heterogeneous populations which showed distinct transcriptional patterns and biological features. Only DHRS11, REEP6 and STX11 were robust signature genes that were consistently up-regulated in different human brown-like fats, especially in creatine-induced UCP1-independent adipocytes. The molecular metrices based on the expression patterns of the three signature genes, named human browning capacity index (HBI) and absolute HBI (absHBI), were superior to 26 traditional human brown-like fat marker genes and previously reported browning classifier in prediction of browning levels of human adipocytes and adipose tissues as well as primary cell cultures upon various physiological and pharmacological stimuli. Notably, these molecular metrics also reflected the insulin sensitivity and glucose-lipid metabolic activity of human adipose samples from obesity and T2DM patients. Conclusions In summary, this study provides promising signatures and computational tools for evaluating browning levels of human adipose samples in response to physiological and medical intervention. The metrices construction pipeline provides an alternative approach for training machine learning models using unlabeled samples.

Fibre-reinforced sand (FRS) is a multiphase and multiscale geo-material, which is widely used in geotechnical engineering as supporting structure of excavation of underground space and reinforcement of foundation of underground structures, and its strength is determined by the properties of the heterogeneous substances of the FRS and their coupling mechanical responses. In order to investigate the influence of fibre characteristics and mechanical properties on the shear strength of the FRS, according to the microscopic interface slip effect generated by the interaction between sand particles and the interaction between these particles and fibre, the material phase of the FRS is divided to conceptualize a micro cell element of the FRS that is capable of reflecting the internal material characteristic information of the FRS. Moreover, based on the coordinated deformation condition between fibres and sand particles at the microscale and the couple stress theory that is capable of effectively describing the discontinuous mechanical responses at the sand-fibre interface, a mesomechanism-based multiscale Mohr–Coulomb shear strength criterion of the FRS is derived, and the yield locus of the FRS is also drawn on the π plane. Furthermore, a series of FRS samples with different fibre content and fibre length were prepared by adopting the freezing method, and consolidated and drained triaxial compression tests were conducted on these samples to validate the proposed multiscale coupled Mohr–Coulomb shear strength criterion. Results show that the multiscale coupled Mohr–Coulomb shear strength criterion is capable of effectively reproducing and predicting the yield strength of the FRS. The yield locus of the FRS extends outwards as fibre content and fibre length increase. The yield stress of the FRS predicted by the proposed multiscale coupled Mohr–Coulomb shear strength criterion is in good agreement with that of the test result.

Although three-dimensional visual training (3DVT) has been used for myopia intervention, its neural mechanisms remain largely unknown. In this study, visual function was examined before and after 3DVT, while resting-state EEG-fNIRS signals were recorded from 38 myopic participants. A graph theoretical analysis was applied to compute the neurovascular properties, including static brain networks (SBNs), dynamic brain networks (DBNs), and dynamic neurovascular coupling (DNC). Correlations between the changes in neurovascular properties and the changes in visual functions were calculated. After 3DVT, the local efficiency and node efficiency in the frontal lobes increased in the SBNs constructed from EEG $\delta $ -band; the global efficiency and node efficiency in the frontal-parietal lobes decreased in the DBNs variability constructed from EEG $\delta $ -band. For the DNC constructed with EEG $\alpha $ -band and oxyhemoglobin (HbO), the local efficiency decreased, for EEG $\alpha $ -band and deoxyhemoglobin (HbR), the node efficiency in the frontal-occipital lobes decreased. For the SBNs constructed from HbO, the functional connectivity (FC) between the frontal-occipital lobes increased. The DNC constructed between the FC of the frontal-parietal lobes from EEG $\beta $ -band and the FC of the frontal-occipital lobes from HbO increased, and between the FC of the frontal-occipital lobes from EEG $\beta $ -band and the FC of the inter-frontal lobes from HbR increased. The neurovascular properties were significantly correlated with the amplitude of accommodation and accommodative facility. The result indicated the positive effects of 3DVT on myopic participants, including improved efficiency of brain networks, increased FC of SBNs and DNC, and enhanced binocular accommodation functions.

Abstract Background Psychological distress is common in maintenance hemodialysis patients, and high psychological resilience can promote psychological well-being. The current research focuses on psychological resilience protective factors such as family resilience and social support. However, the trajectories of psychological resilience, family resilience, and social support over time and their longitudinal relationships in maintenance hemodialysis patients have not been fully explored yet. Therefore, this study aims to explore the longitudinal relationship between these factors. Methods Patients who received regular hemodialysis treatment for more than three months at dialysis centers of three tertiary hospitals in Zhejiang, China, were recruited from September to December 2020. A total of 252 patients who met the inclusion and exclusion criteria completed three follow-up surveys, including social support, family resilience, and psychological resilience assessments. A repeated measures ANOVA was used to explore differences in their respective scores at different time points. The cross-lagged analysis was performed in AMOS using the maximum likelihood method to examine the the reciprocal predictive relationships between these factors. Results Social support and psychological resilience remained relatively stable over time, whereas family resilience indicated a little increasing trend. According to the cross-lagged analysis, higher T1 social support predicted higher family resilience at T2 [β = 0.123, 95% CI (0.026–0.244)]. Further, the effects of T2 social support to T3 family resilience [β = 0.194, 95%CI (0.039–0.335)] and psychological resilience [β = 0.205, 95%CI (0.049–0.354)] were significant. Finally, the effects of T2 family resilience to T3 social support [β = 0.122, 95%CI (0.010–0.225)] and psychological resilience [β = 0.244, 95%CI (0.119–0.359)] were also significant. Conclusions The study showed that the directionality of the relationship appears to be from social support or family resilience to patients’ psychological resilience but not vice versa. This finding reminds healthcare professionals to emphasize the vital role of social and family resources in providing appropriate support and interventions for maintenance hemodialysis patients to promote psychological resilience and mental health development.

Due to the accelerated development of population growth and urbanization, water resources are facing increasing pressure. In this context, the sustainable use of water resources has become a top priority. At the same time, the construction of urban green space and public space has also received increasing attention, as they not only enhance the image of the city but also provide services such as leisure and entertainment for people. In this context, how to combine the sustainable use of water resources with the visual design of a water-based landscape environment has become a new research direction. This paper analyzes the visual design of the water-based landscape environment. In terms of whether the water-based environmental visual design can create a different artistic conception for urban green space, 78% of white-collar workers in enterprises, 88% of sanitation workers, and 79% of technicians from different professions thought so. Results showed that in the construction of urban green space, people should pay attention to the interaction between people and the environment to achieve the coordination between people and society, nature, and culture. HIGHLIGHTS Based on the sustainable utilization of water resources, this paper analyzes and studies the visual design of the water-based landscape environment.; The experimental results of this paper show whether environmental visual design is widely used in urban green space.;