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Abstract Echinoderm microtubule-associated protein 4 (EML4) - anaplastic lymphoma kinase (ALK) fusion gene detection is of great significance in personalized tumor treatment. With the development of EML4-ALK fusion variants detection, it is necessary to establish traceability to ensure the consistency and comparability of its detection results in clinical practice. The establishment of traceability relies on SI traceable reference materials (RMs) and potential reference measurement procedures (RMPs). In this study, a potential RMP for the quantitative detection of V1 and V3 fusion mutations and the reference type (ALK-ref, including wild type, V1 and V3 mutant type) based on reverse transcription dPCR (RT-dPCR) and EML4-ALK fusion gene RMs were established. The proposed potential RMP has high specificity, good inter-laboratory reproducibility (CV

Abstract Objectives This study examined the potential association between nucleated red blood cell (NRBC) levels and mortality in critically ill patients with acute pancreatitis (AP) in the intensive care unit, due to limited existing research on this correlation. Methods This retrospective cohort study utilized data from the MIMIC-IV v2.0 and MIMIC-III v1.4 databases to investigate the potential relationship between NRBC levels and patient outcomes. The study employed restricted cubic splines (RCS) regression analysis to explore non-linear associations. The impact of NRBC on prognosis was assessed using a generalized linear model (GLM) with a logit link, adjusted for potential confounders. Furthermore, four machine learning models, including Gradient Boosting Classifier (GBC), Random Forest, Gaussian Naive Bayes, and Decision Tree Classifier model, were constructed using NRBC data to generate risk scores and evaluate the potential of NRBC in predicting patient prognosis. Results A total of 354 patients were enrolled in the study, with 162 (45.8%) individuals aged 60 years or older and 204 (57.6%) males. RCS regression analysis demonstrated a non-linear relationship between NRBC levels and 90-day mortality. Receiver Operating Characteristic (ROC) analysis identified a 1.7% NRBC cutoff to distinguish survivor from non-survivor patients for 90-day mortality, yielding an Area Under the Curve (AUC) of 0.599, with a sensitivity of 0.475 and specificity of 0.711. Elevated NRBC levels were associated with increased risks of 90-day mortality in both unadjusted and adjusted models (all Odds Ratios > 1, P

Abstract Background Sarcopenia is an important indicator of ill health and is linked to increased mortality and a reduced quality of life. Age‐associated muscle mass indices provide a critical tool to help understand the development of sarcopenia. This study aimed to develop sex‐ and age‐specific percentiles for muscle mass indices in a Chinese population and to compare those indices with those from other ethnicities using the National Health and Nutrition Examination Survey (NHANES) data. Methods Whole‐body and regional muscle mass was measured by dual‐energy X‐ray absorptiometry (DXA) in participants of the China Body Composition Life‐course (BCL) study (17 203 healthy Chinese aged 3–60 years, male 48.9%) and NHANES (12 663 healthy Americans aged 8–59 years, male 50.4%). Age‐ and sex‐specific percentile curves were generated for whole‐body muscle mass and appendicular skeletal muscle mass using the Generalized Additive Model for Location Scale and Shape statistical method. Results Values of upper and lower muscle mass across ages had three periods: an increase from age 3 to a peak at age 25 in males (with the 5th and 95th values of 41.5 and 66.4 kg, respectively) and age 23 in females (with the 5th and 95th values of 28.4 and 45.1 kg, respectively), a plateau through midlife (30s–50s) and then a decline after their early 50s. The age at which muscle mass began to decline was 52 years in men with the 5th and 95th percentile values of 43.5 and 64.6 kg, and 51 years in women with the 5th and 95th percentile values of 31.6 and 46.9 kg. Appendicular skeletal muscle mass decreased earlier than whole body muscle mass, especially leg skeletal muscle mass, which decreased slightly after age 49 years in both sexes. In comparison with their US counterparts in the NHANES, the Chinese participants had lower muscle mass indices (all P

β-Glucan derived from cereals is a crucial dietary fiber primarily found in pastes, sub-pastes, and endosperm of cereals, which has a positive impact on human health. The integration of cereal β-glucan in the food industry is widespread due to its proven effectiveness in preventing diabetes, reducing the incidence of cardiovascular disease, modulating intestinal microbiota, and enhancing immune cell function. This comprehensive review thoroughly examines the extraction, isolation, purification, structure, and biological properties of cereal β-glucans. Furthermore, the article explores the utilization of cereal β-glucans in dairy, bakery, and meat products. It provides a comprehensive overview of current research in this field, addressing both challenges and solutions, while laying the theoretical foundations for future advancements in incorporating cereal β-glucan-based foods.

The building sector plays a crucial role in the worldwide shift toward achieving net-zero emissions. Building energy efficiency standards (BEESs) are highly effective policies for reducing carbon emissions. Therefore, exploring the provincial variations in carbon emission efficiency (CEE) in the building sector and identifying the effect of BEESs on CEE is crucial. This study focuses on commercial buildings in China and applies a difference in differences model to evaluate the impact of BEESs on the CEE of commercial buildings. The slacks-based measure–data envelopment analysis model is employed to assess the CEE of commercial buildings in 30 Chinese provinces from 2000 to 2019. Furthermore, heterogeneous tests are used to explore how climate characteristics and economic conditions affect the efficiency of BEESs. The results indicate that BEESs positively influence the CEE of commercial buildings. Specifically, a 1% increase in the intensity of BEESs causes a 0.148 4% increase in the CEE of commercial buildings. Moreover, the impact of BEESs is particularly pronounced in the southern and western provinces. This study provides valuable scientific evidence for governments to enhance BEESs implementation.

Abstract Background Infertility is a growing global health concern affecting millions of couples worldwide. Among several factors, an extreme body weight adversely affects reproductive functions. Leptin is a well-known adipokine that serves as an endocrine signal between adiposity and fertility. However, the exact mechanisms underlying the effects of high leptin level on female reproduction remain unclear. Methods Transgenic pigs overexpressing leptin (♀) were produced by backcrossing and screened for leptin overexpression. The growth curve, fat deposition, reproductive performance, apoptosis, serum hormones and cholesterol production, RNA sequencing, and single-nucleus RNA sequencing (snRNA-seq) of the leptin-overexpressing pigs and wild-type group were evaluated. Results Transgenic pigs overexpressing leptin (♀) were obtained, which exhibited significantly reduced body weight, body size, and back fat thickness. These pigs manifested a late onset of puberty (330 ± 54.3 vs. 155 ± 14.7 days), irregular estrous behavior characterized by increased inter-estrous interval (29.2 ± 0 vs. 21.3 ± 0.7 days), and more number of matings until pregnancy (at least 3 times). This reproductive impairment in leptin pigs was related to hormonal imbalances characterized by increased levels of FSH, LH, prolactin, E2, P4, and TSH, altered steroidogenesis such as increased levels of serum cholesterol esters along with steroidogenic markers (StAR, CYP19A), and ovarian dysfunctions manifested by neutrophilic infiltration and low expression of caspase-3 positive cells in the ovaries. Moreover, bulk RNA sequencing of the ovaries also revealed neutrophilic infiltration followed by upregulation of inflammation-related genes. Furthermore, snRNA-seq reflected that leptin overexpression triggered immune response, suppressed follicle development and luteinization, resulting in metabolic dysfunction and hormone imbalance in the ovary. Conclusions Low body weight in leptin overexpressing pigs adversely affects the reproductive performance, causing delayed puberty, irregular estrous cycles, and reduced breeding efficiency. This is linked to metabolic imbalances, an increased immune response, and altered ovarian functions. This study provides a theoretical basis for the complex mechanisms underlying leptin, and infertility by employing leptin-overexpressing female pigs.

Abstract Background Plant-associated microorganisms can be found in various plant niches and collectively comprise the plant microbiome. The plant microbiome assemblages have been extensively studied, primarily in model species. However, a deep understanding of the microbiome assembly associated with plant health is still needed. Ginger rhizome rot has been variously attributed to multiple individual causal agents. Due to its global relevance, we used ginger and rhizome rot as a model to elucidate the metabolome-driven microbiome assembly associated with plant health. Results Our study thoroughly examined the biodiversity of soilborne and endophytic microbiota in healthy and diseased ginger plants, highlighting the impact of bacterial and fungal microbes on plant health and the specific metabolites contributing to a healthy microbial community. Metabarcoding allowed for an in-depth analysis of the associated microbial community. Dominant genera represented each microbial taxon at the niche level. According to linear discriminant analysis effect size, bacterial species belonging to Sphingomonas, Quadrisphaera, Methylobacterium-Methylorubrum, Bacillus, as well as the fungal genera Pseudaleuria, Lophotrichus, Pseudogymnoascus, Gymnoascus, Mortierella, and Eleutherascus were associated with plant health. Bacterial dysbiosis related to rhizome rot was due to the relative enrichment of Pectobacterium, Alcaligenes, Klebsiella, and Enterobacter. Similarly, an imbalance in the fungal community was caused by the enrichment of Gibellulopsis, Pyxidiophorales, and Plectosphaerella. Untargeted metabolomics analysis revealed several metabolites that drive microbiome assembly closely related to plant health in diverse microbial niches. At the same time, 6-({[3,4-dihydroxy-4-(hydroxymethyl)oxolan-2-yl]oxy}methyl)oxane-2,3,4,5-tetrol was present at the level of the entire healthy ginger plant. Lipids and lipid-like molecules were the most significant proportion of highly abundant metabolites associated with ginger plant health versus rhizome rot disease. Conclusions Our research significantly improves our understanding of metabolome-driven microbiome structure to address crop protection impacts. The microbiome assembly rather than a particular microbe’s occurrence drove ginger plant health. Most microbial species and metabolites have yet to be previously identified in ginger plants. The indigenous microbial communities and metabolites described can support future strategies to induce plant disease resistance. They provide a foundation for further exploring pathogens, biocontrol agents, and plant growth promoters associated with economically important crops. Video Abstract

Abstract Oocyte aging is a key constraint on oocyte quality, leading to fertilization failure and abnormal embryonic development. In addition, it is likely to generate unfavorable assisted reproductive technology (ART) outcomes. SCM-198, a synthetic form of leonurine, was found to rescue the rate of oocyte fragmentation caused by postovulatory aging. Therefore, the aim of this study was to conduct a more in-depth investigation of SCM-198 by exploring its relationship with aged oocytes after ovulation or maternal aging and clarifying whether it affects cell quality. The results indicate that, compared to the postovulatory aged group, the 50 µM SCM-198 group significantly improved sperm-egg binding and increased fertilization of aged oocytes, restoring the spindle apparatus/chromosome structure, cortical granule distribution, and ovastacin and Juno protein distribution. The 50 µM SCM-198 group showed significantly normal mitochondrial distribution, low levels of reactive oxygen species (ROS), and a small quantity of early oocyte apoptosis compared to the postovulatory aged group. Above all, in vivo supplementation with SCM-198 effectively eliminated excess ROS and reduced the spindle/chromosome structural defects in aged mouse oocytes. In summary, these findings indicate that SCM-198 inhibits excessive oxidative stress in oocytes and alters oocyte quality both in vitro and in vivo. Graphical Abstract

Abstract Background Obesity is a global health issue with detrimental effects on various human organs, including the reproductive system. Observational human data and several lines of animal experimental data suggest that maternal obesity impairs ovarian function and early embryo development, but the precise pathogenesis remains unclear. Methods We established a high-fat diet (HFD)-induced obese female mouse model to assess systemic metabolism, ovarian morphology, and oocyte function in mice. For the first time, this study employed single-cell RNA sequencing to explore the altered transcriptomic landscape of preimplantation embryos at different stages in HFD-induced obese mice. Differential gene expression analysis, enrichment analysis and protein-protein interactions network analysis were performed. Results HFD-induced obese female mice exhibited impaired glucolipid metabolism and insulin resistance. The ovaries of HFD mice had a reduced total follicle number, an increased proportion of atretic follicles, and irregular granulosa cell arrangement. Furthermore, the maturation rate of embryonic development by in vitro fertilization of oocytes was significantly decreased in HFD mice. Additionally, the transcriptional landscapes of preimplantation embryos at different stages in mice induced by different diets were significantly distinguished. The maternal-to-zygotic transition was also affected by the failure to remove maternal RNAs and to turn off zygotic genome expression. Conclusions HFD-induced obesity impaired ovarian morphology and oocyte function in female mice and further led to alterations in the transcriptional landscape of preimplantation embryos at different stages of HFD mice.

Abstract Enterovirus 71 (EV-71) has strong neurotropism, and it is the main pathogen causing severe hand, foot, and mouth disease (HFMD). In clinical observations, significant differences were observed in the severity and prognosis of HFMD among children who were also infected with EV-71. Genetic differences among individuals could be one of the important causes of differences in susceptibility to EV-71–induced HFMD. As P-selectin glycoprotein ligand-1 (PSGL-1) is an important receptor of EV-71, the correlation between single-nucleotide polymorphisms (SNPs) in PSGL-1 and the susceptibility to severe HFMD following EV-71 infection is worth studying. Given the role of PSGL-1 in immunity, the correlations between PSGL-1 SNPs and the immune status after EV-71 infection are also worth studying. Meanwhile, PSGL-1 variable number of tandem repeats (VNTR) represents a research hotspot in cardiovascular and cerebrovascular diseases, but PSGL-1 VNTR polymorphism has not been investigated in HFMD caused by EV-71 infection. In this study, specific gene fragments were amplified by polymerase chain reaction, and PSGL-1 VNTR sequences were genotyped using an automatic nucleic acid analyzer. The correlations of PSGL-1 VNTR polymorphism with the susceptibility to EV-71–associated severe HFMD and the post-infection immune status were analyzed. The PSGL-1 VNTR A allele was identified as a susceptible SNP for severe HFMD. The risk of severe HFMD was higher for AA + AB genotype carriers than for BB genotype carriers. The counts of peripheral blood lymphocyte subsets were lower in AA + AB genotype carries than in BB genotype carries. In conclusion, PSGL-1 VNTR polymorphism is associated with the susceptibility to EV-71–induced severe HFMD and the immune status after infection. PSGL-1 VNTR might play a certain role in the pathogenesis of severe cases.

The flesh color of pummelo (Citrus maxima) fruits is highly diverse and largely depends on the level of carotenoids, which are beneficial to human health. It is vital to investigate the regulatory network of carotenoid biosynthesis to improve the carotenoid content in pummelo. However, the molecular mechanism underlying carotenoid accumulation in pummelo is not fully understood. In this study, we identified a novel histone methyltransferase gene, CgSDG40, involved in carotenoid regulation by analyzing the flesh transcriptome of typical white-fleshed pummelo, red-fleshed pummelo and extreme-colored F1 hybrids from a segregated pummelo population. Expression of CgSDG40 corresponded to flesh color change and was highly coexpressed with CgPSY1. Interestingly, CgSDG40 and CgPSY1 are located physically adjacent to each other on the chromosome in opposite directions, sharing a partially overlapping promoter region. Subcellular localization analysis indicated that CgSDG40 localizes to the nucleus. Overexpression of CgSDG40 significantly increased the total carotenoid content in citrus calli relative to that in wild type. In addition, expression of CgPSY1 was significantly activated in overexpression lines relative to wild type. Taken together, our findings reveal a novel histone methyltransferase regulator, CgSDG40, involved in the regulation of carotenoid biosynthesis in citrus and provide new strategies for molecular design breeding and genetic improvement of fruit color and nutritional quality.

Abstract Female urethral caruncle is the most common urethral mass in postmenopausal women, yet there is a lack of studies on its imaging. The aim of this study was to provide a summary of the clinical and ultrasound features as well as the precise location of female urethral caruncle. This study reviewed the clinical and ultrasonographic records of 20 consecutive women with pathologically confirmed urethral caruncle. Data on patient demographics, symptoms, and transperineal and transrectal ultrasound imaging features, including location, shape, margin, size, blood flow, and inner echo of the caruncle, were extracted. Each patient presented with only one mass at the urethral meatus. Most caruncles were located on the posterior lip (75%) of the urethra, presenting as oval (80%), mixed-echoic (50%), or hypo-echoic (40%) nodules with abundant linear (40%) or dendritic (60%) blood flow. The average distance between the bladder neck and the cranial end of the masses was 28 mm. Hyper-echogenic spots, cystic echo areas, and macrocalcifications were detected in thirteen caruncles (70%). This study shows that transperineal combined with transrectal ultrasound can be used to assess female urethral caruncle, and its relative location to the urethra can be accurately described, which is helpful for surgeons making preoperative localization and conversations.

Abstract. Objectives. This study aims to not only investigate the prevalence of social alienation among elderly patients undergoing radical prostatectomy for prostate cancer but also identify the contributing factors. Materials and methods. A total of 245 elderly patients diagnosed with prostate cancer and undergoing radical prostatectomy at a tertiary care general hospital in Jinan were included in this study. To assess the patients, several questionnaires were used. These included the General Situation Questionnaire, General Alienation Scale, Social Impact Scale, Modified Memorial Anxiety Scale for Prostate Cancer, and Perceived Social Support Scale. Pearson correlation analysis was conducted to examine the relationships between variables, whereas multiple linear regression was used to identify the factors influencing social alienation among patients who underwent radical prostatectomy. Results. Patients who underwent radical prostatectomy had a mean total score of 44.13 ± 7.24 on the Social Alienation Scale. The results of the Pearson correlation analysis indicated that social alienation showed an inverse association with social support (r = −0.627, p < 0.05) and positive associations with age, disease stigma, and anxiety (r = 0.325, 0.575, 0.421, all p’s < 0.01) among patients who underwent radical prostatectomy. The findings from multiple linear regression analysis demonstrated that educational level, age, urinary incontinence, disease stigma, anxiety, and social support significantly influenced social alienation among elderly patients who underwent radical prostatectomy (p < 0.05). Conclusions. Elderly patients who undergo radical prostatectomy often experience social alienation. This study found that social alienation was associated with factors such as educational level, age, urinary incontinence, social support, anxiety, and disease stigma. Consequently, healthcare providers should actively monitor the degree of social alienation in elderly patients after radical prostatectomy and provide suitable psychological care to facilitate positive social reintegration and alleviate their feelings of social alienation.

ABSTRACT Importance Systemic lupus erythematosus (SLE) is a diffuse connective tissue disease with complex clinical manifestations and prolonged course. The early diagnosis and condition monitoring of SLE are crucial to disease prognosis. Objective To assess the diagnostic value of long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) in childhood‐onset SLE (cSLE). Methods Fifty‐seven children diagnosed with SLE, 40 children diagnosed with juvenile idiopathic arthritis (JIA), and 40 healthy children were included. Peripheral blood samples from each patient were collected. A quantitative polymerase chain reaction was used to confirm the expression of lncNEAT1_1 and lncNEAT1_2 in peripheral blood. Associations among parameters were analyzed using the Mann‐Whitney U test or independent sample t‐test. Results The expression of both lncNEAT1_1 and lncNEAT1_2 in patients with cSLE were significantly higher than that of healthy control and patients with JIA. Receiver operating characteristic curves revealed an area under the curve (AUC) of 0.633 (95% confidence interval [CI], 0.524–0.742; P = 0.024) for lncNEAT1_1. The AUC of lncNEAT1_2 was 0.812 (95% CI, 0.727–0.897; P < 0.0001) to discriminate individuals with cSLE from health control and children with JIA with a sensitivity of 0.622 and a specificity of 0.925. Moreover, lncNEAT1_2 expression was higher in patients with cSLE presenting with fever, lupus nephritis, elevated erythrocyte sedimentation rate, active disease activity, and decreased C3 level, compared with those without these conditions. However, no similar correlation was observed for lncNEAT1_1. Interpretation The expression of lncNEAT1_2 was significantly elevated in children with SLE, especially those with fever, renal involvement, and low C3 levels. These findings suggest that lncNEAT1_2 may represent a potential biomarker for cSLE.

Abstract With the high incidence of urogenital tumors worldwide, urinary system tumors are among the top 10 most common tumors in men, with prostate cancer ranking first and bladder cancer fourth. Patients with resistant urogenital tumors often have poor prognosis. In recent years, researchers have discovered numerous specific cancer antigens, which has led to the development of several new anti-cancer drugs. Using protein analysis techniques, researchers developed immune checkpoint inhibitors (ICIs) and antibody-conjugated drugs (ADCs) for the treatment of advanced urogenital tumors. However, tumor resistance often leads to the failure of monotherapy. Therefore, clinical trials of the combination of ICIs and ADCs have been carried out in numerous centers around the world. This article reviewed phase 2 and 3 clinical studies of ICIs, ADCs, and their combination in the treatment of urogenital tumors to highlight safe and effective methods for selecting individualized therapeutic strategies for patients. ICIs activate the immune system, whereas ADCs link monoclonal antibodies to toxins, which can achieve a synergistic effect when the two drugs are combined. This synergistic effect provides multiple advantages for the treatment of urogenital tumors.

Abstract Heart failure is the final stage of several cardiovascular diseases, and the key to effectively treating heart failure is to reverse or delay ventricular remodelling. Levosimendan is a novel inotropic and vasodilator agent used in heart failure, whereas the impact of levosimendan on ventricular remodelling is still unclear. This study aims to investigate the impact of levosimendan on ventricular remodelling in patients with left ventricular systolic dysfunction. Electronic databases were searched to identify eligible studies. A total of 66 randomized controlled trials involving 7968 patients were included. Meta‐analysis results showed that levosimendan increased left ventricular ejection fraction [mean difference (MD) = 3.62, 95% confidence interval (CI) (2.88, 4.35), P

Due to the complicated metabolic and regulatory networks of l-serine biosynthesis and degradation, microbial cell factories for l-serine production using non-model microorganisms have not been reported. In this study, a combination of synthetic biology and process optimization were applied in an ethanologenic bacterium Zymomonas mobilis for l-serine production. By blocking the degradation pathway while introducing an exporter EceamA from E. coli, l-serine titer in recombinant Z. mobilis was increased from 15.30 mg/L to 62.67 mg/L. It was further increased to 260.33 mg/L after enhancing the l-serine biosynthesis pathway. Then, 536.70 mg/L l-serine was achieved by removing feedback inhibition with a SerA mutant, and an elevated titer of 687.67 mg/L was further obtained through increasing serB copies while enhancing the precursors. Finally, 855.66 mg/L l-serine can be accumulated with the supplementation of the glutamate precursor. This work thus not only constructed an l-serine producer to help understand the bottlenecks limiting l-serine production in Z. mobilis for further improvement, but also provides guidance on engineering non-model microbes to produce biochemicals with complicated pathways such as amino acids or terpenoids.

To effectively combat emerging infectious diseases like COVID-19, it is crucial to adopt strict prevention and control measures promptly to effectively contain the spread of the epidemic. In this paper, we propose a transmission model to investigate the influence of two control strategies: reducing contact numbers and improving medical resources. We examine these strategies in terms of constant control and time-varying control. Through sensitivity analysis on two reproduction numbers of the model with constant control, we demonstrate that reducing contact numbers is more effective than improving medical resources. Furthermore, these two constant controls significantly influence the peak values and timing of infections. Specifically, intensifying control measures can reduce peak values, albeit at the expense of delaying the peak time. In the model with time-varying control, we initially explore the corresponding optimal control problem and derive the characteristic expression of optimal control. Subsequently, we utilize real data from January 10th to April 12th, 2020, in Wuhan city as a case study to perform parameter estimation by using our proposed improved algorithm. Our findings illustrate that implementing optimal control measures can effectively reduce infections and deaths, and shorten the duration of the epidemic. Then, we numerically explore that implementing control measures promptly and increasing intensity to reduce contact numbers can make actual control be more closer to optimized control. Finally, we utilize the real data from October 31st to November 18th, 2021, in Hebei province as a second case study to validate the feasibility of our proposed suggestions.

Abstract Background LncRNA colorectal neoplasia differentially expressed (CRNDE) was found to be an important regulator in many cancers. This project focuses on the function of CRNDE on macrophage metabolic reprogramming and Hepatocellular carcinoma (HCC). Method qRT-PCR and Immunofluorescence were used to analyze Arg-1, IL-10, CD163, CCL-18, CD206, and CRNDE expression in HCC tissues and macrophages. Western Blotting was used to analyze ERK and p-ERK expression. Edu assay, transwell assay and xenograft experiments were carried out to study cell viability, migrated and invasive capability. Immunohistochemical staining was used to evaluate Ki67 expression. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed for macrophages metabolites analysis. Results Arg-1, IL-10, CD163, CD206, and CRNDE were significantly up-regulated in HCC tissues, M2 macrophage and M0 macrophage with CRNDE overexpressed (OV-CRNDE-M0), which downregulated in M0 macrophage with CRNDE knockdown (sh-CRNDE-M0). The conditioned medium (CM) of M2 cells and OV-CRNDE-M0 cells promoted cell viability, invasion, and migration of HCC cells, the effect was reversed by sh-CRNDE-M0 cells CM. OV-CRNDE-M0 cells promoted tumor growth, Ki67 and CD206 expression in xenograft model. 61 metabolites were detected, of which 18 metabolites changed significantly in OV-CRNDE-M0 group compared to M0 group, with 9 upregulated and 9 downregulated. KEGG analysis showed the enrichment pathways were biosynthesis, glyoxylate and dicarboxylate metabolism. SMPDB analysis showed the enrichment pathways were hypoacetylaspartia, canavan disease, and aspartate metabolism. Conclusion CRNDE regulated the metabolic reprogramming of M2 macrophage via ERK pathway, which thereby contributed to HCC proliferation, migration, and invasion.

Abstract Objective To explore the factors affecting delayed medical decision-making in older patients with acute ischemic stroke (AIS) using logistic regression analysis and the Light Gradient Boosting Machine (LightGBM) algorithm, and compare the two predictive models. Methods A cross-sectional study was conducted among 309 older patients aged ≥ 60 who underwent AIS. Demographic characteristics, stroke onset characteristics, previous stroke knowledge level, health literacy, and social network were recorded. These data were separately inputted into logistic regression analysis and the LightGBM algorithm to build the predictive models for delay in medical decision-making among older patients with AIS. Five parameters of Accuracy, Recall, F1 Score, AUC and Precision were compared between the two models. Results The medical decision-making delay rate in older patients with AIS was 74.76%. The factors affecting medical decision-making delay, identified through logistic regression and LightGBM algorithm, were as follows: stroke severity, stroke recognition, previous stroke knowledge, health literacy, social network (common factors), mode of onset (logistic regression model only), and reaction from others (LightGBM algorithm only). The LightGBM model demonstrated the more superior performance, achieving the higher AUC of 0.909. Conclusions This study used advanced LightGBM algorithm to enable early identification of delay in medical decision-making groups in the older patients with AIS. The identified influencing factors can provide critical insights for the development of early prevention and intervention strategies to reduce delay in medical decisions-making among older patients with AIS and promote patients’ health. The LightGBM algorithm is the optimal model for predicting the delay in medical decision-making among older patients with AIS.

Abstract Chimeric antigen receptor engineered T (CAR T) cell therapy has developed rapidly in recent years, leading to profound developments in oncology, especially for hematologic malignancies. However, given the pressure of immunosuppressive tumor microenvironments, antigen escape, and diverse other factors, its application in solid tumors is less developed. Urinary system tumors are relatively common, accounting for approximately 24% of all new cancers in the United States. CAR T cells have great potential for urinary system tumors. This review summarizes the latest developments of CAR T cell therapy in urinary system tumors, including kidney cancer, bladder cancer, and prostate cancer, and also outlines the various CAR T cell generations and their pathways and targets that have been developed thus far. Finally, the current advantages, problems, and side effects of CAR T cell therapy are discussed in depth, and potential future developments are proposed in view of current shortcomings.

Recent studies have demonstrated the superiority of cell-to-cell transmission over cell-free virus infection, and highlighted the role of inflammatory cytokines in enhancing viral infection. To investigate their impacts on viral infection dynamics, we have proposed an HIV infection model incorporating general incidence rates, these infection modes, and two time delays. We derived the basic reproduction number and showed that it governs the existence and local stability of steady states. Through the construction of appropriate Lyapunov functionals and application of the LaSalle invariance principle, we established the global asymptotic stability of both the infection-free and infected steady states.

Abstract To explore the impacts of continuous Ganoderma lucidum cultivation on soil physicochemical factors, soil enzyme activity, and the metabolome of Ganoderma lucidum fruiting bodies, this study conducted two consecutive years of cultivation on the same plot of land. Soil physicochemical factors and enzyme activity were assessed, alongside non-targeted metabolomic analysis of the Ganoderma lucidum fruiting bodies under continuous cultivation. The findings unveiled that in the surface soil layer (0–15 cm), there was a declining trend in organic matter, ammonium nitrogen, available phosphorus, available potassium, pH, polyphenol oxidase, peroxidase, alkaline phosphatase, and sucrase, whereas nitrate nitrogen, electrical conductivity (EC), and salt content exhibited an upward trend. Conversely, in the deeper soil layer (15–30 cm), organic matter, ammonium nitrogen, available potassium, alkaline phosphatase, and sucrase demonstrated a decreasing trend, while nitrate nitrogen, available phosphorus, pH, EC, salt content, polyphenol oxidase, and soil peroxidase showed an increasing trend. Metabolomic analysis of Ganoderma lucidum fruiting bodies distinguished 64 significantly different metabolites between the GCK and GT groups, with 39 components having markedly higher relative contents in GCK and 25 components having significantly lower relative contents in GCK compared to GT. Moreover, among these metabolites, there were more types with higher contents in the fruiting bodies harvested in the first year (GCK) compared to those harvested in the second year (GT), with pronounced differences. KEGG pathway analysis revealed that GCK exhibited more complex metabolic pathways compared to GT. The metabolites of Ganoderma lucidum fruiting bodies were predominantly influenced by soil physicochemical factors and soil enzyme activity. In the surface soil layer (0–15 cm), the metabolome was significantly affected by soil pH, soil organic matter, available phosphorus, and soil alkaline phosphatase, while in the deeper soil layer (15–30 cm), differences in the Ganoderma lucidum metabolome were more influenced by soil alkaline phosphatase, soil catalase, pH, nitrate nitrogen, and soil sucrase.

Abstract Background Protein residue–residue distance maps are used for remote homology detection, protein information estimation, and protein structure research. However, existing prediction approaches are time-consuming, and hundreds of millions of proteins are discovered each year, necessitating the development of a rapid and reliable prediction method for protein residue–residue distances. Moreover, because many proteins lack known homologous sequences, a waiting-free and alignment-free deep learning method is needed. Result In this study, we propose a learning framework named FreeProtMap. In terms of protein representation processing, the proposed group pooling in FreeProtMap effectively mitigates issues arising from high-dimensional sparseness in protein representation. In terms of model structure, we have made several careful designs. Firstly, it is designed based on the locality of protein structures and triangular inequality distance constraints to improve prediction accuracy. Secondly, inference speed is improved by using additive attention and lightweight design. Besides, the generalization ability is improved by using bottlenecks and a neural network block named local microformer. As a result, FreeProtMap can predict protein residue–residue distances in tens of milliseconds and has higher precision than the best structure prediction method. Conclusion Several groups of comparative experiments and ablation experiments verify the effectiveness of the designs. The results demonstrate that FreeProtMap significantly outperforms other state-of-the-art methods in accurate protein residue–residue distance prediction, which is beneficial for lots of protein research works. It is worth mentioning that we could scan all proteins discovered each year based on FreeProtMap to find structurally similar proteins in a short time because the fact that the structure similarity calculation method based on distance maps is much less time-consuming than algorithms based on 3D structures.

AIM: To evaluate the clinical efficacy of small-diameter acellular porcine corneal stroma (SAPS) for the treatment of peripheral corneal ulceration (PCU). METHODS: This retrospective clinical study included 18 patients (18 eyes) with PCU between April 2018 and December 2020. All patients had PCU and underwent lamellar keratoplasty with SAPS. Observation indicators included preoperative and postoperative best-corrected visual acuity (BCVA) and transparency of SAPS. The infection control rate in the surgical eye-lesion area was also calculated. RESULTS: Eighteen patients underwent lamellar keratoplasty with SAPS to treat PCU. None of the patients experienced rejection after 6mo (18/18) and 12mo (16/16) of follow-up. The BCVA (0.47±0.30) at the 6mo follow-up after operation was significantly improved compared with the baseline (0.99±0.80), and the difference was statistically significant (Z=-3.415, P

ObjectivesThe purpose of this study was to compare the interlimb biomechanical differences in patients who had undergone anterior cruciate ligament reconstruction (ACLR) in either dominant (ACLR-D) or nondominant (ACLR-ND) limbs and healthy controls (CON) during drop vertical jump (DVJ) task. To investigate whether the dominant or nondominant limb influences the risk of re-injury in ACLR patients.MethodsThirty-three ACLR patients were divided into ACLR-D and ACLR-ND groups according to whether the surgical limb was dominant or nondominant. Seventeen healthy individuals were selected as the CON group. Three-dimensional kinematic data, ground reaction force (GRF) data, and surface electromyographic (EMG) data from the bilateral lower limbs of all participants were collected during the DVJ task. Two-way repeated-measures ANOVAs (limb × group) were performed on the variables of interest to examine the main effects of limb (dominant vs. nondominant) and group (ACLR-D, ACLR-ND, and CON), as well as the interaction between limb and group.ResultsThe nonsurgical limbs of ACLR group had significantly greater knee valgus angles, knee extension and valgus moments, peak posterior GRF (PPGRF), and peak vertical GRF (PVGRF) compared to the surgical limbs. The nonsurgical limbs of ACLR-ND patients demonstrated significantly greater knee extension and valgus moments, greater PPGRF and PVGRF, and reduced muscle activity in the vastus medialis and vastus lateralis compared to the CON group. The ACLR patients had reduced muscle activity in the quadriceps of the surgical limb and the hamstrings of the bilateral limbs compared to controls.ConclusionThe nonsurgical limbs of ACLR patients may suffer an increased risk of ACL injury due to altered landing mechanics and neuromuscular control strategies compared to the surgical limbs. Additionally, limb dominance influences movement patterns and neuromuscular control during DVJ task, the nonsurgical limbs of the ACLR-ND might be at higher risk of ACL injury compared to the ACLR-D group.

Objective: Behcet's uveitis (BU) is a type of uveitis with a high rate of blindness, characterized by anterior segment inflammation, vitreous opacity, and retinal vasculitis. Its pathogenesis is still unclear. Fuchs syndrome (Fuchs) is another common type of uveitis, which clinically presents with anterior segment inflammation and vitreous opacity, but rarely causes blindness. This study aims to compare the gut microbiota and metabolites of two different types of uveitis to clarify whether the differences in clinical manifestations are relevant to the alterations in gut microbiota. Methods: Faecal samples were collected from new-onset BU (n = 11) patients without systemic treatment and other diseases. 16S rRNA and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were performed to analyze gut microbes and metabolites. Fuchs (n = 15) was used as the disease control, and healthy controls (n = 18) without autoimmune diseases and systemic medication were included. Results: Microbial composition and metabolite profiles differed significantly among the three groups. Compared to controls, Fusicatenibacter and eight metabolites were specifically altered in BU patients, and Pantoea and five metabolites in Fuchs. Pathways involving delta-tocopherol, palmitic acid, and serotonin are significantly disrupted in BU patients. Pathways involving linoleic acid are dysregulated considerably in Fuchs. Microbial markers consisting of 4 genera and 7 metabolites can respectively distinguish BU patients from controls. AUC values of metabolite markers were greater than those of microbial markers. Furthermore, serum zonulin levels were significantly elevated in both types of uveitis, with no difference between them. Correlation analysis revealed correlations between zonulin levels and multiple microbes. Conclusions: Patients with BU and Fuchs syndrome showed significant differences in gut microbiota and metabolites. Disruption of the intestinal mucosal barrier was observed in both types of uveitis. However, the mechanism of different intestinal microbiota causing different clinical manifestations needs to be studied in the future.

Increasing researches reveal gut microbiota was associated with the development of tuberculosis (TB). How to prevent or reduce Mycobacterium tuberculosis colonization in the lungs is a key measure to prevent TB. However, the data on gut microbiota preventing Mycobacterium colonization in the lungs were scarce. Here, we established the clindamycin-inducing intestinal microbiome dysbiosis and fecal microbial transplantation models in mice to identify gut microbiota’s effect on Mycobacterium’s colonization in the mouse lungs and explore its potential mechanisms. The results showed that clindamycin treatment altered the diversity and composition of the intestinal bacterial and fungal microbiome, weakened the trans-kingdom network interactions between bacteria and fungi, and induced gut microbiome dysbiosis in the mice. Gut microbiota dysbiosis increases intestinal permeability and enhances the susceptibility of Mycobacterium colonization in the lungs of mice. The potential mechanisms were gut microbiota dysbiosis altered the lung transcriptome and increased Nos2 expression through the ‘gut–lung axis’. Nos2 high expression disrupts the intracellular antimicrobial and anti-inflammatory environment by increasing the concentration of nitric oxide, decreasing the levels of reactive oxygen species and Defb1 in the cells, and promoting Mycobacteria colonization in the lungs of mice. The present study raises a potential strategy for reducing the risks of Mycobacteria infections and transmission by regulating the gut microbiome balance.

Antimony (Sb) is a metalloid, widely presents in the environment and associates with human health. In this study, we aimed to decipher whether Sb exposure is harmful to female reproduction and explore the underlying mechanisms. The ICR mice were exposed to 0, 5, 10, and 20 mg/kg acetate potassium Sb tartrate trihydrate by intraperitoneal injection for 10 days, then mouse oocytes were collected for further analysis. We first found a significant decrease in the proportion of MII-stage oocytes obtained from supernumerary ovulation in the fallopian tubes and early embryo development under Sb treatment. Then a series of tests showed Sb affects oocyte maturation by damaging the cytoskeleton of microtubule and actin. Moreover, the abnormal distribution of cortical granules and their component Ovastacin in oocytes, combined with reduced expression levels of Juno, affected sperm-oocyte binding and led to fertilization failure. Based on the sequencing results and experimental validation, it was demonstrated that Sb exposure impairs mitochondrial distribution and membrane potential, elevated levels of mitochondrial superoxide, finally caused energy supply deficits. Mitochondrial damage in oocytes after Sb exposure results in the excessive oxidative stress and early apoptosis. Taken together, these data suggest that Sb exposure decreases oocyte quality and female fertilization ability by impairing mitochondrial function and redox perturbation.

In the context of a warming climate, glacial debris flows will inevitably increase under the coupled effect of increased temperature and precipitation. However, the extent of future losses is unclear due to the complexity of modelling glacial debris flow processes. This study integrated the degree-day model, the TRIGRS model, and the LS-RAPID model to assess increasing risk in the future period (2071–2100) under the SSP2-4.5 scenario compared to the present. A fatal glacial debris flow in the Tianmo Gully that occurred on September 4, 2007 (hereafter referred to as “the event”) was taken as an example. By the 2090s, compared to the event, the contribution of temperature to the occurrence of glacial debris flows was projected to increase significantly, from 77.05 % to 89.68 % under the SSP2-4.5 scenario. Combining meltwater and precipitation, the study reproduced the propagation of the event and simulated the future extreme debris flow event. Although the section of National Highway 318 (G318) below Tianmo Gully was relocated and reconstructed 150 m away from the historic sedimentary fan, a section of 88.46 m remained at risk of inundation in the future. The maximum height of the debris flow dam in the Parlung Zangbo River could reach up to 34.50 m, doubling the height of the event. Debris removal from the road is estimated to take 1 day, resulting in a projected loss of tourism revenue amounting to RMB 17.82 million. Without relocation, the clearing time would take up to 3 days. The economic benefit of rerouting the section was projected at RMB 13.81 million. The mechanisms of glacial debris flow in Parlung region are similar. Both the concept of model integration and the comparison of the simulation results are of great importance for risk assessments under global warming.

IntroductionWith the goal of patient engagement, an initiative was formulated to equip each patient in the general wards with a tablet whereby they can access their health information and patient education materials and communicate with their healthcare team. This paper presented the methodology of the implementation efforts as well as an evaluation of the preliminary outcomes.MethodsThe process of hospital-wide implementation was shared using the implementation research logic model. The bedside tablets were rolled out hospital-wide in a step-wedge manner over 12 months. Barriers and facilitators to this implementation were discussed together with strategies to optimize the situation. Preliminary outcomes of the implementation were evaluated using the RE-AIM framework.ResultsThe initial adoption rate for the bedside tablet was low. Additional strategies, such as survey audits and provision of feedback, development of education materials for patients, facilitation, and purposefully re-examining the implementation strategies, were used to improve adoption. The trend of adoption increased over the course of 2 years from the start of implementation.DiscussionThe initial lower adoption rates may reflect Singapore's paternalistic healthcare culture. While this implementation was driven by the need to move away from paternalism and toward patient engagement, more time is required for significant cultural change.

Abstract Co3O4 nanoparticles were sandwiched into interlayers between ZIF‐8 and ZIF‐67 to form ZIF‐Co3O4@ZIF precursors. Pyrolysis of ZIF‐Co3O4@ZIF yielded an urchin‐like hierarchically porous carbon (Co@CNT/NC), the thorns of which were carbon nanotubes embedded Co nanoparticles. With large specific surface area and hierarchically porous structure, as‐prepared Co@CNT/NC exhibited excellent bifunctional oxygen electrocatalytic performances. It has good ORR performance with E1/2 of 0.85 V, which exceeds the Pt/C half‐wave potential (E1/2=0.83 V). In addition, Co@CNT/NC has an OER performance close to that of RuO2. To further demonstrate the effect of Co modifying on the properties, the samples were subjected to acid washing treatment. Co‐based nanoparticles were proved to After acid washing, there was obvious loss of Co particles in Co@CNT/NC, resulting in poor oxygen electrocatalysis. So, the pyrolysis products of ZIF‐8‐Co3O4@ZIF‐67 retained large specific surface area and porous structure can be retained, and on the other hand, the carbon tube structure and original polyhedron framework. Besides, existence of Co nanoparticle@carbon nanotube provided more active sites and improved the ORR and OER performances.

BackgroundGliomas are aggressive brain tumors associated with a poor prognosis. Cancer stem cells (CSCs) play a significant role in tumor recurrence and resistance to therapy. This study aimed to identify and characterize glioma stem cells (GSCs), analyze their interactions with various cell types, and develop a prognostic signature.MethodsSingle-cell RNA sequencing data from 44 primary glioma samples were analyzed to identify GSC populations. Spatial transcriptomics and gene regulatory network analyses were performed to investigate GSC localization and transcription factor activity. CellChat analysis was conducted to infer cell-cell communication patterns. A GSC signature (GSCS) was developed using machine learning algorithms applied to bulk RNA sequencing data from multiple cohorts. In vitro and in vivo experiments were conducted to validate the role of TUBA1C, a key gene within the signature.ResultsA distinct GSC population was identified, characterized by high proliferative potential and an enrichment of E2F1, E2F2, E2F7, and BRCA1 regulons. GSCs exhibited spatial proximity to myeloid-derived suppressor cells (MDSCs). CellChat analysis revealed an active MIF signaling pathway between GSCs and MDSCs. A 26-gene GSCS demonstrated superior performance compared to existing prognostic models. Knockdown of TUBA1C significantly inhibited glioma cell migration, and invasion in vitro, and reduced tumor growth in vivo.ConclusionThis study offers a comprehensive characterization of GSCs and their interactions with MDSCs, while presenting a robust GSCS. The findings offer new insights into glioma biology and identify potential therapeutic targets, particularly TUBA1C, aimed at improving patient outcomes.

Background This study was conducted to determine optimal predictive ability of National Institutes of Health Stroke Scale (NIHSS) measurements at baseline, 24 hours, and change from baseline to 24 hours after thrombolysis on functional recovery in patients with acute ischemic stroke who participated in the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study). Methods and Results ENCHANTED was an international, multicenter, 2×2 quasifactorial, prospective, randomized open trial of low‐dose versus standard‐dose intravenous alteplase and intensive versus guideline‐recommended blood pressure lowering in thrombolysis‐eligible patients with acute ischemic stroke. Absolute (baseline minus 24 hours) and percentage (absolute change/baseline × 100) changes in NIHSS scores were calculated. Receiver operating characteristic curve analyses assessed performance of different NIHSS measurements on 90‐day favorable functional recovery (modified Rankin Scale [mRS] score 0–2) and excellent functional recovery (mRS score 0–1). Youden index was used to identify optimal predictor cutoff points. A total of 4410 patients in the ENCHANTED trial were enrolled. The 24‐hour NIHSS score had the highest discriminative ability for predicting favorable 90‐day functional recovery (mRS score 0–2; area under the curve 0.866 versus 0.755, 0.689, 0.764; P

BackgroudScrophularia L., a genus of the Scrophulariaceae, is a group of important medicinal plants used for eliminating heat and detoxifying. East Asia has an abundance of potentially medicinal Scrophularia species, and it serves as a secondary diversity center of the genus. However, the genomic resources available for germplasm identification and pharmaceutical exploration of East Asian Scrophularia are insufficient, hindering its commercial and industrial development. Additionally, the interspecific relationships of most East Asian Scrophularia species remain unclear.MethodsIn this study, we sequenced the leaves of 25 East Asian species of the genus Scrophularia, assembled and annotated the complete chloroplast genomes, and subsequently performed comparative and phylogenetic analyses on these genomes.Results and discussionThe conserved plastome length of these 25 species ranged from 151,582 bp to 153,239 bp, containing a total of 132 coding genes, including 18 duplicated genes and 114 unique genes. Through genome alignment of these 25 species, 38-53 repeated sequences and 7 shared SSRs were identified, along with regions with high nucleotide polymorphism (Pi), which could potentially serve as molecular markers for species identification. The genome structure, gene content, and arrangement showed conservation, while variations were observed in the IR boundary regions and IGS. Phylogenetic inferences based on whole plastomes or on coding sequences (CDS) only yielded congruent results. We categorized the 25 East Asian Scrophularia species into six distinct clades and further explored their interspecies relationships using morphological characteristics, such as flower color, the relative position of stamens and corolla, and plant height. This could lay a genetic basis for future resource development of Scrophularia in East Asia.

The endothelium is crucial in regulating vascular function. Extracellular vesicles (EVs) serve as membranous structures released by cells to facilitate intercellular communication through the delivery of nucleic acids, lipids, and proteins to recipient cells in an paracrine or endocrine manner. Endothelial cell-derived EVs (EndoEVs) have been identified as both biomarkers and significant contributors to the occurrence and progression of cardiovascular disease (CVD). The impact of EndoEVs on CVD is complex and contingent upon the condition of donor cells, the molecular cargo within EVs, and the characteristics of recipient cells. Consequently, elucidating the underlying molecular mechanisms of EndoEVs is crucial for comprehending their contributions to CVD. Moreover, a thorough understanding of the composition and function of EndoEVs is imperative for their potential clinical utility. This review aims provide an up-to-date overview of EndoEVs in the context of physiology and pathophysiology, as well as to discuss their prospective clinical applications.

Residues of herbicides with the extensive applications may impact the soil ecosystem and ultimately threaten agricultural sustainability. However, the effects of long-term herbicide residues on soil multifunctionality and the soil microbial community remain poorly understood. Here, we evaluated relationships between soil multifunctionality and soil microbial communities with residual herbicide concentrations by surveying and analyzing 62 black soil samples collected from an agricultural area in northeastern China. Total residual herbicide concentrations varied from 35 to 568 μg/kg in the soil samples. The response of soil multifunctionality to increasing residual herbicide concentrations exhibited an inverted U-shaped relationship with a peak at approximately 310 μg/kg, with net mineralized organic nitrogen (Nm) and total nitrogen (TN) exhibiting the same trend. Microbial community richness was significantly lower in soil samples with high residual herbicide concentrations (> 310 μg/kg, HG) compared to low residual herbicide concentrations (< 310 μg/kg, LG). In addition, the relative abundances of specific keystone microbial genera differed significantly between LG and HG: norank_f_Acetobacteraceae, norank_f_Caldilineaceae, Candidatus_Alysiosphaera, and Gonytrichum. The relative abundances of these genera were also significantly correlated with soil multifunctionality. Structural equation models (SEMs) further showed that herbicide residues influenced soil multifunctionality by affecting these specific keystone genera. Our study demonstrates that long-term herbicide residues significantly impact the multifunctionality of agricultural black soil, where low concentrations stimulate while high concentrations inhibit, underscoring the need for reasonable application of herbicides to maintain soil ecosystem health.

Abstract Cardiovascular disease (CVD) and its complications are a leading cause of death worldwide. Endothelial dysfunction plays a crucial role in the initiation and progression of CVD, serving as a pivotal factor in the pathogenesis of cardiovascular, metabolic, and other related diseases. The regulation of endothelial dysfunction is influenced by various risk factors and intricate signaling pathways, which vary depending on the specific disease context. Despite numerous research efforts aimed at elucidating the mechanisms underlying endothelial dysfunction, the precise molecular pathways involved remain incompletely understood. This review elucidates recent research findings on the pathophysiological mechanisms involved in endothelial dysfunction, including nitric oxide availability, oxidative stress, and inflammation‐mediated pathways. We also discuss the impact of endothelial dysfunction on various pathological conditions, including atherosclerosis, heart failure, diabetes, hypertension, chronic kidney disease, and neurodegenerative diseases. Furthermore, we summarize the traditional and novel potential biomarkers of endothelial dysfunction as well as pharmacological and nonpharmacological therapeutic strategies for endothelial protection and treatment for CVD and related complications. Consequently, this review is to improve understanding of emerging biomarkers and therapeutic approaches aimed at reducing the risk of developing CVD and associated complications, as well as mitigating endothelial dysfunction.

Realizing efficient immobilization of lithium polysulfides (LiPSs) as well as reversible catalytic conversion between LiPSs and the insoluble Li2S is vital to restrain the shuttle effect, which requires highly reactive catalysts for high-performance Li-S batteries. Here, three-dimensional ordered porous Mo-based metal phosphides (3DOP Mo3P/Mo) with heterogeneous structures were fabricated and utilized as separator-modified coatings for Li-S batteries to catalyze the conversion of LiPSs. The adsorption, catalytic and electrochemical performance of the corresponding cells were compared among 3DOP Mo3P/Mo and 3DOP Mo, by kinetic and electrochemical performance measurements. It was found that the cell with 3DOP Mo3P/Mo modified separator deliver better electrochemical performance, with a high specific capacity of 469.66 mAh g−1 after 500 cycles at a high current density of 1°C. This work provides an idea and a guideline for the design of the separator modification for high-performance Li-S batteries.

In recent decades, more and more studies have been conducted on source appointment of heavy metals, since they can accumulate in the food chain and have a negative impact on the ecological environment and human health. However, almost never before had scholars tried to make a comprehensive and methodical review in this field from the scientometric and bibliometric perspective. The purpose of this review is to offer insights into the research topics and trend evaluation in terms of source appointment of heavy metals over time using the visualization and analysis software, CiteSpace. We retrieved a total of 2,533 articles from the Web of Science Core Collection (WoSCC) dated between 1994 and 2022, and analysed the progress, hotspots, and trends in this field by synthesized networks of cooperation analysis, co-citation analysis, keyword co-occurrence and cluster analysis, and keywords burst analysis. The overall development of the topic can be divided into four periods, and the rapid development began from 2010. Environmental Sciences was the leading subject category, and the journal Science of the Total Environment had the highest number of publications (9.51%), which was most cited as well (2,390 times). China published the most articles in this field, in which Chinese Academy of Sciences was the leading institution. Said Muhammad and Xinwei Lu were the top two most productive authors. According to citation frequency, Hakanson L was the movers and shakers. Keyword co-occurrence and cluster analysis results showed that “the health risk assessment,” “lake sediments”, “trace elements,” “positive matrix factorization,” “air pollution,” “road dust,” and “megacity” are likely to be hotspots. The “particulate matter,” “China,” “sediments” and “road dust” demonstrated the research tendencies of this domain by keyword burst analysis.

With the continuous development of the economy and society, the engineering construction industry has experienced rapid growth, and higher requirements have been put forward for engineering consulting services. Currently, most engineering consulting service enterprises in China only provide relevant consulting services for engineering construction at a certain stage, lacking overall planning and overall control over the entire lifecycle of engineering construction. In order to improve the scientific level of fixed assets investment decision-making and construction management, it is of great value to explore professional engineering consulting services covering the whole process of project construction in the project decision-making stage and implementation stage to achieve the optimization of project quality and economic benefits. The whole process engineering consulting service modes (ECSM) evaluation is a multiple-attribute group decision-making (MAGDM). Recently, the TODIM technique and MACONT technique was created to put forward MAGDM. The interval neutrosophic sets (INSs) are created as a tool for managing fuzzy information during the whole process ECSM evaluation. In this work, the interval neutrosophic number TODIM-MACONT (INN-TODIM-MACONT) technique is created to put forward the MAGDM under INSs. Finally, a numerical analysis for whole process ECSM evaluation is given to validate the proposed technique. The main contributions are outlined: (1) the TODIM and MACONT technique was enhanced under INSs; (2) Information Entropy is created to conduct the weight information under INSs. (3) the INN-TODIM-MACONT technique is created to implement the MAGDM under INSs; (4) a numerical example for whole process ECSM evaluation and some comparative analysis is created to verify the INN-TODIM-MACONT technique.

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.

Abstract Background Recent studies have more focused on gut microbial alteration in tuberculosis (TB) patients. However, no detailed study on gut fungi modification has been reported till now. So, current research explores the characteristics of gut microbiota (bacteria)- and mycobiota (fungi)-dysbiosis in TB patients and also assesses the correlation between the gut microbiome and serum cytokines. It may help to screen the potential diagnostic biomarker for TB. Results The results show that the alpha diversity of the gut microbiome (including bacteria and fungi) decreased and altered the gut microbiome composition of TB patients. The bacterial genera Bacteroides and Prevotella were significantly increased, and Blautia and Bifidobacterium decreased in the TB patients group. The fungi genus Saccharomyces was increased while decreased levels of Aspergillus in TB patients. It indicates that gut microbial equilibrium between bacteria and fungi has been altered in TB patients. The fungal-to-bacterial species ratio was significantly decreased, and the bacterial-fungal trans-kingdom interactions have been reduced in TB patients. A set model including Bacteroides, Blautia, Eubacterium_hallii_group, Apiotrichum, Penicillium, and Saccharomyces may provide a better TB diagnostics option than using single bacterial or fungi sets. Also, gut microbial dysbiosis has a strong correlation with the alteration of IL-17 and IFN-γ. Conclusions Our results demonstrate that TB patients exhibit the gut bacterial and fungal dysbiosis. In the clinics, some gut microbes may be considered as potential biomarkers for auxiliary TB diagnosis.

Abstract Objective To explore the relationship between body mass index (BMI ) and the severity of tic disorders (TDs) in children 6–14 years old. Methods A total of 86 children diagnosed with TDs in a hospital between Jan. 2023 and Sept. 2023 were collected by convenient sampling method, and the general data and TD-specific data were collected and analyzed. Results Univariate analysis showed that patients with different Yale Global Tic Severity Scale (YGTSS) grades had statistically significant differences in age, BMI, residence, snacking pattern, weekly physical exercise frequency, weekly physical exercise time, and proportion of cesarean birth. Multiple linear regression analysis showed that the YGTSS score grades were related to BMI, snacking pattern, and cesarean birth of the patients. Correlation analysis revealed a positive correlation between BMI grades and the YGTSS score grades, with a higher BMI indicating more severe TDs. Predictive value evaluation showed that BMI, snacking pattern, and cesarean birth had predictive values for TD severity, and the highest value was found in the combined prediction. Conclusion BMI, snacking pattern, and cesarean birth are of predictive values for the severity of TDs. In addition, BMI is positively correlated with the severity of TDs, and a higher BMI suggests more severe TDs.

Abstract Iron oxide nanomaterials play important roles in biogeochemical processes. This study investigates the effects of representative natural carbonaceous materials (humic acid [HA] and extracellular polymeric substances [EPS]) and cations on the heteroaggregation and sedimentation of engineered and natural iron oxide nanomaterials with montmorillonite and sulfate- and amine-modified polystyrene (PS) nanoparticles (NPs) (S- and N-PS NPs, respectively) in water, assessing their environmental behavior and differences in colloidal stability parameters. In addition, a novel extended Derjaguin–Landau–Verwey–Overbeek theory (XDLVO) was developed to describe the mechanism of colloidal behavior that concurrently considers gravitational and magnetic attraction forces. In CaCl2 solution and most natural water samples, negatively charged S-PS NPs promoted heteroaggregation with goethite and iron oxide (Fe3O4) NPs more than positively charged N-PS NPs with increased nanoplastic particle concentration. In seawater, the introduction of S- and N-PS NPs increased the maximum net energy (barrier) (ΦMAX) of heteroaggregation and sedimentation with goethite and Fe3O4 NPs, facilitating dispersal and suspension of the system. The X-ray photoelectron spectroscopy (XPS) and molecular dynamics simulation results suggested that Ca2+ forms bridging interactions between Fe3O4 and S-PS NPs to promote aggregation, while competitive adsorption occurs between the N atoms of N-PS NPs and Ca2+ on the surface of Fe3O4 NPs. The study findings will help to improve the understanding of interfacial processes affecting ions at nanomaterial/water interfaces and assessments of the geochemical behavior and ecological risks of nanoplastics.

Abstract N6-methyladenosine (m6A) methylation, a prevalent eukaryotic post-transcriptional modification, is involved in multiple biological functions, including mediating variable splicing, RNA maturation, transcription, and nuclear export, and also is vital for regulating RNA translation, stability, and cytoplasmic degradation. For example, m6A methylation can regulate pre-miRNA expression by affecting both splicing and maturation. Non-coding RNA (ncRNA), which includes microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), does not encode proteins but has powerful impacts on transcription and translation. Conversely, ncRNAs may impact m6A methylation by affecting the expression of m6A regulators, including miRNAs targeting mRNA of m6A regulators, or lncRNAs, and circRNAs, acting as scaffolds to regulate transcription of m6A regulatory factors. Dysregulation of m6A methylation is common in urinary tumors, and the regulatory role of ncRNAs is also important for these malignancies. This article provides a systematic review of the role and mechanisms of action of m6A methylation and ncRNAs in urinary tumors.

Abstract Left ventricular hypertrophy (LVH) is a hypertensive heart disease that significantly escalates the risk of clinical cardiovascular events. Its etiology potentially incorporates various clinical attributes such as gender, age, and renal function. From mechanistic perspective, the remodeling process of LVH can trigger increment in certain biomarkers, notably sST2 and NT‐proBNP. This multicenter, retrospective study aimed to construct an LVH risk assessment model and identify the risk factors. A total of 417 patients with essential hypertension (EH), including 214 males and 203 females aged 31–80 years, were enrolled in this study; of these, 161 (38.6%) were diagnosed with LVH. Based on variables demonstrating significant disparities between the LVH and Non‐LVH groups, three multivariate stepwise logistic regression models were constructed for risk assessment: the “Clinical characteristics” model, the “Biomarkers” model (each based on their respective variables), and the “Clinical characteristics + Biomarkers” model, which amalgamated both sets of variables. The results revealed that the “Clinical characteristics + Biomarkers” model surpassed the baseline models in performance (AUC values of the “Clinical characteristics + Biomarkers” model, the “Biomarkers” model, and the “Clinical characteristics” model were .83, .75, and .74, respectively; P

Population aging is a common problem facing the world, and as a developing country, China has a particularly prominent problem of population aging.With the increasing aging trend of the population, the incidence of critical illness in the elderly continues to rise, which has become an increasingly serious challenge in the medical field.Elderly critically ill patients have certain common characteristics.Understanding these characteristics and objectively evaluating and monitoring them is helpful to determine the changes of disease condition, evaluate the clinical prognosis and provide the basis for formulating more reasonable diagnosis and treatment strategies.In this paper, the characteristics, evaluation and monitoring of critical illness in the elderly are briefly reviewed.

Abstract Background Circular RNA (circRNA) plays an important role in the pathogenesis of many diseases and can be used as a biomarker for diagnosis or disease monitoring. However, reports on circRNA in childhood‐onset systemic lupus erythematosus (cSLE) are limited. Therefore, this study aimed to investigate circEPSTI1 expression in cSLE and evaluate its potential as a biomarker for diagnosing cSLE. Methods This study included 70 children diagnosed with cSLE, 20 diagnosed with juvenile idiopathic arthritis (JIA), 20 diagnosed with juvenile dermatomyositis (JDM), and 50 healthy children at the Rheumatology Department of Beijing Children's Hospital from January 2019 to December 2019. Quantitative polymerase chain reaction was used to determine circEPSTI1 expression in the children. Correlations between circEPSTI1 and clinical features were assessed using Spearman's correlation test. Additionally, we calculated the receiver operating characteristic curve to assess the diagnostic efficacy. Results We found that circEPSTI1 expression was higher in children with cSLE (4.62 ± 3.55) than that in healthy children (1.00 ± 0.45), those with JDM (1.06 ± 0.76), and those with JIA (0.96 ± 0.48). The area of the curve of circEPSTI1 was 0.892 (95% confidence interval [CI]: 0.832–0.952, p

Abstract International initiatives set ambitious targets for ecological restoration, which is considered a promising greenhouse gas mitigation strategy. Here, we conduct a meta-analysis to quantify the impacts of ecological restoration on greenhouse gas emissions using a dataset compiled from 253 articles. Our findings reveal that forest and grassland restoration increase CH4 uptake by 90.0% and 30.8%, respectively, mainly due to changes in soil properties. Conversely, wetland restoration increases CH4 emissions by 544.4%, primarily attributable to elevated water table depth. Forest and grassland restoration have no significant effect on N2O emissions, while wetland restoration reduces N2O emissions by 68.6%. Wetland restoration enhances net CO2 uptake, and the transition from net CO2 sources to net sinks takes approximately 4 years following restoration. The net ecosystem CO2 exchange of the restored forests decreases with restoration age, and the transition from net CO2 sources to net sinks takes about 3-5 years for afforestation and reforestation sites, and 6-13 years for clear-cutting and post-fire sites. Overall, forest, grassland and wetland restoration decrease the global warming potentials by 327.7%, 157.7% and 62.0% compared with their paired control ecosystems, respectively. Our findings suggest that afforestation, reforestation, rewetting drained wetlands, and restoring degraded grasslands through grazing exclusion, reducing grazing intensity, or converting croplands to grasslands can effectively mitigate greenhouse gas emissions.