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Abstract The aim of this study was to investigate whether triglyceride glucose-body mass index (TyG-BMI) plays a mediating role between obstructive sleep apnoea syndrome (OSAS) and hypertension. The study analyzed clinical data from a total of 840 OSAS patients at Wuhan Union Hospital between January 2020 to December 2023. The association between TyG-BMI and hypertension was examined using restricted cubic spline regression and logistic regression. Mediation effect analysis was conducted to explore the relationship between OSAS, TyG-BMI, and the risk of hypertension. Severe OSAS was associated with a significantly increased risk of hypertension compared to mild OSAS (OR = 1.752, p = 0.013). There was a positive linear relationship between TyG-BMI and the risk of hypertension (P-non-linear = 0.535). The risk of hypertension increased with increasing TyG-BMI, with a significantly higher risk of hypertension in the fourth quartile (OR = 3.407, p

Abstract Background Controversy surrounding Family Presence during Resuscitation (FPDR) continues internationally. The attitudes of medical professionals toward FPDR are particularly important for its clinical implementation. Currently, there is a lack of validated tools to evaluate medical professionals’ perceptions of FPDR in China. The study aimed to: (1) Cross-culturally adapt and validate the Family Presence Risk-Benefit Scale (FPR-BS) and the Self-Confidence Scale (FPS-CS) for use in China; and (2) investigate the nurses’ perceptions of FPDR and explore the relationships between the nurses’ perceptual variables and demographic variables. Methods The English version of the FPR-BS and FPS-CS underwent a rigorous process of translation, back-translation, proofreading, and cultural adaptation to create the Chinese versions. In the first stage, a sample of 200 nurses were recruited to evaluate the reliability and validity of the scales. In the second stage, a larger cohort 519 nurses were invited to assess their perceptions of FPDR and the relationships between these perceptual variables and demographic variables. Results Exploratory factorial analysis identified a single dimension for both the FPR-BS and FPS-CS, explaining 43.84% and 48.43% of the variance, respectively. The Scale-level content validity index (S-CVI) of the FPR-BS and the FPS-CS was 0.98 and 0.97, respectively. Reliability assessments yielded Cronbach’s alpha coefficients of 0.933 for the FPR-BS and 0.930 for the FPS-CS. The split-half reliability coefficients were 0.832 for the FPR-BS and 0.835 for the FPS-CS, while the retest reliability coefficients were 0.742 and 0.927, respectively. The average scores obtained were 2.76 (SD = 0.52) for the FPR-BS and 3.43 (SD = 0.58) for the FPS-CS. Statistical analyses revealed that factors such as patient type, family members’ prior experience with resuscitation, and the number of times nurses invited family members during resuscitation significantly influenced perceptions of the benefits and risks associated with FPDR (P

Abstract Background Spermidine (SPD) is an intermediate compound in the polyamine metabolism which takes critical part in a variety of cellular processes. In particular, it has been reported to exert anti-aging effects, suppress the age-related diseases, and extend lifespan across species. However, whether it has the favorable influence on the quality of postovulatory aged oocytes remains elusive. Methods Immunostaining and fluorescence intensity measurement were used to evaluate the effects of postovulatory aging and SPD supplementation on the oocyte fragmentation, spindle/chromosome structure, actin polymerization, dynamics of cortical granules (CGs) and ovastacin, mitochondrial distribution and function, as well as autophagy levels. In addition, in vitro sperm binding assay and in vitro fertilization (IVF) experiment were applied to assess the impacts of postovulatory aging and SPD supplementation on the sperm binding ability and fertilization capacity of oocytes. Results Here, we showed that supplementation of SPD during postovulatory aging could relieve the deterioration of porcine oocytes. Specifically, we found that postovulatory aging impaired the oocyte quality by damaging the morphological integrity of oocytes, maintenance of spindle/chromosome structure, and dynamics of actin cytoskeleton. Postovulatory aging also weakened the sperm binding ability and fertilization capacity of oocytes by compromising the distribution pattern of CGs and their content ovastacin. Notably, supplementation of SPD attenuated these defects in postovulatory aged porcine oocytes via strengthening mitochondrial function, eliminating excessive reactive oxygen species (ROS), inhibiting apoptosis, and enhancing autophagy levels. Conclusion Altogether, our findings demonstrate that SPD supplementation is a feasible approach to ameliorate the quality of postovulatory aged oocytes, which can be potentially applied to the human assisted reproductive technology (ART) and in vitro production of animal embryos.

Abstract Background Immune checkpoint inhibitors (ICIs) are rapidly evolving in the management of bladder cancer (BLCA). Nevertheless, effective biomarkers for predicting immunotherapeutic outcomes in BLCA are still insufficient. Ferroptosis, a form of immunogenic cell death, has been found to enhance patient sensitivity to ICIs. However, the underlying mechanisms of ferroptosis in promoting immunotherapy efficacy in BLCA remain obscure. Methods Our analysis of The Cancer Genome Atlas (TCGA) mRNA data using single sample Gene Set Enrichment Analysis (ssGSEA) revealed two immunologically distinct subtypes. Based on these subtypes and various other public cohorts, we identified Apolipoprotein L6 (APOL6) as a biomarker predicting the efficacy of ICIs and explored its immunological correlation and predictive value for treatment. Furthermore, the role of APOL6 in promoting ferroptosis and its mechanism in regulating this process were experimentally validated. Results The results indicate that APOL6 has significant immunological relevance and is indicative of immunologically hot tumors in BLCA and many other cancers. APOL6, interacting with acyl-coenzyme A synthetase long-chain family member 4 (ACSL4), mediates immunotherapy efficacy by ferroptosis. Additionally, APOL6 is regulated by signal transducer and activator of transcription 1 (STAT1). Conclusions To conclude, our findings indicate APOL6 has potential as a predictive biomarker for immunotherapy treatment success estimation and reveal the STAT1/APOL6/GPX4 axis as a critical regulatory mechanism in BLCA.

ABSTRACT Background Renal ischaemia‒reperfusion injury (IRI) is the primary cause of acute kidney injury (AKI). To date, effective therapies for delaying renal IRI and postponing patient survival remain absent. Ankyrin repeat domain 1 (ANKRD1) has been implicated in some pathophysiologic processes, but its role in renal IRI has not been explored. Methods The mouse model of IRI‐AKI and in vitro model were utilised to investigate the role of ANKRD1. Immunoprecipitation‐mass spectrometry was performed to identify potential ANKRD1‐interacting proteins. Protein‒protein interactions and protein ubiquitination were examined using immunoprecipitation and proximity ligation assay and immunoblotting, respectively. Cell viability, damage and lipid peroxidation were evaluated using biochemical and cellular techniques. Results First, we unveiled that ANKRD1 were significantly elevated in renal IRI models. Global knockdown of ANKRD1 in all cell types of mouse kidney by recombinant adeno‐associated virus (rAAV9)‐mitigated ischaemia/reperfusion‐induced renal damage and failure. Silencing ANKRD1 enhanced cell viability and alleviated cell damage in human renal proximal tubule cells exposed to hypoxia reoxygenation or hydrogen peroxide, while ANKRD1 overexpression had the opposite effect. Second, we discovered that ANKRD1's detrimental function during renal IRI involves promoting lipid peroxidation and ferroptosis by directly binding to and decreasing levels of acyl‐coenzyme A synthetase long‐chain family member 3 (ACSL3), a key protein in lipid metabolism. Furthermore, attenuating ACSL3 in vivo through pharmaceutical approach and in vitro via RNA interference mitigated the anti‐ferroptotic effect of ANKRD1 knockdown. Finally, we showed ANKRD1 facilitated post‐translational degradation of ACSL3 by modulating E3 ligase tripartite motif containing 25 (TRIM25) to catalyse K63‐linked ubiquitination of ACSL3, thereby amplifying lipid peroxidation and ferroptosis, exacerbating renal injury. Conclusions Our study revealed a previously unknown function of ANKRD1 in renal IRI. By driving ACSL3 ubiquitination and degradation, ANKRD1 aggravates ferroptosis and ultimately exacerbates IRI‐AKI, underlining ANKRD1's potential as a therapeutic target for kidney IRI. Key Points/Highlights Ankyrin repeat domain 1 (ANKRD1) is rapidly activated in renal ischaemia‒reperfusion injury (IRI) models in vivo and in vitro. ANKRD1 knockdown mitigates kidney damage and preserves renal function. Ferroptosis contributes to the deteriorating function of ANKRD1 in renal IRI. ANKRD1 promotes acyl‐coenzyme A synthetase long‐chain family member 3 (ACSL3) degradation via the ubiquitin‒proteasome pathway. The E3 ligase tripartite motif containing 25 (TRIM25) is responsible for ANKRD1‐mediated ubiquitination of ACSL3.

To overcome challenges in the traditional melt casting process of zine alloys, such as oxidative burnout, compositional segregation, and grain coarsening, this study carried out hot compression deformation tests on Zn-0.5Mg-0.05Fe alloys prepared by powder metallurgy. The results show that increasing deformation temperature and decreasing strain rate reduce rheological stress. The hot compression deformation process exhibits three phases, as rheological stress increases, work hardening, dynamic softening, and steady-state fluidization are observed, respectively. An intrinsic equation for the hot compression process is derived as = 1.334 × 1010 × [sinh(0.0053σ)]7.62947exp(-109.931691/RT). Processing conditions for Zn-0.5Mg-0.05Fe alloy are determined from a processing map, suggesting that a safe zone of 25°C–130 °C deformation temperatures with 0.13s−1-0.36s−1 strain rates, and 120°C–200 °C deformation temperatures with 0.01s−1-0.6s−1 strain rates. Electron Back-scattering Patterns (EBSD) and Transmission Electron Microscope (TEM) results show both discontinuous dynamic recrystallization (DDRX) and continuous dynamic recrystallization (CDRX) during the hot deformation compression process. DRX reduces deformation resistance, refines the grains, and improves the mechanical properties of the alloys. This study provides theoretical insights and process guidance for preparing degradable zinc alloys with excellent mechanical properties.

Abstract Background Cervical cancer is a human papillomavirus (HPV)-related disease. HPV type 16 (HPV16), which is the predominant cause of cervical cancer, can encode miRNAs (HPV16-miRNAs). However, the role of HPV16-miRNAs in the pathogenesis of cervical cancer remains unclear. Methods Human cervical cancer cell lines SiHa (HPV16-positive) and C33A (HPV-negative), and cervical cancer tissues were collected to investigate the expression levels of two HPV16-miRNAs (HPV16-miR-H1 and HPV16-miR-H6). The overexpression and knockdown of HPV16-miR-H1 and HPV16-miR-H6 were performed using the lentiviral vector system and miRNA inhibitors, respectively. RNA-sequencing (RNA-seq) analysis and H3K27ac chromatin immunoprecipitation and sequencing (CHIP-seq) experiments were utilized to explore the roles of HPV16-miR-H1 and HPV16-miR-H6 facilitated by enhancers. CCK8, EdU, transwell, and wound healing assays were performed to verify the effects of HPV16-miR-H1 and HPV16-miR-H6 on cell proliferation and migration. Results HPV16-miR-H1 and HPV16-miR-H6 were highly expressed in both SiHa cells and tissue samples from HPV16-positive cervical cancer patients. RNA-seq analysis showed that HPV16-miR-H1 and HPV16-miR-H6 induced the upregulation of numerous tumor progression-associated genes. H3K27ac CHIP-seq experiments further revealed that HPV16-miR-H1 and HPV16-miR-H6 modulated the expression of critical genes by regulating their enhancer activity. The functional study demonstrated that HPV16-miR-H1 and HPV16-miR-H6 increased the migratory capacity of SiHa cells. Conclusions Our data shed light on the role of HPV16-encoded miRNAs in cervical cancer, particularly emphasizing their involvement in the miRNA-enhancer-target gene system. This novel regulatory mechanism of HPV16-miRNAs provides new insights and approaches for the development of therapeutic strategies by targeting HPV16-positive cervical cancer.

Introduction: The epithelial immunomodulation and regeneration are intrinsic critical events against inflammatory bowel disease (IBD). MiR-7 is well documented as a promising regulator in the development of various diseases including inflammatory diseases. Objectives: This study aimed to assess the effect of miR-7 in intestinal epithelial cells (IECs) in IBD. Methods: MiR-7def mice were given dextran sulfate sodium (DSS) to induce enteritis model. The infiltration of inflammatory cells was measured by FCM and immunofluorescence assay. 5′deletion assay and EMSA assays were performed to study the regulatory mechanism of miR-7 expression in IECs. The inflammatory signals and the targets of miR-7 were analyzed by RNA-seq and FISH assay. IECs were isolated from miR-7def, miR-7oe and WT mice to identify the immunomodulation and regeneration capacity. IEC-specific miR-7 silencing expression vector was designed and administered by the tail vein into murine DSS-induced enteritis model to evaluate the pathological lesions of IBD. Results: We found miR-7 deficiency improved the pathological lesions of DSS-induced murine enteritis model, accompanied by elevated proliferation and enhanced transduction of NF-κB/AKT/ERK signals in colonic IECs, as well as decreased local infiltration of inflammatory cells. MiR-7 was dominantly upregulated in colonic IECs in colitis. Moreover, the transcription of pre-miR-7a-1, orchestrated by transcription factor C/EBPα, was a main resource of mature miR-7 in IECs. As for the mechanism, EGFR, a miR-7 target gene, was downregulated in colonic IECs in colitis model and Crohn's disease patients. Furthermore, miR-7 also controlled the proliferation and inflammatory-cytokine secretion of IECs in response to inflammatory-signals through EGFR/NF-κB/AKT/ERK pathway. Finally, IEC-specific miR-7 silencing promoted the proliferation and transduction of NF-κB pathway in IECs and alleviated the pathological damage of colitis. Conclusion: Our results present the unknown role of miR-7/EGFR axis in IEC immunomodulation and regeneration in IBD and might provide clues for the application of miRNA-based therapeutic strategies in colonic diseases.

As the global incidence of diabetes rises and diagnoses among younger patients increase, transplant centers worldwide are encountering more organ donors with diabetes. This study examined 80 donors and 160 recipients, including 30 donors with diabetes (DD) and their 60 recipients (DDR). The control group comprised 50 non-diabetic donors (ND) and 100 recipients (NDR). We analyzed clinical, biochemical, and pathological data for both diabetic and control groups, using logistic regression to identify risk factors for delayed graft function (DGF) after kidney transplantation. Results showed that pre-procurement blood urea nitrogen levels were significantly higher in DD [18.20 ± 10.63 vs. 10.86 ± 6.92, p = 0.002] compared to ND. Renal pathological damage in DD was notably more severe, likely contributing to the higher DGF incidence in DDR compared to NDR. Although DDR had poorer renal function during the first three months post-transplant, both groups showed similar renal function thereafter. No significant differences were observed in 1-year or 3-year mortality rates or graft failure rates between DDR and NDR. Notably, according to the Renal Pathology Society (RPS) grading system, kidneys from diabetic donors with a grade > IIb are associated with significantly lower postoperative survival rates. Recipient gender [OR: 5.452 (1.330–22.353), p = 0.013] and pre-transplant PRA positivity [OR: 34.879 (7.698–158.030), p

This study focuses on the problem of ‘teachers’ teaching’ and ‘students’ learning’ in college education courses. It aims to introduce the Deep Learning theory into the teaching of ideological and political theory courses in universities; deepen the theoretical framework of education courses and the associated learning, maintenance, promotion, and support mechanisms; and realise the modernisation of teaching ideas and strategies. A quantitative and qualitative questionnaire survey was used to analyse respondents’ learning experience and effect. Most participants had a significant learning experience and effect under the DL mechanism, a large sense of gain, and a strong cognition and acceptance of IPTCs. We also found positive correlations between whether participants chose political subjects and their learning motivation and interest, between classroom attention and overall sense of gain, and between learning interest and overall sense of gain. The results can inform teaching innovations, optimise teaching strategies, and improve the teaching effect of IPTCs in the digital education era.

ABSTRACTChronic obstructive pulmonary disease (COPD), a condition primarily linked to oxidative stress, poses significant health burdens worldwide. Recent evidence has shed light on the association between the dysbiosis of gut microbiota and COPD, and their metabolites have emerged as potential modulators of disease progression through the intricate gut-lung axis. Here, we demonstrate the efficacy of oral administration of the probiotic Pediococcus pentosaceus SMM914 (SMM914) in delaying the progression of COPD by attenuating pulmonary oxidative stress. Specially, SMM914 induces a notable shift in the gut microbiota toward a community structure characterized by an augmented abundance of probiotics producing short-chain fatty acids and antioxidant metabolisms. Concurrently, SMM914 synthesizes L-tryptophanamide, 5-hydroxy-L-tryptophan, and 3-sulfino-L-alanine, thereby enhancing the tryptophan-melatonin pathway and elevating 6-hydroxymelatonin and hypotaurine in the lung environment. This modulation amplifies the secretion of endogenous anti-inflammatory factors, diminishes macrophage polarization toward the M1 phenotype, and ultimately mitigates the oxidative stress in mice with COPD. The demonstrated efficacy of the probiotic intervention, specifically with SMM914, not only highlights the modulation of intestine microbiota but also emphasizes the consequential impact on the intricate interplay between the gastrointestinal system and respiratory health.

Sweet sorghum can be used to produce a substantial quantity of biofuel due to its high biological yield and high carbohydrate content. In this study, we investigated the dynamic changes in fermentation characteristics, carbohydrate components, and the bacterial community during the ensiling of wilted and unwilted sweet sorghum. The results revealed a rapid fermentation pattern and high-quality fermentation quality in wilted and unwilted sweet sorghum, wherein lactic acid, and acetic acid accumulated and stabilized during the initial 9 days of ensiling, with the pH values less than 4.2, until 60 days of ensiling. We found that the ensiling of sweet sorghum involved the degradation (5% ~ 10%) of neutral detergent fiber (NDF) and hemicellulose and that the degradation of NDF fit a first-order exponential decay model. A shift in dominance from Lactococcus to Lactobacillus occurred before the first 9 days of ensiling, and the abundance of Lactobacillus (r = −0.68, p

Abstract Purpose PAQR7 plays a key role in cell apoptosis as a progesterone membrane receptor. The physiological mechanism of PAQR7 in ovarian function and its anti-apoptotic action in mammals remain poorly understood. Methods We first added 0.2 µM aminoglutethimide (AG), an inhibitor of endogenous progesterone (P4) secretion, and transfected siPAQR7 co-incubated with P4 in human KGN cells to identify granulosa cell apoptosis, respectively. Additionally, we used Paqr7 knockout (PAQR7 KO) mice to assess the role of PAQR7 in the ovary. Results The PAQR7 deficiency significantly increased apoptosis of KGN cells, and this significant difference disappeared following P4 supplementation. The Paqr7 −/− female mice showed a prolonged estrous cycle, reduced follicular growth, increased the number of atresia follicles, and decreased the concentrations of E2 and AMH. The litters, litter sizes, and spontaneous ovulation in the Paqr7−/− mice were significantly decreased compared with the Paqr7+/+ mice. In addition, we also found low expression of PAQR7 in GCs from human follicular fluids of patients diagnosed with decreased ovarian reserve (DOR) and ovaries of mice with a DOR-like phenotype, respectively. Conclusions The present study has identified that PAQR7 is involved in mouse ovarian function and fertilization potential. One possible mechanism is mediating the anti-apoptotic effect of P4 on GC apoptosis via the BCL-2/BAX/CASPASE-3 signaling pathway. The mechanism underlying the effect of PAQR7 on ovarian development and aging remains to be identified.

Abstract Background The aim of this study was to analyse the differences in the phenotypes of missing teeth between a pair of brothers with hypohidrotic ectodermal dysplasia (HED) and to investigate the underlying mechanism by comparing the mutated gene loci between the brothers with whole-exome sequencing. Methods The clinical data of the patients and their mother were collected, and genomic DNA was extracted from peripheral blood samples. By Whole-exome sequencing filtered for a minor allele frequency (MAF) ≤0.05 non-synonymous single-nucleotide variations and insertions/deletions variations in genes previously associated with tooth agenesis, and variations considered as potentially pathogenic were assessed by SIFT, Polyphen-2, CADD and ACMG. Sanger sequencing was performed to detect gene variations. The secondary and tertiary structures of the mutated proteins were predicted by PsiPred 4.0 and AlphaFold 2. Results Both brothers were clinically diagnosed with HED, but the younger brother had more teeth than the elder brother. An EDA variation (c.878 T > G) was identified in both brothers. Additionally, compound heterozygous variations of WNT10A (c.511C > T and c.637G > A) were identified in the elder brother. Digenic variations in EDA (c.878 T > G) and WNT10A (c.511C > T and c.637G > A) in the same patient have not been reported previously. The secondary structure of the variant WNT10A protein showed changes in the number and position of α-helices and β-folds compared to the wild-type protein. The tertiary structure of the WNT10A variant and molecular simulation docking showed that the site and direction where WNT10A binds to FZD5 was changed. Conclusions Compound heterozygous WNT10A missense variations may exacerbate the number of missing teeth in HED caused by EDA variation.

Swine Glasser’s disease, instigated by Haemophilus parasuis (H. parasuis), is a significant bacterial infection that causes substantial economic losses in pig farming operations. The role of mucosal immunity is pivotal in defending against H. parasuis. This study focused on the construction of PLGA microspheres that encapsulate the outer membrane protein OMP16 from H. parasuis (PLGA-OMP16) and evaluated their immunological effectiveness in a mouse model. After being intranasally immunized twice, the PLGA-OMP16 microspheres effectively induced IgAs in saliva and nasal and lung fluids. The PLGA-OMP16 microspheres also significantly increased the number of anti H. parasuis IgGs in serum. Furthermore, the PLGA-OMP16 microspheres triggered elevated levels of IL-2, IL-4, and IFN-γ. The mice vaccinated with PLGA-OMP16 showed a significant reduction in H. parasuis burden in the spleen and lungs following bacterial challenge. These results indicate that intranasal immunization using PLGA microspheres is a promising adjuvant delivery system for vaccines targeting H. parasuis.

The research on developing a purification technology for 2,4-dichlorophenol (2,4-DCP) polluted water with high efficiency and the low energy consumption is crucial for achieving several Sustainable Development Goals (SDGs). In order to achieve these goals, MWCNTs-Pd/Fe nanocomposites were prepared by Fe nanoparticles modified with multi-walled carbon nanotubes (MWCNTs) and palladium (Pd) in the presence of ultrasonic irradiation. The MWCNTs-Pd/Fe nanocomposites were characterized by using Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and X-Ray Diffraction (XRD), and others. Characterization results confirmed that the MWCNTs-Pd/Fe was successfully prepared, with the particle size of 80 nm and the specific surface area of 89.5 m2/g confirmed. We studied the reductive dechlorination of 2,4-Dichlorophenol (2,4-DCP) by MWCNTs-Pd/Fe nanocomposites under different conditions, and the optimized experimental results were found when the Pd loading was 0.4 %, the pH was 3, and the temperature was 30 °C. The phenol yield increased from 76.5 % (without ultrasonic irradiation) to 92.3 % (with ultrasonic irradiation) in 300 min and the 2,4-DCP removal rate reached 98.7 % under the optimal conditions. Therefore, ultrasonic irradiation enhanced the performance of MWCNTs-Pd/Fe nanocomposites for 2,4-DCP removal. We also established the degradation mechanism of chlorophenol by analyzing the intermediates, and proposed the degradation kinetics model. The degradation of 2,4-DCP followed the pseudo-first-order kinetics with the rate constant of 0.05988 min−1. Also, this study demonstrated the potential of using ultrasonic irradiation to improve the properties and recovery of MWCNTs-Pd/Fe nanocomposites, contributing to achievement of the Sustainable Development Goals (SDGs), including SDG-3, SDG-6.

The ultra-short baseline(USBL) positioning system is widely used in the integrated navigation and positioning of underwater vehicles. Knowing the precise position of the transponder is a prerequisite for the application of the USBL system for navigation and positioning. The traditional calibration method of transponder position takes the slant distance as the observational variable. The calibration accuracy is not high, and the robustness is poor. The linearized measurement equation based on the Kalman filter was derived by taking slant distance and bearing angles as observational variables in this paper. In view of the non-Gaussian distribution of noise caused by complex underwater environments, a maximum correntropy filtering method was used to calibrate the position of an underwater acoustic transponder by suppressing outliers. Calibration experiments on the transponder position were carried out under the typical environment of the Yangtze River. Experimental results show that the proposed calibration method has higher calibration accuracy than the traditional method. It has better robustness under outlier interference. After calibration, the positioning accuracy of the USBL system has been improved by 48.3%, 48.2%, and 40.4% in the east-north-up coordinates. It can provide high-precision navigation and positioning functions for underwater vehicles.

Understanding the macro and micro characteristics of precipitation in landfall typhoons is crucial to predicting the path and intensity of tropical cyclones by using numerical models. In this study, we use observations from the Global Precipitation Measurement Mission to analyze the microphysics of convection and stratiform precipitation during the landfall of Typhoon Lekima. The statistical results show that the correlation coefficient of the reflectivity factors of the spaceborne and ground-based radars is 0.77 and that the water content detected by the 18.7 GHz low-frequency vertical channel is positively correlated with the intense-precipitation rate. The storm top height is generally consistent with the location of heavy precipitation. The average near-surface precipitation rate and liquid water content of convective precipitation are higher than those of stratiform precipitation. The average mass-weighted raindrop diameter and particle number concentration of convective (stratiform) precipitation at a distance of 2 km above ground level are 1.52 mm (1.29 mm) and 39.52 (36.44, in decibel scale), respectively. Below the melting layer, there is a significant increase in average particle diameter, indicating that the collision aggregation growth process of raindrops is dominant. These results are potentially helpful in validating and improving microphysics parameterization in numerical models.

Abstract Objective The purpose of this study was to investigate the associations between mobile phone dependency, bedtime procrastination, FoMO, and sleep quality among college students during the COVID-19 outbreak. Specifically, we examined whether bedtime procrastination and FoMO mediate the relationship between mobile phone dependency and sleep quality. Methods A total of 881 college students completed an online survey in May 2022 in Shanghai, China. Mobile Phone Involvement Questionnaire, Bedtime Procrastination Scale, Fear of Missing Out Scale and Pittsburgh Sleep Quality Index were used to assess mobile phone dependency, bedtime procrastination, fear of missing out, and sleep quality, respectively. Multiple linear regression and mediation analysis were conducted. Results The correlation analyses indicated mobile phone dependency was positively associated with fear of missing out, bedtime procrastination, and poor sleep quality among college students. The structural equation modeling analyses revealed that mobile phone dependency had significant indirect effects on sleep quality through bedtime procrastination (indirect effect: 0.030, 95%CI: 0.022–0.041) and fear of missing out (indirect effect: 0.013, 95%CI: 0.003–0.023). Conclusion The findings indicated that bedtime procrastination and fear of missing out are mediators mediating the relationship between mobile phone dependency with sleep quality. Bedtime procrastination and fear of missing out should be considered as potential intervention targets for reducing mobile phone dependency and improving sleep quality in college students.

Abstract In mixed‐phase cumulus clouds, droplets and ice crystals are inhomogeneously distributed, such spatial inhomogeneity can be enhanced by inhomogeneous entrainment as it can strengthen the particle clustering, which may further influence the phase partitioning and interactions among hydrometeors. However, the scale of particle clustering induced by inhomogeneous entrainment is not well known. Utilizing high‐resolution in‐situ aircraft measurements in mixed‐phase cumulus clouds, this study shows due to inhomogeneous entrainment‐mixing, the cluster scales of droplets and ice crystals decrease by approximately 10 m from the cloud center to the edge. Changes in the clustering are correlated with the intensity of entrainment‐mixing. Clouds that are significantly affected by entrainment exhibit stronger enhancement of particle clustering and a more noticeable reduction in cluster scale. The findings from this study improve our understanding of the scale of particle clustering induced by entrainment‐mixing, and are potentially helpful in evaluating models.

The rapidly evolving field of Digital Finance necessitates a new, interdisciplinary approach to doctoral training. This manuscript presents a comprehensive curriculum designed to equip early-stage researchers with the skills and knowledge required to navigate the complexities of modern finance. The curriculum is structured around four pillars: Training through Research and Mandatory Scientific Training, Advanced Scientific Training, Transferable Skills Training, and Training through Secondments. Together, these pillars provide a balanced mix of theoretical knowledge, practical experience, and soft skills. The program also emphasizes international collaboration through conferences and offers online courses for accessibility and sustainability. By addressing key challenges such as data quality, deployment of complex models, trust in AI-supported products, and labor shortages, the program aims to foster innovation and competitiveness in the European Finance industry. The curriculum's alignment with the European Digital Finance Package and integration with leading institutions ensures its relevance and potential for significant impact.

Objectives: To analyse the pathogenic genes in a patient with hypohidrotic ectodermal dysplasia (HED) and explore the relationship between pathogenic genes and the oligodontia phenotype. Methods: Clinical data and peripheral blood were collected from a patient with HED. Pathogenic genes were analysed by whole-exon sequencing (WES) and verified by Singer sequencing. The secondary and tertiary structures of the variant proteins were predicted to analyse their toxicity. Results: The patient exhibited a severe oligodontia phenotype, wherein only two deciduous canines were left in the upper jaw. WES revealed a hemizygous EDA variant c.466C > T p.(Arg156Cys) and a novel heterozygous EVC2 variant c.1772T > C p.(Leu591Ser). Prediction of the secondary and tertiary structures of the EDA variant p.(Arg156Cys) and EVC2 variant p.(Leu591Ser) indicated impaired function of both molecules. Conclusion: The patient demonstrated a more severe oligodontia phenotype when compared with the other patients caused by the EDA variant c.466C > T. Since Evc2 is a positive regulator of the Sonic Hedgehog (Shh) signal pathway, we speculated that the EVC2 variant p.(Leu591Ser) may play a synergistic role in the oligodontia phenotype of HED, thereby exacerbating the oligodontia phenotype. Knowledge of oligodontia caused by multiple gene variants is of great significance for understanding individual differences in oligodontia phenotypes.

ABSTRACTAcute pancreatitis (AP) is a common abdomen clinical emergency. Most APs have mild clinical symptoms and a good prognosis. However, about 20% of patients develop severe acute pancreatitis (SAP), increasing morbidity and mortality. The microbiome’s impact on AP pathophysiology has received increasing attention. Hence, to explore changes in oral microbial composition in acute pancreatitis, we collected clinical information and oral saliva samples from 136 adult participants: 47 healthy controls, 43 acute mild AP (MAP), 29 moderate AP (MSAP), and 17 severe AP (SAP). Using 16S rRNA gene sequencing, 663,175 high-quality sequences were identified. The relative abundance and diversity of oral microorganisms in AP patients increased, with decreased beneficial bacteria such as Streptococcus, Neisseria, and Gemella, and increased Prevotella, Veillonella, Granulicatella, Actinomyces, and Peptostreptococcus in the AP group. Further changes in microbial composition occurred with increasing disease severity, including a decreased abundance of beneficial bacteria such as Neisseria, Haemophilus, and Gemella in MSAP and SAP compared to MAP. Moreover, the Lefse analysis showed that Prevotella, Peptostreptococcus, Actinomyces, and Porphyromonas were better microbial markers for AP. Therefore, oral microbiome changes could distinguish AP from healthy individuals and serve as an early novel predictor of disease severity in AP patients.

Background Acne vulgaris (AV) is a common skin disease. Fire needle is a method of quickly piercing the local skin lesions with red-hot needles for AV. This work aimed to evaluate the efficacy and safety of fire needle combined with chemical peels for AV. Methods Eight databases including PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Internet, Wanfang, Sinomed, and VIP databases were searched to enrolled randomized controlled trials (RCTs) comparing fire needle therapy combined with chemical peels with chemical peels alone. The risk of bias was evaluated by the Cochrane Collaboration’s tool. Statistical analysis was completed by RevMan 5.3 and Stata 14.0. Results Altogether 18 studies including 1213 patients were enrolled. Compared with chemical peels alone, fire needle adjuvant chemical peels therapy improved the total effective rate (RR = 1.37,95% CI [1.26,1.48], p

Abstract The non-structural (NS) NS4A protein in flaviviruses has three predicted transmembrane domains, is critical for virulence and participates in membrane morphogenesis. In Dengue virus (DENV), both hydrophylic N-terminal tail and its first transmembrane domain participate in the formation of oligomers which are important for pathogenicity. However, the relative importance of the N-terminal domain in oligomerization has been under debate. In particular, since in the absence of detergent or lipids, this domain (residues 1–48) in both DENV and Zika virus (ZIKV) NS4A, was found to be disordered. Recently, however, we reported preliminary data that showed that peptide ZIKV NS4A 4–58 adopts a defined secondary structure in aqueous solution and forms oligomers, signaling its importance for full length NS4A oligomerization. Herein we have performed detailed analytical ultracentrifugation experiments to further characterize the oligomerization of this peptide and also a shorter variant (residues 4–44). In both cases, sedimentation velocity produced a single species with concentration-dependent sedimentation coefficient, consistent with a fast equilibrium between at least two species. Combining sedimentation velocity and equilibrium experiments, data is best fitted to a monomer–dimer–trimer equilibrium. Possible models of NS4A oligomers obtained with AlphaFold-2 predict the stabilizing role for residues in this N-terminal domain, such as Arg20, Asn27, Ala44 and Glu50, all at highly conserved positions in flavivirus NS4A proteins. Our results are thus consistent with N-terminal domain interactions acting as one of the driving forces for NS4A homo-oligomerization.

To address path planning for unmanned surface vessels(USVs) in ocean environments affected by physical disturbances, such as ocean currents and obstacles, an energy-optimal algorithm based on improved reinforcement learning is proposed. First, a two-dimensional ocean-current model comprising multiple random vortices and a plane kinematic model of the USV is established. Then, the study determined whether a waypoint is reachable using the relative velocity relationship between the USV and the ocean current. An improved reward function, an action set, and a state set are used to obtain a global optimal path, and the B-spline method is applied to smooth the plan. Finally, numerical simulations are performed in two typical environments. The simulation results show that a path with optimal energy consumption and smoothness can be planned based on the proposed algorithm.

Liquid fermentation is an efficient culture for obtaining polysaccharides from edible mushrooms. In this study, the polysaccharide content and biomass were examined by introducing microorganisms into the Wolfiporia cocos fermentation system. Three edible mushroom co-fermentation systems were established, among which the Wolfiporia cocos-Ganoderma lucidum co-fermentation system significantly increased the mycelial biomass of the system by 57.71% compared to Wolfiporia cocos alone and 91.22% compared to Ganoderma lucidum alone, and the intracellular polysaccharide content was significantly increased. Physiological activities of polysaccharides showed that mycelial polysaccharides in the Wolfiporia cocos-Ganoderma lucidum system had stronger anti-tumor cell value-adding and anti-tumor cell migration activities compared with Wolfiporia cocos and Ganoderma lucidum fermentation alone. The transcriptomic study of Wolfiporia cocos mycelium induced by exogenous substances suggested that the exogenous substances could enhance the intracellular polysaccharide content of Wolfiporia cocos through the upregulation of the expression of α-glycosyltransferase encoded by ALG10 and the downregulation of α-glycosidases encoded by MAN1B in the glycolytic metabolism of Wolfiporia cocos. This study provides a new direction for the transformation of polysaccharides from Wolfiporia cocos and Ganoderma lucidum into functional foods and new product development, and provides an experimental basis.

Premature ovarian insufficiency (POI) is a clinical syndrome of ovarian dysfunction characterized by the abnormal alteration of hormone levels such as FSH and E2. POI causes infertility, severe daily life disturbances, and long-term health risks. However, the underlying mechanism remains largely unknown. In this study, we found that POI is associated with the cellular senescence of ovarian granulosa cells, and TRIM28 mediates oxidative stress (OS)-induced cellular senescence in granulosa cells. Mechanistically, OS causes a decrease in TRIM28 protein levels in KGN cells. Subsequently, it triggers an increase in the levels of autophagy marker proteins ATG5 and LC3B-II, and the downregulation of P62. Abnormal autophagy induces an increase in the levels of cellular senescence markers γ-H2A.X, P16, and P21, provoking cellular senescence in vitro. The overexpression of ovarian TRIM28 through a microinjection of lentivirus attenuated autophagy, cellular senescence, and follicular atresia in the ovaries of POI mice and improved mouse fertility in vivo. Our study highlights the triggers for POI, where the reduction of TRIM28, which is regulated by reactive oxygen species, causes follicular atresia and POI via triggering autophagy and inducing granulosa cell senescence. Shedding light on TRIM28 may represent a potential intervention strategy for POI.

Angle-of-arrival (AOA) measurements are often used in underwater acoustical localization. Different from the traditional AOA model based on azimuth and elevation measurements, the AOA model studied in this paper uses bearing measurements. It is also often used in the Ultra-Short Baseline system (USBL). However, traditional acoustical localization needs additional range information. If the range information is unavailable, the closed-form solution is difficult to obtain only with bearing measurements. Thus, a localization closed-form solution using only bearing measurements is explored in this article. A pseudo-linear measurement model between the source position and the bearing measurements is derived, and considering the nonlinear relationship of the parameters, a weighted least-squares optimization equation based on multiple constraints is established. Different from the traditional two-step least-squares method, the semidefinite programming (SDP) method is designed to obtain the initial solution, and then a bias compensation method is proposed to further minimize localization errors based on the SDP result. Numerical simulations show that the performance of the proposed method can achieve Cramer–Rao lower bound (CRLB) accuracy. The field test also proves that the proposed method can locate the source position without range measurements and obtain the highest positioning accuracy.

BackgroundNew reports suggest that anti-inflammatory drugs are widely used to treat respiratory tract infections caused by SARS-CoV-2. Anti-inflammatory drugs were the most frequently used treatment for the COVID-19-related cytokine storm in China. However, the efficacy of anti-inflammatory drugs has yet to be systematically analyzed, and clinicians are often uncertain which class of anti-inflammatory drug is the most effective in treating patients with respiratory tract infections caused by SARS-CoV-2, especially those with severe disease.MethodsFrom 1 October 2022, relevant studies were searched in the PubMed, Embase, Medline, Cochrane Library, and Web of Science databases. A total of 16,268 publications were retrieved and collated according to inclusion and exclusion criteria, and sensitivity analyses were performed using STATA 14 software. Publication bias was assessed using funnel plots and Egger’s test. Study quality was assessed using the PEDro scale, and the combined advantage ratio was expressed as a 95% confidence interval (CI). In total, 19 randomized controlled trials were included in the study. STATA 14 software was used for all random effects model analyses, and the results are expressed as relative risk ratios (RR) with 95% CI.ResultsQuantitative analyses were performed on 14,514 patients from 19 relevant randomized controlled clinical trials. Pooled estimates (RR = 0.59, 95% CI 0.44–0.80) revealed that the use of anti-inflammatory drugs resulted in a significant reduction in mortality in patients with respiratory tract infection caused by SARS-CoV-2 compared with controls, and methylprednisolone (RR = 0.14, 95% CI 0.03–0.56) was more effective than other anti-inflammatory drugs. Anti-inflammatory drugs were effective in reducing mortality in critically ill patients (RR = 0.67, 95% CI 0.45–0.98) compared with non-critically ill patients (RR = 0.50, 95% CI 0.34–0.76); however, more clinical evidence is needed to confirm these findings.ConclusionThe use of anti-inflammatory drugs in patients with respiratory infections caused by SARS-CoV-2 reduces patient mortality, especially in severe cases. In individual studies, methylprednisolone was more effective than other drugs.

The internal mechanism of the high hydrophobicity of the coal samples from the Pingdingshan mining area was studied through industrial, element, and surface functional group analysis. Laboratory testing and molecular dynamics simulations were employed to study the impact of three types of surfactants on the surface adsorption properties and wettability of highly hydrophobic bituminous coal. The results show that the surface of highly hydrophobic bituminous coal is compact, rich in inorganic minerals, and poorly wettable and that coal molecules are dominated by hydrophobic functional groups of aromatic rings and aliphatic structures. The wetting performance of surfactants as the intermediate carrier to connect coal and water molecules is largely determined by the interaction force between surfactants and coal (Fs-c) and the interaction force between surfactants and water (Fs-w), which effectively improve the wettability of modified coal dust via modifying its surface electrical properties and surface energy. A new type of wetting agent with a dust removal rate of 89% has been developed through discovery of a compound wetting agent solution with optimal wetting and settling performance. This paper provides theoretical and technical support for removing highly hydrophobic bituminous coal dust in underground mining.

Abstract Triggering receptors expressed on myeloid cells 2 (TREM2) is considered a protective factor to protect host from bacterial infection, while how it elicits this role is unclear. In the present study, we demonstrate that deficiency of triggering receptors expressed on myeloid cells 2 (TREM2) significantly enhanced macrophage pyroptosis induced by four common pyogenic bacteria including Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, and Escherichia coli. TREM2 deficiency also decreased bacterial killing ratio of macrophage, while Caspase-1 or GSDMD inhibition promoted macrophage-mediated clearance to these bacteria. Further study demonstrated that the effect of TREM2 on macrophage pyroptosis and bacterial eradication mainly dependents on the activated status of NLRP3 inflammasome. Moreover, as the key downstream of TREM2, β-catenin phosphorylated at Ser675 by TREM2 signal and accumulated in nucleus and cytoplasm. β-catenin mediated the effect of TREM2 on NLRP3 inflammasome and macrophage pyroptosis by reducing NLRP3 expression, and inhibiting inflammasome complex assembly by interacting with ASC. Collectively, TREM2/β-catenin inhibits NLRP3 inflammasome to regulate macrophage pyroptosis, and enhances macrophage-mediated pyogenic bacterial clearance.

This white paper explores the construction of a reliable Environmental, Social, and Governance (ESG) scoring engine, with a focus on the importance of data sources and quality, selection of ESG indicators, weighting and aggregation methodologies, and the necessary validation and benchmarking procedures. The current challenges in ESG scoring and the importance of a robust ESG scoring system are addressed, citing its increasing relevance to stakeholders. Furthermore, different data types, namely self-reported data, third-party data, and alternative data, are critically evaluated for their respective merits and limitations. The paper further elucidates the complexities and implications involved in the choice of ESG indicators, illustrating the trade-offs between standardized and customized approaches. Various weighting methodologies including equal weighting, factor weighting, and multi-criteria decision analysis are dissected. The paper culminates in outlining processes for validating the ESG scoring engine, emphasizing the correlation with financial performance, and conducting robustness and sensitivity analyses. Practical examples through case studies exemplify the implementation of the discussed techniques. The white paper aims to provide insights and guidelines for practitioners, academics, and policy makers in designing and implementing robust ESG scoring systems.

BackgroundBK virus infection after kidney transplantation can negatively impact the prognosis of patients. However, current risk factor analyses primarily focus on BK virus nephropathy, while BK viruria and BK viruria progressing to BK viremia receive less attention. This study aims to analyze the risk factors associated with BK viruria and BK viruria progressing to BK viremia in recipients of donation after cardiac death (DCD), with the goal of facilitating early intervention.MethodsDonor characteristics and clinical data of recipients before and after transplantation were evaluated, and logistic univariate and multivariate analyses were performed to determine the risk factors associated with BK viruria and the progression of BK viruria to BK viremia. Additionally, machine learning techniques were employed to identify the top five features associated with BK viruria evolving into BK viremia.ResultsDuring a median follow-up time of 1,072 days (range 739–1,418), 69 transplant recipients (15.6% incidence rate) developed BK viruria after transplantation, with 49.3% of cases occurring within 6 months post-transplantation. Moreover, 19 patients progressed to BK viremia. Donor age [OR: 1.022 (1.000, 1.045), p = 0.047] and donor procalcitonin (PCT) levels [0.5–10 ng/ml; OR: 0.482 (0.280, 0.828), p = 0.008] were identified as independent risk factors for BK viruria. High BK viruria [OR: 11.641 (1.745, 77.678), p = 0.011], recipient age [OR: 1.106 (1.017, 1.202), p = 0.018], and immunoinduction regimen [ATG; OR: 0.063 (0.006, 0.683), p = 0.023] were independent risk factors for BK viruria progressing to BK viremia. Machine learning analysis confirmed the importance of high BK viruria, recipient age, and immunoinduction regimen (ATG) in predicting the progression of BK viruria to BK viremia.ConclusionThe development and progression of BK virus in DCD kidney transplant recipients is influenced by multiple factors. Early intervention and treatment could potentially extend the lifespan of the transplanted organ.

The research on developing a purification technology for Cr(Ⅵ) polluted water with high efficiency and the low energy consumption is crucial for achieving several Sustainable Development Goals (SDGs). In order to achieve these goals, Fe3O4@SiO2-APTMS nanocomposites were prepared by Fe3O4 nanoparticles modified with silica and 3-aminopropyltrimethoxysilane in the presence of ultrasonic irradiation. The nanocomposites were characterized by TEM, FT-IR, VSM, TGA, BET, XRD, XPS and these analytic results proved that the nanocomposites were successfully prepared. The influential factors of Fe3O4@SiO2-APTMS on Cr(Ⅵ) adsorption have been explored and better experimental conditions have been obtained. The adsorption isotherm conformed to the Freundlich model. Pseudo-second-order kinetic model provided a better correlation for the experimental data compared to other kinetic models. Thermodynamic parameters for adsorption indicated that the adsorption of Cr(Ⅵ) was a spontaneous process. It was speculated that the adsorption mechanism of this adsorbent includes redox, electrostatic adsorption and physical adsorption. In summary, the Fe3O4@SiO2-APTMS nanocomposites were of great significance to human health and the remediation of heavy ion pollution, contributing to achievement of the Sustainable Development Goals (SDGs), including SDG-3, SDG-6.

Background: This study aimed to develop a simple predictive model for early identification of the risk of adverse outcomes in kidney transplant-associated Pneumocystis carinii pneumonia (PCP) patients. Methods: This study encompassed 103 patients diagnosed with PCP, who received treatment at our hospital between 2018 and 2023. Among these participants, 20 were categorized as suffering from severe PCP, and, regrettably, 13 among them succumbed. Through the application of machine learning techniques and multivariate logistic regression analysis, two pivotal variables were discerned and subsequently integrated into a nomogram. The efficacy of the model was assessed via receiver operating characteristic (ROC) curves and calibration curves. Additionally, decision curve analysis (DCA) and a clinical impact curve (CIC) were employed to evaluate the clinical utility of the model. The Kaplan–Meier (KM) survival curves were utilized to ascertain the model’s aptitude for risk stratification. Results: Hematological markers, namely Procalcitonin (PCT) and C-reactive protein (CRP)-to-albumin ratio (CAR), were identified through machine learning and multivariate logistic regression. These variables were subsequently utilized to formulate a predictive model, presented in the form of a nomogram. The ROC curve exhibited commendable predictive accuracy in both internal validation (AUC = 0.861) and external validation (AUC = 0.896). Within a specific threshold probability range, both DCA and CIC demonstrated notable performance. Moreover, the KM survival curve further substantiated the nomogram’s efficacy in risk stratification. Conclusions: Based on hematological parameters, especially CAR and PCT, a simple nomogram was established to stratify prognostic risk in patients with renal transplant-related PCP.

BackgroundSeveral clinical trials of corticosteroids have been carried out in the treatment of septic shock, however, the therapeutic effect of the most widely used hydrocortisone is still controversial, and no studies have directly compared hydrocortisone versus hydrocortisone plus fludrocortisone for patients with septic shock.MethodsBaseline characteristics and treatment regimens of patients with septic shock treated with hydrocortisone from the Medical Information Mart for Intensive Care-IV database were collected. Patients were divided into hydrocortisone treatment groups and hydrocortisone plus fludrocortisone treatment groups. The primary outcome was 90-day mortality, and secondary outcomes included 28-day mortality, in-hospital mortality, length of hospital stay, and length of intensive care unit (ICU) stay. Binomial Logistic regression analysis was performed to identify independent risk factors for mortality. Survival analysis was performed and Kaplan–Meier curves were drawn for patients in different treatment groups. Propensity score matching (PSM) analysis was performed to reduce bias.ResultsSix hundred and fifty three patients were enrolled, of which 583 were treated with hydrocortisone alone, and 70 with hydrocortisone plus fludrocortisone. After PSM, 70 patients were included in each group. The proportion of patients with acute kidney injury (AKI) and the proportion of renal replacement therapy (RRT) treatment in the hydrocortisone plus fludrocortisone group were higher than those in the hydrocortisone alone group, and there was no significant difference in other baseline characteristics. Compared with hydrocortisone alone, hydrocortisone plus fludrocortisone did not reduce the 90-day mortality (after PSM, relative risk/RR = 1.07, 95%CI 0.75–1.51), 28-day mortality (after PSM, RR = 0.82, 95%CI 0.59–1.14) and in-hospital mortality (after PSM, RR = 0.79, 95%CI 0.57–1.11) of the enrolled patients, nor did it affect the length of hospital stay (after PSM, 13.9 days vs. 10.9 days, p = 0.34) and ICU stay (after PSM, 6.0 days vs. 3.7 days, p = 0.14), and the survival analysis showed no statistically significant difference in the corresponding survival time. After PSM, binomial Logistic regression analysis showed that SAPS II score was an independent risk factor for 28-day morality (OR = 1.04, 95%CI 1.02–1.06, p

Background and aimsIn the course of clinical practice, hepatic ischemia/reperfusion (I/R) injury is a prevalent pathophysiological event and is caused by a combination of complex factors that involve multiple signaling pathways such as MAPK and NF-κB. USP29 is a deubiquitinating enzyme important during the development of tumors, neurological diseases, and viral immunity. However, it is unknown how USP29 contributes to hepatic I/R injury.Methods and resultsWe systematically investigated the role of the USP29/TAK1-JNK/p38 signaling pathway in hepatic I/R injury. We first found reduced USP29 expression in both mouse hepatic I/R injury and the primary hepatocyte hypoxia-reoxygenation (H/R) models. We established USP29 full knockout mice (USP29-KO) and hepatocyte-specific USP29 transgenic mice (USP29-HTG), and we found that USP29 knockout significantly exacerbates the inflammatory infiltration and injury processes during hepatic I/R injury, whereas USP29 overexpression alleviates liver injury by decreasing the inflammatory response and inhibiting apoptosis. Mechanistically, RNA sequencing results showed the effects of USP29 on the MAPK pathway, and further studies revealed that USP29 interacts with TAK1 and inhibits its k63-linked polyubiquitination, thereby preventing the activation of TAK1 and its downstream signaling pathways. Consistently, 5z-7-Oxozeaneol, an inhibitor of TAK1, blocked the detrimental effects of USP29 knockout on H/R-induced hepatocyte injury, further confirming that USP29 plays a regulatory role in hepatic I/R injury by targeting TAK1.ConclusionOur findings imply that USP29 is a therapeutic target with promise for the management of hepatic I/R injury via TAK1-JNK/p38 pathway-dependent processes.

Abstract 2D Ruddlesden–Popper perovskites have attracted increasing attention for their outstanding optoelectronic properties and improved stability compared to the 3D counterparts. The unique nature of the crystal growth orientations and the uneven distribution in the 2D perovskites provide a great opportunity to construct a promising lateral photodetector device that has not been fully uncovered. Here, by improving the random orientation to the vertical orientation of the film in the lateral device structure, the dark current is expected to be significantly suppressed in the photodetector. Accompanied by the gradient phase distribution, a p‐type conductive channel at the bottom and another electron collection layer on the top are applied to achieve a high on/off ratio. Overall, the resultant photodetector realizes a low dark current of 10−10 A and exhibits impressive photodetection performance, including a high responsivity of 10.10 A W−1, a notable detectivity of 6.83 × 1012 Jones, and fast response speeds (14 ms/31 ms).

Background: The episode of acute decompensated heart failure (ADHF) is the main cause of hospitalization for heart failure (HF). Sacubitril–valsartan has been proven to be effective in reducing the risks of hospitalization for HF in ADHF. When to initiate sacubitril–valsartan in ADHF to make it the most cost-effective in China remains unclear.Methods: A lifetime Markov model with a 1-month cycle length was developed to evaluate the cost-effectiveness of early or late initiation of sacubitril–valsartan versus enalapril in ADHF. Early initiation of sacubitril–valsartan meant that it was initiated after stabilization from ADHF, and late initiation of sacubitril–valsartan meant that it was initiated after stabilization from HF, which includes no hospitalization for at least three consecutive months. The primary outcome was the incremental cost-effectiveness ratio (ICER), expressed as the ratio of incremental cost to incremental effectiveness. The secondary outcomes were total costs and total effectiveness. Three times of per capita GDP of China in 2021 was set as the willingness-to-pay threshold. One-way sensitivity analysis and probabilistic sensitivity analysis were employed to test the robustness of the results.Results: The early initiation of sacubitril–valsartan treatment resulted in an ICER of 3,662.4 USD per quality-adjusted life year, lower than the willingness-to-pay threshold, and the late initiation of sacubitril–valsartan treatment gained an ICER of 4,444.4 USD/QALY, still lower than the willingness-to-pay threshold. One-way sensitivity analysis showed that our results were robust, and probabilistic sensitivity analysis suggested that early initiation of sacubitril–valsartan in ADHF was cost-effective under a 97.4% circumstance.Conclusion: Early initiation of sacubitril–valsartan after stabilization of ADHF is highly cost-effective compared with the use of enalapril; late initiation of sacubitril–valsartan after stabilization of HF is still cost-effective but not as cost-effective as early initiation of sacubitril–valsartan in ADHF. For Chinese ADHF patients, the time to initiate sacubitril–valsartan should be when the patient is stabilized from ADHF rather than when stabilized from HF, from the perspective of economic evaluation.

In the functioning of the hand–eye collaboration of an apple picking robot, the accuracy of the hand–eye relationship is a key factor affecting the efficiency and accuracy of the robot’s operation. In order to enhance the low accuracy of traditional hand–eye calibration methods, linear and nonlinear solving methods based on mathematical tools such as quaternions are commonly adopted. To solve the loss of accuracy in decoupling during the linearization solution and to reduce the cumulative error that occurs during nonlinear solutions, a hand–eye calibration method, based on the ICP algorithm, is proposed in this paper. The method initializes the ICP matching algorithm with a solution derived from Tsai–Lenz, and substitutes it for iterative computation, thereby ascertaining a precise hand–eye conversion relationship by optimizing the error threshold and iteration count in the ICP matching process. Experimental results demonstrate that the ICP-based hand–eye calibration optimization algorithm not only circumvents the issues pertaining to accuracy loss and significant errors during solving, but also enhances the rotation accuracy by 13.6% and the translation accuracy by 2.47% compared with the work presented by Tsai–Lenz.

Abstract Background Lipid accumulation product (LAP) and cardiometabolic index (CMI) are two novel obesity-related indexes associated with enhancing metabolic disease (MD) risk. Current evidences suggest that the differences in sex hormones and regional fat distribution in both sexes are directly correlated with MD and nonalcoholic fatty liver disease (NAFLD) risk. Hence, NAFLD incidences reflect sex differences. Herein, we examined the accuracy of LAP and CMI in diagnosing NAFLD in both sexes. Methods Overall, 14,407 subjects, who underwent health check-up in the northeastern China, were enrolled in this study, and their corresponding LAP and CMI were calculated. Abdominal ultrasonography was employed for NAFLD diagnosis. Multivariate analyses were analyzed potential correlations between LAP and/or CMI and NAFLD. Odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated. Receiver operating characteristic curve analyses was executed for the exploration of the diagnostic accuracies. Areas under the curves (AUCs) with 95%CIs were calculated. Results NAFLD prevalence increased with elevated quartiles of LAP and CMI in both sexes. In multivariate logistic regression analyses, LAP and CM expressed as continuous variables or quartiles, significantly correlated with NAFLD. The ORs for the top versus bottom quartile of LAP and CMI for NAFLD were 13.183 (95%CI = 8.512–20.417) and 8.662 (95%CI = 6.371–11.778) in women and 7.544 (95%CI = 5.748–9.902) and 5.400 (95%CI = 4.297–6.786) in men. LAP and CMI exhibited larger AUCs, compared to other obesity-related indexes in terms of discriminating NAFLD. The AUCs of LAP and CMI were 0.860 (95%CI = 0.852–0.867) and 0.833 (95%CI = 0.825–0.842) in women and 0.816 (95%CI = 0.806–0.825) and 0.779 (95%CI = 0.769–0.789) in men. Conclusions LAP and CMI are convenient indexes for the screening and quantification of NAFLD within a Chinese adult population. Their associations with NAFLD are substantially greater in women than men.

Abstract Background E2 ubiquitin-conjugating (UBC) enzymes are an integral component of the ubiquitin proteasome system that play an important role in plant development, growth, and external stress responses. Several UBC genes have been identified in various plants. However, no studies exploring the functions of UBC genes in regulating fruit of strawberry have been reported. In the present study, a systematic analysis of the entire UBC family members were conducted in the genome of strawberry (Fragaria ×ananassa) based on bioinformatics method, and the gene functioning in strawberry ripening was explored. Results A total of 191 UBC genes were identified in the genome of cultivated strawberry. These genes were unevenly distributed across the 28 chromosomes from the 4 subgenomes of cultivated strawberry, ranging from 3 to 11 genes per chromosome. Moreover, the expansion of FaUBC genes in strawberry was mainly driven by WGD. All the FaUBC genes were clarified into 13 groups and most of them were included in the group VI. The gene structure analysis showed that the number of exons varied from 1 to 23, and the structure of genes had few differences within the same groups but a distinction in different groups. Identification of the cis-acting elements of the promoter revealed multiple regulatory elements that responded to plant growth and development, phytohormone responsive, and abiotic and biotic stress. Data from functional annotation indicated that FaUBC genes play a role in a variety of biological processes. The RNA-seq data showed that FaUBC genes displayed different expression pattern during the fruit ripening process and clarified into 6 clusters. In particular, cluster 3 exhibiting a sudden expression increase in the turning red stage were speculated to be involved in fruit ripening. Hence, two FaUBC genes (FaUBC76 and FaUBC78) were selected for gene function analysis by transient over-expression method. The results indicated that FaUBC76 has a positive effect on the fruit development and ripening in strawberry by up-regulating accumulation of anthocyanins. Moreover, expression of some maturity-related genes were also significantly increased, further supporting a role for FaUBC76 in the regulation of fruit ripening or softening. On the contrary, the overexpression of FaUBC78 significantly increased the firmness of strawberry fruit, indicating that FaUBC78 had a positive role in inhibiting the decrease of strawberry fruit firmness. Conclusion Our study not only provide comprehensive information on system evolution and function on UBC genes, but also give a new insight into explore the roles of FaUBC genes in the regulation of strawberry ripening.

Background: A goal of 10,000 steps per day is widely advocated, but there is little evidence to support that goal. Our purpose was to examine the dose–response relationships between step count and all-cause mortality and cardiovascular disease risk. Methods: Cochrane Central Register of Controlled Trials, EMBASE, OVID, PubMed, Scopus, and Web of Science databases were systematically searched for studies published before July 9, 2021, that evaluated the association between daily steps and at least 1 outcome. Results: Sixteen publications (12 related to all-cause mortality, 5 related to cardiovascular disease; and 1 article contained 2 outcomes: both all-cause death and cardiovascular events) were eligible for inclusion in the meta-analysis. There was evidence of a nonlinear dose–response relationship between step count and risk of all-cause mortality or cardiovascular disease (p = 0.002 and p = 0.014 for nonlinearity, respectively). When we restricted the analyses to accelerometer-based studies, the third quartile had a 40.36% lower risk of all-cause mortality and a 35.05% lower risk of cardiovascular event than the first quartile (all-cause mortality: Q1 = 4183 steps/day, Q3 = 8959 steps/day; cardiovascular event: Q1 = 3500 steps/day, Q3 = 9500 steps/day; respectively). Conclusion: Our meta-analysis suggests inverse associations between higher step count and risk of premature death and cardiovascular events in middle-aged and older adults, with nonlinear dose–response patterns.

The small regulatory C-TERMINALLY ENCODED PEPTIDE (CEP) peptide family plays crucial roles in plant growth and stress response. However, little is known about this peptide family in Brassica species. Here, we performed a systematic analysis to identify the putative Brassica rapa L. CEP (BrCEP) gene family. In total, 27 BrCEP genes were identified and they were classified into four subgroups based on the CEP motifs similarity. BrCEP genes displayed distinct expression patterns in response to both developmental and several environmental signals, suggesting their broad roles during Brassica rapa development. Furthuremore, the synthetic BrCEP3 peptide accelerated Brassica rapa primary root growth in a hydrogen peroxide (H2O2) and Ca2+ dependent manner. In summary, our work will provide fundamental insights into the physiological function of CEP peptides during Brassica rapa development.

Abstract Negative effects of long‐term overgrazing have been seriously, grasslands temporal stability is an important ecological concern we need to research. Here, we performed a 12‐year‐long (2007–2018) two‐factor controlled experiment on Kobresia humilis meadow on the Tibetan Plateau. The manipulations included three clipping levels (no clipping, NC; moderate clipping, MC; heavy clipping, HC) and two fertilization levels (no fertilization, NF; fertilization, F). Our results revealed that the two clipping manipulations significantly increased the temporal stability of alpine meadow communities, whose significant increase was more pronounced under the MC than HC treatment. Species asynchrony had a significant positive correlation with species abundance along with compound community gradient. Moreover, asynchrony effects, portfolio effects, and facilitation interactions were all present in the communities under the six types of experimental treatment combinations. Additionally, a selection effect was detected in the compound communities, demonstrating characteristics that are common to different mechanisms. There were no significant differences in the effects of these mechanisms on community temporal stability between the NC–NF and MC–NF interactive communities. The portfolio effects predominated when clipping intensity was moderate under both fertilization and nonfertilization conditions. By contrast, in the compound communities, the selection effect predominated. In summary, we conclude that in meadow communities that undergo clipping and fertilization disturbances, facilitation interactions and weak interactions make a greater contribution toward maintaining their temporal stability.

Abstract Background This study was designed to probe into the effect of cisplatin combined with capecitabine on nasopharyngeal carcinoma (NPC). Methods A total of 136 NPC patients treated for the first time in our hospital from January 2016 to March 2017 were collected and divided into two groups: A and B. Among them, 66 in group A were treated with cisplatin intravenous drip, while 70 in group B were treated with capecitabine on the basis of group A. The efficacy, toxic and side effects, and quality of life of the two groups were observed. Results The short-term efficacy of group B was better than that of group A (p

Objectives This study is conducted to examine whether overall workplace violence (WPV) and its five types are associated with high burn-out among healthcare workers in China.Design A WeChat-based cross-sectional survey. Snowball sampling was used in this study.Participants Front-line healthcare workers (N=3706) from 149 cities across 23 provinces in China responded to the survey, and 22 questionnaires were excluded because of incomplete data.Primary and secondary outcome measures (1) The Chinese Maslach Burnout Inventory-General Survey was used to measure high burn-out. (2) WPV was assessed using the Chinese version of the Workplace Violence Scale. (3) An anonymous self-designed web-based questionnaire consisting of demographic, behavioural and occupational information was used to identify covariates.Results A total of 3684 front-line healthcare workers (934 physicians and 2750 nurses) were included. Of all participants, 13.3% (491/3193) experienced high burn-out. Adjusted logistic regression revealed that experience of WPV in the past year was associated with high burn-out (OR 2.10, 95% CI 1.69 to 2.62). Healthcare workers who had suffered emotional abuse, threat or verbal sexual harassment were more vulnerable to high burn-out.Conclusion This study finds that healthcare workers with WPV, especially emotional abuse, threat and verbal sexual harassment, are more likely to experience burn-out. These types of WPV should be considered in interventions to reduce and prevent burn-out for healthcare workers.

Advances in synthetic biology and the clinical application of bacteriotherapy enable the use of genetically engineered bacteria (GEB) to combat various diseases. GEB act as a small ‘machine factory’ in the intestine or other tissues to continuously produce heterologous proteins or molecular compounds and, thus, diagnose or cure disease or work as an adjuvant reagent for disease treatment by regulating the immune system. Although the achievements of GEBs in the treatment or adjuvant therapy of diseases are promising, the practical implementation of this new therapeutic modality remains a grand challenge, especially at the initial stage. In this review, we introduce the development of GEBs and their advantages in disease management, summarize the latest research advances in microbial genetic techniques, and discuss their administration routes, performance indicators and the limitations of GEBs used as platforms for disease management. We also present several examples of GEB applications in the treatment of cancers and metabolic diseases and further highlight their great potential for clinical application in the near future.

Background: The objective of this study was to formulate and validate a prognostic model for postoperative severe Pneumocystis carinii pneumonia (SPCP) in kidney transplant recipients utilizing machine learning algorithms, and to compare the performance of various models. Methods: Clinical manifestations and laboratory test results upon admission were gathered as variables for 88 patients who experienced PCP following kidney transplantation. The most discriminative variables were identified, and subsequently, Support Vector Machine (SVM), Logistic Regression (LR), Random Forest (RF), K-Nearest Neighbor (KNN), Light Gradient Boosting Machine (LGBM), and eXtreme Gradient Boosting (XGB) models were constructed. Finally, the models’ predictive capabilities were assessed through ROC curves, sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and F1-scores. The Shapley additive explanations (SHAP) algorithm was employed to elucidate the contributions of the most effective model’s variables. Results: Through lasso regression, five features—hemoglobin (Hb), Procalcitonin (PCT), C-reactive protein (CRP), progressive dyspnea, and Albumin (ALB)—were identified, and six machine learning models were developed using these variables after evaluating their correlation and multicollinearity. In the validation cohort, the RF model demonstrated the highest AUC (0.920 (0.810–1.000), F1-Score (0.8), accuracy (0.885), sensitivity (0.818), PPV (0.667), and NPV (0.913) among the six models, while the XGB and KNN models exhibited the highest specificity (0.909) among the six models. Notably, CRP exerted a significant influence on the models, as revealed by SHAP and feature importance rankings. Conclusions: Machine learning algorithms offer a viable approach for constructing prognostic models to predict the development of severe disease following PCP in kidney transplant recipients, with potential practical applications.