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Abstract Background Cisplatin (DDP) is an efficacious and widely applied chemotherapeutic drug for cervical cancer patients who are diagnosed as metastatic and inoperable, or desiring fertility preservation. Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) selectively triggers cancer cells apoptosis by binding to cognate death receptors (DR4 and DR5). Mesenchymal stem cells-derived exosomes (MSCs-Exo) have been regarded as ideal drug carriers on account of their nanoscale, low toxicity, low immunogenicity, high stability, biodegradability, and abundant sources. Methods Human chorion-derived mesenchymal stem cells (hCD-MSCs) were isolated by adherent culture method. TRAIL-engineered hCD-MSCs (hCD-MSCsTRAIL) were constructed by lentivirus transfection, and its secreted Exo (hCD-MSCs-ExoTRAIL) were acquired by differential centrifugation and confirmed to overexpress TRAIL by western blotting. Next, nanoscale drug delivery systems (DDP & hCD-MSCs-ExoTRAIL) were fabricated by loading DDP into hCD-MSCs-ExoTRAIL via electroporation. The CCK-8 assay and flow cytometry were conducted to explore the proliferation and apoptosis of cervical cancer cells (SiHa and HeLa), respectively. Cervical cancer-bearing nude mice were constructed to examine the antitumor activity and biosafety of DDP & hCD-MSCs-ExoTRAIL in vivo. Results Compared with hCD-MSCs-Exo, hCD-MSCs-ExoTRAIL weakened proliferation and enhanced apoptosis of cervical cancer cells. DDP & hCD-MSCs-ExoTRAIL were proved to retard cervical cancer cell proliferation and propel cell apoptosis more effectively than DDP or hCD-MSCs-ExoTRAIL alone in vitro. In cervical cancer-bearing mice, DDP & hCD-MSCs-ExoTRAIL evidently hampered tumor growth, and its role in inducing apoptosis was mechanistically associated with JNK/p-c-Jun activation and survivin suppression. Moreover, DDP & hCD-MSCs-ExoTRAIL showed favorable biosafety in vivo. Conclusions DDP & hCD-MSCs-ExoTRAIL nanoparticles exhibited great promise for cervical cancer treatment as an Exo-based chemo-gene combinational therapy in clinical practice. Graphical abstract

Abstract Clubroot disease caused by the infection of Plasmodiophora brassicae is widespread in China, and significantly reduces the yield of Chinese cabbage (Brassica rapa L. ssp. pekinensis). However, the resistance mechanism of Chinese cabbage against clubroot disease is still unclear. It is important to exploit the key genes that response to early infection of P. brassicae. In this study, it was found that zoospores were firstly invaded hair roots on the 8th day after inoculating with 1 × 107 spores/mL P. brassicae. Transcriptome analysis found that the early interaction between Chinese cabbage and P. brassicae caused the significant expression change of some defense genes, such as NBS-LRRs and pathogenesis-related genes, etc. The above results were verified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Otherwise, peroxidase (POD) salicylic acid (SA) and jasmonic acid (JA) were also found to be important signal molecules in the resistance to clubroot disease in Chinese cabbage. This study provides important clues for understanding the resistance mechanism of Chinese cabbage against clubroot disease.

Background: The use of high-flow nasal cannula (HFNC) oxygen therapy is gaining popularity for the treatment of acute hypoxic respiratory failure. However, limited evidence exists regarding the effectiveness of HFNC for acute respiratory distress syndrome (ARDS) in patients with acute pancreatitis (AP). Methods: This retrospective analysis focused on AP patients with mild-moderate ARDS, who were treated with either HFNC or noninvasive ventilation (NIV) in the emergency medicine department, from January 2020 to December 2022. The primary endpoint was treatment failure, defined as either invasive ventilation or a switch to any other study treatment (NIV for patients in the NFNC group and vice versa). Results: A total of 146 patients with AP (68 in the HFNC group and 78 in the NIV group) were included in this study. The treatment failure rate in the HFNC group was 17.6% and 19.2% in the NIV group – a risk difference of -1.6% (95% CI, -11.3 to 14.0%; P = 0.806). The most common causes of failure in the HFNC group were aggravation of respiratory distress and hypoxemia. However, in the NIV group, the most common reasons for failure were treatment intolerance and exacerbation of respiratory distress. Treatment intolerance in the HFNC group was significantly lower than that in the NIV group (16.7% vs 60.0%, 95% CI -66.8 to -6.2; P = 0.023). Multivariate logistic regression analysis showed that body mass index (≥28), acute physiology and chronic health evaluation II score (≥15), partial arterial oxygen tension/fraction of inspired oxygen (≤200), and respiratory rate (≥32/min) at 1 hour were independent predictors of HFNC failure. Conclusion: In AP patients with mild-moderate ARDS, the usage of HFNC did not lead to a higher rate of treatment failure when compared to NIV. HFNC is an ideal choice of respiratory support for patients with NIV intolerance, but clinical application should pay attention to the influencing factors of its treatment failure.

Abstract DNA methylation (DNAm) has been implicated in acute coronary syndrome (ACS), but the causality remains unclear in cross-sectional studies. Here, we conduct a prospective epigenome-wide association study of incident ACS in two Chinese cohorts (discovery: 751 nested case-control pairs; replication: 476 nested case-control pairs). We identified and validated 26 differentially methylated positions (DMPs, false discovery rate [FDR]

Abstract Purpose There is a lack of adequate models specifically designed for elderly patients with severe acute pancreatitis (SAP) to predict the risk of death. This study aimed to develop a nomogram for predicting the overall survival of SAP in elderly patients. Methods Elderly patients diagnosed with SAP between January 1, 2017 and December 31, 2022 were included in the study. Risk factors were identified through least absolute shrinkage and selection operator regression analysis. Subsequently, a novel nomogram model was developed using multivariable logistic regression analysis. The predictive performance of the nomogram was evaluated using metrics such as the receiver operating characteristic curve, calibration curve, and decision curve analysis (DCA). Results A total of 326 patients were included in the analysis, with 260 in the survival group and 66 in the deceased group. Multivariate logistic regression indicated that age, respiratory rate, arterial pH, total bilirubin, and calcium were independent prognostic factors for the survival of SAP patients. The nomogram demonstrated a performance comparable to sequential organ failure assessment (P = 0.065). Additionally, the calibration curve showed satisfactory predictive accuracy, and the DCA highlighted the clinical application value of the nomogram. Conclusion We have identified key demographic and laboratory parameters that are associated with the survival of elderly patients with SAP. These parameters have been utilized to create a precise and user-friendly nomogram, which could be an effective and valuable clinical tool for clinicians.

Abstract The senescence of nucleus pulposus (NP) cells (NPCs), which is induced by the anomalous accumulation of reactive oxygen species (ROS), is a major cause of intervertebral disc degeneration (IVDD). In this research, glutathione-doped carbon dots (GSH-CDs), which are novel carbon dot antioxidant nanozymes, were successfully constructed to remove large amounts of ROS for the maintenance of NP tissue at the physical redox level. After significantly scavenging endogenous ROS via exerting antioxidant activities, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and total antioxidant capacity, GSH-CDs with good biocompatibility have been demonstrated to effectively improve mitochondrial dysfunction and rescue NPCs from senescence, catabolism, and inflammatory factors in vivo and in vitro. In vivo imaging data and histomorphological indicators, such as the disc height index (DHI) and Pfirrmann grade, demonstrated prominent improvements in the progression of IVDD after the topical application of GSH-CDs. In summary, this study investigated the GSH-CDs nanozyme, which possesses excellent potential to inhibit the senescence of NPCs with mitochondrial lesions induced by the excessive accumulation of ROS and improve the progression of IVDD, providing potential therapeutic options for clinical treatment. Graphical Abstract

Abstract Background Extensive evidence indicates that both lifestyle factors and air pollution are strongly associated with all-cause mortality. However, little studies in this field have integrated these two factors in order to examine their relationship with mortality and explore potential interactions. Methods A cohort of 271,075 participants from the UK Biobank underwent analysis. Lifestyles in terms of five modifiable factors, namely smoking, alcohol consumption, physical activity, diet, and sleep quality, were classified as unhealthy (0–1 score), general (2–3 score), and healthy (4–5 score). Air pollution, including particle matter with a diameter ≤ 2.5 μm (PM2.5), particulate matter with a diameter ≤ 10 μm (PM10), particulate matter with a diameter 2.5–10 μm (PM2.5−10), nitrogen dioxide (NO2), and nitrogen oxides (NOx), was divided into three levels (high, moderate, and low) using Latent Profile Analysis (LPA). Cox proportional hazard regression analysis was performed to examine the links between lifestyle, air pollution, and all-cause mortality before and after adjustment for potential confounders. Restricted cubic spline curves featuring three knots were incorporated to determine nonlinear relationships. The robustness of the findings was assessed via subgroup and sensitivity analyses. Results With unhealthy lifestyles have a significantly enhanced risk of death compared to people with general lifestyles (HR = 1.315, 95% CI, 1.277–1.355), while people with healthy lifestyles have a significantly lower risk of death (HR = 0.821, 95% CI, 0.785–0.858). Notably, the difference in risk between moderate air pollution and mortality risk remained insignificant (HR = 0.993, 95% CI, 0.945–1.044). High air pollution, on the other hand, was independently linked to increased mortality risk as compared to low air pollution (HR = 1.162, 95% CI, 1.124–1.201). The relationship between NOx, PM10, and PM2.5−10 and all-cause mortality was found to be nonlinear (p for nonlinearity

The gut-liver axis in ruminants can explain nutrient regulation, the gut-liver cycle, and immune function in ruminant biology through the gut microbe-gut metabolite-liver metabolite relationship. to investigate the effects of herbal feed additives on the gut-liver axis of Hu sheep. In this study, a broadly targeted UPLC-MS/MS metabolomics approach and 16s sequencing of gut microorganisms were used to detect, identify and quantify changes in ileal microorganisms, liver metabolites and ileal metabolites following the addition of Chinese herbal preparations. The addition of a 0.5% herbal feed additive increased ileal IgA, IgG and complement C3 levels. The addition of Chinese herbal preparations can increase the abundance of Firmicutes, Actinobacteriota, Bacteroidota, at the portal level of the ileum, increase the metabolism of organic matter and its derivatives, bile acids, amino acids and their metabolites, coenzymes, and vitamins in the liver and ileum, enhance nutrient absorption and waste metabolism, accelerate liver metabolism, promote gut-liver circulation, and improve ileal and liver immunity. This study provides a theoretical basis for understanding the effects of herbal feed additives on the gut-liver axis in ruminants.

BackgroundCupping therapy has been indicated effective in reducing muscle fatigue after 24 h based on the spectral analyses of surface electromyography (sEMG). However, there is no sufficient evidence showing changes of sEMG nonlinear indexes at more time points after cupping therapy. Furthermore, it is unclear whether the intervention timings of cupping therapy affect the recovery from muscle fatigue. The purpose of this study was to use the sEMG nonlinear analysis to assess the difference of time response of cupping therapy between different intervention timings after muscle fatigue.Materials and methodsThis randomized controlled trial recruited 26 healthy volunteers. Cupping therapy (−300 mmHg pressure for 5 min by the 45 mm-diameter cup) was applied before (i.e., pre-condition) or after (i.e., post-condition) muscle fatigue induced by performing repeated biceps curls at 75% of the 10 repetitions of maximum (RM) on the non-dominant upper extremity. Subjects were randomly allocated to the pre-condition group or the post-condition group. The sEMG signals during the maximal voluntary isometric contractions (MVC) of the biceps were recorded at four time points (i.e., baseline; post 1: immediate after cupping-fatigue/fatigue-cupping interventions; post 2: 3 h after cupping-fatigue/fatigue-cupping interventions; post 3: 6 h after cupping-fatigue/fatigue-cupping interventions). Two nonlinear sEMG indexes (sample entropy, SampEn; and percent determinism based on recurrence quantification analysis, %DET) were used to evaluate the recovery from exercise-introduced muscle fatigue. The Friedman test followed by the Nemenyi test and the Mann-Whitney U test were applied in statistics.ResultsThe SampEn and %DET change rate did not show any significant differences at four time points in the pre-condition group. However, there were significant delayed effects instead of immediate effects on improving muscle fatigue in the post-condition group (SampEn change rate: baseline 0.0000 ± 0.0000 vs. post 2 0.1105 ± 0.2253, p < 0.05; baseline 0.0000 ± 0.0000 vs. post 3 0.0627 ± 0.4665, p < 0.05; post 1–0.0321 ± 0.2668 vs. post 3 0.0627 ± 0.4665, p < 0.05; and %DET change rate: baseline 0.0000 ± 0.0000 vs. post 2–0.1240 ± 0.1357, p < 0.01; baseline 0.0000 ± 0.0000 vs. post 3 0.0704 ± 0.6495, p < 0.05; post 1 0.0700 ± 0.3819 vs. post 3 0.0704 ± 0.6495, p < 0.05). Moreover, the SampEn change rate of the post-condition group (0.1105 ± 0.2253) was significantly higher than that of the pre-condition group (0.0006 ± 0.0634, p < 0.05) at the post 2 time point. No more significant between-groups difference was found in this study.ConclusionThis is the first study demonstrating that both the pre-condition and post-condition of cupping therapy are useful for reducing muscle fatigue. The post-condition cupping therapy can e ffectively alleviate exercise-induced muscle fatigue and there is a significant delayed effect, especially 3 h after the interventions. Although the pre-condition cupping therapy can not significantly enhance muscle manifestations, it can recover muscles into a non-fatigued state.

Drought is a pressing environmental issue with profound socio-economic impacts. Frequent drought disasters around the world have brought huge impacts and challenges, severely constraining the sustainable development of cities. How to improve drought resilience to guarantee regional sustainable development has become a hot research topic. In this study, we developed a comprehensive framework to assess drought resilience in China, analyzing its spatiotemporal evolution characteristics, uncovering the underlying impact mechanisms, and projecting future resilience trends across different regions of the country. Over the past 12 years, the average drought resilience level in China has risen by 14.4 %. Central and eastern coastal provinces demonstrated higher resilience levels, contrasting with the western inland regions' lower resilience. A significant positive spatial correlation was observed in China's drought resilience, with high-value clusters emerging in the southeastern and northeastern regions. Among the sub-resilience dimensions, social resilience had the most substantial impact. The prediction model suggests that the drought resilience level will increase modestly by 6.2 % across provinces, maintaining the spatial pattern of higher resilience in the eastern coastal areas and the southern and northern extremities, with lower resilience in the central region. Our findings underscore the significance of understanding regional variations in drought resilience to inform targeted and efficient policy interventions.

Output power is an important performance metric related to static or quasi-static wireless power transfer (WPT). As an important component of WPT, the electrical parameters of a magnetic coupling mechanism (MCM) are directly related to its output characteristics. Notably, an optimal WPT design is largely based on MCMs using the same primary and secondary coils. However, in some scenarios involving limited space, the physical structure and electrical parameters of the coils cannot be kept completely consistent. Based on the influence of physical parameters on coupling performance and system characteristics, an optimal design method for MCMs using different primary and secondary coils to ensure maximum output power is proposed. The best receiving coil within a limited space that achieves maximum power at a specific location was selected. Experiments were conducted, with the corresponding results verifying the correctness of theoretical and simulation analyses, as well as the effectiveness of the proposed method.

Abstract Background Cold hardiness is fundamental for amphibians to survive during the extremely cold winter on the Qinghai-Tibet plateau. Exploring the gene regulation mechanism of freezing-tolerant Rana kukunoris could help us to understand how the frogs survive in winter. Results Transcriptome of liver and muscle of R. kukunoris collected in hibernation and spring were assisted by single molecule real-time (SMRT) sequencing technology. A total of 10,062 unigenes of R. kukunoris were obtained, and 9,924 coding sequences (CDS) were successfully annotated. Our examination of the mRNA response to whole body freezing and recover in the frogs revealed key genes concerning underlying antifreeze proteins and cryoprotectants (glucose and urea). Functional pathway analyses revealed differential regulated pathways of ribosome, energy supply, and protein metabolism which displayed a freeze-induced response and damage recover. Genes related to energy supply in the muscle of winter frogs were up-regulated compared with the muscle of spring frogs. The liver of hibernating frogs maintained modest levels of protein synthesis in the winter. In contrast, the liver underwent intensive high levels of protein synthesis and lipid catabolism to produce substantial quantity of fresh proteins and energy in spring. Differences between hibernation and spring were smaller than that between tissues, yet the physiological traits of hibernation were nevertheless passed down to active state in spring. Conclusions Based on our comparative transcriptomic analyses, we revealed the likely adaptive mechanisms of R. kukunoris. Ultimately, our study expands genetic resources for the freezing-tolerant frogs.

Since 2021, EAST tokamak has been operated with full tungsten divertors. Tungsten accumulation has been frequently observed in NBI-heated H-mode discharges, resulting in the degradation of plasma confinement performance. Control of tungsten impurity is thus critical for the maintenance of high-confinement plasmas. In this work the impact of the n = 1 resonant magnetic perturbation (RMP) on the behavior of intrinsic low- and high-Z impurities in EAST H-mode discharges are experimentally studied, utilizing high-performance extreme ultraviolet spectroscopic diagnostics. In the dedicated discharge, ELM mitigation, ELM suppression, H-L back transition, RMP penetration occurs in succession with increasing RMP current (IRMP). When IRMP is below the threshold for H-L back transition, IRMP_H-L = 2.29 kA, increasing influx of C2+ and C3+ ions and decreasing influx of C4+ and C5+ ions are observed simutaneously with enhancement of the RMP field. This opposite time behavior in the influx of C4+ and C3+ ion is then observed to be magnified during the RMP penetration phase. It indicates a impurity screening layer formed between the locations where C4+ and C3+ ions distribute during RMP application based on our previous analysis (W.M. Zhang et al 2024 Nucl. Fusion 64 086004). A large step of increase in C4+ influx after H-L back transition indicates C4+ ion mainly located at bottom of pedestal. A higher RMP coil currents threshold capable of impurity screening is found for high-Z impurity ions of Cu25+, Mo30+, W42+, i. e. 0.53–0.75 kA, than that for C4+ and C5+, i. e. 0.33 kA. Meanwhile, it is found that comparing to C4+ and C5+ ions the decontamination effect by this impurity screening layer is more efficient for these high-Z impurity ions in plasma core region, e.g. up to 70 % reduction in the impurity density, leading to a significant reduction of radiation power. Furthermore, the continuous reduction of core high-Z impurities level both in ELM mitigation and suppression phase proved that this impurity decontamination effect by RMP field is dominant over the impact of ELM activity to core high-Z impurities transport since tungsten is frequently observed to accumulate during original ELM-free phase. Experimental results from this work would contribute to further understanding of the underlying mechanism how the RMP field impacts the impurity transport.

During the metamorphosis of anuran amphibians, the tail resorption process is a necessary and crucial change. One subject that has received relatively little or no attention is the expression patterns of proteins and metabolites in the different tail portions during metamorphosis, especially in highland amphibians. The mechanisms of tail resorption in three portions (the tip, middle and root) of the tail were investigated in N. pleskei G43 tadpole based on two omics (proteomic and metabolomic). Integrin αVβ3 was found to be high expressed in the distal portion of the tail, which could improve the sensitiveness to thyroid hormones in the distal portion of the tail. Muscle regression displayed a spatial pattern with stronger regression in distal and weaker one in proximal portion. Probably, this stronger regression was mainly performed by the proteases of proteasome from the active translation by ribosomes. The suicide model and murder model coexisted in the tail resorption. Meanwhile, fatty acids, amino acids, pyrimidine, and purine which derived from the breakdown of tissues can be used as building blocks or energy source for successful metamorphosis. Our data improved a better comprehension of the tail resorption mechanisms underlying the metamorphism of N. pleskei tadpole through identifying important participating proteins and metabolites.

Summary: Ovarian cancer is a highly lethal gynecological malignancy, emphasizing the need for effective treatment strategies. This study investigated the synergistic effects of quercetin and paclitaxel on ovarian cancer. Using SKOV3 and A2780 cell lines, we found that the combined treatment significantly enhanced cell apoptosis and inhibited invasion and migration compared to individual treatments. Then, we identified 32 common targets between quercetin/paclitaxel and ovarian cancer, with 29 genes showing differential expression between normal ovarian tissue and ovarian tumor tissue. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that quercetin and paclitaxel modulated cancer-related pathways in ovarian cancer treatment. Mechanistic analysis further discovered that the synergistic effect was mediated by downregulating ERBB2 and BIRC5 and upregulating CASP3 expression. This study provides strong evidence that quercetin enhances the effectiveness of paclitaxel in treating ovarian cancer.

ABSTRACT Osseointegrated dental implants replace missing teeth and create an artificial surface for biofilms of complex microbial communities to grow. These biofilms on implants and dental surfaces can trigger infection and inflammation in the surrounding tissue. This study investigated the microbial characteristics of peri-implant mucositis (PM) and explored the correlation between microbial ecological imbalance, community function, and disease severity by comparing the submucosal microflora from PM with those of healthy inter-subject implants and intra-subject gingivitis (G) within a group of 32 individuals. We analyzed submucosal plaques from PM, healthy implant (HI), and G sites using metagenome shotgun sequencing. The bacterial diversity of HIs was higher than that of PM, according to the Simpson index. Beta diversity revealed differences in taxonomic and functional compositions across the groups. Linear discriminant analysis of the effect size identified 15 genera and 37 species as biomarkers that distinguished PM from HIs. Pathways involving cell motility and protein processing in the endoplasmic reticulum were upregulated in PM, while pathways related to the metabolism of cofactors and vitamins were downregulated. Microbial dysbiosis correlated positively with the severity of clinical inflammation measured by the sulcus bleeding index (SBI) in PM. Prevotella and protein processing in the endoplasmic reticulum also correlated positively with the SBI. Our study revealed PM’s microbiological and functional traits and suggested the importance of certain functions in disease severity.IMPORTANCEPeri-implant mucositis is an early stage in the progression of peri-implantitis. The high prevalence of it has been a threat to the widespread use of implant prosthodontics. The link between the submucosal microbiome and peri-implant mucositis was demonstrated previously. Nevertheless, the taxonomic and functional composition of the peri-implant mucositis microbiome remains controversial. In this study, we comprehensively characterize the microbial signature of peri-implant mucositis and for the first time, we investigate the correlations between microbial dysbiosis, functional potential, and disease severity. With the help of metagenomic sequencing, we find the positive correlations between microbial dysbiosis, genus Prevotella, pathway of protein processing in the endoplasmic reticulum, and more severe mucosal bleeding in the peri-implant mucositis. Our studies offer insight into the pathogenesis of peri-implant mucositis by providing information on the relationships between community function and disease severity.

Constructed wetlands purify water quality by synergistically removing nitrogen and phosphorus pollutants from water, among other pollutants such as organic matter through a physical, chemical, and biological composite remediation mechanism formed between plants, fillers, and microorganisms. Compared with large-scale centralized wastewater treatment systems with high cost and energy consumption, the construction and operation costs of artificial wetlands are relatively low, do not require large-scale equipment and high energy consumption treatment processes, and have the characteristics of green, environmental protection, and sustainability. Gradually, constructed wetlands are widely used to treat nitrogen and phosphorus substances in wastewater. Therefore, this article discusses in detail the role and interaction of the main technical structures (plants, microorganisms, and fillers) involved in nitrogen and phosphorus removal in constructed wetlands. At the same time, it analyses the impact of main environmental parameters (such as pH and temperature) and operating conditions (such as hydraulic load and hydraulic retention time, forced ventilation, influent carbon/nitrogen ratio, and feeding patterns) on nitrogen and phosphorus removal in wetland systems, and addresses the problems currently existing in relevant research, the future research directions are prospected in order to provide theoretical references for scholars’ research. HIGHLIGHTS Plants, microorganisms, and fillers play their respective roles, and also have complex relationships in constructed wetlands.; Environmental parameters and operating conditions are the main factors affecting nitrogen and phosphorus removal efficiency of constructed wetlands.; From the actual operating results, there are still some shortcomings in controlling nitrogen and phosphorus pollution.;

Abstract Chirality is an important topic in biology, chemistry and physics. Here we show that ultrashort circularly polarized laser pulses, which are chiral, can be fired on achiral oriented molecules to induce chirality in their electronic densities, with chirality flips within femtoseconds or even attoseconds. Our results, obtained by quantum dynamics simulations, use the fact that laser pulses can break electronic symmetry while conserving nuclear symmetry. Here two laser pulses generate a superposition of three electronic eigenstates. This breaks all symmetry elements of the electronic density, making it chiral except at the periodic rare events of the chirality flips. As possible applications, we propose the combination of the electronic chirality flips with Chiral Induced Spin Selectivity.

Abstract Background Both mitophagy and long non-coding RNAs (lncRNAs) play crucial roles in ovarian cancer (OC). We sought to explore the characteristics of mitophagy-related gene (MRG) and mitophagy-related lncRNAs (MRL) to facilitate treatment and prognosis of OC. Methods The processed data were extracted from public databases (TCGA, GTEx, GEO and GeneCards). The highly synergistic lncRNA modules and MRLs were identified using weighted gene co-expression network analysis. Using LASSO Cox regression analysis, the MRL-model was first established based on TCGA and then validated with four external GEO datasets. The independent prognostic value of the MRL-model was evaluated by Multivariate Cox regression analysis. Characteristics of functional pathways, somatic mutations, immunity features, and anti-tumor therapy related to the MRL-model were evaluated using abundant algorithms, such as GSEA, ssGSEA, GSVA, maftools, CIBERSORT, xCELL, MCPcounter, ESTIMATE, TIDE, pRRophetic and so on. Results We found 52 differentially expressed MRGs and 22 prognostic MRGs in OC. Enrichment analysis revealed that MRGs were involved in mitophagy. Nine prognostic MRLs were identified and eight optimal MRLs combinations were screened to establish the MRL-model. The MRL-model stratified patients into high- and low-risk groups and remained a prognostic factor (P

Liquid crystal (LC) droplets are highly attractive for applications in privacy windows, optical switches, optical vortices, optical microresonators, microlenses, and biosensors due to their ease of fabrication and easy alignment at surfaces. This review presents the latest advancements in LC droplets, which have nematic, chiral nematic, and twist–bend nematic and ferroelectric nematic phases, or blue phases. Finally, it discusses the challenges and opportunities for applications based on LC droplets. The main challenges encompass the precise control of internal structures and defects to meet diverse application requirements, enhancing stability and durability across various environments, reducing large-scale production costs to improve commercial feasibility, increasing response speeds to external stimuli to adapt to rapidly changing scenarios, and developing tunable LC droplets to achieve broader functionalities.

This study aimed to investigate the effect of prickly ash seeds (PAS) on the microbial community found in rumen microbes of Hu sheep by adding different percentages of prickly ash seeds and to carry out research on the relation between rumen flora and production performance. Twenty-seven male lambs of Hu sheep were classified into three groups based on the content of prickly ash seeds (PAS) fed for 90 days, i.e., 0%, 3%, and 6%. At the end of the feeding trial, rumen fluid samples were collected from six sheep in each group for 16S amplicon sequencing. The results showed that the addition of prickly ash seeds significantly increased both Chao1 and ACE indices (P < 0.05), and the differences between groups were greater than those within groups. The relative content of Bacteriodota decreased, and the relative content of Fusobacteriota, Proteobacteria, Acidobacteriota, and Euryarchaeota increased. The relative content of Papillibacter and Saccharofermentans was increased at the genus level, and the relative content of Bacteroides and Ruminococcus was decreased. The test group given 3% of prickly ash seeds was superior to the test group given 6% of prickly ash seeds. In addition, the addition of 3% of prickly ash seeds improved the metabolism or immunity of sheep. Fusobacteriota and Acidobacteriota were positively correlated with total weight, dressing percentage, and average daily gain (ADG) and negatively correlated with average daily feed intake (ADFI), feed-to-gain ratio (F/G), and lightness (L*). Methanobrevibacter and Saccharofermentans were positively correlated with ADG and negatively correlated with ADFI and L*. In conclusion, under the present experimental conditions, the addition of prickly ash seeds increased the abundance and diversity of rumen microorganisms in Hu sheep and changed the relative abundance of some genera. However, the addition of 6% prickly ash seeds may negatively affect the digestive and immune functions in sheep rumen.

ObjectiveSeveral observational studies have shown that high-volume and high-intensity exercise training increases the prevalence and severity of coronary atherosclerosis, but the causal effect still remains uncertain. This study aims to explore the causal relationship between the volume of strenuous exercise (SE) and coronary atherosclerosis (CA) using the Mendelian randomization (MR) method.MethodThe exposure factors were two basic parameters of the volume of strenuous exercise (duration and frequency of strenuous exercise), the outcome factor was coronary atherosclerosis, and the relevant genetic loci were extracted from the summary data of the genome-wide association study (GWAS) as the instrumental variables, and MR analyses were performed using the inverse variance weighting (IVW) method, the weighted median method, and the MR-egger method. Sensitivity analyses were performed using heterogeneity analysis, pleiotropy analysis, and the “leave-one-out” method. The original results were tested using other coronary atherosclerosis data sets.ResultIVW results showed no causal association between duration of strenuous exercise (DOSE) [OR = 0.9937, 95% CI (0.9847, 1.0028), P = 0.1757] and frequency of strenuous exercise (FOSE) in the last 4 weeks [OR = 0.9930, 95% CI (0.9808, 1.0054), P = 0.2660] and coronary atherosclerosis. All of the above results were validated with other coronary atherosclerosis data sets.ConclusionThe present study supports that the causal association of duration and frequency of SE with CA was not found, and provides valuable insights into the choice of scientific and correct volume of SE to cardiac rehabilitation (CR).

This work aimed to explore the mechanisms underlying the interaction of the active furanocoumarins in P. corylifolia on tofacitinib both in vivo and in vitro. The concentration of tofacitinib and its metabolite M8 was determined using UPLC-MS/MS. The peak area ratio of M8 to tofacitinib was calculated to compare the inhibitory ability of furanocoumarin contained in the traditional Chinese medicine P. corylifolia in rat liver microsomes (RLMs), human liver microsomes (HLMs) and recombinant human CYP3A4 (rCYP3A4). We found that bergapten and isopsoralen exhibited more significant inhibitory activity in RLMs than other furanocoumarins. Bergapten and isopsoralen were selected to investigate tofacitinib drug interactions in vitro and in vivo. Thirty rats were randomly allocated into 5 groups (n = 6): control (0.5% CMC-Na), low-dose bergapten (20 mg/kg), high-dose bergapten (50 mg/kg), low-dose isopsoralen (20 mg/kg) and ketoconazole. 10 mg/kg of tofacitinib was orally intervented to each rat and the concentration level of tofacitinib in the rats were determined by UPLC-MS/MS. More imporrantly, the results showed that bergapten and isopsoralen significantly inhibited the metabolism of tofacitinib metabolism. The AUC(0-t), AUC(0-∞), MRT(0-t), MRT(0-∞) and Cmax of tofacitinib increased in varying degrees compared with the control group (all p < 0.05), but CLz/F decreased in varying degrees (p < 0.05) in the different dose bergapten group and isopsoralen group. Bergapten, isopsoralen and tofacitinib exhibit similar binding capacities with CYP3A4 by AutoDock 4.2 software, confirming that they compete for tofacitinib metabolism. P. corylifolia may considerably impact the metabolism of tofacitinib, which can provide essential information for the accurate therapeutic application of tofacitinib.

Summary: Gametogenesis drives the maturation of germ cell precursors into functional gametes, facilitated by interactions with the niche environment. However, the molecular mechanisms, especially in invertebrates, remain incompletely understood. In this study, the gonadal microenvironment and gametogenic processes in the Pacific oyster, a model for diffuse gonadal organization and periodic gametogenesis, are investigated. We combine single-nucleus RNA-seq and bulk RNA-seq to analyze gonadal microenvironments in oysters. Twenty-three male and nineteen female gonadal cell clusters are identified, revealing four male and three female germ cell types, alongside follicular cells in females and Sertoli/Leydig cells in males. The NOTCH and BMP (bone morphogenetic protein) signaling pathways play a significant role in the male germline niche, suggesting similarities with mammalian germ cell microenvironment. This study offers valuable insights into germ cell developmental transitions and microenvironmental characteristics.

This investigation delves into the intricacies of the process mechanism for generating a gradient nanostructured surface (GNS) layer on M50 bearing steel, with the aim of augmenting its surface hardness and wear resistance under elevated temperature. The electron backscatter diffraction and transmission electron microscopy substantiate the successful formation of a GNS layer, surpassing 200 µm in thickness, on the M50 bearing steel treated by Ultrasonic shot peening (USP) technology. The severe plastic deformation (SPD) induced by the USP process resulted in a significant refinement of the martensite in M50 bearing steel, leading to a remarkable 32.25 % increase in surface hardness compared to its untreated coarse-grained (CG) counterpart. Pin-on-Disk wear tests were conducted at an elevated temperature of 300 °C on both the as-received CG-M50 and USP-treated M50 bearing steel samples to evaluate the impact of USP treatment on the wear resistance of M50 bearing steel. Experimental results reveal that the volume loss of the USP-treated M50 bearing steel is 94.9 % less than that of the untreated CG-M50 bearing steel after 4 h of wear tests. The improved wear resistance of the USP-treated M50 bearing steel can be attributed to the creation of an ultrastrong and stable GNS layer facilitated by USP.

Abstract Programmable artificial photosynthetic cell is the ultimate goal for mimicking natural photosynthesis, offering tunable product selectivity via reductase selection toward device integration. However, this concept is limited by the capacity of regenerating the multiple cofactors that hold the key to various reductases. Here, we report the design of artificial photosynthetic cells using biotic–abiotic thylakoid–CdTe as hybrid energy modules. The rational integration of thylakoid with CdTe quantum dots substantially enhances the regeneration of bioactive NADPH, NADH and ATP cofactors without external supplements by promoting proton-coupled electron transfer. Particularly, this approach turns thylakoid highly active for NADH regeneration, providing a more versatile platform for programming artificial photosynthetic cells. Such artificial photosynthetic cells can be programmed by coupling with diverse reductases, such as formate dehydrogenase and remodeled nitrogenase for highly selective production of formate or methane, respectively. This work opens an avenue for customizing artificial photosynthetic cells toward multifarious demands for CO2 conversion.

Abstract Today performance and operational efficiency of computer systems on digital image processing are exacerbated owing to the increased complexity of image processing. It is also difficult for image processors based on complementary metal–oxide–semiconductor (CMOS) transistors to continuously increase the integration density, causing by their underlying physical restriction and economic costs. However, such obstacles can be eliminated by non-volatile resistive memory technologies (known as memristors), arising from their compacted area, speed, power consumption high efficiency, and in-memory computing capability. This review begins with presenting the image processing methods based on pure algorithm and conventional CMOS-based digital image processing strategies. Subsequently, current issues faced by digital image processing and the strategies adopted for overcoming these issues, are discussed. The state-of-the-art memristor technologies and their challenges in digital image processing applications are also introduced, such as memristor-based image compression, memristor-based edge and line detections, and voice and image recognition using memristors. This review finally envisages the prospects for successful implementation of memristor devices in digital image processing.

Abstract Background Copy number variation (CNV) is an important source of structural variation in the mammalian genome. CNV assays present a new method to explore the genomic diversity of environmental adaptations in animals and plants and genes associated with complex traits. In this study, the genome-wide CNV distribution characteristics of 20 Tibetan sheep from two breeds (10 Oula sheep and 10 Panou sheep) were analysed using whole-genome resequencing to investigate the variation in the genomic structure of Tibetan sheep during breeding. Results CNVs were detected using CNVnator, and the overlapping regions of CNVs between individual sheep were combined. Among them, a total of 60,429 CNV events were detected between the indigenous sheep breed (Oula) and the synthetic sheep breed (Panou). After merging the overlapping CNVs, 4927 CNV regions (CNVRs) were finally obtained. Of these, 4559 CNVRs were shared by two breeds, and there were 368 differential CNVRs. Deletion events have a higher percentage of occurrences than duplication events. Functional enrichment analysis showed that the shared CNVRs were significantly enriched in 163 GO terms and 62 KEGG pathways, which were mainly associated with organ development, neural regulation, immune regulation, digestion and metabolism. In addition, 140 QTLs overlapped with some of the CNVRs at more than 1 kb, such as average daily gain QTL, body weight QTL, and total lambs born QTL. Many of the CNV-overlapping genes such as PPP3CA, SSTR1 and FASN, overlap with the average daily weight gain and carcass weight QTL regions. Moreover, VST analysis showed that XIRP2, ABCB1, CA1, ASPA and EEF2 differed significantly between the synthetic breed and local sheep breed. The duplication of the ABCB1 gene may be closely related to adaptation to the plateau environment in Panou sheep, which deserves further study. Additionally, cluster analysis, based on all individuals, showed that the CNV clustering could be divided into two origins, indicating that some Tibetan sheep CNVs are likely to arise independently in different populations and contribute to population differences. Conclusions Collectively, we demonstrated the genome-wide distribution characteristics of CNVs in Panou sheep by whole genome resequencing. The results provides a valuable genetic variation resource and help to understand the genetic characteristics of Tibetan sheep. This study also provides useful information for the improvement and breeding of Tibetan sheep in the future.

Abstract Background The chimeric antigen receptor (CAR)-T therapy has a limited therapeutic effect on solid tumors owing to the limited CAR-T cell infiltration into solid tumors and the inactivation of CAR-T cells by the immunosuppressive tumor microenvironment. Macrophage is an important component of the innate and adaptive immunity, and its unique phagocytic function has been explored to construct CAR macrophages (CAR-Ms) against solid tumors. This study aimed to investigate the therapeutic application of CAR-Ms in ovarian cancer. Methods In this study, we constructed novel CAR structures, which consisted of humanized anti-HER2 or CD47 scFv, CD8 hinge region and transmembrane domains, as well as the 4-1BB and CD3ζ intracellular domains. We examined the phagocytosis of HER2 CAR-M and CD47 CAR-M on ovarian cancer cells and the promotion of adaptive immunity. Two syngeneic tumor models were used to estimate the in vivo antitumor activity of HER2 CAR-M and CD47 CAR-M. Results We constructed CAR-Ms targeting HER2 and CD47 and verified their phagocytic ability to ovarian cancer cells in vivo and in vitro. The constructed CAR-Ms showed antigen-specific phagocytosis of ovarian cancer cells in vitro and could activate CD8+ cytotoxic T lymphocyte (CTL) to secrete various anti-tumor factors. For the in vivo model, mice with human-like immune systems were used. We found that CAR-Ms enhanced CD8+ T cell activation, affected tumor-associated macrophage (TAM) phenotype, and led to tumor regression. Conclusions We demonstrated the inhibition effect of our constructed novel HER2 CAR-M and CD47 CAR-M on target antigen-positive ovarian cancer in vitro and in vivo, and preliminarily verified that this inhibitory effect is due to phagocytosis, promotion of adaptive immunity and effect on tumor microenvironment.

Abstract Background Many studies exist on the living arrangements and health status of older adults, but the findings have been inconsistent. Therefore, we examined the relationship between living arrangements and all-cause mortality in older adults. Methods This perspective study was based on the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2011 to 2018. We used a sample aged 65 years and over included in the study in 2011. Propensity score matching was performed to minimize bias and Cox proportional hazards regression models were conducted. Results A total of 7,963 participants were included. Of these, 1,383 were living alone, 6,424 were living with families, and 156 were living in nursing homes. In the propensity score-matched cohort, older adults living alone had a significantly lower risk of all-cause mortality than those living with families (hazard ratio 0.85; 95% confidence intervals 0.76 to 0.95). Living alone was prominently associated with a decline in mortality compared with living in nursing homes (hazard ratio 0.61; 95% confidence intervals 0.44 to 0.84). There was no significant difference in mortality between living in nursing homes and living with families (hazard ratio 1.19; 95% confidence intervals 0.89 to 1.60). Subgroup analyses indicated that there was no significant interaction with age, sex, education, or residence. Conclusions The risk of all-cause mortality was significantly lower in older adults living alone than in those living with families or living in nursing homes. This article’s findings suggest the need to adopt multiple approaches to meet the needs of senior care services.

Collaborative designing of service networks using multiple logistics carriers can bring advantages in both economic and environmental terms, and these carriers have symmetry in their service areas. To enable such a collaborative service network and the corresponding benefits, this study proposes a problem of collaborative service network design (CSND) considering demand uncertainty. This problem is formulated as a two-stage robust optimization model using a budget uncertainty set to handle the uncertain demand. A column-and-constraint generation algorithm is developed to accurately solve the robust model. Numerical experiments show that the proposed algorithm outperforms the Benders decomposition algorithm in terms of solving efficiency and quality. Through comparative experiments, this research validates the advantages of collaborative designing and the robustness of model solutions. In addition, three allocation mechanisms are tested to investigate the importance of allocation in CSND.

Circular RNAs (circRNAs) are endogenous non-coding RNAs with covalently closed structures, which have important functions in plants. However, their biogenesis, degradation, and function upon treatment with gibberellins (GAs) and auxins (1-naphthaleneacetic acid, NAA) remain unknown. Here, we systematically identified and characterized the expression patterns, evolutionary conservation, genomic features, and internal structures of circRNAs using RNase R-treated libraries from moso bamboo (Phyllostachys edulis) seedlings. Moreover, we investigated the biogenesis of circRNAs dependent on both cis- and trans-regulation. We explored the function of circRNAs, including their roles in regulating microRNA (miRNA)-related genes and modulating the alternative splicing of their linear counterparts. Importantly, we developed a customized degradome sequencing approach to detect miRNA-mediated cleavage of circRNAs. Finally, we presented a comprehensive view of the participation of circRNAs in the regulation of hormone metabolism upon treatment of bamboo seedlings with GA and NAA. Collectively, our study provides insights into the biogenesis, function, and miRNA-mediated degradation of circRNAs in moso bamboo.

Abstract Background Follicular development in mammalian ovaries is a complex and dynamic process, and the interactions and regulatory-feedback loop between the follicular microenvironment, granulosa cells (GCs), and oocytes can affect follicular development and normal ovary functions. Abnormalities in any part of the process may cause abnormal follicular development, resulting in infertility. Hence, exploring the pathogenesis of abnormal follicular development is extremely important for diagnosing and treating infertile women. Methods RNA sequencing was performed with ovarian cortical tissues established in vitro. In situ-hybridization assays were performed to study microRNA-338-3p (miR-338-3p) expressed in GCs and oocytes. In vitro culture models were established with GCs and neonatal mouse ovaries to study the biological effects of miR-338-3p. We also performed in vivo experiments by injecting adeno-associated virus vectors that drive miR-338-3p overexpression into the mouse ovarian bursae. Results Sequencing analysis showed that miR-338-3p was expressed at significantly higher levels in ovarian cortical tissues derived from patients with ovarian insufficiency than in cortical tissues derived from patients with normal ovarian function; miR-338-3p was also significantly highly expressed in the GCs of patients with diminished ovarian reserve (P

Abstract Backgroud Recurrent laryngeal nerve (RLN) injury is one of the serious complications of thyroid tumour surgery, surgical treatment of thyroid cancer requires careful consideration of the RLN and its impact on glottis function. There has been no unified standard for precise neuromuscular block monitoring to guide the monitoring of RLN in thyroid surgery. This study aimed to investigate the correlation between Train-of-four stabilization ratio (TOFr) and neural signal values of intraoperative neurophysiological monitoring (INOM) during thyroid operation, and further to determine the optimal timing for INOM during thyroid operation. Methods Patients scheduled for thyroid tumour resection with INOM and RLN monitoring from April 2018 to July 2018 in our center were recruited. Electromyography (EMG) signals and corresponding TOFr were collected. All nerve stimulation data were included in group VR. Vagus nerve stimulation data were included in Subgroup V. RLN stimulation data were included in Subgroup R. The timing of recording was as follows: Vagus nerve EMG amplitude after opening the lateral space between the thyroid and carotid sheath and before the initiation of thyroid dissection, RLN EMG amplitude at first recognition, RLN EMG amplitude after complete thyroid dissection (Repeat three times), and Vagus nerve EMG amplitude after resection of the thyroid (Repeat three times). Correlation analysis of continuous variables was described by a scatter diagram. Pearson correlation analysis or Spearman correlation analysis was used for the two groups of variables. Results Finally, 134 vagus nerve signals and 143 RLN signals were analysed after matching with TOFr. The EMG amplitude in the VR group and subgroups after nerve stimulation was positively correlated with TOFr (p 0.05). Conclusions The EMG signals of the RLN and vagus nerve stimulation during thyroid surgery were positively correlated with TOFr. TOFr > 0.75 could reflect more than 50% of the effective nerve electrophysiological signals, 0.75

Abstract Background Iron sulfide nanomaterials have been successfully employed as therapeutic agents for bacterial infection therapy and catalytic-ferroptosis synergistic tumor therapy due to their unique structures, physiochemical properties, and biocompatibility. However, biomedical research and understanding of the biological functions of iron sulfides are insufficient, and how iron sulfide nanomaterials affect reactive oxygen species (ROS) in diseases remains unknown. Acute kidney injury (AKI) is associated with high levels of ROS, and therefore nanomedicine-mediated antioxidant therapy has emerged as a novel strategy for its alleviation. Results Here, mackinawite nanozymes were synthesized from glutathione (GSH) and iron ions (Fe3+) (denoted as GFeSNs) using a hydrothermal method, and then evaluated as ROS scavengers for ROS-related AKI treatment. GFeSNs showed broad-spectrum ROS scavenging ability through synergistic interactions of multiple enzymes-like and hydrogen polysulfide-releasing properties. Furthermore, both in vitro and in vivo experiments demonstrated that GFeSNs exhibited outstanding cytoprotective effects against ROS-induced damage at extremely low doses and significantly improved treatment outcomes in AKI. Conclusions Given the synergetic antioxidant properties and high biocompatibility, GFeSNs exhibit great potential for the treatment of AKI and other ROS-associated diseases. Graphical Abstract

The pathogenesis of head and neck squamous cell carcinoma (HNSCC) is associated with human papillomavirus (HPV) infection. However, the molecular mechanisms underlying the interactions between HNSCC and HPV remain unclear. Bioinformatics was used to analyze the gene expression dataset of HPV-associated HNSCC based on the Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) in HPV-positive and HPV-negative HNSCC were screened. Gene function enrichment, protein–protein interactions (PPI), survival analysis, and immune cell infiltration of DEGs were performed. Furthermore, the clinical data of HNSCC tissue samples were analyzed using immunohistochemistry. In total, 194 DEGs were identified. A PPI network was constructed and 10 hub genes (EREG, PLCG1, ERBB4, HBEGF, ZFP42, CBX6, NFKBIA, SOCS1, ATP2B2, and CEND1) were identified. Survival analysis indicated that low expression of SOCS1 was associated with worse overall survival. Immunohistochemistry demonstrated that SOCS1 expression was higher in HPV-negative HNSCC than in HPV-positive HNSCC, and there was a positive correlation between SOCS1 expression and patient survival. This study provides new information on biological targets that may be relevant to the molecular mechanisms underpinning the occurrence and development of HNSCC. SOCS1 may play an important role in the interaction between HPV and HNSCC and serve as a potential biomarker for future therapeutic targets.

Abstract Background Famine is a risk factor for non-communicable chronic diseases (NCDs), which account for over 80% of deaths in China. The effect of famine on the prevalence of NCDs in terms of various age groups, time periods and cohorts is currently poorly understood. Objective This study aims to explore long-term trends in the impact of China’s Great Famine (1959–1961) on NCDs in China. Methods This study used data from the 2010–2020 China Family Panel Longitudinal Survey across 25 provinces in China. The subjects were aged 18–85 years, and the total number of subjects was 174,894. The prevalence of NCDs was derived from the China Family Panel Studies database (CFPS). An age-period-cohort (APC) model was used to estimate the age, period and cohort effects of NCDs in 2010–2020 and the effect of famine on the risk of NCDs in terms of cohort effects. Results The prevalence of NCDs increased with age. Additionally, the prevalence did not clearly decrease over the survey period. Regarding the cohort effect, people born in the years adjacent to the famine period had a higher risk of NCDs; additionally, females, those born in rural areas, and those who lived in provinces with severe famine and post-famine had a higher likelihood of NCDs. Conclusions Experiencing famine at an early age or the experience of famine in a close relative’s generation (births after the onset of famine) are associated with an increased risk of NCDs. Additionally, more severe famine is associated with a higher risk of NCDs.

PurposeTo develop deep-learning radiomics model for predicting biochemical recurrence (BCR) of advanced prostate cancer (PCa) based on pretreatment apparent diffusion coefficient (ADC) maps.MethodsData were collected retrospectively from 131 patients diagnosed with advanced PCa, randomly divided into training (n = 93) and test (n = 38) datasets. Pre-treatment ADC images were segmented using a pre-trained artificial intelligence (AI) model to identify suspicious PCa areas. Three models were constructed, including a clinical model, a conventional radiomics model and a deep-radiomics model. The receiver operating characteristic (ROC), precision-recall (PR) curve and decision curve analysis (DCA) were used to assess predictive performance in test dataset. The net reclassification index (NRI) and integrated discrimination improvement (IDI) were employed to compare the performance enhancement of the deep-radiomics model in relation to the other two models.ResultsThe deep-radiomics model exhibited a significantly higher area under the curve (AUC) of ROC than the other two (P = 0.033, 0.026), as well as PR curve (AUC difference 0.420, 0.432). The DCA curve demonstrated superior performance for the deep-radiomics model across all risk thresholds than the other two. Taking the clinical model as reference, the NRI and IDI was 0.508 and 0.679 for the deep-radiomics model with significant difference. Compared with the conventional radiomics model, the NRI and IDI was 0.149 and 0.164 for the deep-radiomics model without significant difference.ConclusionThe deep-radiomics model exhibits promising potential in predicting BCR in advanced PCa, compared to both the clinical model and the conventional radiomics model.

Background With the rapid urbanization in many countries, more attention is being paid to the relationship between urbanization and mental health, especially depression. However, in countries with rapid urbanization, few empirical studies exist on the relationship between urbanization and adolescent depression. Methods Nationally representative survey data from the China Family Panel Studies in 2012, 2016 and 2018 were used. Data of 1,588 adolescents were obtained from 25 provinces. Depression was measured using the Center for Epidemiology Studies of Depression 20-item score. The urbanization rate was obtained from the National Bureau of Statistics of China. The generalized estimating equation was used to estimate the statistical relationship. Results The participants’ mean age at baseline was 15 years, and 51.2% (813/1,588) of participants were male. After adjusting for all covariates (gender, age, ethnicity, level of education, marital status, urban/rural areas, body mass index, self-rated health, academic pressure, smoking, drinking and exercise), the rate of urbanization was monotonically and negatively associated with adolescent depression (odds ratio 0.34, 95% CI [0.14–0.79]). Compared with female adolescents, male adolescents had a lower risk of depression (odds ratio 0.80, 95% CI [0.67–0.97]). Conclusion In the context of China, urbanization has a positive effect on the mental health of adolescents. Female adolescents are more likely to experience depression than male adolescents.

The purpose of this experiment was to study the effect of Allium mongolicum Regel powder (AMR) and yeast cultures (YC) on rumen microbial diversity in Tibetan sheep in different Ecological niches. A total of 40 male Tibetan lambs with an initial weight of 18.56 ± 1.49 kg (6 months old) were selected and divided into four groups (10 sheep/pen; n = 10). In the Control Group, each animal was grazed for 8 h per day, in Group I, each animal was supplemented with 200 g of concentrate per day, in Group II, each animal was supplemented with 200 g of concentrate and 10 g of AMR per day, in Group III, each animal was supplemented with 200 g of concentrate and 20 g of YC per day. The experiment lasted 82 days and consisted of a 7-day per-feeding period and a 75-day formal period. The results indicated that at the phylum level, the abundance of Bacteroidota and Verrucomimicrobiota in L-Group II and L-Group III was increased, while the abundance of Proteobacteria was decreased in the LA (Liquid-Associated) groups. The proportion of F/B in S-Group II and S-Group III was increased compared to S-Group I and S-CON in the SA (Soild-Associated) group. At the genus level, the abundance of uncultured_rumen_bacterium and Eubacterium_ruminantium_group in L-Group II and L-Group III was increased. Furthermore, while the abundance of Rikenellaceae_RC9_gut_group was decreased in the LA, the abundance of Prevotella and Eubacterium_ruminantium_group was increased in the S-Group II and S-Group III compared to S-Group I and S-CON. The abundance of probable_genus_10 was the highest in S-Group II in the SA group. After the addition of YC and AMR, there was an increase in rumen microbial abundance, which was found to be beneficial for the stability of rumen flora and had a positive impact on rumen health.

Currently, there is limited research on the influence of gas ionization on the pulse formation process in pulse power source-driven loads. This paper introduces a road-field-Particle-In-Cell (PIC)/Monte Carlo Collision (MCC) collaborative simulation method that can accurately simulate gas ionization in Linear Transformer Driver (LTD) electron beam generation (EBG). The method couples the electromagnetic field and charged particle simulated through PIC/MCC with the circuit modules, and the load's voltammetry characteristics can real-time feedback to the Blumlein Pulse Forming Network (BPFN) of the LTD. In contrast to prior simulations that used fitted ideal T-shaped pulse input waveforms to model the load, this method provides a clearer depiction of the influence of gas ionization on the pulse shape. Additionally, the paper conducts simulation studies on LTD electron beam generator operating at different argon gas pressures. The findings indicate that introducing gas can effectively increase current while reducing voltage amplitude, thereby lowering the diode impedance. A small amount of gas can slightly enhance peak power, but excessive gas diminishes peak power and significantly shortens voltage pulse width. This is attributed to the beneficial effect of a small amount of gas ionization-produced plasma on the device. However, an excessive amount of gas ionization-generated plasma can lead to impedance mismatch in the device, even resulting in a load short circuit. This phenomenon causes a decrease in pressure drop at the top, consequently shortening the pulse width.

ABSTRACT: The objective of this study was to investigate the preventive effects and mechanisms of genistein (GEN) on production performance and metabolic disorders in broilers under chronic heat stress (HS). A total of 120 male 3-wk-old Ross broilers were randomly assigned to 5 groups: a thermoneutral zone (TN) group maintained at normal temperature (21°C ± 1°C daily), an HS group subjected to cyclic high temperature (32°C ± 1°C for 8 h daily), and 3 groups exposed to HS with varying doses of GEN (50, 100, or 150 mg/kg diet). The experimental period lasted for 3 wk. Here, HS led to a decline in growth performance parameters and hormone secretion disorders (P < 0.05), which were improved by 100 and 150 mg/kg GEN treatment (P < 0.05). Moreover, the HS-induced increases in the liver index (P < 0.01) and abdominal fat rate (P < 0.05) were attenuated by 150 mg/kg GEN (P < 0.05). The HS-induced excessive lipid accumulation in the liver and serum (P < 0.01) was ameliorated after 100 and 150 mg/kg GEN treatment (P < 0.05). Furthermore, the HS-induced decreases in lipolysis-related mRNA levels and increases in lipid synthesis-related mRNA levels in the liver (P < 0.01) were effectively blunted after 100 and 150 mg/kg GEN treatment (P < 0.05). Importantly, the HS-stimulated hepatic mitochondrial energetic dysfunction and decreases in the mRNA or protein levels of peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α), nuclear respiratory factor 1, and mitochondrial transcription factor A in the liver were ameliorated by 150 mg/kg GEN (P < 0.05). Moreover, 50 to 150 mg/kg GEN treatment resulted in a significant increase in the mRNA or protein levels of G protein-coupled estrogen receptor (GPR30), AMP-activated protein kinase (AMPK) α1, phosphorylated AMPKα, and phosphorylated acetyl-CoA carboxylase α. Collectively, GEN alleviated metabolic disorders and hepatic mitochondrial energetic dysfunction under HS, possibly through the activation of GPR30-AMPM-PGC-1α pathways. These data provide a sufficient basis for GEN as an additive to alleviate HS in broilers.

This study delves into the impact of yeast culture (YC) on rumen epithelial development, microbiota, and metabolome, with the aim of investigating YC’s mechanism in regulating rumen fermentation. Thirty male lambs of Hu sheep with similar age and body weight were selected and randomly divided into three groups with 10 lambs in each group. Lambs were fed a total mixed ration [TMR; rough: concentrate (R:C) ratio ≈ 30:70] to meet their nutritional needs. The experiment adopted completely randomized design (CRD). The control group (CON) was fed the basal diet with high concentrate, to which 20 g/d of YC was added in the low dose YC group (LYC) and 40 g/d of YC in the high dose YC group (HYC). The pretrial period was 14 days, and the experimental trial period was 60 days. At the end of a 60-day trial, ruminal epithelial tissues were collected for histomorphological analysis, and rumen microorganisms were analyzed by 16S rDNA sequencing and rumen metabolites by untargeted liquid chromatography-mass spectrometry (LC–MS) metabolomics techniques. The results showed that YC improved rumen papilla development and increased rumen papilla length (p

BackgroundMyopia, a condition affecting approximately one-quarter of the world' s population, has been projected to double in prevalence by the year 2050. It can have an impact on postural control during walking and can increase the risk of falls and injuries.Objective(1) To examine the abnormal performance of postural control during walking in male college students who used convex lenses for myopia intervention from a kinematic perspective; (2) to establish theoretical foundation for preventing falls and injuries in the myopic population.MethodsA total of 22 male college students participated in this study. The center of gravity (COG), the percentage of gait cycle (PGC) and the joint angle(JT) were collected as indications of postural control during walking. A quantitative analysis was conducted using a One-Way Repeated Measures ANOVA to examine the variations among the three groups.ResultsDuring myopic interventions, (1) the range of vertical COG changes is significant to be greater compared with normal vision (P < 0.05). (2) there was an significant increase in the PGC in single-legged support, accompanied by a decrease in the PGC in double-legged support, compared with normal vision (P < 0.05). (3) The myopic intervention leads to increased variability in JT of the hip and the knee during the single-leg support and swing, as compared to individuals with normal vision (P < 0.05). Severe myopic interventions result in more changes in JT of ankle.ConclusionMyopia has been found to have a negative impact on postural control during walking, leading to changes in balance, increased instability, and an elevated risk of injury.

Introduction: Pregnanediol-3-glucuronide (PdG), as the main metabolite of progesterone in urine, plays a significant role in the prediction of ovulation, threatened abortion, and menstrual cycle maintenance.Methods: To achieve a rapid and sensitive assay, we have designed a competitive model-based time-resolved fluorescence microsphere-lateral flow immunochromatography (TRFM-LFIA) strip.Results: The optimized TRFM-LFIA strip exhibited a wonderful response to PdG over the range of 30–2,000 ng/mL, the corresponding limit of detection (LOD) was calculated as low as 8.39 ng/mL. More importantly, the TRFM-LFIA strip was innovatively used for the quantitative detection of PdG in urine sample, and excellent recovery results were also obtained, ranging from 97.39% to 112.64%.Discussion: The TRFMLFIA strip possessed robust sensitivity and selectivity in the determination of PdG, indicating the great potential of being powerful tools in the biomedical and diagnosis region.

AbstractBackground In colorectal cancer (CRC), both tumor invasion and immunological analysis at the tumor invasive margin (IM) are significantly associated with patient prognosis, but have traditionally been reported independently. We propose a new scoring system, the TGP-I score, to assess the association and interactions between tumor growth pattern (TGP) and tumor infiltrating lymphocytes at the IM and to predict its prognostic validity for CRC patient stratification.Materials and Methods The types of TGP were assessed in hematoxylin and eosin-stained whole-slide images. The CD3+ T-cells density at the IM was automatically quantified on immunohistochemical-stained slides using a deep learning method. A discovery (N = 347) and a validation (N = 132) cohorts were used to evaluate the prognostic value of the TGP-I score for overall survival.Results The TGP-I score3 (trichotomy) was an independent prognostic factor, with higher TGP-I score3 associated with worse prognosis in the discovery (unadjusted hazard ratio [HR] for high vs. low 3.62, 95% confidence interval [CI] 2.22–5.90; p

Abstract Health care workers (HCWs) experienced greater risk of SARS-CoV-2 infection during the COVID-19 pandemic. This study applies a cost-of-illness (COI) approach to model the economic burden associated with SARS-CoV-2 infections among HCWs in five low- and middle-income sites (Kenya, Eswatini, Colombia, KwaZulu-Natal province, and Western Cape province of South Africa) during the first year of the pandemic. We find that not only did HCWs have a higher incidence of COVID-19 than the general population, but in all sites except Colombia, viral transmission from infected HCWs to close contacts resulted in substantial secondary SARS-CoV-2 infection and death. Disruption in health services as a result of HCW illness affected maternal and child deaths dramatically. Total economic losses attributable to SARS-CoV-2 infection among HCWs as a share of total health expenditure ranged from 1.51% in Colombia to 8.38% in Western Cape province, South Africa. This economic burden to society highlights the importance of adequate infection prevention and control measures to minimize the risk of SARS-CoV-2 infection in HCWs.

Abstract Exosomal miRNAs are known to play important roles in ovarian cancer and chemotherapeutic resistance. However, a systematic evaluation of characteristics of exosomal miRNAs involved in cisplatin resistance in ovarian cancer remains totally unclear. Exosomes (Exo-A2780, Exo-A2780/DDP) were extracted from cisplatin-sensitive cells (A2780) and cisplatin-resistant cells (A2780/DDP). Differential exosomal miRNA expression profiles were found by high-throughput sequencing (HTS). Target genes of the exo-miRNAs were predicted by using two online databases to increase the prediction accuracy. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were utilized to find biological relationships with chemoresistance. RT‒qPCR of three exosomal miRNAs was performed, and a protein‒protein interaction (PPI) network was established to identify the hub genes. The GDSC database was used to prove the association between hsa-miR-675-3p expression and the IC50 value. An integrated miRNA–mRNA network was constructed to predict miRNA–mRNA associations. The connection between hsa-miR-675-3p and ovarian cancer was discovered by immune microenvironment analyses. The upregulated exosomal miRNAs could regulate gene targets through signalling pathways such as the Ras, PI3K/Akt, Wnt, and ErbB pathways. GO and KEGG analyses indicated that the target genes were involved in protein binding, transcription regulator activity and DNA binding. The RT‒qPCR results were consistent with the HTS data, and the results of PPI network analysis suggested that FMR1 and CD86 were the hub genes. GDSC database analysis and construction of the integrated miRNA–mRNA network suggested that hsa-miR-675-3p was associated with drug resistance. Immune microenvironment analyses showed that hsa-miR-675-3p was crucial in ovarian cancer. The study suggested that exosomal hsa-miR-675-3p is a potential target for treating ovarian cancer and overcoming cisplatin resistance.

Modern technological lifestyles promote allergic diseases, especially food allergies. The underlying molecular mechanisms remain to be uncovered. Protein acetylation is one of the most important post-translational modifications, and it is involved in regulating multiple body metabolic processes. This study aimed to clarify the effects of a high-fat diet (HFD) on allergy risk and the underlying mechanisms. Four-week-old male C57BL/6J mice were randomly divided into two groups and fed a normal fat diet (NFD) or HFD for 24 weeks. Then, serum lipids were measured, and skeletal muscle was collected for acetylome analysis. Compared with the findings in the NFD group, HFD-fed mice were obese and hyperlipidemic. Acetylome analysis also revealed 32 differentially expressed proteins between the HFD and NFD groups. Among these, eight acetylated proteins were upregulated in the HFD group. In addition, 13 and 11 proteins were acetylated only in the HFD group and NFD group, respectively. These proteins were mainly involved in regulating energy metabolism and mitochondrial function. This study provides information regarding the underlying molecular mechanisms by which HFD promotes allergy.

Abstract Background and objectives Real-time blood flow variation is crucial for understanding the dynamic development of coronary atherosclerosis. The main objective of this study is to investigate the effect of varying extent of stenosis on the hemodynamic features in left anterior descending coronary artery. Methods Various Computational fluid dynamics (CFD) models were constructed with patient-specific CT image data, using actual fractional flow reserve (FFR) as boundary conditions to provide a real-time quantitative description of hemodynamic properties. The hemodynamic parameters, such as the local and instantaneous wall shear stress (WSS), oscillating shear index (OSI) and relative residence time (RRT), blood flow velocity and pressure drop during various phases of cardiac cycle were provided in detail. Results There was no evident variation in hemodynamic parameters in the cases of less than 50% stenosis while there were abrupt and dramatic changes in hemodynamics when the stenosis aggravated from 60 to 70%. Furthermore, when the stenosis was beyond 70%, there existed substantial pressure difference, WSS, and blood flow velocity in the center of the stenosis. Although OSI and RRT increased along with the aggravation of stenosis, they appeared with obvious abnormalities across all cases, even in mild stenosis. Conclusion The simulation could present a dynamic and comprehensive profile of how hemodynamic parameters vary in accordance with divergent severities of stenosis, which could serve as an effective reference for the clinicians to have a deeper insight into the pathological mechanism of coronary atherosclerosis and stenosis.