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Abstract Background Radial head fractures are the most common bony injury of the elbow in adults. The current literature does not agree on whether isolated stable type II radial head fractures should be treated operatively or nonoperatively. This review aims to determine the preferred treatment for Mason type II radial head fractures and compare the outcomes of conservative and surgical treatment. Methods Our study used PRISMA guidelines and conducted a thorough search of multiple electronic databases, including PubMed, Cochrane, Embase, Web of Science, CNKI, and Wanfang databases, initially identifying 545 relevant publications on surgical and conservative treatment of Mason type II radial head fractures. The final search date for this study is July 7, 2024.Through a comprehensive meta-analysis, we evaluated several outcomes, including functional scores (DASH, OES, and MEPS scores), clinical outcomes (elbow flexion, elbow extension deficit, elbow pronation, and elbow supination), and complication rate (total complications and elbow pain). The mean difference (MD) was compared for continuous outcomes, and the odds ratios (ORs) were compared for categorical outcomes. Result A total of 271 patients from 4 studies met the inclusion criteria. Among them, 142 patients received surgical treatment and 129 patients received non-surgical treatment. The study found no statistically significant differences between surgical and non-surgical treatments in DASH, OES, MEPS, elbow flexion, elbow extension impairment, and elbow pain. Compared with surgical treatment, non-surgical treatment was associated with greater elbow pronation (OR = -3.10, 95% CI = [-4.96, -1.25], P = 0.55, I2 = 0%) and a lower complication rate (OR = 5.54, 95% CI = [1.79, 17.14], P = 0.42, I2 = 0%). Conclusion Based on the current evidence, conservative management of isolated Mason II radial head fractures yields favorable therapeutic outcomes with a low incidence of complications.

Abstract Background Methionine (Met) is the only sulfur-containing amino acid among animal essential amino acids, and methionine deficiency (MD) causes tissue damage and cell death in animals. The common modes of cell death include apoptosis, autophagy, pyroptosis, necroptosis. However, the studies about the major modes of cell death caused by MD have not been reported, which worth further study. Methods Primary hepatocytes from grass carp were isolated and treated with different doses of Met (0, 0.5, 1, 1.5, 2, 2.5 mmol/L) to examine the expression of apoptosis, pyroptosis, autophagy and necroptosis-related proteins. Based on this, we subsequently modeled pyroptosis using lipopolysaccharides and nigericin sodium salt, then autophagy inhibitors chloroquine (CQ), AMP-activated protein kinase (AMPK) inhibitors compound C (CC) and reactive oxygen species (ROS) scavengers N-acetyl-L-cysteine (NAC) were further used to examine the expression of proteins related to pyroptosis, autophagy and AMPK pathway in MD-treated cells respectively. Results MD up-regulated B-cell lymphoma protein 2 (Bax), microtubule-associated protein 1 light chain 3 II (LC3 II), and down-regulated the protein expression levels of B-cell lymphoma-2 (Bcl-2), sequestosome 1 (p62), cleaved-caspase-1, cleaved-interleukin (IL)-1β, and receptor-interacting protein kinase (RIP) 1 in hepatocytes, while it did not significantly affect RIP3. In addition, MD significantly increased the protein expression of liver kinase B1 (LKB1), p-AMPK, and Unc-51-like kinase 1 (ULK1) without significant effect on p-target of rapamycin. Subsequently, the use of CQ increased the protein expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cleaved-caspase-1, and cleaved-IL-1β inhibited by MD; the use of CC significantly decreased the protein expression of MD-induced LC3 II and increased the protein expression of MD-suppressed p62; then the use of NAC decreased the MD-induced p-AMPK protein expression. Conclusion MD promoted autophagy and apoptosis, but inhibited pyroptosis and necroptosis. MD inhibited pyroptosis may be related regarding the promotion of autophagy. MD activated AMPK by inducing ROS production which in turn promoted autophagy. These results could provide partial theoretical basis for the possible mechanisms of Met in ensuring the normal structure and function of animal organs. Furthermore, ferroptosis is closely related to redox states, it is worth investigating whether MD affects ferroptosis in hepatocytes.

Abstract Background The health effects of Life’s Essential 8 (LE8) on chronic diseases have been disclosed, but its association with hypertension remains unknown. The current study aimed to explore the potential link between 10-year LE8 trajectory and the incidence of hypertension. Methods LE8 was constructed from four behaviors and four metabolic factors, ranging from 0 to 100. Latent mixture models were used to identify trajectories of LE8 scores during 2006 to 2016. Incident hypertension was diagnosed based on self-reported clinical diagnoses and physical examinations from 2016 to 2020. Cox models were employed to assess the association of LE8 trajectories with hypertension. In addition to incorporating the mean hs-CRP levels from 2006 to 2016, age, sex, monthly income, educational level, and occupation at recruitment were adjusted for as confounding factors. Results 7500 participants aged 40.28 ± 10.35 years were included in the study, of whom 2907 (38.76%) were women. Five LE8 trajectory patterns were identified. After around four-year follow-up, 667 hypertension events were observed. Compared to the Low-Stable trajectory, the hazard ratios and 95% confidence intervals for the Moderate-Increasing, Moderate-Decreasing, Moderate-Stable, and High-Stable trajectories were 0.51 (0.40, 0.65), 0.81 (0.64, 1.02), 0.45 (0.36, 0.58), 0.23 (0.16, 0.33), respectively. The risk of incident hypertension decreased as participants improved their LE8 status. The robustness of the primary results was confirmed through several sensitivity analyses. Conclusions LE8 trajectories were associated with the incident hypertension. People who improved their LE8 scores over time experienced a decreased risk of hypertension, even if they started with lower LE8 scores initially.

Abstract Ferroptosis, triggered by iron overload and excessive lipid peroxidation, plays a pivotal role in the progression of DOX-induced cardiomyopathy (DIC), and thus limits the use of doxorubicin (DOX) in clinic. Here, we further showed that cardiac ferroptosis induced by DOX in mice was attributed to up-regulation of Hmox1, as knockdown of Hmox1 effectively inhibited cardiomyocyte ferroptosis. To targeted delivery of siRNA into cardiomyocytes, siRNA-encapsulated exosomes were injected followed by ultrasound microbubble targeted destruction (UTMD) in the heart region. UTMD greatly facilitated exosome delivery into heart. Consistently, UTMD assisted exosomal delivery of siHomox1 nearly blocked the ferroptosis and the subsequent cardiotoxicity induced by doxorubicin. In summary, our findings reveal that the upregulation of HMOX1 induces ferroptosis in cardiomyocytes and UTMD-assisted exosomal delivery of siHmox1 can be used as a potential therapeutic strategy for DIC. Graphical Abstract

Abstract In this research, we introduce a novel optimization algorithm termed the dual-relaxed inertial alternating direction method of multipliers (DR-IADM), tailored for handling nonconvex and nonsmooth problems. These problems are characterized by an objective function that is a composite of three elements: a smooth composite function combined with a linear operator, a nonsmooth function, and a mixed function of two variables. To facilitate the iterative process, we adopt a straightforward parameter selection approach, integrate inertial components within each subproblem, and introduce two relaxed terms to refine the dual variable update step. Within a set of reasonable assumptions, we establish the boundedness of the sequence generated by our DR-IADM algorithm. Furthermore, leveraging the Kurdyka–Łojasiewicz (KŁ) property, we demonstrate the global convergence of the proposed method. To validate the practicality and efficacy of our algorithm, we present numerical experiments that corroborate its performance. In summary, our contribution lies in proposing DR-IADM for a specific class of optimization problems, proving its convergence properties, and supporting the theoretical claims with numerical evidence.

Ochratoxin A (OTA) is one of the most common pollutants in aquatic feed. As a first line of defense, intestinal barriers could be utilized against OTA in order to prevent disorders. Natural product supplementation is one of the most popular strategies to alleviate toxicity induced by mycotoxins, but there is a lack of knowledge about how it functions in the teleost intestine. In this study, 720 juvenile grass carp of about 11 g were selected and four treatment groups (control group, OTA group, curcumin [Cur] group, and OTA + Cur group) were set up to conduct a 60-day growth test. After the test, the growth performance and intestinal health related indexes of grass carp were investigated. The addition of dietary Cur could have the following main results: (1) inhibit absorption and promote efflux transporters mRNA expression, reducing the residuals of OTA, (2) decrease oxidative stress by reducing oxidative damage and enhancing the expression of antioxidant enzymes, (3) promote mitochondrial fusion proteins to inhibit the expression of mitotic proteins and mitochondrial autophagy proteins and enhance mitochondrial function, (4) reduce necroptosis-related gene expression through inhibiting the tumor necrotic factor receptor-interacting protein kinase/mixed lineage kinase domain-like pathway, (5) reduce the expression of pro-inflammatory factors by inhibiting the Toll-like receptor 4/nuclear factor-κB signaling pathway to alleviate the intestinal inflammatory response. In summary, the results suggested that Cur could alleviate OTA-induced intestinal damage by enhancing antioxidant capacity and mitochondrial function as well as reducing necroptosis and inflammation in the grass carp intestine. This study provided a theoretical basis and production implications for dietary Cur that could improve growth performance and alleviate the intestinal damage induced by OTA in fish.

Per- and polyfluoroalkyl substances (PFAS) can pass through the placenta and adversely affect fetal development. However, there is a lack of comparison of legacy and emerging PFAS levels among different biosamples in pregnant women and their offspring. This study, based on the Shanghai Maternal–Child Pairs Cohort, analyzed the concentrations of 16 PFAS in the maternal serum, cord serum, and breast milk samples from 1,076 mother-child pairs. The placental and breastfeeding transfer efficiencies of PFAS were determined in maternal-cord and maternal-milk pairs, respectively. The binding affinities of PFAS to five transporters were simulated using molecular docking. The results suggested that PFAS were frequently detected in different biosamples. The median concentration of perfluorooctane sulfonate (PFOS) was the highest at 8.85 ng/mL, followed by perfluorooctanoic acid (PFOA) at 7.13 ng/mL and 6:2 chlorinated polyfluorinated ether sulfonate at 5.59 ng/mL in maternal serum. The median concentrations of PFOA were highest in cord serum (4.23 ng/mL) and breast milk (1.08 ng/mL). PFAS demonstrated higher placental than breastfeeding transfer efficiencies. The transfer efficiencies and the binding affinities of most PFAS to proteins exhibited alkyl chain length-dependent patterns. Furthermore, we comprehensively assessed the estimated daily intakes (EDIs) of PFAS in breastfeeding infants of different age groups and used the hazard quotient (HQ) to characterize the potential health risk. EDIs decreased with infant age, and PFOS had higher HQs than PFOA. These findings highlight the significance of considering PFAS exposure, transfer mechanism, and health risks resulting from breast milk intake in early life.

There are major gaps in illustrating the risk to freshwater fish that are exposed to environmental microplastics (MPs), even though MPs in freshwater environments has drawn much concern. To explore the potentially negative effects of microplastics on freshwater fish, grass carp (averaging 9.215 ± 0.035g) were exposed to microplastics (32–40 μm in diameter) at two environmental concentrations (100 and 1000 μg/L) for 21 days, and evaluated for physio-biochemical performance, gut microbiome, and metabolome responses. After exposure, microplastics were detected in the intestine and within basal nuclei and goblet cells hyperplasia. Antioxidant enzyme activities (superoxide dismutase and catalase) also significantly decreased within the intestines (P

Abstract Background Despite the adverse effects of ambient fine particulate matter (PM2.5) on type 2 diabetes and the beneficial role of physical activity (PA), the influence of PM2.5 on the relationship between PA and type 2 diabetes remains unclear. Methods In this prospective study with 71,689 participants, PA was assessed by a questionnaire and was categorized into quartiles for volume and three groups for intensity. Long‐term PM2.5 exposure was calculated using 1‐km resolution satellite‐based PM2.5 estimates. PM2.5 exposure and PA's effect on type 2 diabetes were assessed by cohort‐stratified Cox proportional hazards models, individually and in combination. Results In 488,166 person‐years of follow‐up, 5487 incident type 2 diabetes cases were observed. The association between PA and type 2 diabetes was modified by PM2.5. Compared with the lowest quartile of PA volume, the highest quartile was associated with reduced type 2 diabetes risk in low PM2.5 stratification (≤65.02 µg/m3) other than in high PM2.5 stratification (>65.02 µg/m3), with the hazard ratio (HR) of 0.75 (95% confidence interval [CI]: 0.66–0.85) and 1.10 (95% CI: 0.99–1.22), respectively. Similar results were observed for PA intensity. High PM2.5 exposure combined with the highest PA levels increased the risk of type 2 diabetes the most (HR = 1.79, 95% CI: 1.59–2.01 for PA volume; HR = 1.82, 95% CI: 1.64–2.02 for PA intensity). Conclusion PA could reduce type 2 diabetes risk in low‐pollution areas, but high PM2.5 exposure may weaken or even reverse the protective effects of PA. Safety and health benefits of PA should be thoroughly assessed for long‐term polluted residents.

This research evaluated the effects of copper (Cu) on intestinal antioxidant capacity and apical junctional complex (AJC) in juvenile grass carp. A total of 1080 healthy juvenile grass carp (11.16 ± 0.01 g) were fed six diets including different dosages of Cu, namely 0, 2, 4, 6, 8 mg/kg (Cu citrate [CuCit] as Cu source) and 3 mg/kg (CuSO4·5H2O as Cu source). The trial lasted for 9 weeks. The findings revealed that dietary optimal Cu supplementation (2.2 to 4.1 mg/kg) promoted intestinal growth, including intestinal length, intestinal length index, intestinal weight, and intestinal somatic index (P 0.05). On the other hand, optimal Cu increased intestinal tight junction (TJ) proteins (except for claudin 15b) and adherens junction (AJ) proteins (E-cadherin, α-catenin, β-catenin, nectin and afadin) mRNA levels (P

In nature, aflatoxins, especially aflatoxin B1 (AFB1), are the common mycotoxins, which cause serious health problems for humans and animals. This paper aimed to study the effects of AFB1 on flesh flavor and muscle development of grass carp (Ctenopharyngodon idella) and its mechanism. There were 1440 individual fish in total, with 6 treatments and each treatment replicated 3 times. The 6 treatments were fed a control diet with different doses of AFB1 (0.04, 29.48, 58.66, 85.94, 110.43 and 146.92 μg/kg diet) for 60 d. AFB1 increased myofiber diameter, as well as decreased myofiber density of grass carp muscle (P

Diabetic ulcers (DUs) are persistent and challenging complications of diabetes. The consequences of DUs include a decline in functional status, increased risk of infection, hospitalization, and even death. Our study revealed a significant decrease in the levels of cortistatin (CST) in the skin tissue of patients with DUs and diabetic rats. This finding led us to hypothesize that the administration of exogenous CST is an effective strategy to promote wound healing in patients with DUs. We herein successfully prepared CST-loaded pDMA-pEPEMA nanoparticles (CST@NPs) designed to exhibit localized, acid-responsive behavior for enhanced wound healing. These CST@NPs were sensitive to acidic environments, triggering the rapid release of CST. In vitro experiments showed that CST@NPs effectively alleviated oxidative stress and reduced apoptosis in human umbilical vein endothelial cells (HUVECs). Our findings further demonstrated that CST@NPs accelerated re-epithelialization of the wound, enhanced collagen deposition, and stimulated angiogenesis, while alleviating the local inflammatory response. Both in vivo and in vitro results indicate that CST@NPs possess precise and rapid response capabilities in acidic environments, ensuring effective CST release to promote diabetic wound healing. In summary, this acid-responsive nanoparticle system presents a highly efficient therapeutic strategy for the treatment of chronic diabetic wounds.

Chaotic systems exhibit a random behavior that may result in undesired system performance. In this context, diverse strategies have been proposed to control the chaos that appears in various areas of applications. Most of them presented in the deterministic case without taking the environmental noises into account, although many systems in practice are often-times exposed to some external disturbances that affect the structure of the considered system. The key aim in this article is to stabilize a chaotic finance model (CFM) by designing feedback controllers in the stochastic and fractional cases. Firstly, we establish a novel set of suitable hypotheses to demonstrate the uniqueness of solutions. Secondly, we discuss the Hyers–Ulam stability (HUS) and the generalized HUS for the controlled CFM under sufficient conditions. Finally, we provide several examples attached with numerical findings which clearly support the validity of theoretical findings and highlight their benefits. The numerical simulations are done based on the Euler–Maruyama method and with the help of Lagrange polynomial interpolation, enabling the authors to extract meaningful results from the model. Compared to the existing CFMs, the present study proposes a novel type of nonlinear controller for the stabilization of the fractional stochastic CFM, providing a substantial analysis based on the HUS theory and computer simulation results to verify the rapid convergence of the state variables to the origin.

Aflatoxin B1 (AFB1), an important fungal toxin, exists mainly in plant feed ingredients and animals consuming feed contaminated with AFB1 will have reduced growth and impaired health condition mainly due to oxidative stress and reduced immunity. Our previous study found that AFB1 caused oxidative damage and inhibited muscle development of zebrafish. 4-Methylesculetin (4-ME), a coumarin derivative, is now used in biochemistry and medicine widely because of its antioxidant function. Whether 4-ME could alleviate the inhibition of muscle development in grass carp induced by AFB1 has not been reported. In this experiment, 720 healthy grass carp (11.40 ± 0.01 g) were randomly divided into 4 groups with 3 replicates of 60 fish each, including control group, AFB1 group (60 μg/kg diet AFB1), 4-ME group (10 mg/kg diet 4-ME), and AFB1+4-ME group (60 μg/kg diet AFB1 + 10 mg/kg 4-ME diet), for a 60-d growth experiment. In vitro, we also set up 4 treatment groups for grass carp primary myoblast, including control group, AFB1 group (15 μmol/L AFB1), 4-ME group (0.5 μmol/L 4-ME) and AFB1+4-ME group (15 μmol/L AFB1+0.5 μmol/L 4-ME). The results showed that dietary AFB1 decreased growth performance of grass carp, damaged the ultrastructure and induced oxidative damage in grass carp muscle, and significantly decreased the mRNA and protein expression levels of myogenin (MyoG), myogenic differentiation (MyoD), myosin heavy chain (MYHC), as well as the protein expression levels of laminin β1, fibronectin and collagen Ⅰ (P

The Pacific white shrimp or white leg shrimp, Penaeus vannamei, is native to the tropical coastal regions of Central and South America. It is one of the three major shrimp species with high production worldwide. It was brought from Hawaii, USA, in 1988 and introduced into China. It has been widely promoted and cultivated due to its adaptability to the environment, fast growth rate, and suitability for high-density industrial farming. As of 2022, China's total production of P. vannamei reached 2.09 million tons, accounting for > 90% of the country's total shrimp farming production. It has become one of the pillar industries in China's aquaculture sector.With the continuous expansion of aquaculture, diseases are becoming increasingly severe. Among them, acute hepatopancreatic necrosis disease (AHPND) hinders the development of the global shrimp farming industry and causes catastrophic economic losses. After infection, most shrimp show hepatopancreatic enlargement, which appears pale white or light yellow. In the later stages of infection, some diseased shrimp may exhibit atrophy of the hepatopancreas, appearing reddish-brown and blackened, with a hardened texture. Within 20–30 d after infection, death can occur, with a mortality rate of up to 90%. As of 2021, the economic losses caused by this disease to the major P. vannamei farming areas (China, Malaysia, Thailand, Vietnam, and Mexico) have exceeded 43 billion US dollars. Cultivating novel P. vannamei germplasm with AHPND resistance is an effective way to solve AHPND.Recently, domestic researchers have established independent shrimp breeding systems and cultivated 12 novel P. vannamei strains, such as "Hai Xing Nong No.2", "Ren Hai No.1", and "Zheng Jin Yang No.1". These varieties mainly target traits such as growth, resistance to white spot syndrome virus, farming survival rate, and temperature, salinity, and ammonia nitrogen tolerance. However, no reports of novel varieties specifically targeting AHPND resistance are available. Growth traits are essential economic traits in the genetic breeding of aquatic animals. Among the 12 novel P. vannamei varieties in China, 11 have excellent traits related to growth. Evaluating the genetic relationship between growth and AHPND resistance in the core breeding population of P. vannamei is important for fully utilizing existing high-quality germplasm and breeding novel varieties with composite traits and AHPND resistance.Genetic parameters reflect the genetic variation of target traits in a breeding population and are important references for breeding decisions. Due to the complex genetic background of existing P. vannamei germplasm resources in China, genetic parameters are influenced considerably by the tested population, infection methods, and other factors. Before breeding, stable infection tests must be conducted on the base population and obtain accurate parameters.This study used two independently bred P. vannamei strains as research objects to test their growth and AHPND resistance. Among them, 40 families were selected for high resistance (20 individuals per family, total 800 experimental individuals), and 30 families were selected for fast growth (32 individuals per family, total 960 experimental individuals). The test was conducted at P70–P90 by feeding with VpAHPND quantitative oral infection. Feeding with toxic bait was stopped after 50% of the experimental individuals died. The genetic heritability and correlation of the weight, individual survival time after VpAHPND infection, and half-lethal survival rate of the two strains were evaluated using individual animal and male and female threshold models. The results showed that the weight heritability estimate of the highly resistant strain was 0.599±0.120, indicating a high level of genetic heritability. The heritability estimates of survival time and half-lethal survival rate were 0.240±0.072 and 0.173±0.051, respectively, indicating a moderate to low level of genetic heritability, and all significantly different from 0 (P < 0.01). The weight heritability estimate of the fast-growth strain was 0.266±0.082, indicating a low level of genetic heritability. The heritability estimates of survival time and half-lethal survival rate were 0.374± 0.096 and 0.257±0.048, respectively, indicating a moderate level of genetic heritability, and all significantly different from 0 (P < 0.01). The genetic correlation between weight and AHPND resistance traits (survival time and half-lethal survival rate) in both strains showed a low positive correlation (0.061–0.235), and no significant difference was observed from 0 (P > 0.05). The genetic correlation between survival time and half-lethal survival rate in both strains was highly positively correlated, with estimates of 0.997±0.129 and 0.967±0.044, respectively. The results indicate that growth and AHPND resistance can be included as selection indicators in the comprehensive selection index for breeding and seed production in the actual breeding process. Under limited conditions, the infection program can be simplified, and the half-lethal survival rate can be used as the AHPND resistance indicator for the breeding population. This study provides a primary reference for utilizing existing germplasm resources to develop high-quality P. vannamei strains for growth and AHPND resistance breeding.

Extracellular microRNA (miRNA) expression data generated by different laboratories exhibit heterogeneity, which poses challenges for biologists without bioinformatics expertise. To address this, we introduce ExomiRHub (http://www.biomedical-web.com/exomirhub/), a user-friendly database designed for biologists. This database incorporates 191 human extracellular miRNA expression datasets associated with 112 disease phenotypes, 62 treatments, and 24 genotypes, encompassing 29,198 and 23 sample types. ExomiRHub also integrates 16,012 miRNA transcriptomes of 156 cancer subtypes from The Cancer Genome Atlas. All the data in ExomiRHub were further standardized and curated with annotations. The platform offers 25 analytical functions, including differential expression, co-expression, Weighted Gene Co-Expression Network Analysis (WGCNA), feature selection, and functional enrichment, enabling users to select samples, define groups, and customize parameters for analyses. Moreover, ExomiRHub provides a web service that allows biologists to analyze their uploaded miRNA expression data. Four additional tools were developed to evaluate the functions and targets of miRNAs and miRNA variations. Through ExomiRHub, we identified extracellular miRNA biomarkers associated with angiogenesis for monitoring glioma progression, demonstrating its potential to significantly accelerate the discovery of extracellular miRNA biomarkers.

Adenoid cystic carcinoma (ACC) is a rare malignancy predominantly found in the salivary, lacrimal, upper gastrointestinal, and respiratory mucosal glands; adenoid cystic carcinoma of the external auditory canal (EAC) is particularly rare. Characterized by a proclivity for recurrence and metastasis, advanced adenoid cystic carcinoma often proves refractory to conventional chemotherapy. Novel therapeutic approaches, notably targeted therapies, are imperative to enhance treatment response rates in advanced adenoid cystic carcinoma patients. Herein, we present a case of primary adenoid cystic carcinoma affecting the right external auditory canal in a 56-year-old male presenting with symptoms of pruritus, swelling, pain, and hearing loss in the affected ear. Despite multiple attempts with diverse chemotherapy regimens yielding no success, the patient developed advanced lung metastases, prompting the utilization of anlotinib-targeted therapy. Subsequent administration of anlotinib led to a partial remission (PR), resulting in approximately 8 months of progression-free survival (PFS) in this individual.

RNA-binding proteins (RBPs) are key post-transcriptional regulators, and the malfunctions of RBP-RNA binding lead to diverse human diseases. However, prediction of RBP binding sites is largely based on RNA sequence features, whereas in vivo RNA structural features based on high-throughput sequencing are rarely incorporated. Here, we designed a deep bimodal information fusion network called DeepFusion for unraveling protein-RNA interactions by incorporating structural features derived from DMS-seq data. DeepFusion integrates two sub-models to extract local motif-like information and long-term context information. We show that DeepFusion performs best compared with other cutting-edge methods with only sequence inputs on two datasets. DeepFusion’s performance is further improved with bimodal input after adding in vivo DMS-seq structural features. Furthermore, DeepFusion can be used for analyzing RNA degradation, demonstrating significantly different RBP-binding scores in genes with slow degradation rates versus those with rapid degradation rates. DeepFusion thus provides enhanced abilities for further analysis of functional RNAs. DeepFusion’s code and data are available at http://bioinfo.org/deepfusion/.

Objective To explore the factors that affect the coordinated development of blood banks and apheresis plasma collection banks (hereinafter referred to as plasma banks), and explore feasible measures for the coordinated development of blood banks and plasma banks. Methods The blood information management system and blood source information management system were used to retrieve related data of blood and plasma donation from 9 cities in Shandong province from 2017 to 2021. The number of blood donors and plasma donors and the intersection of them were analyzed. The data analysis was performed using chi-square test, and a questionnaire survey was conducted to investigate the policies and information status, as well as expectations for coordinated development for blood and plasma donation. Results From 2017 to 2021, the total number of blood donors in 9 cities was higher than that of plasma donors, both have been increasing year by year, and the increase in plasma donors was significantly higher than that of blood donors (131.78% vs 23.90%, P

This paper is concerned with a class of viscoelastic plate equations with past history. We first transform the original initial-boundary value problem into an equivalent one by means of the history space framework. Then we use the perturbed energy method to establish a stabilizability estimate. By employing the gradient property and quasi-stability of the dynamical system, we obtain the existence of a global attractor with finite fractal dimension.

Green and low-carbon is a new development model that seeks balance between environmental sustainability and high economic growth. If explainable and available carbon emission data can be accurately obtained, it will help policy regulators and enterprise managers to more accurately implement this development strategy. A lot of research has been carried out, but it is still a difficult problem that how to accommodate and adapt the complex carbon emission data computing models and factor libraries developed by different regions, different industries and different enterprises. Meanwhile, with the rapid development of the Industrial Internet, it has not only been used for the supply chain optimization and intelligent scheduling of the manufacturing industry, but also been used by more and more industries as an important way of digital transformation. Especially in China, the Industrial Internet identification and resolution system is becoming an important digital infrastructure to uniquely identify objects and share data. Hence, a compatible carbon efficiency information service framework based on the Industrial Internet Identification is proposed in this paper to address the problem of computing and querying multi-source heterogeneous carbon emission data. We have defined a multi cooperation carbon emission data interaction model consisting of three roles and three basic operations. Further, the implementation of the framework includes carbon emission data identification, modeling, calculation, query and sharing. The practice results show that its capability and effectiveness in improving the responsiveness, accuracy, and credibility of compatible carbon efficiency data query and sharing services.

Abstract The development of unstable carotid atherosclerotic plaques is associated with the induction of neutrophil extracellular traps (NETs) via the activation of diverse inflammatory mediators in the circulating bloodstream. However, the underlying mechanisms through which NETs influence the microenvironment of atherosclerotic plaques and contribute to the development of unstable carotid plaques remain largely elusive. The objective of this study was to elucidate the role of myeloid differentiation protein 1 (MD-1, LY86)-induced NETs underlying the crosstalk between unstable plaque formation and the plaque microenvironment. We employed bioinformatics analysis to identify key genes associated with carotid-unstable plaque, followed by comprehensive validation using various experimental approaches on tissue specimens and plasma samples classified based on pathological characteristics. Patients with carotid-unstable plaques exhibited elevated plasma concentrations of MD-1 (LY86), while patients with stable plaques demonstrated comparatively lower levels. Furthermore, soluble MD-1 was found to induce the formation of NETs through activation of Toll-like receptor signaling pathway. The proliferative and immature vascularization effects of NETs on endothelial cells, as well as their inhibitory impact on cell migration, are directly correlated with the concentration of NETs. Additionally, NETs were found to activate the NF-κB signaling pathway, thereby upregulating ICAM1, VCAM1, MMP14, VEGFA, and IL6 expression in both Human umbilical vein endothelial cells (HUVECs) and HAECs. Subsequently, a significant increase in intraplaque neovascularization by NETs results in poor carotid plaque stability, and NETs in turn stimulate macrophages to produce more MD-1, generating a harmful positive feedback loop. Our findings suggest that soluble MD-1 in the bloodstream triggers the production of NETs through activation of the Toll-like receptor signaling pathway and further indicate NETs mediate a crosstalk between the microenvironment of the carotid plaque and the neovascularization of the intraplaque region. Inhibiting NETs formation or MD-1 secretion may represent a promising strategy to effectively suppress the development of unstable carotid plaques.

Abstract Background There are few studies on death education models for nursing students in China. It is of great significance to construct a model of nursing students’ death education combined with clinical practice. This study aims to evaluate the effect of death education on nursing students based on the Peace of Mind Tea House. Methods The randomized controlled trial commenced from February 7 to March 18, 2021,featuring a two-month intercession at a hospital situated in Xiamen, China. The research subjects were chosen using a convenient sampling approach with nursing students from the hospital's internship program. Ninety-two participants were enrolled, with 46 in each group. Thirteen participants were lost to follow-up, corresponding to 14% of the total study population. The samples were then allocated randomly into either the intervention group or the control group. In addition to their hospital internship, the intervention group participated in six death education courses that focused on cognitive, emotional, and motor skills as well as the “Peace of Mind Tea House” program. Control participants will undergo regular internships. Before and two weeks after the course, both groups were evaluated for death anxiety, attitude towards death, and the meaning of life to assess the intervention's effectiveness. Results In the fear of death item of the Death Attitude Scale and the meaning of life section, the post-test score minus the pre-test score of the intervention group were 2.50 ± 3.90 (p = 0.011), and 8.90 ± 11.07 (p = 0.035), respectively. During the communication and sharing session of the reassurance card activity, 41 participants (95.3%) found the activity meaningful. Conclusion Our data analysis demonstrates that nursing students have accepted and acknowledged the Peace of Mind Tea House-based education on death, which positively impacted their attitudes towards deathand the meaning of life. The content of death education should be integrated with traditional culture, and a new model of death education should be constructed with the Heart to Heart cards as its core. This research presents proof of the efficacy of implementing appropriate death education for nursing students, and provides a successful intervention plan to alleviate their future death anxiety and develop a positive outlook on death. Trial registration This study was approved by the Ethical Committee of Xiamen University School of Medicine (No. XDYX202304K21)(Date:18/01/2021). Written consent to participate was obtained from all the students.

Abstract Hepatocellular carcinoma (HCC) is the primary malignant tumor of the liver. c-Myc is one of the most common oncogenes in clinical settings, and amplified levels of c-Myc are frequently found in HCC. Histone deacetylase inhibitors (HDACi), such as Trichostatin A (TSA), hold enormous promise for the treatment of HCC. However, the potential and mechanism of TSA in the treatment of c-Myc-induced HCC are unclear. In this study, we investigated the effects of TSA treatment on a c-Myc-induced HCC model in mice. TSA treatment delayed the development of HCC, and liver function indicators such as ALT, AST, liver weight ratio, and spleen weight ratio demonstrated the effectiveness of TSA treatment. Oil red staining further demonstrated that TSA attenuated lipid accumulation in the HCC tissues of mice. Through mRNA sequencing, we identified that TSA mainly affected cell cycle and fatty acid degradation genes, with alcohol dehydrogenase 4 (ADH4) potentially being the core molecular downstream target. QPCR, immunohistochemistry, and western blot analysis revealed that ADH4 expression was repressed by c-Myc and restored after TSA treatment both in vitro and in vivo. Furthermore, we observed that the levels of total NAD+ and NADH, NAD+, NAD+/NADH, and ATP concentration increased after c-Myc transfection in liver cells but decreased after TSA intervention. The levels of phosphorylated protein kinase B (p-AKT) and p-mTOR were identified as targets regulated by TSA, and they governed the ADH4 expression and the downstream regulation of total NAD+ and NADH, NAD+, NAD+/NADH, and ATP concentration. Overall, our study suggests that TSA has a therapeutic effect on c-Myc-induced HCC through the AKT-mTOR-ADH4 pathway. These findings provide valuable insights into the potential treatment of HCC using TSA and shed light on the underlying molecular mechanisms involved.

Abstract Background Remnant cholesterol (RC) exert a significant influence on atherosclerotic cardiovascular disease development. However, the prognostic implications of RC in menopausal women received percutaneous coronary intervention (PCI) who experiencing acute coronary syndrome (ACS) remain uncertain. Methods RC was derived by subtracting the sum of high-density lipoprotein cholesterol and low-density lipoprotein cholesterol from the total cholesterol. Kaplan-Meier survival and Cox regression analysis were employed for assessing the correlation between continuous RC levels and composite and individual adverse events in Q1-Q4 quartiles. Receiver operator characteristic (ROC) curves, derived from Cox regression, were employed for analyzing the relationship between RC and both composite and individual adverse events. Results 1505 consecutive menopausal women who underwent PCI and diagnosed with ACS were included. Kaplan-Meier survival analysis demonstrated a progressive reduction in composite adverse event survival rates across the four groups, observed in both the general population and among diabetic individuals, as RC values increased (Log-rank P

Soil salinization/alkalization is a complex environmental factor that includes not only neutral salt NaCl but also other components like Na2CO3. miRNAs, as small molecules that regulate gene expression post-transcriptionally, are involved in plant responses to abiotic stress. In this study, maize seedling roots were treated for 5 h with 100 mM NaCl, 50 mM Na2CO3, and H2O, respectively. Sequencing analysis of differentially expressed miRNAs under these conditions revealed that the Na2CO3 treatment group had the most differentially expressed miRNAs. Cluster analysis indicated their main involvement in the regulation of ion transport, binding, metabolism, and phenylpropanoid and flavonoid biosynthesis pathways. The unique differentially expressed miRNAs in the NaCl treatment group were related to the sulfur metabolism pathway. This indicates a significant difference in the response patterns of maize to different treatment groups. This study provides theoretical evidence and genetic resources for further analysis of the molecular mechanisms behind maize’s salt–alkali tolerance.

Purpose This study investigates shifts in scientific research focus, particularly the decline in COVID-19-related research and the rapid growth of artificial intelligence (AI) publications. Methods We analyzed publication data from the Web of Science, comparing yearly publication counts for COVID-19 and AI research. The study also tracked changes in the impact factors of leading journals like Science and Nature, alongside those of top AI journals over the past decade. Additionally, we reviewed the top 10 most cited articles in 2021 from Science and Nature and the most influential AI publications from the past five years according to Google Scholar. The impact trends of the top 100 AI journals in computer science were also explored. Results The analysis reveals a noticeable decline in COVID-19 related publications as the pandemic urgency diminishes, contrasted with the continued rapid growth of AI research. Impact factors for prestigious journals have shifted, with AI journals increasingly dominating the academic landscape. The review of top-cited articles further emphasizes these trends. Conclusion Our findings indicate a significant shift in research priorities, with AI emerging as a dominant field poised to address future challenges, reflecting the evolving focus of the scientific community.

Abstract In order to study the mechanics, acoustic emission (AE) and electromagnetic emission (EME) response law of bursting liability coal at different loading rates, uniaxial compression tests were carried out on coal mass from Konggu Coal Mine. The corresponding relations among mechanical properties, AE and EME signals in the process of coal failure under loading were analyzed, and the energy evolution law of coal failure with bursting liability under loading rate was discussed. The results show that within a certain range of loading rate, the higher the loading rate, the higher the compressive strength and peak load of bursting liability coal, and the shorter the time for coal to reach the peak load. Under different loading rates, the mechanics, AE and EME signals of coal samples can be well corresponded. When the loading rate is low, the number of blocks destroyed of coal sample is large and the block size is relatively small, and the blocks are mainly scattered around the test platform. When the loading rate is high, the number of damaged blocks is relatively small and the block size is relatively large, and the blocks are far away from the test bench. When loading at a low rate, the internal cracks in coal can be fully developed and connected, and the energy release rate is relatively uniform in the process of loading and failure of coal sample. In the case of high loading rate, the energy release rate of coal sample in the loading process is much smaller than that in the moment of failure. Combining the above test results with the actual situation of the working face, it can be concluded that the total energy stored in the coal of fast mining increases and the threshold of impact decreases compared with that of slow mining. Therefore, under the disturbance of external dynamic load, rapid mining is more likely to induce rock burst.

Abstract Background Empowerment is a comprehensive concept involving intrapersonal, interactional, and behavioral aspects. However, there is a lack of a specific empowerment scale for Coronary artery disease (CAD) related to knowledge and skills in China. The reliability and validity of the Coronary Artery Disease Empowerment Scale (CADES) need to be tested. This study aimed to assess the reliability and validity of the Chinese version of CADES among patients with CAD in China. Methods The study adopted a cross-sectional design. After obtaining the copyright by contacting the author, the original English CADES was developed into Chinese by forward translation, back-translation, cross-cultural adaptation, and a pretest (30 patients). The Chinese version of CADES was administered to 391 CAD patients between September 2022 and June 2023, with the reliability and validity of the version evaluated. Exploratory factor analysis and confirmatory factor analysis were performed to examine the underlying factor structure of the translated questionnaire. The Cronbach’s α coefficient, Guttman’s split-half coefficient, and McDonald’s omega coefficient were calculated to verify the scale’s reliability. Results For the Chinese version of CADES, the scale-content validity index was 0.972, with the item-content validity index ranging from 0.86 to 1.00. The questionnaire comprised 25 items, and exploratory factor analysis extracted four factors with loadings > 0.40, explaining 62.382% of the total variance. An acceptable model fit was achieved (χ2/df = 1.764, RMSEA = 0.060, TLI = 0.901, CFI = 0.912, IFI = 0.913). The Cronbach’s α coefficient of the total questionnaire was 0.928, with coefficients for the four factors ranging from 0.683 to 0.913. The split-half reliability coefficient was 0.777, and the McDonald’s omega reliability coefficient was 0.926. Conclusions The Chinese version of CADES is reliable and valid among CAD patients in China. This instrument can serve as a valuable reference for guiding the implementation of targeted intervention strategies tailored to the empowerment status of CAD patients in clinical practice.

Abstract This single-arm phase 2 trial (ChiCTR2100046715) examined previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) who received four cycles of paclitaxel with carboplatin every 3 weeks. Toripalimab was infused intravenously every 3 weeks for 12 months, or until disease progression or intolerable toxicity. Radiotherapy that encompassed the primary lesions and metastases commenced in the third cycle. The median progression-free survival time was 9.8 months (95% confidence interval [CI]: 6.8–not estimable) in the intent-to-treat population, failing to meet the pre-specified primary endpoints. Secondary endpoints included an objective response rate of 45.5%, a disease control rate of 57.6%, and a median duration of response of 11.5 months (interquartile range, 6.4–15.0). The 1-year progression-free survival and overall survival rates were 41.9% (95% CI: 27.7–63.5) and 69.7% (95% CI: 55.7–87.3), respectively. Lymphopenia was the most frequent grade ≥3 adverse event (82%), and an esophageal fistula developed in three patients (9.1%). No treatment-related deaths occurred. In prespecified exploratory biomarker analysis, higher densities of CD8 + T cells, CD11c+ dendritic cells, and CD68+ macrophages correlated with improved tumor response and prognosis. Radiotherapy supplementation to first-line chemo-immunotherapy for treatment-naive advanced ESCC demonstrated some antitumor activity and manageable safety profiles, warranting further randomized controlled trials.

Abstract Background There are many options for the surgical treatment of pronation external rotation (PER) type IV ankle fractures, including the use of fibular plates and screws, the aim of this study was to investigate the biomechanical stability and safety of different internal fixation methods for PER type IV ankle fractures via finite element analysis. Methods A three-dimensional finite element model of the ankle joint and the whole foot of a healthy 26-years-old adult male was established and validated based on computed tomography images of his lower limb, and a computer-aided design was used to produce a PER type IV ankle fracture and plate and screw model. Four different internal fixation modes were simulated, including a (all ankle fixation—utilizing a fibular plate and screws for comprehensive stabilization of the ankle), b (inferior tibiofibular joint fixation + all ankle fixation), c (inferior tibiofibular joint fixation + unfixed anterior ankle), and d (inferior tibiofibular joint fixation + unfixed anterior and posterior ankles). The results of the four different fixation methods were compared via finite element analysis, and the von Mises stresses. The displacements of the four different fixation methods were analyzed as the output indices. Results There were no significant differences between the results of using fibular plates and screws and the displacement of fracture breaks among the four internal fixation modalities. The von Mises stress in the tibiotalar joint, median ankle, posterior ankle, and anterior ankle was minimized in the working condition of d, d, b, and d respectively. The von Mises stress in the fibular plate and screws was minimized in the working condition of a. The von Mises stress in the distal fibula was minimized in the working condition of a. However, the stress was mainly concentrated at the attachment point of the inferior tibiofibular anterior ligament, and in the working condition with inferior tibiofibular joint fixation, the stress was significantly concentrated in the inferior tibiofibular joint screw in all the fibular plates and screws. Conclusions The results of this study demonstrate the feasibility of using finite element analysis to compare the biomechanical stability and safety of four configurations of fibular plates and screws for treating PER type IV ankle fractures. All four modalities provided comparable biomechanical stability and safety, showing no significant differences. However, the current limitations of the finite element analysis methodology preclude specific clinical inferences. Further refinement of the methodology in future studies is necessary to enable reliable clinical applications.

Highlights A novel cascade strategy is proposed to construct Pd-NiCo2O4 electrocatalyst. First time discovery that Ni incorporation together with Pd loading is able to balance the competitive adsorption of OH– and 5-hydroxymethylfurfural. Pd–NiCo2O4 promotes both the indirect and direct synergistic oxidation process. Pd–NiCo2O4 catalyst exhibits extraordinary current density and excellent Faradaic Efficiency at a low potential.

Abstract Tumor cells can survive when detached from the extracellular matrix (ECM) or lose cell–cell connections, a phenomenon known as anoikis-resistance (AR). AR is closely associated with tumor cell metastasis and recurrence, enabling tumor cells to disseminate, migrate, and invade after detachment. To address this issue, a novel intervention method combining intraoperative hemostasis with multifunctional nanozyme driven-enhanced chemodynamic therapy (ECDT) has been proposed, which holds the potential to weaken the AR capability of tumor cells and suppress tumor recurrence. Here, a nanocomposite containing a dendritic mesoporous nanoframework with Cu2+ was developed using an anion-assisted approach after surface PEG grafting and glucose oxidase (GOx) anchoring (DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG was further encapsulated in a thermal-sensitive hydrogel (H@DMSN-Cu@GOx/PEG). DMSN-Cu@GOx/PEG utilizes its high peroxidase (POD) activity to elevate intracellular ROS levels, thereby weakening the AR capability of bladder cancer cells. Additionally, through its excellent catalase (CAT) activity, DMSN-Cu@GOx/PEG converts the high level of hydrogen peroxide (H2O2) catalyzed by intracellular GOx into oxygen (O2), effectively alleviating tumor hypoxia, downregulating hypoxia-inducible factor-1α (HIF-1α) expression, inhibiting epithelial-mesenchymal transition (EMT) processes, and ultimately suppressing the migration and invasion of bladder cancer cells. Interestingly, in vivo results showed that the thermosensitive hydrogel H@DMSN-Cu@GOx/PEG could rapidly gel at body temperature, forming a gel film on wounds to eliminate residual tumor tissue after tumor resection surgery. Importantly, H@DMSN-Cu@GOx/PEG exhibited excellent hemostatic capabilities, effectively enhancing tissue coagulation during post-tumor resection surgery and mitigating the risk of cancer cell dissemination and recurrence due to surgical bleeding. Such hydrogels undoubtedly possess strong surgical application. Our developed novel nanosystem and hydrogel can inhibit the AR capability of tumor cells and prevent recurrence post-surgery. This study represents the first report of using dendritic mesoporous silica-based nanoreactors for inhibiting the AR capability of bladder cancer cells and suppressing tumor recurrence post-surgery, providing a new avenue for developing strategies to impede tumor recurrence after surgery. Graphical Abstract

In order to solve the problem of image denoising in irradiation fields such as nuclear waste disposal hot cells，this study made corresponding improvements to the algorithm based on the idea of median filtering for radiation noise points，and finally proposed an algorithm suitable for image denoising in strong irradiation fields. The algorithm process is divided into three steps: noise recognition，noise processing and detail protection. Noise recognition starts from visual perception. If the pixel value is higher than its surrounding value and reaches the set threshold，it is marked as suspicious. By setting the maximum area threshold of radiation noise，the area larger than the threshold is excluded. The idea of median filtering is used to deal with noise，and the size of filtering window is adjusted adaptively. The protection of detail borrows from the idea of image fusion. Compared with other noise reduction algorithms，the results show that the proposed algorithm is accurate in the identification of radiated noise points，has obvious noise reduction effect，and protects the details of the picture to the greatest extent. The algorithm demonstrates good robustness under radiation environments with different dose rates，and still achieves effective denoising even under a strong irradiation field of 100 Gy/h. This can provide technical support for intelligent applications in nuclear waste disposal.

Abstract Background Anxiety and depression are prevalent comorbidities in patients with chronic obstructive pulmonary disease (COPD). However, existing research has yielded conflicting findings regarding the effects of social frailty on anxiety and depression. The primary aim of this study is to validate the relationship between social frailty and social support with anxiety and depression in patients with acute exacerbations of COPD (AECOPD) and to investigate whether social support could explain the variations in prior study outcomes for patients with AECOPD. Methods Of the 315 patients hospitalized with AECOPD at the respiratory intensive care unit of a large tertiary care institution in Sichuan Province of China, between August 2022 and June 2023 who were surveyed, 306 were included in the analysis after excluding missing data. We conducted a logistic regression analysis to examine the associations of social frailty and social support with anxiety and depression and performed mediation analyses to examine whether social support mediates the relationship of social frailty with anxiety and depression. Results The logistic regression analysis revealed that social frailty did not associate anxiety or depression in patients with AECOPD. The mediation analysis supported this idea and indicated that while social frailty does not directly influence anxiety or depression, it can through social support. Conclusions The findings suggest that while social frailty may not directly impact anxiety or depression in patients with AECOPD, social support plays a crucial mediating role. Enhancing social support can indirectly alleviate anxiety and depression among these patients. Enhancing social support networks should thus be prioritized by healthcare providers and family members to improve mental health outcomes in this patient population.

Abstract Background Human adipose-derived stem cells (ADSCs) exert a strong anti-inflammatory effect, and synovium-derived stem cells (SDSCs) have high chondrogenic potential. Thus, this study aims to investigate whether a combination of human ADSCs and SDSCs will have a synergistic effect that will increase the chondrogenic potential of osteoarthritis (OA) chondrocytes in vitro and attenuate the cartilage degeneration of early and advanced OA in vitro. Methods ADSCs, SDSCs, and chondrocytes were isolated from OA patients who underwent total knee arthroplasty. The ADSCs–SDSCs mixed cell ratios were 1:0 (ADSCs only), 8:2, 5:5 (5A5S), 2:8, and 0:1 (SDSCs only). The chondrogenic potential of the OA chondrocytes was evaluated in vitro with a transwell assay or pellet culture with various mixed cell groups. The mixed cell group with the highest chondrogenic potential was then selected and injected into the knee joints of nude rats of early and advanced OA stages in vivo. The animals were then evaluated 12 and 20 weeks after surgery through gait analysis, von frey test, microcomputed tomography, MRI, and immunohistochemical and histological analyses. Finally, the mechanisms underlying these findings were investigated through the RNA sequencing of tissue samples in vivo and Western blot of the OA chondrocyte autophagy pathway. Results Among the MSCs treatment groups, 5A5S had the greatest synergistic effect that increased the chondrogenic potential of OA chondrocytes in vitro and inhibited early and advanced OA in vivo. The 5A5S group significantly reduced cartilage degeneration, synovial inflammation, pain sensation, and nerve invasion in subchondral nude rat OA, outperforming both single-cell treatments. The underlying mechanism was the activation of chondrocyte autophagy via the FoxO1 signaling pathway. Conclusion A combination of human ADSCs and SDSCs demonstrated higher potential than a single type of stem cell, demonstrating potential as a novel treatment for OA.

Abstract Radiation-free one-stage bedside endoscopic stone removal and biliary drainage for severe acute cholangitis (SAC) caused by choledocholithiasis in intensive care unit (ICU) has not been reported. Herein, we introduce our preliminary experience of such intervention. Radiation-free bedside digital cholangioscope-assisted one-stage endoscopic stone removal and biliary drainage was performed in an urgent manner. Data on clinical outcomes and follow-up from thirty patients were retrospectively analyzed. Time interval was 7.6 ± 4.7 (2–18) h between ICU admission and endoscopic intervention, and was 35.5 ± 14.5 (5–48) h between the seizure and endoscopic intervention. A 100% technical success was achieved. Except for one mild pancreatitis, no other complication occurred. Patients showed good responses to endoscopic interventions, which were reflected by ameliorated disease severities and laboratory findings. Time lengths of ICU stay and total in-hospital stay were 8.7 ± 4.9 (2–23) days and 14.5 ± 7.4 (5–39) days, respectively. In-hospital mortality occurred in three patients. According to a 6-month follow-up, two patients died of pneumonia and acute myocardial infarction. No SAC and/or biliary stone residual occurred. The current intervention demonstrated favorable results compared to traditional endoscopic retrograde cholangiopancreatography. Our study provides a novel bedside endoscopic intervention method for SAC caused by choledocholithiasis.

Abstract Background The prognosis nutritional index (PNI) and the systemic inflammatory immunological index (SII) are characteristic indicators of the nutritional state and the systemic inflammatory response, respectively. However, there is an unknown combined effect of these indicators in the clinic. Therefore, the practicality of using the SII-PNI score to predict prognosis and tumor response of locally advanced gastric cancer (LAGC) following chemotherapy was the main focus of this investigation. Methods We retrospectively analyzed 181 patients with LAGC who underwent curative resection after neoadjuvant chemotherapy in a prospective study (NCT01516944). We divided these patients into tumour regression grade(TRG) 3 and non-TRG3 groups based on tumor response (AJCC/CAP guidelines). The SII and PNI were assessed and confirmed the cut-off values before treatment. The SII-PNI values varied from 0 to 2, with 2 being the high SII (≥ 471.5) as well as low PNI (≤ 48.6), a high SII or low PNI is represented by a 1 and neither is represented by a 0, respectively. Results 51 and 130 samples had TRG3 and non-TRG3 tumor responses respectively. Patients with TRG3 had substantially higher SII-PNI scores than those without TRG3 (p

Abstract Glycosphingolipids (GSLs) are abundantly expressed in cancer cells. The effects of GSL-targeted immunotherapies are not fully understood. Here, we show that the inhibition of GSL synthesis with the UDP-glucose ceramide glucosyltransferase inhibitor eliglustat can increase the exposure of the major histocompatibility complex (MHC) and tumour antigen peptides, enhancing the antitumour response of CD8+ T cells in a range of tumour models. We therefore conducted a proof-of-concept phase I trial on the combination of eliglustat and an anti-PD-1 antibody for the treatment of advanced cancers (NCT04944888). The primary endpoints were safety and feasibility, and the secondary endpoint was antitumor activity. All prespecified endpoints were met. Among the 31 enrolled patients, only 1 patient experienced a grade 3 adverse event (AE), and no grade 4 AEs were observed. The objective response rate was 22.6% and the disease control rate reached 71%. Of the 8 patients with proficient mismatch repair/microsatellite stable (pMMR/MSS) colorectal cancer, one achieved complete response and two each had partial response and stable disease. In summary, inhibiting the synthesis of GSLs might represent an effective immunotherapy approach.

Abstract The analysis of trace Pt single-atom (SA) represents a significant challenge, given the crucial role of single-atom platinum (Pt) in energy storage and electrocatalysis. Here, we present an electrochemiluminescence (ECL) platform that enables the qualitative and quantitative analysis of trace Pt SA using luminol as the ECL luminophore. It is observed that different Pt species in Ti3-xC2Ty MXenes resulted in distinct reactive oxygen species (ROS) potentials for luminol cathodic electrochemiluminescence (ECL), achieved through distinctive oxygen reduction reaction (ORR) pathways, in which oxygen acts as the co-reactant. Furthermore, the cathodic luminol ECL intensity increases in proportion to the Pt atom content, thereby enabling quantitative analysis of trace Pt single atoms. The detection limit is 0.014 wt%, which is comparable to the current mainstream Pt SA quantification techniques. By utilizing this ECL method, it is possible to successfully evaluate both qualitatively and quantitatively the changes in Pt SA during the ORR processes. This ECL platform provides a valuable toolbox for the analysis of Pt SA catalysts and for the evaluation of the mechanisms involved in electrocatalysis applications.

Abstract Background Globally, the majority of kindergarten-aged children face obesity issues and insufficient physical activity (PA) engagement. Regular PA participation can provide various health benefits, including obesity reduction, for kindergarten-aged children. However, limited studies have investigated the factors influencing kindergarten-aged children’s PA engagement from the perspective of their teachers. This qualitative study aimed to identify factors that could help promote PA among kindergarten-aged children from teachers’ perspectives, including facilitators, barriers, and teachers’ recommendations. Methods Fifteen kindergarten teachers (age range: 28–50 years; mean age: 38.53 years) with teaching experience ranging from 2 to 31 years (mean: 16.27 years) were recruited from Shanghai municipality, Henan, and Jiangsu provinces in China. One-on-one semi-structured interviews were conducted via face-to-face (n = 7) or telephone (n = 8) to gather insights into factors influencing PA promotion among kindergarten-aged children. The interviews were audio-recorded, transcribed, and analyzed using a constant comparison approach based on grounded theory, which involved open, axial, and selective coding processes. Results The study revealed mutual theoretical support between themes and the social-ecological model (SEM), as factors identified in the study are distributed at various levels of the SEM. Twelve factors were identified at four levels of the SEM: (1) intrapersonal level (children’s personality and skills), (2) interpersonal level (family, peers, and teachers influence), (3) organizational level (school environment and resources, opportunities for kindergarten teachers’ training and children’s PA, design and organization of PA, and PA that children need), (4) community level (family-school partnerships). Conclusion Various factors at different levels can influence kindergarten-aged children’s PA. The study’s findings revealed that these factors are distributed across the first four levels of SEM, with the majority being at the organizational level. These multilevel findings are expected to assist in developing and implementing more effective PA interventions for kindergarten-aged children. Future research is warranted to identify strategies for promoting PA among kindergarten-aged children at the policy level of the SEM.

Abstract We examine the descent via membrane nucleation through a landscape of vacua where the cosmological constant is given by a combination of four-form fluxes. It has been shown that this descent can be slowed exponentially for very low curvature vacua close to Minkowski space in a wide class of models satisfying certain parametric conditions, providing a possible solution to the cosmological constant problem. We explore in detail whether or not those parametric conditions are compatible with the membrane weak gravity conjecture. Whilst it is true that there is often tension, we show that this is not always the case and present an explicit model where Minkowski space is absolutely stable and the weak gravity conjecture is satisfied. This corresponds to an extension of the Bousso-Polchinski model into a generalised DBI action for four-forms. We also clarify how the landscape should be populated in a consistent model.

Abstract Background Impaired hospitalizations for heart failure (HHF) and mortality are associated with tricuspid regurgitation (TR). Objectives The objective of this study was to investigate the benefit of transcatheter tricuspid valve replacement (TTVR) over guideline-directed medical therapy (GDMT) in patients with symptomatic severe TR. Methods Between May 2020 and April 2023, 88 patients with symptomatic severe TR were treated in our center. Of these, 57 patients received GDMT alone, and 31 patients underwent combined TTVR and GDMT. We collected and analyzed baseline data, and follow-up information for both groups. The primary endpoints were all-cause mortality and the combined endpoint (including all-cause mortality and HHF). Results At a median follow-up of 20 (IQR 10–29) months, significant improvements were shown in TR severity, right ventricular function, and dimensions in TTVR group (all P

Abstract Background Frailty is a multifactorial syndrome; through this study, we aimed to investigate the physiological, psychological, and social factors associated with frailty and frailty worsening in community-dwelling older adults. Methods We conducted a cross-sectional and longitudinal study using data from the “Community Empowerment and Well-Being and Healthy Long-term Care: Evidence from a Cohort Study (CEC),” which focuses on community dwellers aged 65 and above in Japan. The sample of the cross-sectional study was drawn from a CEC study conducted in 2014 with a total of 673 participants. After excluding those who were frail during the baseline assessment (2014) and at the 3-year follow-up (2017), the study included 373 participants. Frailty assessment was extracted from the Kihon Checklist, while social relationships were assessed using the Social Interaction Index (ISI). Variable selection was performed using Least Absolute Shrinkage and Selection Operator (LASSO) regression and their predictive abilities were tested. Factors associated with frailty status and worsening were identified through the Maximum-min Hillclimb algorithm applied to Bayesian networks (BNs). Results At baseline, 14.1% (95 out of 673) participants were frail, and 24.1% (90 out of 373) participants experienced frailty worsening at the 3-years follow up. LASSO regression identified key variables for frailty. For frailty identification (cross-sectional), the LASSO model’s AUC was 0.943 (95%CI 0.913–0.974), indicating good discrimination, with Hosmer–Lemeshow (H–L) test p = 0.395. For frailty worsening (longitudinal), the LASSO model’s AUC was 0.722 (95%CI 0.656–0.788), indicating moderate discrimination, with H–L test p = 0.26. The BNs found that age, multimorbidity, function status, and social relationships were parent nodes directly related to frailty. It revealed an 85% probability of frailty in individuals aged 75 or older with physical dysfunction, polypharmacy, and low ISI scores; however, if their social relationships and polypharmacy status improve, the probability reduces to 50.0%. In the longitudinal-level frailty worsening model, a 75% probability of frailty worsening in individuals aged 75 or older with declined physical function and ISI scores was noted; however, if physical function and ISI improve, the probability decreases to 25.0%. Conclusion Frailty and its progression are prevalent among community-dwelling older adults and are influenced by various factors, including age, physical function, and social relationships. BNs facilitate the identification of interrelationships among these variables, quantify the influence of key factors. However, further research is required to validate the proposed model.

Abstract The active distribution network (ADN) can obtain measurement data, estimate system states, and control distributed energy resources (DERs) and flexible loads to ensure voltage stability. However, the ADN is more vulnerable to cyber attacks due to the recent wave of digitization and automation efforts. In this article, false data injection (FDI) attacks are focused on and they are classified into two types, that is, type I attacks on measurement data and type II attacks on control commands. After studying the impact of these two FDI attacks on the ADN, a new threat is revealed called coordinated FDI attack, which can maximize the voltage deviation by coordinating type I and type II FDI attacks. From the attacker's perspective, the scheme of CFDI is proposed and an algorithm is developed to find the optimal attack strategy. The feasibility of CFDI attacks has been validated on a smart distribution testbed. Moreover, simulation results on an ADN benchmark have demonstrated that CFDI attacks could cause remarkable voltage deviation that may deteriorate the stability of the distribution network. Moreover, the impact of CFDI attacks is higher than pure type I or type II attacks. To mitigate the threat, some countermeasures against CFDI attacks are also proposed.

Background: The procedures of transcatheter tricuspid valve-in-valve (TTViV) replacement are challenging, and the clinical outcomes are still unclear. Our goal was to report the short- and mid-term clinical outcomes of patients who underwent a TTViV implantation guided by 3-dimensional (3D) printing. Methods: A retrospective analysis was performed on 6 patients who had TTViV implantation from May 2021 to March 2022. The median age was 51 years (range: 18-71 years), and 50.0% of the patients were male. Imaging assessments and 3D printing were performed on all 6 patients before the procedures. The perioperative data were evaluated, and the patients were followed up. Results: Among the 6 patients, the etiologies of conditions affecting the tricuspid valves at baseline varied widely, including 1 case of Ebstein anomaly, 2 cases of infective endocarditis, 1 case of ventricular septal defect, and 2 cases of rheumatic heart disease. TTViV implantation was successfully performed in all 6 patients via the femoral vein approach; postoperative tricuspid regurgitation disappeared immediately, and the hemodynamic results were satisfactory. During the follow-up, all patients had significant improvement in symptoms and functional status. Conclusions: TTViV implantation for the treatment of degenerated tricuspid bioprostheses should be considered safe and effective. Multimodal imaging and 3D printing may provide effective guidance for conducting the procedure. Clinical Trial Registration: ClinicalTrials.gov Protocol Registration System (NCT02917980). Résumé: Contexte: Les interventions de remplacement par cathéter de la valve tricuspide avec la technique dite « valve-in-valve » (TTViV) sont délicates, et les résultats cliniques sont encore peu clairs. Notre objectif était de rapporter les résultats cliniques à court et à moyen terme obtenus chez des patients ayant subi une implantation TTViV guidée par l’impression en trois dimensions (3D). Méthodologie: Une analyse rétrospective portant sur six patients ayant subi une implantation TTViV entre mai 2021 et mars 2022 a été réalisée. L’âge médian était de 51 ans (min.-max. : 18-71 ans), et 50,0 % des patients étaient des hommes. Des examens d’imagerie et des impressions 3D ont été effectués avant l’intervention pour chacun des six patients. Les données périopératoires ont été analysées, et les patients ont fait l’objet d’un suivi. Résultats: Les affections initiales touchant la valve tricuspide chez les six patients avaient des causes variables, soit un cas de maladie d’Ebstein, deux cas d’endocardite infectieuse, un cas de défaut de communication interventriculaire, et deux cas de cardiopathie rhumatismale. Une implantation TTViV a été réalisée chez les six patients, par cathétérisme fémoral. La régurgitation tricuspide postopératoire a disparu immédiatement et les résultats hémodynamiques étaient satisfaisants. Durant le suivi, tous les patients ont obtenu une amélioration significative de leurs symptômes et de leur état fonctionnel. Conclusions: L’implantation TTViV pour le traitement d’une bioprothèse tricuspide dégénérée devrait être considérée comme sûre et efficace. L’imagerie multimodale et l’impression 3D peuvent fournir des directives efficaces pour la réalisation de l’intervention. Enregistrement des essais cliniques: ClinicalTrials.gov Protocol Registration System (NCT02917980).

Abstract Background Small songbirds respond and adapt to various geographical barriers during their annual migration. Global flyways reveal the diverse migration strategies in response to different geographical barriers, among which are high-elevation plateaus. However, few studies have been focused on the largest and highest plateau in the world, the Qinghai–Tibet Plateau (QTP) which poses a significant barrier to migratory passerines. The present study explored the annual migration routes and strategies of a population of Siberian Rubythroats (Calliope calliope) that breed on the north-eastern edge of the QTP. Methods Over the period from 2021 to 2023, we applied light-level geolocators (13 deployed, seven recollected), archival GPS tags (45 deployed, 17 recollected), and CAnMove multi-sensor loggers (with barometer, accelerometer, thermometer, and light sensor, 20 deployed, six recollected) to adult males from the breeding population of Siberian Rubythroat on the QTP. Here we describe the migratory routes and phenology extracted or inferred from the GPS and multi-sensor logger data, and used a combination of accelerometric and barometric data to describe the elevational migration pattern, flight altitude, and flight duration. All light-level geolocators failed to collect suitable data. Results Both GPS locations and positions derived from pressure-based inference revealed that during autumn, the migration route detoured from the bee-line between breeding and wintering grounds, leading to a gradual elevational decrease. The spring route was more direct, with more flights over mountainous areas in western China. This different migration route during spring probably reflects a strategy for faster migration, which corresponds with more frequent long nocturnal migration flights and shorter stopovers during spring migration than in autumn. The average flight altitude (1856 ± 781 m above sea level) was correlated with ground elevation but did not differ between the seasons. Conclusions Our finding indicates strong, season-dependent impact of the Qinghai–Tibet Plateau on shaping passerine migration strategies. We hereby call for more attention to the unexplored central-China flyway to extend our knowledge on the environment-migration interaction among small passerines.

Abstract Fractional tree cover facilitates the depiction of forest density and its changes. However, it remains challenging to estimate tree cover from satellite data, leading to substantial uncertainties in forest cover changes analysis. This paper generated a global annual fractional tree cover dataset from 2000 to 2021 with 250 m resolution (GLOBMAP FTC). MODIS annual observations were realigned at the pixel level to a common phenology and used to extract twelve features that can differentiate between trees and herbaceous vegetation, which greatly reduced feature dimensionality. A massive training data, consisting of 465.88 million sample points from four high-resolution global forest cover products, was collected to train a feedforward neural network model to predict tree cover. Compared with the validation datasets derived from the USGS circa 2010 global land cover reference dataset, the R2 value, MAE, and RMSE were 0.73, 10.55%, and 17.98%, respectively. This dataset can be applied for assessment of forest cover changes, including both abrupt forest loss and gradual forest gain.

ABSTRACT Aims Very few cohort studies are available about the relation between remnant cholesterol (RC) and diabetes. Based on a prospective cohort survey, this research aimed at investigating if high RC was related to a future diabetes risk in the Chinese population, as well as to compare the association between RC, high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), total cholesterol (TC), triglycerides (TG), TG/HDL‐C, LDL‐C/HDL‐C, TC/HDL‐C, and non‐high‐density lipoprotein cholesterol (non‐HDL‐C), and future diabetes risk. Materials and Methods 6,700 baseline normoglycemic participants of the REACTION study's Beijing center were recruited in 2011–2012 and followed up in 2015. Multivariate Cox regression analyses were performed to explore the relationship of RC, HDL‐C, LDL‐C, TC, TG, LDL‐C/HDL‐C, TG/HDL‐C, TC/HDL‐C, and non‐HDL‐C and a future diabetes risk. Results After potential confounders were adjusted for, only RC (HR 1.134, 95% CI 1.016–1.267, P = 0.025) was positively related to a future diabetes risk, and only HDL‐C (HR 0.728, 95% CI 0.578–0.918, P = 0.007) was negatively related to a future diabetes risk. The rest of the lipid parameters were not related to a future risk of diabetes. Sensitivity and stratification analyses revealed that the relation between RC and future diabetes risk was stable. RC and future diabetes risk were still positively correlated even when the HDL‐C was ≥1.04 mmol/L (HR 1.167, 95% CI 1.050–1.297, P = 0.004). Conclusions It was RC, but not other lipid parameters, that was independently and positively related to a future risk of diabetes among the Chinese general population. Moreover, the relationship between RC and diabetes risk was stable, even with appropriate levels of HDL‐C.