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Abstract Background Cognitive training has been confirmed to significantly improve the overall cognitive function in patients. For patients with coronary heart disease, in addition to controlling common risk factors, there is a lack of effective evidence for the treatment of cognitive function in patients with coronary heart disease and its effectiveness. This randomized controlled study was designed to evaluate the effectiveness of computer-based cognitive training for improving cognitive function in such patients. Methods COG-T CHD is a multicenter, double-blind, parallel-designed, randomized controlled trial. The patients will be divided 1:1 into two groups by a central randomized system, a cognitive digital therapy group or a positive control group. Patients assigned to the cognitive digital therapy group will undergo computer-based cognitive training for 30 min at least five times a week for 12 weeks. At the end of the 12 weeks, the subjects were randomly divided into two groups. One group continued the 12 weeks of cognitive digital therapy training and the other group stopped the training. Patients assigned to the positive control group will undergo computer-based cognitive training with little or no difficulty changes for 30 min at least five times a week for 12 weeks. The study will last approximately 2 years, with enrollment completed in approximately 18 months, with the last enrolled patient followed for at least 24 weeks. The primary outcome is the proportion of improvement in overall cognitive function at 12 weeks, using the Basic Cognitive Ability Test (BCAT). Secondary outcomes are the proportion of improvement in the overall cognitive function from baseline at 24 weeks, the change in overall cognitive function scores at 12 and 24 weeks, and the proportion of improvement in each cognitive domain, General Self-Efficacy Scale score, EuroQol five-dimension three-level questionnaire score, and Generalized Anxiety Disorder-7 score at 12 and 24 weeks from baseline. The investigational outcome is the change in head MRI structure and function from baseline at weeks 12/24. Discussion COG-T CHD is the first clinical trial to evaluate the efficacy of computer-based cognitive training in patients with coronary heart disease, filling an important gap in the treatment evidence for cognitive digital therapy. Trial registration ClinicalTrials.gov, NCT05735041. Registered on Jan. 18, 2023.

Abstract This study seeks to address the challenge of melanoma identification in immunohistochemical (IHC) diagnosis, which is complicated by the similar coloration of melanin and DAB (Diaminobenzidine) staining, by introducing methylene blue counterstaining as an innovative solution. We compared the effectiveness of methylene blue counterstaining with that of the traditional hydrogen peroxide bleaching method in the diagnosis of melanoma. The study included 46 paraffin-embedded melanoma samples, and the staining efficacy for markers such as Melan A, HMB-45, PRAME, and Ki-67 was assessed via both methods. The results demonstrated that methylene blue counterstaining effectively converted the brownish-yellow melanin granules to a deep green color, significantly enhancing contrast and clarity with DAB staining. The average contrast and clarity scores for the methylene blue counterstaining method were 1.96 ± 0.21 and 1.91 ± 0.28, respectively, which were significantly greater than those of the conventional IHC group and the hydrogen peroxide bleaching group (P 0.05). Although the contrast and clarity also improved in the hydrogen peroxide bleaching group, it resulted in a significant decrease in tissue integrity (P

Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury. Microglia and astrocytes play key roles in the spinal cord injury micro-environment and share a close interaction. However, the mechanisms involved remain unclear. In this study, we found that after spinal cord injury, resting microglia (M0) were polarized into pro-inflammatory phenotypes (MG1 and MG3), while resting astrocytes were polarized into reactive and scar-forming phenotypes. The expression of growth arrest-specific 6 (Gas6) and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord injury. In vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia, and even inhibited the cross-regulation between them. We further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway. This, in turn, inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling pathways. In vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord, thereby promoting tissue repair and motor function recovery. Overall, Gas6 may play a role in the treatment of spinal cord injury. It can inhibit the inflammatory pathway of microglia and polarization of astrocytes, attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment, and thereby alleviate local inflammation and reduce scar formation in the spinal cord.

Abstract The Japanese anchovy (Engraulis japonicus), a finfish with the largest biomass of a single species in the Yellow and East China Seas, plays an important pivotal role in converting zooplanktons into high trophic fish in the food web. As a result, the fish is regard as a key species in its habiting ecosystem. However, the lack of genomic resources hampers our understanding of its genetic diversity and differentiation, as well as the evolutionary dynamics. Here, we firstly report a complex chromosome-level genome assembly of E. japonicus with a large size of 1.4 Gb, with features of high repetitive sequences (54.9%), high heterozygosity (2.3%) and a number of protein-coding genes (24,405). The genome sequence exhibited a remarkable degree of completeness, valued 94.07% of the complete BUSCO. This work firstly reported the genome sequence of E. japonicus, offering the crucial resources for further studies on the genetic diversity and adaptive evolution of this species.

Abstract Allylic ethers and alcohols are essential structural motifs commonly present in natural products and pharmaceuticals. Direct allylic C–H oxygenation of internal alkenes is one of the most direct methods, bypassing the necessity for an allylic leaving group that is needed in the traditional Tsuji–Trost reaction. Herein, we develop an efficient and practical method for synthesizing (E)-allyl ethers from readily available internal alkenes and alcohols or phenols via selective allylic C–H oxidation. Key advances include the use of a Cu/Azodiformate catalyst system to facilitate remote allylic C–H activation and the achievement of excellent chemoselectivity through a dynamic ligand exchange strategy using a bis(sulfonamide) ligand. This method features a broad substrate scope and functional group tolerance, successfully applied to the synthesis of various challenging medium-sized cyclic ethers (7-10 members) and large-ring lactones (14-20 members), with high regioselectivity and stereoselectivity.

Abstract Lactate produced during ischemia-reperfusion injury is known to promote lactylation of proteins, which play controversial roles. By analyzing the lactylomes and proteomes of mouse myocardium during ischemia-reperfusion injury using mass spectrometry, we show that both Serpina3k protein expression and its lactylation at lysine 351 are increased upon reperfusion. Both Serpina3k and its human homolog, SERPINA3, are abundantly expressed in cardiac fibroblasts, but not in cardiomyocytes. Biochemically, lactylation of Serpina3k enhances protein stability. Using Serpina3k knockout mice and mice overexpressing its lactylation-deficient mutant, we find that Serpina3k protects from cardiac injury in a lysine 351 lactylation-dependent manner. Mechanistically, ischemia-reperfusion-stimulated fibroblasts secrete Serpina3k/SERPINA3, and protect cardiomyocytes from reperfusion-induced apoptosis in a paracrine fashion, partially through the activation of cardioprotective reperfusion injury salvage kinase and survivor activating factor enhancement pathways. Our results demonstrate the pivotal role of protein lactylation in cardiac ischemia-reperfusion injury, which may hold therapeutic value.

[Objective] Establishment of a fingerprinting assay for Ganoderma lucidum spore powder and investigation of the effects of Ganoderma lucidum spore oil on the inflammatory factors IL-1β, IL-6, and TNF-α. [Methods] High Performance Liquid Chromatography and High Performance Thin-layer Chromatography techniques were used to analyze the chemical composition of Ganoderma lucidum spore powder from different origins; MTT method was used to determine the cell viability; ELISA was used to determine the RAW264.7 IL-1β, IL-6 and TNF-α levels in cell supernatant. [Results] The HPLC fingerprints were calibrated with a total of 12 peaks, of which peaks 1-5 were ganoderic acid C2, ganoderic acid G, ganoderic acid B, ganoderic acid A, ganoderic acid D, respectively; the current version of the Pharmacopoeia method of HPTLC showed that 10 batches of samples complied with the regulations, and the quality of raw materials of different origins was found to be similar to that of the HPLC fingerprints after 2 unfoldings by using trichloromethane-acetonitrile-methanol-formic acid (26∶4 ∶1∶1) as the unfolding agent. The differences of the spots were significant and similar to the HPLC fingerprints. Ganoderma lucidum spore oil concentration less than or equal to 180 μg/mL had no significant effect on the activity of RAW264.7 cells; the protective effect on LPS-induced RAW264.7 cells was dose-dependent; compared with the model group, the medium-dose group (90 μg/mL) significantly decreased the expression of IL-1β (P0.05). [Conclusion] Ganoderma lucidum spore oil is used to reduce the inflammation of the body by inhibiting the release of inflammatory factors to achieve the protective effect on immune cells. The quality of spore powder can be initially identified by HPTLC, and HPLC fingerprinting can accurately control the quality of raw materials and guarantee the efficacy of Ganoderma lucidum spore oil.

Abstract Background Influenza virus is a contagious respiratory pathogen that can cause severe acute infections with long-term adverse outcomes. For paediatric patients at high risk of severe influenza, the readmission and the associated risk factors remain unclear. Methods Children discharged with a diagnosis of severe or critical influenza from October 2021 to March 2022 were included. The disease severity was categorized according to the “2020 edition of the Chinese expert consensus on the diagnosis and treatment of influenza in children”. Demographic data, clinical characteristics, underlying medical conditions, microbiology, treatment outcomes, and 90-day readmissions were retrieved and retrospectively analyzed. Those who tested positive for COVID-19 were excluded. Risk factors independently associated with readmission were identified using multiple logistic regression models. Results During the study period, 225 children with severe influenza were hospitalized and 14.7% (33/225) of them were readmitted within 90 days. The median length of readmission was 62 (IQR, 31–76) days, and the most common cause of readmission was pneumonia. M. pneumoniae and influenza virus are the most common infections for readmission The children who were readmitted were more likely to have critical influenza and neurological comorbidities compared to patients without readmission. The readmitted children had a significantly higher proportion of natural killer cells and a shorter febrile duration and length of stay on their first admission, compared with those who were not readmitted. Rhinosinusitis (OR = 30.085, p = .008) and high level of natural killer cells (OR = 1.107, p = .012) were independent risk factors and febrile duration (OR, 0.748, p = .018) was a protective factor for 90-day readmission. Conclusions Our findings suggest that, to reduce the potential readmission of children with severe influenza, a sustained focus on the risk factors including rhinosinusitis and over-activated host immune response during the index hospitalization is needed.

Abstract Background Watching short videos is an integral part of the daily lives of young and middle-aged people. Nevertheless, the correlation between the screen time spent watching short videos at bedtime and essential hypertension in young and middle-aged people remains unclear. We aimed to explore the correlation between the screen time spent watching short videos at bedtime and essential hypertension among young and middle-aged people and construct a nomogram prediction model for assessing the probability of developing essential hypertension for these age groups. Methods This study included 4318 young and middle-aged people who underwent medical examinations at Hengshui People’s Hospital between January 2023 and September 2023. The collected data, including self-reported screen time spent watching short videos at bedtime and general information, were partitioned into a training set and a test set, with the former being divided into hypertensive and non-hypertensive groups. R programming language was used for statistical analysis and processing. Results The results of multifactorial logistic analysis showed that screen time of 0< time ≤ 1 h (95% confidence interval [CI]: 2.022–6.082, P4 h (95% CI: 21.382–78.15, P

Extracellular vesicles (EVs) have garnered significant attention in biomedical applications. However, the rapid, efficient, and unbiased separation of EVs from complex biological fluids remains a challenge due to their heterogeneity and low abundance in biofluids. Herein, we report a novel approach to reconfigure and modify an artificial insertion peptide for the unbiased and rapid isolation of EVs in 20 min with ∼80% recovery in neutral conditions. Moreover, the approach demonstrates exceptional anti-interference capability and achieves a high purity of EVs comparable to standard ultracentrifugation and other methods. Importantly, the isolated EVs could be directly applied for downstream protein and nucleic acid analyses, including proteomics analysis, exome sequencing analysis, as well as the detection of both epidermal growth factor receptor (EGFR) and V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homologue (KRAS) gene mutation in clinical plasma samples. Our approach offers great possibilities for utilizing EVs in liquid biopsy, as well as in various other biomedical applications.

Abstract During the procedure of three‐dimensional (3D) moving target localisation in multistatic passive radar (MPR) system, conventional closed‐form algorithms and their enhanced versions necessitate at least four transmitters to obtain unambiguous localisation, and they are prone to poor noise resistance. In this paper, based on multiple sets of bistatic range difference (BRD) and bistatic range rate difference (BRRD) measurements, an innovative closed‐form algorithm is proposed which, combines an improved two‐step weighted least squares (ITSWLS) using the Newton method (NM) to minimise the number of transmitters required for localization. In a 3D environment, this algorithm can precisely localise targets with merely three transmitters. Compared with the existing closed‐form algorithms, this algorithm saves one transmitter resource, breaking through the constraints of traditional approaches. After theoretical analysis and simulation verification, in the presence of just three transmitters, the estimation accuracy of the algorithm for both near‐field and far‐field target parameters can reach the Cramér–Rao lower bound (CRLB) when the measurement noise is low. If an additional transmitter is incorporated, this algorithm has higher localization accuracy and better noise resistance compared to the elliptic localization (EL), TSWLS, ITSWLS, and Taylor algorithms.

Abstract Islet transplantation is a promising therapy for diabetes, yet the limited survival and functionality of transplanted islet grafts hinder optimal outcomes. Glucagon-like peptide-1 (GLP-1), an endogenous hormone, has shown potential to enhance islet survival and function; however, its systemic administration can result in poor localization and undesirable side effects. To address these challenges, we developed a novel peptide-based nanofiber hydrogel incorporating GLP-1 functionality for localized delivery. By conjugating the FFG tripeptide (a self-assembling motif derived from phenylalanine-phenylalanine-glycine) to the C-terminus of native GLP-1, we engineered GLP-1-FFG, a self-assembling peptide that forms a robust nanofiber structure resistant to enzymatic degradation. When GLP-1-FFG co-assembles with the biotin-DFYIGSRGD peptide (referred to as SupraGel), a self-assembling supramolecular polypeptide hydrogel we previously identified containing motifs derived from extracellular matrix components, the resulting hydrogel (SupraGel + GLP-1-FFG) creates a stable nanofibrous network with excellent rheological properties. In vitro, this nanofiber hydrogel significantly improves islet function and survival. Bulk RNA sequencing results demonstrate that the hydrogel suppresses the expression of hypoxia-related genes, downregulates pro-inflammatory genes, and upregulates genes associated with islet function. Further analysis reveals that these effects are related to the activation of the AKT signaling pathway. In a syngeneic mouse islet transplantation model, the localized application of SupraGel + GLP-1-FFG at the renal subcapsular islet transplant site significantly enhanced the efficacy of marginal-dose islet transplantation, as shown by improved glycemic control, faster and higher rates of diabetes reversal, better glucose tolerance, and greater islet graft survival in diabetic recipient mice. This innovative nanotechnology-based hydrogel offers a promising strategy for enhancing the efficacy of islet grafts in transplantation therapy. Graphical Abstract

Abstract Wild relatives of wheat are valuable sources for enhancing the genetic diversity of common wheat. Aegilops comosa, an annual diploid species with an MM genome constitution, possesses numerous agronomically valuable traits that can be exploited for wheat improvement. In this study, we report a chromosome-level genome assembly of Ae. comosa accession PI 551049, generated using PacBio high-fidelity (HiFi) reads and high-throughput chromosome conformation capture (Hi-C) data. The assembly spans 4.47 Gb, featuring a contig N50 of 23.59 Mb and a scaffold N50 of 619.05 Mb. A total of 39,057 gene models were annotated through a combination of homoeologous proteins, Iso-seq, and RNA-seq data. Comparative genome analysis revealed a terminal intrachromosomal translocation on chromosome 2 M in Ae. comosa. This newly constructed reference genome of Ae. comosa will serve as an important genomic resource for comparative genomic studies and the cloning of agriculturally important genes.

Abstract Background Liver fibrosis is a complex reparative process in response to chronic liver injuries, with limited effective therapeutic options available in clinical practice. During liver fibrosis, liver sinusoidal endothelial cells (LSECs) undergo phenotypic changes and also play a role in modulating cellular communications. Si-Wu-Tang (SWT), a traditional Chinese herbal remedy, has been extensively studied for its effectiveness in treating hematological, gynecological and hepatic diseases. Materials and methods The component of SWT were identified by ultra-high-performance liquid chromatography (UHPLC). After establishing bile duct ligation (BDL)-induced liver fibrosis mice model and VEGFA-stimulated LSEC model, we invested the mechanism of SWT through RNA sequencing combined with molecular biology techniques. Results SWT significantly improved the sinusoidal permeability and liver fibrosis induced by BDL and effectively regulated pathological processes in LSECs, such as angiogenesis, cell adhesion, basement membrane formation and defenestration. The anti-fibrosis effects of SWT were attributed to the inhibition on LSEC adhesion via COL8A1, on LSEC angiogenesis via IL-1β and the induction of LSEC defenestration by OLR1. Additionally, SWT disrupted the intercellular crosstalk between LSECs and hepatic stellate cells (HSCs) driven by IL-1β, thus alleviating liver fibrosis. Conclusion SWT collectively ameliorated liver fibrosis by inhibiting the COL8A1/IL-1β/OLR1 pathways associated with LSEC angiogenesis, adhesion and defenestration, as well as suppressing LSEC secretion of IL-1β to reduce HSC activation.

Abstract Fundamental machine learning theory shows that different samples contribute unequally to both the learning and testing processes. Recent studies on deep neural networks (DNNs) suggest that such sample differences are rooted in the distribution of intrinsic pattern information, namely sample regularity. Motivated by recent discoveries in network memorization and generalization, we propose a pair of sample regularity measures with a formulation-consistent representation for both processes. Specifically, the cumulative binary training/generalizing loss (CBTL/CBGL), the cumulative number of correct classifications of the training/test sample within the training phase, is proposed to quantify the stability in the memorization-generalization process, while forgetting/mal-generalizing events (ForEvents/MgEvents), i.e., the misclassification of previously learned or generalized samples, are utilized to represent the uncertainty of sample regularity with respect to optimization dynamics. The effectiveness and robustness of the proposed approaches for mini-batch stochastic gradient descent (SGD) optimization are validated through sample-wise analyses. Further training/test sample selection applications show that the proposed measures, which share the unified computing procedure, could benefit both tasks.

Abstract The objective of this study is to utilize optical coherence tomography angiography (OCTA) techniques for the purpose of identifying abnormalities in retinal and conjunctival vascular density among patients afflicted with renal hypertension. From October 2022 to October 2023, a cohort of sixteen patients diagnosed with renal hypertension (RH), comprising a total of 32 eyes, was selected from the Department of Nephrology at the First Affiliated Hospital of Nanchang University. Concurrently, a group of sixteen healthy individuals, carefully matched in characteristics, was recruited from volunteers at the Ophthalmology Research Center and designated as the healthy controls (HCs) group. Optical coherence tomography angiography was employed to assess and examine the superficial vascular plexus (SVP) and deep vascular plexus (DVP) of the macular retina in both eyes. Subsequently, a comparative analysis was conducted between the two groups, focusing on the superficial and deep retinal microvessels (MIR), macrovascular (MAR), and total microvascular (TMI). The present study employed the central annuli segmentation method (C1–C6), the hemispheric segmentation method (SL, IL, SR, IR), and the Early Treatment Diabetic Retinopathy Study (S, I, L, R) to evaluate deviations in retinal blood vessel density. The investigation aimed to examine the association between blood vessel density and TMI in conjunctival capillaries. A statistically significant difference (p

Titanium alloy chemical milling wastewater contains a significant amount of ethylene glycol monobutyl ether (EGBE), which is toxic and difficult to be degraded by microorganisms, and the emission will lead to severe environmental pollution. To solve this problem, the electrocatalytic oxidation method was employed to remove EGBE in the wastewater, in which a porous Ti4O7/Ti electrode were prepared and employed as the anode, while stainless steel acted as the cathode. The effects of current density, interelectrode distance, and stirring mode on the COD removal rate were also investigated. Results show that the COD of the wastewater significantly decreases from 12410 to 15 mg L−1 after 16 h of electrolysis at 10 mA cm−2 and electrode spacing of 1.0 cm as well as aeration stirring at 100 mL min−1. Moreover, pilot-plant scale testing reveals that the COD decreasing from 11980 to 183 mg L−1 after 24 h of electrolysis. Consequently, the utilization of porous Ti4O7/Ti electrode as anode in the electrocatalytic oxidation method presents significant potential in removal of EGBE in aviation industry wastewater.

Simvastatin (SIM), a commonly prescribed drug for lowering serum-lipid, has been detected in many aquatic environments. Exposure to high concentrations of SIM in rats and aquatic organisms resulted in toxicity to hepatocytes and negative effects on development. However, there is a paucity of studies on the effects of long-term exposure to low concentrations of SIM on aquaculture species. This study aimed to analyze the effects of environmentally relevant concentrations (0.1 μg/L and 1 μg/L) of SIM exposure for two months on developing Mozambique tilapias. Surprisingly, the growth of male tilapias was enhanced after a 2-month SIM exposure. The analysis of testis histology revealed that after the SIM exposure, the development of the testis was delayed, and sperm production was reduced. Sequencing of testis transcriptomes showed that the exposure to SIM altered the expression of many genes related to the development of testes and spermatogenesis. These data suggest that a 2-month exposure to environmentally relevant concentrations of increases the growth of male tilapias by inhibiting sexual development of males.

Abstract Multi‐organ segmentation from abdominal CT scans is crucial for various medical examinations and diagnoses. Despite the remarkable achievements of existing deep‐learning‐based methods, accurately segmenting small organs remains challenging due to their small size and low contrast. This article introduces a novel knowledge‐guided cascaded framework that utilizes two types of knowledge—image intrinsic (anatomy) and clinical expertise (radiology)—to improve the segmentation accuracy of small abdominal organs. Specifically, based on the anatomical similarities in abdominal CT scans, the approach employs entropy‐based registration techniques to map high‐quality segmentation results onto inaccurate results from the first stage, thereby guiding precise localization of small organs. Additionally, inspired by the practice of annotating images from multiple perspectives by radiologists, novel Multi‐View Fusion Convolution (MVFC) operator is developed, which can extract and adaptively fuse features from various directions of CT images to refine segmentation of small organs effectively. Simultaneously, the MVFC operator offers a seamless alternative to conventional convolutions within diverse model architectures. Extensive experiments on the Abdominal Multi‐Organ Segmentation (AMOS) dataset demonstrate the superiority of the method, setting a new benchmark in the segmentation of small organs.

Abstract Background Epidemiological studies show inconsistent links between hearing/vision impairment and dementia risk. Using multisource data, we investigated how single or combined sensory impairments relate to risks of all-cause and specific types of dementia. Methods We employed a triangulation approach combining three methodologies. We analyzed 90,893 UK Biobank (UKB) adults to explore single and joint effects of hearing and vision impairments on all-cause and Alzheimer’s disease (AD), vascular dementia (VD) and non-AD non-VD (NAVD). A meta-analysis of prospective studies involving 937,908 participants provided stronger evidence. Finally, we conducted Mendelian randomization (MR) analysis using genome-wide association studies from UKB (361,194 participants) and FinnGen (412,181 participants) to validate relationships between sensory impairments and dementia occurrence. Results In the UKB cohort study, compared to participants with normal hearing, those in the mild and severe hearing impairment groups had progressively and significantly higher risk of all-cause dementia (mild: HR1.52, 95%CI 1.31–1.77; severe: HR1.80, 95%CI 1.36–2.38), AD (mild: HR1.63, 95%CI 1.30–2.04; severe: HR2.18, 95%CI 1.45–3.27), VD (mild: HR1.68, 95%CI 1.19–2.37; severe: HR1.47, 95%CI 1.22–1.78), and NAVD (mild: HR1.47, 95%CI 1.22–1.78; severe: HR1.98, 95%CI 1.43–2.75). Besides, vision impairment was associated with an increased risk of all-cause dementia (HR1.55, 95%CI 1.18–2.04) and NAVD (HR1.51, 95%CI 1.07–2.13). Furthermore, dual sensory impairment was associated with stepwise increased risks of all-cause and cause-specific dementia than single hearing or vision impairment. In the meta-analysis of 31 prospective cohort studies, risks of all-cause dementia and AD were elevated in participants with single hearing impairment (all-cause dementia: HR1.30, 95%CI 1.21–1.40; AD: HR1.30, 95%CI 1.21–1.40) and dual sensory impairment (all-cause dementia: HR1.63, 95%CI1.14–2.12; AD: HR 2.55, 95%CI 1.19–3.91), while single vision impairment only associated with higher risk of all-cause dementia (HR1.43, 95%CI 1.16–1.71) but not AD. Finally, the MR analysis revealed a significant association between hearing impairment and all-cause dementia (OR1.74, 95%CI 1.01–2.99), AD (OR1.56, 95%CI 1.09–2.23), and NAVD (OR1.14, 1.02–1.26), as well as vision impairment and NAVD (OR1.62, 95%CI 1.13–2.33). Conclusions Our findings showed significant associations between hearing and vision impairments and increased risks of all-cause and cause-specific dementia. Standardized hearing and vision assessment and intervention should be emphasized in dementia prevention strategies.

Background/Objective: Probiotic supplementation has a positive effect on endurance exercise performance and body composition in athletes, but the underlying mechanisms remain unclear. Gut microbiota can provide measurable markers of immune function in athletes, and microbial composition analysis may be sensitive enough to detect stress and metabolic disorders caused by exercise. Methods: Nineteen healthy active amateur marathon runners (15 male and 4 female) with a mean age of 29.11 years volunteered to participate in this double-blind controlled study. Based on the performance of the Cooper 12-min running test (CRT), the participants were allocated into two groups to receive either a probiotic formulation comprising lactobacillus acidophilus and bifidobacterium longum (n = 10) or placebo containing maltodextrin (n = 9) for five weeks. Consistency of diet and exercise was ensured throughout the experimental period. Before and after the intervention, all participants were assessed for CRT, emotional stability and gastrointestinal symptoms, gut microbiota composition, body composition and magnetic resonance imaging (MRI) indicators of skeletal muscle microcirculation. Results: Compared to before the intervention, the probiotics group showed an increase in CRT score (2.88 ± 0.57 vs 3.01 ± 0.60 km, P＜0.05), significant improvement in GSRS and GIQLI (9.20 ± 4.64 vs 7.40 ± 3.24, 118.90 ± 12.30 vs 127.50 ± 9.85, P＜0.05), while these indicators remained unchanged in the control group, with a significant time-group interaction effect on gastrointestinal symptoms. Additionally, some MRI metabolic cycling indicators of the thigh skeletal muscle also changed in the probiotics group (P＜0.05). Regarding microbiota abundance, the probiotics group exhibited a significant increase in the abundance of beneficial bacteria and a significant decrease in the abundance of harmful bacteria post-intervention (P＜0.05). Conclusion: As a sports nutritional supplement, probiotics have the potential to improve athletic performance by optimizing the balance of gut microbiota, alleviating gastrointestinal symptoms.

Abstract The vacancy effect in quantum spin liquid (QSL) has been extensively studied. A finite density of random vacancies in the Kitaev model can lead to a pileup of low-energy density of states (DOS), which is generally experimentally determined by a scaling behavior of thermodynamic or magnetization quantities. Here, we report detailed muon spin relaxation (μSR) results of H3LiIr2O6, a Kitaev QSL candidate with vacancies. The absence of magnetic order is confirmed down to 80 mK, and the spin fluctuations are found to be persistent at low temperatures. Intriguingly, the time-field scaling law of longitudinal-field (LF)-μSR polarization is observed down to 0.1 K. This indicates a dynamical scaling, whose critical exponent of 0.46 is excellently consistent with the scaling behavior of specific heat and magnetization data. All the observations point to the finite DOS with the form $$N(E)\sim {E}^{-\nu }$$ N ( E ) ∼ E − ν , which is expected for the Kitaev QSL in the presence of vacancies. Our μSR study provides a dynamical fingerprint of the power-law low-energy DOS and introduces a crucial new insight into the vacancy effect in QSL.

Abstract Objectives This study aimed to evaluate the diagnostic significance of computed tomography (CT) detected ascites in gastric cancer (GC) with peritoneal metastasis (PM) and investigate its association with systemic inflammatory response. Methods This retrospective study included 111 GCs with ascites (PM: n = 51; No PM: n = 60). Systemic inflammatory indexes, tumor markers, and the CT-assessed characteristics of ascites were collected. The differences in parameters between the two groups were analyzed. Diagnostic performance was obtained by receiver operating characteristic curve analysis. The association between the volume of ascites and clinical characteristics was evaluated with correlation analysis. Results In this study, over half of GCs with ascites were not involved with PM. The systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), five tumor markers, and the characteristics of ascites showed significant differences between the two groups (all p

Abstract Promoters play a crucial role in regulating gene transcription. However, our understanding of how genetic variants influence alternative promoter selection is still incomplete. In this study, we implement a framework to identify genetic variants that affect the relative usage of alternative promoters, known as promoter usage quantitative trait loci (puQTLs). By constructing an atlas of human puQTLs across 49 different tissues from 838 individuals, we have identified approximately 76,856 independent loci associated with promoter usage, encompassing 602,009 genetic variants. Our study demonstrates that puQTLs represent a distinct type of molecular quantitative trait loci, effectively uncovering regulatory targets and patterns. Furthermore, puQTLs are regulating in a tissue-specific manner and are enriched with binding sites of epigenetic marks and transcription factors, especially those involved in chromatin architecture formation. Notably, we have also found that puQTLs colocalize with complex traits or diseases and contribute to their heritability. Collectively, our findings underscore the significant role of puQTLs in elucidating the molecular mechanisms underlying tissue development and complex diseases.

Abstract NLRP3 inflammasomes- pyroptosis axis is activated by microcirculation dysfunction and touched off severe acute pancreatitis (SAP). Activation of PGC-1α can improve microcirculation dysfunction by promoting mitochondrial biogenesis. Resveratrol (RSV), one typical SIRT1 agonist, possesses the ability of alleviating SAP and activing PGC-1α. Therefore, the study was designated to explore whether the protective effect of RSV in SAP was though suppressing NLRP3 inflammasomes- pyroptosis axis via advancing SIRT1/PGC-1α-dependent mitochondrial biogenesis. The models of SAP were induced by treating with sodium taurodeoxycholate in rats and AR42J cells. The pathological injury, water content (dry/wet ratio) and microcirculation function of pancreas, activity of lipase and amylase were used to evaluate pancreatic damage. The expression of inflammatory cytokine was measured by ELISA and RT-PCR. The damage of mitochondrial was evaluated by measuring the changes in Mitochondrial Membrane Potential (ΔΨm), mitochondrial ROS, ATP content and MDA as well as relocation of mtDNA and the activity of SOD and GSH. The expressions of NLRP3 inflammasomes- pyroptosis axis proteins were detected by Western blotting as well as SIRT1/PGC-1α/NRF1/TFAM pathway protein. Moreover, the modification of PGC-1α was measured by co-immunoprecipitation. The results displayed that RSV can significantly improve the damage of pancreas and mitochondrial, decrease the expression of pro-inflammatory factor and the activation of NLRP3 inflammasomes- pyroptosis axis, promote the expression of an-inflammatory factor and the deacetylation of PGC-1α together with facilitating SIRT1/PGC-1α-mediating mitochondrial biogenesis. Therefore, the protective effect of RSV in SAP is though inactivation of NLRP3 inflammasomes- pyroptosis axis via promoting mitochondrial biogenesis in a SIRT1/PGC-1α-dependent manner.

IntroductionIn recent years, river ecosystem stability has been increasingly threatened by human activities and climate change. Comprehensive quantification of river ecosystem stability and systematic analysis of its response to human activities and climate change are essential for effective conservation and management.MethodsThus, this study proposed a novel quantitative approach to integrating the stability of river ecosystem and its driving factors. The Han River Basin in China was selected as the study area due to its distinctive climate characteristics and significant anthropogenic impact. Both external factors, including urbanization, dam construction, and precipitation, and internal factors, such as TP, DO, and EC, were considered as driving factors.ResultsThe results revealed that compared to the upstream, resilience in the lower reaches decreased by 35.75% and the resistance decreased by 8.2%, suggesting that the stability decreased from upstream to downstream. Urbanization had the most significant negative impact on ecosystem stability, followed by precipitation and dam construction. Among the internal factors, TP, DO, and EC were the three main factors affecting ecosystem stability and the increases in these factors contributed positively to enhancing ecosystem stability.DiscussionThese findings highlight the need for targeted conservation strategies to mitigate human-induced disturbances and enhance river ecosystem stability. Based on the results, specific recommendations were proposed to support watershed management and ecological restoration, providing valuable insights for sustainable river conservation.

Summary: Background: Type 1 diabetes (T1D) is an autoimmune disease characterised by the attack of pancreatic β cells by “self” immune cells. Although previous studies demonstrated that B cells contribute to T1D through antigen presentation and autoantibody production, the involvement of different populations of B cells, particularly in the early stages of T1D, has not been fully elucidated. Methods: In this study, we employed single-cell RNA sequencing (scRNA-seq) and flow cytometry to investigate immune cell populations in patients with newly diagnosed T1D, their relative controls and age-matched healthy controls. Phosphoprotein microarray analysis was employed to investigate changes in protein phosphorylation in B cells. Furthermore, we developed a siRNA-based nanomedicine and evaluated its therapeutic potential in the NOD mouse. The integration of scRNA-seq, flow cytometry, phosphoprotein microarrays, and functional assays established a robust framework for understanding and targeting B cell-mediated autoimmunity in T1D. Findings: Using single-cell RNA sequencing, we discovered that patients with T1D exhibited increased humoural immunity in the early stage of T1D. Specifically, the population of naïve B cells increased in patients with newly diagnosed T1D who expressed elevated levels of the AKT kinase coactivator TCL1A. Using a protein phosphorylation microarray, we confirmed that TCL1A knockdown specifically impaired AKT2 phosphorylation and affected B cell survival and proliferation. Notably, we discovered that the naïve B cell population increased and TCL1A expression was upregulated in NOD mice that developed T1D. Both the levels of naïve B cells and TCL1A were strongly associated with glucose intolerance in T1D mice. Importantly, treatment with a siRNA-based nanomedicine targeting Tcl1a mRNA effectively reduced the number of naïve B cells, prevented the loss of pancreatic β cells, and improved glucose intolerance in T1D mice. Interpretation: Using single-cell RNA-seq, we have not only uncovered a naïve B cell specific gene that may contribute to the pathogenesis of T1D but also highlighted the potential of siRNA-based nanomedicine for treating T1D. The clinical translation of these findings offers a new approach for the treatment of T1D. Funding: See Acknowledgements.

Background: Gastric cancer (GC) is the fifth most prevalent and the fifth deadliest cancer worldwide, and timely diagnosis of GC contributes to an increased survival rate. However, current detection methods for GC mainly rely on gastroscopy examination, limited by relatively low compliance. We attempted to identify plasma metabolite biomarkers and develop a diagnostic model for GC. Methods: A total of 597 subjects, including healthy controls and GC patients were recruited from multiple centers in China. Ultra-performance liquid chromatography–mass spectrometry–based metabolomics methods were used to characterize the subjects’ plasma metabolic profiles and to screen and validate the GC biomarkers. Five machine learning algorithms (neural network, support vector machine, ridge regression, lasso regression and Naïve Bayes) were used to build a diagnostic model. We compared the performance of the metabolic panel with risk factors and clinical protein biomarkers (CA724, CA199, CA242, CA125, CEA and AFP), involving sensitivity, specificity, accuracy, AUC and clinical net benefit. Findings: A plasma metabolite biomarker panel consisting of 6 metabolites was constructed and identified for GC diagnosis. Among the five machine learning algorithms, the neural network algorithm demonstrated the best diagnostic performance, achieving AUC of 0.982 (95% CI: 0.965–0.998) and 0.951 (95% CI: 0.931–0.970) in the discovery and validation dataset, respectively. The panel's sensitivity, specificity, and accuracy (95% CI) were 0.940 (0.825–0.984), 0.936 (0.861–0.974), and 0.938 (0.881–0.969) in the discovery set, and 0.925 (0.881–0.954), 0.867 (0.814–0.907), and 0.896 (0.864–0.922) in the validation set, respectively. The panel also exhibited superior diagnostic performance in detecting early-stage GC, with the ridge regression algorithm achieving the best performance (AUC: 0.982, 95% CI: 0.965–0.998 and 0.951, 0.931–0.970 in the discovery and validation dataset). This panel significantly outperforms clinical protein biomarkers in sensitivity. For instance, CA724, the most sensitive clinical biomarker for GC, showed sensitivities of only 0.240 (95% CI: 0.131–0.382) in the discovery dataset and 0.148 (95% CI: 0.103–0.203) in the validation dataset. Interpretation: The discovered and validated serum metabolite biomarker panel exhibits good diagnostic performance for the early detection of GC, highlighting the potential in clinical practice for GC diagnosis and offering insights into the metabolic characterization of diseases including but not limited to GC. Funding: This study was supported by grants from the Medical and Health Research Project of Zhejiang Province (2024KY050), Zhejiang Cancer Hospital's National Natural Science Foundation Cultivation Fund (PY2022042) and Zhejiang Cancer Hospital Youth Research Fund (QN202201).

BackgroundN6-methyladenosine (m6A) RNA modification is crucial for tumor development and progression; however, which m6A regulators play a pivotal role in head and neck squamous cell carcinoma (HNSCC) remains ambiguous.MethodsUtilizing the Cancer Genome Atlas (TCGA) database, the expression levels of m6A regulators in HNSCC were examined, which led to the identification of heterogeneous nuclear ribonucleoprotein C (HNRNPC) as a key gene. Further experiments were performed in patient samples, stable cell lines, and a murine xenograft tumor model.ResultsA reliable survival risk model of m6A was constructed based on the TCGA database. Gene Expression Omnibus (GEO), normal and tumor tissue microarrays (TMA), and tumor tissue samples from patients with HNSCC were observed that a high level of HNRNPC expression was closely linked to a poor prognosis among patients. Knockdown of HNRNPC in the HNSCC cell lines HSC-3 and CAL-27 resulted in a significant decrease in proliferation, invasion, and malignant transformation abilities. RNA sequencing (RNA-seq) and methylated RNA immunoprecipitation and sequencing (MeRIP-seq) data revealed that HNRNPC is involved in cell differentiation, cell migration and apoptosis. The mouse xenograft model elucidated that HNRNPC can promote tumorigenesis and progression of HNSCC.ConclusionsHNRNPC can serve as a valuable predictor of tumor progression and prognosis in patients with HNSCC.

In recent years, Ulva prolifera green tide, as a large-scale marine ecological phenomenon, has occurred frequently in coastal areas such as the Yellow Sea and the East China Sea, significantly affecting marine ecosystems and fishery resources. With the continuous advancement of remote sensing technologies, these technologies have become indispensable tools for monitoring Ulva prolifera green tides. This review provides a comprehensive overview of the advances in remote sensing band indices for detecting green tides, including spatiotemporal distribution analysis, area and biomass estimation, drift trajectory modeling, and investigations of their driving mechanisms. Additionally, it identifies the limitations and unresolved challenges in current approaches, such as constraints on data resolution, algorithmic biases, and environmental variability. The potential for integrating multi-source remote sensing data with marine environmental parameters and deep learning techniques is discussed, emphasizing their roles in improving the accuracy and reliability of monitoring and predicting Ulva prolifera green tides. This review aims to guide future research efforts and technological innovations in this field.

ObjectiveTo systematically compare the benefits and risks of all thrombolytic agents (tenecteplase, reteplase, and alteplase) at different doses for thrombolytic therapy in patients with acute ischemic stroke (AIS).BackgroundAlteplase is the cornerstone treatment for AIS, but alternative thrombolytic agents are needed. The efficacy and safety of tenecteplase and reteplase, compared to alteplase, remain unclear, as does the optimal dosing for these treatments.MethodA systematic search was conducted in PubMed, Web of Science, SCOPUS, and the Cochrane Central Register of Controlled Trials (CENTRAL) for relevant English-language studies up to July 5, 2024. Randomized controlled trials (RCTs) comparing standard-dose alteplase with varying doses of tenecteplase or reteplase in AIS patients were included. Primary outcomes were functional outcome at 90 days, symptomatic intracranial hemorrhage, death within 90 days, and serious adverse events. Data on study characteristics, patient demographics, interventions, and outcomes were extracted, and bias risk assessed. A multivariate random-effects model was used for network meta-analysis to derive odds ratios (OR) and 95% confidence intervals (CI).ResultTwelve RCTs were included (10 with tenecteplase, 2 with reteplase) involving 6,633 patients, all compared against 0.9 mg/kg alteplase. In comparison with alteplase, tenecteplase demonstrated OR of 1.08 for achieving an excellent functional outcome at 90 days (95% CI: 0.97 to 1.22, P = 0.17). Reteplase, on the other hand, showed a significantly higher OR of 1.55 for the same outcome (95% CI: 1.23 to 1.95, P = 0.0002). Reteplase at 18 mg + 18 mg (OR 1.6, 95% CI: 0.91–2.5) showed a higher probability of achieving an excellent functional outcome at 90 days compared to alteplase. When considering a good functional outcome at 90 days, tenecteplase had an OR of 1.03 (95% CI: 0.81 to 1.3, P = 0.82), while reteplase had an OR of 1.15 (95% CI: 0.61 to 2.19, P = 0.66). Tenecteplase at 0.25 mg/kg (OR 1.3, 95% CI: 0.79–2.5) had the highest probability of achieving a good functional outcome at 90 days. For safety outcomes, 0.25 mg/kg tenecteplase had lower incidences of symptomatic intracranial hemorrhage (OR 0.88, 95% CI: 0.35–1.8), death within 90 days (OR 0.91, 95% CI: 0.54–1.4), and serious adverse events (OR 1.0, 95% CI: 0.47–2.3) compared to alteplase, though differences were not statistically significant. Reteplase at 18 mg + 18 mg had higher incidences of death within 90 days (OR 1.2, 95% CI: 0.48–3) and serious adverse events (OR 1.4, 95% CI: 0.4–5.0) compared to alteplase, without significant differences. Subgroup analysis showed better efficacy with 0.25 mg/kg tenecteplase in Asians (OR 1.18, 95% CI 0.96–1.45, P = 0.12) than in Caucasians (OR 1.08, 95% CI 0.9–1.3, P = 0.39).ConclusionThis study suggests that tenecteplase and reteplase are viable alternatives to alteplase for thrombolysis in AIS. Tenecteplase at 0.25 mg/kg and reteplase at 18 mg + 18 mg may offer better efficacy compared to standard-dose alteplase, although the risk of adverse events with reteplase should be considered. Tenecteplase at 0.25 mg/kg appears to provide the best benefit-risk profile based on current evidence. Further head-to-head trials of tenecteplase and reteplase are needed to determine the optimal thrombolytic agent and dosing.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, PROSPERO CRD42024566146.

The intricate link between cholesterol metabolism and host immune responses is well recognized, but the specific mechanisms by which cholesterol biosynthesis influences hepatitis B virus (HBV) replication remain unclear. In this study, we show that SREBP2, a key regulator of cholesterol metabolism, inhibits HBV replication by interacting directly with the HBx protein, thereby preventing its nuclear translocation. We also found that inhibiting the ER-to-Golgi transport of the SCAP-SREBP2 complex or blocking SREBP2 maturation significantly enhances HBV suppression. Notably, we demonstrate that the C-terminal domain (CTD) of SREBP2, rather than its N-terminal domain (NTD), mediates this inhibition by interacting with HBx and promoting its extracellular secretion, thus reducing nuclear HBx accumulation. These findings reveal a novel regulatory pathway that links cholesterol metabolism to HBV replication via SREBP2-mediated control of HBx localization. This insight provides a potential basis for new therapeutic strategies against HBV infection, addressing an important global health issue.

Asian seabass (Lates calcarifer) is an important foodfish species. It has been cultured in Singapore since the 1980s. A selective breeding program to improve growth, meat quality and disease resistance has been ongoing in Singapore since 2004. In 2012, outbreaks of the big belly disease (BBD) occurred in two batches of offspring generated by a mass-cross among F1 brooders in a hatchery. After the outbreaks, only 437 survived in 6000 F2 juveniles. Molecular parentage analysis with 10 microsatellites revealed that four parents (F1) produced high percentage of offspring that survived the BBD outbreaks. Eighty-two BBD survivor offspring (F2) were selected based on their growth performance at 90 days post hatch (dph), family origin and allelic diversity. They were used as brooders to generate F3. In a period of five years, these F2 brooders produced six batches of offspring, where no outbreak of BBD occurred. In the same period, outbreaks of BBD occurred in 4 out of 18 batches produced by F2 brooders selected for growth, with mortality rates ranging from 85.1% to 95.4%. In F3, the average body weight (57.1 ± 1.09 g, n = 3068) of the line for BBD survival was slightly lower than that (60.6 ± 2.29 g, n = 4280) of the line for growth at 90 dph. In both lines, the body weight of F3 was much higher than that (46.90 ± 0.19 g, n = 12117) of F2. The genetic diversity in the line for BBD survival (F3) was much lower than that in F3 line for growth due to small founder population. These data indicate that the selection of BBD survival during BBD outbreaks using molecular parentage analysis is effective to reduce BBD outbreaks. Avoiding further reduction of genetic diversity is essential in the line selected for increased survival against BBD.

X-chromosomal genetic markers are frequently employed in forensic parentage determination owing to their distinctive inheritance patterns. The kinship analysis revealed that two sisters who were not identical twins had identical genotypes on the X chromosome, encompassing 36 X-chromosomal short tandem repeats (X-STRs) and 29 X-chromosomal single-nucleotide polymorphisms (X-SNPs) that spanned the whole X chromosome from the p-telomere to the q-telomere. The identical X-STRs and X-SNPs in the daughters could be the result of linkage or a rare chance of occurrence. This highlights the need for careful analysis and interpretation when dealing with X chromosome markers and that in individual cases, even if two women share an allele at each locus, this does not necessarily mean that they are paternal sisters. The likelihood of random concordance due to maternal alleles must be taken into account.

The emerging virtual coupling technology aims to operate multiple train units in a Virtually Coupled Train Set (VCTS) at a minimal but safe distance. To guarantee collision avoidance, the safety distance should be calculated using the state-of-the-art space-time separation principle that separates the Emergency Braking (EB) trajectories of two successive units during the whole EB process. In this case, the minimal safety distance is usually numerically calculated without an analytic formulation. Thus, the constrained VCTS control problem is hard to address with space-time separation, which is still a gap in the existing literature. To solve this problem, we propose a Distributed Economic Model Predictive Control (DEMPC) approach with computation efficiency and theoretical guarantee. Specifically, to alleviate the computation burden, we transform implicit safety constraints into explicitly linear ones, such that the optimal control problem in DEMPC is a quadratic programming problem that can be solved efficiently. For theoretical analysis, sufficient conditions are derived to guarantee the recursive feasibility and stability of DEMPC, employing compatibility constraints, tube techniques and terminal ingredient tuning. Moreover, we extend our approach with globally optimal and distributed online EB configuration methods to shorten the minimal distance among VCTS. Finally, experimental results demonstrate the performance and advantages of the proposed approaches.

This research explores the profound impact of digital media on the lives of Chinese immigrants in Ikebukuro Chinatown. It illustrates how the Internet and digital platforms have transformed their economic, social, and identity landscapes. Employing qualitative methods such as surveys and interviews, this study underscores the pivotal role of social media in creating expansive networks. These networks facilitate ethnic entrepreneurship and enhance cultural visibility, contributing to the deterritorialization of traditional community confines. This empowerment enables the Chinese diaspora in Ikebukuro to cultivate a rich, interconnected social tapestry that extends beyond geographic limitations. The findings underscore the central role of digital media mediatization processes in redefining immigrant experiences. Additionally, they promote deeper, more dynamic integration within the host society’s multicultural environment. This transformative shift emphasizes the emergence of a more fluid, networked form of community and identity among immigrants. It challenges conventional enclave models and offers new perspectives on diaspora engagement in the digital age.

Abstract Background There is a high incidence of cervical cancer in Xinjiang. Genetic variation in human papillomavirus may increase its ability to invade, spread, and escape host immune response. Methods HPV16 genome was sequenced for 90 positive samples of HPV16 infection. Sequences of the E4, E5 and L2 genes were analysed to reveal sequence variation of HPV16 in Xinjiang and the distribution of variation among the positive samples of HPV16 infection. Results Eighty-one of the 90 samples of HPV16 infection showed variation in HPV16 E4 gene with 18 nucleotide variation sites, of which 8 sites were synonymous variations and 11 missense variations. 90 samples of HPV16 infection showed variation in HPV16 E5 and L2 genes with 16 nucleotide variation sites (6 synonymous, 11 missense variations) in the E5 gene and 100 nucleotide variation sites in L2 gene (37 synonymous, 67 missense variations). The frequency of HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A was higher in the case groups than in the control groups. Conclusions Phylogenetic tree analysis showed that 87 samples were European strains, 3 cases were Asian strains, there were no other variations, and G4181A was related to Asian strains. HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A were significantly more frequent in the case groups than in the control groups.

Abstract Objective Medical staff, especially nurses, suffered great anxiety and stress from the COVID-19 pandemic, which negatively affected their sleep quality. In this study, we aimed to analyze the sleep quality of nursing staff after terminating the Zero-COVID-19 policy in China. Methods 506 participants were involved in our study. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep status of the participants. Binary regression was performed to evaluate the impact factors related to sleep difficulty. Results The majority of participants (96.44%) suffered from sleep disturbances. There were significant differences in age, education level and front-line activity between participants with good sleep quality and sleep difficulty. Younger age (16–25 years old) was independently associated with less sleep difficulty, while front-line activity was independently associated with severe sleep difficulty. Conclusion Sleep disorder was very common among nurses after ending the Zero-COVID-19 policy in China. More front-line nurses suffered severe sleep difficulty in particular, which should be worthy of attention.

Liver sinusoidal endothelial cells (LSECs) are liver-specific endothelial cells with the highest permeability than other mammalian endothelial cells, characterized by the presence of fenestrae on their surface, the absence of diaphragms and the lack of basement membrane. Located at the interface between blood and other liver cell types, LSECs mediate the exchange of substances between the blood and the Disse space, playing a crucial role in maintaining substance circulation and homeostasis of multicellular communication. As the initial responders to chronic liver injury, the abnormal LSEC activation not only changes their own physicochemical properties but also interrupts their communication with hepatic stellate cells and hepatocytes, which collectively aggravates the process of liver fibrosis. In this review, we have comprehensively updated the various pathways by which LSECs were involved in the initiation and aggravation of liver fibrosis, including but not limited to cellular phenotypic change, the induction of capillarization, decreased permeability and regulation of intercellular communications. Additionally, the intervention effects and latest regulatory mechanisms of anti-fibrotic drugs involved in each aspect have been summarized and discussed systematically. As we studied deeper into unraveling the intricate role of LSECs in the pathophysiology of liver fibrosis, we unveil a promising horizon that pave the way for enhanced patient outcomes.

Highlights A carbon free self supported Mott-Schottky heterostructure was constructed as an efficient cathode catalyst for lithium oxygen batteries, achieving homogeneous contact between the two materials for strong interfacial interactions. The heterostructure triggered interfacial perturbations and band structure changes, which accelerated oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) kinetics, resulting in an extremely long cycle life of 800 cycles and an extremely low overpotential of 0.73 V. Combined with advanced characterization techniques and density functional theory calculations, the underlying mechanism behind the boosted ORR/OER activities and the electrocatalytic mechanism were revealed.

Abstract BackgroundLiver cancer continues to pose a significant burden in China. To enhance the efficiency of screening, it is crucial to implement population stratification for liver cancer surveillance. ObjectiveThis study aimed to develop a simple prediction model and risk score for liver cancer screening in the general population, with the goal of improving early detection and survival. MethodsThis population-based cohort study focused on residents aged 40 to 74 years. Participants were enrolled between 2014 and 2019 and were prospectively followed until June 30, 2021. Data were collected through interviews at enrollment. A Cox proportional hazards regression was used to identify predictors and construct the prediction model. A risk score system was developed based on the weighted factors included in the prediction model. ResultsA total of 153,082 study participants (67,586 males and 85,496 females) with a mean age of 55.86 years were included. During 781,125 person-years of follow-up (length of follow-up: median 6.07, IQR 3.07‐7.09 years), 290 individuals were diagnosed with liver cancer. Key factors identified for the prediction model and risk score system included age (hazard ratio [HR] 1.06, 95% CI 1.04‐1.08), sex (male: HR 3.41, 95% CI 2.44‐4.78), education level (medium: HR 0.84, 95% CI 0.61‐1.15; high: HR 0.37, 95% CI 0.17‐0.78), cirrhosis (HR 11.93, 95% CI 7.46‐19.09), diabetes (HR 1.59, 95% CI 1.08‐2.34), and hepatitis B surface antigen (HBsAg) status (positive: HR 3.84, 95% CI 2.38‐6.19; unknown: HR 1.04, 95% CI 0.73‐1.49). The model exhibited excellent discrimination in both the development and validation sets, with areas under the curve (AUC) of 0.802, 0.812, and 0.791 for predicting liver cancer at the 1-, 3-, and 5-year periods in the development set and 0.751, 0.763, and 0.712 in the validation set, respectively. Sensitivity analyses applied to the subgroups of participants without cirrhosis and with a negative or unknown HBsAg status yielded similar performances, with AUCs ranging from 0.707 to 0.831. Calibration plots indicated an excellent agreement between the observed and predicted probabilities of developing liver cancer over the 1-, 3-, and 5-year periods. Compared to the low-risk group, participants in the high-risk and moderate-risk groups had 11.88-fold (95% CI 8.67‐16.27) and 3.51-fold (95% CI 2.58‐4.76) higher risks of liver cancer, respectively. Decision curve analysis demonstrated that the risk score provided a higher net benefit compared to the current strategy. To aid in risk stratification for individual participants, a user-friendly web-based scoring system was developed. ConclusionsA straightforward liver cancer prediction model was created by incorporating easily accessible variables. This model enables the identification of asymptomatic individuals who should be prioritized for liver cancer screening.

Extracellular vesicles (EVs), submicron-sized membranous structures released by cells, serve as vehicles of tissue-specific proteins and nucleic acids, facilitating intercellular communication and playing roles in pathophysiological processes. Leveraging their unique characteristics, EVs have emerged as promising drug delivery nanocarriers. Electroporation (EP) and ultrasonication (US) are among the prevalent techniques used for loading exogenous drugs into EVs owing to their simplicity and efficiency. However, the effectiveness of the two methods in depleting initial EV cargo has been overlooked. But this information is indispensable, as the bioactive residuals of EVs, notably derived from tumor or stem donor cells, may impact downstream therapeutic effects. Bridging this knowledge gap, therefore, can guide the selection of optimal drugs and loading methods tailored to therapeutic objectives. Here, we used high-throughput sequencing to investigate the protein and small RNA cargo of EVs treated with EP and US, respectively. We found that US exhibits higher efficacy in depleting EV cargo compared to EP, while US may also deplete essential endogenous molecules for combination therapy. Neither method demonstrated significant selectivity in cargo depletion, but they might preferentially retain few specific molecules. Additionally, membrane proteins are more prone to loss during US and EP treatments than cytoplasmic proteins.

Background: Multiple brands of immune checkpoint inhibitors (ICIs), including domestic and imported agents, have been approved as front-line therapy in China. However, little is known about the difference in efficacy and safety of these agents of different origins. This study aims to systematically compare the difference between National Medical Products Administration (NMPA) approved domestic and imported ICIs regarding their efficacy, safety, and price. Methods: We systematically searched PubMed, Embase, and Cochrane Central, from inception to July 1st, 2023, for phase III trials evaluating ICIs as first- or second-line settings that have available hazard ratio (HR) for Asians or non-Asians. Studies of domestic and imported ICIs were screened and paired by the matching clinical characteristics as mirror groups. The primary endpoint was to assess the difference in efficacy between domestic and imported ICIs regarding overall survival. An effect size was derived from each mirror group and then pooled across all groups using a random-effects model. Heterogeneity was assessed by I2 statistics. Monthly treatment costs for each drug were calculated based on dosing information on National Medical Products Administration (NMPA) label and prices extracted from INSIGHT database. The difference in monthly treatment costs was compared by unpaired T-test. The protocol is registered on PROSPERO, CRD42024580753. Results: Overall, domestic ICIs exhibited better efficacy regarding overall survival (HR, 0.87; 95 % CI, 0.79–0.97; P < 0.05; I2 = 0) compared with imported agents. No difference was observed regarding benefits in progression free survival (HR, 0.95; 95 % CI, 0.82–1.09; P > 0.05; I2 = 0). Consistent results were obtained through frequentists and Bayesian approaches. The differences in safety; measured by relative risk of treatment-related adverse events (TARE) of any grade, TARE of grade 3 or higher, immune-related adverse events(irAE) of any grade, irAE of grade 3 or higher, discontinuation due to treatment, and death due to treatment; were also similar between domestic and imported ICIs. Moreover, in current Chinese market, the monthly treatment prices of domestic ICIs was statistically lower than that of imported ICIs (P < 0.01). Conclusions: Our research provides an essential reference of cost-effectiveness of ICIs manufactured in China for clinicians in routine practice of cancer care as well as public health authorities for decision making process.

AbstractBackground Robot-assisted upper-limb rehabilitation has been studied for many years, with many randomised controlled trials (RCTs) investigating the effects of robotic-assisted training on affected limbs. The current trend directs towards end-effector devices. However, most studies have focused on the effectiveness of rehabilitation devices, but studies on device sizes are relatively few.Goal Systematically review the effect of a portable rehabilitation robot (PRR) on the rehabilitation effectiveness of paralysed upper limbs compared with non-robotic therapy.Methods A meta-analysis was conducted on literature that included the Fugl-Meyer Assessment (FMA) obtained from the PubMed and Web of Science (WoS) electronic databases until June 2023.Results A total of 9 studies, which included RCTs, were completed and a meta-analysis was conducted on 8 of them. The analysis involved 295 patients. The influence on upper-limb function before and after treatment in a clinical environment is analysed by comparing the experimental group using the portable upper-limb rehabilitation robot with the control group using conventional therapy. The result shows that portable robots prove to be effective (FMA: SMD = 0.696, 95% = 0.099 to.293, p

The purpose of this study is to explore the impact of challenge and hindrance stressors on employees’ knowledge-hiding behavior, based on self-reported data from 493 Chinese preschool teachers. The findings indicate that both challenge and hindrance stressors significantly increase knowledge hiding, with hindrance stressors exerting a more pronounced effect. Furthermore, the study reveals the mediating roles of job crafting and work withdrawal, highlighting the distinct mechanisms involved with these stressors. Specifically, challenge stressors increase the likelihood of knowledge hiding through work withdrawal while simultaneously decreasing it through job crafting; notably, the former pathway has a greater effect. In contrast, hindrance stressors consistently exert detrimental effects, amplifying the probability of knowledge hiding through both mediators, which explains their stronger impact compared to challenge stressors. Additionally, empowering leadership plays a crucial moderating role in this relationship. The adverse influence of hindrance stressors on knowledge hiding, as mediated by job crafting, intensifies under high levels of empowering leadership. These findings not only validate the newly constructed parallel mediation model within an educational context but also provide practical strategies for kindergarten administrators regarding knowledge management. Such strategies include effectively distinguishing and managing different types of job stressors, enhancing skills to empower employees, and organizing regular knowledge-sharing activities.

The ABC1K (activity of bc1 complex kinase) atypical protein kinase family regulates diverse physiological functions in plants, including the development, growth, and response of plants to various stress stimuli. However, to date, only a few members of the alfalfa (Medicago sativa) ABC1K gene family have been identified, which severely limits the exploration of the functional mechanism of alfalfa ABC1K. Here, we identified 22 ABC1K genes from the alfalfa genome and categorized them into four types on the basis of phylogenetic analysis results and gene structure. We then characterized the physical and biochemical properties, chromosomal location, subcellular localization, cis-regulatory elements, and conserved motifs of these genes. Transcript profiling analysis confirmed that MsABC1Ks were widely expressed in various alfalfa tissues, with tissue-specific expression. We also found that salt and drought conditions significantly regulated MsABC1K gene expression, thus indicating that MsABC1K genes perform critical functions in alfalfa’s response to abiotic stress. In summary, the findings of our study serve as an important basis to enhance the stress resistance of alfalfa and provide valuable insights to better comprehend the functions of the MsABC1K gene family.

The primary function of plant fibers in reconstituted tobacco is to enhance the physical strength, and it can quite modify their physical properties. This study demonstrated the effect of various plant fibers and their beating degrees on the physical properties of reconstituted tobacco. Tensile index, burst index, uniformity, tensile stiffness orientation, and thermal conductivity coefficient were examined. The result revealed that the mechanical properties of reconstituted tobacco varied according to the type and beating degree of the fibers. The mechanical properties of softwood, cotton, and bast fibers showed an initial increase followed by a decrease with increasing beating degree, while bamboo fiber showed a continuous improvement in mechanical properties proportional to the beating degree. Conversely, hardwood fiber displayed an inverse relationship with its beating degree. Under identical beating conditions, reconstituted tobacco containing softwood fibers showed the greatest improvement in tensile properties, achieving the highest tensile strength, thermal conductivity, and specific heat capacity. In particular, when softwood fibers were beaten to 50 °SR, the physical properties of the reconstituted tobacco peaked, with longitudinal and transverse tensile indices improving by 42.48% and 12.11%, respectively. Additionally, the bursting resistance index increased by 61.93%, and the thermal conductivity coefficient increased by 5.94%.

Understanding the puff-by-puff delivery mechanisms of key components of heated tobacco products is critical to developing product designs. This study investigates the puff-by-puff release patterns of key components in Natural Smoke Cigarettes (NSCs), which are designed to deliver nicotine without combustion by reducing oxygen content, utilizing a 30-s puff interval, a 2-s puff duration, and a 55 mL puff volume to simulate realistic smoking conditions. By establishing models to analyze the variation of nicotine, glycerol, 1,2-propylene glycol (PG), and water in different functional sections of the cigarette under controlled smoking conditions. These sections include the tobacco, hollow, cooling, and filter sections, constituting the structure of NSCs. In addition, the model calculates the port-by-port release of the components in the flue gas aerosol and compares it with the measured value. The results showed that: The retention amount in the tobacco section showed a steep decline in the first three puffs, with an overall exponential decrease. The amounts in the other sections were consistent, increasing in the first two puffs and then stabilizing. The retention amount decreased linearly with each puff, with a similar pattern across sections. The release amount peaked at the fourth to fifth puffs and then stabilized. The retention amount in the tobacco section declined exponentially in the first three puffs. It peaked in the second to third puffs in other sections, then decreased with each subsequent puff. The retention amount in the tobacco section showed a significant decline in the first puff, stabilizing at around 4 mg. In other sections, it peaked at the first puff and then rapidly declined. These findings can inform the development of reduced-harm smoking products and contribute to a better understanding of the dynamics of smoke generation. Additionally, the study offers a reference for the puff-by-puff release stability of NSCs and the improvement of consumers’ sensory quality.