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Abstract Inflammatory signals lead to recruitment of circulating monocytes and induce their differentiation into pro-inflammatory macrophages. Therefore, whether blocking inflammatory monocytes can mitigate disease progression is being actively evaluated. Here, we employ multiple lineage-tracing models and show that monocyte-derived macrophages (mo-mac) are the major population of immunosuppressive, liver metastasis-associated macrophages (LMAM), while the proportion of Kupffer cells (KC) as liver-resident macrophages is diminished in metastatic nodules. Paradoxically, genetic ablation of mo-macs results in only a marginal decrease in LMAMs. Using a proliferation-recording system and a KC-tracing model in a monocyte-deficient background, we find that LMAMs can be replenished either via increased local macrophage proliferation or by promoting KC infiltration. In the latter regard, KCs undergo transient proliferation and exhibit substantial phenotypic and functional alterations through epigenetic reprogramming following the vacating of macrophage niches by monocyte depletion. Our data thus suggest that a simultaneous blockade of monocyte recruitment and macrophage proliferation may effectively target immunosuppressive myelopoiesis and reprogram the microenvironment towards an immunostimulatory state.

Abstract Multifunctional composites have been continuously developed for a myriad of applications with remarkable adaptability to external stimuli and dynamic responsiveness. This study introduces a 4D printing method for liquid crystal elastomer (LCE) composites with continuous fibers and unveils their multifunctional actuation and exciting mechanical responses. During the printing process, the relative motion between the continuous fiber and LCE resin generates shear force to align mesogens and enable the monodomain state of the matrix materials. The printed composite lamina exhibits reversible folding deformations that are programmable by controlling printing parameters. With the incorporation of fiber reinforcement, the LCE composites not only demonstrate high actuation forces but also improved energy absorption and protection capabilities. Diverse shape-changing configurations of 4D composite structures can be achieved by tuning the printing pathway. Moreover, the incorporation of conductive fibers into the LCE matrix enables electrically induced shape morphing in the printed composites. Overall, this cost-effective 4D printing method is poised to serve as an accessible and influential approach when designing diverse applications of LCE composites, particularly in the realms of soft robotics, wearable electronics, artificial muscles, and beyond.

Abstract Hydrocephalus can affect brain function and motor ability. Current treatments mostly involve invasive surgeries, with a high risk of postoperative infections and failure. A successful animal model plays a significant role in developing new treatments for hydrocephalus. Hydrocephalus was induced in Sprague–Dawley rats by injecting 25% kaolin into the subarachnoid space at the cerebral convexities with different volumes of 30, 60 and 90 μL. Magnetic resonance imaging (MRI) was performed 1 month and 4 months after kaolin injection. The behavioral performance was assessed weekly, lasting for 7 weeks. The histopathological analyses were conducted to the lateral ventricles by hematoxylin–eosin (HE) staining. Transcriptomic analysis was used between Normal Pressure Hydrocephalus (NPH) patients and hydrocephalus rats. MRI showed a progressive enlargement of ventricles in hydrocephalus group. Kaolin‐60 μL and kaolin‐90 μL groups showed larger ventricular size, higher anxiety level, bigger decline in body weight, motor ability and cognitive competence. These symptoms may be due to higher‐grade inflammatory infiltrate and the damage of the structure of ependymal layer of the ventricles, indicated by HE staining. The overlap upregulated genes and pathways mainly involve immunity and inflammation. Transcriptomic revealed shared pathogenic genes CD40, CD44, CXCL10, and ICAM1 playing a dominance role. 60 μL injection might be recommended for the establishment of hydrocephalus animal model, with a high successful rate and high stability. The hydrocephalus model was able to resemble the inflammatory mechanism and behavioral performance observed in human NPH patients, providing insights for identifying therapeutic targets for hydrocephalus.

Abstract Background Delivering HD-tDCS on individual motor hotspot with optimal electric fields could overcome challenges of stroke heterogeneity, potentially facilitating neural activation and improving motor function for stroke survivors. However, the intervention effect of this personalized HD-tDCS has not been explored on post-stroke motor recovery. In this study, we aim to evaluate whether targeting individual motor hotspot with HD-tDCS followed by EMG-driven robotic hand training could further facilitate the upper extremity motor function for chronic stroke survivors. Methods In this pilot randomized controlled trial, eighteen chronic stroke survivors were randomly allocated into two groups. The HDtDCS-group (n = 8) received personalized HD-tDCS using task-based fMRI to guide the stimulation on individual motor hotspot. The Sham-group (n = 10) received only sham stimulation. Both groups underwent 20 sessions of training, each session began with 20 min of HD-tDCS and was then followed by 60 min of robotic hand training. Clinical scales (Fugl-meyer Upper Extremity scale, FMAUE; Modified Ashworth Scale, MAS), and neuroimaging modalities (fMRI and EEG-EMG) were conducted before, after intervention, and at 6-month follow-up. Two-way repeated measures analysis of variance was used to compare the training effect between HDtDCS- and Sham-group. Results HDtDCS-group demonstrated significantly better motor improvement than the Sham-group in terms of greater changes of FMAUE scores (F = 6.5, P = 0.004) and MASf (F = 3.6, P = 0.038) immediately and 6 months after the 20-session intervention. The task-based fMRI activation significantly shifted to the ipsilesional motor area in the HDtDCS-group, and this activation pattern increasingly concentrated on the motor hotspot being stimulated 6 months after training within the HDtDCS-group, whereas the increased activation is not sustainable in the Sham-group. The neuroimaging results indicate that neural plastic changes of the HDtDCS-group were guided specifically and sustained as an add-on effect of the stimulation. Conclusions Stimulating the individual motor hotspot before robotic hand training could further enhance brain activation in motor-related regions that promote better motor recovery for chronic stroke. Trial registration This study was retrospectively registered in ClinicalTrials.gov (ID NCT05638464).

Abstract Feline mesenchymal stem cells (fMSCs) are well known for their robust differentiation capabilities and are commonly used in studying immune-related diseases in cats. Despite their importance, the susceptibility of fMSCs to viral infections remains uncertain. This study aimed to assess the susceptibility of feline adipose-derived mesenchymal stem cells (fAD-MSCs) and feline umbilical cord-derived mesenchymal stem cells (fUC-MSCs) to common feline viruses, including feline coronavirus (FCoV), feline herpesvirus type 1 (FHV-1), and feline panleukopenia virus (FPV). The results demonstrated that both FCoV and FHV-1 were able to infect both types of cells, while FPV did not exhibit cytopathic effects on fUC-MSCs. Furthermore, all three viruses were successfully isolated from fAD-MSCs. These findings suggest that certain feline viruses can replicate in fMSCs, indicating potential limitations in using fMSCs for treating viral diseases caused by these specific viruses. This study has important clinical implications for veterinarians, particularly in the management of viral diseases.

Abstract Background Higher mammographic density (MD), a radiological measure of the proportion of fibroglandular tissue in the breast, and lower terminal duct lobular unit (TDLU) involution, a histological measure of the amount of epithelial tissue in the breast, are independent breast cancer risk factors. Previous studies among predominantly white women have associated reduced TDLU involution with higher MD. Methods In this cohort of 611 invasive breast cancer patients (ages 23–91 years [58.4% ≥ 50 years]) from China, where breast cancer incidence rates are lower and the prevalence of dense breasts is higher compared with Western countries, we examined the associations between TDLU involution assessed in tumor-adjacent normal breast tissue and quantitative MD assessed in the contralateral breast obtained from the VolparaDensity software. Associations were estimated using generalized linear models with MD measures as the outcome variables (log-transformed), TDLU measures as explanatory variables (categorized into quartiles or tertiles), and adjusted for age, body mass index, parity, age at menarche and breast cancer subtype. Results We found that, among all women, percent dense volume (PDV) was positively associated with TDLU count (highest tertile vs. zero: Expbeta = 1.28, 95% confidence interval [CI] 1.08–1.51, ptrend =

Abstract A brain-computer interface (BCI) enables users to control devices with their minds. Despite advancements, non-invasive BCIs still exhibit high error rates, prompting investigation into the potential reduction through concurrent targeted neuromodulation. Transcranial focused ultrasound (tFUS) is an emerging non-invasive neuromodulation technology with high spatiotemporal precision. This study examines whether tFUS neuromodulation can improve BCI outcomes, and explores the underlying mechanism of action using high-density electroencephalography (EEG) source imaging (ESI). As a result, V5-targeted tFUS significantly reduced the error in a BCI speller task. Source analyses revealed a significantly increase in theta and alpha activities in the tFUS condition at both V5 and downstream in the dorsal visual processing pathway. Correlation analysis indicated that the connection within the dorsal processing pathway was preserved during tFUS stimulation, while the ventral connection was weakened. These findings suggest that V5-targeted tFUS enhances feature-based attention to visual motion.

Abstract Ancient murals have suffered from continuous damage over time, and especially paint loss disease. Therefore, disease labeling, as the basis for ancient mural restoration, plays an important role in the protection of cultural relics. The predominant method of disease labeling is currently manual labeling, which is highly dependent on expert experience, time consuming, inefficient and results in inconsistent accuracy of the marking effect. In this paper, we propose a labeling framework for paint loss disease of ancient murals based on hyperspectral image classification and segmentation. The proposed framework involves first the extraction of features from the hyperspectral image, and then image segmentation is performed based on the spatial features to obtain more accurate region boundaries. Then, the hyperspectral image’s regions are classified based on their spatial-spectral characteristics, and the candidate areas of paint loss disease are obtained. Finally, by leveraging the true color image segmentation results, the proposed disease labeling strategy combines the results of classification and segmentation to propose the final paint loss disease labeling areas. The experimental results show that the proposed method can not only combine the hyperspectral space and spectral information effectively to obtain accurate labeling of paint loss disease, but can also mark the paint loss disease not easily observed using ordinary digital cameras. Compared with the state-of-the-art methods, the proposed framework could be promising for accurate and effective paint loss disease labeling for ancient murals.

BackgroundLiposarcoma (LPS) is a kind of malignancy of soft tissue usually found in the retroperitoneal, limb, or neck region, and some may be detected with delayed symptoms (pain or palpable mass), and less frequently occurs in organs of the digestive system. In contrast, Dedifferentiated liposarcoma (DDLPS) is a common histological subtype of LPS. The present study reported a case of dedifferentiated liposarcoma originating in the gallbladder. Differentiated liposarcoma originating from the gallbladder is rarely reported.Case descriptionA 64-year-old female patient presented to our hospital with a painless abdominal mass. Abdominal computed tomography (CT) showed that the gallbladder had lost its normal shape, and a 9.1 cm × 7.1 cm × 12.1 cm mass was seen in the area of the gallbladder fossa and the right upper abdomen below it, which had an irregular morphology, inhomogeneous density, and nodular calcification, with marked inhomogeneous enhancement on enhancement scan. Preoperative tumor markers and liver function indicators were not abnormal. With suspicion of a giant malignant tumor of the gallbladder, she underwent a cholecystectomy combined with abdominal mass resection. After surgery, the tumor and gallbladder, were completely resected, and postoperative pathological results confirmed the diagnosis of dedifferentiated liposarcoma deriving from gallbladder. After surgery, the patient and his family refused to continue treatment. After 15 months follow-up, the patient remains asymptomatic and does not show any signs of recurrence. And she is now under continued follow - up.ConclusionsTreatment of dedifferentiated liposarcoma is still at exploratory stage, and a lack of clinical evidence for this condition might hinder access to clinical trials and studies. Currently, the treatment of choice for dedifferentiated liposarcoma remains radical resection. In the available clinical studies, there are no robust data to support clinical use of neoadjuvant and adjuvant radiochemotherapy. As with other diseases, the use of radiotherapy and chemotherapy before and after surgery may be a potential future treatment.

As more multi-ancestry GWAS summary data become available, we have developed a comprehensive trans-ancestry pathway analysis framework that effectively utilizes this diverse genetic information. Within this framework, we evaluated various strategies for integrating genetic data at different levels-SNP, gene, and pathway-from multiple ancestry groups. Through extensive simulation studies, we have identified robust strategies that demonstrate superior performance across diverse scenarios. Applying these methods, we analyzed 6,970 pathways for their association with schizophrenia, incorporating data from African, East Asian, and European populations. Our analysis identified over 200 pathways significantly associated with schizophrenia, even after excluding genes near genome-wide significant loci. This approach substantially enhances detection efficiency compared to traditional single-ancestry pathway analysis and the conventional approach that amalgamates single-ancestry pathway analysis results across different ancestry groups. Our framework provides a flexible and effective tool for leveraging the expanding pool of multi-ancestry GWAS summary data, thereby improving our ability to identify biologically relevant pathways that contribute to disease susceptibility.

Abstract Macropsini is a tribe of Eurymelinae in the family Cicadellidae that is widely distributed worldwide. Still, its taxonomic status has been unstable, and the classification of certain clades at the genus level has been controversial. The aim of this study is to address the patterns and processes that explain the structure and the evolution of the mitogenomes of Macropsini, while contributing to the resolution of systematic issues involving five of their genera. To this task, the mitogenomes of 26 species of the tribe were sequenced and characterized, and their phylogenetic relationships were reconstructed. The results revealed that the nucleotide composition of mitochondrial genes in these 26 species was significantly skewed toward A and T. Codons ending with T or A in relative synonymous codon usage were significantly more prevalent than those ending with C or G. The parity plot, neutrality plot, and correspondence analysis revealed that mutation and selective pressure affect codon usage patterns. In the phylogenetic relationships of the Macropsini, the monophyly of Pedionis and Macropsis was well‐supported. Meanwhile, Oncopsis revealed paraphyletic regarding Pediopsoides. In conclusion, this research not only contributes the valuable data to the understanding of the mitogenome of the Macropsini but also provides a reference for future investigations on codon usage patterns, potential adaptive evolution, and the phylogeny of the mitogenome within the subfamily Eurymelinae.

Abstract Spike length (SL) is one of the most important agronomic traits affecting yield potential and stability in wheat. In this study, a major stable quantitative trait locus (QTL) for SL, i.e., qSl-2B, was detected in multiple environments in a recombinant inbred line (RIL) mapping population, KJ-RILs, derived from a cross between Kenong 9204 (KN9204) and Jing 411 (J411). The qSl-2B QTL was mapped to the 60.06–73.06 Mb region on chromosome 2B and could be identified in multiple mapping populations. An InDel molecular marker in the target region was developed based on a sequence analysis of the two parents. To further clarify the breeding use potential of qSl-2B, we analyzed its genetic effects and breeding selection effect using both the KJ-RIL population and a natural mapping population, which consisted of 316 breeding varieties/advanced lines. The results showed that the qSl-2B alleles from KN9204 showed inconsistent genetic effects on SL in the two mapping populations. Moreover, in the KJ-RILs population, the additive effects analysis of qSl-2B showed that additive effect was higher when both qSl-2D and qSl-5A harbor negative alleles under LN and HN. In China, a moderate selection utilization rate for qSl-2B was found in the Huanghuai winter wheat area and the selective utilization rate for qSl-2B continues to increase. The above findings provided a foundation for the genetic improvement of wheat SL in the future via molecular breeding strategies.

Asymmetric rolling is beneficial for grain refinement and properties improvement through mass production of metals. This study introduces a novel asymmetric rolling technology, known as dynamic offsets and shear force adjustment (DS) rolling. DS rolling not only achieves roll offset and differential speed/diameter, but maintains a constant offset angle in multiple passes. And rolling mechanics model, finite element model, and rolling experiment is established. The results indicate the advantages of DS rolling in reducing the vertical rolling force with increasing offset angles. Moreover, it is observed that the vertical rolling force initially decreases and subsequently increases as the roll-to-diameter ratio increases. DS rolling enhances both average strain and core strain compared to symmetrical rolling, consequently promoting uniformity in strain distribution and permeability into the core region. The shear stress is the primary factor contributing to the increase in equivalent strain during DS rolling. The adjustment of roller diameter ratio and offset angle allows for control over the shear stress level. DS rolling enhances mechanical properties and refines the grain structure. Notably, at an offset angle of 9°, DS rolling results in a substantial increase in microhardness on the upper surface, center, and lower surface of Cu by 3.31 %, 8.40 %, and 8.19 %, respectively, when compared to symmetrical rolling. Furthermore, DS rolling exhibits an enhanced tensile strength and elongation, yielding improvements of 5.12 % and 38.9 % compared to symmetrical rolling, respectively. Additionally, DS rolling leads to a reduction in grain size by 5.77 %, 17.3 %, and 21.7 % on the upper surface, center, and lower surface, respectively.

The gut microbiota has been shown to be associated with a range of illnesses and disorders, including hypertension, which is recognized as the primary factor contributing to the development of serious cardiovascular diseases. In this review, we conducted a comprehensive analysis of the progression of the research domain pertaining to gut microbiota and hypertension. Our primary emphasis was on the interplay between gut microbiota and blood pressure that are mediated by host and gut microbiota-derived metabolites. Additionally, we elaborate the reciprocal communication between gut microbiota and antihypertensive drugs, and its influence on the blood pressure of the host. The field of computer science has seen rapid progress with its great potential in the application in biomedical sciences, we prompt an exploration of the use of microbiome databases and artificial intelligence in the realm of high blood pressure prediction and prevention. We propose the use of gut microbiota as potential biomarkers in the context of hypertension prevention and therapy.

BackgroundThe stress hyperglycemia ratio (SHR) has emerged as a potential prognostic indicator for various critical illnesses. However, its role in determining outcomes in patients with atrial fibrillation (AF) within the intensive care unit (ICU) remains unclear. This study aimed to elucidate the association between SHR and all-cause mortality in this clinical setting.MethodsWe conducted a retrospective cohort study utilizing data from a large, retrospective database. Critically ill patients with documented AF were stratified based on quartiles of SHR. The primary outcome was 365-day all-cause mortality, with secondary outcomes including 90-day and 28-day mortality. COX proportional hazards models adjusted for confounders and Kaplan-Meier curve analyses were used to explore the relationship between SHR and mortality.Results2,679 patients with critical AF were enrolled in the final study. Among the patients studied, those in the highest SHR quartiles exhibited an increased risk of 365-day all-cause mortality (HR:1.32, 95%CI=1.06-1.65). Notably, in subgroup analyses, the prognostic value of SHR was particularly pronounced in patients with hypertension. Sensitivity analyses confirmed the persistence of these findings after excluding cohorts with malignant tumors, and heart failure.ConclusionsOur research discerns a positive association between SHR and all-cause mortality in critically ill patients with AF, highlighting the significance of acute glycemic dysregulation on patient outcomes. Longer follow-up is still needed in the future to study the association between SHR and all-cause mortality in critically ill patients with AF.

This study investigated influences of faba bean (Vicia faba L.) supplementary diet (VFSD) on tilapia muscle texture through muscle-gut axis. Tilapia were fed diets with varying VSFD contents for 60 days. Results indicated no significantly growth changes across groups. However, VFSD increased muscle hardness and chewiness, with higher collagen deposition between muscle fibers. Transcriptome revealed an increase in differentially-expressed genes (DEGs) related to myofibril component and TGF-β, MAPK, FOXO, insulin pathways. Crucial DEGs among interaction network between these pathways, including foxo3, mitf, smad1, smad7, and flt1, were validated via qPCR. Gut microbiota analysis showed VFSD decreased Pseudomonas, Ralstonia, and Aurantimicrobium abundance, while increased Rhodobacter, Akkermansia, and Propionibacteriaceae, which significantly impacting quorum sensing and ABC transporters. Microbiota variation highly correlated with muscle DEGs, suggesting a link between muscle phenotype and gut microbiota. In summary, VFSD alters meat texture by influencing collagen deposition and myofibril reconstruction, which may be regulated by LPS- and ROS-related pathways through altering the composition of the microbial community.

This study investigated the effects of adding various concentrations of cholesterol and soy lecithin to feed on the growth performance, physiology, biochemistry, and serum metabolomics of Cyprinus carpio var. Two cholesterol concentrations (1 % and 2 %) and four soy lecithin concentrations (0 %, 2 %, 4 %, and 6 %) were employed, resulting in eight experimental groups (C1S0, C1S2, C1S4, C1S6, C2S0, C2S2, C2S4, and C2S6) that were cultivated for 60 days. The addition of C2S2 to the feeds enhanced the growth (WGR and SGR), antioxidant capacity (CAT, SOD, MDA, T-AOC, and GSH-Px), and lipid metabolism (TG, LDL-C, HDL-C, LPL, and HL) in C. carpio var. A significant interaction (P < 0.05) was observed between cholesterol and soy lecithin concentrations for WGR, SGR, and FCR, and a highly significant interaction (P < 0.01) was observed for CAT, SOD, T-AOC, GSH-Px, TG, LDL-C, and HDL-C in C. carpio var. Based on these results, three comparisons (C1S4-vs-C1S0, C2S2-vs-C2S0, and C2S2-vs-C1S2) were selected to analyze the serum metabolic profiles of C. carpio var. through LC-MS. The differential metabolites screened included amino acids and their metabolites, nucleotides and their metabolites, bile acids, fatty acids, carbohydrates and their metabolites. The metabolic pathways involved were purine metabolism, glycine, serine, and threonine metabolism, arginine and proline metabolism, and ABC transporter proteins. In summary, the interaction between cholesterol and soy lecithin significantly influenced the growth performance, antioxidant capacity, and cholesterol metabolism of C. carpio var. The most beneficial effects on growth and lipid metabolism were observed when both cholesterol and soy lecithin were added at a concentration of 2 %. The present study provides theoretical guidance for the appropriate concentrations of cholesterol and lecithin in aquafeeds.

Abstract Memristors are a candidate device for artificial neural systems due to their excellent conductance‐regulation ability and potential to simulate the characteristics of biological synapses. This study fabricated a Pt/TaOx/TiOy/Ti analog artificial synapse memristor that exhibits excellent multilevel storage property with a large on/off ratio of ≈660 times. The dynamic resistive switching mechanism is well expounded and validated by the reset stopping voltage dependent Schottky fitting results. Moreover, the essential biological synaptic characteristics such as long‐term potentiation/depression (LTP/D) and paired‐pulse facilitation (PPF) are successfully mimicked with a low pulse energy consumption of 12.69 nJ. A neuromorphic network constructed on the enhanced symmetry and linearity of conductance for this Pt/TaOx/TiOy/Ti memristive device can achieve 92.45% accuracy in recognizing handwritten pattern. These results demonstrate a significant potential for application Pt/TaOx/TiOy/Ti memristor in non‐volatile memory and bioinspired neuromorphic systems.

BackgroundAlthough diabetic retinopathy (DR) is closely related to dietary patterns and oxidative stress, there is little research on the relationship between the compound dietary antioxidant index (CDAI) and DR. This study aims to fill this gap by analyzing data from the National Health and Nutrition Examination Survey (NHANES) to explore the association between CDAI and DR in patients with type 2 diabetes, in order to provide a basis for dietary guidance to prevent DR.MethodsData for this study was obtained from NHANES conducted between 1999 and 2020. Information regarding dietary intake was collected through 24 h dietary recall interviews. Multivariate logistic regression analyses and restricted cubic splines (RCS) were employed to explore the association between CDAI and DR. Furthermore, subgroup analyses were conducted to further examine the relationship.ResultsIn this study, a total of 2,158 participants were included, with a mean age of 58.87 years. After adjusting for all potential confounding factors, multivariate logistic regression analyses consistently demonstrated a negative correlation between CDAI and DR (OR = 0.94, 95%CI: 0.90–0.98, p = 0.007). Specifically, individuals in the highest quartile of CDAI had a significantly reduced risk of DR compared to those in the lowest quartile (OR = 0.51, 95%CI: 0.34–0.75, p

Supervised machine learning (SML) has become a crucial tool for estimating water quality parameters (WQPs) from satellite images. Its effectiveness relies heavily on synchronised in-situ datasets covering diverse water bodies. However, collecting such datasets is time-consuming, resulting in temporal gaps between sampling and imaging. In addition, the in situ dataset may exhibit an imbalance. These imperfections could introduce uncertainties to SML-derived models, compromising the accuracy of the WQP estimates. Using in situ data collected automatically every four hours, the estimation of both optically active parameters (OAPs) and non-optically active parameters (nOAPs) in the Middle Reaches of the Yangtze River (MRYR) serves as an example to illustrate the importance of this challenge in freshwater remote sensing. Additionally, the investigation was extended to estimate OAPs and nOAPs in lakes of Wuhan through manual sampling measurements, thereby bridging theoretical insights with real-world applications. Employing four ML algorithms, the SML-based models for each WQP were calibrated using in situ datasets with different spatio-temporal distributions. The results demonstrated that precision decreased with increasing time gaps, whereas most nOAPs (COD, TP, TN, pH, and DO) showed greater robustness to the time gap than the OAPs (turbidity, Secchi depth, Chl-a, and algae density). The mean absolute percentage errors (MAPEs) of these nOAPs were as follows: for all models, pH MAPEs

ObjectiveThis study aimed to examine the relationship between lipoprotein (a) (Lp[a]) and other blood lipid indexes and carotid artery atherosclerosis in patients with acute ischemic stroke (AIS).MethodsA total of 2,018 patients were selected from the hospital “acute stroke intervention and secondary prevention registration database” by identifying blood fat indexes (cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and Lp[a]). Based on the results of carotid artery ultrasound examinations, the patients were divided into a “no plaque” group, comprising 400 patients, a “plaque and no stenosis” group, comprising 1,122 patients and a “carotid stenosis” group, comprising 496 patients. The relationship between Lp(a) and blood lipid indexes and carotid artery atherosclerosis was then investigated using multi-factor logistics regression analysis.ResultsThere were 400 patients (19.8%) with no carotid plaque, 1,122 patients (55.6%) with plaque and no carotid stenosis and 496 patients (24.6%) with carotid stenosis. As the degree of carotid artery atherosclerosis increased, the Lp(a) level gradually increased; Lp(a) and cholesterol were identified as independent risk factors for carotid atherosclerosis.ConclusionLipoprotein (a) and cholesterol are independent risk factors for patients with AIS with carotid atherosclerosis, and their levels increase with the degree of carotid artery atherosclerosis; therefore, attention should focus on levels of cholesterol and Lp(a) in acute stroke patients to control atherosclerosis effectively.

BackgroundIncreased levels of serum Klotho have been associated with a reduced risk of several cardiovascular diseases (CVD). However, limited studies exist on the association between serum Klotho and mortality in patients with CVD.MethodsWe collected data from CVD patients in the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2016. We linked NHANES data with the National Death Index to determine the survival status of participants. Univariate and multivariable Cox regression models were used to investigate the relationship between serum Klotho levels and mortality in CVD patients. The relationship between serum Klotho quartiles and mortality in CVD patients was visualized using Kaplan-Meier (KM) curves and restricted cubic spine. Finally, subgroup analyses were used to examine the association between serum Klotho and all-cause mortality in different populations.Results1905 patients with CVD were finally enrolled in our study with a mean follow-up of 7.1 years. The average age of the participants was 63.4 years, with 58.40% being male. KM showed that lower Klotho levels were associated with lower survival rates. After adjusting for potential confounders, patients with higher serum Klotho levels had lower all-cause mortality (Q1: 1.00, Q2: 0.58 (0.42–0.80), Q3: 0.69 (0.47–1.01), and Q4:0.64 (0.45–0.92). However, the relationship between serum Klotho levels and cardiovascular mortality was not statistically significant. Dose-response analysis shows a U-shaped relationship between serum Klotho levels and all-cause mortality in patients with CVD (P nonlinear=0.002). Subgroup analysis indicated that participants with a history of hypertension had a higher risk of all-cause mortality in serum Klotho Q4 compared to Q1 (P trend

Summary: The cyclic AMP-responsive element-binding protein (CREB)-regulated transcription coactivator 2 (CRTC2) is a crucial regulator of hepatic lipid metabolism and gluconeogenesis and correlates with tumorigenesis. However, the mechanism through which CRTC2 regulates hepatocellular carcinoma (HCC) progression is largely unknown. Here, we found that increased CRTC2 expression predicted advanced tumor grade and stage, as well as worse prognosis in patients with HCC. DNA promoter hypomethylation led to higher CRTC2 expression in HCC. Functionally, CRTC2 contributed to HCC malignant phenotypes through the activated Wnt/β-catenin pathway, which could be abrogated by the small-molecular inhibitor XAV-939. Moreover, Crtc2 facilitated tumor growth while concurrently downregulating the PD-L1/PD-1 axis, resulting in primary resistance to immunotherapy. In immunocompetent mice models of HCC, targeting Crtc2 in combination with anti-PD-1 therapy prominently suppressed tumor growth by synergistically enhancing responsiveness to immunotherapy. Collectively, targeting CRTC2 might be a promising therapeutic strategy to sensitize immunotherapy in HCC.

Abstract Extractive approaches have been the mainstream paradigm for identifying overlapping entity–relation extraction. However, limited by their inherently methodological flaws, which hardly deal with three issues: hierarchical dependent entity–relations, implicit entity–relations, and entity normalization. Recent advances have proposed an effective solution based on generative language models, which cast entity–relation extraction as a sequence-to-sequence text generation task. Inspired by the observation that humans learn by getting to the bottom of things, we propose a novel framework, namely GenRE, Generative multi-turn question answering with contrastive learning for entity–relation extraction. Specifically, a template-based question prompt generation first is designed to answer in different turns. We then formulate entity–relation extraction as a generative question answering task based on the general language model instead of span-based machine reading comprehension. Meanwhile, the contrastive learning strategy in fine-tuning is introduced to add negative samples to mitigate the exposure bias inherent in generative models. Our extensive experiments demonstrate that GenRE performs competitively on two public datasets and a custom dataset, highlighting its superiority in entity normalization and implicit entity–relation extraction. (The code is available at https://github.com/lovelyllwang/GenRE ).

The Environmental Trace Gases Monitoring Instrument 2 (EMI-02) payload, embarked on a hyperspectral observation satellite, was launched on September 7, 2021. The satellite's transit time is 10:30 local time. This article, drawing on data from EMI-02, introduces a methodology for measuring the tropical tropospheric ozone column (TOC) using the convective-cloud-differential method. We successfully applied this method to derive TOC in tropical regions from the EMI-02 data. The results indicate a general consistency between the EMI-02 TOC and TROPOspheric Monitoring Instrument (TROPOMI) TOC. However, owing to the difference in transit times, the TOC observed by TROPOMI at 13:30 is higher than that observed by EMI-02 at 10:30. Comparisons with ozonesonde data revealed discrepancies attributed to varying observation times, but nonetheless presented a high degree of consistency. These findings affirm the efficacy of our algorithm in providing reliable and precise TOC data. This capability is instrumental in understanding the diurnal variations of tropical TOC, where concentrations are higher in the afternoon than in the morning. The characteristics of tropical TOC varied by month. From June to October, the tropical TOC predominantly accumulated over the South Atlantic region, whereas, it tended to disperse and distribute near the 20°N latitude from November to May.

EMG-driven robot hand training can facilitate motor recovery in chronic stroke patients by restoring the interhemispheric balance between motor networks. However, the underlying mechanisms of reorganization between interhemispheric regions remain unclear. This study investigated the effective connectivity (EC) between the ventral premotor cortex (PMv), supplementary motor area (SMA), and primary motor cortex (M1) using Dynamic Causal Modeling (DCM) during motor tasks with the paretic hand. Nineteen chronic stroke subjects underwent 20 sessions of EMG-driven robot hand training, and their Action Reach Arm Test (ARAT) showed significant improvement ( $\beta $ =3.56, $\text{p} < 0.001$ ). The improvement was correlated with the reduction of inhibitory coupling from the contralesional M1 to the ipsilesional M1 (r=0.58, p=0.014). An increase in the laterality index was only observed in homotopic M1, but not in the premotor area. Additionally, we identified an increase in resting-state functional connectivity (FC) between bilateral M1 ( $\beta $ =0.11, p=0.01). Inter-M1 FC demonstrated marginal positive relationships with ARAT scores (r=0.402, p=0.110), but its changes did not correlate with ARAT improvements. These findings suggest that the improvement of hand functions brought about by EMG-driven robot hand training was driven explicitly by task-specific reorganization of motor networks. Particularly, the restoration of interhemispheric balance was induced by a reduction in interhemispheric inhibition from the contralesional M1 during motor tasks of the paretic hand. This finding sheds light on the mechanistic understanding of interhemispheric balance and functional recovery induced by EMG-driven robot training.

Background & Aims: Metabolic dysfunction–associated steatohepatitis (MASH) is a common chronic liver disease worldwide. No effective pharmacologic therapies for MASH have been developed; to develop such promising drugs, the underlying mechanisms regulating MASH need to be elucidated. Here, we aimed to determine the role of ovarian tumor domain-containing protein 5 (OTUD5) in MASH progression and identify a specific mechanism. Methods: The expression levels of OTUD subfamily under palmitic acid/oleic acid (PAOA) stimulation were screened. OTUD5 expression was assessed in human liver tissues without steatosis, those with simple steatosis, and those with MASH. MASH models were developed in hepatocyte-specific Otud5-knockout mice that were fed high-fat high-cholesterol and high-fat high-cholesterol plus high-fructose/sucrose diet for 16 weeks. Results: The expression of OTUD5 was down-regulated in fatty liver and was negatively related to the progression of MASH. Lipid accumulation and inflammation were exacerbated by Otud5 knockdown but attenuated by Otud5 overexpression under PAOA treatment. Hepatocyte-specific Otud5 deletion markedly exacerbated steatosis, inflammation, and fibrosis in the livers of 2 MASH mouse models. We identified voltage-dependent anion channel 2 (VDAC2) as an OTUD5-interacting partner; OTUD5 cleaved the K48-linked polyubiquitin chains from VDAC2, and it inhibited subsequent proteasomal degradation. The anabolic effects of OTUD5 knockdown on PAOA-induced lipid accumulation were effectively reversed by VDAC2 overexpression in primary hepatocytes. Metabolomic results revealed that VDAC2 is required for OTUD5-mediated protection against hepatic steatosis by maintaining mitochondrial function. Conclusions: OTUD5 may ameliorate MASH progression via VDAC2-maintained mitochondrial homeostasis. Targeting OTUD5 may be a viable MASH-treatment strategy.

The Environmental Trace Gases Monitoring Instrument (EMI) series are second-generation Chinese spectrometers on board the GaoFen-5 (GF-5) and DaQi-1 (DQ-1) satellites. In this study, a comparative analysis of EMI series data was conducted to determine the daily trend of ozone concentration changes owing to different transit times and to improve the overall quality and reliability of EMI series datasets. The daily EMI total ozone column (TOC) obtained using the Differential Optical Absorption Spectroscopy (DOAS) method were compared to vertical column density (VCD) gathered by the TROPOspheric Monitoring Instrument (TROPOMI). The results from October to November 2023 indicated a fine correlation (R = 0.98) between the daily EMI series data and a fine correlation (R ≥ 0.95) and spatial distribution closely resembling that of the TROPOMI TOCs. Furthermore, the EMI series data fusion results were highly correlated with TROPOMI TOCs (R = 0.99). Since the EMI series instruments had two different overpass times and the volume of available data at same pixel was increased by approximately three-fold, the temporal and spatial resolution was improved a lot. The results indicated that, compared to a single sensor, the EMI series DOAS TOCs generated more accurate and stable global TOC results and also enabled looking at the changes in the intraday TOCs. These outcomes highlight the potential of the EMI instruments for reliably monitoring the ozone variations in polar regions.

To provide reference for the design of the air-suction tea sorting device, the coupled numerical simulation model was established by the coupling method of computational fluid dynamics (CFD) and discrete element method (DEM) with tea of different quality as test objects, and the model was verified experimentally. Regarding tea particles of different quality, when the test tea particle mass was 0.215, the test value was located in the simulation value with a minimum error of 9 mm, which an error rate of 3.33%, and maximum error of 19 mm, with an error rate of 7.03%. When the test tea particle mass was 0.145, the minimum error of the test value was 5 mm and the error rate was 1.54%, and the maximum error was 9 mm and the error rate was 3.33%. The verification results established the accuracy of the model. During the suspension test and simulation, tea particles were affected by the air flow field of the observation tube, and tea particles fluctuated. During suspension, tea particles were attached to the inner wall of the observation tube under the action of the air flow field. An in-depth study showed that the relationship between the different distances from the initial position of the particles during suspension and the simulation time was a peak function. The extreme function is used to fit the actual trajectory, and the fitting degree is good. The fitting degree of the particle closest to the initial position was 0.9455, and the fitting degree of the particle farthest from the initial position was 0.9981.

PurposeThe aim of this study is to provide treatment for patients with urinary incontinence at different periods after radical prostatectomy.MethodsThe PubMed, Embase, Cochrane, and Web of Science were searched for all literature on the effectiveness on urinary control after radical prostate cancer between the date of database creation and 15 November 2023 and performed a quality assessment. A network meta-analysis was performed using RevMan 5.3 and Stata 17.0 software and evaluated using the surface under the cumulative ranking curve.ResultsThe results of the network meta-analysis showed that pelvic floor muscle therapy including biofeedback with professional therapist–guided treatment demonstrated better results at 1 month to 6 months; electrical stimulation, biofeedback, and professional therapist guidance may be more effective at 3 months of treatment; professional therapist–guided recovery may be less effective at 6 months of treatment; and combined therapy demonstrated better results at 1 year of treatment. During the course of treatment, biofeedback with professional therapist–guided treatment may have significant therapeutic effects in the short term after surgery, but, in the long term, the combination of multiple treatments (pelvic floor muscle training+ routine care + biofeedback + professional therapist–guided treatment + electrical nerve stimulation therapy) may address cases of urinary incontinence that remain unrecovered long after surgery.ConclusionIn general, all treatment methods improve the different stages of functional recovery of the pelvic floor muscles. However, in the long term, there are no significant differences between the treatments. Given the cost-effectiveness, pelvic floor muscle training + routine care + biofeedback + professional therapist–guided treatment + electrical nerve stimulation therapy within 3 months and pelvic floor muscle + routine care after 3 months may be a more economical option to treat urinary incontinence.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=331797, identifier CRD42022331797.

Abstract Background Timely and systematic professional treatment is crucial in schizophrenia prognosis, but the global rate of mental health service, now, use or help-seeking behavior is low. Methods In-depth semi-structured interviews were conducted with 13 participants with the diagnosis of schizophrenia between October to December 2021. The participants were purposively sampled from a psychiatric hospital’s. Interviews were recorded and transcribed verbatim into NVivo 12.0. Results The findings were summarized under 3 themes and 12 subthemes: (1) capability (lack of knowledge due to insufficient mental health literacy or lack of insight, inability to access disease information due to a lack of mental health literacy, and symptoms-related barriers); (2) opportunity (lack of disease information sources, inability to balance work and study during prolonged hospitalization, accessibility and convenience of medical resources, and the acquisition and utilization of social support); and (3) motivation (awareness of the disease and professional treatment, negative experiences of disease episodes, past medical experience, confidence in tcuring the disease, and the fulfillment of daily life and self-worth). Conclusion The medical help-seeking behavior of people with the diagnosis of schizophrenia is the result of the interaction of many barriers and facilitators, and challenges persist today. Interventions can be implemented with the BCW framework and our results to precisely eliminate delays in the diagnosis and treatment of mental problems.

Objective: To explore a method of visually establishing preperitoneal space. In this paper, the procedure is described in detail and its safety and efficacy evaluated. Methods: A retrospective style was adopted. The clinical data of 33 patients who accepted the total visceral sac separation (TVS) procedure from December 2019 to November 2021 were collected. Observation indices included location and area of abdominal defect; surgical method and duration of operation to establish preperitoneal space and any postoperative complications; developments during follow-up. Follow-up was performed up to December 2021 using outpatient examination and telephone interview to detect any complications of incision or recurrence of ventral hernia. Results: For operative indices, all patients underwent the TVS procedure successfully except for one who had to be converted to laparoscopic intraperitoneal onlay mesh (IPOM) due to failure to establish preperitoneal space. The time required to establish preperitoneal space was 185.75 ± 44.37 s and the duration of hospital stay was 8.27 ± 1.42 days. No complications, such as abdominal bleeding or digestive tract injury, occurred during hospitalization. No complications of incision were observed during follow up, which lasted 2–24 months with an average of 7 months. Conclusions: Preliminary results of the novel attempt to establish the preperitoneal space visually confirmed this to be a safe and feasible method. However, the sample size used here was small, with a short follow up. The details and notes need to be further discussed.

Abstract Clonal hematopoiesis (CH)—age-related expansion of mutated hematopoietic clones—can differ in frequency and cellular fitness by CH type (e.g., mutations in driver genes (CHIP), gains/losses and copy-neutral loss of chromosomal segments (mCAs), and loss of sex chromosomes). Co-occurring CH raises questions as to their origin, selection, and impact. We integrate sequence and genotype array data in up to 482,378 UK Biobank participants to demonstrate shared genetic architecture across CH types. Our analysis suggests a cellular evolutionary trade-off between different types of CH, with LOY occurring at lower rates in individuals carrying mutations in established CHIP genes. We observed co-occurrence of CHIP and mCAs with overlap at TET2, DNMT3A, and JAK2, in which CHIP precedes mCA acquisition. Furthermore, individuals carrying overlapping CH had high risk of future lymphoid and myeloid malignancies. Finally, we leverage shared genetic architecture of CH traits to identify 15 novel loci associated with leukemia risk.

Bovine infectious rhinotracheitis (IBR), caused by bovine alphaherpesvirus 1 (BoAHV1), poses significant challenges to the global cattle industry due to its high contagiousness and economic impact. In our study, we successfully isolated a BoAHV1 strain from suspected infected bovine nasal mucus samples in Yanji city, revealing genetic similarities with strains from Sichuan, Egypt, and the USA, while strains from Xinjiang, Beijing, Hebei, and Inner Mongolia showed more distant associations, indicating potential cross-border transmission. Additionally, our investigation of BoAHV1 infection dynamics within host cells revealed early upregulation of gB, which is critical for sustained infection, while the expression of gC and gD showed variations compared to previous studies. These findings enhance our understanding of BoAHV1 diversity and infection kinetics, underscoring the importance of international collaboration for effective surveillance and control strategies. Furthermore, they lay the groundwork for the development of targeted therapeutics and vaccines to mitigate the impact of IBR on the cattle industry.

Cipangopaludina cathayensis is a snail species unique to China. Domestic research on C. cathayensis has mainly focused on aquaculture technology, especially the paddy field breeding method, where water quality plays a critical role in the cultivation of C. cathayensis. Dissolved oxygen is one of the most important factors in the aquatic environment because it impacts a series of biological activities such as the growth and development, metabolism, reproduction, and breeding of aquatic animals. When the dissolution of oxygen in water is less than 2 mg/L, the water is in a low oxygen or anoxic state. Hypoxia can slow the growth and development of aquatic animals, reduce their disease resistance and reproductive ability, and, in serious cases, can lead to their death. In recent years, research on C. cathayensis has mainly focused on the anti-tumor mechanism, immune response, nutritional value evaluation, and antibiotic resistance. However, there is currently no report on the regulation of response to hypoxia in C. cathayensis either domestically or internationally. The purpose of this study was to explore the differential expression of genes in the liver of C. cathayensis under hypoxic stress.In this study, healthy C. cathayensis without mechanical damage were cultured in a hypoxia stress group (2.5 mg/L) and a normoxia (control) group (6.9 mg/L), with 90 C. cathayensis in each group and 3 replicates. For the low oxygen stress treatment, dissolved oxygen was decreased from 6.9 mg/L to 2.5 mg/L within 1 h and maintained for 24 h. The liver tissue was taken as the experimental material in both the hypoxia stress group and normoxic group. The total RNA was extracted and an mRNA library was constructed. The liver tissue samples of C. cathayensis from both groups were sequenced and analyzed using an Illumina HiSeq-2500 technology platform, and unigenes were compared and annotated in GO, KOG, Nr, and KEGG databases. The differentially expressed genes were analyzed using DESeq. Bioinformatics analysis was performed on the function of GO and KEGG of differentially expressed genes, and the key differentially expressed genes were further validated by qPCR.Transcriptome analysis results showed that 500 584 transcripts were assembled from the original data and 23 379 unigenes were obtained by sequencing, with an average length of 686.65 bp and N50 of 1 127 bp. Among the unigenes, 26 636 were found to be homologous to genes in the Nr protein database. Additionally, 22 907 unigenes were annotated in the GO database, 13 290 in the KOG database, and at least 4 179 in the KEGG database. Compared with the control group, 176 differentially expressed genes were screened in the hypoxia stress group, among which 64 and 112 were up- and down-regulated, respectively. Further, GO functional enrichment analysis found that the differential genes were mainly enriched in chitin metabolic and glucosamine-containing compound metabolic processes in the biological process. Differential genes were also enriched in collagen trimer in the cellular component and chitin binding in the molecular function. The enrichment analysis results of the KEGG pathway mainly focused on four pathway categories, namely environmental information processing, genetic information processing, metabolism, and organismal systems. Finally, the qPCR results of six key differentially expressed genes were obtained by RT-qPCR. Among the up-regulated genes under hypoxic stress were the heat shock proteins 70B2 and beta-6, and the down-regulated genes were chitinase-like protein 4, collagen alpha-1 chain (XIV), collagen alpha-4 chain (XIV), and phosphatase-related protein type 5, which confirmed the reliability of the transcriptome sequencing results.Studies have shown that, through transcriptome sequencing, the expression information of relevant functional genes in C. cathayensis liver tissues under hypoxic stress can be obtained. Among them, the expression of heat shock protein genes were up-regulated, indicating that hypoxic stress activated the physiological activities of C. cathayensis to adapt to hypoxia and protected the body from hypoxic damage. In addition, the down-regulated expression of related genes in the metabolic pathway indicates that the growth of C. cathayensis is affected under hypoxic environments. In conclusion, the results of this study provide basic data and a theoretical basis for the in-depth study of the regulatory mechanism of C. cathayensis in response to hypoxic stress.

Abstract Background Patients suffering from schizophrenia are at a higher risk of relapse. The perception of the risk of relapse in patients is critical for relapse prevention. In the field of psychiatry, the study of risk perception of relapse has been neglected. Methods We carried out a qualitative study using a descriptive phenomenological approach. Data were collected at two psychiatric hospitals in China. In total, 22 patients with schizophrenia were recruited through purposive sampling. Face to face semi-structured in-depth interviews were conducted. Interview recordings were transcribed by the research team, and transcripts were analysed by two independent coders with Colaizzi’s descriptive analysis framework. The consolidated criteria for reporting qualitative research checklist were used for reporting. Results The data of first-episode patients yielded three themes: (i) lack of knowledge about disease recognition and medical treatment; (ii) overoptimistic estimation of the risk of relapse; (iii) perceived importance of treatment. For first-relapse patients : (i) initial awareness of relapse warning signs; (ii) lack of systematic and accurate assessment of disease information; (iii) the perception that drug withdrawal is related to relapse. Patients with multiple relapses: (i) susceptibility to relapse: confusion and powerlessness; (ii) the severity of relapse: suicidal thoughts and behavior; (iii) effects of perceived benefits and barriers of medication behaviour. Conclusions In schizophrenic patients with first-episode, first-relapse, and multiple relapses, there were dynamic changes in the perception of disease relapse risk and medication behaviour. Medical workers must improve risk awareness education. They should provide patients with scientific, accurate, and timely communication channels, and dynamically assess and manage the risk of relapse in various patients.

Prostate cancer is a common malignancy in urology which often develops into castration-resistant prostate cancer (CRPC) after hormone therapy. Studies have shown that the mechanism of its occurrence is related to androgen receptor splice variants (AR splice variants). This work employs a bibliometric approach to explore the knowledge structure and emerging trends of AR variants in prostate cancer. The literature from 2000 to 2021 was obtained from Web of Science Core Collection (WoSCC), and the results were analyzed and visualized via CiteSpace and VOSviewer regarding publication number, citation number, country, region, institution, journal, author, keyword and reference. A total of 1503 publications were obtained. The number of publications and citations in this field is increasing. United States is the most prominent country, and University of Washington is the most influential institution in terms of this research field. European Urology is the most authoritative journal regarding this field. Gleave, Martin is the most productive author, and collaborated closely with others having centrality >0.1. The keywords abiraterone and AR-V7 have the strongest citation bursts in recent years and continuing to the end of 2021 which indicate the trend and further research directions. The most cited papers and co-cited references were related to the clinical significance of AR-V7 and its mechanism of promoting CRPC. This study used visualization software CiteSpace and VOSviewer to analyze the current status and the research trends of AR variants in prostate cancer (PCa) over the past 20 years. The findings can identify research hotspots and reveal future research directions.

Highlights A bimetallic lanthanum-nickel oxysulfide based on a La2O2S prototype was developed as a precatalyst for the electrochemical alkaline oxygen evolution reaction (OER). The in situ, ex situ, and theoretical investigations demonstrated that the precatalyst underwent a deep OER-driven reconstruction into a porous heterostructure where NiOOH nanodomains were uniformly separated and confined by La(OH)3 barrier. Oxyanion (SO4 2−) was steadily adsorbed on the surface of this in situ reconstructed NiOOH/La(OH)3 heterostructure, enabling it for enhanced OER activity and durability.

The complete mitochondrial genome (mitogenome) of the leafhopper Atkinsoniella nigrita Zhang & Kuoh, was determined in this study. The entire sequence was 16,011 base pairs (bp) in length. The new mitogenome consists of a typical set of genes: 13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and one control region of 1720 bp in length. The base composition of the mitogenome was A = 41.7%, T = 38.2%, C = 10.7%, and G = 9.4%. This is the classical structure for most insect mitogenomes without any gene arrangement observed. Compared with other known mitochondrial genomes of 15 Atkinsoniella species, the new mitogenome with three PCGs (ND2, ND5, and ND4L) shared the same gene base length, start codon and stop codon, and the shortest 12S rRNA (729 bp) and the longest tRNA-Lys (73 bp) within the genus Atkinsoniella. A phylogenetic analysis of 31 Cicadellinae and two Ledrinae concatenated sequences of 13 PCGs of their mitogenomes using Bayesian inference (BI) revealed that A. nigrita belongs to the genus Atkinsoniella with strong nodal support (BI posterior probability = 1).

Abstract Background The rule of thumb that there is little gain in statistical power by obtaining more than 4 controls per case, is based on type-1 error α = 0.05. However, association studies that evaluate thousands or millions of associations use smaller α and may have access to plentiful controls. We investigate power gains, and reductions in p-values, when increasing well beyond 4 controls per case, for small α. Methods We calculate the power, the median expected p-value, and the minimum detectable odds-ratio (OR), as a function of the number of controls/case, as α decreases. Results As α decreases, at each ratio of controls per case, the increase in power is larger than for α = 0.05. For α between 10–6 and 10–9 (typical for thousands or millions of associations), increasing from 4 controls per case to 10–50 controls per case increases power. For example, a study with power = 0.2 (α = 5 × 10–8) with 1 control/case has power = 0.65 with 4 controls/case, but with 10 controls/case has power = 0.78, and with 50 controls/case has power = 0.84. For situations where obtaining more than 4 controls per case provides small increases in power beyond 0.9 (at small α), the expected p-value can decrease by orders-of-magnitude below α. Increasing from 1 to 4 controls/case reduces the minimum detectable OR toward the null by 20.9%, and from 4 to 50 controls/case reduces by an additional 9.7%, a result which applies regardless of α and hence also applies to “regular” α = 0.05 epidemiology. Conclusions At small α, versus 4 controls/case, recruiting 10 or more controls/cases can increase power, reduce the expected p-value by 1–2 orders of magnitude, and meaningfully reduce the minimum detectable OR. These benefits of increasing the controls/case ratio increase as the number of cases increases, although the amount of benefit depends on exposure frequencies and true OR. Provided that controls are comparable to cases, our findings suggest greater sharing of comparable controls in large-scale association studies.

BackgroundGender disparities in mortality have drawn great interest, with previous studies identifying various biological, social, and behavioral factors contributing to the observed gender differences. This study aims to identify the sources of gender disparities in mortality rates and quantify the extent to which these factors mediate the gender differences in all-cause mortality.MethodsData from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2018 were analyzed. A total of 38,924 participants were included in the study. Gender information, socioeconomic status, lifestyle factors, and baseline disease status were obtained through questionnaires. Blood samples were collected to assess serological indicators. All-cause and cardiovascular mortality were considered as primary and secondary outcomes, respectively.ResultsThe study with an average age of 50.1 ± 17.9 years. Among the participants, 50.7% were women, and 41.8% were non-Hispanic White. The median follow-up length was 87 months [Inter-Quartile Range (IQR): 47–128]. Men showed higher rates of all-cause and cardiovascular mortality compared to women in both the general population and the population with cardiovascular disease. After adjustment for potential confounders (age, race, marital status, socioeconomic status, lifestyle level, smoking status, cardiovascular disease, hypertension, diabetes and cancer), the men: women hazard ratios (HRs) for all-cause and cardiovascular mortality were 1.58 [95% Confidence Interval (CI): 1.48–1.68] and 1.60 (95%CI:1.43–1.80) in the general population. Among individuals with cardiovascular disease, the fully adjusted HR for all-cause mortality was 1.34 (95% CI: 1.20 to 1.51), and for cardiovascular mortality, the fully adjusted HRs was 1.52 (95% CI: 1.26 to 1.83). Mediation analysis revealed that uric acid levels significantly mediated the association between gender and all-cause mortality, accounting for 17.53% (95% CI: 11.0% to 23.7%) in the general population and 27.47% (95% CI: 9.0% to 13.6%) in the population with cardiovascular disease.ConclusionsThe study highlights the complex interplay of biological and social factors contributing to gender disparities in mortality. Uric acid was identified as key mediators of the gender-mortality association. These findings can inform targeted interventions aimed at reducing gender disparities in mortality and promoting better public health outcomes.

Sarmentosin (SA) and Quercetin (QC) are two active components of Sedum Sarmentosum Bunge, which is a traditional Chinese herbal medicine. This study aimed to investigate the role and regulatory mechanism of SA and QC in fatty liver of Genetic Improvement of Farmed Tilapia (GIFT) tilapia. GIFT tilapia were randomly divided into two groups with three replicates per treatment (30 fish in each replicate): normal diet group (average weight 3.51±0.31 g) and high-fat diet group (average weight 3.44±0.09 g). After 8 weeks feeding trial, growth index, lipid deposition, and biochemical indexes were measured. Lipid deposition, and lipid and inflammation-related gene expression were detected in a primary hepatocyte model of fatty liver of GIFT tilapia treated with SA or QC. Our results showed that high-fat diet caused lipid deposition and peroxidative damage in the liver of GIFT tilapia. The cell counting kit-8 assay results indicated that 10 μM SA and 10 μM of QC both had the least effect on hepatocyte proliferation. Moreover, both 10 μM of SA and 10 μM of QC showed lipolytic effects and inhibited the expression of lipid-related genes (FAS, Leptin, SREBP-1c, and SREBP2) in fatty liver cells. Interestingly, QC induced autophagosome-like subcellular structure and increased the expression of IL-8 in fatty liver cells. In conclusion, this study confirmed that SA and QC improved fatty liver caused by high-fat diet, providing a novel therapeutic approach for fatty liver of GIFT tilapia.

Introduction: Idiopathic normal pressure hydrocephalus (iNPH) is a kind of hydrocephalus that is easily to be misdiagnosed with brain atrophy due to the similarity of ventricular dilation and cognitive impairment. In this case, we present an old male patient who was diagnosed with iNPH by multimodality approaches. Outcomes: A 68-year-old male patient, with deteriorated gait, declined cognitive function for at least 3 years and urinary incontinence for 3 months. The doctors suspected him a patient with hydrocephalus or Alzheimer's disease based on his symptoms. We used multimodality diagnostic approaches including brain imaging, cerebrospinal fluid tap test, continuous intracranial pressure monitoring, and infusion study to make the final diagnosis of iNPH. He underwent ventriculoperitoneal shunt surgery and was well recovered. Conclusion: This case demonstrates the efficacy of using multimodality approaches for iNPH diagnosis, which saves patient time and clinical cost, worthy of further promotion.

BackgroundRecent an observational study has suggested a potential connection between gut microbiota (GM) and peptic ulcer diseases (PUDs), particularly gastric ulcer (GU) and duodenal ulcer (DU). However, the causal connection remains unsure.MethodsA two-sample Mendelian randomization (MR) is carried out to explore the connection between the GM and DU or GU. Data on the GM comes from the MiBioGend database, and GU or DU data are based on the FinnGen database. One group of single nucleotide polymorphisms (SNPs) (P < 5 × 10−8) are served as instrumental variables (IVs). To obtain a more comprehensive conclusion, the other SNPs (P < 1 × 10−5) are selected as IVs. Inverse variance weighting (IVW) is used to determine the causal relationship.ResultsAt the level of P < 1 × 10−5, the IVW analysis suggests that Clostridiaceae1, Butyriccoccus, and Peptcoccus have harmful effects on GU, while LachnospiraceaeUCG004 and MollicutesRF9 have beneficial effects on GU. Then, in the case of DU, the IVW analysis suggested that Lentisphaeria, Negativicutes, Clostridiaceae1, ClostridiumseMnsustricto1, ErysipelotrichaceaeUCG003, LachnospiraceaeNC2004group, Selenomonadale, Victivallales, and Lentisphaerae have harmful effects, while Catenibacterium, Escherichia.Shigella, LachnospiraceaeUCG008, and Sutterella have beneficial effects. When P < 5 × 10−8, IVW analysis suggests that GM has no significant influence on GU or DU.ConclusionThis two-sample MR indicates a causal relationship between GM and GU or DU.

Background: This study aimed to investigate the specific roles of the long non-coding RNA (lncRNA) proteasome 20S subunit beta 8 (PSMB8)-antisense RNA 1 (AS1)/microRNA (miR)-382–3p/branched-chain amino acid transaminase 1 (BCAT1) interaction network in gliomas. Methods: Western blotting and quantitative reverse transcription-polymerase chain reaction were performed to assess the expression levels of lncRNA PSMB8-AS1, BCAT1, and miR-382-3p. Moreover, the cell proliferation, migration, and apoptosis were assessed using the cell counting kit-8, Transwell, and caspase-3 activity assays, respectively. The biological role of lncRNA PSMB8-AS1 in glioma was investigated in vivo using a xenograft mouse model. Additionally, the associations among lncRNA PSMB8-AS1, miR-382-3p, and BCAT1 were analyzed using dual-luciferase and RNA immunoprecipitation assays and bioinformatics analyses. Results: Glioma cell lines and tissues exhibited overexpression of lncRNA PSMB8-AS1 and BCAT1 and low expression of miR-382-3p. Knockdown of PSMB8-AS1 remarkably repressed the tumor growth in vivo and the migration and proliferation of glioma cells in vitro. In contrast, knockdown of lncRNA PSMB8-AS1 increased the cell apoptosis. Mechanistically, PSMB8-AS1 directly targeted miR-382-3p. By sponging miR-382-3p, lncRNA PSMB8-AS1 stimulated the migration and proliferation of glioma cells and suppressed their apoptosis. Additionally, miR-382-3p directly targeted BCAT1. Inhibition of miR-382-3p reversed the antitumor effects of BCAT1 silencing on glioma progression. Conclusion: Our study revealed that lncRNA PSMB8-AS1 aggravated glioma malignancy by enhancing BCAT1 expression after competitively binding to miR-382-3p. Therefore, lncRNA PSMB8-AS1 may be a potential biomarker and therapeutic target for glioma treatment.

Prokaryotic communities play important roles in sewer sediment ecosystems, but the community composition, functional potential, and assembly mechanisms of sewer sediment prokaryotic communities are still poorly understood. Here, we studied the sediment prokaryotic communities in different urban functional areas (multifunctional, commercial, and residential areas) through 16S rRNA gene amplicon sequencing. Our results suggested that the compositions of prokaryotic communities varied significantly among functional areas. Desulfomicrobium, Desulfovibrio, and Desulfobacter involved in the sulfur cycle and some hydrolytic fermentation bacteria were enriched in multifunctional area, while Methanospirillum and Methanoregulaceae, which were related to methane metabolism were significantly discriminant taxa in the commercial area. Physicochemical properties were closely related to overall community changes (p < 0.001), especially the nutrient levels of sediments (i.e., total nitrogen and total phosphorus) and sediment pH. Network analysis revealed that the prokaryotic community network of the residential area sediment was more complex than the other functional areas, suggesting higher stability of the prokaryotic community in the residential area. Stochastic processes dominated the construction of the prokaryotic community. These results expand our understanding of the characteristics of prokaryotic communities in sewer sediment, providing a new perspective for studying sewer sediment prokaryotic community structure.

Procambarus clarkii Girard is an economically important cultured shrimp in China, and lipids are an important component of its raw feed materials. Studies have shown that adequate lipid content in feed can promote the health of aquatic animals, improve the utilization efficiency of feed protein, save protein, reduce feed costs, and reduce nitrogen emissions. Insufficient lipid content in feed leads to metabolic disorders in breeding animals, reduces the utilization rate of feed protein, and is accompanied by a deficiency of fat-soluble vitamins and essential fatty acids. However, a high fat content inhibits feeding and growth and leads to excessive fat deposition in the fish body, which decreases disease resistance and is not conducive to feed processing and storage. At present, studies on the dietary lipid content of P. clarkii have mainly focused on growth performance, biochemical indices, and conventional nutritional components of muscle; however, studies on muscle quality, amino acid composition, and content have not yet been reported. This study investigated the growth performance, muscle texture indices, nutritional components, and food flavor of P. clarkii by determining the effect of dietary lipid content on the growth performance and muscle quality of juveniles. The aim of this study was to provide a reference for the development of compound feed for juvenile P. clarkii and to provide a theoretical and scientific basis for rationally evaluating the effects of fat on the muscle quality of the species.Five experimental diets with lipid levels of 2.86%, 5.11%, 7.67%, 10.19%, and 13.02% were prepared using fishmeal, soybean meal, and rapeseed meal as the main protein sources, and a mixture of fish oil and soybean oil in a ratio of 1:1 as the lipid source. A total of 600 juvenile P. clarkii with an initial body weight of (4.00±1.00) g was randomly divided into five groups (L1, L2, L3, L4, and L5 groups) with three replicates per group and 40 shrimps per replicate. They were fed five groups of experimental diets at 6:00 and 19:30 each day and cultured for 60 days. The experiment was carried out in an aquaculture pond (square, 1.0 m × 1.0 m × 0.6 m) at the Guangxi University.The results showed that as the dietary lipid level increased, the specific growth rate (SGR) and survival rate (SR) of juvenile P. clarkii first increased and then decreased and were the highest when the dietary lipid level was 7.67%. The feed conversion ratio (FCR) at first decreased before increasing again and that of the L3 group was significantly lower than that of the other groups (P < 0.05). Using the specific growth rate as an evaluation index, through broken-line analysis, the optimal dietary lipid level of juvenile P. clarkii was estimated as 6.82%. Dietary lipid levels had no significant effect on the moisture, crude protein, and ash contents in the muscle (P > 0.05). With the increase in dietary lipid levels, the cooking loss (CL) and crude lipid, polyunsaturated fatty acids (∑PUFA), and total amino acid (∑TAA) contents of the muscle showed an increasing trend. The content of eicosapentaenoic acid (EPA) in the L5 group was significantly higher than that in the other groups, and the docosahexaenoic acid (DHA) content in the L5 group was significantly higher than that in the L1 and L2 groups (P < 0.05). With increasing dietary lipid levels, muscle hardness, elasticity, cohesiveness, and gumminess decreased and there were no significant differences between the L1 and L3 groups (P > 0.05), whereas dietary lipid levels showed no significant difference in muscle saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) contents (P > 0.05). The contents of umami amino acids (∑FAA), alanine (Ala), and aspartate (Asp) in the L5 group were significantly lower than those in the L1 group (P < 0.05).Under the conditions of this study, within a suitable range of fat content, growth performance increased with increased fat content; however, the addition of excessive fat cannot promote growth. According to the broken-line regression analysis of the specific growth rate, the optimal dietary lipid level was 6.82%. When the dietary lipid level was higher than 10.19%, the deposition and efficiency of muscle fat, muscle fat content, and nutrient loss increased, and the muscle texture index and Asp and Ala contents significantly decreased. The nutritional value, taste, delicious degree, and flavor of the muscle of P. clarkii were significantly decreased. As it does not affect the muscle quality of the shrimp, the dietary lipid content should not exceed 10.19%.Based on the analysis of various factors, the optimal dietary lipid content is beneficial to the healthy growth of juvenile P. clarkii and improves nutritional value and muscle quality. It is suggested that the dietary lipid supplemental level of juvenile shrimp should be 6.82%~10.19%. This study provides a theoretical basis for the scientific optimization of feed preparation for P. clarkii juvenile.

Objective Compared with total hip replacement, conventional collum femoris preserving prosthesis has a better bone retention effect. However, damage to the trabecular bone of the proximal femur leads to inevitable abnormal stress distribution, which leads to increased risks of femoral neck bone absorption, periprosthetic fracture, prosthesis loosening, rotation, and sinking. Thus, we compare the biomechanical properties of collum femoris preserving (CFP) and bionic collum femoris preserving (BCFP) hip prostheses. Methods The Sawbone digital model (#3503, left, medium) was selected as the research object. We used the Mimics 21.0 software to reconstruct the digital model of the femur and the SolidWorks 2019 software to build and assemble the three‐dimensional models of CFP and BCFP prostheses. With the ANSYS Workbench 2021R1 software, the models were meshed and assigned values to simulate the load of a single foot under slow walking. We measured the mechanical distribution of the whole model and obtained the stress nephogram. Results For CFP prosthesis, the peak stresses of the medial interface of the stem neck, the lateral interface of the stem neck, and the end of the stem were 64.894, 32.199, and 8.578 MPa, respectively; the peak stresses of the medial surface of the femoral shaft, the lateral surface of femoral shaft, the medial femoral neck bone‐prosthesis interface (osteotomy interface), the lateral femoral neck bone‐prosthesis interface (basal area), the lateral femoral neck bone‐prosthesis interface (osteotomy interface), and the greater trochanter area were 28.093, 24.790, 14.388, 5.118, 4.179, and 8.245 MPa, respectively; the valley stress of the greater trochanter area was 1.134 MPa. For BCFP prosthesis, the peak stresses of the medial interface of the stem neck, the lateral interface of the stem neck, and the end of the stem were 47.015, 26.771, and 47.593 MPa, respectively; the peak stress of tension screw was 15.739 MPa; the peak stresses of the medial surface of the femoral shaft, the lateral surface of femoral shaft, the medial femoral neck bone‐prosthesis interface (osteotomy interface), the lateral femoral neck bone‐prosthesis interface (basal area), the lateral femoral neck bone‐prosthesis interface (osteotomy interface) and the greater trochanter area were 28.581, 25.364, 15.624, 6.434, 4.986, and 8.796 MPa, respectively; the valley stress of the greater trochanter area was 1.419 MPa; the peak stress of bone‐metal interface between the tension screw and the lateral surface of the femur was 5.858 MPa. Conclusion Compared with the CFP prosthesis, the design of the BCFP prosthesis is based on the lever balance theory. With the bionic reconstruction of tension trabeculae, BCFP prosthesis makes up for the defects of CFP prosthesis design, optimizes the stress distribution, and reduces the stress shelter effect of the proximal femur, which has better biomechanical properties.