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Objective: Osteoclast (OC) over-activation is an important cause of bone loss that is strongly correlated with inflammation. Although the CD163/TWEAK/Fn14 axis has been implicated in several inflammatory pathologies, its contributions to inflammatory bone loss remain poorly understood. This study aimed to evaluate the interaction of the CD163/TWEAK/Fn14 axis with OC in inflammatory bone loss. Methods: To assess the role of CD163 in bone homeostasis, we characterized the bone phenotypes of CD163-deficient mice and their wild-type littermates. CD163 and TWEAK levels were evaluated in the bone marrow of mice with LPS-induced bone loss and individuals with rheumatoid arthritis (RA). Bone mass changes were assessed using uCT and histology following supplementation with recombinant mouse CD163 protein (rCD163) or blockade of TWEAK/Fn14 signaling in CD163-deficient mice and mice with LPS-induced bone loss. The impact of CD163/TWEAK on OC differentiation and bone resorption capacity was analyzed in vitro. Results: CD163 deficiency caused decreased bone mass and increased OC abundance. Lower CD163 expression and higher TWEAK expression were observed in the bone marrow of mice with LPS-induced bone loss and individuals with RA. TWEAK, mainly derived from CD68+ macrophages, was responsible for bone loss, and supplementing rCD163 or blocking TWEAK/Fn14 signaling contributed to rescue bone loss. TWEAK/Fn14 synergistically promoted RANKL-dependent OC differentiation and bone resorption capability through downstream mitogen-activated protein kinases (MAPK) signaling, while the pro-osteoclastic effect of TWEAK was suppressed by CD163. Conclusion: Our findings suggest that the CD163/TWEAK/Fn14 axis is a potential therapeutic target for inflammatory bone loss by regulating osteoclastogenesis.

Background and objective The incidence rate of lung cancer in Xuanwei has been continuously increasing in recent years, and it also features high incidence across all age groups and high mortality rates among female lung cancer patients. Therefore, the search for more stable biomarkers for the diagnosis of Xuanwei lung cancer holds tremendous clinical application prospects. This study aims to explore the clinical application value of these four microRNAs (miRNAs) individually and in combination with traditional lung cancer tumor markers in the detection and diagnosis of Xuanwei lung cancer. Methods By detecting the expression levels of four miRNAs and five traditional lung cancer tumor markers in the serum of 45 Xuanwei lung cancer patients and healthy physical examination participants, the Logistic regression model was employed to comprehensively evaluate the sensitivity, specificity, diagnostic efficacy, and other relevant statistical indicators of the four miRNAs in the diagnosis of Xuanwei lung cancer. Results Among the individual miRNAs, miR-4646-5p and miR-3654 showed significant differences in expression levels between the Xuanwei lung cancer group and the control group (P

Background: In the recent decade, there has been substantial progress in the technologies and philosophies associated with diagnosing and treating anterior cruciate ligament (ACL) injuries in China. The therapeutic efficacy of ACL reconstruction in re-establishing the stability of the knee joint has garnered widespread acknowledgment. However, the path toward standardizing diagnostic and treatment protocols remains to be further developed and refined. Objective: In this context, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) collaboratively developed an expert consensus on diagnosing and treating ACL injury, aiming to enhance medical quality through refining professional standards. Methods: The consensus drafting team invited experts across the Greater China region, including the mainland, Hong Kong, Macau, and Taiwan, to formulate and review the consensus using a modified Delphi method as a standardization approach. As members of the CSSM Lower Limb Study Group and the CAOS Arthroscopy and Sports Medicine Study Group, invited experts concentrated on two pivotal issues: “Graft Selection” and “Clinical Outcome Evaluation” during the second part of the consensus development. Results: This focused discussion ultimately led to a strong consensus on nine specific consensus terms. Conclusion: The consensus clearly states that ACL reconstruction has no definitive “gold standard” graft choice. Autografts have advantages in healing capability but are limited in availability and have potential donor site morbidities; allografts reduce surgical trauma but incur additional costs, and there are concerns about slow healing, quality control issues, and a higher failure rate in young athletes; synthetic ligaments allow for early rehabilitation and fast return to sport, but the surgery is technically demanding and incurs additional costs. When choosing a graft, one should comprehensively consider the graft's characteristics, the doctor's technical ability, and the patient's needs. When evaluating clinical outcomes, it is essential to ensure an adequate sample size and follow-up rate, and the research should include patient subjective scoring, joint function and stability, complications, surgical failure, and the return to sport results. Medium and long-term follow-ups should not overlook the assessment of knee osteoarthritis.

Objective To explore the predictive factors of acute kidney injury （AKI） in patients with hepatitis B cirrhosis plus ascites and establish a new prediction model. Methods Fom January 1, 2018 to December 31, 2022, the relevant clinical data were retrospectively reviewed for 1350 patients with hepatitis B cirrhosis admitted into Department of Infection of First Affiliated Hospital of Xinjiang Medical University. According to the diagnostic criteria for AKI of International Ascites Club in 2015, they were divided into two groups of AKI and non-AKI. According to the types of variables, the data differences between two groups were compared by χ2, T and Mann-Whitney U. The risk factors for AKI were screened by binary Logistic regression and ROC curve was plotted for evaluating the diagnostic value of each risk factor for AKI. An end-stage liver disease model was utilized for predicting AKI and short-term outcomes. Results Among 446 patients with hepatitis B cirrhosis and ascites, 111 cases developed AKI. The results of multivariate Logistic regression analysis revealed that prothrombin activity （OR = 1.031, 95%CI: 1.005-1.058）, blood urea nitrogen （BUN） （OR = 1.305, 95%CI:1.175-1.450）, MELD score （OR = 1.181, 95%CI: 1.100-1.267） and moderate ascites （OR = 7.218, 95%CI: 2.170-24.008） were independent risk factors for AKI （P＜0.05）. In ROC curve, AUC value of four-party combined predictor was the greatest （AUC = 0.895）. Conclusion Prothrombin activity, BUN, MELD score and ascitic severity are independent risk factors for AKI in patients with hepatitis B cirrhosis plus ascites. And combined prediction model established by these four factors has a high predictive value.

Abstract Background Non-invasive chromosome screening (NICS) and trophectoderm biopsy preimplantation genetic testing for aneuploidy (TE-PGT) were both applied for embryo ploidy detection, However, the cumulative live birth rates (CLBR) of NICS and TE-PGT in older age groups have yet to be reported. This study aimed to ascertain whether NICS and TE-PGT could enhance the cumulative live birth rates among patients of advanced maternal age. Methods A total of 384 couples aged 35–40 years were recruited. The patients were assigned to three groups: NICS, TE-PGT, and intracytoplasmic sperm injection (ICSI). All patients received frozen single blastocyst transfer. Patients in the NICS and TE-PGT groups underwent aneuploidy screening. Results When compared to the ICSI group, the CLBR was significantly higher in the NICS and TE-PGT groups (27.9% vs. 44.9% vs. 51.0%, p = 0.003 for NICS vs. ICSI, p

Implant-related osteomyelitis is a formidable hurdle in the clinical setting and is characterized by inflammation, infection, and consequential bone destruction. Therefore, effective reactive oxygen species (ROS) scavenging, bacterial killing, and subsequent bone tissue repair are urgently needed for the treatment of difficult-to-heal osteomyelitis. Herein, we utilized the eddy-thermal effect of magnesium (Mg) implants under an alternating magnetic field (AMF) for the controlled release of H2 gas and ions (OH− and Mg2+) for the treatment of osteomyelitis. H2 released by Mg rods under AMFs effectively scavenged cytotoxic ROS, exhibiting anti-inflammatory effects and consequently disrupting the environment of bacterial infections. In addition, the OH− hindered the energy metabolism of bacteria by effectively neutralizing protons within the microenvironment. Moreover, H2 impaired the permeability of bacterial membranes and expedited the damage induced by OH−. This synergistic AMF-induced H2 and proton depletion treatment approach not only killed both gram-negative and gram-positive bacteria but also effectively treated bacterial infections (abscesses and osteomyelitis). Moreover, Mg2+ released from the Mg rods enhanced and accelerated the process of bone osteogenesis. Overall, our work cleverly exploited the eddy-thermal effect and chemical activity of Mg implants under AMFs, aiming to eliminate the inflammatory environment and combat bacterial infections by the simultaneous release of H2, OH−, and Mg2+, thereby facilitating tissue regeneration. This therapeutic strategy achieved multiple benefits in one, thus presenting a promising avenue for clinical application.

Abstract Background Although broadband music with inaudible high-frequency components may benefit human well-being, this research area is largely unexplored and lacks sufficient studies on the topic. This study aimed to investigate and compare the effects of broadband and audible band music on relaxation states and cognitive function in young adults. Methods A single-blind randomized controlled trial was conducted in a professional soundproof laboratory from December 22, 2022, to January 18, 2023 with 32 participants randomly assigned to two groups, “Day 1 broadband + Day 2 audible band” (n = 16) and “Day 1 audible band + Day 2 broadband” (n = 16), listening to either broadband or audible band music (the same music piece played on the piano and harp) for two sessions of 15 min each on two consecutive days. Cognitive function was measured using CNS Vital Signs at pre-listening, after the 1st session, and after the 2nd session, while heart rate was monitored throughout the experiment. Visual Analog Scale was also administered for self-reported arousal, stress, thinking ability, and attention following each listening session. Results No significant differences were found in heart rate, cognitive flexibility, and executive function between the broadband listening group and the audible band-listening group (p > 0.05). However, the broadband group exhibited significant differences in mean heart rate at several time points, as well as a significant improvement in VAS stress level during the 2nd listening session compared to the 1st (p

With an insidious onset and a rapid progression, pregnancy-related acute kidney injury (PR-AKI) is an important cause of adverse maternal and infant outcomes and fatal complications in obstetric patients. A unique physiologic environment of pregnancy brings great challenges to clinical practices of nephrologists and obstetricians. With a recent liberalization of national two-child policy and a rapid development of assisted reproductive technology, there has been a growing number of elderly and high-risk women in labor. It is imperative to raise the awareness of PR-AKI. This review focused on the research advances in the outcomes of PR-AKI to provide references for clinicians to better understand the maternal-fetal outcomes of PR-AKI, identify which women are at a higher risk of poor prognosis and develop strategies for optimal managements and treatments.

Abstract Objectives To assess the effectiveness of HRCT-based radiomics in predicting rapidly progressive interstitial lung disease (RP-ILD) and mortality in anti-MDA5 positive dermatomyositis-related interstitial lung disease (anti-MDA5 + DM-ILD). Methods From August 2014 to March 2022, 160 patients from Institution 1 were retrospectively and consecutively enrolled and were randomly divided into the training dataset (n = 119) and internal validation dataset (n = 41), while 29 patients from Institution 2 were retrospectively and consecutively enrolled as external validation dataset. We generated four Risk-scores based on radiomics features extracted from four areas of HRCT. A nomogram was established by integrating the selected clinico-radiologic variables and the Risk-score of the most discriminative radiomics model. The RP-ILD prediction performance of the models was evaluated by using the area under the receiver operating characteristic curves, calibration curves, and decision curves. Survival analysis was conducted with Kaplan-Meier curves, Mantel-Haenszel test, and Cox regression. Results Over a median follow-up time of 31.6 months (interquartile range: 12.9–49.1 months), 24 patients lost to follow-up and 46 patients lost their lives (27.9%, 46/165). The Risk-score based on bilateral lungs performed best, attaining AUCs of 0.869 and 0.905 in the internal and external validation datasets. The nomogram outperformed clinico-radiologic model and Risk-score with AUCs of 0.882 and 0.916 in the internal and external validation datasets. Patients were classified into low- and high-risk groups with 50:50 based on nomogram. High-risk group patients demonstrated a significantly higher risk of mortality than low-risk group patients in institution 1 (HR = 4.117) and institution 2 cohorts (HR = 7.515). Conclusion For anti-MDA5 + DM-ILD, the nomogram, mainly based on radiomics, can predict RP-ILD and is an independent predictor of mortality.

The adverse metabolic impacts of branched-chain amino acids (BCAA) have been elucidated are mediated by isoleucine and valine. Dietary restriction of isoleucine promotes metabolic health and increases lifespan. However, a high protein diet enriched in BCAA is presently the most useful therapeutic strategy for nonalcoholic fatty liver disease (NAFLD), yet, its underlying mechanism remains largely unknown. Fatty liver hemorrhagic syndrome (FLHS), a specialized laying hen NAFLD model, can spontaneously develop fatty liver and hepatic steatosis under a high-energy and high-protein dietary background that the pathogenesis of FLHS is similar to human NAFLD. The mechanism underlying dietary BCAA control of NAFLD development in laying hens remains unclear. Herein, we demonstrate that dietary supplementation with 67 % High BCAA has unique mitigative impacts on NAFLD in laying hens. A High BCAA diet alleviates NAFLD, by inhibiting the tryptophan-ILA-AHR axis and MAPK9-mediated de novo lipogenesis (DNL), promoting ketogenesis and energy metabolism, and activating PPAR-RXR and pexophagy to promote fatty acid β-oxidation. Furthermore, we uncover that High BCAA strongly activates ubiquitin-proteasome autophagy via downregulating UFMylation to trigger MAPK9-mediated DNL, fatty acid elongation and lipid droplet formation-related proteins ubiquitination degradation, activating PPAR-RXR and pexophagy mediated fatty acid β-oxidation and lipolysis. Together, our data highlight moderating intake of high BCAA by inhibiting the AHR/MAPK9 are promising new strategies in NAFLD and FLHS treatment.

ObjectiveIn 2007, entosis was proposed as a form of programmed cell death, distinct from apoptosis. This process involves a living cell (internalized cell) actively invading a neighboring live cell of the same type (host cell), forming a cell-in-cell structure. Recently, entosis has been increasingly associated with cancer, leading to significant advancements in research. Despite this progress, a comprehensive and unbiased review of the current state of entosis research is lacking. This study aims to evaluate the developments in the field of entosis over the past decade and highlight emerging research trends.Materials and methodsWe performed a literature search for studies published since the introduction of the entosis concept, using the Web of Science Core Collection database. The bibliometric analysis was conducted using VOSviewer, CiteSpace, Microsoft Excel, and the Bibliometrix R package.ResultsA total of 196 articles from 39 countries and 346 institutions were included. Between 2007 and 2024, research on entosis has seen rapid growth, with most publications originating from China and the United States. The United States also leads in total citations, with Memorial Sloan Kettering Cancer Center emerging as the top research institution. Sun Qiang is the most prolific author in this field, while Overholtzer M has the highest number of citations. Current Molecular Medicine has published the most articles related to entosis. Frequently occurring keywords include “entosis,” “cannibalism,” “autophagy,” and “apoptosis.” In recent years, keywords such as “phagocytosis,” “drug resistance,” and “human cancers” have surged, indicating a growing focus on understanding the role of entosis in tumor progression and exploring its potential as a therapeutic target for cancer treatment.ConclusionsThis study provides the first bibliometric analysis of entosis, detailing its evolution over the last decade. It highlights critical areas of interest, including the development of inhibitors targeting entosis and their potential clinical applications. This research aims to guide future investigations and serve as a valuable resource for scholars exploring entosis in cancer biology.

The plate counting method is a traditional and widely accepted technique for live cell counting, often employed for Bacillus enumeration and spore forming rate calculations. However, this method requires at least 12 h to generate results, making it unsuitable for real-time monitoring of bacterial growth status and spore transformation rate. Bacillus thuringiensis crystals, produced during sporulation, are widely used as microbial pesticides, with high demand for industrial scale production. Variations in cultivation conditions and harvest timing during large-scale pore production of Bacillus thuringiensis significantly affect spore forming rate, impacting crystallization yield. Nevertheless, there is a lack of real-time monitoring methods for spore conversion rate. Flow cytometry (FCM), a well-established technique for single-cell analysis in eukaryotic cells, has been successfully applied in bacterial detection in environmental and food samples. In this study, we introduced a rapid flow cytometry-based method for determining spore forming rate of Bacillus thuringiensis, with two nucleic acid dyes, SYTO24 and LDS751. The method enables dynamic monitoring of spore, vegetative cell, and viable but non-culturable/dead cell proportions during the whole cultivation process, and spore forming rate could be gained within 30 min. Data of spore forming rate by FCM method is consistent with that by plate counting method, offering a faster and more efficient approach for assessing sporulation status in industrial Bacillus thuringiensis microbial pesticide production.

Based on the need for optimal spatial configuration of national land, this study utilizes a multi-source data integration method at the grid scale to precisely assess the levels of production, living, and ecological functions (PLEFs) in the Nanjing Metropolitan Area (NMA). Simultaneously, we develop an identification system for both the mechanistic equilibrium model and the comparative advantage index, which is applied to identify and enhance the zoning of production, living, and ecological space (PLES) within the NMA. The findings indicate that: (1) The production function in the NMA has shown a significant growth trend, while the increments in living and ecological functions are relatively modest, with each function transitioning from concentration to dispersion. (2) The spatial distribution of PLEFs in the NMA exhibits distinct characteristics: High production function values are concentrated in the northeast, while the southwest exhibits lower values. Living function values are elevated in the central region but diminish toward the northern and southern regions. Ecological function values are elevated in the south and decline toward the central and northern regions. There are also significant variations in the centers of gravity for these functions. (3) The NMA consists of six functionally-dominant spaces and twelve functionally-composite spaces, each showing significant fluidity during the study period. (4) In response to the demand for orderly development of national land and sustainable economic growth, this study categorizes the NMA into four zones: production priority, livelihood protection, ecological preservation, and ecological restoration. The production priority zone comprises the largest proportion, while the livelihood protection zone comprises the smallest. Additionally, this study proposes a tailored optimization strategy, designed to serve as a scientific benchmark for advancing and harmonizing the development of national land space.

Abstract As a typical E3 ligase, TRIM65 (tripartite motif containing 65) is involved in the regulation of antiviral innate immunity and the pathogenesis of certain tumors. However, the role of TRIM65 in renal cell carcinoma (RCC) and the underlying mechanism has not been determined yet. In this study, we identified TRIM65 as a novel oncogene in RCC, which enhanced the tumor cell proliferation and anchorage-independent growth abilities both in vitro and in vivo. Moreover, we found that TRIM65-regulated RCC proliferation mainly via direct interaction with BTG3 (BTG anti-proliferation factor 3), which in turn induced the K48-linked ubiquitination and subsequent degradation through K41 amino acid. Furthermore, TRIM65 relieved G2/M phase cell cycle arrest via degradation of BTG3 and regulated downstream factors. Further studies revealed that TRIM65 acts through TRIM65-BTG3-CyclinD1 axis and clinical sample IHC chip data indicated a negative correction between TRIM65 and BTG3. Taken together, our findings demonstrated that TRIM65 promotes RCC cell proliferation via regulation of the cell cycle through degradation of BTG3, suggesting that TRIM65 may be a promising target for RCC therapy.

Abstract Ovarian cancer is one of the common tumors of the female reproductive organs. It has a high mortality rate, is highly heterogeneous, and early detection and primary prevention are very complex. Autophagy is a cellular process in which cytoplasmic substrates are targeted for degradation in lysosomes through membrane structures called autophagosomes. The periodic elimination of damaged, aged, and redundant cellular molecules or organelles through the sequential translation between amino acids and proteins by two biological processes, protein synthesis, and autophagic protein degradation, helps maintain cellular homeostasis. A growing number of studies have found that autophagy plays a key regulatory role in ovarian cancer. Interestingly, microRNAs regulate gene expression at the posttranscriptional level and thus can regulate the development and progression of ovarian cancer through the regulation of autophagy in ovarian cancer. Certain miRNAs have recently emerged as important regulators of autophagy-related gene expression in cancer cells. Moreover, miRNA analysis studies have now identified a sea of aberrantly expressed miRNAs in ovarian cancer tissues that can affect autophagy in ovarian cancer cells. In addition, miRNAs in plasma and stromal cells in tumor patients can affect the expression of autophagy-related genes and can be used as biomarkers of ovarian cancer progression. This review focuses on the potential significance of miRNA-regulated autophagy in the diagnosis and treatment of ovarian cancer.

Abstract Strategies to improve T cell therapy efficacy in solid tumors such as hepatocellular carcinoma (HCC) are urgently needed. The common cytokine receptor γ chain (γc) family cytokines such as IL-2, IL-7, IL-15 and IL-21 play fundamental roles in T cell development, differentiation and effector phases. This study aims to determine the combination effects of IL-21 in T cell therapy against HCC and investigate optimized strategies to utilize the effect of IL-21 signal in T cell therapy. The antitumor function of AFP-specific T cell receptor-engineered T cells (TCR-T) was augmented by exogenous IL-21 in vitro and in vivo. IL-21 enhanced proliferation capacity, promoted memory differentiation, downregulated PD-1 expression and alleviated apoptosis in TCR-T after activation. A novel engineered IL-21 receptor was established, and TCR-T armed with the novel engineered IL-21 receptors (IL-21R-TCR-T) showed upregulated phosphorylated STAT3 expression without exogenous IL-21 ligand. IL-21R-TCR-T showed better proliferation upon activation and superior antitumor function in vitro and in vivo. IL-21R-TCR-T exhibited a less differentiated, exhausted and apoptotic phenotype than conventional TCR-T upon repetitive tumor antigen stimulation. The novel IL-21 receptor in our study programs powerful TCR-T and can avoid side effects induced by IL-21 systemic utilization. The novel IL-21 receptor creates new opportunities for next-generation TCR-T against HCC.

Abstract Background Broodiness significantly impacts poultry egg production, particularly notable in specific breeds such as the black-boned Silky, characterized by pronounced broodiness. An understanding of the alterations in ovarian signaling is essential for elucidating the mechanisms that influence broodiness. However, comparative research on the characteristics of long non-coding RNAs (lncRNAs) in the ovaries of broody chickens (BC) and high egg-laying chickens (GC) remains scant. In this investigation, we employed RNA sequencing to assess the ovarian transcriptomes, which include both lncRNAs and mRNAs, in eight Taihe Black-Bone Silky Fowls (TBsf), categorized into broody and high egg-laying groups. This study aims to provide a clearer understanding of the genetic underpinnings associated with broodiness and egg production. Results We have identified a total of 16,444 mRNAs and 18,756 lncRNAs, of which 349 mRNAs and 651 lncRNAs exhibited significantly different expression (DE) between the BC and GC groups. Furthermore, we have identified the cis-regulated and trans-regulated target genes of differentially abundant lncRNA transcripts and have constructed an lncRNA-mRNA trans-regulated interaction network linked to ovarian follicle development. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analyses have revealed that DE mRNAs and the target genes of DE lncRNAs are associated with pathways including neuroactive ligand-receptor interaction, CCR6 chemokine receptor binding, G-protein coupled receptor binding, cytokine-cytokine receptor interaction, and ECM-receptor interaction. Conclusion Our research presents a comprehensive compilation of lncRNAs and mRNAs linked to ovarian development. Additionally, it establishes a predictive interaction network involving differentially abundant lncRNAs and differentially expressed genes (DEGs) within TBsf. This significantly contributes to our understanding of the intricate interactions between lncRNAs and genes governing brooding behavior.

Abstract Background Cervical cancer (CC) is a danger to women’s health, especially in many developing countries. Metabolomics can make the connection between genotypes and phenotypes. It provides a wide spectrum profile of biological processes under pathological or physiological conditions. Method In this study, we conducted plasma metabolomics of healthy volunteers and CC patients and integratively analyzed them with public CC tissue transcriptomics from Gene Expression Omnibus (GEO). Result Here, we screened out a panel of 5 metabolites to precisely distinguish CC patients from healthy volunteers. Furthermore, we utilized multi-omics approaches to explore patients with stage I-IIA1 and IIA2-IV4 CC and comprehensively analyzed the dysregulation of genes and metabolites in CC progression. We identified that plasma levels of trimethylamine N-oxide (TMAO) were associated with tumor size and regarded as a risk factor for CC. Moreover, we demonstrated that TMAO could promote HeLa cell proliferation in vitro. In this study, we delineated metabolic profiling in healthy volunteers and CC patients and revealed that TMAO was a potential biomarker to discriminate between I-IIA1 and IIA2-IV patients to indicate CC deterioration. Conclusion Our study identified a diagnostic model consisting of five metabolites in plasma that can effectively distinguish CC from healthy volunteers. Furthermore, we proposed that TMAO was associated with CC progression and might serve as a potential non-invasive biomarker to predict CC substage. Impact These findings provided evidence of the important role of metabolic molecules in the progression of cervical cancer disease, as well as their ability as potential biomarkers.

Abstract Background Despite advances in treatments for gastric cancer (GC), new targets are needed to enhance treatment, especially when mesenchymal‐epithelial transition (MET) amplification is involved. Therefore, we investigated the genomic features of MET‐amplified GC and efficacy of anti‐MET therapy. Methods Genomic features were investigated in 2284 patients (cohort 1) and 438 patients in the Cancer Genome Atlas (TCGA cohort). RNA data were obtained from TCGA for expression analysis. Clinical responses of 71 patients (cohort 2) were investigated. Survival rates were compared by Kaplan–Meier and log‐rank tests. Results In cohort 1, 95 (4.2%) exhibited MET amplifications. In TCGA cohort, 15 (3.4%) exhibited MET amplifications. The five top mutated genes were TP53, CDH1, ARID1A, KMT2D and PIK3CA in cohort 1 and TTN, TP53, MUC16, LRP1B and SYNE1 in TCGA cohort. TP53, PIK3CA, KRAS and GNAS showed significant single nucleotide variants (SNVs) in cohort 1, and TP53 SNVs were significant in TCGA cohort. Fifteen and 18 genes showed significant copy number variations (CNVs) between the MET‐ and non‐MET‐amplified groups in cohort 1 and TCGA cohort, respectively. The PI3K pathway was significantly activated in Chinese patients with MET‐amplified GC (p = 0.002). TP53 expression is negatively associated with MET amplification. Real‐world data obtained with cohort 2 revealed that anti‐MET treatment significantly affected overall survival (OS) (p = 0.002), whereas CNVs did not affect progression‐free or OS even when treatment lines were considered. Conclusions MET‐amplified GC has a distinctive mutation landscape. Our findings provide valuable information for clinicians who treat patients with MET‐amplified GC.

Currently, the continuous expansion of the credit card business and the increasingly fierce competition have made all kinds of fraud risks in the overall credit card business the biggest threat. How to detect credit card fraud accurately and effectively through machine learning algorithms has become a research hotspot and challenge in this field. This project addresses the problems of existing credit card fraud detection methods and, based on the domain knowledge of credit card fraud and machine learning theory, proposes a method based on Mahalanobis distance SMOTE-ENN hybrid sampling and Random Forest for credit card fraud detection. First, fraud detection experiments were conducted by selecting credit card fraud datasets published on the Kaggle platform. Then, to further confirm the effectiveness of the method, the method was used for the credit card customer default dataset in Taiwan for further experimental proof. Finally, the experimental results in this paper were compared with the best experimental results in other articles, reflecting that the method based on Mahalanobis distance SMOTE-ENN hybrid sampling and Random Forest can be more effective for credit card fraud detection compared with other methods. The proposed method demonstrates a strong application potential and practical effect in credit card fraud detection, which not only improves the accuracy and efficiency of fraud detection but also provides a wide range of insights and methodological references for the solution of similar problems.

In the event of a fault in the AC/DC distribution network with modular multilevel converter (MMC), the current will surge and have a large amplitude, which seriously threatens the secure and reliable operation of the distribution network. In order to handle the fault, this paper presents an integrated control and protection strategy for AC/DC distribution network, which is based on the active current limiting control (ACLC) and single-terminal fault identification and protection principle. Firstly, an ACLC technique utilizing virtual reactance is introduced to reduce the rising rate of fault current by real-time monitoring of fault current slope. Then, taking into account the impact of ACLC, the characteristics and dynamic deviation value of single terminal current are analyzed, and a fast fault area identification method is designed. Through the cooperation of circuit breakers, this method achieves the goal of fast fault isolation. Finally, the simulation model of AC/DC distribution network is built in PSCAD/EMTDC, where the ACLC described in this paper can reduce the average rising rate of fault current by 38.4%. Moreover, the efficacy of the suggested plan is verified under different fault situations.

Abstract Background The contribution of genetic variants to congenital heart defects (CHDs) has been investigated in many postnatal cohorts but described in few prenatal fetus cohorts. Overall, specific genetic variants especially copy number variants (CNVs) leading to CHDs are somewhat diverse among different prenatal cohort studies. In this study, a total of 1118 fetuses with confirmed CHDs were recruited from three units over a 5-year period, composing 961 of singleton pregnancies and 157 of twin pregnancies. We performed chromosomal microarray analysis on all cases to detect numerical chromosomal abnormalities (NCAs) and pathogenic/likely pathogenic CNVs (P/LP CNVs) and employed whole-exome sequencing for some cases without NCAs and P/LP CNVs to detect P/LP sequence variants (P/LP SVs). Results Overall, NCAs and P/LP CNVs were identified in 17.6% (197/1118) of cases, with NCA accounting for 9.1% (102/1118) and P/LP CNV for 8.5% (95/1118). Nonisolated CHDs showed a significantly higher frequency of NCA than isolated CHD (27.3% vs. 4.4%, p

Abstract Intestinal ischemia-reperfusion (II/R) injury is an urgent clinical disease with high incidence and mortality, and impaired intestinal barrier function caused by excessive apoptosis of intestinal cells is an important cause of its serious consequences. Tripartite motif-containing protein 65 (TRIM65) is an E3 ubiquitin ligase that is recently reported to suppress the inflammatory response and apoptosis. However, the biological function and regulation of TRIM65 in II/R injury are totally unknown. We found that TRIM65 was significantly decreased in hypoxia-reoxygenation (H/R) induced intestinal epithelial cells and II/R-induced intestine tissue. TRIM65 knockout mice markedly aggravated intestinal apoptosis and II/R injury. To explore the molecular mechanism of TRIM65 in exacerbating II/R-induced intestinal apoptosis and damage, thymocyte selection-associated high mobility group box factor 4 (TOX4) was screened out as a novel substrate of TRIM65 using the yeast two-hybrid system. TRIM65 binds directly to the N-terminal of TOX4 through its coiled-coil and SPRY structural domains. Immunofluorescence confocal microscopy showed that they can co-localize both in the cytoplasm and nucleus. Furthermore, TRIM65 mediated the K48 ubiquitination and degradation of TOX4 depending on its E3 ubiquitin ligase activity. In addition, TRIM65 inhibits H/R-induced intestinal epithelial apoptosis via TOX4. In summary, our results indicated that TRIM65 promotes ubiquitination and degradation of TOX4 to inhibit apoptosis in II/R. These findings provide a promising target for the clinical treatment of II/R injury.

Abstract The relationship between single nucleotide polymorphisms (SNPs) at various loci and adverse drug reactions (ADRs) in patients with gynecologic cancer receiving platinum‐based chemotherapy (PPCT) remains unexplored. This research aimed to investigate the correlation between SNPs at several loci (e.g., GSTP1 rs1695, MTHFR rs1801133, XPC rs2228001, TP53 rs1042522, and ERCC1 rs3212986) and ADRs in patients with gynecologic cancer receiving PPCT. A total of 244 patients with gynecologic cancer who received first‐line PPCT were included in this retrospective study. Blood fluorescence quantitative polymerase chain reaction was used to detect genotypes. Logistic regression, Pearson's Chi‐square test, and Fisher's exact test were used to explore the correlations between these SNPs and the occurrence of ADRs. The logistic regression results showed that different genotypes of the five genes had no statistical significance in the overall grade greater than or equal to 3 ADRs. The results of Pearson's Chi‐square test showed the same results. On specific adverse reactions, we found that the rs1042522 GG genotype significantly increased the risk of grade greater than or equal to 3 leucopenia compared with the CG and the CC genotypes (p = 0.002). The rs1695 AG genotype showed higher correlation for grade greater than or equal to 3 neutropenia (p = 0.020). The rs2228001 CC genotype also had a higher risk for grade greater than or equal to 3 neutropenia (p = 0.003). This study found that whereas the overall grade greater than or equal to 3 adverse reactions in patients with gynecologic cancer receiving PPCT were not associated with SNPs, specific SNPs (rs1042522 GG, rs1695 AG, and rs2228001 CC) were linked to higher risks of leucopenia and neutropenia, indicating their potential as predictors of hematotoxicity in PPCT‐treated patients with gynecologic cancer.

AbstractEpigallocatechin gallate (EGCG) is a main component in green tea extract, which possesses multiple bioactivities. The present research studied the effects of EGCG on the laying performance, egg quality, immune status, antioxidant capacity, and hepatic metabolome of Linwu laying ducks reared under high temperature. A total of 180 42-w-old healthy Linwu laying ducks were allocated into control or EGCG-treated groups. Each treatment had 6 replicates with 15 ducks in each replicate. Diets for the two groups were basal diets supplemented with 0 or 300 mg/kg EGCG, respectively. All ducks were raised in the high temperature condition (35 ± 2 °C for 6 h from 10:00 to 16:00, and 28 ± 2 °C for the other 18 h from 16:00 to 10:00 the next day) for 21 days. Results showed that EGCG increased the egg production rate (p = 0.014) and enhanced the immunocompetence by improving serum levels of immunoglobulin A (p = 0.008) and immunoglobulin G (p = 0.006). EGCG also fortified the antioxidant capacity by activating superoxide dismutase (p = 0.012), catalase (p = 0.009), and glutathione peroxidase (p = 0.021), and increasing the level of heat-shock protein 70 (p = 0.003) in laying ducks’ liver. At the same time, hepatic metabolomics result suggested that EGCG increased the concentration of several key metabolites, such as spermidine (p = 0.031), tetramethylenediamine (p = 0.009), hyoscyamine (p = 0.026), β-nicotinamide adenine dinucleotide phosphate (p = 0.038), and pantothenic acid (p = 0.010), which were involved in the metabolic pathways of glutathione metabolism, arginine and proline metabolism, β-alanine metabolism, and tropane, piperidine, and pyridine alkaloid biosynthesis. In conclusion, 300 mg/kg dietary EGCG showed protection effects on the laying ducks reared in high temperature by improving the immune and antioxidant capacities, which contributed to the increase of laying performance of ducks. The potential mechanism could be that EGCG modulate the synthesis of key metabolites and associated metabolic pathways.

In the context of rapid urbanization and digitalization, scientifically assessing the spatio-temporal interaction between digital inclusive finance (DIF) and urban ecological resilience (UER) is crucial for promoting the coordinated development of the regional ecology and economy. This study investigates the spatiotemporal evolution of the coupled coordination degree (CCD), the decoupling phenomenon, and its hindering factors in the Yangtze River Economic Belt (YREB) by utilizing the kernel density analysis, standard deviation ellipse, decoupling model, and obstacle degree analysis. Through systematic analyses, this paper aims to elucidate the development disparities among regions within the YREB, identify problematic areas, and propose targeted improvement measures. The results show that (1) The CCD between DIF and UER in the YREB has increased annually from 2011 to 2020. However, there are persistent imbalances, with an overall low level of coordination and uneven spatial development, and a trend of “higher coordination in the east and lower coordination in the west”. (2) The overall CCD of the YREB has reached at least the primary coordination level, with the coupling enhancement speed ranked as “downstream > midstream > upstream”, and regional differences decreasing. (3) The decoupling analysis reveals a predominant decoupling trend between DIF and UER, indicating that the digitization of financial services has not concurrently increased ecological pressures. (4) The obstacle degree analysis identifies resilience and digitalization as major barriers hindering CCD. This study provides a scientific basis and analytical framework for understanding the current spatiotemporal interaction between DIF and UER in the YREB, offering an important reference for formulating more effective policies.

Oxidative stress is a major factor that limits the development of the poultry industry. Ferulic acid (FA) has an antioxidant effect in birds, but the mechanism is not fully understood. In this study, we stimulated oxidative stress in 28-day-old female Linwu ducks by lipopolysaccharide (LPS) and fed them a diet supplemented with FA for 28 days. Results showed that FA alleviated LPS-induced growth performance regression, oxidative stress, and microbiota imbalance in ducks. An integrated metagenomics and metabolomics analysis revealed that s_Blautia_obeum, s_Faecalibacterium_prausnitzii, s_gemmiger_formicilis, and s_Ruminococcaceae_bacterium could be the biomarkers in the antioxidant effect of FA, which interacted with dihydro-3-coumaric acid, L-phenylalanine, and 13(S)-HODE, and regulated the phenylalanine metabolism and PPAR signaling pathway. This study revealed the mechanism of the antioxidant effect of FA, which provided evidence of applying FA as a new antioxidant in commercial duck production.

Previous research has already provided evidence regarding the favorable impact of green walls and outdoor views on stress reduction and anxiety alleviation. However, there has been limited exploration into the combined effects of green walls and outdoor views on older adults. In this study, a between-subjects experiment was conducted using virtual reality (VR) technology with 23 participants. Following exposure to stressors, each participant underwent four randomized sessions, each lasting 5 min, in various virtual reality (VR) environments, encompassing non-biophilic and biophilic environments (including green walls, outdoor views, and their combination). Throughout the process, we measured physiological indicators of stress responses, including heart rate, heart rate variability, skin conductance levels, and blood pressure, using biometric sensors. Psychological changes in participants, including anxiety levels, were evaluated through the State–Trait Anxiety Inventory, recovery scales, and self-reported emotional assessments. In conclusion, in comparison to non-biophilic environments, older adults consistently exhibited lower stress levels, experienced superior anxiety relief, and demonstrated improved recovery in nature connectedness environments, with a notably faster recovery rate. These findings suggest that the incorporation of nature connectedness principles into the indoor environments of public activity spaces within older adults care facilities can significantly contribute to stress reduction and anxiety alleviation among older adults. Furthermore, these effects appear to be contingent on the specific types of nature connectedness environments. These results can provide substantial evidence to support the design of indoor common activity spaces within older adults care facilities.

Aristolochic acid (AA)-induced acute kidney injury (AKI) presents with progressive decline in renal function and rapid progression to end-stage renal disease. Among the multiple mechanisms identified in AKI, ferroptosis has been shown to be involved in various forms of AKI. But few studies have elucidated the role of ferroptosis in AA-induced AKI. In this study, we investigated the role of ferroptosis in AA-induced acute renal tubular injury in vivo and in vitro. Mice with acute aristolochic acid nephropathy showed increased malondialdehyde levels, aggravated lipid peroxidation, decreased superoxide dismutase activity, and glutathione depletion. The expression of glutathione peroxidase 4 was decreased and the expression of acyl-CoA synthetase long-chain family member 4 was increased. Inhibition of ferroptosis by ferrostatin-1 significantly improved the renal function, reduced histopathological lesions, partially alleviated lipid peroxidation, and restored the antioxidant capacity. In vitro studies also revealed that AA significantly reduced cell viability, induced reactive oxygen species production, increased intracellular iron level and decreased ferroptosis-related protein expression. Inhibition of ferroptosis significantly increased cell viability and attenuated AA-induced renal tubular epithelial cell injury. It is suggested that ferroptosis plays an important role in AA-induced acute tubular injury. And inhibition of ferroptosis may exert renoprotective effects possibly by preventing lipid peroxidation, restoring the antioxidant activity or regulating iron metabolism.

Inflammatory bowel disease (IBD) comprises a collection of chronic, non-specific inflammatory disorders affecting the gastrointestinal tract, the exact causes of which remain undefined. Research has indicates that the elderly population accounts for 10%-20% of IBD cases, and the prevalence of IBD among the elderly is steadily increasing alongside the patient base. In comparison to their younger counterparts with IBD, genetic factors play a diminished role in the development of elderly IBD, whereas immune system dysregulation and disruptions in gut microbiota assume greater significance. Among the elderly, various other prevalent conditions frequently exhibit symptoms akin to IBD, thereby rendering diagnosis notably challenging. Given that both IBD and aging process independently constitute risk factors for malnutrition, the probability of concurrent malnutrition substantially escalates within this subgroup. However, the realm of research regarding malnutrition in elderly IBD patients remains constrained. This review delves comprehensively into the status of malnutrition among elderly IBD patients, encompassing aspects of screening, assessment, and dietary management.

Abstract Objectives To compare the clinical outcomes of different multifetal pregnancy reduction (MFPR) programs in dichorionic (DC) triplets, and explore the association between early ultrasound characteristics and co-twin death after potassium chloride (KCl) injection into one monochorionic (MC) twin. Methods We retrospectively reviewed the data of DC triplets who underwent MFPR at our center during 2012–2021. Patients were grouped as follows: intracardiac KCl injection into one MC twin (group A), intracardiac KCl injection into both MC twins simultaneously (group B), and reduction of the singleton fetus (group C) and pregnancy outcomes were compared. Logistic regression was used to determine whether ultrasound measurements at 11–13+6 weeks predicted co-twin death and the receiver operator characteristic (ROC) analysis was conducted to assess the predictive performance. Results Finally, we enrolled 184 patients. 153 cases were in group A, and 18, 13 cases were in group B and C respectively. Gestational age at the time of MFPR did not differ among the 3 groups (median: $$12^\frac67$$ 12 6 7 weeks). The survival rate was 89.6%, 88.9%, and 92.3% in group A, B, and C respectively, which was comparable among groups. Preterm birth was more common in group C (10/12, 83.3%). After KCl injection into one MC twin, co-twin death occurred in 86.3% cases (132/153) within 1 day; however, 3 patients had 2 live births each, with normal postnatal development. Intertwin nuchal translucency (NT) difference/discordance significantly predicted co-twin death within 1 day after MFPR, and the areas under the ROC curve were 0.694 and 0.689, respectively. Conclusions For MFPR in DC triplet pregnancies, reduction of the MC twins results in less preterm birth, and women with KCl injection into either one or both MC twins had similar outcomes. Large intertwin NT difference/discordance was associated with co-twin death within 1 day after KCl injection into one of the MC twins.

Abstract Introduction The aim of this study was to determine the factors associated with the concentrations of hydroxychloroquine (HCQ) and its major metabolite, desethylhydroxychloroquine (DHCQ), in patients with systemic lupus erythematosus (SLE). Methods Patients with SLE taking oral HCQ for at least 3 months were recruited from the Department of Rheumatology and Immunology of Nanjing Drum Tower Hospital. Clinical characteristics and laboratory values were examined. The concentrations of HCQ and DHCQ were measured by high-performance liquid chromatography, and the effects of various factors on the concentrations were investigated. Results A total of 272 patients were included in this study. The average concentration of HCQ was 690.90 ng/ml and the average concentration of DHCQ was 431.84 ng/ml. Multivariate analysis indicated that gender (P = 0.015), age (year) (P

Abstract The future vehicle‐to‐everything (V2X) scenarios greatly call for reliable and efficient communication links between roadside units (RSUs) and vehicles. Integrated sensing and communication (ISAC) represents one of the key candidate technologies for 6G, which provides new solutions for this problem. In this paper, the beam tracking design for V2X communication is investigated by exploiting the ISAC technique, where the RSU uses the echoes of the ISAC signals to estimate the motion parameters of the vehicles. Compared with traditional feedback‐based beam tracking, the proposed method can reduce the overall signaling costs and improve communication robustness. Furthermore, to achieve high accuracy and low latency for beam alignment, a Trajectory Adaptive Unscented Kalman Filter (TA‐UKF) beam tracking algorithm is proposed, which obtains the optimal state transition model following the change of the vehicle state. Considering practical application scenarios, an ISAC‐based adaptive beam coverage (ISAC‐AC) scheme is further developed for the beam tracking of extended targets, which can achieve the beam misalignment of vehicles in practical scenarios. Numerical results demonstrate that the proposed beam tracking and coverage strategies outperform baseline approaches.

In isolated operation, DC microgrids require multiple distributed energy storage units (DESUs) to accommodate the variability of distributed generation (DG). The traditional control strategy has the problem of uneven allocation of load current when the line impedance is not matched. As the state-of-charge (SOC) balancing proceeds, the SOC difference gradually decreases, leading to a gradual decrease in the balancing rate. Thus, an improved SOC droop control strategy is introduced in this paper, which uses a combination of power and exponential functions to improve the virtual impedance responsiveness to SOC changes and introduces an adaptive acceleration factor to improve the slow SOC balancing problem. We construct a sparse communication network to achieve information exchange between DESU neighboring units. A global optimization controller employing the consistency algorithm is designed to mitigate the impact of line impedance mismatch on SOC balancing and current allocation. This approach uses a single controller to restore DC bus voltage, effectively reducing control connections and alleviating the communication burden on the system. Lastly, a simulation model of the DC microgrid is developed using MATLAB/Simulink R2021b. The results confirm that the proposed control strategy achieves rapid SOC balancing and the precise allocation of load currents in various complex operational scenarios.

Lead toxicity has hindered the wide applications of lead halide perovskites in optoelectronics and bioimaging. A significant amount of effort has been made to synthesize lead-free halide perovskites as alternatives to lead halide perovskites. In this work, we demonstrate the feasibility of synthesizing CsSnI3-based powders mechanochemically with dual light emissions under ambient conditions from CsI and SnI2 powders. The formed CsSnI3-based powders are divided into CsSnI3-dominated powders and CsSnI3-contained powders. Under the excitation of ultraviolet light of 365 nm in wavelength, the CsSnI3-dominated powders emit green light with a wavelength centered at 540 nm, and the CsSnI3-contained powders emit orange light with a wavelength centered at 608 nm. Both the CsSnI3-dominated and CsSnI3-contained powders exhibit infrared emission with the peak emission wavelengths centered at 916 nm and 925 nm, respectively, under a laser of 785 nm in wavelength. From the absorbance spectra, we obtain bandgaps of 2.32 eV and 2.08 eV for the CsSnI3-dominated and CsSnI3-contained powders, respectively. The CsSnI3-contained powders exhibit the characteristics of thermal quenching and photoelectrical response under white light.

Introduction: Long non-coding RNA (lncRNA) refers to a category of non-coding RNA molecules exceeding 200 nucleotides in length, which exerts a regulatory role in the context of ovarian development. There is a paucity of research examining the involvement of lncRNA in the regulation of ovary development in Taihe Black-Bone Chickens. In order to further investigate the egg laying regulation mechanisms of Taihe Black-Bone Chickens at different periods, transcriptome analysis was conducted on the ovarian tissues at different laying periods.Methods: This study randomly selected ovarian tissues from 12 chickens for RNA-seq. Four chickens were selected for each period, including the early laying period (102 days, Pre), the peak laying period (203 days, Peak), and the late laying period (394 days, Late). Based on our previous study of mRNA expression profiles in the same ovarian tissue, we identified three differentially expressed lncRNAs (DE lncRNAs) at different periods and searched for their cis- and trans-target genes to draw an lncRNA-mRNA network.Results and discussion: In three groups of ovarian tissues, we identified 136 DE lncRNAs, with 8 showing specific expression during the early laying period, 10 showing specific expression during the peak laying period, and 4 showing specific expression during the late laying period. The lncRNA-mRNA network revealed 16 pairs of lncRNA-target genes associated with 7 DE lncRNAs, and these 14 target genes were involved in the regulation of reproductive traits. Furthermore, these reproductive-related target genes were primarily associated with signaling pathways related to follicle and ovary development in Taihe Black-Bone Chickens, including cytokine-cytokine receptor interaction, TGF-beta signaling pathway, tyrosine metabolism, ECM-receptor interaction, focal adhesion, neuroactive ligand-receptor interaction, and cell adhesion molecules (CAMs). This study offers valuable insights for a comprehensive understanding of the influence of lncRNAs on poultry reproductive traits.

Background. Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) is a common food-borne pathogen that causes gastroenteritis and can lead to life-threatening systemic disease when it spreads to vital organs, such as the liver. Stimulator of interferon genes (STING) is a crucial regulator of the host’s innate immune response to viral infections, while its role in bacterial infections remains controversial. This study aims to establish a STING-deficient HepG2 cell line through the CRISPR/Cas9 system and evaluate its effects on Salmonella replication. Methods. In this study, a STING knockout HepG2 cell line was constructed through the application of CRISPR/Cas9 technology. We assessed cell viability and proliferation using the CCK-8 assay. Subsequently, we investigated the effect of STING deletion on Salmonella replication and the expression of type I interferon-related genes. Results. The STING knockout HepG2 cell line was successfully constructed using the CRISPR/Cas9 system. The proliferation capability was diminished in STING-deficient HepG2 cells, while Salmonella Typhimurium replication in these cells was augmented compared to the wild-type (WT) group. Following Salmonella infection, the transcriptional responses of type I interferon-related genes, such as IFNB1 and ISG15, were inhibited in STING-deficient HepG2 cells. Conclusions. We successfully constructed a STING-deficient cell line. Our finding of increased Salmonella Typhimurium replication in STING-deficient HepG2 cells provides the basis for further studies on pathogen-host interactions.

Abstract Background To develop prediction models for extubation time and midterm recovery time estimation in ophthalmic patients who underwent general anesthesia. Methods Totally 1824 ophthalmic patients who received general anesthesia at Joint Shantou International Eye Center were included. They were divided into a training dataset of 1276 samples, a validation dataset of 274 samples and a check dataset of 274 samples. Up to 85 to 87 related factors were collected for extubation time and midterm recovery time analysis, respectively, including patient factors, anesthetic factors, surgery factors and laboratory examination results. First, multiple linear regression was used for predictor selection. Second, different methods were used to develop predictive models for extubation time and midterm recovery time respectively. Finally, the models’ generalization abilities were evaluated using a same check dataset with MSE, RMSE, MAE, MAPE, R-Squared and CCC. Results The fuzzy neural network achieved the highest R-Squared of 0.956 for extubation time prediction and 0.885 for midterm recovery time, and the RMSE value was 6.637 and 9.285, respectively. Conclusion The fuzzy neural network developed in this study had good generalization performance in predicting both extubation time and midterm recovery time of ophthalmic patients undergoing general anesthesia. Trial registration This study is prospectively registered in the Chinese Clinical Trial Registry, registration number: CHiCRT2000036416, registration date: August 23, 2020.

The space–air–ground integrated network can provide services to ground users in remote areas by utilizing high-altitude platform (HAP) drones to support stable user access and using low earth orbit (LEO) satellites to provide large-scale traffic backhaul. However, the rapid movement of LEO satellites requires dynamic maintenance of the matching relationship between LEO satellites and HAP drones. Additionally, different traffic types generated at HAP drones hold varying levels of values. Therefore, a tripartite matching problem among LEO satellites, HAP drones, and traffic types jointly considering multi-dimensional characteristics such as remaining visible time, channel condition, handover latency, and traffic storage capacity is formulated as mixed integer nonlinear programming to maximize the average transmitted traffic value. The traffic generation state for HAP drones is modeled as a mixture of stochasticity and determinism, which aligns with real-world scenarios, posing challenges for traditional optimization solvers. Thus, the original problem is decoupled into two independent sub-problems: traffic–drone matching and LEO–drone matching, which are addressed by mathematical simplification and multi-agent deep reinforcement learning with centralized training and decentralized execution, respectively. Simulation results verify the effectiveness and superiority of the proposed tripartite matching approach.

Knowledge of wind field characteristics and variation principles in complex topographical regions is of great importance for the development of numerical prediction models, aviation safety support, and wind energy utilization. However, there has been limited research focused on the lower-tropospheric wind fields in the Qinghai-Tibet Plateau. This paper aims to study the wind characteristics, vertical distributions, and temporal variations in the northeast of the plateau by analyzing a four-year continuous dataset collected from a Doppler wind LiDAR deployed in Xining, Qinghai Province of China. The results indicate that the prevailing horizontal wind direction in the low levels is primarily influenced by the mountain-valley wind circulation. However, as the altitude increases, the prevailing winds are predominantly affected by the westerlies. From a diurnal perspective, noticeable transition processes between up-valley and down-valley winds can be observed. The west-northwest wind (down-valley wind) dominates from late night to morning, while the east-southeast wind (up-valley wind) prevails from afternoon to early evening. The vertical winds in the low levels exhibit a downward motion during the daytime and an upward motion during the nighttime. In this plateau valley, the wind shear exponent is found to be highest in spring and lowest in winter, and it is generally lower during the daytime compared to the nighttime.

Objectives The study aims to investigate the impact of gene polymorphisms on blood hydroxychloroquine (HCQ) concentrations in patients with SLE and provide guidelines for individualised care.Methods 489 Chinese patients with SLE taking HCQ for more than 3 months were collected in this study. The blood HCQ, desethylhydroxychloroquine (DHCQ) and desethylchloroquine concentrations were measured. The optimal blood concentration of HCQ was determined by receiver operating characteristic curve analysis. Single nucleotide polymorphisms of metabolic enzymes involved in HCQ metabolism were genotyped and the associations with treatment effects were investigated.Results The cut-off value of HCQ was 559.67 ng/mL, with sensitivity and specificity values of 0.51 and 0.89, respectively. The TC and CC genotypes of CYP2C8 (rs7910936) were significantly related to the increase in blood HCQ concentrations, and the CYP2C8 (rs10882521) TT genotype was associated with lower blood HCQ concentrations. The DHCQ:HCQ ratio was highest in patients with the GG genotype of the CYP2D6*10 (rs1065852) polymorphism and lowest in those with the AA genotype. Patients with the CYP2C8 (rs7910936) CC genotype were more likely to achieve the optimal blood concentration (p=0.030) in HCQ 200 mg/day group and patients with the CYP2D6*10 (rs1065852) GG genotype were more likely to reach the optimal blood concentration (p=0.049) in 400 mg/day group.Conclusions Our results suggest that the optimal blood concentration of HCQ measured approximately 12–18 hours after the last dosage may be between 500 and 600 ng/mL in Chinese patients with SLE. The observed variations in HCQ concentrations between individuals can potentially be attributed to genetic polymorphisms in CYP2D6*10 (rs1065852) and CYP2C8 (rs7910936 and rs10882521). Genotypical testing of patients and regular monitoring of blood levels are recommended for optimising HCQ dosage management in Chinese patients with SLE.Trial registration number ChiCTR2300070628.

The poor reproductive performance of most local Chinese chickens limits the economic benefits and output of related enterprises. As an excellent local breed in China, Taihe black-bone silky fowl is in urgent need of our development and utilization. In this study, we performed transcriptomic and metabolomic analyses of the ovaries of Taihe black-bone silky fowls at the peak egg-laying period (PP) and nesting period (NP) to reveal the molecular mechanisms affecting reproductive performance. In the transcriptome, we identified five key differentially expressed genes (DEGs) that may affect the reproductive performance of Taihe black-bone silky fowl: BCHE, CCL5, SMOC1, CYTL1, and SCIN, as well as three important pathways: the extracellular region, Neuroactive ligand-receptor interaction and Cytokine-cytokine receptor interaction. In the metabolome, we predicted three important ovarian significantly differential metabolites (SDMs): LPC 20:4, Bisphenol A, and Cortisol. By integration analysis of transcriptome and metabolome, we identified three important metabolite-gene pairs: “LPC 20:4-BCHE”, “Bisphenol A-SMOC1”, and “Cortisol- SCIN”. In summary, this study contributes to a deeper understanding of the regulatory mechanism of egg production in Taihe black-bone silky fowl and provides a scientific basis for improving the reproductive performance of Chinese local chickens.

Recently, the control plane of the core network (CN) has introduced a flat service-based architecture to improve flexibility, openness, and intelligence. And a novel radio access network (RAN)-CN converged network architecture was proposed to leverage the advantages of virtualization and cloudification, reduce network delay and overhead, and increase the network processing efficiency. In this paper, in order to fully utilize the advantages of the RAN-CN converged network and move services closer to user equipment, a multi-layer network architecture is proposed, where some CN network functions (NFs) are moved from the CN to the edge node (EN) and integrate with corresponding RAN functions to avoid unnecessary signaling and data forwarding. And all NFs in the EN except converged data storage management function (cDSM) are designed to be stateless to decouple the storage resources from these NFs. Based on the proposed multi-layer network architecture, a cDSM placement approach based on improved non-dominated sorting genetic algorithm II (iNSGA-II) is proposed to balance the data forwarding cost and the maximum load on cDSMs. Simulation results demonstrate that compared with the conventional NSGA-II, the convergence speed and distribution of the proposed iNSGA-II are improved. And according to different network requirements, the proposed scheme can achieve a trade-off between the data forwarding cost and the maximum load on cDSMs.

Background: Many factors were reported associated with the pregnancy rate of intrauterine insemination (IUI), which played key role is still debated. Aims: The aim of this study was to explore related clinical pregnancy outcome factor in IUI cycles of non-male factor. Settings and Design: The clinical data of 1232 IUI cycles in 690 couples experiencing infertility who attended the Reproductive Center of Jinling Hospital between July 2015 and November 2021 were retrospectively analysed. Materials and Methods: Female and male age, body mass index (BMI), anti-Müllerian hormone (AMH), male semen parameters before and after wash, endometrial thickness (EMT), artificial insemination timing and ovarian stimulation (OS) protocols were compared between the pregnant group and the non-pregnant group in order to explore any correlation. Statistical Analysis Used: Continuous variables were analysed using independent-samples t-test, and Chi-square test was used for comparison of measurement data between the two groups. P 4.5 ng/ml, EMT between 8 and 12 mm and letrozole + human menopausal gonadotropin stimulation with higher clinical pregnancy. However, there were no differences between the pregnant group and the non-pregnant group amongst the female and male age, BMI, hormones on baseline and day of human chorionic gonadotrophin, number of ovulated oocytes, sperm parameters before and after wash, treatment protocols and the timing of IUI (P > 0.05). Furthermore, there were 240 couples who not pregnant received one or more cycles of in vitro fertilisation/intracytoplasmic sperm injection/ pre-implantation genetic technology treatment, and another 182 couples forgo follow-up treatment. Conclusion: The results of the present study demonstrate that the clinical IUI pregnancy rate is correlated with the factors of female AMH, EMT and OS protocol; more studies and samples are necessary to evaluate whether other factors affect pregnancy rate.

A series of LaFe11.8Si1.2/La65Co35 bulk composites were fabricated by spark plasma sintering (SPS) followed by diffusion annealing. The effect of sintering temperature (1073–1223 K) on the magnetocaloric and other properties of LaFe11.8Si1.2/La65Co35 bulk composites were investigated. The 1:13 phase content in all the annealed samples was ∼90 wt%. The mechanical and magnetocaloric properties of these annealed bulk composites could be improved by tuning the sintering temperature. The Curie temperature (TC) and maximum magnetic entropy change (−ΔSM)max of the annealed samples varied in the range of 211–228 K and 5.56–9.33 J kg−1 K−1, respectively. Selected samples exhibited excellent mechanical and magnetocaloric properties. The (−ΔSM)max value was 9.33 J kg−1 K−1 at TC of 217.8 K. Its maximum compressive strength (σbc)max value was 540 MPa at a strain of 3.48%, which exceeded the mechanical properties of most La–Fe–Si based bulk composites prepared by hot-pressing sintering (HPS). Thus, La–Fe–Si based bulk composites with good comprehensive properties could be obtained by combining SPS and diffusion annealing.

Abstract Enhancer release and retargeting (ERR) events could activate disease-causing gene promoters for increasing the expression level of oncogenes. Meanwhile, class A orphan GPCRs (oGPCRs) are known as potential biomarkers or drug targets for various cancers, such as gastric cancer (GC). Hence, systemic investigation of ERR events for class A oGPCRs in GC could help to explore biomarkers for GC. In this study, ENCODE and GTEx eQTL data were utilized to define ERR events in GC. Only GPR35 was then detected that could be activated by ERR in GC based on these data and ChIP-seq. Then, activated GPR35 functional in GC cells were explored by flow cytometry, cell-based wound healing assay, Transwell migration assay, and M2 polarization of macrophages assay. Meanwhile, according to TCGA and GEO database, overall survival, immune-related gene expression, and immune cell infiltration level in different GPR35 expressions were calculated. Here, we found ERR event activate GPR35 results in GC cells proliferation and migration, and partly immune cells significance exhaustion (CD8 + T-cells and CD4 + memory T-cells) and/or infiltration (T-cells and macrophage). Meanwhile, high GRP35 level leads to a poor prognosis in GC patients, probably partly due to it promoting the immune infiltration level of macrophages and then inducing polarization of M2 macrophages. Notably, GPR35’s high expression in CTSB+ and CD68 + macrophage could be a genetic indicator for early warning of primary GC. Hence, our findings provide a novel activation approach for oGPCRs, and GPR35 could be determined as a new drugable receptor and early genetic indicator for GC.

Collagen, the most abundant protein in mammal, is widely expressed in tissues and organs, as well as tumor extracellular matrix. Tumor collagen mainly accumulates in tumor stroma or beneath tumor blood vessel endothelium, and is exposed due to the fragmentary structure of tumor blood vessels. Through the blood vessels with enhanced permeability and retention (EPR) effect, collagen-binding macromolecules could easily bind to tumor collagen and accumulate within tumor, supporting tumor collagen to be a potential tumor-specific target. Recently, numerous studies have verified that targeting collagen within tumor extracellular matrix (TEM) would enhance the accumulation and retention of immunotherapy drugs at tumor, significantly improving their anti-tumor efficacy, as well as avoiding severe adverse effects. In this review, we would summarize the known collagen-binding domains (CBD) or proteins (CBP), their mechanism and application in tumor-targeting immunotherapy, and look forward to future development.

IntroductionThe retina represents a critical ocular structure. Of the various ophthalmic afflictions, retinal pathologies have garnered considerable scientific interest, owing to their elevated prevalence and propensity to induce blindness. Among clinical evaluation techniques employed in ophthalmology, optical coherence tomography (OCT) is the most commonly utilized, as it permits non-invasive, rapid acquisition of high-resolution, cross-sectional images of the retina. Timely detection and intervention can significantly abate the risk of blindness and effectively mitigate the national incidence rate of visual impairments.MethodsThis study introduces a novel, efficient global attention block (GAB) for feed forward convolutional neural networks (CNNs). The GAB generates an attention map along three dimensions (height, width, and channel) for any intermediate feature map, which it then uses to compute adaptive feature weights by multiplying it with the input feature map. This GAB is a versatile module that can seamlessly integrate with any CNN, significantly improving its classification performance. Based on the GAB, we propose a lightweight classification network model, GABNet, which we develop on a UCSD general retinal OCT dataset comprising 108,312 OCT images from 4686 patients, including choroidal neovascularization (CNV), diabetic macular edema (DME), drusen, and normal cases.ResultsNotably, our approach improves the classification accuracy by 3.7% over the EfficientNetV2B3 network model. We further employ gradient-weighted class activation mapping (Grad-CAM) to highlight regions of interest on retinal OCT images for each class, enabling doctors to easily interpret model predictions and improve their efficiency in evaluating relevant models.DiscussionWith the increasing use and application of OCT technology in the clinical diagnosis of retinal images, our approach offers an additional diagnostic tool to enhance the diagnostic efficiency of clinical OCT retinal images.

In this study, we investigated the effects of modified aging treatments on the microstructures and hardness in a commercial 6016 Al alloy through hardness tests and transmission electron microscopy (TEM) observations. The results demonstrate that many fine needle-like β″ phases contribute to the high hardness of peak-aged (T6) alloys. Over-aging treatments lead to the precipitation of lath-like β′, β″/disordered, or B′/disordered composite phases. Moderate over-aging treatment results in the coarsening of grain boundary precipitates (GBPs) and widening of the precipitate-free zone (PFZ), while heavy over-aging treatment triggers the re-precipitation of Cu-containing GBPs and increases the number density of GBPs. A retrogression and re-aging (RRA) treatment precipitates β″, lath-like β′, and disordered phases, while a two-step aging (T78) treatment precipitates β″, B′, and disordered phases. Both the T78 and the RRA treatments lead to the coarsening of GBPs and the widening of PFZs. The decreased hardness during over-aging treatments is attributed to a combination of coarsening intragranular precipitates and/or wider PFZs. The T78 and RRA tempers achieve 95.5% and 94% of the hardness values of the T6 treatment, respectively. The hardness values of the RRA and T78 treated alloys are related to the finer nano-sized precipitates formed during the high temperature process. These precipitates can compensate for the loss of hardness caused by the increase in the widths of the PFZs and the coarsening of the matrix precipitates. The relationship between the hardness and microstructures such as PFZs and precipitates in the matrix during various heat treatments is elucidated.

The engineering geological classification method has been widely used for determining the shear strength parameters of waste disposal areas in engineering practice; however the calculation error is large.It is necessary to use various methods to comprehensively estiamte the shear strength parameters of the spoil field. Taking a road waste slag yard as an example, the particle size distribution of the slag in the waste disposal area is determined by laboratory particle grading testing, and on this basis, the shear strength of the waste slag is comprehensively determined by indoor large-scale shear testing and engineering geological analogy method parameters.The shear strength is used to perform the stability analysis of the slag body. The results show that the factor of safety of the slag body is 1.369 under natural working conditions and 1.083 under heavy rain conditions, respectively. Additionally, the monitoring results are consistent with the stability analysis, proving that the determination of the shear strength parameter of the slag is reasonable and accurate, and it can provide a reference for the parameter value of the highway waste disposal engineering.