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Abstract The attainment of white emission from a light-emitting electrochemical cell (LEC) is important, since it enables illumination and facile color conversion from devices that can be cost-efficient and sustainable. However, a drawback with current white LECs is that they either employ non-sustainable metals as an emitter constituent or are intrinsically efficiency limited by that the emitter only converts singlet excitons to photons. Organic compounds that emit by thermally activated delayed fluorescence (TADF) can address these issues since they can harvest all excitons for light emission while being metal free. Here, we report on the first white LEC based on solely metal-free TADF emitters, as accomplished through careful tuning of the energy-transfer processes and the electrochemically formed doping structure in the single-layer active material. The designed TADF-LEC emits angle-invariant white light (color rendering index = 88) with an external quantum efficiency of 2.1 % at a luminance of 350 cd/m2.

Abstract Brain glymphatic activity, as indicated by diffusion-tensor imaging analysis along the perivascular space (ALPS) index, is involved in developmental neuropsychiatric and neurodegenerative diseases, but its genetic architecture is poorly understood. Here, we identified 17 unique genome-wide significant loci and 161 candidate genes linked to the ALPS-indexes in a discovery sample of 31,021 individuals from the UK Biobank. Seven loci were replicated in two independent datasets. Genetic signals located at the 2p23.3 locus yielded significantly concordant effects in both young and aging cohorts. Genetic correlation and polygenic overlap analyses indicate a common underlying genetic mechanism between the ALPS-index, ventricular volumes, and cerebrospinal fluid tau levels, with GMNC (3q28) and C16orf95 (16q24.2) as the shared genetic basis. Our findings enhance the understanding of the genetics of the ALPS-index and provide insight for further research into the neurobiological mechanisms of glymphatic clearance activity across the lifespan and its relation to neuropsychiatric phenotypes.

Abstract Digestive and psychiatric disorders tend to co-occur, yet mechanisms remain unclear. Leveraging genetic and transcriptomic data integration, we conduct multi-trait analysis of GWAS (MTAG) and weighted gene co-expression network analysis (WGCNA) to explore shared mechanism between psychiatric and gastrointestinal disorders. Significant genetic correlations were found between these disorders, especially in irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), depression (DEP), and neuroticism (NE). MTAG identify 60 novel pleiotropic loci for IBS and 14 for GERD, predominantly located near genes associated with neurological pathways. Further WGCNA identifies multiple co-expression modules enriched with genes involved in neurological pathways in digestive tissues, with some modules strongly preserved across brain and digestive tissues. Moreover, our network analysis suggests BSN, CELF4, and NRXN1 as central players in the regulation of the gut-brain axis (GBA). This study enhances our understanding of the GBA and underscores BSN, CELF4, and NRXN1 as crucial targets for future research.

Chi Zhang,1,2,* Chao Yang,3,* Qingming Shi1,2 1Department of Oncology, Anhui Chest Hospital, Hefei, 230022, People’s Republic of China; 2Anhui Medical University Clinical College of Chest, Hefei, 230022, People’s Republic of China; 3Department of Urology, Anhui Provincial Children’s Hospital, Hefei, 230022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qingming Shi, Email shqm0324@163.com, shqm0324@hotmail.comAbstract: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Mutations within the TP53 gene represent critical molecular events in NSCLC, contributing to the tumorigenesis in the pulmonary epithelial tissues. TP53 is a widely researched prognostic indicator in NSCLC, and pathological investigations have revealed a weak to mild negative predictive effect for TP53. Mutated p53 protein may have some pro-oncogenic impact, and the variations may change tumor inhibitors into oncogenes. The diverse mutational spectrum of TP53 in NSCLC with different mutations is linked to varied treatment responses. In contrast, first-line chemotherapeutics to this progress are limited, however, randomized trials with new chemotherapeutics have shown significant survival benefits. This review highlighted the critical influence of TP53 gene mutations on pathological-sensitivity and overall survival outcomes in NSCLC. Further research is needed to explore TP53 mutation-specific pathways and their effects on NSCLC progression and treatment effectiveness. Keywords: non-small cell lung cancer, TP53 gene, treatment, survival analysis, mutations

Jiaqi Leng,1 Huilin Cai,1 Fei Liu,2 Xiaoli Shi,3 Zhiguang Fan4 1School of English, Jilin International Studies University, Changchun, 130117, People’s Republic of China; 2Section of Student Affair, ChangChun Vocational School of Technology, Changchun, 130117, People’s Republic of China; 3Department of Psychology, University of Exeter, Exeter, EX4 4 QG, UK; 4Department of Psychology, Shaoxing University, Shaoxing, 312000, People’s Republic of ChinaCorrespondence: Zhiguang Fan, Department of Psychology, Shaoxing University, Shaoxing, 312000, People’s Republic of China, Tel +86-0431-84924101, Fax +86 1 594-831-4623, Email fanyqm@126.comBackground: Stigma can not only threaten the self-identity of secondary vocational students, but also have negative effects on their mental health and behavior.Objective: This study aimed to develop the Self-Stigma Scale for Secondary Vocational Students (SSS-SVS) and test its reliability and validity.Patients and Methods: This study formed a scale based on the stigma conceptualization model and open questionnaire. The formal survey was divided into two stages. In the first stage, a preliminary questionnaire was administered to 328 secondary vocational students to develop a formal SSS-SVS according to the results of the data check. In the second stage, the SSS-SVS, Social Recognition of Secondary Vocational Students (SR-SVS), Intensity of Willingness to Become a Secondary Vocational Student (IWB-SVS), Stigma-Consciousness Scale (SCS), Learning Adjustment Scale (LAS), Professional Identity Scale for Secondary Vocational Students (PIS-SVS), and the Self-Compassion Scale (SCoS) were administered to 1079 vocational secondary school students.Results: The SSS-SVS consisted of 21 items which were divided into three dimensions of negative characteristics, self-deprecation, and opportunity loss, reflecting secondary vocational students’ perception of negative public evaluation, self-feeling under the influence of stigma, and cognition of negative impact on their identity. The confirmatory factor analysis (CFA) shows that the three-factor model has good fit indices. The total score and the scores of each dimension of the SSS-SVS were significantly and positively correlated with Stigma Consciousness; they were significantly and negatively correlated with SA-SVS, IDB-SVS, SVS-PIS, Learning Adjustment, and Self-Compassion. Both the Cronbach’s α coefficients of the total scale and each dimension and the McDonald’s ω coefficients were satisfactory. Additionally, the scale had measurement equivalence across gender and grade levels. The SSS-SVS has limitations and may be affected by cultural background. Future studies should expand the sample and conduct cross-cultural verification.Conclusion: The SSS-SVS is a reliable and valid instrument for assessing secondary vocational students’ self-stigma, providing support for developing relevant programs and policies. It also advances secondary vocational education and enhances students’ mental health.Keywords: secondary vocational students, self-stigma, reliability, validity

Qiu Dong,1,* Jiayang Wu,2,3,* Huaguo Zhang,4,* Xinhui Chen,2,3 Xi Xu,2,3 Jifeng Chen,3 Changzheng Shi,2,3,5 Liangping Luo,3,5 Dong Zhang2,3 1Department of Bone and Joint Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China; 2Medical Imaging Centre, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China; 3The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China; 4Department of Ultrasonography, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, People’s Republic of China; 5Medical Imaging Centre, the Fifth Affiliated Hospital of Jinan University, Heyuan, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dong Zhang, Email lbzhangdong@126.comPurpose: Immunometabolism is pivotal in rheumatoid arthritis (RA) pathogenesis, yet the intricacies of its pathological regulatory mechanisms remain poorly understood. This study explores the complex immunometabolic landscape of RA to identify potential therapeutic targets.Patients and Methods: We integrated genome-wide association study (GWAS) data involving 1,400 plasma metabolites, 731 immune cell traits, and RA outcomes from over 58,000 participants. Mendelian randomization (MR) and mediation analyses were applied to evaluate causal relationships among plasma metabolites, immune cells, and RA. We further analyzed single-cell and bulk transcriptomes to investigate differential gene expression, immune cell interactions, and relevant biological processes. Machine learning models identified hub genes, which were validated via quantitative real-time PCR (qRT-PCR). Then, potential small-molecule drugs were screened using the Connectivity Map (CMAP) and molecular docking. Finally, a phenome-wide association study (PheWAS) was conducted to evaluate potential side effects of drugs targeting the hub genes.Results: Causalities were found between six plasma metabolites, five immune cells and RA in genetically determined levels. Notably, DC mediated 18% of the protective effect of PE on RA. Autophagy-related scores were elevated in both RA and DC subsets in PE-associated biological processes. Through observation in the functional differences in cellular interactions between the identified clusters, DCs with high autophagy scores may process such as necroptosis and the activation of the Jak-STAT signaling pathway in contributing the pathogenesis of RA. Explainable machine learning, PPI network analysis, and qPCR jointly identified four hub genes (PFN1, SRP14, S100A11, and SAP18). CMAP, molecular docking, and PheWAS analysis further highlighted vismodegib as a promising therapeutic candidate.Conclusion: This study clarifies the key immunometabolic mechanisms in RA, pinpointing promising paths for better prevention, diagnosis, and treatment.Keywords: rheumatoid arthritis, dendritic cells, single-cell sequencing, bulk transcriptome, explainable machine learning, drug repositioning

Understanding the mesoscopic tensile fracture damage of rock is the basis of evaluating the deterioration process of mechanical properties of heat-damaged rock. For this, tensile tests of rocks under high-temperature treatment were conducted with a ϕ75 mm split Hopkinson tension bar (SHTB) to investigate the mesoscopic fracture and damage properties of rock. An improved scanning electron microscopy (SEM) experimental method was used to analyze the tensile fracture surfaces of rock samples. Qualitative and quantitative analyses were performed to assess evolution of mesoscopic damage of heat-damaged rock under tensile loading. A constitutive model describing the mesoscopic fractal damage under thermo-mechanical coupling was established. The results showed that the high temperatures significantly reduced the tensile strength and fracture surface roughness of the red sandstone. The three-dimensional (3D) reconstruction of the fracture surface of the samples that experienced tensile failure at 900 °C showed a flat surface. The standard deviation of elevation and slope angle of specimen fracture surface first increased and then decreased with increasing temperature. The threshold for brittle fracture of the heat-damaged red sandstone specimens was 600 °C. Beyond this threshold temperature, local ductile fracture occurred, resulting in plastic deformation of the fracture surface during tensile fracturing. With increase of temperature, the internal meso-structure of samples was strengthened slightly at first and then deteriorated gradually, which was consistent with the change of macroscopic mechanical properties of red sandstone. The mesoscopic characteristics, such as the number, mean side length, maximum area, porosity, and fractal dimension of crack, exhibited an initial decline, followed by a gradual increase. The development of microcracks in samples had significant influence on mesoscopic fractal dimension. The mesoscopic fractal characteristics were used to establish a mesoscopic fractal damage constitutive model for red sandstone, and the agreement between the theoretical and experimental results validated the proposed model.

Kairong Su,1,&ast; Sinan Xiao,1,&ast; Mei Wang,2 Kairuo Wang,1 Qing Fan,1 Sumei Sha,1 Yongli Cheng,3 Xin Liu,1 Haitao Shi1 1Department of Gastroenterology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Gastroenterology, Xi’an International Medical Center Hospital, Xi’an, Shaanxi, People’s Republic of China; 3Department of Gastroenterology, Xi’an Chang’an District Hospital, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Liu, Department of Gastroenterology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China, Email docliuxin126@xjtu.edu.cn Haitao Shi, Department of Gastroenterology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China, Email shihaitao7@xjtu.edu.cnPurpose: The albumin to fibrinogen ratio (AFR), a biomarker associated with inflammatory, nutritional, and coagulation status, and the CALLY index, a biomarker combining C-reactive protein, albumin, and lymphocyte count, have been suggested to correlate with prognosis in a variety of diseases in previous studies; however, studies of these two markers in ulcerative colitis (UC) are lacking. The aim of this study was to evaluate the clinical significance of AFR and CALLY index in UC.Methods: The study included 109 UC patients and 126 healthy controls. For UC patients treated with Vedolizumab (50 patients), they were categorized into mucosal healing group (MH group) and non- mucosal healing group (non-MH group) based on Mayo endoscopic score (MES) after 14 weeks of treatment. The differences in AFR and CALLY index were compared between the UC group and the healthy control group, and between the MH group and the non-MH group. Then, the correlation of the AFR and CALLY index with UC activity was assessed, and the predictive value of the AFR and CALLY index was evaluated using the receiver operating characteristic (ROC) curve.Results: The results showed that both AFR and CALLY index were significantly decreased in the UC group compared with the healthy control group (both p< 0.001); the area under the curve (AUC) of the AFR and CALLY index differentiating between the healthy control group and the UC group were 0.782 and 0.773, respectively. For Vedolizumab treatment, the non-MH group had significantly lower baseline AFR and CALLY index compared to the MH group; the AUC for baseline AFR and CALLY index discriminating the MH group from the non-MH group were 0.665 and 0.721, respectively. In addition, AFR and CALLY index were negatively correlated with the MES and inflammatory load of UC. The results of multivariate logistic regression analysis showed that the CALLY index was an independent predictor of UC diagnosis and mucosal healing after 14 weeks of Vedolizumab treatment.Conclusion: AFR and CALLY index can be used as novel serologic markers for diagnosing UC and predicting the efficacy of Vedolizumab treatment.Keywords: albumin to fibrinogen ratio, CALLY index, ulcerative colitis, Vedolizumab, mucosal healing, biomarkers

Hailun Xie,1,&ast; Lishuang Wei,1,&ast; Guotian Ruan,2– 5 Heyang Zhang,2– 5 Hanping Shi1 1Department of Gastrointestinal and Gland Surgery, the First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Department of Gastrointestinal Surgery, Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, People’s Republic of China; 5Laboratory for Clinical Medicine, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hanping Shi, Department of Gastrointestinal and Gland Surgery, the First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China, Email shihp@ccmu.edu.cnPurpose: Interleukin-6 (IL-6) is a central factor linking inflammation to cancer. This study aimed to provide a comprehensive assessment of the prognostic value of IL-6 and its immunotherapeutic features using a population-based pan-cancer analysis and comprehensive bioinformatic analysis.Patients and Methods: In the cohort study, 540 patients were included to explore the prognostic value of serum IL-6 levels in cancer. The differential expression of IL-6 and its association with survival and immune cell infiltration were investigated using the TCGA database. The SangerBox database was used to analyze the correlation between IL-6 expression and immune checkpoint (ICP), tumor mutation burden (TMB), and microsatellite instability (MSI) in cancer. Genomic changes in the IL-6 levels were studied using the c-BioPortal database. The IL-6 co-expression network was analyzed using the LinkedOmics database.Results: Serum IL-6 is an independent prognostic factor for cancer, especially gastrointestinal cancers. Compared to other serum inflammatory markers, serum IL-6 is an optimal biomarker for cancer prognosis. A comprehensive bioinformatics analysis showed higher IL-6 expression in human cancers than in the paired normal tissues. The IL-6 expression is closely associated with prognosis, ICP, TMB, and MSI. In addition, it is also strongly correlated with tumor-infiltrating cells. IL-6 levels are significantly associated with the prognosis of stomach adenocarcinoma (STAD). The IL-6 co-expression network in STAD is mainly involved in regulating inflammatory pathways and cell communication.Conclusion: IL-6 is a potential prognostic and immune biomarker of cancer. Compared to other clinical inflammatory biomarkers, IL-6 demonstrates superior prognostic efficacy.Keywords: Interleukin-6, Prognostic marker, Bioinformatic analysis, STAD

Baolan Ji,1 Guanqi Gao,2 Hongyan Zhao,2,3 Jie Sheng,2,3 Xuan Ma,2,3 Shuwei Shi,1– 3 Bo Ban1,2 1Department of Endocrinology, Affiliated Hospital of Jining Medical University, Jining, Shandong, 272029, People’s Republic of China; 2Department of Endocrinology, Linyi People’s Hospital Affiliated to Shandong Second Medical University, Linyi, Shandong, 276034, People’s Republic of China; 3School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, 261000, People’s Republic of ChinaCorrespondence: Bo Ban, Department of Endocrinology, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, Jining, Shandong, 272029, People’s Republic of China, Email banbo2011@163.com Shuwei Shi, School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, 261000, People’s Republic of China, Email ssw15689286547@163.comAim: Attenuated insulin-sensitivity (IS) is a characteristic of type 2 diabetes (T2D) and is closely linked to non-alcoholic fatty liver disease (NAFLD). In recent years, many surrogate markers of IS have emerged to predict NAFLD. A natural log transformation of the glucose disposal rate (loge GDR) has been proposed as a new model for IS in patients with T2D. Our aim is to explore the correlation between loge GDR and NAFLD in normoalbuminuric patients with T2D.Methods: A total of 1227 normoalbuminuric patients with T2D were involved in our study. NAFLD was evaluated by ultrasound. Biochemical and clinical data were collected, including parameters essential for calculating the loge GDR (triglycerides, urinary albumin-to-creatinine ratio, γ-glutamyl transferase and body mass index), as well as other relevant covariates required for adjustment. The relationship between the loge GDR and NAFLD was analyzed.Results: NAFLD patients showed lower loge GDR values than non-NAFLD (P < 0.001). As the loge GDR tertiles increased, the prevalence of NAFLD was decreased (P < 0.001). Multivariate analysis displayed that loge GDR was independently corrected with NAFLD (OR: 0.084; 95% CI: 0.040– 0.177). Furthermore, receiver operating characteristic (ROC) analysis showed that loge GDR (area under the curves: 0.797) was superior to other evaluation variables.Conclusion: The loge GDR was strongly associated with NAFLD and might be a useful predictor in normoalbuminuric patients with T2D.Keywords: type 2 diabetes, NAFLD, insulin sensitivity, loge GDR

Guanglu Jiang,1,&ast; Rongmei Liu,2,&ast; Yi Xue,1 Qiping Ge,2 Lihui Nie,2 Zizheng Lv,2 Zhongshun Kong,2 Jin Shi,2 Hongmei Chen,2 Hua Li,2 Xiaoguang Wu,2 Li Xie,2 Yanhua Song,2 Hairong Huang,1 Mengqiu Gao2 1National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory on Drug-Resistant Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mengqiu Gao; Hairong Huang, Email gaomqwdm@aliyun.com; huanghairong@tb123.orgBackground: Contezolid (CZD) is an analog of Linezolid (LZD) that has demonstrated potent in vitro and in vivo activity against tuberculosis (TB) while presenting a safer side-effect profile. In this study, we evaluated the early bactericidal activity (EBA) of CZD compared to LZD, with LZD serving as a control.Methods: Naive, smear-positive pulmonary TB patients were enrolled and randomly assigned to receive either a 14-day monotherapy regimen of 600 mg LZD once daily (QD) or 800 mg CZD twice daily (BID). Sputum samples were collected daily starting one day before treatment initiation and continuing throughout the treatment period. Each sample was processed for the enumeration of acid-fast bacilli (AFB) colonies, and time-to-positivity (TTP) during MGIT960 liquid culture was recorded.Results: A total of 10 eligible patients were enrolled in each treatment group, although one patient in the CZD group was later excluded from the analysis. The early bactericidal activity (EBA0-14) was 0.08 ± 0.12 log CFU/mL/day (95% CI: − 0.02 to 0.18 CFU/mL/day) in the CZD group, compared to 0.03 ± 0.10 log CFU/mL/day (95% CI: − 0.05 to 0.10 CFU/mL/day) in the LZD group. The increase in time-to-positivity (TTP0-14) was 38.6 ± 43.69 hours (95% CI: − 1.85 to 79 hours) in the CZD group and 27.7 ± 78.21 hours (95% CI: − 28.15 to 83.75 hours) in the LZD group. LZD showed rapid bacterial reduction in sputum during the first two days of treatment, whereas CZD demonstrated superior efficacy after a few days of treatment.Conclusion: 800 mg BID contezolid exhibited comparable efficacy to 600 mg QD LZD in treating pulmonary TB in this EBA study. While CZD showed slower initial bactericidal action compared to LZD, its efficacy surpassed that of LZD after a few days of treatment. Given its similar efficacy and superior safety profile, contezolid may serve as an alternative to linezolid for the treatment of tuberculosis.Keywords: contezolid, linezolid, early bactericidal activity, time-to-positivity

Excellent disturbance rejection ability is essential for a photoelectric tracking system (PTS) based on the Charge-Couple Device (CCD) sensor, which is a premise guarantee for obtaining highly accurate tracking, especially under the condition of moving carriers with intense disturbances. The feedforward control method based on disturbance estimated from the system model output and sensor output is currently a commonly used strategy for disturbance compensation due to its ability to directly counteract the disturbances. This disturbance feedforward compensation method behaves sensitively in case of model mismatch caused by internal disturbances, which may lead to a significant reduction in the disturbance compensation effect or even cause system instability. In this paper, unlike disturbance feedforward compensation, a pure disturbance sliding-mode feedback control (DSMFBC) based on disturbance observation without additional sensors is proposed, ensuring faster and precise compensation for disturbance. In case of model mismatch, the observed disturbance is used to build the disturbance feedback control to maintain a more efficient disturbance compensation through the robustness that feedback naturally possesses. To achieve a stronger anti-disturbance capability, a sliding-mode nonlinear control method is used to design the control law. The experimental setup of PTS based on the fast-steering mirror (FSM) demonstrates that the method has better dynamic performance and disturbance rejection ratio.

ABSTRACT: Understanding and assessing dairy cattle behavior is critical for developing sustainable breeding programs and management practices. The behavior of individual animals can provide valuable information on their health and welfare status, improve reproductive management, and predict efficiency traits such as feed efficiency and milking efficiency. Routine genetic evaluations of animal behavior traits can contribute to optimizing breeding and management strategies for dairy cattle but require the identification of traits that capture the most important biological processes involved in behavioral responses. These traits should be heritable, repeatable, and measured in noninvasive and cost-effective ways in many individuals from the breeding populations or related reference populations. Although behavior traits are heritable in dairy cattle populations, they are highly polygenic, with no known major genes influencing their phenotypic expression. Genetically selecting dairy cattle based on their behavior can be advantageous because of their relationship with other key traits such as animal health, welfare, and productive efficiency, as well as animal and handler safety. Trait definition and longitudinal data collection are still key challenges for breeding for behavioral responses in dairy cattle. However, the more recent developments and adoption of precision technologies in dairy farms provide avenues for more objective phenotyping and genetic selection of behavior traits. Furthermore, there is still a need to standardize phenotyping protocols for existing traits and develop guidelines for recording novel behavioral traits and integrating multiple data sources. This review gives an overview of the most common indicators of dairy cattle behavior, summarizes the main methods used for analyzing animal behavior in commercial settings, describes the genetic and genomic background of previously defined behavioral traits, and discusses strategies for breeding and improving behavior traits coupled with future opportunities for genetic selection for improved behavioral responses.

Objective In this study, the effects of dietary ferulic acid (FA) on the growth traits, antioxidant capacity, and intestinal barrier function of broilers were investigated. Methods In total, 192 male Arbor Acres broilers were randomly allocated to one of three dietary groups (8 replicates of 8 birds each): control (CON) group (basal diet), FA100 group (basal diet + 100 mg/kg FA), or FA200 group (basal diet + 200 mg/kg FA). The duration of the feeding trial was 42 days. Results Higher average daily gain (ADG) and lower feed to gain (F/G) ratio during day 0 to day 21 were found in the FA100 and FA200 groups, while higher ADG and lower F/G during day 21 to day 42 were only found in FA200 group, compared to the CON group (p

Photocatalysis has emerged as an effective approach to sustainably convert biomass into value-added products. CoSe2 is a promising non-precious, efficient cocatalyst for photooxidation, which can facilitate the separation of photogenerated electron–holes, increase the reaction rates, and enhance photocatalytic efficiency. In this work, we synthesized a stable and efficient photocatalysis system of CoSe2/g-C3N4 through attaching CoSe2 on g-C3N4 sheets, with a yield of 50.12% for the selective photooxidation of xylose to xylonic acid. Under light illumination, the photogenerated electrons were prone to migrating from g-C3N4 to CoSe2 due to the higher work function of CoSe2, resulting in the accelerated separation of photogenerated electron–holes and the promoted photooxidation. Herein, this study reveals the unique function of CoSe2, which can significantly promote oxygen adsorption, work as an electron sink and accelerate the generation of ·O2−, thereby improving the selectivity toward xylonic acid over other by-products. This work provides useful insights into the design of selective photocatalysts by engineering g-C3N4 for biomass high-value utilization.

Abstract The objective of this study is to investigate the association between the Systemic Immune-Inflammation Index (SII) and cataracts. This cross-sectional study analyzed data from the 2005–2008 NHANES to examine the relationship between the SII and cataract prevalence. Covariates included age, race/ethnicity, gender, education level, marital status, Body Mass Index (BMI), smoking, alcohol consumption, hypertension, hyperlipidemia, and diabetes. Multivariable logistic regression was used to assess the association, while spline curve fitting explored potential non-linear relationships. Threshold analysis identified critical inflection points. To address age-related bias, Propensity Score Matching (PSM) was performed, aligning cataract patients with comparable non-cataract individuals for further evaluation. Our study included 3,623 participants, of whom 730 (20.15%) were diagnosed with cataracts. After adjusting for all covariates, multivariable logistic regression analysis demonstrated that elevated levels of the SII were significantly associated with increased odds of cataracts (Model1: OR = 1.56; 95%CI [1.33–1.85]; Model2: OR = 1.55; 95%CI [1.32–1.84]; Model3: OR = 1.57; 95%CI [1.33–1.86]). In the spline curve fitting model, the relationship between ln-SII and cataract prevalence was non-linear (P

Abstract While self-assembled material based inverted perovskite solar cells have surpassed power conversion efficiencies of 26%, enhancing their performance in large-area configurations remains a significant challenge. In this work, we report a self-assembled material based hole-selective layer 4-(7H-dibenzo[c,g]carbazol-7-yl)phenyl)phosphonic acid, with a π-expanded conjugation. The enhanced intermolecular π–π interactions facilitate the self-assembly of 4-(7H-dibenzo[c,g]carbazol-7-yl)phenyl)phosphonic acid molecules to form an ordered bilayer with a hydrophilic surface, which passivates the buried perovskite interface defect and enables high-quality and large-area perovskite preparation, while simultaneously enhancing interfacial charge extraction and transport. The certified efficiency of 4-(7H-dibenzo[c,g]carbazol-7-yl)phenyl)phosphonic acid based small-area (0.0715 cm2) device is 26.39% with high stability. Furthermore, a certified efficiency of 25.21% is achieved for a 99.12 mm2 large area device.

Abstract Background Empathy of medical students is crucial, yet it tends to decline as students enter later academic years. Empathy appeared to be affected by the learning environment (LE), which could be a potential contributor. We conducted a cross-sectional study to investigate the association between LE and empathy. Method The study comprised overall 10,901 medical students from 12 Chinese medical schools. Jefferson Scale of Empathy (JSE) was utilized to assess empathy, while a 5-point question and the Johns Hopkins Learning Environment Scale were employed to evaluate LE. JSE scores were compared across LE levels using Pearson Chi-square, Welch’s ANOVA, and univariable linear regression. After adjusting for covariates, multivariable linear and logistic regression were used to assess the independent connection between LE and empathy. Confounders were controlled by stratified subgroup analysis. Results LE was significantly associated with medical students’ empathy, as shown by the Pearson Chi-square test (p

Mengli Tian,1 Jinlong Huang,2 Yingrong Chen,1 Qiuyue Jin,1 Hong Jiang,2 Cunyuan Shi,2 Jue Mei,1 Min Xu,1 Xiang Yu,1 Shuixin Yang1 1Clinical Trial Center, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou, 313000, People’s Republic of China; 2Zhejiang Jianfeng Pharmaceutical Co Ltd., Jinhua, 321025, People’s Republic of ChinaCorrespondence: Shuixin Yang, Clinical Trial Center, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, 1558, North Third Ring Road, Huzhou, 313000, People’s Republic of China, Tel +86-0572-2978254, Email ysx@hzhospital.comPurpose: The study aimed to investigate the pharmacokinetics and bioequivalence of coformulations of valsartan and amlodipine in healthy Chinese subjects under both fasting and fed conditions.Methods: The research was conducted under both fasting and fed studies and employed a single-center, randomized, open-label, single-dose, three-period design with partial-repeat and crossover elements. A total of 71 healthy Chinese adult participants were included under fasting (n = 36) and fed (n = 35) conditions. The subjects were orally administered valsartan/amlodipine tablets (80/5 mg) per cycle either as the test (T) or reference (R) formulation. The washout period was 14 days. Plasma concentrations of valsartan and amlodipine were determined using ultrahigh-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS), and the noncompartmental analysis method was used for estimating the pharmacokinetic parameters.Results: Under fasting conditions, the within-subject standard deviations (Swr) of maximum plasma concentration (Cmax), area under the concentration–time curve from time 0 to the time of the last-measurable plasma concentration (AUC0−t), and area under the concentration–time curve from time 0 extrapolated to infinity (AUC0−∞) for valsartan were calculated to be ≥ 0.294 and evaluated by the reference-scaled average bioequivalence (RSABE) method. The point estimates of the geometric mean ratios (GMRs) of Cmax, AUC0−t, and AUC0−∞ for valsartan were 1.0805, 1.0991, and 1.1015 respectively, and the critical bounds were all less than 0. The Swr of Cmax, AUC0−t, and AUC0−∞ for amlodipine were all < 0.294, and the 90% confidence intervals (CIs) of the GMRs fell within the bioequivalence range, as evaluated by the average bioequivalence (ABE) method. Under the fed condition, the Swr of Cmax, AUC0−t, and AUC0−∞ were all < 0.294 for both valsartan and amlodipine; the ABE method was therefore employed for the evaluation of bioequivalence, and the 90% CIs of the GMRs fell within the bioequivalence range. All the observed adverse events were mild and transient.Conclusion: The two formulations of valsartan/amlodipine (80/5 mg) tablets were bioequivalent and safe.Keywords: valsartan, amlodipine, bioequivalence, pharmacokinetics, safety

Chang Li,1,&ast; Jinling Ji,1,&ast; Ting Shi,2 Shennan Pan,1 Kun Jiang,1 Yuzhang Jiang,1,&ast; Kai Wang3,&ast; 1Department of Medical Laboratory, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, Jiangsu, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, Jiangsu, People’s Republic of China; 3Department of Immunology and Rheumatology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Wang, Department of Immunology and Rheumatology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, No. 6 Beijing West Road, Huaiyin District, Huaian, Jiangsu, People’s Republic of China, Tel +8613770351754, Email morrosun@hotmail.comPurpose: Sepsis-associated liver injury (SALI) leads to increased mortality in sepsis patients, yet no specialized tools exist for early risk assessment. This study aimed to develop and validate a risk prediction model for early identification of SALI before patients meet full diagnostic criteria.Patients and Methods: This retrospective study analyzed 415 sepsis patients admitted to ICU from January 2019 to January 2022. Patients with pre-existing liver conditions were excluded. Using LASSO regression and multivariate logistic analysis, we developed a predictive nomogram incorporating clinical variables. Model performance was evaluated through internal validation using bootstrapping method.Results: Among the cohort, 97 patients (23.4%) developed SALI. The final model identified five key predictors: total bilirubin, ALT, γ-GGT, mechanical ventilation, and kidney failure. The model demonstrated good discrimination (AUC=0.841, 95% CI: 0.795– 0.887) and calibration. Decision curve analysis showed clinical utility across a threshold probability range of 4– 87%. The model outperformed traditional scoring systems (SOFA and SAPS II) in predicting SALI risk.Conclusion: This novel nomogram effectively predicts SALI risk in sepsis patients by integrating readily available clinical parameters. While external validation is needed, the model shows promise as a practical tool for early risk stratification, potentially enabling timely interventions in high-risk patients.Keywords: SALI, variable, nomogram, risk, probability

Yingxu Shi,1 Yu Tang,2 Zhiwei Sun,3 Ping Sui,4 Yiming Shao,4 Zhonghao Wang,4 Jian Zhang,1 Ming Gao1 1Department of Trauma Orthopedics, Affiliated Hospital of Jining Medical University, Jining, Shandong, 272007, People’s Republic of China; 2Pharmaceutical Department, Affiliated Hospital of Jining Medical University, Jining, Shandong, 272007, People’s Republic of China; 3Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA; 4Department of Clinical Medicine, Jining Medical University, Jining, Shandong, 272067, People’s Republic of ChinaCorrespondence: Ming Gao, Department of Trauma Orthopedics, Affiliated Hospital of Jining Medical University, No. 129 hehua Road, Jining, Shandong, 272007, People’s Republic of China, Tel + 86-0537-0298202, Email gaoming3661@mail.jnmc.edu.cnPurpose: Osteosarcoma (OS) is the most common malignant tumor associated with poor patient outcomes and a limited availability of therapeutic agents. Scutellarein (SCU) is a monomeric flavone bioactive compound with potent anti-cancer activity. However, the effects and mechanisms of SCU on the growth of OS remain unknown.Methods: The Cell Counting Kit-8, colony formation assay and 5-ethynyl-2′-deoxyuridine (EdU) incorporation assays were used to analyze cell proliferation ability in vitro. TLR4/TRAF6/NF-κB signaling transduction was investigated by RNA sequencing analysis, quantitative real-time polymerase chain reaction, Western blotting, NF-κB luciferase reporter assay, immunofluorescent staining, and immunoprecipitation. Molecular docking and cellular thermal shift assay were employed to confirm the binding interaction between SCU and TLR4. The effects of SCU and TLR4 overexpression on OS growth were analyzed using a xenograft tumor model and immunohistochemical staining.Results: SCU was found to significantly inhibit OS cell proliferation, and RNA sequencing analysis suggested that the NF-κB pathway is closely associated with this process. Further studies revealed that SCU inhibited the canonical NF-κB pathway through its binding with TLR4, which disrupted the interaction of TLR4 and TRAF6. Moreover, SCU also repressed NF-κB signal transduction by inhibiting TLR4 expression. Furthermore, SCU was revealed to suppress OS cell proliferation by targeting TLR4 in vitro and in vivo.Conclusion: SCU exhibited a dual impact by inhibiting TLR4 expression and disrupting TLR4–TRAF6 interaction, resulting in NF-κB inactivation, thereby blocking OS growth. Keywords: scutellarein, osteosarcoma, TLR4, NF-κB pathway, molecular modeling

Huiyi Deng,1,2 Qintai Yang,1,2 Zhaohui Shi1,2 1Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Department of Allergy, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Zhaohui Shi, Department of Otolaryngology-Head and Neck Surgery, Department of Allergy, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China, Email shizhh35@mail.sysu.edu.cnBackground: Extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT) is a rare, highly invasive Epstein-Barr virus associated hematological malignant tumor with an unfavorable prognosis. Although ENKTCL-NT has been previously reported, no relevant article has provided an intuitive, progressive series of schematic illustrations of the rapid progression of facial ulcers.Objective: This article reports a serious case of ENKTCL-NT that involved the entire process from onset to death.Case Summary: A 67-year-old man suffered a facial lesion started at the right ala nasi. The wound continued to spread uncontrollably to the nasion and the nasolabial groove. Subsequently, he used an unauthorized external application of herbal medicine, which unfortunately resulted in further expansion of the wound, encompassing the area from the right eyelid to the left inner canthus, extending up to the eyebrow arch, down to the right ala nasi, and deep into the nasal bone over six months. Histopathological analysis of the two biopsies revealed inflammatory necrotic granulation tissue.Conclusion: Nasal extranodal NK/T-cell lymphoma presenting with non-specific symptoms could easily lead to misdiagnosis. It progresses quickly, while adequate, repeated, and multiple spot biopsies for histopathologic examination help confirm the diagnosis.Keywords: ENKTCL-NT, misdiagnose, biopsy, pathology

Weiguo Gu,1,2,&ast; Jiaming Tang,2,&ast; Penghui Liu,1 Jinyu Gan,1 Jianfei Lai,1 Jinbiao Xu,2 Jianxiong Deng,2 Chaoxing Liu,1 Yuhua Wang,2 Guohua Zhang,3 Feng Yu,1,2 Chao Shi,2,3 Ke Fang,2 Feng Qiu2,3 1Department of Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Oncology, Gaoxin Branch of the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Nanchang Key Laboratory of Tumor Gene Diagnosis and Innovative Treatment Research, Gaoxin Branch of the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Qiu, Department of Oncology, Gaoxin Branch of the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China, Email ndyfy01149@ncu.edu.cn Ke Fang, Department of Oncology, Gaoxin Branch of the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Jiangxi, People’s Republic of China, Email fangkeqq88@163.comBackground: The relationship between molecular phenotype and prognosis in high-grade gliomas (WHO III and IV, HGG) treated with radiotherapy and chemotherapy is not fully understood and needs further exploration.Methods: The HGG patients following surgery and treatment with radiotherapy and chemotherapy. Univariate and multivariate Cox analyses were used to assess the independent prognostic factors. The nomogram model was established, and its accuracy was determined via the calibration plots.Results: A total of 215 and 88 patients had grade III glioma and grade IV glioma, respectively. Grade III oligodendroglioma (OG-G3) patients had the longest mPFS and mOS than other grade III pathology, while grade III astrocytoma (AA-G3) patients were close to IDH-1 wildtype glioblastoma (GBM) and had a poor prognosis. The IDH-1 mutant group had a better mPFS and mOS than the IDH-1 wildtype group in all grade III patients, OG-G3 and AA-G3 patients. Furthermore, 1p/19q co-deletion group had a longer mPFS and mOS than 1p/19q non-deletion group in all grade III patients. IDH-1 mutation and 1p/19q co-deletion patients had the best prognosis than other molecular types. Also, the MGMT methylation and IDH-1 mutation or 1p/19q co-deletion group had a longer mPFS and mOS than the MGMT unmethylation and IDH-1 wildtype or 1p/19q non-codeletion of grade III patients. In addition, the low Ki-67 expression group had a better prognosis than high Ki-67 expression group in grade III patients. Univariate and multivariate COX showed that 1p/19q co-deletion and MGMT methylation were the independent prognostic factors for mPFS and mOS. The calibration curve showed that the established nomogram could well predict the survival based on these covariates.Conclusion: The AA-G3 with IDH-1 wildtype, MGMT unmethylation or 1p/19q non-codeletion patients was resistant to radiotherapy and chemotherapy, has a poor prognosis and needs a more active treatment.Keywords: glioma, radiotherapy, prognosis, nomogram

Huiya Zhu,1 Aihua Liu,1 Zhongyan Han,2 Yanling Yang,3 Xiao Ma,2 Haiyan Shi2 1Department of Cardiovasology, the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Department of Gastroenterology, the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Neurology, PLA Rocket Force Characteristic Medical Center, Beijing, People’s Republic of ChinaCorrespondence: Haiyan Shi, Department of Gastroenterology, the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China, Email shihyan662@163.comPurpose: To evaluate and summarize the best evidence of home enteral tube feeding (HETF) care management in the elderly to provide an evidence-based basis for caregivers to implement care interventions.Patients and Methods: Evidence on HETF care management in the elderly was retrieved from Chinese and international databases, guidelines, and websites of professional associations, including systematic reviews and expert consensuses, using the keywords of home enteral nutrition, home tube feeding, old, elder, home care, etc. The literature considered in this study was published from April 2019 to April 2024. Two trained researchers independently evaluated the quality of the included literature, graded the literature using the JBI evidence pre-grading system, classified and summarized the extracted evidence.Results: A total of 15 articles were included, including 1 clinical decision, 1 guideline, 3 best evidence summaries, 4 systematic reviews, 2 randomized controlled trials, and 4 quasi-experimental studies. 18 pieces of the best evidence were summarized in 3 aspects, including the NST administration, education of caregivers, and selection of nutrition formulas.Conclusion: This study comprehensively summarized the best evidence of home enteral tube feeding care management in the elderly and provided a scientific basis for caregivers to implement care interventions. In home care settings, using evidence-based practices requires developing a comprehensive care management system based on the trinity of hospital, community and home, in order to reduce the incidence of HETF-related complications, improve the quality of life of the elderly with HETF, and provide a practical reference for NST members and caregivers.Keywords: enteral nutrition, nutritional support, quality of life, complication prevention, patient education

Qingqing Li,&ast; Jing Yin,&ast; Qibin Lin, Jilong He, Xiu Shi, Hanxiang Nie Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hanxiang Nie, Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuchang District, Wuhan, 430060, People’s Republic of China, Email nhxiang@whu.edu.cnBackground: Lung transplantation is the only effective therapeutic option for patients with end-stage lung disease. However, ischemia/reperfusion injury (IRI) during transplantation is a leading cause of primary graft dysfunction (PGD). Ferroptosis, a form of iron-dependent cell death driven by lipid peroxidation, has been implicated in IRI across various organs. This study aims to explore the role of ferroptosis in lung transplantation-related ischemia/reperfusion injury and to identify its potential molecular mechanisms through bioinformatics analysis.Methods: Transcriptome data from lung transplant patients were obtained from the Gene Expression Omnibus (GEO) database. Ferroptosis-related differentially expressed genes (FRGs) were identified by analyzing gene expression profiles before and after reperfusion. Weighted gene co-expression network analysis (WGCNA) was used to identify module genes, and overlapping genes were further analyzed using two machine learning algorithms. The CIBERSORT algorithm was applied to assess immune cell infiltration, while Mendelian randomization (MR) analysis was used to investigate causal relationships between candidate genes and PGD. Finally, Consensus clustering based on FRGs was performed to identify subtypes.Results: We identified four candidate genes associated with ferroptosis during lung reperfusion: tumor necrosis factor alpha-induced protein 3 (TNFAIP3), C-X-C motif chemokine ligand 2 (CXCL2), neural precursor cell expressed developmentally down-regulated 4-like (NEDD4L), and sestrin 2 (SESN2). These genes were closely associated with immune cell infiltration. MR analysis suggested that SESN2 might play a protective role against PGD. Additionally, consensus clustering revealed distinct immune infiltration patterns across subtypes, providing insights for personalized therapeutic approaches to lung ischemia/reperfusion injury (LIRI).Conclusion: This study highlights TNFAIP3, CXCL2, NEDD4L, and SESN2 as candidate genes associated with ferroptosis during LIRI, with SESN2 potentially protecting against PGD. These findings offer promising therapeutic targets for preventing LIRI and improving outcomes in lung transplantation.Keywords: lung ischemia/reperfusion injury, ferroptosis, biomarkers, immune cell infiltration

Zhiguang Fan,1 Xiaoli Shi,2 Jiaqi Leng,3 Dan Cui,3 Deming Li4 1Department of Psychology, Shaoxing University, Shaoxing, People’s Republic of China; 2Department of Psychology, University of Exeter, Exeter, UK; 3School of English, Jilin International Studies University, Changchun, People’s Republic of China; 4Shanghai Municipal Institute for Lifelong Education, East China Normal University, Shanghai, People’s Republic of ChinaCorrespondence: Deming Li, Email lideming0513@163.comObjective: Loneliness and psychological distress are serious challenges for older adults to cope with and factors threatening life quality and happiness during their remaining years. Older people’s attitudes and evaluations towards loneliness potentially affect psychological distress. Therefore, the current study aimed to examine the relationship between the stigma of loneliness and the psychological distress of older adults, further exploring the mediating effect of distress disclosure and loneliness.Methods: Conducted during February and March 2024, the questionnaire survey included 933 older adults (age 65– 89) using the Stigma of Loneliness Scale (SLS), Distress Disclosure Index (DDI), UCLA Loneliness scale (ULS-6), and 6-item Kessler Psychological Distress Scale (K6). The obtained data were for descriptive statistical analysis, correlation analysis, and chain mediation model testing.Results: Stigma of loneliness was significantly positively correlated with loneliness and psychological distress (r=0.61– 0.69, p< 0.01), and distress disclosure was negatively correlated with stigma of loneliness, loneliness, and psychological distress (r=− 0.37–− 0.48, p< 0.01). Stigma of loneliness can not only directly affect the psychological distress of older adults (effect value=0.38), but also indirectly affect psychological distress through the mediating roles of distress disclosure (effect value=0.04) and loneliness (effect value=0.20), and the chain mediating effect of the two (effect value=0.05).Conclusion: The study redounds to the in-depth understanding of the effect of the stigma of loneliness on psychological distress among older people and its internal mechanism. The research results contribute to theoretical reference in explaining the formation background of psychological distress among older cohorts, which intends to provide empirical evidence for intervention studies of reducing psychological distress.Keywords: older adults, stigma of loneliness, psychological distress, distress disclosure, loneliness

Yujia Fu,1,2,&ast; Jingjie Wu,3,&ast; Zhiting Guo,4 Yajun Shi,1 Binyu Zhao,1,2 Jianing Yu,1,2 Dandan Chen,3 Qiwei Wu,1,2 Erxu Xue,3 Haoyang Du,3 Huafang Zhang,1 Jing Shao1,2 1Department of Nursing, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, People’s Republic of China; 2School of Nursing and Institute of Nursing Research, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Nursing, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Nursing, The Second Affiliated Hospital of Zhejiang University School of Medicine (SAHZU), Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Shao, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou, 310058, People’s Republic of China, Email 11318202@zju.edu.cnPurpose: This study aims to identify self-management behavior profiles in multimorbid patients, and explore how workload, capacity, and their interactions influence these profiles.Patients and Methods: A sequential explanatory mixed-methods design was employed. In the quantitative phase (August 2022 to May 2023), data were collected from 1,920 multimorbid patients across nine healthcare facilities in Zhejiang Province. Latent Profile Analysis (LPA) was used to identify distinct self-management behavior profiles. Multinomial logistic regression was then used to assess the influence of workload and capacity dimensions (independent variables in Model 1), as well as their interaction (independent variables in Model 2), on these profiles (dependent variables in two models). The qualitative phase (May to August 2023) included semi-structured interviews with 16 participants, and the Giorgi analysis method was used for data categorization and coding.Results: Quantitative analysis revealed three self-management behavior profiles: Symptom-driven Profile (8.0%), Passive-engagement Profile (29.5%), and Active-cooperation Profile (62.5%). Compared to the Active-cooperation Profile, both the Symptom-driven and Passive-engagement Profiles were associated with a higher workload (OR > 1, P < 0.05) and lower capacity (OR < 1, P < 0.05). An interaction of the overall workload and capacity showed a synergistic effect in the Passive-engagement Profile (OR = 1.08, 95% CI = 1.03– 1.13, P < 0.05). Qualitative analysis identified six workload themes, and related coping strategies of three self-management behavior profiles. The integrated results highlighted distinct characteristics: Symptom-driven Profile patients exhibited reactive behaviors with limited health awareness, Passive-engagement Profile patients reduced engagement once symptoms stabilized, while Active-cooperation Profile patients proactively managed their conditions.Conclusion: Identifying three distinct self-management behavior profiles and their relationship with workload and capacity provides valuable insights into multimorbid patients’ experiences, emphasizing the need for tailored interventions targeting workload and capacity to improve health outcomes.Keywords: multimorbidity, self-management, workload, capacity, interaction, mixed-methods study

Rong Yu,1,&ast; Qin Yu,1,&ast; Jie Shi,2,&ast; Xue Meng,3 Zhiyuan Deng,3 Jing Suo,4 Hao Yang1 1Department of Radiation Oncology, Peking University Cancer Hospital (Inner Mongolia Campus) & Affiliated Cancer Hospital of Inner Mongolia Medical University, Huhhot, Inner Mongolia Autonomous Region, 010020, People’s Republic of China; 2Department of Gynecology and Oncology, Peking University Cancer Hospital (Inner Mongolia Campus) & Affiliated Cancer Hospital of Inner Mongolia Medical University, Huhhot, Inner Mongolia Autonomous Region, 010020, People’s Republic of China; 3Department of Graduate School, Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, 010059, People’s Republic of China; 4Department of Gynecology and Obstetrics, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region, 010050, China&ast;These authors contributed equally to this workCorrespondence: Hao Yang, Department of Radiation Oncology, Peking University Cancer Hospital (Inner Mongolia Campus) & Affiliated Cancer Hospital of Inner Mongolia Medical University, No. 42, Zhao Wu Da Road, Huhhot, Inner Mongolia Autonomous Region, 010020, People’s Republic of China, Tel +86 471-3280801, Email hdgeu98@163.com Jing Suo, Department of Gynecology and Oncology, Affiliated People’s Hospital of Inner Mongolia Medical University, 1 Tongdao North Street, Hohhot, Inner Mongolia Autonomous Region, 010050, People’s Republic of China, Tel +86 471-3451350, Email suojing49@sina.comBackground: Gene methylation in cells is an important factor in tumorigenesis, and radiotherapy can change DNA methylation in cells. In this study, complete genome methylation sequencing (BS-Seq) technology was used to analyze the genome-wide methylation of patients with cervical cancer before and after radiotherapy.Methods: Three pairs of cervical squamous cell carcinoma samples were collected from patients before and after radiotherapy in July 2020. Genome-wide DNA methylation profiles were generated using WGBS. Bioinformatics analysis was conducted to identify differential methylation regions (DMRs) and their associated genes and pathways. The study focused on the methylation changes of LHX2, LHX5, and LHX9 genes, assessing their expression levels using qRT-PCR and correlating these changes with cervical cancer stages.Results: MCG was the main way of genomic DNA methylation in the three patients. The DNA methylation level and methylation density on each chromosome varied greatly. As revealed by comparison of methylation before and after radiation in the three patients, 1287, 1261 and 789 differential methylation genes were identified, respectively. 3) Combined with clinical treatment, methylation level difference and correlation enrichment analysis, it was found that LHX2, LHX5 and LHX9 were closely related to the occurrence and development of cervical cancer. After 5-Aza-DC and radiotherapy, the methylation of the CpG islands in LHX2, LHX5 and LHX9 genes in these patients was decreased (p < 0.01), and the mRNA and protein expression levels were relatively increased (p < 0.01).Conclusion: In our present work, genome-wide DNA methylation maps of cervical cancer tissues before and after radiotherapy were successfully constructed. We found that LHX5 and LHX9 genes are closely related to cervical cancer. LHX5 and LHX9 have a negative effect on cervical cancer. The migration ability of LHX9 silenced cells was significantly enhanced after irradiation.Keywords: cervical cancer, radiation therapy, whole-genome bisulfite sequencing, WGBS, LHX2, LHX5, LHX9

Abundant coal and oil shale resources are developed in the coal-bearing member of the Shimengou Formation (J2sh1) in the northern Qaidam Basin, NW China. A better understanding of the formation mechanism of these oil shales is of great significance for the exploration of potential unconventional oil and gas resources, and the co-development of coal and oil shale resources. In this study, the geochemistry of 16 samples from drilling cores was used to determine paleoclimate, paleosalinity, redox conditions, chemical weathering intensity, provenance, and tectonic setting. The results show that the geochemical characteristics of the samples are similar to the composition of the upper continental crust, with a warm and humid paleoclimate, a freshwater to brackish paleosalinity condition, a generally anoxic condition, and intense weathering during the Middle Jurassic. The provenance was mainly felsic igneous rocks, and the prevailing tectonic setting was passive margin. During the Middle Jurassic, the warm and humid climate, caused by the low paleolatitude and water vapor from the Tethys Ocean, made the provenance mainly from Hercynian intrusive rocks, which underwent intense weathering and entered the northern Qaidam Basin along with plant material. During water regression periods, abundant terrestrial plants formed coal, while during flooding periods, the increasing water depth and the input of nutrients from terrestrial debris promoted the development of lake algae. Algae and other lake organisms, as well as terrestrial plants, provided the material basis for the formation of organic matter. The anoxic preservation conditions enabled the preservation of organic matter, resulting in the formation of oil shale. This study helps to understand the formation mechanism of the J2sh1 oil shale and promotes the utilization of oil shale in the studied area.

Retinal fundus images are widely utilized in clinical screening and diagnosis of ocular diseases. However, in practical scenarios, the obtained fundus images are prone to be low-resolution (LR). LR fundus images increase the uncertainty in clinical observations, thereby heightening the risk of misdiagnosis. Despite this, popular super-resolution methods often yield unsatisfied results, especially when fundus images suffer from multiple degradations. In this article, we first analyze the degradation models of fundus images during the super-resolution reconstruction (SR) process. Then, we specially design a dual-branch U-Net network for retinal fundus images SR which incorporates our proposed muti-scale residual encoders (MSRE) with channel and spatial attention block (CSAB), while simultaneously preserving anatomical retinal structures and global features during SR process. Extensive experimental results on synthetically degraded LR fundus images demonstrate that our method can produce favorable results across multiple degradation models.

Meruliaceae is one of the three major families of the phlebioid clade in the Polyporales that consists primarily of wood-decaying species. We undertook an in-depth survey on species diversity, generic delimitations, phylogeny, and divergence times within the Meruliaceae with an emphasis on specimens from East Asia. In total, 26 genera including two new genera, Meruliella and Porophlebia, are recognised; ten new species, viz. Crustodontia vietnamensis, Luteochaete odontoidea, Meruliella hainanensis, Merulius pinicola, Mycoacia beijingensis, Phlebiporia crystallifera, P. odontoidea, Pseudophlebia vesiculosa, Scopuloides ellipsoidea, and S. grandinioides are introduced; eleven new combinations, viz. Allophlebia formosana, Aurantiopileus albidus, A. semisupina, Meruliella lindtneri, Merulius croceum, M. leptospermi, M. serialis, Phlebicolorata austroasiana, Phlebiodontia caspica, P. fissurata and Porophlebia fimbriata, and one new name, Mycoacia neotuberculata, are proposed. Noblesia is placed as a synonymy of Merulius, whereas Ceriporiopsis and Lilaceophlebia are accepted as synonyms of Mycoacia. Descriptions and illustrations are provided for the new genera and species, and discussions are provided for all 26 genera and new taxa. The molecular clock analysis results show that the Meruliaceae emerged with a mean stem age of 186.71 Mya of the early Jurassic, and the genera diverged with a mean stem age between 44.29 to 169.46 Mya.

Abstract Background Pancreatic adenocarcinoma (PAAD) has a very poor prognosis, and there are few treatments for PAAD. Therefore, it is important to find some biomarkers for the diagnosis and treatment of PAAD. Although some members of Armadillo repeat containing proteins (ARMCs) have been implicated in the development of certain cancers, their relationship with PAAD remains unknown. In this study, we aimed to explore the expression and prognostic value of ARMCs in PAAD. Methods We used the The Cancer Genome Atlas (TCGA) database for survival analysis. Then, Gene Expression Profiling Interactive Analysis (GEPIA), the cBioPortal database, the Human Protein Atlas (HPA), Kaplan-Meier Plotter, LinkedOmics Database, Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG), Cytoscape and Timer were used to analyze the relationship between ARMCs and PAAD. In addition, we established a prognostic model of ARMCs for PAAD. Immunohistochemistry (IHC) was also performed. Then Image-J was used to analyze all images obtained from the experiment, and GraphPad-Prism (9.5.1) was used for statistical analysis to verify the expression of ARMCs in PAAD. Results In the TCGA database, the expressions of ARMC1, 2, 3, 5, 6, 7, 8, 9 and 10 in PAAD tissues were significantly higher than those in normal tissues. And higher expressions of ARMC1 and 10 were associated with lower survival rate of PAAD patients. In addition, ARMC2, 5, 6, and 10 were positively associated with advanced stages of PAAD. ARMCs mutations occur in 11% of PAAD patients, and missense mutations and amplification of ARMCs account for most of them. In addition, ARMC5 and ARMC10 were independent prognostic factors in univariate and multivariate Cox regression analyses. Finally, through our confirmation experiment, it was found that the expression of ARMC1 and 10 in PAAD tissues was significantly increased compared with those in paracancer tissue. Conclusion This study suggests that ARMCs may be able to play important roles in PAAD, and they can act as biomarkers, providing valuable clues for the treatment and diagnosis of PAAD.

Abstract Electric polarization typically originates from non-centrosymmetric charge distributions in compounds. In elemental crystalline materials, chemical bonds between atoms of the same element favor symmetrically distributed electron charges and centrosymmetric structures, making elemental ferroelectrics rare. Compared to atoms, elemental clusters are intrinsically less symmetric and can have various preferred orientations when they are assembled to form crystals. Consequently, the assembly of clusters with different orientations tends to break the inversion symmetry. By exploiting this concept, we show that sliding ferroelectricity naturally emerges in trilayer quasi-hexagonal phase (qHP) C60, a cluster-assembled carbon allotrope recently synthesized. Compared to many metallic or semi-metallic elemental ferroelectrics, trilayer qHP C60’s have sizable band gaps and several ferroelectric structures, which are distinguishable by measuring their second-harmonic generation (SHG) responses. Some of these phases show both switchable out-of-plane and in-plane polarizations on the order of 0.2 pC/m. The out-of-plane and in-plane polarizations can be switched independently and enable an easy-to-implement construction of Van der Waals homostructures with ferroelectrically switchable chirality.

Abstract Objective This study aims to develop a novel risk assessment tool for coronary artery disease (CAD) based on data of patients with chest pain in outpatient and emergency department, thereby facilitating the effective identification and management of high-risk patients. Methods A retrospective analysis was conducted on patients hospitalized for chest pain. Patients were divided into a control group and a CAD group based on angiographic results. Logistic regression was used to identify factors associated with CAD, and R-Studio was utilized to construct the CAD risk prediction model. Results Multivariate logistic regression analysis indicated that age, gender, diabetes, ECG (electrocardiogram) ST-T changes, neutrophils (NE), coronary artery calcification (CAC), and typical chest pain were independent factors associated with CAD. Based on the results of multifactorial logistic analysis, the CAD risk prediction model built with R-Studio had a highest C-index of 0.909, and a validation cohort C-index of 0.897, demonstrating excellent predictive ability. Decision Curve Analysis showed that the model significantly outperformed others in terms of clinical net benefit. Conclusion The present study successfully developed a CAD risk assessment model based on Chinese population. This novel model could be used to assess CAD risk in patients with chest pain, optimize clinical decision making, and improve patient outcomes, regardless of whether it is applied in large hospitals or resource-limited Community Healthcare Center.

Zihe Zhao,1,&ast; Taicai Chen,2,3,&ast; Qingyuan Liu,4 Jianhang Hu,1 Tong Ling,2,3 Yuanhao Tong,5 Yuexue Han,1 Zhengyang Zhu,6 Jianfeng Duan,7 Yi Jin,1 Dongsheng Fu,1 Yuzhu Wang,1 Chaohui Pan,1 Reyaguli Keyoumu,1 Lili Sun,1 Wendong Li,1 Xia Gao,8,9 Yinghuan Shi,2,3 Huan Dou,10,11 Zhao Liu1 1Department of Vascular Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 2The State Key Laboratory for Novel Software Technology, Nanjing University, Nanjing, People’s Republic of China; 3National Institute of Healthcare Data Science, Nanjing University, Nanjing, People’s Republic of China; 4Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Department of Thoracic Surgery, BenQ Medical Center, Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 6Department of Radiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 7Department of Critical Care Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 8Department of Otolaryngology, Head and Neck Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 9Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 10The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, People’s Republic of China; 11Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhao Liu, Department of Vascular Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, &num;321 Zhongshan Road, Nanjing, 210008, People’s Republic of China, Email liuzhao@nju.edu.cn Huan Dou, The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, People’s Republic of China, Email douhuan@nju.edu.cnPurpose: Stanford Type B Aortic Dissection (TBAD), a critical aortic disease, has exhibited stable mortality rates over the past decade. However, diagnostic approaches for TBAD during routine health check-ups are currently lacking. This study focused on developing a model to improve the diagnosis in a population.Patients and Methods: Serum biomarkers were investigated in 88 participants using proteomic profiling combined with machine learning. The findings were validated using ELISA in other 80 participants. Subsequently, a diagnostic model for TBAD integrating biomarkers with clinical indicators was developed and assessed using machine learning.Results: Six differentially expressed proteins (DEPs) were identified through proteomic profiling and machine learning in discovery and derivation cohorts. Five of these (GDF-15, IL6, CD58, LY9, and Siglec-7) were further verified through ELISA validation within the validation cohort. In addition, ten blood-related indicators were selected as clinical indicators. Combining biomarkers and clinical indicators, the machine learning-based models performed well (AUC of the biomarker model = 0.865, AUC of the clinical model = 0.904, and AUC of the combined model = 0.909) using relative quantitation. The performance of the three models was verified (AUC of biomarker model = 0.866, AUC of clinical model = 0.868, and AUC of combined model = 0.886) using absolute quantitation. Crucially, the combined models outperformed individual biomarkers and clinical models, demonstrating superior efficacy.Conclusion: Using proteomic profiling, we identified serum IL-6, GDF-15, CD58, LY9, and Siglec-7 as TBAD biomarkers. The machine-learning-based diagnostic model exhibited significant potential for TBAD diagnosis using only blood samples within the population.Keywords: type B aortic dissection, proteomics, machine learning, serum biomarkers, diagnostic model

Geochemical data and remote sensing data are two typical exploratory datasets widely employed in various kinds of research, such as mineral development and environmental protection. The fusion of these two types of datasets can provide richer and more accurate information for geoscience analysis. But the existing remote sensing–geochemical data fusion methods have problems; there is a big gap between the two kinds of data in resolution. And there are other limitations, such as low fusion quality, few optional fusion methods, and not suitable for practical production applications. This article proposes a novel convolutional neural network that effectively fuses high-resolution remote sensing data with low-resolution geochemical data, enhancing the quality of geochemical data. A new data augmentation method, which mixes data of different resolutions but with the same mapping relationship, is applied to the fusion process of remote sensing data and geochemical data in this article. Experiments show that this method can improve the quality of fusion results. And transfer learning is applied to the fusion of different elements. Ag and Cr are selected to verify the mobility and generalization of the model. Compared with the existing interpolation methods, the results show that the fusion method based on the model can better characterize the distribution law of geochemical data.

Hyperspectral imaging for satellites is currently an important tool for global monitoring of methane point sources, and it can be used to retrieve methane concentration to enable source location and “top-down” emission estimation. The matched filter (MF) is the main method used to retrieve methane enhancement from hyperspectral imaging. However, many false positive retrievals occur over heterogeneous land surfaces because of the confusion between methane absorption and surface reflectance spectra. This hinders the accurate quantification of methane point source emissions from hyperspectral imaging. To overcome this hindrance, we present an improved matched filter that includes background filtering to mitigate the reflectance spectra mismatch between the target and background. By analyzing the land cover shortwave-infrared spectral library, we found that wideband spectral slopes can be used to distinguish between surface types. Based on this, we designed the background sample filtering process and verified its performance using simulation and the advanced hyperspectral imager data. The results show that the improved matched filter can effectively reduce false retrievals over heterogeneous land surfaces and obtain a more realistic methane plume. For example, near an emission source with a $\Delta$XCH$_{4}$ of 1000 ppb, the simulated retrieval bias can be less than 1.3% using a 1% filter threshold. Our method can enhance the ability of satellites to quantify methane concentrations on complex land surfaces.

The secure condition of the tunnel face perpetually remains as a matter of substantial concern throughout the execution of tunnel-construction endeavors. Especially in composite formations, the presence of longitudinal stratigraphic interfaces makes it an exceptionally complicated issue. An improved segmented three-dimensional collapse mechanism was constructed to account for the effects of lithological mutations on the face instability characteristics of tunnels. Then, the critical support pressure was evaluated in the context of kinematic limit analysis and the nonlinear Hoek-Brown failure criterion. The validity of the proposed model was confirmed by comparison with numerical simulations and theoretical results from literature. The impact of the distance between the tunnel face and the stratigraphic interface (L), the tunnel diameter (d), and the Hoek-Brown parameters on the support pressure and collapse mode were analyzed further. The results indicate that the face stability is predominantly determined by the geological parameters of the fractured rock mass and exhibits a consistent decrement with the increase of both L and d. A decline in the geological strength index (GSI), material constant (mi) and uniaxial compressive strength (σci), or an escalation in the disturbance factor (D) of the fractured rock mass results in an increase in the critical support pressure and an expansion of the potential failure range.

This is an article in the field of ceramics and composites. In order to investigate the basic road performance of mica powder modified asphalt mixture, modified asphalt with 0%, 3%, 5%, 7%, 9%, and 11% content was prepared. Through rotational viscosity test, penetration test and Fourier infrared spectroscopy test, the performance of mica powder modified asphalt was analyzed. AC-20 mica powder modified asphalt mixture was prepared to explore its road performance and the influence law of mica powder dimension content on asphalt mixture road performance was determined by grey correlation analysis. The test results show that the addition of mica powder can reduce the temperature sensitivity of the asphalt, and the addition of mica powder to the asphalt only causes physical blending. As the content of mica powder increases, the improvement effect of mica powder on asphalt pavement performance first increases and then decreases. When the content of mica powder is 7%, the road performance of mica powder modified asphalt mixture reaches the best. The grey correlation analysis shows that the influence degrees of mica powder dosage on road performance indicators are high temperature stability > moisture stability > low temperature crack resistance．

Objective Explore the therapeutic effect of Yangpafang on behavior and pain in subacute Parkinson's disease (PD) model mice and its possible mechanism. Methods Total 42 specific pathogen⁃free (SPF) C57BL/6J mice were randomly divided into control group, model group, Yangpafang low⁃ dose group [13.50 g/(kg·d)], medium ⁃dose group [40.50 g/(kg·d)] and high⁃dose group [121.50 g/(kg·d)], levodopa and benserazide group (7 mice in each group). The behavioral changes of mice were evaluated by Pole Climbing Test, Suspension Test and Field Test. The thermal nociceptive threshold and mechanical nociceptive threshold were measured by thermal pain response latency measuring instrument and electronic pressure pain measuring instrument. Immunohistochemical staining was used to detect the positive expression of tyrosine hydroxylase (TH) in substantia nigra and amygdala. Results There were significant differences in pole climbing time (F = 14.625, P = 0.000), suspension score (F = 24.493, P = 0.000), resting time of Field Test (F = 24.506, P = 0.000), thermal nociceptive threshold (F = 24.726, P = 0.000) and mechanical nociceptive threshold (F = 21.052, P = 0.000), TH positive expression in substantia nigra (F = 19.663, P = 0.000) and amygdala (F = 36.513, P = 0.000) among different treatment groups. Compared with the control group, the pole climbing time (P = 0.000) and resting time (P = 0.000) of the model group were prolonged, and the suspension score (P = 0.000), thermal nociceptive threshold (P = 0.000) and mechanical nociceptive threshold (P = 0.000), substantia nigra (P = 0.000) and amygdala (P = 0.000) TH positive expression decreased. Compared with the model group, the pole climbing time (P = 0.020, 0.000, 0.000, 0.000) and resting time (P = 0.000, 0.000, 0.000, 0.000) of Yangpafang low⁃dose group, medium⁃dose group, high ⁃ dose group and levodopa and benserazide group were shortened, but still longer than those of the control group (P < 0.05, for all). The suspension score (P = 0.000, 0.000, 0.000, 0.000, 0.000), thermal nociceptive threshold (P = 0.008, 0.000, 0.000, 0.000) and mechanical nociceptive threshold (P = 0.003, 0.000, 0.000, 0.000), TH positive expression in substantia nigra (P = 0.031, 0.001, 0.000, 0.000) and amygdala (P = 0.007, 0.000, 0.000, 0.000) increased. The thermal nociceptive threshold in other 3 groups was still lower than that in the control group (P < 0.05, for all), except that the levodopa and benserazide group returned to the level of the control group (P = 0.063). Compared with the Yangpafang low⁃dose group, the pole climbing time (P = 0.009, 0.009, 0.006) and resting time (P = 0.024, 0.018, 0.001) in the Yangpafang medium ⁃ dose group, high ⁃ dose group and the levodopa and benserazide group were also shortened, but still longer than those in the control group (P < 0.05, for all). Suspension score (P = 0.015, 0.011, 0.002), thermal nociceptive threshold (P = 0.001, 0.001, 0.000) and mechanical nociceptive threshold (P = 0.035, 0.001, 0.001) also increased, TH positive expression was also increased in the substantia nigra (P = 0.043, 0.023, 0.001) and amygdala (P = 0.007, 0.005, 0.000). Except that the TH positive expression in the amygdala of the levodopa and benserazide group was higher than that of the Yangpafang medium⁃dose group (P = 0.009) and the high⁃dose group (P = 0.012), there was no significant difference in each index between the latter 3 groups (P > 0.05, for all). Conclusions Yangpafang can improve the behavior and pain of subacute PD model mice, which is related to the protection of amygdala and substantia nigra dopaminergic neurons.

Existing anonymous communication systems that resisted traffic analysis could hide the identities of the communicating parties from the attacker. However, the identities of the communicating parties couldn’t be hidden from each other, and thus these systems did not apply to the scenario of anonymous whistleblowing and replying, where it was necessary to protect the identity of the whistleblower. To address this issue, an efficient anonymous whistleblower response scheme was proposed. With the technology of distributed point functions and secret sharing, the message was stored in two separate mailbox databases of non-colluding servers, so that the identity of the data receiver was hidden from the attacker. With the technology of secret sharing and encryption, the email address of the whistleblower was hidden, so that the receiving organization could reply without learning the whistleblower’s identity. The security analysis showed that the proposed scheme enabled the anonymity of both data receivers and whistleblowers at the same time. The experimental results show that compared to the Express scheme, the proposed scheme reduces the computational complexity during a reply to O(1) from O(logN), resulting in a 60% reduction in computational overhead for the receiving organization and a 50% reduction for the server.

Surgery-based multidisciplinary comprehensive treatment is the preferred treatment strategy for local advanced esophageal cancer. Neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy have been recommended by the Chinese Society of Clinical Oncology (CSCO) guideline. With the advent of immunotherapy, neoadjuvant immunotherapy combined with chemotherapy has received much attention, and the first phase Ⅲ study has also confirmed that neoadjuvant immunotherapy combined chemotherapy is a promising treatment option. This article will review the recent advances and hot spots of neoadjuvant immunotherapy combined with chemotherapy.

Abstract Background After the exit “zero-COVID” strategy in mainland China by the end of 2022, a large-scale COVID-19 outbreak seeded by Omicron variants occurred. An inhaled adenovirus type-5 vector-based (i.e., inhaled Ad5-nCoV) COVID-19 vaccine was licensed earlier in 2021. In this study, we aimed to assess the real-world effectiveness of a heterologous booster of inhaled Ad5-nCoV vaccine against Omicron infection and compared with the protection from hybrid immunity (i.e., prior breakthrough infection). Methods In this retrospective cohort study, we identified 1087 out of a total of 1146 hospital staff from a tertiary hospital in Urumqi city, China from November 22 to December 29, 2022. Demographic characteristics, baseline health status, occupation, behavioral factors, laboratory test of serological IgG antibody, and timeline from immunization to laboratory-testing outcome were obtained. We analysed the individual-level vaccination status of inhaled Ad5-nCoV vaccine, prior SARS-CoV-2 infection status and baseline vaccination status, and other risk factors before follow-up. The protective effects of the heterologous inhaled Ad5-nCoV vaccine and hybrid immunity against Omicron BA.5 infection and hospitalization were calculated as relative rate reduction (RRR), which was estimated using multivariate Poisson regression models. Results A total of 1087 hospital staff (median age of 34 years, and 343 males [31.6%]), including 931 accepted for serological antibody tests, were recruited to assess the vaccine effectiveness (VE) of the inhaled Ad5-nCoV booster and hybrid immunity. Among the 1087 participants, 413 had a history of prior SARS-CoV-2 infection (before follow-up) but did not receive an inhaled Ad5-nCoV booster, and 674 reported no prior infection, including 390 who received an inhaled Ad5-nCoV booster. The highest serological IgG antibody level was detected among the inhaled Ad5-nCoV group, with a median of 294.59 S/CO, followed by the hybrid immunity group, with a median of 93.65 S/CO compared to the reference level of the inactivated vaccine group (most of whom received the Sinopharm/BBIBP-CorV vaccine). The inhaled Ad5-nCoV booster and hybrid immunity yielded RRRs of 41.9% (95% CI: 24.8, 55.0) and 97.9% (95% CI: 94.2, 99.2), respectively, against Omicron BA.5 infection, regardless of symptom status. Conclusion We found that hybrid immunity could provide a high level of protection against Omicron infection, while a heterologous inhaled Ad5-nCoV booster conferred a moderate level of protection. Our findings supported the rollout of a heterologous vaccination strategy regardless of preexisting vaccine coverage.

Abstract Directional solidification experiments of Al-3.5 wt.% Si and Al-10 wt.% Cu alloys were conducted under gravity and microgravity conditions using a 50-m-high drop tube. The solidification morphology of the two alloys is mainly columnar dendrites and equiaxed dendrites, respectively. The dendrite arm spacing (DAS), eutectic content, grain size, and compositional distribution of both alloys exhibit distinct characteristics under gravity and microgravity conditions. The study introduces an innovative perspective by taking solute density and its redistribution behavior into account when discussing the gravity effects during the directional solidification of alloys. The results indicate that the way gravity works on the solidification behavior of alloys depends strongly on the redistribution behavior and density of solute as well as crystallization modes, such as columnar grain or equiaxed grain. These findings are helpful in clarifying the coupling mechanism of gravity and relevant factors on the solidification of alloys, not only contributing to understanding the effect of gravity on solidification better but also offering valuable guidance for eliminating solidification segregation and producing high-performance alloys.

Abstract Background Cochlear implants have helped over one million individuals restore functional hearing globally, but their clinical utility in suppressing tinnitus has not been firmly established. Methods In a decade-long study, we examined longitudinal effects of cochlear implants on tinnitus in 323 post-lingually deafened individuals including 211 with pre-existing tinnitus and 112 without tinnitus. The primary endpoints were tinnitus loudness and tinnitus handicap inventory. The secondary endpoints were speech recognition, anxiety and sleep quality. Results Here we show that after 24 month implant usage, the tinnitus cohort experience 58% reduction in tinnitus loudness (on a 0–10 scale from 4.3 baseline to 1.8 = −2.5, 95% CI: −2.7 to −2.2, p = 3 x 10−6; effect size d’ = −1.4,) and 44% in tinnitus handicap inventory (=−21.2, 95% CI: −24.5 to −17.9, p = 1 x 10−15; d’=−1.0). Conversely, only 3.6% of those without pre-existing tinnitus develop it post-implantation. Prior to implantation, the tinnitus cohort have lower speech recognition, higher anxiety and poorer sleep quality than the non-tinnitus cohort, measured by Mandarin monosyllabic words, Zung Self-rating Anxiety Scale and Pittsburgh Sleep Quality Index, respectively. Although the 24 month implant usage eliminate the group difference in speech and anxiety measures, the tinnitus cohort still face significant sleep difficulties likely due to the tinnitus coming back when the device was inactive at night. Conclusions The present result shows that cochlear implantation can offer an alternative effective treatment for tinnitus. The present result also identifies a critical need in developing always-on and atraumatic devices for tinnitus patients, including potentially those with normal hearing.

Abstract Background Musculoskeletal disorders pose major public health challenges, and accelerated biological aging may increase their risk. This study investigates the association between biological aging and musculoskeletal disorders, with a focus on sex-related differences. Methods We analyzed data from 172,332 UK Biobank participants (mean age of 56.03 ± 8.10 years). Biological age was calculated using the KDM-BA and PhenoAge algorithms based on blood biomarkers. Musculoskeletal disorders were diagnosed using the ICD-10 criteria, with sample sizes ranging from 1,182 to 23,668. Logistic regression assessed cross-sectional associations between age acceleration (AA) metrics and musculoskeletal disorders. Accelerated Failure Time (AFT) model was used for survival analysis to evaluate the relationships between AAs and musculoskeletal disorders onset. Models were adjusted for demographic, lifestyle, and socio-economic covariates. The threshold of P-values were set by the Holm-Bonferroni correction. Results Cross-sectional analyses reveal significant associations between AAs and fourteen musculoskeletal disorders. Survival analyses indicate that AAs significantly accelerate the onset of nine musculoskeletal disorders, including inflammatory polyarthropathies (RTKDM-BA = 0.993; RTPhenoAge = 0.983), systemic connective tissue disorders (RTKDM-BA = 0.987; RTPhenoAge = 0.980), spondylopathies (RTPhenoAge= 0.994), disorders of bone density and structure (RTPhenoAge= 0.991), gout (RTPhenoAge= 0.968), arthritis (RTPhenoAge= 0.991), pain in joint (RTPhenoAge= 0.989), low back pain (RTPhenoAge= 0.986), and osteoporosis (RTPhenoAge= 0.994). Sensitivity analyses are consistent with the primary findings. Sex-specific variations are observed, with AAs accelerating spondylopathies, arthritis, and low back pain in females, while osteoporosis is accelerated in males. Conclusion Accelerated biological aging is significantly associated with the incidence of several musculoskeletal disorders. These insights highlight the importance of biological age assessments in gauging musculoskeletal disorder risk, aiding early detection, prevention, and management.

Meihong Shi,1– 3,&ast; Xi Yang,4,&ast; Pan Song,1 Huarong Xiong,5 Dan Wang,6 Xiaoyan Quan,1 Xinjun Liu,7 Xiuying Hu,3 Jia Zhou8 1School of Nursing, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Nursing Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Innovation Center of Nursing Research, West China Hospital, Sichuan University/Nursing Key Laboratory of Sichuan Province/ West China School of Nursing, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Vascular Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Department of Endocrinology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 7Department of Vascular Surgery, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 8School of Humanities and Management Science, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jia Zhou; Xiuying Hu, Email zhoujia@swmu.edu.cn; westchinahuxiuying@163.comIntroduction: To develop and psychometrically validate the Self-management Questionnaire for Patients with Lower Extremity Arterial Disease Patients Who Underwent Endovascular Revascularization (LESQ).Methods: We developed the LESQ and validated it in a Chinese population. A three-round cross-sectional descriptive survey in six hospitals in China, involving samples of 271, 269, and 623 participants, respectively. The surveys were conducted between February 2021 to March 2022.Results: The final version of the LESQ, with 22 items, was divided into three domains using exploratory factor analysis: medical management, rehabilitation exercise management, and daily life management. The questionnaire had good internal consistency reliability, with a Cronbach’s α of 0.953 and good retest reliability, with the coefficients of 0.917, respectively. The content validity of the LESQ was 0.939. The three domains of the questionnaire were confirmed by confirmatory factor analysis. The optimal cut-off points were 52 and 70, respectively, using latent profile analysis.Discussion: The LESQ is a new self-report questionnaire for measuring self-management ability with good reliability and validity through validation.Keywords: lower extremity arterial disease, endovascular revascularization, self-management, questionnaire, reliability, validity

Yonglong Su,1,&ast; Zitong Wang,1,&ast; Huanhuan Chang,2,&ast; Simin Zhu,1 Yanuo Zhou,1 Zine Cao,1 Lina Ma,1 Yuqi Yuan,1 Yushan Xie,1 Xiaoxin Niu,1 Chendi Lu,1 Yitong Zhang,1 Haiqin Liu,1 Na Shao,1 Libo Yin,3 Chao Si,2 Xiaoyong Ren,1 Yewen Shi1 1Department of Otorhinolaryngology Head and Neck Surgery, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Otorhinolaryngology Head and Neck Surgery, Xi’an Children’s Hospital, Xi’an, People’s Republic of China; 3Department of Otorhinolaryngology Head and Neck Surgery, Xi’an Central Hospital, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyong Ren; Yewen Shi, Department of Otorhinolaryngology Head and Neck Surgery, the Second Affiliated Hospital of Xi’an Jiaotong University, 157 Xi Wu Road, Xi’an, Shaan’xi Province, 710004, People’s Republic of China, Email cor_renxiaoyong@126.com; shiyewen59@outlook.comPurpose: Aimed to analyze the developmental characteristics of craniofacial structures and soft tissues in children with obstructive sleep apnea (OSA) and to establish and evaluate prediction model.Methods: It’s a retrospective study comprising 747 children aged 2– 12 years (337 patients and 410 controls) visited the Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated Hospital of Xi’an Jiaotong University (July 2017 to March 2024). Lateral head radiographs were obtained to compare the cephalometric measurements. The clinical prediction model was constructed using LASSO regression analysis. We analyzed 300 children from the Xi’an Children’s Hospital for external validation.Results: Children with OSA had a higher body mass, a higher tonsil grade, larger AN ratio (ratio of the adenoids to the skeletal upper airway width), larger radius of the tonsils, a smaller angle between the skull base and maxilla (SNA) and smaller angle between the skull base and mandible (SNB), a larger distance from the hyoid to the mandibular plane (H-MP) and smaller distance between the third cervical vertebra and hyoid (H-C), a larger thickness of the soft palate (SPT) and smaller inclination angle of the soft palate than those of the controls (all p < 0.05). A prediction model was constructed for 2– 12 years group (AUC of 0.812 [95% CI: 0.781– 0.842]). Age-specific prediction models were developed for preschool children (AUC of 0.769 [95% CI: 0.725– 0.814]), for school-aged children (AUC of 0.854 [95% CI: 0.812– 0.895]).Conclusion: Our study findings support the important role of craniofacial structures such as the hyoid, maxilla, mandible, and soft palate in pediatric OSA. Age-stratified predictive models for pediatric OSA indicated varying parameters across different age groups which underscore the necessity for stratifying by age in future research. The prediction model designed will greatly assist health care practitioners with rapidly identifying.Keywords: pediatric, OSA, cephalometric measurements, prediction model

Yanhai Wang,1 Yupeng Shi,2 Zhongwei Wu,1 Jiangfeng Gao,3 Jing Wang,3 Lei Li,4 Yugang Wan,4 MuGu Lang A,1 Jianwen Zhang,1 Hongbo Wang,3 Yu Hou3,5 1Department of Clinical Laboratory, Hohhot First Hospital, Hohhot, 010030, People’s Republic of China; 2Zhejiang Digena Diagnosis Technology CO., LTD, Zhejiang, 310030, People’s Republic of China; 3Cardiology Department, Hohhot First Hospital, Hohhot, 010030, People’s Republic of China; 4Network Management, Hohhot First Hospital, Hohhot, 010030, People’s Republic of China; 5Cardiology Department, Inner Mongolia People’s Hospital, Hohhot, 010017, People’s Republic of ChinaCorrespondence: Yu Hou, Cardiology Department, Inner Mongolia People’s Hospital, No. 26, Zhaoda Road, Saihan District, Hohhot, Inner Mongolia Autonomous Region, 010017, People’s Republic of China, Tel +86-471-5281258, Email houyucardiac@163.comPurpose: This study aimed to investigate the distribution patterns of PLA2G7 gene variants in Han Chinese patients with coronary heart disease (CHD), and their relationships with serum lipoprotein-associated phospholipase A2 (Lp-PLA2) levels and lipid profiles.Methods: A total of 93 han Chinese CHD patients were recruited. Serum Lp-PLA2 levels were determined using enzyme-linked immunosorbent assay (ELISA), while comprehensive analysis of PLA2G7 gene polymorphisms was conducted through whole-exome sequencing. Concurrently, multiple lipid parameters were measured and analyzed.Results: Among these Han Chinese CHD patients, the PLA2G7 gene rs1051931 (c.1136T>C p.Val379Ala) rare variant was highly prevalent (variant rate: 94.62%) among the study population, and showed negative correlation with serum Lp-PLA2 activity. The rs1765208290 (c.233G>A p.Gly78Asp) rare variant showed positive correlation with TG, ApoA, ApoB, HDL, LDL and TCHO levels in the serum. Strong linkage disequilibrium was observed between the rs1805018 (c.593T>C p.Ile198Thr) and rs76863441 (c.835G>T p.Val279Phe), both of which were related to lower Lp-PLA2 activity.Conclusion: In these Han Chinese CHD patients, the rs1051931 (c.1136T>C p.Val379Ala) rare variant in the PLA2G7 gene is closely linked to decreased Lp-PLA2 activity, whereas the rs1765208290 (c.233G>A p.Gly78Asp) rare variant influences lipid homeostasis. The strong LD between rs1805018 (c.593T>C p.Ile198Thr) and rs76863441 (c.835G>T p.Val279Phe) loci may act synergistically to reduce Lp-PLA2 activity.Keywords: PLA2G7 gene, coronary artery atherosclerotic heart disease, serum Lp-PLA2, lipid profile

Zhijie Shi, Haihong Qin, Hao Wu Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Haihong Qin; Hao Wu, Email tjqhh1982@163.com; seaseewh@163.comIntroduction: Systemic lupus erythematosus is a heterogeneous autoimmune disease. A burst of autoimmune reactions in various systems can lead to severe clinical conditions closely associated with mortality. T cells serve as mediators that drive the occurrence and maintenance of inflammatory processes.Methods: In this work, we employed single-cell transcriptome sequencing (scRNA-seq) involving 27704 cells from the brain and spleen tissues of MRL/lpr mice and 25355 healthy controls from BALB/c mice to explore the heterogeneity of T cells and their migration from the spleen to the brain.Results: We identified a distinct group of double-negative T cells in systemic lupus erythematosus (SLE) mice that significantly expressed Eomes and other specific markers. We used the analysis of pseudotime trajectory and enrichment to show that double-negative T cells in SLE mice are strongly associated with cellular senescence and exhaustion. Additionally, we focused on the interactions among DNT, astrocytes, and microglia in the mice brain. We observed greater expression of MDK-related ligand‒receptor pairs between astrocytes and double-negative T cells, indicating that MDK may be a therapeutic target for treating neuroinflammation in SLE.Discussion: This research sheds light on the intricate dynamics of immune responses in mice with SLE, specifically highlighting the role of double-negative T cells and their connection to cellular senescence. The exploration of interactions between T cells, astrocytes, and microglia in the mice brain unveils potential avenues for therapeutic intervention, particularly in addressing neuronal inflammation in SLE.Keywords: single-cell transcriptome, T cell, SLE, neuroinflammation