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Abstract The prevalence of obesity-associated precocious puberty is gradually increasing, but the relationship between gut flora and obesity-associated precocious puberty remains unclear.We analysed the gut flora characteristics of a clinical sample of 30 girls aged 5–8 years using 16s rRNA sequencing. An obesity rat model and a rat model of gut flora transplantation were also constructed. Body weight, body length, abdominal girth, food intake, vulva opening time, and gonadal index were monitored. The secretion levels of estradiol (E2), total cholesterol (TC), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and thyroglobulin (Tg) were analyzed by ELISA. In addition, ovarian and uterine development was observed by HE staining. The mRNA and protein levels of kisspeptin-1 (Kiss-1) and gonadotropin-releasing.We found that the relative abundance of Dialister, Bacteroides, Bifidobacterium, Collinsella, and Romboutsia may be associated with obesity-associated precocious puberty. Obesity promotes gonadal development, and the gut flora of patients with obesity and obesity-associated precocious puberty regulated the gene and protein expression of Kiss-1 and GnRH, promoting precocious puberty and hypothalamic-gonadal axis hormone secretion in rats. In contrast, probiotic intervention slowed gonadal development, reduced hormone secretion, and attenuated hypothalamic-gonadal axis activity. Gut flora promoted obesity-associated precocious puberty by influencing the hypothalamic-gonadal axis, and probiotics have a therapeutic and preventive role in obesity-associated precocious puberty, which may be associated with the Kiss-1/GnRH pathway. These findings may provide some new strategies for clinical treatment and prevention of obesity-associated precocious puberty in girls.

Abstract To address the issues of node interaction power overrun and high carbon emissions that may arise during distributed optimization in multi‐energy parks (MEPs), this paper proposes a distributed low‐carbon and economic operation method for multi‐energy parks based on a cloud platform that considers network transmission capacity.The proposed method achieves maximun profit by designing a two layer collaborative architecture for distributed optimization operations. At the top level, cloud platform services are utilized to build a model for checking network transport capacity and carbon emission quotas, optimizing network node over‐limit inspection . The bottom layer constructs a distributed optimization model for multi‐energy complementation in each park, taking into account the information privacy and individual interests of each multi‐energy park. An improved alternating direction multiplier method (ADMM) is proposed to effectively solve the two‐layer framework. The case studies show that the distributed optimization method under cloud platform services proposed in this paper can achieve maximum revenue for integrated energy service provider while ensuring the safe operation of multi‐energy parks, and reasonably allocate the benefits of collaborative operation among various parks while promoting carbon emission reduction.

Abstract Chronic pain is a prevalent health condition that imposes a significant burden on the global health system. Health literacy is a determinant of the quality of pain management which directly impacts public and individual health. However, the existing health literacy measurements have predominantly focused on medical models stemmed from Western culture and the knowledge of non-Western health models has largely been neglected. This review scopes refereed health literacy publications with regard to traditional Chinese medicine and chronic pain to explore and identify 1) the conceptual basis underlying the development of traditional Chinese medicine health literacy in this area, and 2) measurement tools used in this area and their associated psychometric qualities. Twenty-eight journal articles were assessed and the results showed that most studies’ conceptual frameworks were unable to cover three key health literacy aspects defined by the World Health Organization (access, understand, and apply). Furthermore, the identified health literacy measurement tools generally lacked rigorous psychometric evaluation. Future studies should focus on exploring a comprehensive model that encompasses various health models and developing measurement tools with more culturally representative psychometric assessments.

Abstract Background With the continuous advancement of modern medical technology, the survival rate of premature infants has significantly increased. Klebsiella pneumoniae (K. pneumoniae) is one of the most common pathogens causing neonatal infections, particularly posing a serious risk to premature infants. This study aimed to analyze the clinical characteristics, antibiotic susceptibility profiles, and treatment outcomes of K. pneumoniae infections in these infants. Methods We retrospectively compared cases of K. pneumoniae infection in premature and term infants admitted in a tertiary hospital from January 2017 to December 2022 in China. Clinical and microbiological characteristics were evaluated. Data analysis was performed using the Statistical Package for the Social Sciences (SPSS), with statistical significance defined as P

Abstract Background Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide, with death rates increasing by approximately 2–3% per year. The high mortality and poor prognosis of HCC are primarily due to inaccurate early diagnosis and lack of monitoring when liver transplantation is not feasible. Fatty acid (FA) metabolism is a critical metabolic pathway that provides energy and signaling factors in cancer, particularly in HCC, and promotes malignancy. Therefore, it is essential to explore specific FA metabolism-related diagnostic and prognostic signatures that can enable the effective early diagnosis and monitoring of HCC. Methods In this study, we used genes associated with FA metabolism pathway and weighted gene co-expression network analysis (WGCNA) to establish a gene co-expression network and identify hub genes related to HCC (disease WGCNA) and FA clusters (cluster WGCNA). A diagnostic model was constructed using data downloaded from the Gene Expression Omnibus database (GSE25097), and a prognostic model was established using The Cancer Genome Atlas cohort, in which Univariate Cox regression analysis, multivariate Cox risk model, and LASSO Cox regression analysis were applied. The immune infiltration of HCC cells was evaluated using CIBERSORT. The function of the key SLC22A1 gene was experimentally verified in vitro and in vivo. Results Twelve overlapping genes (CPEB3, ASPDH, DEPDC7, ETFDH, UGT2B7, GYS2, F11, ANXA10, CYP2C8, GLYATL1, C6, and SLC22A1) from disease and cluster WGCNA were identified as key genes and used in the construction of the diagnostic and prognostic models. The RF model had the highest area under the ROC curve (AUC) of 0.994 was identified as the most effective for distinguishing patients with HCC with different features. The top five important genes (C6, UGT2B7, SLC22A1, F11, and CYP2C8) from the RF model were selected as diagnostic genes for further analysis (ROC curves: AUC value = 0.986, 95% confidence interval [95% CI] = 0.967–0.999). Moreover, a risk score formula consisting of four genes (GYS2, F11, ANXA10 and SLC22A1) was established and its independent prognostic ability was further demonstrated (univariate Cox regression analysis: hazard ratio [HR] = 3.664%, 95% CI = 2.033–6.605, P

Abstract Background Ferroptosis, a form of cell death characterized by lipid peroxidation, plays a crucial role in tumor suppression, offering novel avenues for cancer therapy. Previous studies have indicated that high levels of cyclin-dependent kinase subunit 2 (CKS2) promote the progression of various cancers. However, the potential interplay between CKS2 and ferroptosis in colon cancer (CC) remains unclear. Methods Bioinformatics and RNA-seq analyses were employed to study genes associated with the ferroptosis signaling pathway. CKS2 expression was evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot (WB). The in vitro and in vivo effects of CKS2 on CC cells were assessed through the CCK-8 assay, colony formation assay, propidium iodide (PI) staining, BODIPY staining, DCFH-DA staining, and animal experiments. Additionally, the impact of CKS2 on autophagy and glutathione (GSH) metabolism was investigated using a transmission electron microscope (TEM), immunofluorescence (IF) assays, WB experiments, and relevant assay kits. Results CKS2 expression was elevated in CC, indicating a poor clinical outcome. Knockdown of CKS2 significantly enhanced Erastin-induced ferroptosis in CC cells, leading to reduced GSH metabolism. Conversely, CKS2 overexpression produced opposite effects. Mechanistically, CKS2-induced autophagy reinforced GSH metabolism, thereby increasing resistance to ferroptosis in CC cells. Furthermore, inhibiting CKS2 promoted tumor ferroptosis by downregulating GPX4 expression. Additionally, CKS2 knockdown effectively increased sorafenib-induced ferroptosis both in vitro and in vivo. Conclusion CKS2 suppresses ferroptosis in CC by modulating GSH metabolism in both in vitro and in vivo settings. These findings offer new insights into targeting CKS2 for CC treatment and shed light on the mechanism of ferroptosis in CC.

Abstract Background This study aims to construct predicting models using radiomic and clinical features in predicting first-line vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) early resistance in metastatic clear cell renal cell carcinoma (mccRCC) patients. We also aim to explore the correlation of predicting models with short and long-term survival of mccRCC patients. Materials and methods In this retrospective study, 110 mccRCC patients from 2009 to 2019 were included and assigned into training and test sets. Radiomic features were extracted from tumor 3D-ROI of baseline enhanced CT images. Radiomic features were selected by Lasso method to construct a radiomic score. A combined nomogram was established using the combination of radiomic score and clinical factors. The discriminative abilities of the radiomic, clinical and combined nomogram were quantified using ROC curve. Cox regression analysis was used to test the correlation of nomogram score with progression-free survival (PFS) and overall survival (OS). PFS and OS were compared between different risk groups by log-rank test. Results The radiomic, clinical and combined nomogram demonstrated AUCs of 0.81, 0.75, and 0.83 in training set; 0.79, 0.77, and 0.88 in test set. Nomogram score ≥ 1.18 was an independent prognostic factor of PFS (HR 0.22 (0.10, 0.47), p

Abstract Objectives Patients with rheumatoid arthritis (RA) commonly experience a high prevalence of multiple metabolic diseases (MD), leading to higher morbidity and premature mortality. Here, we aimed to investigate the pathogenesis of MD in RA patients (RA_MD) through an integrated multi-omics approach. Methods Fecal and blood samples were collected from a total of 181 subjects in this study for multi-omics analyses, including 16S rRNA and internally transcribed spacer (ITS) gene sequencing, metabolomics, transcriptomics, proteomics and phosphoproteomics. Spearman’s correlation and protein-protein interaction networks were used to assess the multi-omics data correlations. The Least Absolute Shrinkage and Selection Operator (LASSO) machine learning algorithm were used to identify disease-specific biomarkers for RA_MD diagnosis. Results Our results found that RA_MD was associated with differential abundance of gut microbiota such as Turicibacter and Neocosmospora, metabolites including decreased unsaturated fatty acid, genes related to linoleic acid metabolism and arachidonic acid metabolism, as well as downregulation of proteins and phosphoproteins involved in cholesterol metabolism. Furthermore, a multi-omics classifier differentiated RA_MD from RA with high accuracy (AUC: 0.958). Compared to gouty arthritis and systemic lupus erythematosus, dysregulation of lipid metabolism showed disease-specificity in RA_MD. Conclusions The integration of multi-omics data demonstrates that lipid metabolic pathways play a crucial role in RA_MD, providing the basis and direction for the prevention and early diagnosis of MD, as well as new insights to complement clinical treatment options.

Shear localization is a fundamental and widely observed non-equilibrium phenomenon in metallic materials subjected to impulsive loadings. Despite extensive research over several decades, the evolution of shear bands still remains poorly understood. In this study, we propose a two-stage model to describe the evolution of thermoplastic shear band, where the effects of strain hardening, strain-rate hardening, and thermal softening are involved. Our analysis reveals that the growth of thermoplastic shear band is derived by the competition between momentum diffusion and thermal diffusion processes, which is controlled by the solid-state equivalent of the Prandtl number. By incorporating these factors into our model, we find that the presence of hardening effect retards the evolution of shear bands, resulting in a wider shear band and increased dissipation of energy. Theoretical calculation results of shear bandwidth, shear band strain, propagation velocity, process zone geometry and dimensions, critical dissipation energy, shear band toughness, and shear band spacing are well consistent with available experimental data. Additionally, we explore the potential transition to turbulence controlled by Reynolds number within shear bands and investigate the influence of the Taylor-Quinney coefficient on the evolution of shear bands. These findings are expected to offer valuable insights into the mechanism of shear band evolution.

Abstract Objectives This study investigates curcumin's neuroprotective role and its potential in promoting neurogenesis in progenitor cells within the brain. Notably, curcumin's antioxidant properties have been implicated in Alzheimer's disease treatment. However, the association between curcumin's antioxidative effects and its impact on neural stem cells (NSCs) remains to be elucidated. Methods C17.2 neural stem cells were utilized as a model to simulate oxidative stress, induced by hydrogen peroxide (H2O2). We quantified the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and intracellular reactive oxygen species (ROS), alongside the gene expression of SOD1 and SOD2, to assess intracellular oxidative stress. Additionally, Western blot analysis was conducted to measure the expressions of LC3‐II, Beclin‐1, and phosphorylated ERK (p‐ERK), thereby evaluating autophagy and ERK signaling pathway activation. Results Treatment with curcumin resulted in a reduction of MDA and ROS levels, suggesting a protective effect on NSCs against oxidative damage induced by H2O2. Furthermore, a decrease in the relative expressions of LC3‐II, Beclin‐1, and p‐ERK was observed post‐curcumin treatment. Conclusions The findings suggest that curcumin may confer protection against oxidative stress by attenuating autophagy and deactivating the ERK1/2 signaling pathways, which could contribute to therapeutic strategies for Alzheimer's disease.

Abstract Background Crohn’s disease (CD) is a chronic intestinal inflammatory disorder, the etiology of which remains unknown, and is characterized by symptoms such as chronic abdominal pain, diarrhea, obstruction, and perianal lesions. Histopathology is widely regarded as the preferred method for diagnosing CD, although the histological diagnosis may lack specificity. The identification of granulomas is commonly believed to be the most reliable diagnostic indicator for CD, surpassing all other clinical features in significance. Nevertheless, research indicates that the detection rate of granulomas in CD exhibits considerable variability. Furthermore, granulomas can manifest in various specific infections including tuberculosis and Yersinia, as well as in a range of diseases characterized by macrophage reactions such as sarcoidosis and drug-induced enteritis. Granulomas associated with CD typically do not exhibit necrosis. However, the formation of caseous granulomas may occur as a result of secondary infections related to anti-CD drug treatment or perforation of the intestinal wall. Case presentation In this study, we present a case of a 28-year-old female patient diagnosed with CD exhibiting histologic granulomas, including both caseating and non-caseating forms, which demonstrated a positive response to medical treatment. Conclusion In clinical practice, various forms of granulomas may indicate diverse underlying diseases, yet lack specificity. It is suggested that the presence of caseous granulomas should not be considered as a definitive exclusion criterion for the diagnosis when clinical, endoscopic, imaging and other histopathological features are consistent with CD. This study is the first report of caseous granulomas in CD without concomitant tuberculosis infection.

Polydiacetylene (PDA) liposomes have been widely applied for detection due to their distinctive optical properties. However, the liquid phase in which PDA liposomes are dispersed generates several drawbacks, for instance, instability, compromise of detection sensitivity induced by dilution, and separation of target sampling and detection, making it inconvenient for application. In this paper, various functionalized PDA liposomes for detecting target were prepared, which were also immobilized into swelling microneedles to construct a solid-phase detection system. The PDA liposomes-complexed microneedles (PDA/MNs) enable the integration of target sampling and detection in one platform. The effects of the dispersing matrix phase on the detection sensitivity of PDA liposomes were systematically investigated from both environmental and chemical perspectives. PDA/MNs exhibited higher sensitivity than their counterparts in liquid phase. PDA/MNs were optimized and validated for lead ion (Pb2+) and sialic acid (SA) detections. For Pb2+ detection, the limit of detection (LOD) of the PDA/MNs was 13.7 μM and 2.5 times lower than the liquid phase. For SA detection, the LOD of the PDA/MNs was 0.83 μM and 1.7 times lower than the liquid phase. The results suggested that such PDA/MNs were validated to provide a label-free, stable, sensitive, and convenient tool in an all-in-one manner for physiologic target detection.

Abstract Background maternal health during pregnancy can affect the intestinal microbial community of offspring, but currently the impact of intrauterine environmental changes resulting from gestational diabetes mellitus (GDM) on the microbiota of offspring as well as its interaction with the immune system remains unclear. Aims to explore the impact of intrauterine microbial exposure during pregnancy of gestational diabetes mellitus on the development of neonate’s intestinal microbiota and activation of immune responses. Methods Levels of lipopolysaccharides in cord blood from GDM and expression of microbial recognition-related proteins in the placenta were measured. To evaluate embryonic intestinal colonization, pregnant mice with GDM were administered with labeled Escherichia coli or Lactobacillus. The intestinal colonization of pups was analyzed through 16S rRNA gene sequencing and labeled microbial culture. Additionally, memory T lymphocyte and dendritic cell co-culture experiments were conducted to elucidate the immune memory of intestinal microbes during the embryonic stages. Result Gestational diabetes mellitus led to elevated umbilical cord blood LPS level and increased GFP labeled Escherichia coli in the offspring’s intestine after gestational microbial exposure. The mouse model of GDM exhibited increased immune markers including TLR4, TLR5, IL-22 and IL-23 in the placenta and a recall response from memory T cells in offspring’s intestines, with similar observations found in human experiments. Furthermore, reduced intestinal microbiome diversity and an increased ratio of Firmicutes/Bacteroidetes was found in GDM progeny, with the stability of bacterial colonization been interfered. Conclusions Our investigation has revealed a noteworthy correlation between gestational diabetes and intrauterine microbial exposure, as well as alterations in the neonatal microbiota and activation of immune responses. These findings highlight the gestational diabetes’s role on offspring’s gut microbiota and immune system interactions with early-life pathogen exposure.

Abstract Objective To investigate the safety and efficacy of endoscopic subserosal dissection for patients with submucosal tumors in the upper gastrointestinal tract. Methods This retrospective single-center study included 16 patients who underwent ESSD. All patients were enrolled from July 2018 to Dec 2021. Parameters such as demographics, size, resection margin, complications, pathological features, procedure time and follow-up were investigated and analyzed. Results Our study achieved 100% en bloc resection and 100% R0 resection. The most common location was the corpus with a mean tumor size of 2.78 ± 1.56 cm. The mean age, procedure time, were 53.4 ± 10.3 years, 85.31 ± 46.64 min respectively. Acocording to National Institutes of Health classification, 7 (13, 53.85%), 5 (13, 38.46%) ,and 1 (13, 7.69%) objects belonged to the very low, low, and intermediate classification, respectively. Immunohistochemistry results showed a 100% positive rate of CD34, DOG-1, CD117, and Ki67. A mean follow-up of 9.3 ± 2.5 months showed no recurrence or metastasis. Conclusions ESSD is effective and safe surgical procedure for curative removal of gastrointestinal submucosal tumors in the upper gastrointestinal tract, and it can be preferred for patients with no metastasis.

Abstract Advances in symmetry-breaking engineering of heterointerfaces for optoelectronic devices have garnered significant attention due to their immense potential in tunable moiré quantum geometry and enabling polarization light detection. Despite several proposed approaches to breaking the symmetry of low-dimensional materials, there remains a lack of universal methods to create materials with prominent polarization detection capabilities. Here, we introduce a reliable strategy for manipulating the symmetry of low-dimensional materials through a programmable ferroelectric-doping patterns technique. This method introduces a spontaneous photocurrent and enables the detection of linearly polarization light in isotropic 2H-MoTe2. The 2H-MoTe2 photodetector exhibits a significant short-circuit photocurrent intensity (J sc = 29.9 A/cm2) and open-circuit voltage V oc of 0.12 V ( ~ 3 × 105 V/cm). Under a specific bias, the polarization ratio transitions from 1 to ∞/−∞, shifting from a positive state (unipolar regime) to a negative state (bipolar regime). These findings underscore the potential of ferroelectric-doping patterns as a promising approach to creating composite materials with artificial bulk photovoltaic effect and achieving high-performance polarization light detection.

The orchid Calanthe discolor, which has high ornamental and medicinal value, is mainly distributed in Zhejiang, Jiangsu, and southeast Hubei Provinces of China, as well as in Japan and the southern Korean peninsula. In this study, the whole chloroplast genome sequence of C. discolor was first assembled using high-throughput Illumina paired-end technology, providing data to evaluate the evolution of this species. The C. discolor chloroplast genome was158,286 bp long, including a large single-copy region of 87,095 bp, a small single-copy region of 18,407 bp, and two copies of a repeat region (26,392-bp each). The overall G + C content was 41.2%. A total of 133 genes were predicted from the genome, including 87 protein-coding genes, eight ribosomal RNAs, 38 transfer RNAs. Phylogenetic analysis indicated a close relationship between C. discolor and C. bicolor.

Abstract Circular RNA (circRNA) plays a pivotal role in breast cancer onset and progression. Understanding the biological functions and underlying molecular mechanisms of dysregulated circRNAs in breast cancer is crucial for elucidating its pathogenesis and identifying potential therapeutic targets. In this study, we investigated the role and molecular mechanism of circGSK3β in breast cancer. We found that circGSK3β is highly expressed in breast cancer cell lines, where it promotes cell proliferation, migration, and invasion, thereby driving breast cancer progression. Furthermore, we observed a close association between circGSK3β expression levels and immune evasion in breast cancer cells. Mechanistically, circGSK3β acts as a competing endogenous RNA (ceRNA) by interacting with miR-338-3p, thereby promoting breast cancer cell proliferation, migration, and invasion. Additionally, circGSK3β positively regulates the expression of the target gene PRMT5 through its interaction with miR-338-3p. This, in turn, enhances H3K4me3 recruitment to the promoter region of PD-L1, resulting in upregulation of PD-L1 expression and consequent immune evasion in breast cancer. In summary, our findings underscore the significance of the circGSK3β-miR-338-3p-PRMT5-H3K4me3 axis in promoting breast cancer progression and immune evasion. CircGSK3β emerges as a critical player in breast cancer pathogenesis, potentially serving as a diagnostic and prognostic marker, and offering novel insights into the role of circRNAs in breast cancer progression.

Abstract Simultaneous electromagnetic field probing system (SEMPS) has been popular in recent years. Herein, a simultaneous electromagnetic field probing system with Y‐shaped separation detection structure (SEMPS Y) is first proposed, in which the electric field probing region and the magnetic field probing region of the probe are separated by completely covering the shield along the loop and adding a pin‐shaped metal wire to capture the electric field, which are not the same as the classical dual probe structure. Combined with the non‐rotating asymmetric calibration method (NRACM), a 4‐port vector network analyser (VNA) and a highly symmetric grounded coplanar waveguide (GCPW) calibrator are used to solve the calibration matrix of the asymmetric SEMPS Y. The high symmetry GCPW calibrator is used to generate the standard electromagnetic field for calibration. The results of standing wave measurements show that the SEMPS Y can achieve ultrawideband electromagnetic field measurement of up to 20 GHz. Based on near‐field scanning measurements, SEMP Y can obtain results consistent with the calculation. In addition, when the probe is rotated 90° to invalidate the H‐field input, the decoupling curves of E‐field and H‐field are measured. Results show that the separation detection structure can effectively solve the cross‐coupling problem.

Abstract Background Corynebacterium striatum (C. striatum), a common skin and mucosal colonizer, is increasingly considered as an opportunistic pathogen causing bloodstream infections (BSIs). This study aims to investigate the clinical features and outcomes of C. striatum-BSI. Methods We included hospitalized cases with C. striatum-positive blood cultures from January 2014 to June 2022 and classified them into C. striatum-BSI group and contamination group; Clinical characteristics, treatments, and outcomes were compared between the C. striatum-BSI group and contamination group, Methicillin-resistant Staphylococcus aureus (MRSA)-BSI and Methicillin-resistant Staphylococcus epidermidis (MRSE)-BSI. Results Fifty-three patients with positive C. striatum blood cultures were identified. Among them, 25 patients were classified as C. striatum-BSI, with 21 as contamination cases. And 62 cases of MRSA-BSI and 44 cases of MRSE-BSI were identified. Compared to the contaminated group, the C. striatum-BSI group had a shorter time to positivity of blood cultures (27.0 h vs. 42.5 h, P = 0.011). C. striatum-BSI group had a longer time to positivity (27 h) when compared to both the MRSA (20 h) and MRSE groups (19 h) (p

Abstract Background Serum (1,3)-β-D-glucan (BDG) detection for diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-human immunodeficiency virus (HIV) immunocompromised patients lacks intensive care unit (ICU)-specific data. We aimed to assess its performance and determine the optimal cutoff for PJP in ICU population. Methods This retrospective study included critically ill non-HIV immunocompromised patients admitted to a medical ICU with suspected pneumonia, undergoing simultaneous microbiological testing for P. jirovecii on lower respiratory tract specimens and serum BDG. Confounders affecting BDG positivity were explored by multivariable logistic regression. Optimal cut-offs were derived from Youden’s index for the entire cohort and subgroups stratified by confounders. Diagnostic performance of serum BDG was estimated at different cutoffs. Results Of 400 patients included, 42% were diagnosed with PJP and 58.3% had positive serum BDG. Serum BDG’s area under the receiver operating characteristic curve was 0.90 (0.87–0.93). At manufacturer’s 150 pg/ml cut-off, serum BDG had high sensitivity and negative predictive value (94%), but low specificity and positive predictive value (67%). Confounders associated with a positive serum BDG in PJP diagnosis included IVIG infusion within 3 days (odds ratio [OR] 9.24; 95% confidence interval [CI] 4.09–20.88, p

Abstract Background This study aimed to precisely predict the size and silicone oil injection of a foldable capsular vitreous body (FCVB) via computerized three-dimensional (3D) ocular reconstruction in the treatment of severe retinal detachment in China. Methods The 3D software Unigraphics NX was applied to determine the volume of the inner cavity with 16–30 mm axial length, assigning the anterior and posterior chambers, the FCVB sizes, and the silicone oil injection volume, and modeling the data between the axial length and the FCVB size. In clinical practice, IOL Master was applied to accurately measure the axial length of the contralateral healthy eye to anchor the anterior-posterior and horizontal diameters of the operated eye in horizontal position CT, and compared with the model to recommend the FCVB size and silicone oil amount, and the clinical effect was validated in cases across five hospitals in China. Results For the axial length of 16–30 mm, the volume of the inner cavity is 1.2 ml-8.4 ml. FCVB size and silicone oil volume were recommended based on this volume of the inner cavity. Of 253 cases, we noted 11 cases implanted with AV-10P and 1.05 ± 0.21 ml of silicone oil, 41 with AV-12P and 1.58 ± 0.18 ml of silicone oil, 163 with AV-13.5P and 2.48 ± 0.29 ml of silicone oil, 31 with AV-15P and 3.57 ± 0.39 ml of silicone oil, and 7 with AV-17P and 5.71 ± 0.81 ml of silicone oil. There was no significant difference in postoperative visual acuity scores compared with preoperative (P = 0.097), postoperative IOP(10.29 ± 0.57mmHg)was slightly higher than preoperative IOP (9.76 ± 0.48 mmHg), but there was still no statistically significant difference between the two comparisons (P = 0.405). Conclusion Three-dimensional reconstruction prediction is a good solution for eyeballs with obvious individualized changes in severe retinal detachment, and this method helps doctors standardize FCVB size selection and the silicone oil amount for patients.

Abstract A common wisdom posits that transport of conserved quantities across clean nonintegrable quantum systems at high temperatures is diffusive when probed from the emergent hydrodynamic regime. We show that this empirical paradigm may alter if the strong interaction limit is taken. Using Krylov-typicality and purification matrix-product-state methods, we establish in short-to-intermediate time scales the following observations for the nonintegrable lattice model imitating the experimental Rydberg blockade simulator. Given the strict projection owing to the infinite density-density repulsion V, the Rydberg chain’s energy transport in the presence of a transverse field g is tentatively superdiffusive at infinite temperature featured by an anomalous scaling exponent $$\frac{3}{4}$$ 3 4 , indicating the potential existence of a novel dynamical universality class. Imposing, in addition, a growing longitudinal field h causes a putative superdiffusion-to-ballistic transport transition at h ≈ g. Interestingly, all the above results persist for large but finite interactions and temperatures, provided that the strongly interacting condition g, h ≪ k B T ≪ V is fulfilled. Our predictions are testable by current Rydberg quantum simulation facilities.

Abstract Objective This study sought to explore the efficiency of para-aortic and pelvic lymphadenectomy in the treatment of locally advanced cervical cancer (LACC) with pelvic lymph node (PLN) metastasis. Methods A total of 171 LACC patients with imaging-confirmed pelvic lymph node metastasis were included in this study. These patients were divided into two groups: the surgical staging group, comprising 58 patients who had received para-aortic and pelvic lymphadenectomy (surgical staging) along with concurrent chemoradiation therapy (CCRT), and the imaging staging group, comprising 113 patients who had received only CCRT. The two groups’ progression-free survival (PFS), overall survival (OS) and treatment-related complications were compared. Results The surgical staging group started radiotherapy 10.2 days (range 9–12 days) later than the imaging staging group. The overall incidence of lymphatic cysts was 9.30%. In the surgical staging group, para-aortic lymph node metastasis was identified in 34.48% (20/58) of patients, while pathology-negative PLN was observed in 12.07% (7/58). Over a median follow-up period of 52 months, no significant differences in PFS and OS rates were found between the two groups (p > 0.05). Subgroup analysis of patients with lymph node diameters of ≥ 1.5 cm revealed a five-year PFS rate of 75.0% and an OS rate of 80.0% in the surgical staging group, compared to 41.5% and 50.1% in the imaging staging group, respectively, showing statistically significant differences (p = 0.022, HR:0.34 [0.13, 0.90] and p = 0.038, HR: 0.34 [0.12,0.94], respectively for PFS and OS). Additionally, in patients with two or more metastatic lymph nodes, the five-year PFS and OS rates were 69.2% and 73.1% in the surgical staging group, versus 41.0% and 48.4% in the imaging staging group, with these differences also being statistically significant (p = 0.025, HR: 0.41[0.19,0.93] and p = 0.046, HR: 0.42[0.18,0.98], respectively). Conclusion Performing surgical staging before CCRT is safe and delivers accurate lymph node details crucial for tailoring radiotherapy. This approach merits further investigation, particularly in women with pelvic lymph nodes measuring 1.5 cm or more in diameter or patients with two or more imaging-positive PLNs. Graphical Abstract

Abstract The existence of flaws seriously weakens the rock strength, directly affects the crack expansion morphology, and indirectly affects the slope stability. In this study, uniaxial compression tests were carried out on double-flawed granite to investigate the effects of flaw angle on its compressive strength and crack coalescence based on DIC technology and PFC2D numerical simulation. The result indicates that the UCS values of flawed specimens at angles of 15°, 30°, 45°, and 60° are approximately 25.5–51.7% lower than that of the intact specimen. The failure strength of the double-flawed sample increases with the increase of flaw inclination angle, and the fracture morphology shifts from no expansion to split expansion. When the flaw tip strain of each flaw sample exceeded 0.6%, the stress concentration was generated at the flaw tip, and the sample began to appear macroscopic large cracks. DIC technique can well observe the crack initiation and propagation process, recording inclined shear strain bands at flaw tips, tensile strain bands in the middle of flaws, and tensile shear O-shaped strain ring in rock bridge areas. Numerical simulations using PFC2D software were carried out and showed a good agreement with the physical results. In addition, the effect of structural inclination on specimen failure strength is clearly explained by the theory of compressive damage based on the projected size of flaws. The deformation of rock mass is not a simple material deformation but is composed of material deformation and structural deformation. These experimental and numerical results enhance our understanding of crack initiation and coalescence characteristics, aiding in the analysis of rock structure stability in scenarios such as excavated underground openings, slopes, and tunneling construction, where pre-existing cracks or step-path fractures are pivotal to structural integrity.

Abstract Background The correlation between the triglyceride-glucose (TyG) index and mortality in the general population remains controversial, with inconsistent conclusions emerging from different studies. Objective This study aims to investigate whether there is an association between the TyG index and mortality in the general population in the United States, and to explore whether a new index combining the TyG index with systemic inflammation indicators can better predict all-cause and cardiovascular mortality risks in the general population than using the TyG index alone. Methods Calculate the systemic inflammation indicators and TyG index for each participant based on their complete blood count, as well as their triglyceride and glucose levels in a fasting state. TyG-inflammation indices were obtained by multiplying the TyG index with systemic inflammation indicators (TyG-NLR, TyG-MLR, TyG-lgPLR, TyG-lgSII, and TyG-SIRI). Based on the weighted Cox proportional hazards model, assess whether the TyG and TyG-Inflammation indices are associated with mortality risk in the general population. Restricted cubic splines (RCS) are used to clarify the dose-response relationship between the TyG and TyG-Inflammation indices and mortality, and to visualize the results. Time-dependent receiver operating characteristic (ROC) curves are used to evaluate the accuracy of the TyG and TyG-Inflammation indices in predicting adverse outcomes. Results This study included 17,118 participants. Over a median follow-up period of 125 months, 2595 patients died. The TyG index was not found to be related to mortality after adjusting for potentially confounding factors. However, the TyG-inflammation indices in the highest quartile (Q4), except for TyG-lgPLR, were significantly associated with both all-cause and cardiovascular mortality, compared to those in the lowest quartile (Q1). Among them, TyG-MLR and TyG-lgSII showed the strongest correlations with all-cause mortality and cardiovascular mortality. Specifically, compared to their respective lowest quartiles (Q1), participants in the highest quartile (Q4) of TyG-MLR had a 48% increased risk of all-cause mortality (95% CI: 1.23–1.77, P for trend

Abstract Observational and genetic studies have reported the relationship between dyslexia and Alzheimer’s disease (AD). Until now, the causal effect of dyslexia on AD risk has remained unclear. We conducted a two-sample univariable Mendelian randomization (MR) analysis to determine the causal association between dyslexia and the risk of AD, vascular dementia (VD), Lewy body dementia (LBD), and frontotemporal dementia (FTD) and its four subtypes. First, we selected 42 dyslexia genetic variants from a large-scale genome-wide association studies (GWAS) dataset and extracted their corresponding GWAS summary statistics from AD, VD, LBD, and FTD. Second, we selected four MR methods, including inverse-variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO. Heterogeneity, horizontal pleiotropy, and leave-one-out sensitivity analysis were then used to evaluate the reliability of all causal estimates. We also conducted multivariable MR (MVMR) and mediation analysis to assess the potential mediating role of cognitive performance (CP) or educational achievement (EA) on the causal association between dyslexia and AD. Two MVMR methods, including MV IVW and MV-Egger, and two-step MR were used to perform the analysis. Using IVW, we found a significant causal association between increased dyslexia and increased risk of AD (OR = 1.15, 95% CI: 1.04–1.28, P = 0.006), but not VD, LBD, FTD, or its four subtypes. MR-PRESSO further supported the statistically significant association between dyslexia and AD (OR = 1.15, 95% CI: 1.05–1.27, P = 0.006). All sensitivity analyses confirmed the reliability of causal estimates. Using MV IVW and mediation analysis, we found no causal relationship between dyslexia and AD after adjusting for CP but not EA, CP mediated the total effect of dyslexia on AD with a proportion of 46.32%. We provide genetic evidence to support a causal effect of increased dyslexia on increased risk of AD, which was largely mediated by CP. Reading activity may be a potential intervention strategy for AD by improving cognitive function.

Shaped charge liner (SCL) has been extensively applied in oil recovery and defense industries. Achieving superior penetration capability through optimizing SCL structures presents a substantial challenge due to intricate rate-dependent processes involving detonation-driven liner collapse, high-speed jet stretching, and penetration. This study introduces an innovative optimization strategy for SCL structures that employs jet penetration efficiency as the primary objective function. The strategy combines experimentally validated finite element method with machine learning (FEM-ML). We propose a novel jet penetration efficiency index derived from enhanced cutoff velocity and shape characteristics of the jet via machine learning. This index effectively evaluates the jet penetration performance. Furthermore, a multi-model fusion based on a machine learning optimization method, called XGBOOST-MFO, is put forward to optimize SCL structure over a large input space. The strategy's feasibility is demonstrated through the optimization of copper SCL implemented via the FEM-ML strategy. Finally, this strategy is extended to optimize the structure of the recently emerging CrMnFeCoNi high-entropy alloy conical liners and hemispherical copper liners. Therefore, the strategy can provide helpful guidance for the engineering design of SCL.

Abstract Background Accurate breed identification is essential for the conservation and sustainable use of indigenous farm animal genetic resources. In this study, we evaluated the phylogenetic relationships and genomic breed compositions of 13 sheep breeds using SNP and InDel data from whole genome sequencing. The breeds included 11 Chinese indigenous and 2 foreign commercial breeds. We compared different strategies for breed identification with respect to different marker types, i.e. SNPs, InDels, and a combination of SNPs and InDels (named SIs), different breed-informative marker detection methods, and different machine learning classification methods. Results Using WGS-based SNPs and InDels, we revealed the phylogenetic relationships between 11 Chinese indigenous and two foreign sheep breeds and quantified their purities through estimated genomic breed compositions. We found that the optimal strategy for identifying these breeds was the combination of DFI_union for breed-informative marker detection, which integrated the methods of Delta, Pairwise Wright's FST, and Informativeness for Assignment (namely DFI) by merging the breed-informative markers derived from the three methods, and KSR for breed assignment, which integrated the methods of K-Nearest Neighbor, Support Vector Machine, and Random Forest (namely KSR) by intersecting their results. Using SI markers improved the identification accuracy compared to using SNPs or InDels alone. We achieved accuracies over 97.5% when using at least the 1000 most breed-informative (MBI) SI markers and even 100% when using 5000 SI markers. Conclusions Our results provide not only an important foundation for conservation of these Chinese local sheep breeds, but also general approaches for breed identification of indigenous farm animal breeds.

Abstract Radiomics offers a noninvasive avenue for predicting clinicopathological factors. However, thorough investigations into a robust breast cancer outcome-predicting model and its biological significance remain limited. This study develops a robust radiomic model for prognosis prediction, and further excavates its biological foundation and transferring prediction performance. We retrospectively collected preoperative dynamic contrast-enhanced MRI data from three distinct breast cancer patient cohorts. In FUSCC cohort (n = 466), Lasso was used to select features correlated with patient prognosis and multivariate Cox regression was utilized to integrate these features and build the radiomic risk model, while multiomic analysis was conducted to investigate the model’s biological implications. DUKE cohort (n = 619) and I-SPY1 cohort (n = 128) were used to test the performance of the radiomic signature in outcome prediction. A thirteen-feature radiomic signature was identified in the FUSCC cohort training set and validated in the FUSCC cohort testing set, DUKE cohort and I-SPY1 cohort for predicting relapse-free survival (RFS) and overall survival (OS) (RFS: p = 0.013, p = 0.024 and p = 0.035; OS: p = 0.036, p = 0.005 and p = 0.027 in the three cohorts). Multiomic analysis uncovered metabolic dysregulation underlying the radiomic signature (ATP metabolic process: NES = 1.84, p-adjust = 0.02; cholesterol biosynthesis: NES = 1.79, p-adjust = 0.01). Regarding the therapeutic implications, the radiomic signature exhibited value when combining clinical factors for predicting the pathological complete response to neoadjuvant chemotherapy (DUKE cohort, AUC = 0.72; I-SPY1 cohort, AUC = 0.73). In conclusion, our study identified a breast cancer outcome-predicting radiomic signature in a multicenter radio-multiomic study, along with its correlations with multiomic features in prognostic risk assessment, laying the groundwork for future prospective clinical trials in personalized risk stratification and precision therapy.

Conger myriaster has a high price on the international market and occupies an important position in aquatic product export in China, and it is widely distributed in the Yellow Sea, the Bohai Sea, the East China Sea, the coastal waters of Japan from southern Hokkaido to northern Okinawa, and the sea near the Korean Peninsula. The experimental aquaculture techniques of C. myriaster include pond culture, industrialized open-flowing water culture, and industrialized recirculating aquaculture. No report has been published on the morphological characteristics or the effects of various morphological traits on the body weight and net body weight of C. myriaster in an industrialized open-flowing water culture. In this study, C. myriaster was collected under this industrialized culture mode and assessed using traditional measurement methods, statistical analysis, and other means to systematically measure and analyze morphological traits. A total of 90 C. myriaster were collected equally from three aquaculture companies along the coast of the Yellow Sea. The body weight (BW), net body weight (NW), total length (TL), body length (BL), body height (BH), soma width (SW), head length (HL), head height (HH), head width (HW), proboscis length (PL), proboscis width (PW), eye diameter (ED), vertical eye diameter (VED), and distance between eyes (DE) were measured individually using an electronic balance, a ruler, and a Vernier caliper. We analyzed the relationships between morphological traits and constructed a truss network diagram of morphological traits. The effects of the morphological traits on BW and NW were studied by correlation analysis, path analysis, multiple regression analysis, and curve fitting. The correlation analysis showed that the correlations of BW with TL, BL, BH, SW, HH, and HW were extremely significant (P < 0.01), with correlation coefficient values of 0.818, 0.829, 0.611, 0.697, 0.667, and 0.642, respectively. The correlations of NW with TL, BL, BH, SW, HH, HW, and VED were extremely significant (P < 0.01), with correlation coefficients of 0.848, 0.857, 0.574, 0.591, 0.617, 0.564, and 0.519, respectively. Path analysis revealed that the path coefficients between BW and three morphological traits (namely BL, BH, and SW) were larger than those for other morphological traits, at 0.631, 0.204, and 0.374, respectively. The path coefficients between NW and these three morphological traits (BL, BH, and SW) were larger than those for other morphological traits, at 0.703, 0.213, and 0.239, respectively. Through determination coefficient analysis, it was observed that the determination coefficient for BL to BW was the largest, with a value of 0.398. The combination of SW and BL had the largest determination coefficient for BW, with a value of 0.162. This indicated that BL was a core morphological trait to determine the BW, and the SW was an important morphological trait to determine the BW. The determination coefficient of BL to NW was the largest at 0.494. The combination of SW and TL had the largest coefficient of determination for NW, with a value of 0.116. This showed that the BL was the core morphological trait to determine the NW, and SW was an important morphological trait to determine the NW. A stepwise regression method was used to establish a regression equation in which the three morphological traits were independent variables and the BW or NW was the dependent variable. The multiple regression equation of the important morphological traits for BW was BW = –642.699 + 1.086 × BL + 3.874 × BH + 7.917 × SW (P < 0.01). The multiple regression equation of the important morphological traits for NW was NW = -526.995 + 1.033 × BL + 3.438 × BH + 4.317 × SW (P < 0.01). Further curve fitting was performed for each morphological trait with BW and NW in the equation. The best fitting models of BL, BH, and SW for BW were the logarithmic function, logarithmic function, and power function, respectively, and the model equations were BW = -3, 542.357 + 608.061lnBL (R2 = 0.929), BW = 14.313BH0.941 (R2 = 0.908), and BW = -1, 028.49 + 416.452lnSW (R2 = 0.920), respectively. The best-fitting models of BL, BH, and SW for NW were the logarithmic, linear, and logarithmic functions, respectively. The model equations were NW = -2, 983.881 + 516.411lnBL (R2 = 0.930), NW = -22.252 + 11.392BH (R2 = 0.914), and NW = -774.583 + 329.017lnSW (R2 = 0.921), respectively. In summary, BL was the core morphological trait affecting the BW and NW of C. myriaster in an industrialized culture model. BH and SW were important morphological traits affecting the BW and NW of C. myriaster in the industrialized culture model. These results provide a theoretical basis for the future identification of germplasm characteristics, genetic breeding, and healthy aquaculture of C. myriaster.

Pre-treatment processing technology plays a crucial role in the overall freshwater fish processing procedure, and automatic head and tail cutting stands out as a significant pre-treatment technique within the industry. The system for removing the head and tail of freshwater fish comprised a Cartesian coordinate manipulator, a fish transfer device, a control system, and an image acquisition device. In the vision system, five image segmentation methods were utilized for fish head and tail image segmentation comparison tests. These methods include U-Net (U-shaped Deep Neural Network), DeeplabV3, PSPNet (Pyramid Scene Parsing Network), FastSCNN (Fast Semantic Segmentation Network), and ICNet (Image Cascade Network), all of which were employed to evaluate their performance. Among the tested segmentation methods, the ICNet demonstrated the most excellent segmentation capability. The experimental results indicated a segmentation accuracy of 99.01%, a mean intersection over union (MIoU) of 82.50%, and an image processing time of 15.25 ms. The results showed that the fish head and tail were successfully cut off using this model for recognition with a circular knife. Consequently, the segmentation model employed in the machine vision system within this study has demonstrated successful applicability in automatically cutting the heads and tails of freshwater fish of various sizes.

Abstract Acquiring multi-dimensional optical information, such as intensity, spectrum, polarization, and phase, can significantly enhance the performance of photodetectors. Incorporating these dimensions allows for improved image contrast, enhanced recognition capabilities, reduced interference, and better adaptation to complex environments. However, the challenge lies in obtaining these dimensions on a single photodetector. Here we propose a misaligned unipolar barrier photodetector based on van der Waals heterojunction to address this issue. This structure enables spectral detection by switching between two absorbing layers with different cut-off wavelengths for dual-band detection. For polarization detection, anisotropic semiconductors like black phosphorus and black arsenic phosphorus inherently possess polarization-detection capabilities without additional complex elements. By manipulating the crystal direction of these materials during heterojunction fabrication, the device becomes sensitive to incident light at different polarization angles. This research showcases the potential of the misaligned unipolar barrier photodetector in capturing multi-dimensional optical information, paving the way for next-generation photodetectors.

Abstract Small cell lung cancer (SCLC) is a recalcitrant cancer characterized by early metastasis, rapid tumor growth and poor prognosis. In recent decades, the epidemiology, initiation and mutation characteristics of SCLC, as well as abnormal signaling pathways contributing to its progression, have been widely studied. Despite extensive investigation, fewer drugs have been approved for SCLC. Recent advancements in multi-omics studies have revealed diverse classifications of SCLC that are featured by distinct characteristics and therapeutic vulnerabilities. With the accumulation of SCLC samples, different subtypes of SCLC and specific treatments for these subtypes were further explored. The identification of different molecular subtypes has opened up novel avenues for the treatment of SCLC; however, the inconsistent and uncertain classification of SCLC has hindered the translation from basic research to clinical applications. Therefore, a comprehensives review is essential to conclude these emerging subtypes and related drugs targeting specific therapeutic vulnerabilities within abnormal signaling pathways. In this current review, we summarized the epidemiology, risk factors, mutation characteristics of and classification, related molecular pathways and treatments for SCLC. We hope that this review will facilitate the translation of molecular subtyping of SCLC from theory to clinical application.

Abstract The development of highly efficient and durable alkaline hydrogen evolution reaction (HER) catalysts is crucial for achieving high-performance practical anion exchange membrane water electrolyzer (AEMWE) at ampere-level current density. Herein, we report a design concept by employing Ga single atoms as an electronic bridge to stabilize the Ru clusters for boosting alkaline HER performance in practical AEMWE. Experimental and theoretical results collectively reveal that the bridged Ga sites trigger strong metal-support interaction for the homogeneous distribution of Ru clusters with high density, as well as optimize the Ru–H bond strength due to the electron transfer between Ru and Ga for enhanced intrinsic HER activity. Moreover, the oxophilic Ga sites near the Ru clusters tend to adsorb the hydroxyl species and accelerate the water dissociation for sufficient proton supplement in an alkaline medium. The Ru–GaSA/N–C catalyst exhibits a low overpotential of 4 ± 1 mV (10 mA cm−2) and high mass activity of 9.3 ± 0.5 A mg−1 Ru at −0.05 V vs RHE. In particular, the Ru–GaSA/N–C-based AEMWE in 1 M KOH delivers a voltage of only 1.74 V to reach an industrial current density of 1 A cm−2, and can steadily operate at 1 A cm−2 for more than 170 h.

In this study, aiming at fulfilling the requirement of polarization acquisition and utilization, a method for active deception jamming recognition based on the time-varying polarization-conversion metasurface is investigated. First, an anisotropic phase-modulated metasurface supporting 3-bit phase quantization in the 9.6～10.1 GHz frequency band is designed. By optimizing the periodical phase coding, the polarization state can be converted on demand. And then, loading the polarization-conversion metasurface on a single polarization radar antenna so that the polarization states of the antenna can change along a specific trajectory. By extracting the difference in the polarization domain between target and active deception jamming, the active deception jamming could be distinguished from the radar echo. The simulation results show that under the constraints of three different polarization trajectories, the active deception jamming and targets exhibit a significant clustering effect, and the identification effect is stable. Compared with jamming identification methods that rely on dual-polarization or full-polarization radar systems, the proposed method has both low cost and high efficiency, which has great application potential in radar anti-jamming.

Liver fibrosis is an important step in the transformation of chronic liver disease into cirrhosis and liver cancer, and structural changes and functional disorders of liver sinusoidal endothelial cells (LSECs) are early events in the occurrence of liver fibrosis. Therefore, it is necessary to identify the key regulatory genes of endothelial dysfunction in the process of liver fibrosis to provide a reference for the diagnosis and treatment of liver fibrosis. In this study, we identified 230 common differentially expressed genes (Co-DEGs) by analyzing transcriptomic data of primary LSECs from three different liver fibrosis mouse models (carbon tetrachloride; choline-deficient, l-amino acid-defined diet; and nonalcoholic steatohepatitis). Enrichment analysis revealed that the Co-DEGs were mainly involved in regulating the inflammatory response, immune response, angiogenesis, formation and degradation of the extracellular matrix, and mediating chemokine-related pathways. A Venn diagram analysis was used to identify 17 key genes related to the progression of liver cirrhosis. Regression analysis using the Lasso–Cox method identified genes related to prognosis among these key genes: SOX4, LGALS3, SERPINE2, CD52, and LPXN. In mouse models of liver fibrosis (bile duct ligation and carbon tetrachloride), all five key genes were upregulated in fibrotic livers. This study identified key regulatory genes for endothelial dysfunction in liver fibrosis, namely SOX4, LGALS3, SERPINE2, CD52, and LPXN, which will provide new targets for the development of therapeutic strategies targeting endothelial dysfunction in LSECs and liver fibrosis.

Background Insulin resistance (IR) is the key pathological basis of many metabolic disorders. Lack of asialoglycoprotein receptor 1 (ASGR1) decreased the serum lipid levels and reduced the risk of coronary artery disease. However, whether ASGR1 also participates in the regulatory network of insulin sensitivity and glucose metabolism remains unknown. Methods The constructed ASGR1 knockout mice and ASGR1-/- HepG2 cell lines were used to establish the animal model of metabolic syndrome and the IR cell model by high-fat diet (HFD) or drug induction, respectively. Then we evaluated the glucose metabolism and insulin signaling in vivo and in vitro. Results ASGR1 deficiency ameliorated systemic IR in mice fed with HFD, evidenced by improved insulin intolerance, serum insulin, and homeostasis model assessment of IR index, mainly contributed from increased insulin signaling in the liver, but not in muscle or adipose tissues. Meanwhile, the insulin signal transduction was significantly enhanced in ASGR1-/- HepG2 cells. By transcriptome analyses and comparison, those differentially expressed genes between ASGR1 null and wild type were enriched in the insulin signal pathway, particularly in phosphoinositide 3-kinase-AKT signaling. Notably, ASGR1 deficiency significantly reduced hepatic gluconeogenesis and glycogenolysis. Conclusion The ASGR1 deficiency was consequentially linked with improved hepatic insulin sensitivity under metabolic stress, hepatic IR was the core factor of systemic IR, and overcoming hepatic IR significantly relieved the systemic IR. It suggests that ASGR1 is a potential intervention target for improving systemic IR in metabolic disorders.

Abstract Background Antibiotic resistance is a serious global public health issue. However, there are few reports on trends in antimicrobial susceptibility in Chinese neonates, and most of the existing evidence has been derived from adult studies. We aimed to assess the trends in antimicrobial susceptibility of common pathogens in full-term neonates with invasive bacterial infections (IBIs) in China. Methods This cross-sectional survey study analyzed the antimicrobial susceptibility in Chinese neonates with IBIs from 17 hospitals, spanning from January 2012 to December 2021. Joinpoint regression model was applied to illustrate the trends and calculate the average annual percentage change (AAPC). Using Mantel-Haenszel linear-by-linear association chi-square test, we further compared the antibiotic minimum inhibitory concentrations (MICs) by pathogens between 2019 and 2021 to provide precise estimates of changes. Results The proportion of Escherichia coli with extended-spectrum-beta-lactamase-negative strains increased from 0.0 to 88.5% (AAPC = 62.4%, 95% confidence interval (CI): 44.3%, 82.9%), with two breakpoints in 2014 and 2018 (p-trend

Abstract China’s higher education system is shifting from quantitative expansion to connotative development to advance its quality. Since 2015, Chinese governments have been implementing a strategic policy for higher education called “double first-class”, which aims to promote a number of Chinese top universities to construct world-class universities or to establish world-class disciplines. “Double first-class” universities have received a large amount of educational resources through this policy. Taking advantage of resources efficiently is an important element in promoting the development of higher quality higher education. However, research on resource allocation in China’s “double first-class” universities is incomplete. Current research has not clarified the level of resource allocation efficiency or the factors affecting China’s “double first-class” universities. With the help of the superefficient data envelopment analysis (DEA)-Malmquist–Tobit model, this study actively explores the current status of the resource allocation efficiency of China’s “double first-class” universities to fill this gap in the field. Specifically, the development level and change trend of the resource allocation efficiency of 13 “double first-class” universities in China from 2015 to 2019 were measured with the help of the superefficient DEA-Malmquist model. The internal and external factors affecting the resource allocation efficiency of “double first-class” universities are also analysed with the help of the Tobit model. The overall level of resource allocation efficiency of “double first-class” universities is high, but the internal variability is large. From the perspective of efficiency decomposition, it is found that both technical efficiency change (EFch) and technical progress efficiency (TEch) play important roles in improving the total factor productivity (TFP) of resource allocation. Compared with TEch, EFch plays a more significant pulling role. This study confirms that the factors affecting resource allocation efficiency are complex. Among them, the regional economic environment, faculty title structure, and degree of international exchange have significant roles in promoting the resource allocation efficiency of “double first-class” universities, but local financial support and the time of policy implementation have certain negative effects.

Abstract Rabies is a lethal disease caused by the rabies virus (RABV), which causes acute neurological infections in mammals, including human beings. We previously reported that an mRNA vaccine (LVRNA001) encoding the rabies virus’s glycoprotein induced strong protective immune responses to rabies in mice and dogs. Here, we further evaluate the safety of LVRNA001. First, we performed a confirmative efficacy study in dogs, which showed that LVRNA001 fully protected the animals from the virus, both pre- and post-infection. Moreover, using pre- and post-exposure prophylaxis murine models, we showed that LVRNA001, built from the CTN-1 strain, was able to protect against various representative RABV strains from the China I–VII clades. To evaluate the safety of the vaccine, chronic and reproductive toxicity studies were performed with cynomolgus macaques and rats, respectively. In a repeated-dose chronic toxicity study, vaccinated monkeys displayed no significant alterations in body weight, temperature, or hematological and biochemical markers. Lymphocyte subset measurement and histopathological examination showed that no toxicity was associated with the vaccine. The immunogenicity study in cynomolgus macaques demonstrated that LVRNA001 promoted the generation of neutralizing antibodies and Th1-biased immune response. Evaluation of reproductive toxicity in rats revealed that administration of LVRNA001 had no significant effects on fertility, maternal performance, reproductive processes, and postnatal outcomes. In conclusion, LVRNA001 can provide efficient protection against rabies virus infection in dogs and mice, and toxicity studies showed no significant vaccine-related adverse effects, suggesting that LVRNA001 is a promising and safe vaccine candidate for rabies prophylaxis and therapy.

Abstract Background By combining high-frequency and contrast-enhanced ultrasound (CEUS), the position of the severed end of a finger extensor tendon injury and the injury classification can be determined as part of a comprehensive preoperative evaluation in clinical practice. However, there have been no reports of high-frequency ultrasound combined with CEUS for the preoperative diagnosis of human finger extensor tendon injury. Cases presentation One case of complete rupture of the extensor tendon was diagnosed by ultrasound, which was completely consistent with the surgery; one case of incomplete rupture was ultimately confirmed clinically; and one case of distal phalangeal bone base avulsion fracture with tendon contusion and missed diagnosis on the first radiographic examination was confirmed by follow-up radiographic examination. Conclusions Different types of finger extensor tendon injuries exhibit distinctive contrast-enhanced ultrasonography findings. Combined high-frequency and contrast-enhanced ultrasound can accurately locate the position of the severed end of the finger extensor tendon injury before surgery while observing the contrast agent filling area to clarify injury classification, providing a reliable imaging basis for clinical practice and ultimately developing personalized diagnosis and treatment plans for patients to ensure minimal trauma and pain, as well as optimal treatment effects.

Abstract Background Crohn’s disease (CD) patients require varying levels of supportive care. In order to facilitate caregivers and nurses in precisely evaluating the caregiving requirements of these patients, we developed the CD-specific Care Needs Scale (CD-CNS). Methods This study employed a mixed-methods approach, integrating qualitative and quantitative methodologies. The initial items of the scale were developed through qualitative interviews, Delphi expert consultation, and literature review, while the final items were refined through clinical testing. Qualitative interviews were conducted based on the supportive care needs framework and Maslow’s hierarchy of needs, and scale items were constructed through a literature search and qualitative interviews. The initial version of the scale with 45 items was obtained after the items were verified and modified by expert consultation. A total of 250 CD patients admitted to the gastroenterology department of a hospital in China were selected for verification of the initial version of the scale. A self-designed general questionnaire was used to obtain patients’ medical history and sociodemographic data, and the Chinese version of the Inflammatory Bowel Disease Questionnaire (IBDQ) was used as the criterion. Exploratory factor analysis (EFA) was performed on the CD-CNS to evaluate the dimensions, factor structure, reliability, criterion validity, and construct validity. Results EFA identified 5 dimensions and retained 27 items with strong internal consistency reliability (α = 0.940). The Cronbach’s α coefficients for each dimension ranged from 0.824 to 0.921. Criterion validity was assessed using Spearman’s coefficient, which demonstrated a significant correlation with the IBDQ (P

Abstract Background The taxonomy of Taxus Linn. remains controversial due to its continuous phenotypic variation and unstable topology, thus adversely affecting the formulation of scientific conservation strategies for this genus. Recently, a new ecotype, known as Qinling type, is mainly distributed in the Qinling Mountains and belongs to a monophyletic group. Here, we employed multiple methods including leaf phenotype comparison (leaf shapes and microstructure), DNA barcoding identification (ITS + trnL-trnF + rbcL), and niche analysis to ascertain the taxonomic status of the Qinling type. Results Multiple comparisons revealed significant differences in the morphological characters (length, width, and length/width ratio) among the Qinling type and other Taxus species. Leaf anatomical analysis indicated that only the Qinling type and T. cuspidata had no papilla under the midvein or tannins in the epicuticle. Phylogenetic analysis of Taxus indicated that the Qinling type belonged to a monophyletic group. Moreover, the Qinling type had formed a relatively independent niche, it was mainly distributed around the Qinling Mountains, Ta-pa Mountains, and Taihang Mountains, situated at an elevation below 1500 m. Conclusions Four characters, namely leaf curvature, margin taper, papillation on midvein, and edges were put forward as primary indexes for distinguishing Taxus species. The ecotype Qingling type represented an independent evolutionary lineage and formed a unique ecological niche. Therefore, we suggested that the Qingling type should be treated as a novel species and named it Taxus qinlingensis Y. F. Wen & X. T. Wu, sp. nov.

Abstract Background To assess pregnancy outcomes in women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection. Methods This was a retrospective cohort study that included pregnant women who contracted coronavirus disease 2019 (COVID-19) once or twice during pregnancy and who gave birth between 1 October 2022 and 15 August 2023 in Shanghai First Maternity and Infant Hospital (Shanghai, China). We collected their clinical data and compared the frequency of adverse pregnancy outcomes between the reinfection group and the primary infection group, such as preterm birth, fetal growth restriction (FGR), hypertensive disorders of pregnancy (HDP), common pregnancy-related conditions, birth weight, and neonatal unit admission. Results We observed a 7.7% reinfection rate among the 1,405 women who contracted COVID-19 during pregnancy. There were no significant differences in the frequency of preterm birth, FGR, HDP, other common pregnancy-related conditions, birth weight, or rate of neonatal unit admission between the reinfection and single infection groups. All our participants were unvaccinated, and all had mild symptoms. Conclusion Our study showed no significant association between SARS-CoV-2 reinfection and adverse pregnancy outcomes.

Background: Emerging evidence suggests that minimal acute kidney injury (stage 1 AKI) is associated with increased hospital mortality rates. However, for those who do not meet the AKI diagnostic criteria, whether a small increase in serum creatinine (SCr) levels is associated with an increased mortality rate in elderly patients is not known. Therefore, we aimed to investigate small elevations in SCr of

Abstract Introduction Patients with systemic lupus erythematosus (SLE) have variable treatment pathways, including antimalarials, glucocorticoids, immunosuppressants, and/or biologics. This study describes differences in clinical outcomes when initiating belimumab (BEL) before and after immunosuppressant use. Methods This real-world, retrospective cohort study (GSK Study 217536) used de-identified administrative claims data from January 2015 to December 2022 in the Komodo Health Database. Adults with moderate/severe SLE initiating BEL (index date) were identified from January 2017 to May 2022, allowing a ≥ 24-month baseline period. Patients were stratified into those initiating BEL before immunosuppressant use (no immunosuppressant use within 24 months before index) and those initiating BEL after immunosuppressant use (one immunosuppressant used within 24 months before index). Oral glucocorticoid (OGC) use, SLE flares, new organ damage, and all-cause healthcare resource utilization (HCRU) were analyzed descriptively over a 24-month follow-up. Results Baseline SLE severity was similar for patients initiating BEL before (n = 2295) versus after (n = 4114) immunosuppressant use (moderate, 83.1% vs 79.0%; severe, 16.8% vs 21.0%). Patients initiating BEL before versus after immunosuppressant use had lower SLE flare rates and OGC use. Post-index, patients initiating BEL before versus after immunosuppressant use discontinued their OGC sooner (moderate baseline SLE, 4.5 vs 8.9 months; severe baseline SLE, 6.2 vs 11.6 months). Patients initiating BEL before versus after immunosuppressant use had lower SLE flare rates per person-year at all time points (especially severe flare rates in patients with severe baseline SLE, 0.70 vs 1.48 through 24 months post-index). Median time to new organ damage occurrence was longer in patients initiating BEL before versus after immunosuppressant use (moderate baseline SLE, 32.1 vs 26.7 months; severe baseline SLE, 22.7 vs 21.6 months). All-cause HCRU was similar between cohorts. Conclusions These results suggest that patients initiating BEL before versus after immunosuppressant use had more favorable outcomes.

Abstract Malignant pleural effusion (MPE) is a common occurrence in advanced cancer and is often linked with a poor prognosis. Eosinophils were reported to involve in the development of MPE. However, the role of eosinophils in MPE remains unclear. To investigate this, we conducted studies using both human samples and mouse models. Increased eosinophil counts were observed in patients with MPE, indicating that the higher the number of eosinophils is, the lower the LENT score is. In our animal models, eosinophils were found to migrate to pleural cavity actively upon exposure to tumor cells. Intriguingly, we discovered that a deficiency in eosinophils exacerbated MPE, possibly due to their anti-tumor effects generated by modifying the microenvironment of MPE. Furthermore, our experiments explored the role of the C-C motif chemokine ligand 11 (CCL11) and its receptor C-C motif chemokine receptor 3 (CCR3) in MPE pathology. As a conclusion, our study underscores the protective potential of eosinophils against the development of MPE, and that an increase in eosinophils through adoptive transfer of eosinophils or increasing their numbers improved MPE.

Abstract Background Triple-negative breast cancer (TNBC) is characterized by its high metastatic potential, which results in poor patient survival. Cancer-associated fibroblasts (CAFs) are crucial in facilitating TNBC metastasis via induction of mitochondrial biogenesis. However, how to inhibit CAF-conferred mitochondrial biogenesis is still needed to explore. Methods We investigated metastasis using wound healing and cell invasion assays, 3D-culture, anoikis detection, and NOD/SCID mice. Mitochondrial biogenesis was detected by MitoTracker green FM staining, quantification of mitochondrial DNA levels, and blue-native polyacrylamide gel electrophoresis. The expression, transcription, and phosphorylation of peroxisome-proliferator activated receptor coactivator 1α (PGC-1α) were detected by western blotting, chromatin immunoprecipitation, dual-luciferase reporter assay, quantitative polymerase chain reaction, immunoprecipitation, and liquid chromatography-tandem mass spectrometry. The prognostic role of PGC-1α in TNBC was evaluated using the Kaplan–Meier plotter database and clinical breast cancer tissue samples. Results We demonstrated that PGC-1α indicated lymph node metastasis, tumor thrombus formation, and poor survival in TNBC patients, and it was induced by CAFs, which functioned as an inducer of mitochondrial biogenesis and metastasis in TNBC. Shikonin impeded the CAF-induced PGC-1α expression, nuclear localization, and interaction with estrogen-related receptor alpha (ERRα), thereby inhibiting PGC-1α/ERRα-targeted mitochondrial genes. Mechanistically, the downregulation of PGC-1α was mediated by synthase kinase 3β-induced phosphorylation of PGC-1α at Thr295, which associated with neural precursor cell expressed developmentally downregulated 4e1 recognition and subsequent degradation by ubiquitin proteolysis. Mutation of PGC-1α at Thr295 negated the suppressive effects of shikonin on CAF-stimulated TNBC mitochondrial biogenesis and metastasis in vitro and in vivo. Conclusions Our findings indicate that PGC-1α is a viable target for blocking TNBC metastasis by disrupting mitochondrial biogenesis, and that shikonin merits potential for treatment of TNBC metastasis as an inhibitor of mitochondrial biogenesis through targeting PGC-1α.