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ABSTRACT: Lactiplantibacillus plantarum have been studied for their antioxidant properties, which can mitigate oxidative stress and improve health outcomes. The study aimed to compare the antioxidant properties of single and binary L. plantarum and their impact on yogurt. Lactiplantibacillus plantarum 847 (Lp-C), L. plantarum 8014 (Lp-G), and their combination were chosen for their in vitro antioxidant potential. In vivo experiments were performed in Drosophila melanogaster and results showed that binary L. plantarum notably improved the survival time, weight, catalase activity and intestinal integrity in H2O2-induced flies. As compared with single L. plantarum treated flies, binary strains improved the survival curve, superoxide dismutase and catalase activities in females, prolonged the average survival time in males, and increased the expression level of keap1, Nrf2, and SOD genes in all sexes. To explore the effect of single and binary L. plantarum on milk fermentation, the physicochemical properties and antioxidant activity of yogurt were detected, and results presented that yogurt fermented with L. plantarum exhibited the improved antioxidant capacity, with the binary strain combination demonstrating superior effects in rheological properties and the later period of yogurt storage. This research offers a foundation for choosing the combinations of lactic acid bacteria with antioxidant properties.

To investigate the effect of different particle sizes of large-leaf yellow tea powder on the quality characteristics of wheat dough, this study selected five types of tea powder, namely coarse powder, fine powder, ultra-fine I, ultra-fine II, and ultra-fine III, and added them in equal amounts to the flour to make tea containing dough. The influence of different powders on the quality characteristics of wheat dough was analyzed using instruments such as farinograph, texture analyzer, rheometer, and rapid viscosity analyzer. The results showed that as the particle size of large-leaf yellow tea decreased, the water absorption rate, formation time, and stability time of the dough significantly increased (P

Abstract:

Abstract Conventional targeted therapies primarily rely on small molecules and proteins. However, they often struggle to enter specific protein conformations, which limits their therapeutic effectiveness. In contrast, RNA therapy is emerging as a more precise and effective targeting strategy. Through differential analysis comparing Pandora-Seq data with clinical samples, we discovered that the small RNA piR-28846 naturally, occurring in human body, exhibited low expression levels in ovarian cancer tissues. Experimental results indicate that piR-28846 inhibits the growth of ovarian cancer cells. Additionally, piR-28846 demonstrated significant therapeutic effects in xenograft models and ovarian cancer-like organoids. Further studies revealed that piR-28846 binds to NSUN2 and down-regulates it, which in turn affects the stability of KPNA2 mRNA. Notably, KPNA2 negatively regulates NSUN2 expression and localization. Given its inhibitory effects observed in vivo, in vitro, and in the ovarian cancer organoid model, we believe piR-28846 has strong potential as a small nucleic acid therapy of ovarian cancer.

Abstract The brown lacewing Micromus angulatus (Stephens), a member within the subfamily Microminae of the family Hemerobiidae, is a globally distributed species and an important predatory natural enemy of various agricultural and forestry crop pests. Despite its global distribution and agricultural significance, genomic resources for the development of novel pest management strategies for M. angulatus and the family Hemerobiidae remain limited. Here, we present the first high-quality chromosome-level reference genome for M. angulatus, achieved through PacBio HiFi and Hi-C technologies. The assembled genome spans 1.29 Gb, with scaffold N50 of 63.78 Mb, and complete BUSCO score of 97.00%, containing eight pseudochromosomes, demonstrates a high degree of continuity. Functional annotation identified 13,250 protein-coding genes, and repetitive sequences, which account for 83.65% of the genome, were also characterized. This comprehensive assembly offers a robust reference for in-depth research on the genetic basis of predation and adaptability in M. angulatus, supports further research into the understanding the genetic diversity within Hemerobiidae, contributing to the broader knowledge within the group and its related species.

Abstract Background With the rapid development of high-throughput sequencing technology, high-throughput sequencing data has grown on a massive scale, leading to the emergence of multiple public databases, such as EBI and GEO. Conducting secondary mining of high-throughput sequencing data in these databases can yield more valuable insights. Meta-analysis can quantitatively combine high-throughput sequencing data from the the same topic. It increases the sample size for data analysis, enhances statistical power, and results in more consistent and reliable conclusions. Results This study proposes a new between-study variance estimator $$E_{m}$$ E m . We prove that $$E_{m}$$ E m is non-negative and $$E_{m} \left( {\hat{\tau }_{m}^{2} } \right)$$ E m τ ^ m 2 increases with the increase of $$\hat{\tau }_{m}^{2}$$ τ ^ m 2 , satisfying the general conditions of the between-study variance estimator. We get the DSLE2 (two-step estimation starting with the DSL estimate and the $$E_{m}$$ E m in the second step) random-effects meta-analysis model based on the between-study variance estimator Em. The accuracy and a series of evaluation metrics of the DSLE2 model are better than those of the other 6 meta-analysis models. DSLE2 model is applied to lung cancer and Parkinson’s methylation data. Significantly differentially methylated sites identified by DSLE2 model and the genes with significantly differentially methylated sites are closely related to two diseases, indicating the effectiveness of DSLE2 random-effects model. Conclusions This paper propose the DSLE2 random-effects meta-analysis model based on new between-study variance estimator Em. The DSLE2 model performs well for methylation data.

Abstract Background Kinesin family member 13B (KIF13B), a crucial motor protein, exerts multiple cellular biological functions. However, the implication of KIF13B in metabolic dysfunction-associated fatty liver disease (MAFLD) has not been explored yet. This study aimed to investigate KIF13B’s role and underlying mechanism in MAFLD and proposes it as a potential pharmacological target. Methods We assessed KIF13B expression in MAFLD patients and rodent models. The roles of Kif13b in lipid metabolism and MAFLD were investigated using whole-body Kif13b knockout mice, hepatocyte-specific Kif13b-deficient mice and hamsters exposed to different diets. The underlying mechanisms by which Kif13b governed hepatic lipid homeostasis and MAFLD progression were explored in vitro. Finally, the Kif13b’s impact on atherosclerotic development was studied in the context of MAFLD. Results KIF13B expression was reduced in patients and murine models with MAFLD. Rodents with global or liver-specific knockout of the Kif13b gene exhibit spontaneous hepatic steatosis, which is further exacerbated by different overnutrition diets. Overexpression of human KIF13B by lentivirus effectively prevented metabolic dysfunction-associated steatohepatitis (MASH) in methionine-choline-deficient diet (MCD)-fed mice. Furthermore, Kif13b deficiency accelerates atherosclerosis in the context of MAFLD. Mechanistically, Kif13b depletion increases hepatic lipid synthesis and impairs mitochondrial oxidative phosphorylation. Further screening reveals that Kif13b interacts with AMP-activated catalytic subunit alpha 1 (AMPKα1) to regulate the phosphorylation of AMPKα1, governing mitochondrial homeostasis and suppressing sterol regulatory element binding protein 1 (Srebp1)-mediated de novo lipogenesis in the liver. Conclusion This work establishes a causal relationship between KIF13B deficiency and MAFLD, emphasizing KIF13B as a potential therapeutic target for treating MAFLD.

Abstract Objectives This study aims to present a preliminary exploration of an orthopedic nurse specialist training program in Hunan Province, China, and to explore the effectiveness of training. Methods The training programme consisted of one month of theoretical training and two months of clinical practice training. The training content was set around four modules: theoretical knowledge, professional skills, comprehensive practice, and professional development. The application effect of the curriculum was examined via a nonrandomized controlled experimental study. From December 2022 to December 2023, a total of 102 orthopedic specialist nurses from the selected training bases were trained, and we evaluated the effectiveness of the training by using the reaction, learning, behavioral, and results layers of Kirkpatrick Training Evaluation model. Before and after the training, the core competencies of the training participants were evaluated via the Core Competencies Questionnaire for Orthopedic Nurse Specialists, and paired t tests were used to compare the core competencies before and after the training. Results In total, 102 trainees in Hunan Province participated in the training program. The final score of the training trainees was 89.01 ± 2.16. All trainees passed theoretical and clinical practice examinations and trainee evaluations. Their core competencies significantly improved after training (P

Abstract Periodontitis is a chronic inflammatory disease arising from local microorganisms and the host’s own aberrant immune regulation. Ginsenoside Rg1(GS-Rg1) is an active extract of ginseng known for its anti-inflammatory and osteogenesis effects. However, GS-Rg1 has not been shown to treat periodontitis and its exact mechanism remains elucidated. Orthodontic wires inoculated with Porphyromonas gingivalis were wrapped around the gingiva of the first molar in rats to induce periodontitis. Inflammatory factor secretion was analyzed using RT-PCR and immunohistochemistry. The number of osteoclasts and secretion of osteogenic factors were analyzed using TRAP staining and immunofluorescence. The destruction of periodontal tissues was evaluated using Micro-CT and H&E staining. Keap1/Nrf2 pathway protein expression was analyzed using Western-Blot and RT-PCR. Applying GS-Rg1 significantly reduced the secretion of inflammatory factors IL-6 and increased the secretion of transforming growth factor TGF-β1. Additionally, GS-Rg1 decreased osteoclast numbers and increased RUNX2 and OCN expression. Furthermore, GS-Rg1 was found to enhance the expression of the related protein Nrf2 while reducing Keap1 expression. GS-Rg1 may effectively alleviate periodontitis through the Keap1/Nrf2 pathway. In conclusion, our study provided the first preclinical evidence to support GS-Rg1 as a potential therapeutic agent for treating periodontitis.

Abstract Irritable bowel syndrome (IBS) is a common clinical functional gastrointestinal disease. It has a complex pathophysiological mechanism, in which the imbalance of gut microbiota might play an important role. Lacidophilin tablets (LH) can regulate gut microbiota, but their effect on IBS is unknown. In this study, the IBS model was established by acetic acid enema combined with the constrained stress method, and rats were fed LH for 2 weeks. LH significantly reduced visceral sensitivity and intestinal propulsion rate and improved IBS-induced anxiety and depressive behavior in IBS rats. LH elevated the expression levels of mucin 2, claudin1, and occludin, and ameliorated IBS-induced structural damage to colonic tissues. The gut microbiota analysis revealed that LH altered the structure and composition of the gut microbiota in IBS rats. In addition, LH reduced the expression levels of inflammatory factor-related genes. These results suggest that LH could significantly improve the visceral sensitivity and intestinal motility disorders of IBS rats, relieve anxiety and depression levels, and alleviate the symptoms of IBS rats by regulating gut microbiota and reducing intestinal inflammation.

Abstract Sepsis-associated acute kidney injury (SA-AKI) is a severe complication in critically ill patients, with a complex pathogenesis involving in cell cycle arrest, microcirculatory dysfunction, and inflammation. Current diagnostic strategies remain suboptimal. Therefore, this study aimed to evaluate pathophysiology-based biomarkers and develop an improved predictive model for SA-AKI. The prospective observational study was conducted, enrolling 26 healthy individuals and 96 sepsis patients from Peking University Third Hospital. Clinical and laboratory data were collected, and patients were monitored for AKI development within 72 h. Further, sepsis patients were categorized into SA-noAKI (n = 46) and SA-AKI (n = 50) groups. Novel biomarkers, including tissue inhibitor of metalloproteinase-2 (TIMP-2), insulin-like growth factor-binding protein-7 (IGFBP-7), and angiopoietin-2 (Ang-2), were measured in all participants. Among these sepsis patients, the SA-AKI incidence was 52.08% (50/96). Compared to SA-noAKI, the SA-AKI group had significantly higher levels of TIMP-2 (93.55 [79.36, 119.56] ng/mL), IGFBP-7 (27.8 [21.44, 37.29] ng/mL), TIMP-2×IGFBP-7 (2.91 [1.90, 3.55] (ng/mL)²/1000), and Ang-2 (10.61 [5.79, 14.57] ng/mL) (P

Abstract Betavoltaic (BV) batteries are regarded as appealing power sources due to their high energy densities and long lifetimes. However, the low efficiency and maximum output power density of conventional BV batteries due to the self-absorption effect of radioactive sources, which consist of separate beta-radioactive sources and semiconductor absorbers, limit their applications. In this work, we optimized and compared six 63NiO-related heterojunction nuclear batteries utilizing Monte Carlo software Geant4 and finite element analysis software COMSOL Multiphysics. The 63NiO-related heterojunction nuclear batteries integrate beta-radioactive sources and semiconductor absorbers to overcome the shortcomings of conventional BV batteries. Furthermore, we proposed a parallel connection structure utilizing graphene electrode layer to connect two 63NiO/GaP heterojunctions based on the optimal one from the six heterojunctions in order to maximize the maximum output power density. The total energy conversion efficiency is 2.68% and the maximum output power density is $$5236.2\hbox { nW}\cdot \hbox {cm}^{-2}$$ of the parallel connection nuclear battery. Finally, we investigated the time-related performance of the parallel connection structure nuclear battery within 200 years. It shows that the maximum output power density decreases from $$5236.2\hbox { nW}\cdot \hbox {cm}^{-2}$$ in the beginning to $$1330.5\hbox { nW}\cdot \hbox {cm}^{-2}$$ at 200 years.

Abstract Objectives To determine the threshold size for predicting metastasis of supraclavicular lymph nodes (SCLNs) 6 mm, resulting in sensitivity, specificity, positive predictive value, negative predictive value, accuracy of 77.1%, 80.7%, 65.0%, 88.3%, 79.1%, respectively. In the validation set, these metrics were 87.5%, 74.5%, 61.8%, 92.7%, 81.0%, respectively. Conclusion SAD on CT can suspect metastasis of SCLN 6 mm. Clinical relevance statement Determining the threshold size criterion on CT images may enhance the prediction of supraclavicular lymph node metastasis in esophageal squamous cell carcinoma patients, thereby benefiting diagnostic and therapeutic strategies. Key Points Supraclavicular lymph nodes < 10 mm in esophageal carcinoma are indeterminate for malignancy. Supraclavicular lymph nodes > 6 mm are highly suspicious for malignancy. The metastasis status of supraclavicular lymph nodes is critical for staging esophageal carcinoma. Graphical Abstract

Abstract Background While the value of Des-γ-carboxy prothrombin in hepatocellular carcinoma diagnosis has been widely acknowledged, whether or how Des-γ-carboxy prothrombin could be used in recurrence evaluation remains largely unexplored. Methods We performed a multicenter retrospective analysis including an Exploration Cohort (1074 patients, 5133 Des-γ-carboxy prothrombin measurements) and a Validation Cohort (263 patients, 612 Des-γ-carboxy prothrombin measurements) to investigate whether Des-γ-carboxy prothrombin could evaluate patients’ prognosis. We introduced the Des-γ-carboxy prothrombin dynamic rate as a normalized quantitative measurement of Des-γ-carboxy prothrombin dynamic change. Des-γ-carboxy prothrombin dynamic rates were further applied in a high-risk liver cirrhosis patient cohort (PreCar Cohort, 542 liver cirrhosis patients, 2023 Des-γ-carboxy prothrombin measurements). Results Here, we show a post-operative decrease of Des-γ-carboxy prothrombin in the Exploration Cohort, making the Des-γ-carboxy prothrombin threshold in diagnosis unsuitable for prognosis, while Des-γ-carboxy prothrombin dynamic rates significantly associate with recurrence risk. Categorizing patients based on Des-γ-carboxy prothrombin dynamic rates and final concentrations shows that patients negative for both exhibit the best median recurrence-free survival and patients positive for both show the worst median recurrence-free survival. Patients with consistently positive status have a significantly lower median recurrence-free survival compared to those whose status reverted to negative. These findings are validated in the Validation Cohort. Furthermore, the Des-γ-carboxy prothrombin dynamic rates in the PreCar Cohort can identify an additional 28% of cirrhosis patients progressing to hepatocellular carcinoma. Conclusions These results expand on the clinical utilization of the hepatocellular carcinoma diagnosis biomarker, Des-γ-carboxy prothrombin, by proposing a quantification measurement of Des-γ-carboxy prothrombin dynamics to monitor hepatocellular carcinoma recurrence. This measurement is not limited in prognosis but can also improve the sensitivity of early hepatocellular carcinoma screening.

Abstract Antioxidant enzyme therapy shows promise for treating Alzheimer’s disease (AD), but significant challenges remain in achieving effective blood–brain barrier (BBB) penetration and sustained therapeutic effects. We developed a novel neutrophil membrane (NM)-coated cerium-doped Prussian blue biomimetic nanozyme (NM@PB-Ce) that demonstrates outstanding enzymatic properties and targeted therapeutic efficacy. Extensive physicochemical characterization using transmission electron microscopy, X-ray photoelectron spectroscopy, and dynamic light scattering confirmed the successful synthesis of uniform nanoparticles (~ 142 nm) with preserved membrane protein functionality. In vitro studies utilizing SH-SY5Y neuroblastoma cells revealed that NM@PB-Ce effectively scavenged reactive oxygen species through multiple enzyme-mimetic activities (catalase, superoxide dismutase, and peroxidase). The nanozyme significantly suppressed NLRP3 inflammasome activation and subsequent pyroptosis, reducing inflammatory markers (IL-1β, IL-18) while attenuating Aβ aggregation. Using a sophisticated co-culture BBB model and real-time in vivo fluorescence imaging, we demonstrated NM@PB-Ce’s ability to traverse the BBB and accumulate specifically in AD-affected regions. In an Aβ1-42 oligomer-induced AD mouse model, systematic administration of NM@PB-Ce (320 μg/mL, 0.01 mL/g/day for 14 days) significantly improved cognitive performance across multiple behavioral paradigms, including the Morris water maze, Y-maze, and open field tests. Molecular and histological analyses revealed decreased neuroinflammation markers (GFAP, Iba-1) in the hippocampus, reduced levels of NLRP3, caspase-1, and phosphorylated tau (demonstrated by Western blot and ELISA), and enhanced dendritic spine density (visualized through Golgi staining). This comprehensive study establishes NM@PB-Ce as a promising therapeutic platform for AD treatment, providing both mechanistic insights into its mode of action and robust evidence of its therapeutic efficacy in targeting neuroinflammation and cognitive decline. Graphical Abstract

Abstract Background Sport Mental Health Continuum – Short Form (Sport MHC-SF) is an adaptation of the Mental Health Continuum-Short Form for athletes. Although validated in Western contexts, its applicability to the Chinese population remains unexplored. This study aims to validate the Chinese adaptation of the Sport MHC-SF in Chinese university athletes, evaluate its reliability and validity, and confirm its factorial structure. Methods A total of 1,025 Chinese university athletes (65% male, mean age 20 ± 1.54 years) were included in this study. Confirmatory factor analysis (CFA) and multi-group CFA (MGCFA) were conducted using Mplus 8.0 to evaluate the factorial structure and assess measurement invariance across sports levels. Results Both the three-factor and second-order models demonstrated a good fit for the Chinese adaptation of the Sport MHC-SF. Chi-square values were 262.704 (74) and 262.705 (74), respectively, with a comparative fit index (CFI) of 0.968, a Tucker-Lewis index (TLI) of 0.961, a standardized root mean square residual (SRMR) of 0.027, and a root mean square error of approximation (RMSEA) of 0.050 (90% CI: 0.043–0.056). Measurement invariance across ranked and non-ranked athletes was confirmed, with minimal changes in fit indices (ΔCFI ≤ 0.01, ΔTLI ≤ 0.01, ΔRMSEA ≤ 0.015) from configural to strict invariance. Conclusion The Chinese adaptation of the Sport MHC-SF scale has strong construct validity, reliability, and measurement invariance, making it a reliable tool for future research on the well-being of Chinese athletes. This study fills a critical gap in cross-cultural validation, offering a foundation for future research and practical applications in sports psychology among Chinese athletes.

［Objective］ To address the inefficiency and high operational requirements of existing detection methods for catenary stagger value in electrified railways, special research on catenary stagger value detection method is conducted. ［Method］ A detection method combining continuous wavelet transform (CWT) and random forest (RF) is proposed to effectively detect catenary stagger value across different speed levels. CWT is applied to the blowing acceleration signals at both ends of the pantograph contact strip, enabling time-frequency decomposition to reveal the distribution of time-domain signals across various frequency intervals. The power within relevant frequency ranges is calculated, and an indicator correlated with the trend of stagger values is developed based on these power values. The variation of this indicator is analyzed under different conditions in terms of pantograph head mass, pantograph head suspension stiffness, height, and operating speed, revealing that operating speed has a significant impact. Subsequently, the computed indicator and operating speed are used as input features to train, test, and validate an RF model. ［Result & Conclusion］ The proposed method accurately detects catenary stagger values across various operating speeds, achieving a root mean square error as low as 5.84, outperforming other existing algorithms. In brief, the study effectively enhances the measurement efficiency of catenary stagger values, avoiding the limitations imposed by previous methods on operational environmental conditions, and provides a novel approach for catenary stagger value detection.

Yuqing Xie,1,2,&ast; Fengna Yan,1,2,&ast; Xiaoli Liu,1,2 Lihua Yu,1,2 Huiwen Yan,1,2 Zimeng Shang,1,2 Yaxian Kong,3 Zhiyun Yang1,2 1Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Capital Medical University Research and Translational Laboratory for Traditional Chinese Medicine in the Prevention and Treatment of Infectious Severe Hepatitis, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiyun Yang, Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China, Email yangzhiyun2016@163.com Yaxian Kong, Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China, Email kongyaxian@ccmu.edu.cnPurpose: Yangyin Fuzheng Jiedu Prescription (YFJP) is a traditional Chinese medicine (TCM) used for the treatment of hepatocellular carcinoma (HCC). However, the potential mechanisms remain unclear. The objective of this study is to clarify the mechanism of action of YFJP in treating HCC.Methods: By constructing networks, the active components and molecular targets of YFJP in the treatment of HCC were explored. The TCGA database was utilized to analyze the correlation between the core target and the overall survival (OS) of patients with HCC. The regulatory effect of YFJP on T cell was evaluated by detecting samples from patients with HCC. The molecular mechanism of YFJP in treating HCC was validated through in vivo and in vitro experiments.Results: Constructing networks and analyse indicated that the key targets of YFJP in the treatment of HCC is FoxO1. Analysis of the HCC patient cohort in the TCGA database demonstrated that FoxO1 is an independent protective factor for overall survival in patients with HCC. Pathway enrichment analysis enriched FoxO signaling pathway and Cellular senescence pathway. Prospectively collecting samples from patients with HCC suggested that YFJP treatment increased the proportion of CD8+ T cells. In vivo experiments showed that YFJP treatment ameliorated CD8+ T cell senescence in tumor-bearing mice. Western blot, flow cytometry and multi-color immunofluorescence co-staining showed that YFJP treatment increased the expression of FoxO1 in CD8+ T cells. The primary CD8+ T cells were sorted and co-cultured with an HCC cell line in vitro. Inhibiting the expression of FoxO1 in CD8+T cells confirmed that FoxO1 is a key target for YFJP to improve the senescence of CD8+ T cell.Conclusion: FoxO1 is the key molecular target of YFJP in improving CD8+ T cell senescence in HCC. This study preliminarily clarified the mechanism of YFJP in regulating immunosenescence of HCC. Keywords: hepatocellular carcinoma, senescence, T cell, network pharmacology, Yangyin Fuzheng Jiedu Prescription

Zhi Yang, Wei-Da Fu, Hua-Yan Gu, Jia-Ling Ding, Gui-Long Guo Department of Breast Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of ChinaCorrespondence: Gui-Long Guo, Email guoguilong@sina.comPurpose: To explore the efficacy and safety of pyrotinib in a real-world setting in a population with HER2-positive advanced breast cancer, subgroup analysis was conducted based on different clinicopathological features to further explore the general characteristics of patients, tumor nature, and the effect of various lines of treatment before patients started pyrotinib on the efficacy of pyrotinib in the real-world study.Methods: The clinical pathological characteristics, drug efficacy and related adverse reactions of HER2-positive MBC patients treated with pyrotinib in six hospitals in Southeast Zhejiang Province from February 2018 to December 2023 were collected and analyzed retrospectively.Results: A total of 342 patients with HER2-positive MBC were enrolled. The median follow-up time of 42.0 months. The median age of the overall population was 52 years (range from 25– 90 year old). Median progression-free survival in the total population was 10.0 months, the median overall survival was 29.0 months. The (objective response rate, ORR) was 40.35% and the (disease control rate, DCR) was 83.92%. The median progression-free survival (PFS) in the total population was 10.0 months, the median overall survival was 29.0 months. And pyrotinib had better mPFS for advanced first-line treatment than for second-third-line and beyond(14.0 months vs.10.0 months vs.6.0 months, P< 0.001). Multivariate Cox regression analysis showed that ECOG, HER2 status, brain metastasis, liver metastasis, number of pyrotinib treatment lines, previous lapatinib treatment, combined capecitabine therapy and trastuzumab resistance were independent prognostic factors for PFS. Diarrhea was the most common adverse reaction (ADR) in 205 patients (59.94%), which could be controlled by antidiarrheal drugs.Conclusion: This multicenter study suggested that the use of pyrotinib for HER2 positive MBC had a relatively good efficacy, especially for those who received first-line pyrotinib treatment and those who were sensitive to previous trastuzumab treatment. Patients with brain metastasis and liver metastases also benefit from pyrotinib treatment, especially for patients treated with brain radiotherapy and/or surgery. ECOG, HER2 status, brain metastasis, liver metastasis, number of pyrotinib treatment lines, previous lapatinib treatment, combined capecitabine therapy and trastuzumab resistance were independent prognostic factors for PFS in HER2 Positive MBC patients treated with pyrotinib. The most common adverse reaction associated with pyrotinib is diarrhea, which can be well controlled through antidiarrheal treatment. Pyrotinib combined with vinorelbine has similar efficacy to pyrotinib combined with capecitabine and has fewer side effects, and can be used as an alternative to capecitabine.Keywords: pyrotinib, HER2 positive metastatic breast cancer, real-world study, efficacy, safety

Abstract Metabolic disorders are an important feature of chronic lung disease. Patients diagnosed with chronic obstructive pulmonary disease (COPD) have been found to experience metabolic disorders. Nonetheless, evidence on the causal role of circulating metabolites in promoting or preventing COPD is still lacking. Conducting a methodical examination on the causal connection between blood metabolites and COPD can aid in identifying fresh objectives for the screening and prevention of COPD. Therefore, we performed a two-sample Mendelian randomization (MR) analysis to evaluate the causal association between COPD and 486 blood metabolites.We used two-sample MR techniques and genome-wide association study (GWAS) data to evaluate the correlation between COPD and 486 serum metabolites. To evaluate the causal impact of serum metabolites on the risk of COPD, we predominantly employed inverse variance weighting (IVW) methodology. The MR-Egger regression test was employed to assess multiple validity, while the presence of heterogeneity was examined using the Cochran’s Q test. To ensure the reliability of the findings, a leave-one-out analysis was conducted. The Bonferroni correction is used to adjust for multiple comparisons, ensuring rigorous validation of our results.After filtering by IVW and sensitivity analysis, we identified 10 known metabolites including fructose, margarate (17:0), guanosine, 2-stearoylglycerophosphocholine, hexadecanedioate, lactate, 5-oxoproline, paraxanthine, phenyllactate (PLA) and N-acetylglycine. Of these, fructose, margarate (17:0), guanosine, 2-stearoylglycerophosphocholine and hexadecanedioate are risk metabolites, and additionally, lactate, 5-oxoproline, paraxanthine phenyllactate(PLA) and N-acetylglycine are protective metabolites. In addition, the study identified five currently unknown chemical structures. Cochran’s Q-test showed no significant heterogeneity, and MR Egger’s intercept analysis confirmed the absence of horizontal multidirectionality. Leave-one-out analysis also proved the reliability of the MR analysis.We identified seven COPD-related risks and eight protective human serum metabolites. By combining genomics and metabolism, it provides new insights into the underlying mechanisms of COPD, with important implications for COPD screening and prevention.

This paper proposes an IoT-based vehicle–road cooperative communication system to address real-time collision avoidance and path planning challenges in dynamic traffic environments. Traditional path planning methods often struggle with dynamic obstacles, particularly when vehicles and pedestrians frequently change positions. To overcome these limitations, we introduce the GR-RRT model, which integrates V2X communication, a GRU-based dynamic obstacle prediction module, and an adaptive RRT path planning algorithm. This integration allows for enhanced obstacle trajectory prediction and real-time collision avoidance. Experimental results show that the GR-RRT model significantly outperforms traditional methods in terms of trajectory prediction accuracy, collision avoidance success rate, and path planning efficiency. The model exhibits particularly strong performance in multi-vehicle cooperation and dynamic environments, demonstrating its potential for improving safety and efficiency in future intelligent transportation systems.

Composite carbides (W,Ti)C enhanced Ni-based coatings were fabricated by laser cladding on 316L stainless steel. The impact of composite carbides (W,Ti)C enhanced on Ni-based composite coatings' microstructure, wear and corrosion behavior are largely explored. The results show that the breaking down of composite phase (W,Ti)C speed up the production of MC and M23C6 and makes the distribution denser to improve wear-resisting properties. The particle sizes of W + TiC/Ni-based composite coatings are increasingly refined, and the crystal structure transitions from columnar dendrites, isometric, cellular, and eutectic to the eutectic organization. According to the results of friction and wear property tests, the friction coefficient and wear of W + TiC/Ni-based coatings gradually decreased with the increase of the mass fraction of W + TiC, and according to the friction and wear morphology. The generation of plastic deformation was hindered with MC and M23C6 composite carbides. Based on the results of electrochemical experiments, it can be seen that the corrosion resistance behaviour in sulfur-containing chloride environments gradually deteriorates as the mass fraction of W + TiC increases. In contrast, the corrosion resistance behaviour in chloride environments first deteriorates and then improves, suggesting that the corrosion resistance of MC and M23C6 composite carbides to sulfur-containing environments will deteriorate.

【Objective】Soil salinization induced by poor irrigation management poses a significant challenge to irrigated agriculture, reducing soil productivity and crop yields. Estimating soil salinity and its spatial distribution in irrigated areas can help improve soil and irrigation management. The objective of this paper is to use hyperspectral inversion techniques and a develop model to accurately estimate soil salinity and its distribution in the Hetao Irrigation District. 【Method】The experiment was conducted in the Shenwu Irrigation Area, where spectral reflectance and salinity data were measured and collected from 253 soil samples. Fifteen spectral transformations were applied to improve the correlation between hyperspectral data and soil salinity. Four models, including multiple linear stepwise regression (MLSR), partial least squares regression (PLSR), support vector machine regression (SVR), and backpropagation neural network (BPNN), were evaluated for their accuracy to estimate soil salinity. The most accurate model was then integrated with GIS to map soil salinity across the region.【Result】① Soil spectral reflectance increased with soil salinity, and spectral transformations significantly improved the correlation between hyperspectral data and soil salinity. ② Among the four models we compared, the BPNN model proved to be most accurate and stable. The optimal spectral transformation was the first derivative of the reciprocal logarithm of transformed reflectance data (represented by R), that is, lg(1/R)]'. This model achieved a determination coefficient of 0.825 and a root mean square error of 2.254 g/kg. ③ Integrating the BPNN model with GIS enabled estimation of spatial variation of soil salinity. Validation against ground-truth data revealed spatial pattern in soil salinity distribution, with high soil salinity found in the southeast, west and north, and severe soil salinization found in areas adjacent to the lake.【Conclusion】The BPNN model using [lg(1/R)]' we developed is accurate and reliable for estimating soil salinity using hyperspectral data. Combined with GIS, it facilitates accurate mapping of soil salinization in irrigated areas, offering valuable insights for salinity monitoring and sustainable management in the Hetao Irrigation District and similar regions.

BackgroundIt has been shown that academic procrastination， cognitive emotion regulation strategies， anxiety and mobile phone dependence are closely related， but the detailed mechanism by which academic procrastination contributes to mobile phone dependence remains largely unclear and mediation analysis is currently lacking.ObjectiveTo explore the mediation role of cognitive emotion regulation strategies and anxiety in the relationship between academic procrastination and mobile phone dependence among college students， so as to provide references for the prevention and intervention of college students' mobile phone dependence.MethodsIn March 2023， 474 students from Xinjiang Normal University were selected by random sampling technique， and Mobile Phone Addiction Index （MPAI）， Procrastination Assessment Scale-Students （PASS）， Beck Anxiety Inventory （BAI） and Cognitive Emotion Regulation Questionnaire-Chinese version （CERQ-C） were used to conduct the survey. Pearson correlation analysis was adopted to examine the correlation among all variables， and Process 3.5 macro program was utilized to determine the mediation effect of cognitive emotion regulation strategies and anxiety on the relationship between academic procrastination and mobile phone dependence among college students.Results①PASS scores were positively correlated with the scores on CERQ-C negative cognitive emotion regulation strategy， BAI and MPAI （r=0.374， 0.229， 0.661， P

Abstract In contemporary society, music art plays a pivotal role in enhancing spiritual quality-of-life and optimizing talent cultivation models. The spatial distribution of music educational resources undoubtedly plays a promotional role in enhancing the quality of music education. However, existing research has not conducted specialized and in-depth studies on this topic. This study uses a geographic information system (GIS) and classical geographical research methods such as the nearest neighbor index, kernel density analysis, and geographic detectors to analyze the spatial distribution and influencing factors of music training institutions in Beijing, Shanghai, Guangzhou, and Shenzhen. The results indicate that the distribution of these institutions is obviously clustered, with a "northeast‒southwest" trend in Beijing and Shenzhen and a "northwest‒southeast" trend in Shanghai and Guangzhou. Among the categories of urban facilities, which encompass sports, leisure, shopping, and dining, sports venues exert the most substantial influence on the spatial distribution characteristics of music training institutions. The location of music training institutions should be closely integrated with the spatial distribution of urban facilities. This study provides theoretical foundations and practical guidance for policy-makers in the refined adjustment of urban layouts, the rational allocation of artistic educational resources, and the promotion of cultural industry development.

Abstract With ongoing development of ground transportation system, competing regional airports need to collaborate in order to improve their efficiency and passenger turnover. However, finding the most advantageous dynamic connection between airports’ rivalry and collaboration, passenger market alterations, and influencing factors is quite challenging. To this end, our study proposed a three-stage method combining analytical methodologies and data envelopment analysis (DEA) to analyze the changing trend and correlation of passenger market concentration as well as operational efficiency in ten airports of China’s Yangtze River Delta (YRD) airport group during period from 2011 to 2019, China. As the first step, the current study applied state-of-the-art evaluative methods, including the Hirschmann-Hefenthal index, Gini index, and net-shift effects analysis, to examine passenger concentration. Subsequently, the super-efficiency data envelopment analysis (DEA) model was utilized to explore the correlation of net shift with airport performance. Finally, the OLS model was combined to make a comprehensive analysis. The proposed approach was discussed in detail and yielded the following findings. The YRD airport group was moderately concentrated and had a decentralized trend from 2010 to 2019. Half of the airports in the airport group had an efficiency score lower than one but managed to gain significant market shares in the competition. The analysis shows that in the Yangtze River Delta Airport Group, there is a significant positive correlation between market share and airport efficiency, while Net shift is only negatively correlated with airports that gain market share. The super-efficiency score curve of three airports changed dramatically, presenting a “U” shape, while that of the other seven airports changed steadily, related to their urban economic scale, urban development stage, and government investment pattern.

Abstract Objective Hypopharyngeal squamous cell carcinoma (HSCC) is a highly malignant tumor type in the head and neck region. In recent years, neoadjuvant therapy has significantly improved the laryngeal preservation rate among patients. However, there are variations in the efficacy of neoadjuvant therapy, and the identification of reliable predictive biomarkers for its efficacy remains a challenging research focus. This study aims to explore the correlation between the expression of P53, P16, and Ki67 and the response to neoadjuvant therapy. Methods A retrospective analysis was conducted on 120 patients who underwent neoadjuvant therapy at Beijing Tongren Hospital, Capital Medical University, from January 2021 to June 2024. Patients were grouped based on their treatment response and the type of neoadjuvant therapy received. Group analysis were employed to assess the predictive value of P53, P16, and Ki67 for treatment efficacy across different neoadjuvant therapy groups. Results A total of 120 patients were included in the study, with 60 patients each in the good response and poor response groups. The study comprised three neoadjuvant therapy groups: neoadjuvant chemotherapy, neoadjuvant targeted therapy combined with chemotherapy, and neoadjuvant immunotherapy combined with chemotherapy. Each group had 20 patients with good and poor responses, respectively. Among patients with P53 positivity, the effective rate after neoadjuvant therapy was 35.94%, significantly lower than the 66.07% observed in P53negative patients (p = 0.0017). For P16 positivity, the effective rate was 28.57%, lower than the 52.83% in P16negative patients (p = 0.0880). For patients with Ki67

Abstract Background The accurate prognosis of gastrointestinal stromal tumors (GISTs) has garnered substantial attention, yet a gap persists in understanding the influence of inflammatory markers on the prognosis of high-risk GIST patients. This study investigated the relationship between various factors and the prognosis of high-risk GIST patients, with a specific focus on first recurrence-free survival (RFS) and overall survival (OS) as crucial prognostic indicators. Methods A comprehensive collection of clinical data was conducted on 145 high-risk GIST patients meeting specific inclusion and exclusion criteria at 17 medical centers in Ningxia Hui Autonomous Region, China, covering the period from January 2013 to December 2019. Single-factor analysis and survival curves were used to analyze the variables, while the Cox regression model evaluated independent prognostic factors. Results Within the cohort, a balanced male-to-female ratio of 1:1.1 was observed. Univariate analysis revealed compelling associations between RFS and age, preoperative neutrophil-to-lymphocyte ratio (NLR), preoperative platelet-to-lymphocyte ratio (PLR), preoperative systemic immune-inflammatory index (SII), preoperative prognostic nutritional index (PNI), mitotic index, and whether or not imatinib (IM) was taken regularly in high-risk GIST patients (P

Abstract The electroelastomer cylindrical actuators, a typical representation of soft actuators, have recently aroused increasing interest owing to their advantages in flexibility, deformability, and spatial utilization rate. Proprioception is crucial for controlling and monitoring the shape and position of these actuators. However, most existing flexible sensors have a modulus mismatch with the actuation unit, hindering the free movement of these actuators. Herein, a low-modulus strain sensor based on laser-induced cellular graphitic flakes (CGF) onto the surface of hollow TPU fibers (HTF) is present. Through the electrostatic self-assembly technology, the flexible sensor features a unique hybrid sensing unit including soft HTF as substrate and rigid CGF as conductive path. As a result, the sensor simultaneously possesses desirable modulus (~0.155 MPa), a gauge factor of 220.3 (25%

Abstract Non-adiabatic molecular dynamics (NAMD) simulations have become an indispensable tool for investigating excited-state dynamics in solids. In this work, we propose a general framework, N2AMD (Neural-Network Non-Adiabatic Molecular Dynamics), which employs an E(3)-equivariant deep neural Hamiltonian to boost the accuracy and efficiency of NAMD simulations. Distinct from conventional machine learning methods that predict key quantities in NAMD, N2AMD computes these quantities directly with a deep neural Hamiltonian, ensuring excellent accuracy, efficiency, and consistency. N2AMD not only achieves impressive efficiency in performing NAMD simulations at the hybrid functional level within the framework of the classical path approximation (CPA), but also demonstrates great potential in predicting non-adiabatic coupling vectors and suggests a method to go beyond CPA. Furthermore, N2AMD demonstrates excellent generalizability and enables seamless integration with advanced NAMD techniques and infrastructures. Taking several extensively investigated semiconductors as the prototypical system, we successfully simulate carrier recombination in both pristine and defective systems at large scales where conventional NAMD often significantly underestimates or even qualitatively incorrectly predicts lifetimes. This framework offers a reliable and efficient approach for conducting accurate NAMD simulations across various condensed materials.

Abstract Background Pericoronary adipose tissue (PCAT) attenuation, as assessed by coronary computed tomography angiography (CCTA), has been identified as a marker of pericoronary inflammation and a predictor of future adverse atherosclerotic events. However, the impact of changes in PCAT attenuation, as evaluated by consecutive CCTAs, on plaque progression in high-risk atherosclerotic patients with improved modifiable cardiovascular risk factors (mCRFs) remains unclear. Methods Consecutive patients with type 2 diabetes mellitus (T2DM) who had improved mCRFs and underwent serial, clinically indicated CCTA examinations (time interval ≥ 12 months) at our center between July 2019 and July 2022 were screened. Eligible participants had at least one study plaque, defined as a plaque without significant anatomic stenosis, located in one of the major coronary arteries, which had not been intervened upon or caused adverse events between serial CCTA scans. Percent atheroma volume (PAV) and PCAT attenuation were measured for each study plaque at baseline and follow-up using CCTA plaque analysis software. Changes in PAV (δPAV = follow-up PAV – baseline PAV) were compared based on changes in PCAT attenuation [δPCAT attenuation] (> 0 or ≤ 0). Multivariate linear regression models were used to evaluate the relationship between δPCAT attenuation and δPAV. Results A total of 98 T2DM patients (mean age: 59.9 years; 75.3% men; 152 plaques) had mCRFs that reached therapeutic targets at follow-up CCTA. However, overall PAV progressed from baseline in all patients [(41.68 ± 12.47)% vs. (43.71 ± 12.24)%, p = 0.035], accompanied by an increase in coronary inflammation (i.e., PCAT attenuation) during a median follow-up of 13.5 months (interquartile range [IQR]: 12.2, 17.5 months).Compared to patients with δPCAT attenuation ≤ 0, those with δPCAT attenuation > 0 had a significantly greater increase in overall PAV from baseline [(4.09 ± 12.09)% vs. (-0.82 ± 10.74)%, p = 0.011], calcified PAV [1.57% (IQR: 0.13%, 3.84%) vs. 0.38% (IQR: -0.26%, 2.58%), p = 0.008], and a numerical but non-significant increase in non-calcified PAV [(1.29 ± 11.75)% vs. (-1.87 ± 10.47)%, p = 0.089]. Multivariate linear regression models demonstrated that increased PCAT attenuation was significantly associated with the progression of overall PAV (β = 0.339, 95% CI: 0.129–0.549), non-calcified PAV (β = 0.237, 95% CI: 0.019–0.455), and calcified PAV (β = 0.109, 95% CI: 0.019-0.200), independent of age, sex, cardiovascular risk factors, medications, and baseline PCAT attenuation and PAV (all p 0.05). Conclusion In this longitudinal CCTA cohort of T2DM patients with improved mCRFs, increased pericoronary inflammation was associated with the progression of atherosclerotic plaque, particularly non-calcified plaque.

Abstract In this study, we developed a high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS)-based method for quantitatively tracking the dynamic abundance of TGFβ1, a fibrosis marker, in tumours of mice with bladder cancer in situ. Initially, we screened the amino acid sequence of the characteristic peptide of TGFβ1 (VEQLSNMIVR) in mouse tumours by utilising the sub-ions and retention time of the Orbitrap mass spectrometer and established a standard curve by externally labelling the characteristic peptide at gradient concentrations. Subsequently, real-time feedback on the increasing trend of TGFβ1 was provided in terms of the concentration of the characteristic peptide. The results demonstrated that the quantitative method based on feature peptides had high identification specificity and excellent stability, and the relative standard deviation of the accuracy was less than 3%. Meanwhile, in combination with the established method we found that the growth rate of the relative content of TGFβ1 increased significantly when the tumour invasion extended to the lamina propria. This work provides a new feasible solution for real-time tracking and precise monitoring of small molecular proteins in pathologically complex stroma.

Abstract Cryptocurrency is a remarkable financial innovation that has affected the financial system in fundamental ways. Its increasingly complex interactions with the conventional financial market make precisely forecasting its volatility increasingly challenging. To this end, we propose a novel framework based on the evolving multiscale graph neural network (EMGNN). Specifically, we embed a graph that depicts the interactions between the cryptocurrency and conventional financial markets into the predictive process. Furthermore, we employ hierarchical evolving graph structure learners to model the dynamic and scale-specific interactions. We also evaluate our framework’s robustness and discuss its interpretability by extracting the learned graph structure. The empirical results show that (i) cryptocurrency volatility is not isolated from the conventional market, and the embedded graph can provide effective information for prediction; (ii) the EMGNN-based forecasting framework generally yields outstanding and robust performance in terms of multiple volatility estimators, cryptocurrency samples, forecasting horizons, and evaluation criteria; and (iii) the graph structure in the predictive process varies over time and scales and is well captured by our framework. Overall, our work provides new insights into risk management for market participants and into policy formulation for authorities.

【Objective】Mode-division multiplexing is a key technology to break through the capacity limit of single-mode fiber systems. In the few-mode fiber links, the pulse broadening caused by intermodal dispersion increases the complexity of multiple-input-multiple-output algorithms in the receiving terminal, which is one of the important reasons for limiting the implementation of long-haul transmission in mode-division multiplexing systems. The application of mode permutation methods can effectively compress pulse broadening and reduce mode-dependent loss, making it a mainstream technological approach for achieving long-distance, high-capacity mode-division multiplexing system transmission. However, there are numerous mode-permutation strategies with varying performance, and exploring mode-permutation strategies that are more suitable for long-distance, high-capacity mode-division multiplexing systems has become an urgent problem to be solved.【Methods】In this paper, we propose that the mode permutation strategy should match the mode group delay distribution of the fiber. Besides, we design a Mirror-Flipped Mode Permutation (MFMP) strategy based on few-mode fibers with symmetric mode delay. By modeling on a simulation platform, the transmission performance of mode-division multiplexing system based on the proposed MFMP is analyzed and verified through 6-mode multiplexing transmission experiments.【Results】In this paper，based on the proposed MFMP strategy, 822-km 6-mode transmission over a mode-delay-symmetric few-mode fiber is experimentally demonstrated, carrying quadrature phase shift keying signals at 28 GBaud. At 616 km, compared to Cyclic Mode Permutation (CMP) and Cyclic Mode-Group Permutation (CMGP) methods, the signal pulse broadening is compressed by 37% and 6%, and the Q-factor is increased by 3.0 and 0.4 dB, respectively.【Conclusion】The proposed MFMP strategy can effectively compress pulse broadening, and improve the Q-factor of the system, while the advantages of this method over traditional two types of mode permutation strategies are verified via simulation and experiment. It should be noted that our work provides the theoretical basis and experimental guidance for achieving long-haul and high-capacity mode-division multiplexing transmissions based on mode permutation strategies.

Abstract Metabolic reprogramming in prostate cancer has been widely recognized as a promoter of tumor progression and treatment resistance. This study investigated its association with ferroptosis resistance in prostate cancer and explored its therapeutic potential. In this study, we identified differences in the epithelial characteristics between normal prostate tissue and tissues of various types of prostate cancer using single-cell sequencing. Through transcription factor regulatory network analysis, we focused on the candidate transcription factor, SREBF1. We identified the differences in SREBF1 transcriptional activity and its association with ferroptosis, and further verified this association using hdWGCNA. We constructed a risk score based on SREBF1 target genes associated with the biochemical recurrence of prostate cancer by combining bulk RNA analysis. Finally, we verified the effects of the SREBPs inhibitor Betulin on the treatment of prostate cancer and its chemosensitization effect. We observed characteristic differences in fatty acid and cholesterol metabolism between normal prostate tissue and prostate cancer tissue, identifying high transcriptional activity of SREBF1 in prostate cancer tissue. This indicates that SREBF1 is crucial for the metabolic reprogramming of prostate cancer, and that its mediated metabolic changes promoted ferroptosis resistance in prostate cancer in multiple ways. SREBF1 target genes are associated with biochemical recurrence of prostate cancer. Finally, our experiments verified that SREBF1 inhibitors can significantly promote an increase in ROS, the decrease in GSH, and the decrease in mitochondrial membrane potential in prostate cancer cells and confirmed their chemosensitization effect in vivo. Our findings highlighted a close association between SREBF1 and ferroptosis resistance in prostate cancer. SREBF1 significantly influences metabolic reprogramming in prostate cancer cells, leading to ferroptosis resistance. Importantly, our results demonstrated that SREBF1 inhibitors can significantly enhance the therapeutic effect and chemosensitization of prostate cancer, suggesting a promising therapeutic potential for the treatment of prostate cancer.

Abstract The presence of vulnerable carotid plaques plays a critical role in ischemic stroke pathogenesis, with intraplaque neovascularization (IPN) serving as a key indicator of plaque instability. Contrast-enhanced ultrasound (CEUS) provides a comprehensive evaluation of both plaque surface morphology and microvascular features. This study assesses the utility of CEUS in identifying vulnerable carotid plaques, quantifying IPN, and predicting stroke risk. The study involved 91 patients with carotid stenosis who underwent carotid endarterectomy (CEA). Preoperative assessments included CEUS and high-resolution magnetic resonance imaging (HR-MRI). Following surgery, plaque samples were collected and subjected to pathological analysis. CEUS offered comprehensive morphological insights, categorizing plaques by the direction of diffusion into inside-out and non-inside-out types. Neovascularization was semi-quantitatively evaluated using CEUS. HR-MRI and pathological assessments identified the composition and vulnerability of plaques. Microvessel density (MVD), microvessel area (MVA), and microvessel ratio (MVR) in plaque sections were quantified using high-power microscopy. Among the 91 subjects, 53 had a history of symptomatic stroke, while 38 had experienced asymptomatic stroke events. The analysis identified a significant association between symptomatic stroke events and fibrous cap rupture (FCR), as indicated by CEUS (P = 0.032), contrast agent diffusion within the plaque (P = 0.002), and a semi-quantitative grade 3 neovascularization (P = 0.007). Regression analysis further established CEUS grade 3 as an independent predictor of symptomatic stroke events (OR = 3.39, 95% CI: 1.25–9.19). CEUS showed comparable sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy in identifying vulnerable plaques when compared to HR-MRI, with slightly superior values for CEUS; however, the differences did not reach statistical significance (P = 0.503). Plaques demonstrating inside-out contrast agent diffusion had a markedly higher incidence of FCR and intraplaque hemorrhage (IPH) than those without such diffusion (P

Abstract Seabuckthorn (Hippophae rhamnoides L.) is known for its medicinal properties in treating various diseases, including neurological conditions. However, the therapeutic effect of inhaled seabuckthorn seed oil (SSO) on Alzheimer’s disease (AD) remains not fully understood. This study explores the effects of nebulized inhalation of SSO in 9-month-old APP/PS1 mice over 21 days. The results showed that nebulized SSO improved memory and cognition. Using 7.0T MRI to monitor blood oxygenation level dependent (BOLD) signals revealed that SSO altered the Amplitude of Low Frequency Fluctuations (ALFF) and Regional Homogeneity (ReHo) signaling such as in the amygdala and substantia innominate, and hippocampus. Enzyme-linked immuno sorbent assay (ELISA) and pathological analyses indicated reduced neuroinflammation in plasma and brain, decreased neuronal necrosis, lower β-amyloid (Aβ) protein levels, reduced amyloid deposition, and increased tyrosine hydroxylase activity. Additionally, SSO promoted gut microbiota remodeling by increasing alpha diversity and boosting levels of probiotics such as Verrucomicrobia, Bifidobacterium, Prevotella, and Akkermansia, without adverse effects on lung tissue. Nebulized inhalation of SSO may slow AD progression by modulating inflammation and amyloid deposition. Nebulized inhalation offered a potential method for enhancing drug delivery across the blood-brain barrier with reduced systemic side effects.

Abstract Urbanization induces significant land use changes that profoundly impact carbon stocks by altering terrestrial ecosystems’ carbon storage capacity. This study employs integrated FLUS model and InVEST model alongside land use data to analyze the spatial and temporal dynamics of car-bon stocks in Shanghai from 2010 to 2020. We predict future land use change and carbon stock distribution patterns under various scenarios for Shanghai in 2030. Despite cultivated land representing the largest land use type in terms of area, rapid urbanization has drastically reduced it, largely converting it into construction land. Construction land expands most rapidly under the HUS scenario, prioritizing economic development, and least under the EPS scenario, emphasizing eco-logical protection. Annual carbon stocks declined by 165.06 × 104 Mg from 2010 to 2020, driven by construction land expansion diminishing carbon stocks in cultivated land, woodland, and grassland. Projections for 2030 anticipate carbon stock increases solely under the EPS scenario, contrasting with significant decreases under the NTS and HUS scenarios. This underscores ecological conservation policies’ potential to mitigate carbon stock decline, constrain built-up land expansion, and enhance carbon sequestration capacity. Urbanization profoundly influences land use change and carbon stocks, highlighting the critical role of ecological policies in optimizing urban development space and fostering carbon stock growth.

Abstract Despite extensive research, spinal cord injuries (SCI), which could cause severe sensory, motor and autonomic dysfunction, remain largely incurable. Oligodendrocytes and oligodendrocyte precursor cells (ODC/OPC) play a crucial role in neural morphological repair and functional recovery following SCI. We performed single-cell sequencing (scRNA-seq) on 59,558 cells from 39 mouse samples, combined with microarray data from 164 SCI samples and 3 uninjured samples. We further validated our findings using a large clinical cohort consisting of 38 SCI patients, 10 healthy controls, and 10 trauma controls, assessed with the American Spinal Cord Injury Association (ASIA) scale. We proposed a novel SCI classification model based on the expression of prognostic differentially expressed ODC/OPC differentiation-related genes (PDEODGs). This model includes three types: Low ODC/OPC Score Classification (LOSC), Median ODC/OPC Score Classification (MOSC), and High ODC/OPC Score Classification (HOSC). Considering the relationship between these subtypes and prognosis, we speculated that enhancing ODC/OPC differentiation and inhibiting inflammatory infiltration may improve outcomes. Additionally, we identified potential treatments for SCI that target key genes within these subtypes, offering promising implications for therapy.

Abstract Cardiovascular diseases (CVDs) are the leading cause of premature mortality in patients with schizophrenia spectrum disorders (SSDs). However, the detailed categorization of these conditions remains insufficiently explored. This study aims to identify CVDs comorbidity patterns among inpatients with SSDs and to investigate associated factors. Electronic medical records (EMRs) data from three neuropsychiatric hospitals (2015–2023) in China was conducted. Comorbidity patterns were revealed through latent class analysis (LCA), and multinomial logit analysis were utilized to evaluate the effect of factors on these patterns, calculating odds ratios (ORs) and 95% confidence intervals (CIs). Among the 2830 inpatients with SSD, four distinct comorbidity patterns were identified based on their dominant characteristics: low-risk CVDs (47.86%), primary hypertension (30.15%), heart failure (12.99%), and cardiac valve and vascular disorders (8.99%). Compared to the low-risk CVD group, male patients demonstrated a higher probability of primary hypertension (OR = 1.15) and heart failure (OR = 5.36). Significant associations were observed between comorbid CVDs and the use of typical antipsychotics, atypical antipsychotics, anxiolytics and sedatives, antidepressants, and mood stabilizers. Notably, perphenazine (OR = 22.06) and chlorpromazine hydrochloride (OR = 7.09) were strongly linked to comorbid heart failure. Among Chinese patients with SSDs, four distinct CVD comorbidity patterns were identified, with hypertension and heart failure displaying strong specificity. Variations in demographic characteristics and psychotropic medication use provide valuable insights for treatment and management.

Abstract Colorectal cancer liver metastases (CRLM) are the primary cause of mortality in colorectal cancer (CRC) patients, highlighting the importance of understanding the underlying mechanisms. The tumor microenvironment (TME) and its interaction with tumor cells play a crucial role in CRLM progression. Notably, the stability and peak levels of tumor-derived exosomal miRNAs facilitate intercellular communication in the TME. Hepatic stellate cells (HSCs), key liver mesenchymal cells, constitute about 33% of the liver's nonsolid cell population and exhibit plasticity. However, the specific role of tumor-derived exosomal miRNAs in the crosstalk between HSCs and tumor cells during the CRLM process remains unclear. We studied CRC-secreted exosomal miR-1246 and its impact on HSCs, as well as its effects on CRC cell proliferation and metastasis. Our findings demonstrate that CRC-secreted exosomal miR-1246 can be internalized by HSCs, leading to their activation and facilitating the metastatic potential of CRC cells. Mechanistically, exosomal miR-1246 targets INSIG1, resulting in SREBP2 nucleation and cholesterol metabolism alterations. This accumulation of free cholesterol (FC) regulates the TLR4/NF-κB/TGF-β pathway, promoting HSC activation. Activated HSCs, in turn, enhance liver metastasis of CRC cells through the TNFSF13/TNFRSF13B axis. Our study reveals the role of CRC-secreted exosomal miR-1246 in triggering HSC activation and reprogramming the TME, ultimately facilitating liver metastasis in CRC patients. Exosomal miR-1246 could serve as a potential non-invasive biomarker for predicting colorectal cancer liver metastasis, enhancing our understanding of CRC-associated liver metastases. Graphical abstract

Abstract Marvelous natures of alkali and alkaline earth metal hydrides in catalyzing chemical transformations are being discovered. However, the synthesis of (sub)nanostructured metal hydrides, critically important to enhance their catalytic performances, is yet a very challenging task. Herein, we develop a highly reactive heterogeneous catalyst comprising atomically dispersed barium hydrides on MgO support with an ultrahigh barium loading of up to 20 wt% via a convenient preparation method involving liquid-ammonia impregnation followed by hydrogenation. The surface barium hydride species not only exhibits extraordinary reactivity toward H2 activation at room temperature, but also enables the highly efficient hydrogen isotope exchange (HIE) of both sp3 C–H and sp2 C–H bonds in nonactivated alkylarenes using D2 as the deuterium source under mild conditions. The deuteration rate at benzylic site is two orders of magnitude higher than that of bulk BaH2. This study offers an alternative synthetic route for the manufacture of deuterium-labeled compounds using a heterogenous transition metal-free hydride catalyst beyond the widely studied molecular metal complexe catalysts.

Abstract Duck infectious serositis is a septicemic disease caused by the bacterium Riemerella anatipestifer (R. anatipestifer), which affects ducks, geese, turkeys, and other poultry. While outbreaks have been reported worldwide, the exact mechanisms of infection and disease progression remain unclear. Our previous research identified the two-component system PhoPR within the genome of R. anatipestifer and demonstrated its association with the bacterium’s pathogenicity. Through multi-omics analysis, we found that PhoP directly regulates the expression of several genes, including moxR, within the Bacteroides aerotolerance (Bat) operon. However, the function of MoxR in R. anatipestifer has not yet been reported. To investigate the impact of MoxR on the expression of the bat operon and the pathogenicity of R. anatipestifer, we constructed ΔmoxR and other derivative strains. Our findings revealed that overexpression of MoxR inhibits the transcription of the bat operon. Conversely, deletion of moxR, along with exposure of R. anatipestifer to thermal or oxidative stress, results in increased transcription levels of the bat operon. By measuring the survival ability of each strain under stress, we discovered that MoxR is closely associated with the resistance of R. anatipestifer to thermal and oxidative stress by influencing the expression of the bat operon. Duckling infection experiments, along with adhesion and invasion assays, showed that deletion of moxR in R. anatipestifer led to decreased pathogenicity, and lower bacterial load in various tissues. Collectively, our findings collectively demonstrate the significant role of MoxR in the anti-stress and pathogenicity of R. anatipestifer, providing new insights into its pathogenic mechanisms.

Abstract NOD-like receptor (NLR) family proteins are implicated in various cardiovascular diseases. However, the precise role of NLRC5, the largest member of this family, in myocardial infarction (MI) remains poorly understood. This study reveals that NLRC5 is upregulated in the hearts of both patients with MI and MI mice. Silencing NLRC5 in cardiomyocytes impairs cardiac repair and functional recovery, while its overexpression enhances these processes. Furthermore, NLRC5 promotes autophagy in cardiomyocytes, and its protective effects are diminished upon autophagy inhibition. Mechanistically, NLRC5 interacts with CAVIN1, facilitating its degradation and subsequent downregulation of CAV1, which in turn increases the expression of the ATG12-ATG5 complex to stimulate autophagy. Conversely, CAV1 overexpression partially suppresses autophagy and attenuates the improvements in cardiac function observed in NLRC5-overexpressing MI hearts. This study highlights the critical regulatory role of NLRC5 in modulating cardiomyocyte autophagy flux, suggesting that NLRC5 activation may represent a promising therapeutic strategy for MI.

Highlights The layered arrangement and gradient distribution of magnetic MXene are firstly combined to improve the electromagnetic wave (EMW) RL min and broaden effective absorption bandwidth. Absorption, reflection, and transmission (A–R–T) power coefficient analysis is firstly used to guide the gradient distribution, so as to realize EMW incidence at low-concentration surface, loss at middle concentration interlayer and reflection at high-concentration bottom. The layered gradient composite (LG5-10-15) achieves complete absorption coverage of X-band at thickness of 2.00-2.20 mm with RL min of -68.67 dB.

Abstract Background and aims Short-chain fatty acids (SCFAs), key metabolites produced by gut microbiota, have neuroprotective effects in neurodegenerative diseases by modulating immune responses. However, their role in human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) remains largely unexplored. Methods We recruited HAND patients, HIV Control, and healthy controls (HC). Plasma SCFAs and SCFA-producing gut microbiota were quantified via gas chromatography-mass spectrometry and fecal metagenomic analysis. Inflammatory cytokine levels were measured using liquid chromatography. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive accuracy of SCFAs for HAND. Results Plasma SCFAs were significantly reduced in HAND patients, correlating with a decrease in SCFA-producing gut bacteria, such as Prevotella and its related species. Reduced SCFAs were positively correlated with pro-inflammatory cytokines and cognitive impairment, while being negatively correlated with anti-inflammatory cytokines. ROC curve analysis demonstrated that several SCFAs exhibited strong predictive accuracy for HAND status. Conclusions SCFAs may influence cognitive function by modulating inflammatory responses, and identifies plasma SCFAs as potential biomarkers and therapeutic targets for HAND. Further investigation is needed to delineate the mechanisms that SCFAs influence HAND pathology.

Abstract Background Metabolic syndrome (MetS) is increasingly diagnosed in individuals with normal body weight, and visceral fat emerges as a significant risk factor. However, the relationship between visceral fat area (VFA) and MetS within this population remains inadequately explored, and the diagnostic threshold for MetS in normal-weight individuals is yet to be established. Methods This study used a cross-sectional design combined with longitudinal cohort analysis. Data were collected from 5,944 normal-weight participants who underwent health screenings at Henan Provincial People’s Hospital of China between October 2018 and October 2024. VFA was measured via multislice computed tomography scanning, and VFA-based tertile categorization was applied among the participants. The relationship between VFA and MetS was examined using univariate and multivariate logistic regression analyses. Nonlinear relationship was investigated by restricted cubic spline (RCS) modeling, and diagnostic accuracy was determined by receiver operating characteristic (ROC) curve analysis. Furthermore, data from individuals who completed three or more screenings were used to construct Kaplan–Meier survival curves for MetS events, with significance tested using the log-rank method. Results Among the individuals with a normal BMI, elevated VFA was associated with a high incidence of MetS. After the adjustment for confounders, VFA was significantly associated with MetS risk [odds ratio (OR) = 1.13, 95% confidence interval (CI): 1.12–1.25]. The subjects in the highest VFA tertile showed significantly elevated MetS risk (OR = 30.33; 95% CI: 19.00–48.43, P

Abstract Chondrichthyan egg capsules, fossil and recent, have a taxonomical significance that can provide important insights into the occurrence and reproductive strategy of their producers. However, the rare occurrence of fossil capsules and their sometimes difficult identification hinder our understanding of their systematics and significance. Laffonia from the Late Jurassic of Switzerland and its probable junior synonym, Pseudocaudina, from the Late Jurassic lithographic limestones of southern Germany, have been interpreted in a variety of ways including as a fructification of a plant, a possible egg capsule of a shark or ray, a presumed holothurian, a possible actinarian, or even a ctenophore. Here, we redescribe the holotype of Laffonia, which has a fusiform body that is ornamented with over seven longitudinal ribs and two narrow striated flanges at its lateral edges. These morphological features are incompatible with a diploblast or echinoderm affinity, but highly resemble the characteristics of certain holocephalan egg capsules in several respects. Our phylogenetic analysis places Laffonia within a group containing the Carboniferous fossil capsules Crookallia and Vetacapsula, as well as recent chimaerid capsules. Thus, we suggest that the Mesozoic Laffonia represents an intermediate morphotype between the Carboniferous species and extant chimaerid capsules. Laffonia is the only known fossil chimaerid-like capsule from the Mesozoic so far, which offers novel insights into the morphology and evolution of holocephalan egg capsules.

Linjuan Xia,1 Zehua Yang,2 Qincai Mu,3 Yulin Ji,1 Juncheng Lyu4 1College of Nursing, Dali University, Dali, Yunnan, 671000, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Second People’s Hospital of Dali City, Dali, Yunnan, 671003, People’s Republic of China; 3Department of Obstetrics, The First Affiliated Hospital of Dali University, Dali, Yunnan, 671000, People’s Republic of China; 4School of Public Health, Shandong Second Medical University, Weifang, Shandong, 261053, People’s Republic of ChinaCorrespondence: Juncheng Lyu, Email cheng_china@163.comObjective: This study aimed to identify and evaluate risk factors associated with gestational diabetes mellitus (GDM) in mainland China.Methods: Eight electronic databases were searched for literature published from January 2010 until December 2023. Heterogeneity was quantified using I2. Data were pooled by fixed or random effects models and expressed as odds ratio and 95% confidence intervals.Results: A total of 69 observational studies with an overall sample size of 2,138,032 Chinese women and 219,303 patients with GDM were included in the analysis. After adjusting confounders, older maternal age (OR = 1.12, 95% CI: 1.09– 1.15), maternal age ≥ 35 years (OR = 1.96, 95% CI: 1.74– 2.21), higher pre-pregnancy body mass index (OR = 1.24, 95% CI: 1.17– 1.32), pre-pregnancy overweight (OR = 1.78, 95% CI: 1.64– 1.92) or obesity (OR 2.52, 95% CI: 2.06– 3.08), family history of diabetes (OR = 1.85, 95% CI: 1.58– 2.17), history of GDM (OR = 4.09, 95% CI: 2.13– 7.82), and elevated levels of fasting plasma glucose (OR = 2.54, 95% CI: 2.13– 3.01), hemoglobin (OR = 1.47, 95% CI: 1.14– 1.89) and serum triglycerides (OR = 1.69, 95% CI: 1.31– 2.16) in early pregnancy were associated with an increased risk of GDM in mainland China. But gravidity ≥ 2 (OR = 1.06, 95% CI: 0.89– 1.27), conception by assisted reproductive technology analyses (OR = 1.54, 95% CI: 0.95– 2.51) were not associated with GDM, and parity ≥ 1 (OR = 0.88, 95% CI: 0.82– 0.94) was related to lower risk of GDM. In available unadjusted studies, history of abortion (OR = 1.34, 95% CI: 1.31– 1.37) increased risk of GDM, non-Han ethnicity (OR = 0.78, 95% CI: 0.59– 1.03) and high school or lower education level (OR1.09, 95% CI: 0.94– 1.26) showed no correlation with GDM.Conclusion: The key risk factors for GDM in mainland China included older maternal age, maternal age ≥ 35 years, pre-pregnancy overweight or obesity, family history of diabetes, history of GDM, elevated levels of FPG, Hb, and serum TG in early pregnancy. Early identification and intervention for women at high risk should be performed to prevent the development of GDM.Keywords: gestational diabetes mellitus, risk factors, mainland China, systematic review, meta-analysis

Huayan Gu,1,&ast; Teng Zhu,2,&ast; JiaLing Ding,1 Zhi Yang,1 Shuangyi Qi,1 Guilong Guo1 1Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guilong Guo, Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Street, Wenzhou City, Zhejiang Province, People’s Republic of China, Email guoguilong@sina.comPurpose: This study efforts to explore the association of adverse events (AEs) with efficacy in HER2-positive breast cancer patients treated with TDM1.Methods and Materials: This retrospective study included women diagnosed with HER2+ BC treated with TDM1 from January 2012 to December 2023. Event-free survival (EFS) was the endpoint. Tumour response was assessed by disease control rate (DCR) and objective response rate (ORR). The chi-squared test, analysis of variance (ANOVA), Cox proportional hazards regression and Kaplan-Meier survival analysis was employed to evaluate the association of AEs with tumour efficacy.Results: A total of 48 women with a median age of 52 years (median follow-up 8.4 months) were included in the study. Among them, 33 patients (68.8%) experienced adverse events, including platelet depletion and liver function abnormalities, 3 patients (6.3%) discontinued TDM1 due to severe platelet depletion. The overall objective response rate (ORR) was 25.0% and the disease control rate (DCR) was 43.8%. Using the Chi-squared test, we found a statistically significant difference in ORR and DCR between patients who developed a platelet reduction and those who did not. DCR was significantly higher in patients with liver dysfunction than in those without. ANOVA showed that exposure to hepatic dysfunction and platelet reduction, lines of therapy, and treatment course were associated with EFS. In the Kaplan-Meier survival analysis, both liver dysfunction and platelet reduction were correlated with significantly longer EFS (p=0.033 and p=0.038, respectively).Conclusion: This retrospective study demonstrated that AEs were associated with tumour efficacy in patients with HER2+ BC treated with TDM1.Keywords: HER2-positive breast cancer, adverse events, T-DM1, tumour efficacy