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Abstract Objective Recent studies highlight the role of H-type vasculature in bone regeneration. This study, based on single-cell RNA sequencing (scRNA-seq), aims to explore the changes in H-type vasculature endothelial cells (H_ECs) in osteonecrosis of the femoral head (ONFH) and hip osteoarthritis (HOA), focusing on the death modes such as ferroptosis, pyroptosis, and parthanatos. Methods We re-analyzed the scRNA-seq data of femoral head samples publicly available in 2022. This study selected nine femoral head samples (3 each from HOA, ONFH stage 3 A, and ONFH stage 4). CD31 + EMCN + endothelial cells were classified as H_ECs. Molecular differences were assessed using Gene Ontology and KEGG analysis. Hypoxia, ferroptosis, pyroptosis, and parthanatos indices were calculated, and transcription factors were predicted using SENIC. Cell communication was analyzed with CellChat. Results After integrating the 9 samples, 14 cell types were identified: B cells, Mesenchymal stem cells, Osteoblasts, Endothelial cells, Monocytes, T cells, NK cells, Fibroblasts, Macrophages, Common myeloid progenitors, Chondrocytes, Myelocytes, Osteoclasts, and Pericytes. The number of endothelial cells and H_ECs decreased with necrosis severity. H_ECs showed higher angiogenic capacity but lower stress resistance compared to other endothelial cells. Angiogenic capacity decreased in necrotic samples, accompanied by an elevation in inflammation levels. The hypoxia index was higher, with ferroptosis increased in stage 3 A and parthanatos in stages 3 A and 4. No change was observed in pyroptosis. Cell communication analysis revealed downregulation of SLIT3-ROBO4 signaling during necrosis. Conclusion H_ECs show molecular differences compared to other endothelial cells. Ferroptosis and parthanatos contribute to the demise of H_ECs in ONFH, with pericytes and fibroblasts supporting H_EC angiogenesis.

Abstract Objective We established a prospective cohort study to investigate the differences in motor and non‐motor symptoms between idiopathic Parkinson's disease (IPD) and Parkinson's disease in carriers of leucine‐rich repeat kinase 2 (LRRK2) gene risk variants (LRRK2‐PD). Methods The study included 1407 individuals with IPD and 649 individuals with LRRK2‐PD (comprising 304 with LRRK2‐G2385R, 220 with LRRK2‐R1628P, and 105 with LRRK2‐A419V). Differences in symptoms between LRRK2‐PD and IPD were analyzed using LCMM modeling and Cox regression analysis. Results The LRRK2‐G2385R variant showed slower progression in tremor symptoms and excessive daytime sleepiness compared with IPD. In contrast, symptoms associated with LRRK2‐R1628P and LRRK2‐A419V were more similar to those of IPD. Survival analysis revealed that LRRK2‐PD does not affect life expectancy compared with IPD. Interpretation Our extended longitudinal follow‐up of LRRK2‐PD in the Chinese population provided valuable insights, further confirming the clinical characteristics of the three LRRK2 variants.

Abstract Deep vein thrombosis (DVT) is one of the important factors leading to death in patients undergoing fracture surgery. This study aims to investigating the predictive value of the Caprini score combined with thrombus molecular markers for the risk of DVT in patients after traumatic fracture surgery. A total of 342 patients who underwent surgery for traumatic fractures were included in the study. The patients were divided into two groups based on the occurrence of DVT after surgery: the DVT group (n = 57) and the non-DVT group (n = 285). A univariate analysis and logistic regression analysis were conducted on clinical factors and laboratory indicators that might be associated with DVT in patients with traumatic fractures. A predictive model for DVT risk was then constructed by combining thrombus molecular markers with the Caprini score. The median age of all patients was 65 years (54–75 years), the postoperative Caprini score was 9 (6–11), and the length of hospital stay was 11 days (8–16 days). In univariate analysis, age (P = 0.029), postoperative Caprini score (P

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

Abstract The oral-gut microbiota axis plays a crucial role in cardiometabolic health. This review explores the interactions between these microbiomes through enteric, hematogenous, and immune pathways, resulting in disruptions in microbial balance and metabolic processes. These disruptions contribute to systemic inflammation, metabolic disorders, and endothelial dysfunction, which are closely associated with cardiometabolic diseases. Understanding these interactions provides insights for innovative therapeutic strategies to prevent and manage cardiometabolic diseases.

Abstract Background Ferroptosis was involved in the pathogenesis of intervertebral disc degeneration (IVDD). However, the exact mechanism of IVDD associated with ferroptosis still required deeper studies. Method The differentially expressed genes (DEGs) in rat lumbar disc tissue between the control and IVDD group treated with IL-1β were detected by RNA sequencing (RNA-seq). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on DEGs. We further screened the differential expressed ferroptosis-related genes (DEFRGs). Besides, a protein-protein interaction (PPI) network of DEFRGs was constructed by STRING database. The Cytoscape database identified significant modules and the hub genes. The loss function of PDK4 by siRNA inference was investigated in NPCs by CCK8 assay, ELISA assay, and the analysis of ferroptosis indicators. Result DEGs were identified using RNA-seq. KEGG pathway analysis showed that these genes were mainly involved in Parkinson’s disease, oxytocin signaling pathway, calcium ion signaling pathway, AMPK signaling pathway, and glucagon signaling pathway. Eight hub genes (including LDHA, PKM, EP300, EGFR, EGLN1, SCD, PDK4, and FABP4) were found by the PPI network and Cytoscape on a total of 25 ferroptosis-related genes that were identified in rat lumbar disc tissue after IVDD treatment. PDK4 silencing promoted NPCS proliferation, decreased the levels of the proinflammatory factors, and suppressed ferroptosis. Conclusion The study suggested the potential roles of ferroptosis-related genes in IVDD and further revealed the role of PDK4 in the progression of IVDD.

Hyperspectral lidar (HSL) has high-precision geometric information and high-resolution spectral information, and its advantageous detection capability has been recognized by scientists at home and abroad. However, how to extract massive and complex HSL data effectively and accurately is an important issue in the current development of HSL. A methodological system that caters to HSL data features is required to achieve high-precision spatial–spectral integrated data interpretation. This requirement represents a significant scientific challenge, for which research on appropriate HSL waveform data processing methods remains scarce. This study aims to address the challenges posed by the massive data and complex waveform situations associated with HSL. Based on an experimental verification, the single-channel algorithm suggested in this article proves to be advantageous over Gaussian decomposition, specifically for asymmetric and overlapping echoes. This algorithm produces an average R2 increase of 0.023 and reduces the standard deviation by 63%. It also accurately extracts hidden overlapping echoes. Furthermore, this study proposes a multi-channel-assisted optimization algorithm that can precisely extract faint and overlapping echoes that a single-channel algorithm cannot extract. Its accuracy is remarkably high, with the ranging accuracy boosted by 98% compared with that of the single-channel algorithm.

Abstract Background Recent phase III randomized controlled trials have demonstrated that first-line immune checkpoint inhibitors (ICIs) improve prognosis in advanced HER-2-negative gastric cancer patients with programmed death ligand 1 (PD-L1) combined positive score (CPS) higher than 5. However, these findings are not confirmed in real-world settings, and the benefits in PD-L1 CPS

Abstract Background This study aimed to investigate the potential utility of Epithelial-mesenchymal transition (EMT) signaling cell detection in the early diagnosis of cervical lesions. Methods Enrichment of cervical epithelial cells was carried out using a calibrated membrane with 8-μm diameter pores. RNA-in situ hybridization (RNA-ISH) was employed to detect and characterize EMT cells utilizing specific EMT markers. Results EMT cells were successfully identified in cervical samples, while none were detected in the healthy control group. Meanwhile, the number of EMT cells is not correlated with either the presence or type of HPV infection. Comparison of diagnostic tests showed the area under the curve (AUC) for HPV DNA tests, Thinprep cytologic tests (TCT), colposcopy and EMT signaling tests to be 0.758, 0.800, 0.889 and 0.992, respectively. A higher detection rate of EMT cells was observed in patients with cervical lesions aged ≥ 45 compared to those aged

Abstract Reflector antenna has been widely used in deep space exploration, radar warning, and other fields, all of which requires high pointing accuracy. The antenna elevation bearings are the key component that guarantees its pointing accuracy, while any degradation or fault can seriously affect the antenna’s performance, leading to deviations in antenna pointing and instability during operation. However, the relationship between the antenna elevation bearing fault and its pointing accuracy remains unclear because there is insufficient experimental faulty transmission data and pointing error collected from the test-rig simultaneously. Therefore, this paper aims to establish a deep learning model-based relationship to reveal the underlying relationship between the antenna transmission faults and its pointing accuracy. By linking the two, transmission faults in key components can serve as a substitute for pointing accuracy as one of the criteria for antenna maintenance decisions, vibration signals, serving as a basis for fault diagnosis, can be collected and processed in real-time without the need for equipment shutdowns, undoubtedly bringing convenience to antenna maintenance providing a theoretical basis for the development of antenna maintenance strategies. In order to overcome the problem of insufficient data, this paper has established an antenna elevation system dynamic simulation model containing pre-defined transmission faults. Furthermore, to link antenna fault diagnosis with antenna pointing errors, a mathematical model for antenna axis error analysis has been established. Finally, labeled fault data and antenna pointing errors have been put into the deep neural network model for training to obtain the prediction model for predicting antenna axis error. The results showed that faults in the key transmission components have a significant impact on antenna pointing errors and the proposed deep neural network learning model exhibits a high predictive accuracy.

Abstract The recent worldwide outbreaks of mpox prioritize the development of a safe and effective mRNA vaccine. The contemporary mpox virus (MPXV) exhibits changing virological and epidemiological features, notably affecting populations already vulnerable to human immunodeficiency virus (HIV). Herein, we profile the immunogenicity of AR-MPXV5, a penta-component mRNA vaccine targeting five specific proteins (M1R, E8L, A29L, A35R, and B6R) from the representative contemporary MPXV clade II strain, in both naive and simian immunodeficiency virus (SIV)-infected nonhuman primates. Immunization with two doses of AR-MPXV5 to cynomolgus macaques effectively elicits antibody responses and cellular responses. Importantly, based on the challenge model with a contemporary MPXV clade II strain, AR-MPXV5 demonstrates effective efficacy in preventing skin lesions, eliminating viremia and reducing viral loads in multiple tissues after challenge in naive male animals. More importantly, AR-MPXV5 is well-tolerated in stable chronic SIV-infected rhesus monkeys, while eliciting comparable MPXV-specific humoral and cellular responses in both naive and SIV-infected monkeys. Together, these results support further clinical development of the AR-MPXV5 vaccine.

Abstract Background Successful engraftment and localization of mesenchymal stem cells (MSCs) within target tissues are critical factors influencing their therapeutic efficacy for tissue repair and regeneration. However, the relative contributions of biophysical factors like cell size and adhesion capacity in regulating MSC distribution in vivo remain incompletely understood. Methods Cell adhesion peptides and hanging drop method were used to modify the adhesive capacity and size of MSCs. To quantitatively track the real-time biodistribution of transplanted MSCs with defined size and adhesion profiles in living mice and rats, the non-invasive positron emission tomography (PET) imaging was applied. Results Surface modification with integrin binding peptides like RGD, GFOGER, and HAVDI reduced MSC adhesion capacity in vitro by up to 43.5% without altering cell size, but did not significantly decrease lung entrapment in vivo. In contrast, culturing MSCs as 3D spheroids for 48 h reduced their cell diameter by 34.6% and markedly enhanced their ability to pass through the lungs and migrate to other organs like the liver after intravenous administration. This size-dependent effect on MSC distribution was more pronounced in rats compared to mice, likely due to differences in pulmonary microvessel diameters between species. Conclusion Our findings reveal that cell size is a predominant biophysical regulator of MSC localization in vivo compared to adhesion capacity, providing crucial insights to guide optimization of MSC delivery strategies for enhanced therapeutic efficacy. Graphical abstract

Abstract Core occupational adaptability (COA) is a crucial occupational competency and workplace competitiveness for employees. This study identified significant antecedent variables that impact COA and constructed a structural equation model to test the relationships among these variables. A questionnaire survey was administered to 519 employees from Chinese manufacturing enterprises to validate the model. The results revealed that perceived organizational support (POS), proactive personality (PP), and career-related continuous learning (CCL) positively predicted an employee’s COA. PP and POS indirectly predicted COA through the mediating role of CCL, respectively. Moreover, employees’ age moderated the direct effect between PP and COA positively, while employees’ positions positively moderated the direct effect between POS and COA. This study demonstrated that CCL is critical in enhancing employee initiative, providing organizational support, promoting vocational learning, and improving overall COA levels among employees.

Abstract This research suggests a methodology to examine the effectiveness Artificial Intelligence (AI) on the cognitive abilities of college students so that future researchers can utilize this experimental project to focus on how AI-powered Intelligent Tutoring Systems (ITSs) affect learning outcomes. As AI continues to revolutionize all walks of life, so has its integration with education. ITS is a key application of AI in education, providing a personalized learning experience by analyzing student data and tailoring instructional materials accordingly. This provides a research program to study the effectiveness of ITS in improving cognitive skills such as memory, critical thinking, and problem solving abilities in college students. The research project combined quantitative and qualitative research methods including surveys, pre-tests, post-tests, and in-depth interviews to assess the cognitive differences between students using ITS and those using traditional learning methods. The research project also recognized potential challenges, such as dependence on technology and the risk of increased educational inequality. The action research program concluded by advocating for a balanced integration of AI into education, highlighting the need for ongoing research to optimize its use across different stages of education and to ensure equitable access to AI-powered tools.

Abstract Objective: This study aims to examine the associations between various dimensions of social support and sleep quality in a hospital psychiatric outpatient population using canonical correlation analysis, while also investigating the potential mediating roles of anxiety and depressive symptoms. Methods: Employing a cross-sectional design, survey data were collected from 10,071 individuals visiting Hangzhou Seventh People’s Hospital between October 2020 and October 2023. After excluding invalid cases, a total of 10,063 participants were included for analysis. The survey encompassed gathering basic demographic information as well as administering the Social Support Rating Scale, Self-rating Depression Scale, Self-rating Anxiety Scale, and Pittsburgh Sleep Quality Index Scale. Data analysis was conducted using SPSS 27.0 statistical software with canonical correlation analysis employed to examine the relationships. Additionally, the mediating effects of anxiety and depression symptoms were examined using the SPSS PROCESS macro. Results: Canonical correlation analysis reveals a significant positive correlation between social support dimensions and various aspects of sleep quality. The first pair of canonical variables (r = 0.586, p

The blind box market is fast-growing, from toys, baseball cards, and vibrant second-hand products to the recent growing tourism market, becoming the latest trend sweeping through China, not only in offline retailing but also online businesses and e-commerce. For young consumers, the element of mystery is a big part of the fun that not everyone can obtain the most special and desirable products. The present research aims to elucidate how travel blind boxes attract young consumers in terms of their psychological connections to travel destinations. In particular, building upon psychological distance theory, this study examines the relationship between perceived similarities between travel destinations and hometowns and the attraction of travel blind boxes. Contributing to the existing literature that mainly describes the phenomenon of the blind box craze but often fails to identify its underlying mechanisms, the present study advances our understanding of such trendy marketing practices by investigating the mediating role of the “aha moment” and the boundary conditions of electronic word-of-mouth recommendations and price sensitivity.

AIM: To evaluate the efficacy and safety of the intravitreal dexamethasone implant in naive and refractory patients with diabetic macular edema (DME). METHODS: PubMed, Embase, Web of Science, and Medline databases were searched. The main outcomes were best-corrected visual acuity (BCVA) and central retinal thickness (CRT). The secondary outcomes included mean number of injections, intraoperative or postoperative complications including intraocular pressure (IOP) elevation and cataract. RESULTS: Ten comparative studies involving a total of 1000 DME eyes including 402 naive eyes and 598 refractory eyes were selected. The postoperative BCVA in the naive group was significantly better than in the refractory group [mean difference (MD) -0.11, 95% confidence interval (CI) -0.17 to -0.05, P=0.0003; MD 8.69, 95%CI 5.08 to 12.30, P

Abstract Background The tertiary lymphoid structures (TLSs) have an immunomodulatory function and have a positive impact on the survival outcomes of patients with oral squamous cell carcinoma (OSCC). However, there is a lack of standard approaches for quantifying TLSs and prognostic models using TLS-related genes (TLSRGs). These limitations limit the widespread use of TLSs in clinical practice. Methods A convolutional neural network was used to automatically detect and quantify TLSs in HE-stained whole slide images. By employing bioinformatics and diverse statistical methods, this research created a prognostic model using TCGA cohorts and explored the connection between this model and immune infiltration. The expression levels of three TLSRGs in clinical specimens were detected by immunohistochemistry. To facilitate the assessment of individual prognostic outcomes, we further constructed a nomogram based on the risk score and other clinical factors. Results TLSs were found to be an independent predictor of both overall survival (OS) and disease-free survival in OSCC patients. A larger proportion of the TLS area represented a better prognosis. After analysis, we identified 69 differentially expressed TLSRGs and selected three pivotal TLSRGs to construct the risk score model. This model emerged as a standalone predictor for OS and exhibited close associations with CD4 + T cells, CD8 + T cells, and macrophages. Immunohistochemistry revealed high expression levels of CCR7 and CXCR5 in TLS + OSCC samples, while CD86 was highly expressed in TLS- OSCC samples. The nomogram demonstrates excellent predictive ability for overall survival in OSCC patients. Conclusions This is the first prognostic nomogram based on TLSRGs, that can effectively predict survival outcomes and contribute to individual treatment strategies for OSCC patients.

Abstract While some literature has provided limited information about the potential cardiovascular risk and immune-related adverse events (irAEs) risk associated with PD-1/PD-L1 inhibitors in the treatment of Head and Neck Squamous Cell Carcinoma (HNSCC), the exact relevance is still uncertain. To assess the pharmacovigilance (PV), constituent ratio, severity, and reaction outcomes of major adverse cardiovascular events (MACE) and immune-related adverse events (irAEs) related to PD-1/PD-L1 inhibitors for HNSCC reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS). We analyzed reports of cardiovascular adverse events and irAEs associated with drug therapy for HNSCC submitted to FAERS from the 1st quarter 2015 to the 3rd quarter of 2023. Three PD-1/PD-L1 inhibitors were identified: nivolumab, pembrolizumab and durvalumab. Our primary composite endpoint was the PV of MACE and irAEs related to PD-1/PD-L1 inhibitors in the treatment of HNSCC, and the secondary endpoint was PV of other cardiovascular events. The software implemented was STATA 17.0 MP. 19,372 suspected drug-adverse event reports related to drug treatment in patients with HNSCC were identified, of which 916 reports were cardiovascular events, including 555 reports of MACE and 361 reports of other cardiovascular events. The PV signal regarding MACE was detected in durvalumab (PRR = 2.12, 95% CI: 1.24–3.61; χ2 = 7.71; ROR = 2.19, 95% CI: 1.24–3.86; IC = 1.01; IC025 = 0.07) but not in nivolumab and pembrolizumab. The constituent ratio of MACE in all adverse events caused by nivolumab (OR = 0.38, 95% CI: 0.19–0.73) and pembrolizumab (OR = 0.48, 95% CI: 0.23–0.99) was significantly decreased, compared with durvalumab. A PV signal about other cardiovascular events was detected in durvalumab (PRR = 3.04, 95% CI: 1.73–5.31; χ2 = 16.13; ROR = 3.15, 95% CI: 1.74–5.70; IC = 1.46; IC025 = 0.48), but it was not detected in nivolumab or pembrolizumab. The constituent ratio of other cardiovascular events in all adverse events caused by nivolumab (OR = 0.25, 95% CI: 0.13–0.48) and pembrolizumab (OR = 0.40, 95% CI: 0.20–0.80) was significantly decreased, compared with durvalumab. The constituent ratio of other cardiovascular events in all adverse events caused by nivolumab (OR = 0.61, 95% CI: 0.38–0.99) was significantly decreased, compared with pembrolizumab. There were 40 cases of hypertension. A PV signal about hypertension was detected in pembrolizumab (PRR = 3.72, 95% CI: 1.87–7.43; χ2 = 15.99; ROR = 3.75, 95% CI: 1.87–7.51; IC = 1.53, IC025 = 0.45), but it was not detected in nivolumab. The constituent ratio of hypertension in all adverse events caused by nivolumab (OR = 0.09, 95% CI: 0.09–0.39) was significantly decreased, compared with pembrolizumab. There were 737 cases of irAEs. A PV signal about irAEs was detected in nivolumab (PPR = 1.27, 95% CI: 1.05–1.53; χ2 = 6.38; ROR = 1.28, 95% CI: 1.06–1.56; IC = 0.29, IC025 = −0.00) and pembrolizumab (PPR = 2.20, 95% CI: 1.79–2.71; χ2 = 56.55; ROR = 2.31, 95% CI: 1.84–2.88; IC = 1.03; IC025 = 0.68), but it was not detected in durvalumab. The constituent ratio of irAEs in all adverse events caused by nivolumab (OR = 0.58, 95% CI: 0.44–0.76) significantly decreased, compared with pembrolizumab. By comparing the PV signals, constituent ratio, severity, and reaction outcome of the three drugs, we suppose that nivolumab can be used as the safest PD-1/PD-L1 inhibitor for HNSCC.

Abstract Ulcerative colitis (UC) is a debilitating inflammatory bowel disease characterized by intestinal inflammation, barrier dysfunction, and dysbiosis, with limited treatment options available. This study systematically investigates the therapeutic potential of a synbiotic composed of galactooligosaccharides (GOS) and Limosilactobacillus reuteri in a murine model of colitis, revealing that GOS and L. reuteri synergistically protect against intestinal inflammation and barrier dysfunction by promoting the synthesis of pentadecanoic acid, an odd-chain fatty acid, from Bacteroides acidifaciens. Notably, the synbiotic, B. acidifaciens, and pentadecanoic acid are each capable of suppressing intestinal inflammation and enhancing tight junction by inhibiting NF-κB activation. Furthermore, similar reduction in B. acidifaciens and pentadecanoic acid levels are also observed in the feces from both human UC patients and lipopolysaccharide-induced intestinal inflammation in pigs. Our findings elucidate the protective mechanism of the synbiotic and highlight its therapeutic potential, along with B. acidifaciens and pentadecanoic acid, for UC and other intestinal inflammatory disorders.

Natural polysaccharides named PEP-0.1-1, PEP-0-1 and PEP-0-2 from edible mushroom species Pleurotus eryngii were obtained in the present study. Results showed that molecular weights of these polysaccharides were 3235, 2041 and 23933 Da, respectively. Further, structural characterization revealed that PEP-0.1-1 had a →4-α-D-Glcp-1→ backbone and contained →4)-α-D-Glcp and →4)-β-D-Glcp reducing end groups. PEP-0-1 backbone contained→4-α-D-Glcp-1→ and →6-α-3-O-Me-D-Galp-1→, and the side chains contained α-D-Glcp, β-D-Manp-1→ and α-D-Glcp-3→. However, PEP-0-2 backbone consisted of →4-α-DGlcp-1→ and →6-α-3-O-Me-D-Galp-(1→6)-α-D-Galp-1→ while the side chains contained α-D-Glcp and β-D-Manp-1→. Biological activity analysis was then carried out and found that all these polysaccharides could significantly suppress the relative mRNA expression of toll-like receptor 4, nitric oxide (NO), tumor necrosis factor-α, interleukin (IL)-1β and IL-6 in lipopolysaccharide (LPS)-induced inflammation of RAW264.7 cells, as well as the over secretion of the above cell cytokines. Moreover, Western blotting analysis revealed that all these purified fractions displayed significant inhibition effects on the expression of c-Jun N-terminal kinases protein induced by LPS in mitogen activated protein kinase pathway, along with the relieving on the inhibition effect of LPS on IκB-α protein expression. In summary, the information generated by the present study could provide a theoretical basis for the exploration of novel healthy food materials from edible mushroom with antiinflammation activities.

Check dams are widely used throughout the world to tackle soil and water loss. However, the frequency of extreme rainfall events has increased owing to global climate change and the main structure of check dam is gradually aging, which lead to an increase in the failure risk of check dams. Thus, it is necessary to carry out the study on failure risk diagnosis and assessment of check dams. In the study, machine learning algorithms (ML), including random forests (RF), support vector machine (SVM), and logistic regression (LR), were used to integrate the environmental and engineering factors and then assess the risk of check dam failure due to the “7.26” rainstorm on July 26, 2017, in the Chabagou watershed, located in the hilly-gully region of the Loess Plateau, China. To verify the generalizability of the model in this study, these models were used for the Wangmaogou catchment north of the Loess Plateau. The accuracy assessment by the receiver operating characteristic (ROC) curve indicated that the RF model with an area under the ROC curve (AUC) greater than 0.89 was the most precise model and had a higher generalization ability. In addition, the model dataset was relatively small and easy to obtain, which make the risk modeling of check dam failure in the study has the potential for application in other regions. In the RF model, each factor selected was confirmed to be important, and the importance values for engineering factors were generally higher than those for the environmental factors. The risk map of check dam failure in the RF model indicated that 56.34% of check dams in the study area had very high and high risks of dam failure under high-intensity rainfall in 2017. Based on the importance of factors and the risk map of check dam failure, the prevention and control measures for reducing the risk of check dam failure and promoting the construction of check dam are proposed. These proposals provide a scientific basis for the reinforcement of check dams and the future layout of check dams in the Chinese Loess Plateau.

Abstract Purpose This study utilizes a meta-analytic approach to investigate the effects of cryoablation and robot-assisted partial nephrectomy on perioperative outcomes, postoperative renal function, and oncological results in patients. Methods This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Four electronic databases (PubMed, Embase, Web of Science, and the Cochrane Library database) were systematically searched to identify relevant studies published in English up to November 2023. The primary outcomes were perioperative results, complications, postoperative renal function and oncologic outcomes. Review Manager 5.4 was used for this analysis. Results This study included a total of 10 studies comprising 2,011 patients. Compared to RAPN (Robot-Assisted Partial Nephrectomy), the CA (Cryoablation) group had a shorter hospital stay [MD -1.76 days; 95% CI -3.12 to -0.41; p = 0.01], less blood loss [MD -104.60 ml; 95% CI -152.58 to -56.62; p

Abstract An S‐band near‐field focused array is designed and implemented. Consisting of 4 × 4 metallic Vivaldi elements, the array is designed for focusing the E‐field of several kilovolts per metre within its near‐field region. To minimise the power loss and enhance the synthesis effectiveness, elements are arranged on a sphere surface and oriented towards the sphere centre. When exciting the elements, the waves will be focused to a specific area on the observation plane. By adjusting the excitation phase, the focus position can be tuned. A systematic analysis has been carried out to illustrate the focus scanning process across the entire observation plane. Near‐field two‐dimensional scanning is performed to measure the E‐field distribution of the array. While scanning the focus, the diameter of 3 dB focal area is about 0.3 m, and the maximum field strength in the focus ranges from 1184 to 2129 V/m, which can be used for the radiated susceptibility testing.

Abstract African swine fever (ASF) is a highly fatal hemorrhagic disease affecting domestic pigs caused by African swine fever virus (ASFV). Genetic analysis of ASFV isolates to date has identified 24 geographically related genotypes with various subgroups, but only genotype I and II ASFVs have been reported outside Africa. ASFV genotype II and genotype I viruses were reported in China in 2018 and 2021, respectively. In this study, unique and highly conserved noncoding regions were found between MGF_505-9R and MGF_505-10R in the 188 genomes of ASFV genotypes I and II. A pair of primers was designed on the basis of this region. By optimizing the reaction system and conditions, a SYBR Green I fluorescence PCR assay that can distinguish between ASFV genotypes I and II was established, and the sensitivity, reproducibility and specificity were evaluated. The detection limit was 1 TCID50/0.1 mL for both genotypes, with no cross-reactivity observed with other common pig pathogens. The intra- and interbatch variation coefficients were both less than 1.2%. Clinical sample detection analysis revealed 47 positive cases out of 100, including 3 for genotype I and 44 for genotype II, aligning with results from the WOAH-recommended and national standard methods. The method developed in this study allows for the differentiation of ASFV genotypes I and II without the need for genome sequencing, offering a convenient and rapid approach for ASFV detection and genotype identification.

Precise classification of Light Detection and Ranging (LiDAR) point cloud is a fundamental process in various applications, such as land cover mapping, forestry management, and autonomous driving. Due to the lack of spectral information, the existing research on single wavelength LiDAR classification is limited. Spectral information from images could address this limitation, but data fusion suffers from varying illumination conditions and the registration problem. A novel multispectral LiDAR successfully obtains spatial and spectral information as a brand-new data type, namely, multispectral point cloud, thereby improving classification performance. However, spatial and spectral information of multispectral LiDAR has been processed separately in previous studies, thereby possibly limiting the classification performance of multispectral LiDAR. To explore the potential of this new data type, the current spatial–spectral classification framework for multispectral LiDAR that includes four steps: (1) neighborhood selection, (2) feature extraction and selection, (3) classification, and (4) label smoothing. Three novel highlights were proposed in this spatial – spectral classification framework. (1) We improved the popular eigen entropy-based neighborhood selection by spectral angle match to extract a more precise neighborhood. (2) We evaluated the importance of geometric and spectral features to compare their contributions and selected the most important features to reduce feature redundancy. (3) We conducted spatial label smoothing by a conditional random field, accounting for the spatial and spectral information of the neighborhood points. The proposed method demonstrated by a multispectral LiDAR with three channels: 466 nm (blue), 527 nm (green), and 628 nm (red). Experimental results demonstrate the effectiveness of the proposed spatial – spectral classification framework. Moreover, this research takes advantages of the complementation of spatial and spectral information, which could benefit more precise neighborhood selection, more effective features, and satisfactory refinement of classification result. Finally, this study could serve as an inspiration for future efficient spatial–spectral process for multispectral point cloud.

BackgroundCardiovascular Disease (CVD) is the leading cause of global mortality, with its incidence rate rising year by year due to the prevalence of metabolic diseases. Existing primary and secondary prevention strategies for cardiovascular disease have limitations in identifying some high-risk groups, and 1.5-level prevention aims to achieve more precise intervention by early identification of subclinical target organ damage. This study introduces oral (tongue coating) microbiota as metabolic markers for the first time, in combination with multiple metabolic factors, to explore their potential in assessing subclinical target organ damage and optimizing cardiovascular risk stratification, in order to provide a new path for the early identification and intervention of CVD.MethodsThis study is a prospective cohort study aimed at assessing the association between tongue coating microbiota characteristics and multiple metabolic factors with subclinical target organ damage, and identifying high-risk groups suitable for cardiovascular 1.5-level prevention. The study will be conducted in Suzhou City, Jiangsu Province, China, planning to include 5000-6000 eligible subjects, with inclusion criteria of age ≥18 years, excluding individuals with a history of CVD and other serious diseases. Baseline assessment includes demographic information, lifestyle (including dietary patterns), medical history, physical examination, and collection of tongue coating microbiota samples. Subjects will be followed up every 2 years, with the primary outcome being the first occurrence of coronary heart disease and stroke, and the secondary outcome being subclinical target organ damage.DiscussionThis study focuses on cardiovascular 1.5-level prevention strategy, combining metabolic factors with tongue coating microbiota characteristics, aiming to optimize the risk assessment system for subclinical target organ damage. This approach can not only fill the gap in traditional risk assessment but also provide new ideas for the early identification and intervention of CVD. In the future, the feasibility and effectiveness of this strategy will be verified through multicenter studies, and it is expected to be promoted to a wider medical system, significantly improving the health management level of high-risk groups for CVD.Trial registration numberhttp://itmctr.ccebtcm.org.cn, identifier ITMCTR2024000616.

Perceiving facial expressions plays a crucial role in face-to-face social interactions. A wealth of studies has revealed the unconscious processing of emotional stimuli, including facial expressions. However, the relationship between the unconscious processing of happy faces and socially oriented personality traits—such as extraversion and prosocial tendency—remains largely unexplored. By pairing backward-masked faces with supraliminally presented faces in both visual fields, we found that the discrimination of visible emotional faces was modulated by the facial expressions of the invisible faces in the opposite visual field. The emotionally consistent condition showed a shorter reaction time (Exp 1) or higher accuracy (Exp 2) than the inconsistent condition. Moreover, the unconscious processing of happy faces was positively correlated with prosocial tendency but not with extraversion personality. These findings shed new light on the adaptive functions of unconscious emotional face processing, and highlight the importance of future investigations into the unconscious processing of extrafoveal happy expression.

Abstract The left ventricular trabecular fractal dimension (LVTFD) derived from cardiac magnetic resonance reflects myocardial trabecular complexity, which is associated with cardiovascular disease risk. Baseline risk stratification of cancer therapy–related cardiac dysfunction (CTRCD) in patients with breast cancer who received anthracycline is a very important clinical issue. In this study, we used the Cox model to derive and validate a new score system based on LVTFD for baseline risk stratification of CTRCD in breast cancer patients receiving anthracycline. We also compare the performance of LVTFD‐based score with the Heart Failure Association‐International Cardio‐Oncology Society (HFA‐ICOS) score using C‐index. This study enrolled 370 participants, of whom 73 participants developed CTRCD. The C‐indices of LVTFD‐based score integrating age, hypertension, previous cardiovascular disease, and maximal apical fractal dimension were higher than those of HFA‐ICOS score for stratifying CTRCD (0.834 vs. 0.642 and 0.834 vs. 0.633, respectively, in derivation and validation cohort). LVTFD‐based score can stratify the CTRCD risk, but HFA‐ICOS score cannot. The above results reveal that the LVTFD‐based score is an alternative method for baseline risk stratification of CTRCD in breast cancer who received anthracycline.

A convenient but efficient tool for evaluating dietary intakes in Chinese professional athletes has yet to be established. The aim of this study was to assess the validity of a short semi-quantitative food frequency questionnaire (FFQ) through comparison with 3-day weighed food records (3DWFRs) and corresponding serum biomarkers from a cohort of 102 professional athletes, while also evaluating its reproducibility. The relative validity was assessed using Spearman correlation coefficients, cross-quintiles classification, weighted kappa, and Bland-Altman analysis, while reproducibility was evaluated using the Spearman correlation coefficients and intraclass correlation coefficient (ICC) between two FFQs. The results showed the median (range) crude correlation coefficients (CCs) between the first FFQ and 3DWFRs for energy and nutrients, and the food groups were 0.331 (0.219 to 0.568) and 0.292 (-0.035 to 0.455), respectively. Omega-3 polyunsaturated fatty acid (EPA, DHA, and EPA+DHA) intake estimated from the FFQ significantly correlated with corresponding serum biomarkers, with CCs ranging from 0.389 to 0.520. Weighted kappa statistics, indicating acceptable consistency (> 0.2) for most items, varied from -0.076 to 0.581, except for vitamin C, vegetables, and oils. Misclassification of nutrients and food groups into extreme quartiles was rare, with a median misclassification rate of 2% (ranging from 1% to 12%) and 3% (ranging 0 to 10%), respectively. Bland-Altman analysis revealed good agreement between FFQ and 3DWFRs, with over 90% of data points falling within the limits of agreement (LOA) for all assessed nutrients and food groups. In the reproducibility analysis, the median (range) crude CC and ICC for energy and nutrients were 0.574 (0.423 to 0.643) and 0.668 (0.558 to 0.763), respectively, while for food groups, they were 0.681 (0.242 to 0.764) and 0.640 (0.371 to 0.787), respectively. In conclusion, the short FFQ demonstrated acceptable relative validity and reproducibility for most nutrients and food groups, suggesting its potential as a valuable tool for assessing dietary intake and nutrition status among young Chinese athletes.

Background: Low-dose (LD) or intermediate-dose (MD) immune tolerance induction (ITI) is effective in children with severe hemophilia A (SHA) with high-titer inhibitors (HTIs) and is attractive in countries with economic constraints. However, high-quality evidence of their use is lacking. Objectives: This was a multicenter randomized clinical trial comparing the efficacy, safety, and medication cost between LD-ITI and MD-ITI for SHA-HTI children. Methods: Children with SHA aged 24 months (median, 26.9; range, 24.0-29.5 months). The 2 groups had similar baseline clinical characteristics and similar success rates (93.8% [MD-ITI] vs 86.7% [LD-ITI]). Compared with LD-ITI, MD-ITI patients took a shorter median time to success (4.2 months vs 10.1 months) and partial success (2.7 months vs 6.6 months) and had lower mean rates for all bleeding (0.38/mo vs 1.40/mo) and joint bleeding (0.11/mo vs 0.83/mo). Between the 2 groups, although the MD-ITI group had higher rFVIII consumption (12,775 vs 7680 IU/kg), their total medication costs to success were similar (3626.49 vs 3240.38 US$/kg). Conclusion: For SHA-HTI children, the success rate and cost for MD-ITI and LD-ITI regimens were similar. MD-ITI regimen would be a priority for regions with economic constraints, considering the shorter time to success, better bleeding control, and no increase in medication cost.

BackgroundVascular calcification (VC) commonly occurs in diabetes and is associated with cardiovascular disease incidence and mortality. Currently, there is no drug treatment for VC. The Danlian-Tongmai formula (DLTM) is a traditional Chinese medicine (TCM) prescription used for diabetic VC (DVC), but its mechanisms of action remain unclear. This study aims to elucidate the effects of DLTM on DVC and explore the underlying mechanisms of action.MethodsUltra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to identify the metabolites of DLTM. A DVC rat model was established using streptozotocin (STZ) combined with vitamin D3 (VitD3). The effects of DLTM on DVC were evaluated through alizarin red staining, calcium deposition, and changes in osteogenic and contractile markers. The specific molecular mechanism of DLTM in treating diabetic VC was comprehensively analyzed by transcriptomics, molecular docking and in vivo experimental verification.ResultsWe identified 108 major metabolites of DLTM. In vivo, high-dose DLTM significantly alleviated VC in diabetic rats. Transcriptomic analysis showed that DLTM treatment markedly altered the transcriptomic profile of rat aortas, which was associated with regulating the CCN3/NOTCH signaling pathway, promoting vascular smooth muscle contraction, and inhibiting the inflammatory responses. Molecular docking and molecular dynamics simulation demonstrated strong binding interactions between DLTM metabolites and key molecules within the CCN3/NOTCH pathway, including NOTCH1, DLL1, DLL4, hes1, and hey1. In vivo experiments confirmed that DLTM could upregulate CCN3, inhibit the activation of NOTCH signaling ligands DLL1 and downstream transcription factors hes1 and hey1, and reduce the release of inflammatory cytokines IL6, IL1β, and TNFα.ConclusionDLTM alleviates DVC by regulating the CCN3/NOTCH signaling axis to inhibit inflammatory responses. Our research provides experimental basis for clinical treatment and drug transformation of diabetic VC.

Objective: Cardiovascular diseases (CVDs) and cancer are significant global causes of mortality. However, the link between diets that promote inflammation and various subtypes of CVDs and cancers remains unclear. Methods: Utilizing the dataset from the 2017–2018 National Health and Nutrition Examination Survey (NHANES) data release cycle, our study encompassed 3538 adult participants within the age range of 20 to 80 years. The dietary questionnaire information was utilized to calculate dietary inflammatory index (DII) scores. Logistic regression analysis was employed to validate the association between the DII and CVDs, as well as overall cancer and special type cancer. Mediation analysis was conducted to evaluate the relationship between DII and the aforementioned diseases, with hemoglobin serving as the potential mediator. Mendelian randomization (MR) analysis externally validated hemoglobin's causal link to these diseases. Results: Patients with the highest quartile levels of DII scores demonstrated an elevated prevalence of congestive heart failure (CHF), stroke, overall cancer and some specific types of cancers. The logistic regression analysis revealed a correlation between DII and CHF (OR = 1.197, p = 0.002), stroke (OR = 1.205, p

Triboelectric nanogenerators (TENGs) have attracted great attention due to the simple manufacturing process, low cost, and diverse forms of energy harvesting. However, the energy collected by individual TENG is relatively limited, making it necessary to develop new method to enhance the energy harvesting capability of TENG. Here, we design a hybridized TENG that integrates a droplet-driven TENG and a wind-driven TENG, which exhibits excellent electrical performance. Under the simulated environment of medium rain with medium breeze, the hybridized TENG generates an output voltage of 95.10 V, a maximum average power of 18.15 μW, an energy of 181.54 μJ in 10 s, and charges a 1 μF capacitor to 43.29 V in 120 s. This work enables the harvesting of dispersed wind and droplet energy from the environment, providing new ideas and possibilities for online monitoring in remote areas and the construction of Internet of Things systems.

IntroductionNon-suicidal self-injury is a serious health problem among adolescents. However, the association between parent–child conflict and adolescent non-suicidal self-injury and its underlying mechanisms have not been studied sufficiently. Based on the interpersonal model of non-suicidal self-injury, we tested the relationship between parent–child conflict and adolescent non-suicidal self-injury. Furthermore, based on self-determination theory and the diathesis-stress model, we examined whether psychological needs satisfaction mediated the link between parent–child conflict and adolescent non-suicidal self-injury, and if impulsivity moderated this mediating effect.MethodsUsing cross-sectional design, we recruited 656 adolescents (Mage = 13.43; 47% female) from two junior high schools in the Hubei province of China.ResultsThe results indicated a positive association between parent–child conflict and adolescent non-suicidal self-injury. Psychological needs satisfaction mediated the relationship between parent–child conflict and adolescent non-suicidal self-injury. High impulsivity strengthened the indirect effect of parent–child conflict on adolescent non-suicidal self-injury. Specifically, high impulsivity strengthened the direct relationship between psychological needs satisfaction and adolescent non-suicidal self-injury and further strengthened the indirect association between parent–child conflict and adolescent non-suicidal self-injury.ConclusionsOur findings highlight the potential mechanisms underlining the relationship between parent–child conflict and adolescent non-suicidal self-injury. Our findings can inspire educational practitioners to focus on the interaction of family risk factors and individual risk factors when developing intervention programs for adolescent non-suicidal self-injury.

BackgroundThis study aims to investigate adverse drug reaction signals associated with coagulopathies through data mining using the Adverse Event Reporting System (FAERS) of the US Food and Drug Administration. Prompt identification of high-risk drugs provides a valuable basis for enhancing clinical drug safety.MethodsThe adverse event reports related to coagulopathies from Q1 2004 to Q2 2024 were extracted from the ASCII data packages in FAERS. The reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN) were used to identify adverse drug reaction signals associated with coagulopathies.ResultsDuring the reporting period, 40,545 reports were retrieved, with a slightly higher proportion of females than males. Among the top 30 drugs associated with the occurrence of coagulopathies, 24 drugs exhibited positive signals in risk analysis. Based on the individual drug reporting odds ratio (95% confidence interval) as a measure of risk signal strength, the top five drugs are as follows: gemcitabine [ROR (95% CI):16.87 (15.83–17.98)], busulfan [ROR (95% CI):15.51 (13.69–17.58)], anti-thymocyte globulin [ROR (95% CI):15.49 (13.49–17.78)], tacrolimus [ROR (95% CI):12.7 (11.57–13.95)], etonogestrel and ethinylestradiol vaginal ring [ROR (95% CI):11.88 (10.95–12.89)]. After categorizing the drugs, the strongest risk signal is sex hormones and modulators of the genital system [ROR (95% CI):11.88 (10.95–12.89)], followed by analgesics [ROR (95%CI): 6.73 (6.38–7.1)], immunosuppressants [ROR (95% CI):3.91 (3.76–4.05)], antineoplastic agents [ROR (95% CI):3.33 (3.22–3.45)], corticosteroids for systemic use [ROR (95% CI): 2.94 (2.73–3.18)], antiepileptics [ROR (95% CI):1.93 (1.71–2.18)], drugs used in diabetes [ROR (95% CI):1.5 (1.34–1.67)], antibacterials for systemic use [ROR (95% CI):1.46 (1.28–1.68)].ConclusionOur findings indicate that multiple drugs are associated with an increased risk of coagulopathies. From the pharmacovigilance perspective, proactive analysis of these drugs aids in clinical monitoring and enhances risk identification of coagulopathies.

Scholars indicated that learners who are strategic with their language learning (e.g., self-regulated learning (SRL), cognitive and meta-cognitive strategies) tend to be more efficient, resourceful, and flexible, and thus have better language learning outcomes (Oxford, 2016; Heo et al., 2012; Plonsky, 2011). Besides focusing on knowledge, language learners, as L2 teachers already do, need to prepare themselves with self-regulated learning skills, so they can achieve the target language learning outcomes. This study selected Shanbay Danci (SBDC), a popular mobile vocabulary application (Wang, 2020, Su & Su, 2015), as the intervention. SBDC allows learners to share not only information about their goals but also badges (a gamification feature) demonstrating their learning outcomes. To explore the impacts of the badge-sharing feature on learners’ perceived self-regulation level, vocabulary learning persistence, and self-regulated learning experiences, a total of 77 undergraduates, who were enrolled in College English courses at a Chinese institution, participated in the study. Results showed participants in the badge-sharing group (experimental) tended to have significantly higher SRL levels (e.g., better management of time and the learning environment, being more strategic in completing tasks, selecting an appropriate learning environment, setting learning goals, and self-evaluating their learning progress) than those in the control group who were not enrolled in any badge sharing group. Moreover, those in the badge-sharing group demonstrated higher persistence in learning vocabulary, with a completion rate of 70%, versus 56% in the control group. Qualitative results indicated that badge sharing enhanced learners’ self and shared regulation capacity in the process of learning vocabulary.

Objective Anthropometric measurement provides a simple, noninvasive approach to evaluate obesity in pregnant women. We aimed to develop a predictive model utilizing anthropometric index for gestational diabetes mellitus (GDM), the most common obesity-related complications during pregnancy.Methods A prospective cohort of 4709 women was enrolled in Qingdao, China. Logistic regression model was constructed to determine the association of body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) in the first trimester (.05). Overall, VAT was positively correlated with GDM occurrence, outperforming BMI, WHR, WHtR and SAT in the predicative model. A first-trimester VAT cutoff of 27.05 mm might be promising for GDM risk stratification.Conclusions First-trimester routine ultrasound screening may facilitate earlier identification and intervention of GDM. Pregnant women with VAT above the optimal threshold (27.05 mm) might benefit from targeted GDM monitoring.

Abstract Consensus plays a crucial role in blockchain technology, with the delegated proof of stake (DPoS) consensus mechanism commonly utilized in both public and hybrid chains. However, the current DPoS mechanism faces challenges such as low node engagement in voting and potential security risks posed by malicious nodes. In response, we propose the DL-DPoS (deep link–delegated proof of stake) mechanism, which builds upon the DPoS framework. The DL-DPoS incorporates the LINK incentive mechanism to encourage inactive nodes to participate in voting and leader selection. Furthermore, a comprehensive credit scoring system based on wealth, performance, and stability is introduced to enhance the security of elected nodes. The verification process is optimized to involve all nodes except the leader node, and mechanisms are in place to handle malicious attacks by degrading or removing offending nodes and redistributing their responsibilities to the LINK group. Performance testing of the DL-DPoS mechanism, conducted through blockchain simulation tests using the GO language, shows a 23% increase in throughput compared to DPoS, with over 95% node participation and improved distribution of rights and equity. These results indicate the enhanced performance, security, and stability of the DL-DPoS consensus mechanism.

Objective: We aimed to investigate how hyperglycemia would exacerbate cerebral ischemia-reperfusion injury (CIRI) in a rat model of type 1 diabetes mellitus (T1DM) and explore the beneficial effects of multiple doses of melatonin in T1DM induced CIRI. Method: The T1DM rat model was induced with streptozocin, and melatonin (10 mg/kg) was injected at 0.5 h before ischemia as well as at 24 and 48 h after reperfusion. Results: When compared to normoglycemic (NG) rats, T1DM rats had hyperglycemia with weight loss before CIRI. Despite comparable degrees of ischemia and initial reperfusion, T1DM rats tended to have greater weight loss and had worse neurological deficits and larger infarct volume than NG rats up to 72 h after CIRI. Persistent activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway but not of apoptosis or calpains was a crucial factor in T1DM-mediated exacerbation of CIRI at 72 h. Despite lacking effects on baseline hyperglycemia, ischemia and initial reperfusion, melatonin at multiple doses lessened post-CIRI weight loss, neurological deficits and infarct volume in T1DM rats at 72 h. when compared to vehicle-treated T1DM rats with CIRI. Beneficial effects of melatonin treatment included decreased activation of NF-κB pathway, apoptosis and calpains, leading to reduced expression of inducible nitric oxide synthase and enhanced neuronal density. Conclusion: Melatonin at multiple doses can alleviate T1DM-mediated exacerbation of CIRI at 72 h through anti-inflammation and anti-apoptosis.

Abstract Aims Portal venous pressure frequently increases after a major hepatectomy. We aimed to assess the outcomes of patients with hepatocellular carcinoma (HCC) with different post‐hepatectomy portal pressure statuses and the predictive factors correlated with prognosis and post‐hepatectomy portal hypertension (PHPH). Methods Data from consecutive patients who underwent curative‐intent hepatectomy for HCC at the Eastern Hepatobiliary Surgery Hospital and Mengchao Hepatobiliary Hospital of Fujian Medical University between January 2008 and December 2016 were retrospectively analyzed. Patients were followed up until March 1, 2022. PHPH was defined as new‐onset portal hypertension (PH) in patients without preoperative PH within 1 month of hepatectomy. Patients were classified into two groups according to the presence or absence of PHPH: non‐PH and PHPH. The clinicopathological characteristics were compared between the two groups. Univariate and multivariate analyses were used to identify independent risk factors for early and late recurrence of HCC, overall survival (OS), and PHPH. Results Disease‐free survival rates were significantly higher in the non‐PH group (n = 1068) than those in the PHPH group (n = 423) (62.0%, 39.0%, and 31.0% vs. 46.2%, 24.5%, and 19.3% at 1, 3, and 5 years, respectively; all p 40 U/L, and major hepatectomy were identified as independent risk factors for PHPH. Conclusions PHPH was associated with early recurrence of HCC and poor OS but not with late recurrence. Therefore, PHPH may be an attractive target for therapeutic interventions and follow‐up surveillance to improve prognosis.

Rheumatoid arthritis (RA) is a prevalent autoimmune disease characterized by chronic inflammation and excessive proliferation of the synovium. Currently, treatment options focus on either reducing inflammation or inhibiting synovial hyperplasia. However, these modalities are unsatisfactory in achieving the desired therapeutic outcomes. Halofuginone hydrobromide (HF), an herbal active ingredient, has demonstrated pharmacological effects of both anti-inflammation and inhibition of synovial hyperplasia proliferation. However, HF's medical efficacy is limited due to its poor water solubility, short half-life (t1/2), and non-target toxicity. In the current study, by using the advantages of nanotechnology, we presented a novel dual-targeted nanocomplex, termed HA-M@P@HF NPs, which consisted of a hyaluronic acid (HA)-modified hybrid membrane (M)-camouflaged poly lactic-co-glycolic acid (PLGA) nanosystem for HF delivery. These nanocomplexes not only overcame the limitations of HF but also achieved simultaneous targeting of inflammatory macrophages and human fibroblast-like synoviocytes-RA (HFLS-RA). In vivo experiments demonstrated that these nanocomplexes effectively suppressed immune-mediated inflammation and synovial hyperplasia, safeguarding against bone destruction in rats with adjuvant-induced arthritis (AIA). Remarkable anti-arthritic effects of these nanocomplexes were accomplished through promoting repolarization of M1-to-M2 macrophages and apoptosis of HFLS-RA, thereby offering a promising therapeutic strategy for RA.

ObjectiveThis study aimed to investigate the causal relationship between insomnia and the risk of myocardial infarction (MI) and explore potential mediators such as smoking initiation, alcohol consumption and body mass index (BMI) using mendelian randomization (MR) analysis.MethodsData from 1,207,228 individuals of European ancestry were obtained from the UK Biobank and 23andMe for insomnia-related genetic associations. Genetic instruments for MI, smoking initiation, alcohol consumption, and BMI were derived from large-scale genome-wide association studies. Univariate MR analysis mainly utilized the inverse variance weighting method, and multivariable MR analysis assessed the mediation effects of smoking initiation and BMI.ResultsThe univariate MR analysis revealed a 96% increased risk of MI in individuals with insomnia [odds ratio (OR) = 1.96; 95% CI: 1.67, 2.31]. Smoking initiation and BMI were identified as potential mediators. The multivariable MR analysis indicated smoking initiation accounted for 29% of the total effect (95% CI: 13%, 61%), while BMI accounted for 15% (95% CI: 7%, 27%), with a combined mediation proportion of 54% (95% CI: 31%, 91%).ConclusionsThe results of this MR analysis demonstrate that insomnia increases the risk of MI. Quitting smoking and losing weight may reduce this risk; however, there is still a portion of the impact of insomnia on MI that cannot be explained. Therefore, further investigation into other potentially modifiable intermediate factors is necessary.

In early 2021, China introduced the “30–60” objective of “Carbon Neutral and Carbon Peak,” establishing low-carbon and high-quality development as a pivotal direction for China’s economic and social progress. China’s textile industry assumes a vital role in achieving low-carbon and high-quality development. Technological innovation emerges as a means to meet environmental regulations, facilitating an advantageous synergy between economic prosperity and environmental protection. The purpose of this study is to investigate the relationship between direct environmental regulation (DER) and enterprise innovation in the context of the Chinese textile industry. To achieve it, the study utilizes data collected from publicly listed textile companies in China, covering the period from 2004 to 2018, to construct a moderation-mediation model that explores the complex interplay between DER and enterprise innovation. The study’s novelty lies in comparing the impact of environmental regulation on innovation quality through substantive innovation and green innovation, as well as conducting stratified classification analyses by incorporating heterogeneous factors such as DER intensity, region, and sub-industry. The results demonstrate that DER significantly promotes both the input and output quality of innovation in Chinese textile enterprises, exhibiting a complex pattern of mediating and moderating effects. Specifically, DER exerts a substantial influence on the capital investment in innovation by Chinese textile enterprises, with high-intensity DER yielding more pronounced effects. The impact of DER on enterprise innovation quality is also contingent upon enterprise heterogeneity. Additionally, innovation capital investment serves as a pivotal mediating factor that links DER to the innovation quality of Chinese textile enterprises. The enterprise scale exhibits a moderating effect between DER and enterprise innovation quality. In summary, the mediation of innovation input and the moderation of enterprise scale collectively contribute to a comprehensive moderation-mediation effect on the relationship between DER and innovation quality in Chinese textile enterprises. Based on these findings, this study provides novel empirical support for the narrow “Porter Hypothesis” and offers targeted recommendations for enterprise management and policymakers in future applications.

BackgroundImmunotherapy offers new hope for improved survival in patients with advanced gastric cancer. Although large randomized controlled trials (RCTs) have been conducted to explore the efficacy and safety of first-line immunotherapy plus chemotherapy versus chemotherapy alone for advanced gastric cancer, the results are not completely consistent. And the strict inclusion criteria of RCTs lead to limited extrapolation. Therefore, it is of great significance to continue to conduct real-world studies comparing the clinical efficacy and safety of immunotherapy combined with chemotherapy versus chemotherapy alone in advanced gastric cancer.MethodsThis retrospective study included patients with HER-2 negative, unresectable advanced or recurrent gastric/gastroesophageal junction cancer (GC/GEJC) who received first-line immune checkpoint inhibitors (ICIs) in combination with chemotherapy or chemotherapy alone between January 1, 2018 to May 31, 2023. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), disease control rate (DCR) and adverse events (AEs) were compared between two groups.ResultsA total of 210 patients were enrolled in the combination treatment group (n=100) and chemotherapy alone group (n=110). After 12 months of follow-up, median PFS (mPFS) was 270 days (95%CI 177.510-362.490) in the chemotherapy alone group and 357 days (95%CI 250.103-463.897) in the combination treatment group (P0.05). There was no statistically significant difference in ORR between two groups (P=0.050). The DCR was 14.5% in the chemotherapy alone group and 38% in the combination treatment group (P

Background and ObjectiveEnhancing therapy choices for varying stages of esophageal cancer and improving patient survival depend on timely and precise diagnosis. Blood metabolites may play a role in either causing or preventing esophageal cancer, but further research is needed to determine whether blood metabolites constitute a genetic risk factor for the disease. In order to tackle these problems, we evaluated the causal association between esophageal cancer and 486 blood metabolites that functioned as genetic proxies using a two-sample Mendelian randomization (MR) study.MethodsWe utilized two-sample MR analyses to evaluate the causal links between blood metabolites and esophageal cancer. For the exposure, we used a genome-wide association study (GWAS) of 486 metabolites, and a GWAS study on esophageal cancer from Sakaue et al. was used for preliminary analyses. Causal analyses employed randomized inverse variance weighted (IVW) as the main method, supplemented by MR-Egger and weighted median (WM) analyses. Sensitivity analyses included the MR-Egger intercept test, Cochran Q test, MR-PRESSO, and leave-one-out analysis. Additionally, independent esophageal cancer GWAS data were utilized for replication and meta-analysis. FDR correction was applied to discern features with causal relationships. For conclusive metabolite identification, we conducted Steiger tests, linkage disequilibrium score regression, and colocalization analyses. Moreover, we utilized the program MetaboAnalyst 5.0 to analyze metabolic pathways.ResultsThis study found an important association between esophageal cancer and three metabolites: 1-linoleoylglycerophosphoethanolamine* [odds ratio (OR) = 3.21, 95% confidence interval (CI): 1.42–7.26, p < 0.01], pyroglutamine* (OR = 1.92, 95% CI: 1.17–3.17, p < 0.01), and laurate (12:0) (OR = 3.06, 95% CI: 1.38–6.78, p < 0.01).ConclusionThis study establishes a causal link between three defined blood metabolites and esophageal cancer, offering fresh insights into its pathogenesis.

IntroductionIntersectional hybrids in lilies possess significant breeding value, but the lack of complete lily genomes and complex genotypes pose challenges for early identification of lily hybrids. This study aimed to use intersectional hybrid cultivars as female parents and wild lilies as male parents to facilitate early identification of hybrid offsprings and enhance the efficiency and convenience of the process.MethodsWe investigated the nature of cross combinations using Non-denaturing Fluorescence In Situ Hybridization (ND-FISH) and Genomic In Situ Hybridization (GISH) techniques. Three novel oligonucleotide probes—Oligo-pTa794, Oligo-pITS and Oligo-telo—were developed for lily chromosome research.ResultsOur results demonstrated successful hybridization between wild lilies and intersectional hybrid cultivars, producing a total of 130 hybrid progenies. The combination of ND-FISH and GISH analyses effectively revealed the genomic composition of the hybrid progeny and determined the parental origin of specific chromosomes.DiscussionThis research provides significant guidance for lily breeding practices and offers a valuable reference for the application of ND-FISH and GISH techniques in interspecific hybridization breeding and molecular cytogenetic research across various plant species. The methods developed enable more precise, efficient, and convenient identification of hybrid offsprings.