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Purpose: Road traffic injuries (RTIs) have been one of the most serious public health problems in China. The purpose of this study was to investigate the extent to which traffic investment affects traffic fatalities in China as well as regional differences. Methods: The cohort study analyzed the correlation between traffic investment and traffic fatalities, incorporating additional factors such as economic conditions, road infrastructure, population density, and lighting. The selected variables included the number of traffic fatalities, traffic investment, urban per capita road area, urban road length, road mileage, urban road lighting, population size, and per capita gross domestic product. Relevant data between 2004 and 2020 were collected for an analysis using a fixed effect regression model. A p < 0.05 is considered statistically significant. To reduce the heterogeneity caused by regional differences, the provinces were divided into 6 groups according to administrative districts, and the clustering standard error analysis was carried out. Results: Overall, there has been a significant improvement in road safety in China from 2004 to 2020, but some regions show an increase in traffic fatalities. The model reveals that traffic investment is significantly and positively correlated with the number of traffic fatalities. Holding all other factors constant, each 10,000 yuan increase in transport investment was associated with an average increase of 0.22 road traffic fatalities. In the analysis of regional differences, there was a significant positive correlation between traffic investment and traffic fatalities in the Northwest region and an increase of 10,000 yuan leads to an increase of 0.47. There was a significant negative correlation between road mileage, urban road lighting system, and population and traffic fatalities. For example, holding other factors constant, a 10,000 km reduction in road length would increase the number of traffic deaths by 45.56. The model results of urban per capita road area, urban road length, per capita gross domestic product, and the explained variables showed that p > 0.100, which was not statistically significant. Conclusions: Therefore, traffic investments are essential for governments to develop measures to enhance road safety and reduce the risk of road fatalities. Adjusting traffic road investment and other covariates is conducive to improving traffic safety and reducing the risk of road fatalities. The road safety situation in different regions of China varies greatly. Local governments should consider the actual conditions to provide better road safety configuration policies.

Abstract Background The purpose of the study is to explore the current level of nursing students’ study skills self-efficacy, and whether general self-efficacy and self-directed learning ability mediate the relationship between perceived stress (including positive stress and negative stress) and study skills self-efficacy. Methods The survey was conducted among 1,289 nursing students including 795 students from Jinzhou Medical University and 494 students from Dalian University. Participants completed a self-designed questionnaire, which included the Study Skills Self-Efficacy Scale, Perceived Stress Scale, General Self-Efficacy Scale, Self-Directed Learning Instrument, gender, age, academic year, and other demographic characteristics. Descriptive analysis, independent-samples t-test, one-way analysis of variance, Pearson correlation analyses, and the bootstrap method were used for data analysis. Results Positive stress significantly positively predicted students’ study skills self-efficacy, with an effect size of 0.686. Moreover, general self-efficacy and self-directed learning mediate the relationship between positive stress and study skills self-efficacy in nursing students, with effect sizes of 0.235 and 0.245, respectively. The direct effect of negative pressure on students' study skills self-efficacy is not statistically significant, but it has a significant negative predictive effect on study skills self-efficacy under the mediation of general self-efficacy and self-directed learning, with effect sizes of -0.337 and -0.238, respectively. Conclusion This study explains how stress affects students’ study skills self-efficacy, and the results have certain enlightenment significance for improving the stress management ability and study skills self-efficacy of college students in the future.

Abstract Although there have been remarkable advances in the treatment of hepatocellular carcinoma (HCC), the prognosis remains poor in those with advanced stage and more effective therapeutic options are urgently needed. Lenvatinib (Len), a multiple receptor tyrosine kinase inhibitor, is an emerging molecular targeted agent for HCC, whose immunomodulatory activities have been investigated. However, Len utilization is limited because of its low metabolic stability, poor bioavailability and dose-dependent toxicity, rendering its direct use insufficient for immune modulation. Stimuli-responsive nanoparticles, which are drug-targeted delivery platforms for on-demand drug release, facilitate deeper and uniform tumour penetration, providing alternative solutions to overcome current limitations. Ultrasound (US) exhibits superior tissue penetration abilities and can produce reactive oxygen species (ROS) at the tumour site to treat deeper tumours. In addition, US serves as an excellent and selective drug delivery mediator for tumour treatment. Herein, we designed US-triggered lenvatinib nanoparticles (Len-RNPs) for selective drug delivery that utilize US-triggered ROS to induce in situ oxidation reactions, resulting in nanoparticle disintegration. Len-RNPs mitigate the toxicity of Len and effectively trigger robust systemic anti-tumour immune responses in a H22 tumour model, resulting in a tumour suppression rate of 95.7%, with 60% of mice being cured. Our study elucidates a novel and precise strategy of combining Len and US therapy for enhanced HCC immunotherapy.

This study examines the current research on educational data mining, educational learning support services, personalized learning services, and personalized learning paths in education. The authors aim to integrate personalized learning concepts into traditional support services by drawing on the latest theoretical and practical research. Using multimodal data fusion techniques, the study conduct exploratory analyses on various data types, including learner academic performance, psychological assessments, learning behavior, and physiological information. This leads to the construction of a personalized education learning support service model. The model focuses on objectives such as monitoring learning behavior, identifying preferences, recognizing abilities, optimizing paths, and recommending resources. The goal is to provide learners with sustained support services throughout the personalized learning process, addressing individual needs, fostering enthusiasm, and maintaining long-term motivation.

Abstract Background Modified Si-Miao granule (mSMG), a traditional Chinese medicine, is beneficial for T2DM and insulin resistance (IR), but the underlying mechanism remains unknown. Methods Using network pharmacology, we screened the compounds of mSMG and identified its targets and pathway on hepatic IR in T2DM. Using molecular docking, we identified the affinity between the compounds and hub target TNF-α. Then these were verified in KK-Ay mice and HepG2 cells. Results 50 compounds and 170 targets of mSMG against IR in T2DM were screened, and 9 hub targets such as TNF and MAPK8 were identified. 170 targets were mainly enriched in insulin resistance and TNF pathway, so we speculated that mSMG might act on TNF-α, JNK1 and then regulate insulin signaling to mitigate IR. Experimental validation proved that mSMG ameliorated hyperglycemia, IR, and TNF-α, enhanced glucose consumption and glycogen synthesis, relieved the phosphorylation of JNK1 and IRS-2 (Ser388), and elevated the phosphorylation of Akt (Ser473) and GSK-3β (Ser9) and GLUT2 expression in KK-Ay mice. Molecular docking further showed berberine from mSMG had excellent binding capacity with TNF-α. Then, in vitro validation experiments, we found that 20% mSMG-MS or 50 μM berberine had little effect in IR-HepG2 cell viability, but significantly increased glucose consumption and glycogen synthesis and regulated TNF-α/JNK1/IRS-2 pathway. Conclusion Network pharmacology and molecular docking help us predict potential mechanism of mSMG and further guide experimental validation. mSMG and its representative compound berberine improve hepatic IR and glycogen synthesis, and its mechanism may be related to the inhibition of TNF-α/JNK1/IRS-2 pathway.

Abstract Objective The purpose of this study is to construct an organ system-centered undergraduate nursing professional training model and explore its application effect. Methods This study is divided into two steps. In the early stage, literature review and expert consultation were used to establish the training mode (curriculum and assessment standard) of nursing undergraduate specialty based on organ system reform. Secondly, a cross-sectional survey method was used to investigate the training quality of nursing students who graduated from Jinzhou Medical University from 2007 to 2017 under this model. Results A five-module curriculum system was established, including general courses, public basic courses, professional education courses, expanding elective courses and concentrated practical teaching. Under the teaching reform of organ system, the nursing graduates of Jinzhou Medical University, who are mainly employed in public hospitals, are generally not satisfied with their jobs, salaries, contents and prospects. Their overall satisfaction with their alma mater is very high; Graduates have certain independent core competence; Employers are basically satisfied with graduates. Conclusion The training mode of undergraduate nursing specialty based on organ system reform basically meets the training requirements and objectives.

Abstract Background Calcium silicate-based bioceramics have been applied in endodontics as advantageous materials for years, many chemical components and new synthesizing methods were used to improve the base formulation of the materials for positively affecting the sealers properties. Recently, a novel biomaterial formulation, grounded in strontium silicate, has been introduced to the market, offering potential advancements in the field. Objective To comparatively analyze the cytotoxicity and cell migration effects of a novel strontium silicate-based bioceramic material (CRoot SP) and those of calcium silicate-based (iRoot SP) and epoxide amine resin (AH Plus) sealers on stem cells derived from rat apical papilla(rSCAPs). Methods rSCAPs were isolated and characterized in vitro and subsequently cultured in the presence of various concentrations of CRoot SP, iRoot SP and AH Plus extracts. Cytotoxicity was assessed by CCK-8 assay, and cell-migration capacity was assessed by using wound healing assays . Results No significant differences in cell viability were observed in the 0.02 mg/mL and 0.2 mg/mL sealer groups. The cell viability of CRoot SP was consistently greater than that of iRoot SP at concentrations of 5 mg/mL and 10 mg/mL across all time points. Maximum cytotoxic effect was noted on day 5 with 10 mg/mL AH Plus.The scratch was partly healed by cell migration in all groups at 24 h, and the 0.02 mg/mL, and 0.2 mg/mL CRoot SP exerted beneficial effects on rSCAPs migration. Conclusions CRoot SP exhibited less cytotoxic than the iRoot SP and AH Plus extracts after setting. A lower concentration of CRoot SP thus promotes the cell migration capacity of rSCAPs, and it may achieve better tissue repair during root canal treatment.

Abstract Background To investigate the cross-sectional and longitudinal associations between depressive symptoms and the prevalence of frailty and its components in a nationally representative sample of middle-aged and older Chinese adults. Method The China Health and Retirement Longitudinal Study (CHARLS) provided data on 2581 (after inclusion and exclusion criteria) adults aged ≥ 45 years. Every two years, face-to-face, computer-aided personal interviews (CAPI), and structured questionnaires were used to follow up with the respondents. The Chinese version of the Center for Epidemiologic Studies-Depression Scale (CES-D) was used to evaluate depressive symptoms, and the Fried criteria were used to measure frailty. The odds ratio (OR) and 95% confidence interval (CI) for the association of exposure (depressive symptoms at baseline) with the onset of the outcome (frailty and its components) in the individuals at baseline were analyzed by binary logistic regression. Results At baseline, 11.62% of participants had frailty, and 57.92% had depressive symptoms. In the cross-sectional analysis, depressive symptoms (OR = 5.222, 95%CI 3.665–7.442) were associated with frailty. In the longitudinal analysis, after adjusting for the full set of covariates among participants free of baseline frailty, depressive symptoms were significantly associated with incident frailty during the short term (OR = 2.193, 95%CI 1.324–3.631) and the long term (OR = 1.926, 95%CI 1.021–3.632). Meanwhile, depressive symptoms were associated with an increased risk of weakness (OR = 1.990, 95%CI 1.250–3.166), slowness (OR = 1.395, 95%CI 1.044–1.865), and exhaustion (OR = 2.827, 95%CI 2.150–3.719) onset during the short-term. Depressive symptoms were associated with an increased risk of exhaustion (OR = 2.869, 95%CI 2.004–4.109) onset during the long-term. Conclusion Among middle-aged and older adults, depressive symptoms could predict frailty during 2 years of follow-up and 4 years of follow-up. When considering potential confounding factors, depressive symptoms were considered a predictor of weakness, slowness, and exhaustion. Interventions aimed at preventing depressive symptoms may be beneficial in reducing frailty and its components.

Abstract Background Preeclampsia is a severe obstetric disorder that significantly affects the maternal and neonatal peri-partum safety and long-term quality of life. However, there is limited research exploring the common mechanisms and potential clinical significance between early-onset preeclampsia and full-term preeclampsia from an immunological perspective. Methods In this study, data analysis was conducted. Initially, immune-related co-expressed genes involving both subtypes of preeclampsia were identified through Weighted Gene Co-expression Network Analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were further employed to investigate the shared pathways regulated by immune-related genes. Binary logistic regression identified co-expressed genes with diagnostic value for preeclampsia, and a diagnostic model was constructed. Gene Set Enrichment Analysis (GSEA) predicted the potential biological functions of the selected genes. Lasso and Cox regression analyses identified genes closely associated with gestational duration, and a risk score model was established. A 4-gene feature, immune-related gene model for predicting the risk of preterm birth in preeclamptic pregnant women, was developed and validated through qPCR experiments. Immune cell infiltration analysis determined differences in immune cell infiltration between the two subtypes of preeclampsia. Results This study identified 4 immune-related co-expressed genes (CXCR6, PIK3CB, IL1RAP, and OSMR). Additionally, diagnostic and preterm birth risk prediction models for preeclampsia were constructed based on these genes. GSEA analysis suggested the involvement of these genes in the regulation of galactose metabolism, notch signaling pathway, and RIG-I like receptor signaling pathway. Immune pathway analysis indicated that the activation of T cell co-inhibition could be a potential intervention target for immunotherapy in early-onset preeclampsia. Conclusion Our study provides promising insights into immunotherapy and mechanistic research for preeclampsia, discovering novel diagnostic and intervention biomarkers, and offering personalized diagnostic tools for preeclampsia.

Abstract Background Considering that changes in the choroidal thickness are closely related to ocular growth, we studied the choroidal thickness (CT) and the blood flow features in children with unilateral myopic anisometropia (UMA) as well as investigating the relationship between choroidal changes and myopia. Methods Subjective refractive, axial length (AL), and biometric parameters were measured in 98 UMA children (age: 8–15 years). CT and choroidal blood-flow features, including the choroidal vessel volume (CVV), choroidal vascularity index (CVI), and choriocapillaris perfusion area (CCPA), were measured through swept-source optical coherence tomography angiography. The macular region was categorized into four concentric circles of diameters 0–1 mm (central fovea), 1–3 mm (parafovea), 3–6 mm (perifovea), and 6–9 mm (extended), and further categorized into superior (S), inferior (I), temporal (T), and nasal (N) quadrants. Results The aforementioned four regions of myopic eyes displayed significantly lower CT, CVV, and CVI than those of non-myopic eyes. CCPA changes differed across different regions of both the eyes (parts of N and T quadrants). There was an inverse association between CT and the interocular AL difference (central and other regions S, T quadrant). No correlation was noted between CVV and CVI with interocular AL difference. CT and CVV were positively correlated in the 0–6-mm macular region of myopic eyes (Spearman correlation coefficient = 0.763, P

Abstract Background The prognostic potential of immune-related genes, particularly immune checkpoint inhibitors (ICIs) and long non-coding RNAs (lncRNAs), is gaining attention for evaluating the prognosis of breast cancer patients. Methods We analyzed 23 datasets to identify 15 ICI-related mRNAs and 5 immune-related lncRNAs, creating a robust immune score (IS). This score was used to classify patients into high and low IS groups and assess their survival outcomes. Results Patients with high IS showed significantly poorer overall survival (OS) and progression-free survival (PFS) compared to those with low IS. Multivariate Cox regression analysis confirmed IS as an independent prognostic factor. Additionally, high IS was associated with higher mutation loads and neoantigen profiles, while low IS correlated with enhanced immune cell infiltration. Conclusions The immune score developed from ICI-related mRNAs and lncRNAs effectively predicts the prognosis of breast cancer patients and highlights the differential immune and inflammatory responses between patients with varying levels of immune score. This underscores the relevance of IS in guiding therapeutic decisions and tailoring patient management strategies in clinical settings.

Abstract Background Enterococcus gallinarum is an infrequently intestinal symbiotic pathogen associated with nosocomial infection in immunocompromised individuals. To date, rare cases of pulmonary infection attributable to Enterococcus gallinarum were reported. Herein, we presented the first case of empyema resulting from Enterococcus gallinarum infection. Case presentation An 81-year-old male presented with fever and dyspnea upon admission. Chest CT scan and thoracic ultrasonography confirmed the presence of right pleural effusion. Thoracoscopy revealed extensive adhesion, purulent fluid, and necrotic materials within the thoracic cavity. Enterococcus gallinarum was identified through pleural effusion culture. The patient underwent an intrathoracic injection of urokinase along with thoracic drainage. Following surgery, He took oral linezolid for over one month. Undergoing comprehensive treatment, the patient exhibited favorable recovery. Conclusions We reported the first case of empyema due to Enterococcus gallinarum infection. It should be suspected in patients with impaired immune function and invasive therapies, without responding to conventional anti-infectious treatment.

Abstract Epithelial ovarian cancer (EOC) is a deadly disease with limited diagnostic biomarkers and therapeutic targets. Here we conduct a comprehensive proteomic profiling of ovarian tissue and plasma samples from 813 patients with different histotypes and therapeutic regimens, covering the expression of 10,715 proteins. We identify eight proteins associated with tumor malignancy in the tissue specimens, which are further validated as potential circulating biomarkers in plasma. Targeted proteomics assays are developed for 12 tissue proteins and 7 blood proteins, and machine learning models are constructed to predict one-year recurrence, which are validated in an independent cohort. These findings contribute to the understanding of EOC pathogenesis and provide potential biomarkers for early detection and monitoring of the disease. Additionally, by integrating mutation analysis with proteomic data, we identify multiple proteins related to DNA damage in recurrent resistant tumors, shedding light on the molecular mechanisms underlying treatment resistance. This study provides a multi-histotype proteomic landscape of EOC, advancing our knowledge for improved diagnosis and treatment strategies.

Abstract Background Addressing presbyopia in the aging population, particularly in non-cataractous patients, remains a challenge. This study evaluates the outcomes of refractive lens exchange (RLE) with AT LISA tri 839MP trifocal intraocular lens (IOL) implantation in a Chinese presbyopic population without cataracts. Methods The study included 164 eyes from 82 patients undergoing bilateral RLE at Peking Union Medical College Hospital. Comprehensive evaluations encompassed visual acuities, refraction, ocular aberrometry, and subjective outcomes via the VF-14 questionnaire. The focus was on postoperative visual performance, refractive outcomes, safety, objective optical quality, and patient satisfaction. Results 100%, 90.2%, and 89.0% of patients achieved binocular UDVA, UNVA, and UIVA of logMAR 0.1 or better at 6 months postoperatively. 97.6% of eyes were within ± 1.00 D of emmetropia postoperatively. Optical quality assessments showed increases in modulation transfer function and Strehl ratios (p

Abstract 3-dB couplers, which are commonly used in photonic integrated circuits for on-chip information processing, precision measurement, and quantum computing, face challenges in achieving robust performance due to their limited 3-dB bandwidths and sensitivity to fabrication errors. To address this, we introduce topological physics to nanophotonics, developing a framework for topological 3-dB couplers. These couplers exhibit broad working wavelength range and robustness against fabrication dimensional errors. By leveraging valley-Hall topology and mirror symmetry, the photonic-crystal-slab couplers achieve ideal 3-dB splitting characterized by a wavelength-insensitive scattering matrix. Tolerance analysis confirms the superiority on broad bandwidth of 48 nm and robust splitting against dimensional errors of 20 nm. We further propose a topological interferometer for on-chip distance measurement, which also exhibits robustness against dimensional errors. This extension of topological principles to the fields of interferometers, may open up new possibilities for constructing robust wavelength division multiplexing, temperature-drift-insensitive sensing, and optical coherence tomography applications.

In this paper, the flow behavior, constitutive model and microstructure evolution of solution-treated 2195 Al–Li alloy at temperatures from 123 K to 298 K and strain rates from 2000 s−1 to 5000 s−1 were studied. Experimental results show that the flow stress of the solution-treated 2195 Al–Li alloy is more sensitive to deformation temperature than strain rate. As the temperature declines from 298 K to 123 K, the flow stress at 2000 s−1 and 5000 s−1 increases by nearly 32.8% and 34.5%, respectively; whereas as the strain rate increases from 2000 s−1 to 5000 s−1, the flow stress at 298 K and 123 K only increases by 5.1% and 6.5%, respectively. The average strain hardening rate tends to decline with the increase in strain rate and temperature, and its value at 123 K and 2000 s−1 is about 1.5 times greater than that at 298 K and 5000 s−1. To overcome the very limited applicability of the conventional Arrhenius model with strain compensation, an Arrhenius-based model (c-Arrhenius model) is developed by coupling an independent strain term and then derived by using normalized flow stress and linear regression. To quantify the strain rate effect and temperature effect, a Johnson-Cook-based model (c-Johnson-Cook model) with exponential terms is developed. These two new constitutive models are validated via a comparative analysis, showing good predictability and accuracy. A further microstructure observation shows that the dislocation density is the highest at a strain rate of 5000 s−1 and cryogenic temperature of 123 K, which is beneficial for subsequent aging strengthening.

Breast cancer has become the most prevalent malignant tumor worldwide and remains one of the leading causes of cancer-related mortality among women globally. The prognosis for patients with metastatic breast cancer remains poor, necessitating the exploration of novel therapeutic strategies to improve survival rates. In the era of precision medicine, antibody-drug conjugates (ADCs) have gained significant attention as a targeted therapeutic strategy in breast cancer treatment. ADCs, a relatively new treatment for breast cancer, deliver cytotoxic drugs (payloads), directly into the tumor space, turning chemotherapy into a targeted agent, which enables patients to experience significant improvements with manageable drug toxicity. For the treatment of breast cancer, there are three ADCs approved for breast cancer treatment: Trastuzumab emtansine (T-DM1), Trastuzumab Deruxtecan (T-Dxd) targeting HER-2, and Sacituzumab Govitecan (SG) targeting Trop-2. Recent clinical studies have demonstrated that the benefits of ADC therapies extend beyond HER2-positive breast cancer toinclude hormone receptor (HR)-positive breast cancer, triple-negative breast cancer (TNBC), and HER2-low expressing breast cancer. Notably, the DESTINY-Breast series of studies, particularly focusing on T-Dxd, encompass neoadjuvant, adjuvant, and multiple lines of therapy for advanced breast cancer. This marks the advent of a comprehensive ADC era in breast cancer treatment. This review summarizes the efficacy and adverse effects of ADC therapies that have completed or are currently undergoing phase I-III clinical trials. Additionally, it analyzes potential combination strategies to overcome ADC resistance, aiming to provide clinicians with a comprehensive clinical guide to the use of ADCs in breast cancer treatment.

Despite the well-known health benefits of unsaturated alginate oligosaccharides (UAOS), limited information exists on how they regulate the gut microbiota and intestinal mucosal immunity. In this study, UAOS was produced by alginate lyase degradation. Fourier transform infrared (FTIR), mass spectrometry (MS), and nuclear magnetic resonance (NMR) analyses showed that UAOS primarily consists of oligosaccharides, mainly pentamers, with a G/M ratio of 1.44 and unsaturated double bonds at the non-reducing end. UAOS exhibited good prebiotic effects; increased beneficial intestinal bacteria; improved the diversity, structure, and composition of the gut microbiota; and promoted the production of SCFAs. In particular, UAOS significantly increased the abundance of butyrate levels and their producing microbiota, such as Lachnospiraceae, Alloprevotella, and Butyicicoccus. Moreover, orally administered UAOS alleviated intestinal mucosal immunosuppression by upregulating the levels of the tight junction proteins occludin and ZO-1, enhancing the intestinal biochemical and immune barrier function by increasing levels of mucin-2 and SIgA, upregulating the CD4+/CD8+ ratio, regulating CD4+ T cell differentiation, and stimulated immune cytokine secretion and transcription factor production (T-bet/GATA-3). This process was related to TLR4/MyD88/NF-κB pathway. In summary, UAOS effectively regulates intestinal mucosal immune homeostasis by strengthening the intestinal barrier and regulating the intestinal microbiota and intestinal butyrate levels. Therefore, UAOS acts as a prebiotic and immune stimulator to improve host health.

ABSTRACT: In this study, we investigated the effects of dietary supplementation with Bacillus subtilis (QST713) on the performance and intestinal health of yellow feather broilers under Coccidia and Clostridium perfringens (CP) challenge or CP alone. One-day-old yellow-feathered broiler roosters (n = 600) were randomly assigned to 5 groups (6 replicates with 20 roosters per replicate): the Con blank group, the CIC.p group (d24 Coccidia+d28-30 of CP challenge), the CIC.p + BS group (CIC.p +100 mg/kg B. subtilis), the C.p group (d 28–34 of CP challenge), and the C.p +BS group (C.p +100 mg/kg B. subtilis). The experiment lasted 80 d. The birds were evaluated for parameters such as average daily gain (ADG), average daily feed intake (ADFI), feed efficiency (F/G), intestinal lesion score, villus histomorphometry, intestinal tight junctions, inflammatory factors, and cecal microorganisms. The results revealed that 1) C.p. increased the F/G of broilers from 22 to 42 d (P < 0.05), whereas CIC.p. significantly decreased the 42 d and 80 d body weights (BW) and 22–42 d and 1–80 d ADG (P < 0.05) and significantly increased the 22 to 42 d and 1 to 80 d F/G (P < 0.05). The number of intestinal lesions significantly increased at 35 d and 42 d (P < 0.05). CIC.p significantly decreased the jejunum and ileum villus height (VH) and the ileum villus height/crypt depth (P < 0.05) at 35 d. The challenge significantly upregulated the expression of Claudin-1 and IL-4 mRNAs in the jejunum at 35 d and significantly downregulated the expression of IL-10 mRNA in the ileum at 35 d (P < 0.05); the number of unique OTUs in the challenge group decreased significantly after challenge treatment, and the relative abundances of Romboutsia at 35 d and Cladomyces and Lactobacillus at 42 d decreased significantly (P < 0.05). 2) Compared with the challenge groups, the addition of BS decreased the F/G of broilers from 22 to 42 d. Compared with the CIC group, the addition of BS significantly increased the F/G of broilers from 22 to 42 d. Compared with that in the CIC.p group, the addition of BS significantly increased the VH in the jejunum and ileum at 35 d (P < 0.05). Compared with the challenge groups, the BS groups presented significantly lower mRNA expression levels of Claudin-1 (P < 0.05) in the jejunum at 35 d. The Shannon and Chao indices suggested that BS increased the alpha diversity of cecum microorganisms in broilers. Dietary supplementation with B. subtilis can alleviate the damage to intestinal morphology and intestinal barrier function, as well as the altered cecal flora structure in broilers caused by Coccidia and C. perfringens infections.

ABSTRACTBackground Preeclampsia/eclampsia is a severe pregnancy-related disorder associated with hypertension and organ damage. While observational studies have suggested a link between maternal iron status and preeclampsia/eclampsia, the causal relationship remains unclear. The aim of this study was to investigate the genetic causality between iron status and preeclampsia/eclampsia using large-scale genome-wide association study (GWAS) summary data and Mendelian randomization (MR) analysis.Methods Summary data for the GWAS on preeclampsia/eclampsia and genetic markers related to iron status were obtained from the FinnGen Consortium and the IEU genetic databases. The “TwoSampleMR” software package in R was employed to test the genetic causality between these markers and preeclampsia/eclampsia. The inverse variance weighted (IVW) method was primarily used for MR analysis. Heterogeneity, horizontal pleiotropy, and potential outliers were evaluated for the MR analysis results.Results The random-effects IVW results showed that ferritin (OR = 1.11, 95% CI: .89–1.38, p = .341), serum iron (OR = .90, 95% CI: .75–1.09, p = .275), TIBC (OR = .98, 95% CI: .89–1.07, p = .613), and TSAT (OR = .94, 95% CI: .83–1.07, p = .354) have no genetic causal relationship with preeclampsia/eclampsia. There was no evidence of heterogeneity, horizontal pleiotropy, or possible outliers in our MR analysis (p > .05).Conclusions Our study did not detect a genetic causal relationship between iron status and preeclampsia/eclampsia. Nonetheless, this does not rule out a relationship between the two at other mechanistic levels.

Not available.

BackgroundPollen is the most common outdoor allergen that causes allergic rhinitis and asthma, which seriously affects patient quality of life and extensive cross-reactivity occurs between pollen allergens.MethodsThe study enrolled 84 patients with respiratory allergies and at least one pollen allergy who visited the clinic. Specific-IgE was detected via immunoblotting in the sera of patients with positive respiratory allergies to pollen. IgE of the components and cross-reactive carbohydrate determinants (CCD) were evaluated using a fluorescence-encoded microsphere assay.ResultsOur results suggest that Artemisia absinthium, Artemisia vulgaris, Humulus scandens, Amaranthus, Parietaria micrantha allergies are most common in the northern region, and that weed pollen remains the major pollen allergen in the northern region. Among the different age groups, the positive rate of Platanus pollen allergens was significantly higher in patients ≤18 years of age than in those aged >18 years (55.56% vs. 9.17%, χ² = 0.55, p

Metaflammation is low-grade inflammation triggered by chronic metabolic imbalance and caused by dysregulated metabolites in metabolic inflammatory syndrome (MIS), which includes four diseases: obesity, type 2 diabetes mellitus (T2DM), atherosclerosis (AS), and nonalcoholic fatty liver diseases (NAFLD, recently proposed to be replaced by metabolic dysfunction-associated steatotic liver disease, MASLD). These diseases exhibit apparent sex dimorphism as regards MIS. Estrogen not only plays a crucial role in gender differences in adults but also possesses an anti-inflammatory effect on many metabolic diseases. In this study, we present a prediction of the differential proteins and signal transduction of estrogen in MIS through network pharmacology and review the validated studies on obesity, T2DM, AS, and NAFLD. Subsequently, we compared them to obtain valuable targets, identify current gaps, and provide perspectives for future research on the mechanisms of estrogen in metaflammation.

Summary: Background: China has the largest number of dementia patients in the world, posing a significant health and economic burden. Alzheimer's disease (AD) and other dementia patients face a higher risk of mortality during heatwaves, but relevant studies on this topic have been limited so far. Methods: The study extracted data from the China Cause of Death Reporting System (CDRS) on deaths of AD and other dementia patients aged 60 years and above between 2013 and 2020. Using an individual-level, time-stratified, and case-crossover study design, the effects of heatwaves across nine scenarios on dementia mortality were quantified by conditional logistic regression combined with distributed lag non-linear model (DLNM). Additionally, the attributable fractions (AFs) of deaths due to heatwaves were calculated. Findings: A total of 399,036 death cases were reported caused by AD and other dementias during the study period. It was found that heatwaves significantly increased the risk of death among people with AD and other dementias. As the intensities and durations of the heatwaves increased, the lag0-7 cumulative odds ratios (CORs) of mortality increased progressively from 1.140 (95% CI: 1.118, 1.163) under the mildest heatwave to 1.459 (95% CI: 1.403, 1.518) under the most severe one, across nine heatwave scenarios examined. Additionally, under specific heatwave scenarios, sex and regions modified the mortality risk, but no significant age differences were observed. The AFs of AD and other dementia mortality due to milder heatwaves were lower compared to more severe heatwaves, ranging from 12.281% (95% CI: 10.555%, 14.015%) to 31.460% (95% CI: 28.724%, 34.124%). Interpretation: The study provided critical insights into the substantial increase in heatwave-related mortality among AD and other dementia patients during and after heatwave events. The results from our quantitative analyses will provide needed scientific evidence for policymakers and practitioners to develop relevant policies and guidelines to protect the health and well-beings of vulnerable populations in future in the context of both seasonal changes and long-term climate change. Funding: This work was supported by the Project of Prevention and Intervention on Major Diseases for Elderly in China, NCNCD [00240201307], the National Key Research and Development Program of China [2022YFC2602301, 2023YFC2308703] and the Science and Technology Fundamental Resources Investigation Program of China [2017FY101201].

Abstract A 2 × 2 thermo‐optic (TO) switch using dual topological photonic crystal nanobeam (PCN) cavities on the silicon‐on‐insulator (SOI) platform is proposed and experimentally demonstrated. A Fano resonance is observed due to the interference between the topological interface state of the 1D topological PCN cavity and the Fabry‐Perot (F‐P) cavity mode formed between the two facets of the finitely long nanobeam waveguide. Thanks to the sharp rising edge of the spectral response of the Fano resonance and the high confinement of light in the topological PCN cavities, a 2 × 2 TO switch is realized with short switching time and low power consumption. The measured switching power is only 1.55 mW, and the rising time and the falling time are 3 and 5.6 µs, respectively in the on‐off switching experiments. To the best of the knowledge, this is the first time that a dual topological PCN structure is utilized to realize a high‐speed and low‐power TO switch, revealing the possibility of designing high‐performance reconfigurable optical devices and networks using topological photonics.

As the core component of energy conversion for large wind turbines, the output performance of doubly-fed induction generators (DFIGs) plays a decisive role in the power quality of wind turbines. To realize the fast and accurate design optimization of DFIGs, this paper proposes a novel hybrid-driven surrogate-assisted optimization method. It firstly establishes an accurate subdomain model of DFIGs to analytically predict performance indexes. Furthermore, taking the inexpensive analytical dataset produced by the subdomain model as the source domain and the expensive finite element analysis dataset as the target domain, a high-precision surrogate model is trained in a transfer learning way and used for the subsequent multi-objective optimization process. Based on this model, taking the total harmonic distortion of electromotive force, cogging torque, and iron loss as objectives, and the slot and inner/outer diameters as parameters for optimizing the topology, achieve a rapid and accurate electromagnetic design for DFIGs. Finally, experiments are carried out on a 3MW DFIG to validate the effectiveness of the proposed method.

Interconnection of all things challenges the traditional communication methods, and Semantic Communication and Computing (SCC) will become new solutions. It is a challenging task to accurately detect, extract, and represent semantic information in the research of SCC-based networks. In previous research, researchers usually use convolution to extract the feature information of a graph and perform the corresponding task of node classification. However, the content of semantic information is quite complex. Although graph convolutional neural networks provide an effective solution for node classification tasks, due to their limitations in representing multiple relational patterns and not recognizing and analyzing higher-order local structures, the extracted feature information is subject to varying degrees of loss. Therefore, this paper extends from a single-layer topology network to a multi-layer heterogeneous topology network. The Bidirectional Encoder Representations from Transformers (BERT) training word vector is introduced to extract the semantic features in the network, and the existing graph neural network is improved by combining the higher-order local feature module of the network model representation network. A multi-layer network embedding algorithm on SCC-based networks with motifs is proposed to complete the task of end-to-end node classification. We verify the effectiveness of the algorithm on a real multi-layer heterogeneous network.

Abstract Objective This study assesses the influence of hyperkalemia on both disease severity and the risk of mortality among patients admitted to the emergency room. Methods This retrospective observational study utilized data from the Chinese Emergency Triage Assessment and Treatment database (CETAT, version 2.0), which was designed to evaluate and optimize management strategies for emergency room (ER) patients. Patients were systematically categorized based on serum potassium levels. Relationships between serum potassium levels, risk of mortality, and the severity of illness were then analyzed using multifactorial logistic regression and through Receiver Operating Characteristic (ROC) analysis. The effectiveness of various treatments at lowering potassium levels was also investigated. Results 12,799 emergency patients were enrolled, of whom 20.1% (n = 2,577) were hypokalemic and 2.98% (n = 381) were hyperkalemic. Among hyperkalemic patients, the leading reasons for visiting the ER were altered consciousness 23.88% (n = 91), cardiovascular symptoms 22.31% (n = 85), and gastrointestinal symptoms 20.47% (n = 78). Comparative analysis with patients exhibiting normal potassium levels revealed hyperkalemia as an independent factor associated with mortality in the ER. Mortality risk appears to positively correlate with increasing potassium levels, reaching peaks when blood potassium levels ranged between 6.5 and 7.0. Hyperkalemia emerged as a strong predictor of death in the ER, with an Area Under the Curve (AUC) of 0.89. The most frequently prescribed treatment for hyperkalemia patients was diuretics (57.32%, n = 188), followed by intravenous sodium bicarbonate (50.91%, n = 167), IV calcium (37.2%, n = 122), insulin combined with high glucose (27.74%, n = 91), and Continuous Renal Replacement Therapy (CRRT) for 19.82% (n = 65). Among these, CRRT appeared to be the most efficacious at reducing potassium levels. Diuretics appeared relatively ineffective, while high-glucose insulin, sodium bicarbonate, and calcium preparations having no significant effect on the rate of potassium decline. Conclusion Hyperkalemia is common in emergency situations, especially among patients with altered consciousness. There is a strong positive correlation between the severity of hyperkalemia and mortality risk. CRRT appears to be the most effective potassium reducting strategy, while the use of diuretics should be approached with caution.

Abstract Background Nursing students are encountering a range of health issues. Assessing social support is a key component in most questionnaire surveys related to health status, aiming to investigate the relationships and mechanisms between health status and social support to enhance overall health. Therefore, it is essential to seek out appropriate instruments to evaluate social support for nursing students. The Oslo-3 Social Support Scale (OSSS-3) is a reliable and concise instrument for evaluating social support. To date, there have been no studies validating the OSSS-3 based on Item Response Theory (IRT) models. Also, an officially validated Chinese version has not been found. The current research intended to verify the Chinese version of the OSSS-3. Methods The OSSS-3 was translated into Chinese and culturally adapted. Subsequently, the OSSS-3 was validated by employing the Classical Test Theory (CTT) and IRT models. Results The split-half reliability was 0.622. The Cronbach’s α coefficient was 0.687. The correlations between each item and total scores varied from 0.723 to 0.835. The retest coefficient was 0.907. The content validity index was 0.933. A single common factor was extracted and accounted for 61.559% of the variance. The item loading values on the single factor were between 0.743 and 0.814. The communalities were between 0.552 and 0.663. There was no variance between males and females (P = 0.055). The difference in scores between the top (30%) and bottom (30%) groups attained significance. IRT models results revealed that the discrimination parameters ranged from 1.39 to 2.33 and difficulty parameters increased monotonically. Conclusion The OSSS-3 demonstrates satisfying psychometric properties and is a proper instrument for measuring social support in Chinese nursing students.

Abstract Background Inflammation and dysregulated immunity play vital roles in idiopathic pulmonary arterial hypertension (IPAH), while the mechanisms that initiate and promote these processes are unclear. Methods Transcriptomic data of lung tissues from IPAH patients and controls were obtained from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA), differential expression analysis, protein-protein interaction (PPI) and functional enrichment analysis were combined with a hemodynamically-related histopathological score to identify inflammation-associated hub genes in IPAH. The monocrotaline-induced rat model of pulmonary hypertension was utilized to confirm the expression pattern of these hub genes. Single-cell RNA-sequencing (scRNA-seq) data were used to identify the hub gene-expressing cell types and their intercellular interactions. Results Through an extensive bioinformatics analysis, CXCL9, CCL5, GZMA and GZMK were identified as hub genes that distinguished IPAH patients from controls. Among these genes, pulmonary expression levels of Cxcl9, Ccl5 and Gzma were elevated in monocrotaline-exposed rats. Further investigation revealed that only CCL5 and GZMA were highly expressed in T and NK cells, where CCL5 mediated T and NK cell interaction with endothelial cells, smooth muscle cells, and fibroblasts through multiple receptors. Conclusions Our study identified a new inflammatory pathway in IPAH, where T and NK cells drove heightened inflammation predominantly via the upregulation of CCL5, providing groundwork for the development of targeted therapeutics.

Abstract To investigate the screening and predicting functions of obesity- and lipid-related indices for type 2 diabetes (T2D) in middle-aged and elderly Chinese, as well as the ideal predicted cut-off value. This study's data comes from the 2011 China Health and Retirement Longitudinal Study (CHARLS). A cross-sectional study design was used to investigate the relationship of T2D and 13 obesity- and lipid-related indices, including body mass index (BMI), waist circumference (WC), waist–height ratio (WHtR), visceral adiposity index (VAI), a body shape index (ABSI), body roundness index (BRI), lipid accumulation product (LAP), conicity index (CI), Chinese visceral adiposity index (CVAI), triglyceride- glucose index (TyG index) and its correlation index (TyG-BMI, TyG-WC, TyG-WHtR). The unadjusted and adjusted correlations between 13 indices and T2D were assessed using binary logistic regression analysis. The receiver operating characteristic curve (ROC) was used to determine the usefulness of anthropometric indices for screening for T2D and determining their cut‑off value, sensitivity, specificity, and area under the curve (AUC). The study comprised 9488 people aged 45 years or above in total, of whom 4354 (45.89%) were males and 5134 (54.11%) were females. Among them were 716 male cases of T2D (16.44%) and 870 female cases of T2D (16.95%). A total of 13 obesity- and lipid-related indices were independently associated with T2D risk after adjusted for confounding factors (P

Abstract In this randomized phase II clinical trial, we evaluated the effectiveness of adding the TLR agonists, poly-ICLC or resiquimod, to autologous tumor lysate-pulsed dendritic cell (ATL-DC) vaccination in patients with newly-diagnosed or recurrent WHO Grade III-IV malignant gliomas. The primary endpoints were to assess the most effective combination of vaccine and adjuvant in order to enhance the immune potency, along with safety. The combination of ATL-DC vaccination and TLR agonist was safe and found to enhance systemic immune responses, as indicated by increased interferon gene expression and changes in immune cell activation. Specifically, PD-1 expression increases on CD4+ T-cells, while CD38 and CD39 expression are reduced on CD8+ T cells, alongside an increase in monocytes. Poly-ICLC treatment amplifies the induction of interferon-induced genes in monocytes and T lymphocytes. Patients that exhibit higher interferon response gene expression demonstrate prolonged survival and delayed disease progression. These findings suggest that combining ATL-DC with poly-ICLC can induce a polarized interferon response in circulating monocytes and CD8+ T cells, which may represent an important blood biomarker for immunotherapy in this patient population.Trial Registration: ClinicalTrials.gov Identifier: NCT01204684.

Abstract Background Depressive symptoms are one of the most common psychiatric disorders, with a high lifetime prevalence rate among middle-aged and elderly Chinese. Obesity may be one of the risk factors for depressive symptoms, but there is currently no consensus on this view. Therefore, we investigate the relationship and predictive ability of 13 obesity- and lipid-related indices with depressive symptoms among middle-aged and elderly Chinese. Methods The data were obtained from The China Health and Retirement Longitudinal Study (CHARLS). Our analysis includes individuals who did not have depressive symptoms at the baseline of the CHARLS Wave 2011 study and were successfully follow-up in 2013 and 2015. Finally, 3790 participants were included in the short-term (from 2011 to 2013), and 3660 participants were included in the long-term (from 2011 to 2015). The average age of participants in short-term and long-term was 58.47 years and 57.88 years. The anthropometric indicators used in this analysis included non-invasive [e.g. waist circumference (WC), body mass index (BMI), and a body mass index (ABSI)], and invasive anthropometric indicators [e.g. lipid accumulation product (LAP), triglyceride glucose index (TyG index), and its-related indices (e.g. TyG-BMI, and TyG-WC)]. Receiver operating characteristic (ROC) analysis was used to examine the predictive ability of various indicators for depressive symptoms. The association of depressive symptoms with various indicators was calculated using binary logistic regression. Results The overall incidence of depressive symptoms was 20.79% in the short-term and 27.43% in the long-term. In males, WC [AUC = 0.452], LAP [AUC = 0.450], and TyG-WC [AUC = 0.451] were weak predictors of depressive symptoms during the short-term (P 0.05). Conclusion The research indicates that in the middle-aged and elderly Chinese, most obesity- and lipid-related indices have statistical significance in predicting depressive symptoms, but the accuracy of these indicators in prediction is relatively low and may not be practical predictors.

Abstract The purpose of the study was to determine whether changes in body mass index (BMI) and waist circumference (WC) in middle-aged and elderly Chinese are associated with metabolic syndrome. In this cohort investigation, 3697 middle-aged and elderly people aged 45 or over were recruited from the China Health and Retirement Longitudinal Study (CHARLS). The National Cholesterol Education Program Adult Treatment Panel III (2005) defined metabolic syndrome (MetS). With Cox regression analysis, we calculated hazard ratio (HR) and 95% confidence intervals (CIs) for MetS based on BMI-WC change categories. To assess the prevalence of MetS, the changes in BMI and WC levels were classified into four quartiles based on their relative and absolute changes. In subjects whose BMI and WC decreased (HR = 0.338; 95% CIs 0.264, 0.433) as well as those whose BMI increased and their WC decreased (HR = 0.375; 95% CIs 0.228, 0.499), metabolic syndrome risk was significantly lower compared with those with increases in both BMI and WC. Regarding the absolute changes in BMI, the lowest percentile of BMI was significantly lower in both males (HR = 0.302; 95% CIs 0.204, 0.448) and females (HR = 0.486; 95% CIs 0.354, 0.667) for the risk of metabolic syndrome. Similar results were observed in the absolute changes in WC, with the lowest quantile of WC having a significant impact on MetS risk in males (HR = 0.170; 95% CIs 0.107, 0.270) and females (HR = 0.303; 95% CIs 0.217, 0.424). The risk of metabolic syndrome was significantly associated with changes in BMI and WC in middle-aged and elderly Chinese. A reduced BMI and WC are associated with lower metabolic syndrome risks in middle-aged and elderly people.

Abstract Mechano-sensitive hair-like sensilla (MSHS) have an ingenious and compact three-dimensional structure and have evolved widely in living organisms to perceive multidirectional mechanical signals. Nearly all MSHS are iontronic or electronic, including their biomimetic counterparts. Here, an all-optical mechano-sensor mimicking MSHS is prototyped and integrated based on a thin-walled glass microbubble as a flexible whispering-gallery-mode resonator. The minimalist integrated device has a good directionality of 32.31 dB in the radial plane of the micro-hair and can detect multidirectional displacements and forces as small as 70 nm and 0.9 μN, respectively. The device can also detect displacements and forces in the axial direction of the micro-hair as small as 2.29 nm and 3.65 μN, respectively, and perceive different vibrations. This mechano-sensor works well as a real-time, directional mechano-sensory whisker in a quadruped cat-type robot, showing its potential for innovative mechano-transduction, artificial perception, and robotics applications.

Remediating soil contaminated with polycyclic aromatic hydrocarbons (PAHs) presents a significant environmental challenge due to their toxic and carcinogenic properties. Traditional PAHs remediation methods—chemical, thermal, and bioremediation—along with conventional soil-washing agents like surfactants and cyclodextrins face challenges of cost, ecological harm, and inefficiency. Here we show an effective and environmentally friendly calixarene derivative for PAHs removal through soil washing. Thiacalix[4]arene tetrasulfonate (TCAS) has a unique molecular structure of a sulfonate group and a sulfur atom, which enhances its solubility and facilitates selective binding with PAHs. It forms host-guest complexes with PAHs through π-π stacking, OH-π interactions, hydrogen bonding, van der Waals forces, and electrostatic interactions. These interactions enable partial encapsulation of PAH molecules, aiding their desorption from the soil matrix. Our results show that a 0.7% solution of TCAS can extract approximately 50% of PAHs from contaminated soil while preserving soil nutrients and minimizing adverse environmental effects. This research unveils the pioneering application of TCAS in removing PAHs from contaminated soil, marking a transformative advancement in resource-efficient and sustainable soil remediation strategies.

Fibrosing mediastinitis (FM) is a rare and benign fibroproliferative disease that presents with the proliferation of extensive, dense fibrous tissue in the mediastinum. Hemoptysis is a common clinical manifestation of FM. Clinically, most patients exhibit mild to moderate hemoptysis. We report a case of FM complicated with life-threatening massive hemoptysis. The patient was successfully rescued through a combination of bronchoscopic balloon closure, bronchial artery embolization (BAE), and surgical interventions. Although FM is frequently benign, vascular involvement can progress to life-threatening massive hemoptysis and must be treated appropriately.

IntroductionPodophyllotoxin (PPT) is a high-content and high-activity compound extracted from the traditional Chinese medicinal plant Dysosma versipellis (DV) which exhibits various biological activities. However, its severe toxicity limits its use. In clinical settings, patients with DV poisoning often experience adverse reactions when taking large doses in a short period. The heart is an important toxic target organ, so it is necessary to conduct 24-h acute cardiac toxicity studies on PPT to understand its underlying toxicity mechanism.MethodsBased on the concept of the toxicological evidence chain (TEC), we utilized targeted metabolomic and transcriptomic analyses to reveal the mechanism of the acute cardiotoxicity of PPT. The manifestation of toxicity in Sprague-Dawley rats, including changes in weight and behavior, served as Injury Phenotype Evidence (IPE). To determine Adverse Outcomes Evidence (AOE), the hearts of the rats were evaluated through histopathological examination and by measuring myocardial enzyme and cardiac injury markers levels. Additionally, transcriptome analysis, metabolome analysis, myocardial enzymes, and cardiac injury markers were integrated to obtain Toxic Event Evidence (TEE) using correlation analysis.ResultsThe experiment showed significant epistaxis, hypokinesia, and hunched posture in PPT group rats within 24 h after exposure to 120 mg/kg PPT. It is found that PPT induced cardiac injury in rats within 24 h, as evidenced by increased serum myocardial enzyme levels, elevated concentrations of cardiac injury biomarkers, and altered cardiac cell morphology, all indicating some degree of cardiac toxicity. Transcriptome analysis revealed that primary altered metabolic pathway was arachidonic acid metabolism after PPT exposure. Cyp2e1, Aldob were positively correlated with differential metabolites, while DHA showed positive correlation with differential genes Fmo2 and Timd2, as well as with heart injury markers BNP and Mb.ConclusionThis study comprehensively evaluated cardiac toxicity of PPT and initially revealed the mechanism of PPT-induced acute cardiotoxicity, which involved oxidative stress, apoptosis, inflammatory response, and energy metabolism disorder.