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Abstract Objective To assess the prevalence, timing, and functional impact of neuropsychiatric symptoms in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to assess whether these neuropsychiatric symptoms are associated with magnetic resonance imaging (MRI) features of the patients. Methods Our study included a total of 78 patients with CADASIL. To assess neuropsychiatric symptoms, we evaluated the caregivers using the Neuropsychiatric Inventory (NPI). Patients were considered to have an irritability, depression, apathy, aggression, or anxiety disorder if they scored ≥1 in the NPI. Subsequently, we conducted a more detailed assessment of irritability, depression, apathy, aggression, and anxiety. Multivariate logistic regression was employed to analyze the relationships between neuropsychiatric symptoms and clinical/MRI features in the patients. Results Overall, 57.69% of patients with CADASIL experienced neuropsychiatric symptoms. Among these symptoms, irritability was the most prevalent (52.56%), followed by depression (19.23%), apathy (17.95%), aggression (7.69%), and anxiety (6.41%). The mean age of onset for irritability was the youngest, followed by anxiety, apathy, aggression, and depression. Among patients with both stroke/TIA and neuropsychiatric symptoms, 31.03% reported experiencing neuropsychiatric symptoms prior to stroke/TIA. Furthermore, both irritability and apathy had a negative impact on the patients' daily functioning. Additionally, there was a correlation between the presence of neuropsychiatric symptoms and the patients' MRI lesion burden. Interpretation Our study has discovered that neuropsychiatric symptoms are highly prevalent in patients with CADASIL and may occur before cerebrovascular events, suggesting that neuropsychiatric symptoms of CADASIL deserve more attention and earlier exploration.

Abstract Intermetallic phases with atomic ordering are highly active and stable in catalysts. However, understanding the atomistic mechanisms of disorder-to-order phase transition, particularly in multi-component systems, remains challenging. Here, we investigate the atom diffusion and phase transition within Pd@Pt-Co cubic nanoparticles during annealing, using in-situ electron microscopy and ex-situ atomic resolution element analysis. We reveal that initial outward diffusing Pd partially substitutes Pt, forming a (Pt, Pd)-Co ternary system in the surface region, enabling the phase transition at a low temperature of 400 °C, followed by shape-preserved inward propagation of the ordered phase. At higher temperatures, excessive interdiffusion across the interface changes the stoichiometric ratio, diminishing the atomic ordering, leading to obvious change in morphology. Calculations indicate that the Pd-substitute in (Pt, Pd)-Co system leads to a significantly lower phase transition temperature compared to that of Pt-Co alloy and thus a lower activation energy for atomic diffusion. These insights into atomistic behavior are crucial for future design of multi-component systems.

Abstract Background Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory condition and a leading cause of mortality, with acute exacerbations (AECOPD) significantly complicating its management and prognosis. Despite the development of various prognostic prediction models for patients with AECOPD, their performance and clinical applicability remain unclear, necessitating a systematic review to evaluate these models and provide guidance for their future improvement and clinical use. Method PubMed, Web of Science, CINAHL, Scopus, EMBASE, and Medline were searched for studies published from their inception until February 5, 2024. Data extraction and evaluation were conducted using the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS). The Prediction model Risk Of Bias Assessment Tool (PROBAST) was employed to assess the risk of bias and applicability of the models. Results After deduplication and screening 5942 retrieved articles, 46 studies comprising 53 models were included. Of these, 17 (37.0%) studies developed from studies conducted in China. All models were based on cohort studies. Mortality was the predicted outcome in 27 (50.9%) models. Logistic regression was used in 41 (77.4%) models, while machine learning methods were employed in 9 (17.0%) models. The median (minimum, maximum) sample size for model development was 672 (106, 150,035). The median (minimum, maximum) number of predictors per model was 5 (2, 42). Frequently used predictors included age (n = 28), dyspnea severity scores (n = 12), and PaCO2 (n = 11). The pooled AUC was 0.80 for mortality prediction models and 0.84 for hospitalization-related outcomes. 52 models have a high overall risk of bias, and all models were judged to have low concern regarding applicability. Major sources of bias included insufficient sample sizes (83.0%), reliance on univariate analysis for predictor selection (73.6%), inappropriate internal and external validation methods (54.7%), inappropriate inclusion and exclusion criteria for study subjects (50.9%) and so on. The only model with low bias was the PEARL score. Conclusion Current prognostic risk prediction models for patients with AECOPD generally exhibit high bias. Future efforts should standardize model development and validation methods, and develop widely usable clinical models.

Abstract Background With existing researches identifying an increased rate of long-term conditions (LTCs) among Inflammatory Bowel Disease (IBD) patients, yet there is a lack of exploration into the patterns of comorbidity and prognostic rates for IBD patients with multiple morbidities. Methods The study included 8,305 participants who self-reported having IBD, comprising ulcerative colitis (UC) and Crohn’s disease (CD). Latent class analysis (LCA) was utilized to create optimal categories of LTC combinations for UC and CD patients with additional long-term conditions. Using Cox proportional hazards models, we compared the all-cause mortality rates over a 16-year follow-up among UC and CD patients within different LTC categories, both without LTCs and with the addition of one LTC, the probability of major adverse cardiovascular events (MACE), and the rates of IBD-related surgeries. Results A total of 5,617 participants reported having two or more LTCs, with the LCA method identifying three prevalence categories among CD patients, and four prevalence categories among UC patients. The highest mortality rate among CD patients was found in category 3: (HR 1.789, 95% CI (1.439–2.224)), and the highest rates of MACE were also in category 3: (HR 11.432, 95% CI (9.332–14.005)), with hypertension being the distinguishing characteristic of this category, and the highest rates of IBD-related surgeries being associated with pain in category 1: (HR 1.217, 95% CI (0.983–1.506)). Among UC patients, the highest mortality rate was in category 3: (HR 2.221, 95% CI (1.837–2.684)), with the highest MACE rates found in category 3: (HR 6.422, 95% CI (5.659–7.288)), and the highest rates of IBD-related surgeries being associated with pain, also in category 3: (HR 1.218, 95% CI (1.041–1.425)). Conclusion The rates of adverse health outcomes in IBD patients is closely associated with multimorbidity patterns, underscoring the need to fully consider multimorbidity patterns in the assessment, management, and treatment strategies for IBD.

Abstract Background Hepatitis B virus (HBV) infection is a persistent global public health problem, and curing for chronic hepatitis B (CHB) through the application of existing antiviral drugs is beset by numerous challenges. The viral protein HBx is a critical regulatory factor in the life cycle of HBV. Targeting HBx is a promising possibility for the development of novel therapeutic strategies. Methods The Nano-Glo® HiBiT Lysis Detection System was used to screen the herbal monomer compound library for compounds that inhibit HBx expression. Western blotting was used to examine proteins expression. Southern blotting or Northern blotting were used to detect HBV DNA or HBV RNA. ELISA was performed to detect the HBsAg level. The effect of asiatic acid on HBV in vivo was investigated by using recombinant cccDNA mouse model. Results Asiatic acid, an extract of Centella asiatica, significantly reduced the HBx level. Mechanistic studies demonstrated that asiatic acid may promote the degradation of HBx in an autophagy pathway-dependent manner. Subsequently, asiatic acid was found to reduce the amount of HBx bound to covalently closed circular DNA (cccDNA) microchromosomes, and repressive chromatin modifications then occurred, ultimately inhibiting cccDNA transcriptional activity. Moreover, in HBV-infected cells and a mouse model of persistent HBV infection, asiatic acid exhibited potent anti-HBV activity, as evidenced by decreased levels of HBV RNAs, HBV DNA and HBsAg. Conclusions Asiatic acid was identified as a compound that targets HBx, revealing its potential for application as an anti-HBV agent.

Abstract The instability and failure processes of coal-rock combinations are accompanied by the release of acoustic emission (AE) and infrared radiation (IR) signals. To investigate the characteristics of AE and IR signals during the failure process in coal-rock combinations with different ratios, and to analyze the effectiveness and applicability of the monitoring methods for these two signals in various specimen ratios. In this paper, the uniaxial compression tests were conducted on seven coal-rock combinations with different ratios by using the rock mechanics loading system and the cooperative monitoring platform of infrared and acoustic emission. The results show that (1) the AE counts for failure precursors in coal-rock combinations are positively correlated with the coal-rock ratio, whereas the AE peak counts are negatively correlated. Moreover, as the coal-rock ratio decreases, the slope of the cumulative AE count curve during the peak failure stage approaches 1. (2) During the elastic and yield stages, the maximum infrared radiation temperature (MIRT) curve fluctuates, and just before peak failure, the curve displays a distinctive “V” shape. This “V” shape becomes more pronounced as the coal-rock ratio decreases. (3) In the monitoring of damage precursors of coal-rock combinations, when the ratio of coal to rock is 1:3 or less, IR monitoring is better than AE monitoring. Conversely, when the ratio of coal to rock is greater than 1:3, AE monitoring is more suitable. Consequently, the combined monitoring of AE and IR signals can increase the reliability and precision of early warning signals for coal-rock assemblage damage precursors.

Abstract Objectives This study addresses the growing importance of health economics and pharmacoeconomics in preparing healthcare professionals for economic decision-making, particularly in China’s evolving healthcare system. Despite their significance, these subjects are inconsistently included in health education in Southwest China, making it crucial to assess students' proficiency and educational needs. Methods A cross-sectional study was conducted from July to October 2023, involving medical and pharmaceutical programs across universities in Sichuan, Chongqing, Guizhou, and Yunnan. Data on students' knowledge, attitudes, and proficiency were captured using a structured questionnaire. Advanced statistical methods, including descriptive analysis, ANOVA, regression analysis, PCA, and Spearman correlation heatmaps, were employed for data analysis using IBM SPSS and Python. The sample consisted of 781 students, with the survey facilitated via the Questionnaire Star platform. Results The survey revealed moderate comprehension of health economics and pharmacoeconomics among 781 health-related students, with an average knowledge score of 2.9. The majority were pharmacy students (45.58%) and aged 21–24 years (65.81%) with a significant female majority (64.92%). Academic year significantly influenced understanding, while gender differences were minimal. Spearman correlation indicated a strong linkage (0.78) between Supply and Demand and Cost Effectiveness, with minimal correlations between knowledge and attitudes towards the educational importance of health economics. Multiple regression analysis highlighted the impact of gender and academic progression on students' comprehension of Supply and Demand concepts, as well as the influence of knowledge levels on their attitudes towards the importance of health economics education. PCA indicated the complex structure of knowledge and attitudes. Conclusions The study found moderate knowledge levels in health economics among health professions students in Southwest China, with academic year affecting comprehension and minimal gender differences. Pharmacy students had higher proficiency in pharmaceutical-related areas, but gaps in complex topics like 'Economic Evaluation' highlight the need for targeted educational improvements to better prepare students for healthcare economic decision-making.

Abstract Background Cluster randomized trials (CRTs) are increasingly important for evaluating interventions embedded in health care systems. An essential parameter in sample size calculation to detect both overall and heterogeneous treatment effects for CRTs is the intra-cluster correlation coefficient (ICC) of both outcome and covariates of interest. However, obtaining advance estimates for the ICC can be challenging. When trial outcomes will be obtained from routinely collected data sources, there is an opportunity to obtain reliable ICC estimates in advance of the trial. Using USA national Medicare data, we estimated ICCs for a range of outcomes to inform the design of CRTs for people living with Alzheimer’s and related dementias (ADRD). Method Data from 2018 Medicare Fee-for-Service beneficiaries, specifically, 1,898,812 individuals (≥ 65 years) with diagnosis of ADRD within 3436 hospital service areas (treated as clusters) and 306 hospital referral regions (treated as fixed strata), were used to calculate unadjusted and adjusted ICC estimates for three outcomes: death, any hospitalizations, and any emergency department (ED) visits and three covariates: age, race and sex. We present both overall and stratum-specific ICC estimates. We illustrate their use in sample size calculations for overall treatment effects as well as detecting treatment effect heterogeneity. Results The unadjusted overall ICCs for death, hospitalizations, and ED visits were 0.001, 0.010, and 0.017 respectively. Stratum-specific ICCs varied widely across the 306 HRRs: median 0.001, 0.010 and 0.025 for death, hospitalizations, and ED visits respectively and 0.007, 0.001, and 0.080 for age, sex and race. An interactive R Shiny app is provided that allows users to retrieve estimates overlayed on a map of the USA. Conclusions We presented both adjusted and unadjusted ICCs for outcomes as well as unadjusted ICCs for covariates of potential interest from population-level data in the USA and demonstrated how the estimates may be used in sample size calculations for CRTs in ADRD.

Abstract Hormone receptor-positive breast cancer (BC) is the most prevalent subtype of BC and is generally correlated with a favorable prognosis. This study aimed to determine the incidence and survival trends among women diagnosed with hormone receptor-positive BC between 1990 and 2019. Female patients with hormone receptor-positive BC for calendar years 1990–2019 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database and categorized into six diagnostic groups according to the year of diagnosis. Age-adjusted incidence rates (IRs) were calculated using joinpoint regression. We used the Kaplan–Meier method and multivariate Cox regression analyses to determine the association between diagnostic groups, and overall survival (OS) and BC-specific survival (BCSS). The final analysis included 370,729 women, among whom 37,943 (10.2%), 49,266 (13.3%), 55,652 (15.0%), 64,451 (17.4%), 77,127 (20.8%), and 86,290 (23.3%) were diagnosed between 1990 and 1994, 1995–1999, 2000–2004, 2005–2009, 2010–2014, and 2015–2019, respectively. Within the overall cohort, IRs gradually increased from 70 per 100,000 in 1990 to 113 per 100,000 in 2019 (average annual percent change, 1.59%; 95% CI, 1.18–1.99). Multivariate Cox regression analysis revealed that the survival outcomes gradually improved over nearly three decades among hormone receptor-positive BC patients, with a 0.8% and 1.3% decrease in risk for all-cause and BC-specific mortality each year, respectively. Compared to 1990–1994, hormone receptor-positive BC patients diagnosed in 2015–2019 had a 22% lower risk of all-cause death (hazard ratio [HR], 0.78; 95% CI, 0.76–0.81) and a 27% lower risk of BC-specific death (HR, 0.73; 95% CI, 0.70–0.76). The development of treatment strategies within the past three decades, especially endocrine therapy, may contribute to the continuous improvement of clinical outcomes in patients with hormone receptor-positive BC.

Abstract Purpose The advantages of en bloc resection of bladder tumors (ERBT) over transurethral resection of bladder tumors (TURBT) in terms of patient prognosis are not yet clear, and there are some technical limitations. We aimed to compare the tumor recurrence in non-muscle invasive bladder cancer (NMIBC) patients with tumor diameter ≥ 3 cm undergoing either TURBT or thulium laser ERBT. Methods The patients included were those diagnosed with NMIBC based on pathological confirmation and underwent TURBT or modified thulium laser ERBT in the Department of Urology at Tongji Hospital from 2019 to 2024. The patients’ medical records were meticulously collected and postoperative follow-up was diligently conducted by trained personnel. Recurrence-free survival curves were generated utilizing the Kaplan–Meier method, and group comparisons were performed using the log-rank trend test. To minimize biases, we employed stratified survival analysis, alongside univariate and multivariate Cox regression analysis. Results This study included a total of 396 patients with NMIBC, with 214 undergoing TURBT and 182 undergoing ERBT. For all patients, there was no significant difference (P = 0.180) in RFS between the TURBT and ERBT groups. For patients with tumor diameter ≥ 3 cm, stratified analysis revealed that the RFS of the ERBT group was significantly better than that of the TURBT group (P = 0.033). However, in patients with tumor diameter

Abstract Background Aging negatively impacts tissue repair, particularly in skeletal muscle, where the regenerative capacity of muscle stem cells (MuSCs) diminishes with age. Although aerobic exercise is known to attenuate skeletal muscle atrophy, its specific impact on the regenerative and repair capacity of MuSCs remains unclear. Methods Mice underwent moderate‐intensity continuous training (MICT) from 9 months (aged + Ex‐9M) or 20 months (aged + Ex‐20M) to 25 months, with age‐matched (aged) and adult controls. Histological examinations and MuSC transplantation assays assessed aerobic exercise effects on MuSC function and muscle regeneration. CCN2/connective tissue growth factor modulation (overexpression and knockdown) in MuSCs and AICAR supplementation effects were explored. Results Aged mice displayed significantly reduced running duration (65.33 ± 4.32 vs. 161.9 ± 1.29 min, mean ± SD, P

The waters of the Changdao Archipelago are located at the confluence of the Yellow and Bohai seas, which have high species diversity and spatial and temporal heterogeneity. This area is an important route for migratory fish and macroinvertebrates to enter the Bohai Sea for spawning or to leave the Bohai Sea southward for overwintering. In recent decades, with increasing human activities, fishing pressure, and ocean pollution, the ecosystems of the Yellow and Bohai seas have become fragile with many fishery species evolving towards miniaturization and precociousness. Important fishery resources are unable to fulfill the minimum requirements during the fishing season, and the support function of the Yellow and Bohai seas is diminishing. Research on fishery species in the waters of the Changdao Archipelago is less focused on their composition, community structure, and fishery biological health evaluation. To understand the species composition and diversity of demersal fishery species in the waters of the Changdao Archipelago and to identify keystone species that play important regulatory roles in the biological community, we analyzed the biological diversity and identified the dominant species based on the Changdao Archipelago fishery resource survey data from March to December 2021. Keystone species were determined by food web topology and social network analysis, and the fishery biological health status was determined based on the 2021 survey data. A total of 38 species of fish (mainly warm-water, demersal, and low-value fish) and 50 species of invertebrates (mainly small crustaceans) were caught in the area. There were obvious seasonal variations in the composition of the dominant species, with invertebrates, such as Alpheus japonicus and Oratosquilla oratoria, dominating in the spring, Chaeturichthys stigmatias and O. oratoria in the summer and autumn, and only A. japonicus and C. stigmatias in the winter. The species Margalef richness index (R) was highest in the summer, and the Shannon-Wiener diversity index (H´) and Pielou evenness index (J´) were highest in the autumn, in the waters of the Changdao Archipelago. To further investigate the food web topology of the bottom fishery community in the waters of the Changdao Archipelago, and to identify keystone species, seasonal changes in the topology of the study area were analyzed. Based on field survey data, the main species (IRI > 100) were constructed. The area contained 13–23 main species (S) and 32–113 feeding relationships (L) in four seasons. The node density (Dd) ranged from 0.18–0.41, link density from 2.46–5.65, connectance (C) from 0.18–0.28, clustering coefficient (Cl) from 0.334–0.401, and weighted clustering coefficient (W-Cl) from 0.276–0.373, consistent with the interspecific feeding relationships in communities under natural conditions. There were significant seasonal variations in each topological index. Based on the topological structure index, we analyzed the robustness of keystone species at the bottom of the food web in the waters of the Changdao Archipelago. Using different removal methods, we found that these three species have differences in maintaining the robustness of the food web. To study the importance of keystone species, species were removed in ascending and descending order according to the node degree (D). Under the descending order of removal, the stability of the food web showed a downward trend, showing a "staged" change of first increasing and then decreasing. This change may be due to the reconstruction of the food web caused by the loss of some species. Even if new feeding relationships are created among other species, the number of corresponding feeding relationships decreased exponentially, while feeding relationships with ascending removal patterns showed an inverted U-shaped trend with a significantly slower rate of decline. The most important species in the food web were removed first in descending order, which had the greatest effect on the stability of the food web and the number of feeding relationships. Among them are species that play important roles in the robustness of the food web—C. stigmatias, Pennahia argentata, A. japonicus, and O. oratoria are both dominant and keystone species. The keystone species in the waters of the Changdao Archipelago are diverse and small, as most of the bottom organisms in the area are omnivores with diverse feeding relationships and include many migratory species in addition to native species, which leads to the diversity of keystone species—C. stigmatias, P. argentata, A. japonicus and O. oratoria are both dominant and keystone species. The keystone species are characterized by diversification and miniaturism. When keystone species were removed from the food web, the linkage robustness and number of feeding relationships decreased significantly, indicating that keystone species play important roles in maintaining the stability of the food web. In winter, keystone predator species change from O. oratoria and P. argentat to C. stigmatias, and A. japonicus changes from the keystone prey species to the keystone intermediate species. Niche replacement of keystone species leads to the simplification of the bottom of the food web and, to some extent, increases the vulnerability of the bottom community structure in the waters of the Changdao Archipelago. Therefore, in future studies, dynamic monitoring and protection of keystone species should be strengthened to maintain their robustness function in the food web, to maximize the protection of natural resources in the waters of the Changdao Archipelago.

Abstract Triple-negative breast cancer (TNBC) represents a significant health concern for women worldwide, and the overproduction of MMP9 and CD151 is associated with various cancers, influencing tumour growth and progression. This study aimed to investigate how CD151 and MMP9 affect TNBC cell migration, apoptosis, proliferation, and invasion. Immunohistochemical experiments revealed that CD151 and MMP9 were positively expressed in triple-negative breast cancer, and lymph node metastasis, the histological grade, and CD151 and MMP9 expression were found to be independent prognostic factors for the survival of patients with triple-negative breast cancer. Cytological experiments indicated that the knockdown of CD151 or MMP9 slowed triple-negative breast cancer cell growth, migration, and invasion and increased the apoptosis rate. Compared with CD151 knockdown, double MMP9 and CD151 knockdown further promoted cell death and inhibited TNBC cell proliferation, migration, and invasion. Moreover, β-catenin and p-GSK-3β were significantly downregulated. In summary, simultaneously silencing CD151 and MMP9 further suppressed the proliferation, migration and invasion of TNBC cells and promoted their apoptosis. One possible strategy for inducing this effect is to block the GSK-3β/β-catenin pathway.

Abstract Background Despite major primary health care (PHC) reforms in China with the 2009 launch of the National Essential Public Health Service Package, the country experiences many challenges in improving the management of non-communicable diseases in PHC facilities. “EMERALD” is a multifaceted implementation strategy to strengthen the management of hypertension and type-2 diabetes mellitus (T2DM) in PHC facilities. The study aims to: (1) examine the effectiveness of EMERALD in improving hypertension and T2DM management; (2) evaluate the implementation of the interventions; and (3) use the study findings to model the long-term health economic impact of the interventions. Methods The EMERALD intervention components include: (1) empowerment for PHC providers through training and capacity building; (2) empowerment for patient communities through multi-media health education; and (3) empowerment for local health administrators through health data monitoring and strengthening governance of local PHC programs. An interrupted time series design will be used to determine the effectiveness of the interventions based on routinely collected health data extracted from local health information systems. The primary effectiveness outcome is the guideline-recommended treatment rates for people with hypertension and T2DM. Secondary effectiveness outcomes include hypertension and T2DM diagnosis and control rates, and enrolment and adherence rates to the recommended care processes in the National Essential Public Health Service Package. A mixed-methods process evaluation will be conducted to evaluate the implementation of the interventions, including the reach of the target population, adequacy of adoption, level of implementation fidelity, and maintenance. Qualitative interviews with policy makers, health administrators, PHC providers, and patients with hypertension and/or T2DM will be conducted to further identify factors influencing the implementation. In addition, health economic modelling will be performed to explore the long-term incremental costs and benefits of the interventions. Discussion This study is expected to generate important evidence on the effectiveness, implementation, and health economic impact of complex PHC interventions to strengthen the primary care sector’s contribution to addressing the growing burden of non-communicable diseases in China. Trial registration The study has been registered on Chinese Clinical Trial Registry at https://www.chictr.org.cn/ (Registration number ChiCTR2400082036, on March 19th 2024).

Background: To explore the mediating effect of smartphone addiction between psychological resilience and insomnia among university students. Methods: This study included 581 clinical medical students from the Dalian Medical University, enrolled between September 2020 and May 2023. The Smartphone Addiction Scale (SAS-SV), Insomnia Severity Index (ISI), and Connor–Davidson Resilience Scale (CD-RISC) were used to assess smartphone addiction, insomnia, and psychological resilience among the students. The Process macro and Bootstrap methods were employed to analyze the mediating effect of smartphone addiction between psychological resilience and insomnia. Results: The detection rate of smartphone addiction was 28.06% (163/581), and the detection rate of insomnia was 26.17% (152/581). The total SAS-SV score was 27.60 ± 14.27, the total ISI score was 6.60 ± 5.33, and the total CD-RISC score was 72.86 ± 6.88. There was a significant negative correlation between the total CD-RISC score and the total SAS-SV score (r=–0.4129, P < .0001), and a significant negative correlation between the total CD-RISC score and the total ISI score (r = –2.942, P < .0001). The total SAS-SV score and the total ISI score were significantly positively correlated (r=0.5687, P < .0001). Psychological resilience was used as the independent variable, insomnia as the dependent variable, and smartphone addiction as the mediating variable in the mediation effect analysis. Psychological resilience negatively predicted insomnia (β=–0.0940, P < .0001), smartphone addiction positively predicted insomnia (β=0.1564, P < .0001), and smartphone addiction mediated the relationship between psychological resilience and insomnia (effect value=–0.1339, 95% CI: –0.1680 to –0.1034), with an effect size of 58.75%. Conclusion: Psychological resilience directly affects insomnia and also indirectly affects insomnia through the mediating effect of smartphone addiction.

Abstract Background Children born to women with HIV but who do not become HIV infected experience increased morbidity and mortality compared with children born to women without HIV. The basis of this increased vulnerability is unknown. The microbiome, specifically the infant gut microbiome, likely plays an important role in infant immune development. The human milk microbiome is thought to have an important role in the development of the infant gut and therefore, if perturbed, may contribute to this increased vulnerability. We investigated the effects of HIV and its therapies on the milk microbiome and possible changes in the milk microbiome before or after infant HIV infection. Results Seven-hundred fifty-six human milk samples were selected from three separate studies conducted over a 15-year period to investigate the role of HIV and its therapies on the human milk microbiome. Our data reveal that the milk microbiome is modulated by parity (R 2 = 0.006, p = 0.041), region/country (R 2 = 0.014, p = 0.007), and duration of lactation (R 2 = 0.027–0.038, all p

Interferon-stimulated genes (ISGs) are crucially expressed in response to interferons and play pivotal roles in tumor immunity. These genes can either inhibit or promote tumor growth and infiltration by modulating immunosuppressive molecules, immune checkpoint inhibition, and immune editing. This review examines the specific mechanisms through which ISGs influence tumor immunity and their impact on oncological drugs, aiming to provide a theoretical foundation for developing more precise treatment strategies.

Abstract Flow cytometry is a vital tool in biomedical research and laboratory medicine. However, its accuracy is often compromised by undesired fluctuations in fluorescence intensity. While fluorescence lifetime imaging microscopy (FLIM) bypasses this challenge as fluorescence lifetime remains unaffected by such fluctuations, the full integration of FLIM into flow cytometry has yet to be demonstrated due to speed limitations. Here we overcome the speed limitations in FLIM, thereby enabling high-throughput FLIM flow cytometry at a high rate of over 10,000 cells per second. This is made possible by using dual intensity-modulated continuous-wave beam arrays with complementary modulation frequency pairs for fluorophore excitation and acquiring fluorescence lifetime images of rapidly flowing cells. Moreover, our FLIM system distinguishes subpopulations in male rat glioma and captures dynamic changes in the cell nucleus induced by an anti-cancer drug. FLIM flow cytometry significantly enhances cellular analysis capabilities, providing detailed insights into cellular functions, interactions, and environments.

Achieving diffraction-limited performance in fourth-generation synchrotron radiation sources demands monochromator crystals that can preserve the wavefront across an unprecedented extensive range. There is an urgent need for techniques of absolute crystal diffraction wavefront measurement. At the Beijing Synchrotron Radiation Facility (BSRF), a novel edge scan wavefront metrology technique has been developed. This technique employs a double-edge tracking method, making diffraction-limited level absolute crystal diffraction wavefront measurement a reality. The results demonstrate an equivalent diffraction surface slope error below 70 nrad (corresponding to a wavefront phase error of 4.57% λ) r.m.s. within a nearly 6 mm range for a flat crystal in the crystal surface coordinate. The double-edge structure contributes to exceptional measurement precision for slope error reproducibility, achieving levels below 15 nrad (phase error reproducibility < λ/100) even at a first-generation synchrotron radiation source. Currently, the measurement termed double-edge scan (DES) has already been regarded as a critical feedback mechanism in the fabrication of next-generation crystals.

The present study aims to evaluate the effects of the antibacterial peptide Microcin J25 (ABP MccJ25) on growth performance, intestinal barrier function, antioxidant capacity and ileal microbiota in pigeon squabs. The 80 pairs of American Silver King pigeon parents and 240 healthy day 1 squabs were randomly divided into four groups, including 4 parent pairs and 12 pigeon squabs per group with 5 replicates. Parent pigeons were fed a basal diet (CON) or the addition of 100, 200, 300 mg/kg of ABP MccJ25 (ABP100, ABP200, and ABP300, respectively) for 4 weeks. Results showed that the group ABP200 remarkably reduced the feed conversion ratio and increased average daily gain in pigeon squabs from 7 to 21 d (p

Abstract Background Racial and ethnic disparities in mortality persist among US cancer survivors, with social determinants of health (SDoH) may have a significant impact on these disparities. Methods A population-based cohort study of a nationally representative sample of adult cancer survivors, who participated in the US National Health and Nutrition Examination Survey from 1999 to 2018 was included. Sociodemographic characteristics and SDoH were self-reported using standardized questionnaires in each survey cycle. The SDoH was examined by race and estimated for associations with primary outcomes, which included all-cause and cancer-specific mortality. Multiple mediation analysis was performed to assess the contribution of each unfavorable SDoH to racial disparities to all-cause and cancer-specific mortality. Results Among 5163 cancer survivors (2724 [57.7%] females and 3580 [69.3%] non-Hispanic White individuals), only 881 (24.9%) did not report an unfavorable SDoH. During the follow-up period of up to 249 months (median 81 months), 1964 deaths were recorded (cancer, 624; cardiovascular, 529; other causes, 811). Disparities in all-cause and cancer-specific mortality were observed between non-Hispanic Black and White cancer survivors. Unemployment, lower economic status, education less than high school, government or no private insurance, renting a home or other arrangements, and social isolation were significantly and independently associated with worse overall survival. Unemployment, lower economic status, and social isolation were significantly associated with cancer-specific mortality. Compared to patients without an unfavorable SDoH, the risk of all-cause mortality was gradually increased in those with a cumulative number of unfavorable SDoHs (1 unfavorable SDoH: hazard ratio [HR] = 1.54, 95% CI 1.25–1.89; 2 unfavorable SDoHs: HR = 1.81, 95% CI 1.46–2.24; 3 unfavorable SDoHs: HR = 2.42, 95% CI 1.97–2.97; 4 unfavorable SDoHs: HR = 3.22, 95% CI 2.48–4.19; 5 unfavorable SDoHs: HR = 3.99, 95% CI 2.99–5.33; 6 unfavorable SDoHs: HR = 6.34 95% CI 4.51–8.90). A similar trend existed for cancer-specific mortality. Conclusions In this cohort study of a nationally representative sample of US cancer survivors, a greater number of unfavorable SDoH was associated with increased risks of mortality from all causes and cancer. Unfavorable SDoH levels were critical risk factors for all-cause and cancer-specific mortality, as well as the underlying cause of racial all-cause mortality disparities among US cancer survivors.

Abstract Background This study investigates the molecular mechanisms of CC@AC&SF@PP NPs loaded with AC099850.3 siRNA and sorafenib (SF) for improving hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). Methods A dataset of 44 HBV-HCC patients and their survival information was selected from the TCGA database. Immune genes related to survival status were identified using the ImmPort database and WGCNA analysis. A prognostic risk model was constructed and analyzed using Lasso regression. Differential analysis was performed to screen key genes, and their significance and predictive accuracy for HBV-HCC were validated using Kaplan–Meier survival curves, ROC analysis, CIBERSORT analysis, and correlation analysis. The correlation between AC099850.3 and the gene expression matrix was calculated, followed by GO and KEGG enrichment analysis using AC099850.3 and its co-expressed genes. HepG2.2.15 cells were selected for in vitro validation, and lentivirus interference, cell cycle determination, CCK-8 experiments, colony formation assays, Transwell experiments, scratch experiments, and flow cytometry were performed to investigate the effects of key genes on HepG2.2.15 cells. A subcutaneous transplanted tumor model in mice was constructed to verify the inhibitory effect of key genes on HBV-HCC tumors. Subsequently, pH-triggered drug release NPs (CC@AC&SF@PP) were prepared, and their therapeutic effects on HBV-HCC in situ tumor mice were studied. Results A prognostic risk model (AC012313.9, MIR210HG, AC099850.3, AL645933.2, C6orf223, GDF10) was constructed through bioinformatics analysis, showing good sensitivity and specificity in diagnostic prediction. AC099850.3 was identified as a key gene, and enrichment analysis revealed its impact on cell cycle pathways. In vitro cell experiments demonstrated that AC099850.3 promotes HepG2.2.15 cell proliferation and invasion by regulating immune checkpoint CD276 expression and cell cycle progression. In vivo, subcutaneously transplanted tumor experiments showed that AC099850.3 promotes the growth of HBV-HCC tumors in nude mice. Furthermore, pH-triggered drug release NPs (CC@AC&SF@PP) loaded with AC099850.3 siRNA and SF were successfully prepared and delivered to the in situ HBV-HCC, enhancing the effectiveness of combined therapy for HBV-HCC. Conclusions AC099850.3 accelerates the cell cycle progression and promotes the occurrence and development of HBV-HCC by upregulating immune checkpoint CD276 expression. CC@AC&SF@PP NPs loaded with AC099850.3 siRNA and SF improve the effectiveness of combined therapy for HBV-HCC.

Recent ichthyofauna surveys in Phia Oac-Phia Den National Park, Vietnam, yielded 16 specimens of loach representing the genus Vanmanenia. These specimens were uniform in morphology and distinct from known species, leading to the designation of a new species, Vanmanenia duci sp. nov. This species is distinguished from congeners by the following combination of characters: pectoral fin: I, 15; pelvic fin: I, 8; lateral line scales 77–83; the distance from the anus to the posterior insertion of the pelvic fin being greater than from the anus to the anal fin origin; a lateral black stripe from the gill opening to the caudal fin base; a black spot at the caudal fin origin equal to the eye diameter; and a lower lip with three large papillae, with the middle one being larger. The new species differs from Vanmanenia caldwelli (Nichols, 1925) by its mouth soft-tissue structures and lower morphometric values and from Vanmanenia ventrosquamata (Mai, 1978) and Vanmanenia caobangensis Nguyen, 2005 by having more lateral line scales and lower body depth. Additionally, Vanmanenia duci sp. nov. has a larger eye and wider interorbital space compared to other species in Vietnam. This species is found in the Red River basin in Vietnam and the Bang Giang River flowing into China, indicating high potential for freshwater fish diversity in these river systems.

Abstract Background Breastfeeding is widely recognized for its potential to reduce childhood obesity. However, research investigating these benefits in children breastfed for a short duration (up to 6 months) remains limited despite this being a common practice globally. Methods This study focused on a population breastfed for 6 months or less to determine the potential benefits of short-term breastfeeding for preventing childhood obesity. Data were collected from five survey cycles of an US-based population study (the National Health and Nutrition Examination Survey (NHANES)), spanning 2009–2020. A sample of 3,211 children aged 2–6 years was selected, including 1,373 never breastfed and 1,838 ever breastfed. Logistic regression analysis examined the direct association between short-term breastfeeding and childhood obesity. Subsequent subgroup analyses were conducted. Additionally, stratified logistic regression explored the relationship between childhood obesity and the introduction of other early nutrition in both ever-breastfed and never-breastfed children. Results Overall, breastfeeding for 6 months or less did not directly prevent childhood obesity. However, among participants with older mothers (aged 35 or above), short-term breastfeeding was associated with a lower risk of childhood obesity compared to never being breastfed (OR 0.31, 95% CI: 0.17, 0.59). Similarly, children aged 3–4 years who were breastfed for > 3 ~ 6 months exhibited a lower obesity risk (OR 0.56, 95% CI: 0.35, 0.89). In ever-breastfed children, delayed infant formula introduction was linked to a lower risk of obesity (P-trend 1 ~ 3 vs. >3 months). Conversely, for non-breastfed children, introducing milk (other than breast milk or formula) later (≥ 12 versus

Abstract Background Patients with atrial fibrillation (AF) often have coronary artery disease (CAD), but the biological link between them remains unclear. This study aims to explore the common pathogenesis of AF and CAD and identify common biomarkers. Methods Gene expression profiles for AF and stable CAD were downloaded from the Gene Expression Omnibus database. Overlapping genes related to both diseases were identified using weighted gene co-expression network analysis (WGCNA), followed by functional enrichment analysis. Hub genes were then identified using the machine learning algorithm. Immune cell infiltration and correlations with hub genes were explored, followed by drug predictions. Hub gene expression in AF and CAD patients was validated by real-time qPCR. Results We obtained 28 common overlapping genes in AF and stable CAD, mainly enriched in the PI3K-Akt, ECM-receptor interaction, and relaxin signaling pathway. Two hub genes, COL6A3 and FKBP10, were positively correlated with the abundance of MDSC, plasmacytoid dendritic cells, and regulatory T cells in AF and negatively correlated with the abundance of CD56dim natural killer cells in CAD. The AUCs of COL6A3 and FKBP10 were all above or close to 0.7. Drug prediction suggested that collagenase clostridium histolyticum and ocriplasmin, which target COL6A3, may be potential drugs for AF and stable CAD. Additionally, COL6A3 and FKBP10 were upregulated in patients with AF and CAD. Conclusion COL6A3 and FKBP10 may be key biomarkers for AF and CAD, providing new insights into the diagnosis and treatment of this disease.

Abstract. Background:. Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants. Methods:. A total of 3053 healthy Han Chinese adults (1922 women) aged 18–79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere–Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance. Results:. All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction

Objective The objective of this study was to identify candidate genes that play important roles in skeletal muscle development in ducks. Methods In this study, we investigated the transcriptional sequencing of embryonic pectoral muscles from two specialized lines: Liancheng white ducks (female) and Cherry valley ducks (male) hybrid Line A (LCA) and Line C (LCC) ducks. In addition, prediction of target genes for the differentially expressed mRNAs was conducted and the enriched gene ontology (GO) terms and Kyoto encyclopedia of genes and genomes signaling pathways were further analyzed. Finally, a protein-to-protein interaction network was analyzed by using the target genes to gain insights into their potential functional association. Results A total of 1,428 differentially expressed genes (DEGs) with 762 being up-regulated genes and 666 being down-regulated genes in pectoral muscle of LCA and LCC ducks identified by RNA-seq (p

Abstract Background Gay, bisexual, and other men who have sex with men (GBMSM) represent a high-risk group for HIV transmission in Romania, yet they possess few resources for prevention. Despite having no formal access to pre-exposure prophylaxis (PrEP) through the health system, GBMSM in Romania demonstrate a high need for and interest in this medication. In anticipation of a national rollout of PrEP, this study tests the efficacy of a novel strategy, Prepare Romania, that combines two evidence-based PrEP promotion interventions for GBMSM living in Romania. Methods This study uses a randomized controlled trial design to examine whether GBMSM living in Romania receiving Prepare Romania, a culturally adapted counseling and mobile health intervention (expected n = 60), demonstrate greater PrEP adherence and persistence than those assigned to a PrEP education control arm (expected n = 60). Participants from two main cities in Romania are prescribed PrEP and followed-up at 3 and 6 months post-randomization. PrEP adherence data are obtained through weekly self-report surveys and dried blood spot testing at follow-up visits. Potential mediators (e.g., PrEP use motivation) of intervention efficacy are also assessed. Furthermore, Prepare Romania’s implementation (e.g., proportion of enrolled participants attending medical visits, intervention experience) will be examined through interviews with participants, study implementers, and healthcare officials. Discussion The knowledge gained from this study will be utilized for further refinement and scale-up of Prepare Romania for a future multi-city effectiveness trial. By studying the efficacy of tools to support PrEP adherence and persistence, this research has the potential to lay the groundwork for PrEP rollout in Romania and similar contexts. Trial registration This study was registered on ClinicalTrials.gov, identifier NCT05323123 , on March 25, 2022.

Abstract Since 2017, immune checkpoint inhibitors (ICIs) have been available for the treatment of advanced hepatocellular carcinoma (HCC) or unresectable HCC, but their adoption into national medical insurance programs is still limited. Cost-effectiveness evidence can help to inform treatment decisions. This systematic review aimed to provide a critical summary of economic evaluations of ICIs as a treatment for advanced HCC and identify key drivers (PROSPERO 2023: CRD42023417391). The databases used included Scopus, Web of Science, PubMed, Embase, and Cochrane Central. Economic evaluations of ICIs for the treatment of advanced HCC were included. Studies were screened by two people. Of the 898 records identified, 17 articles were included. The current evidence showed that ICIs, including atezolizumab plus bevacizumab, sintilimab plus bevacizumab/bevacizumab biosimilar, nivolumab, camrelizumab plus rivoceranib, pembrolizumab plus lenvatinib, tislelizumab, durvalumab, and cabozantinib plus atezolizumab, are probably not cost-effective in comparison with tyrosine kinase inhibitors or other ICIs. The most influential parameters were price of anticancer drugs, hazard ratios for progression-free survival and overall survival, and utility for health statest. Our review demonstrated that ICIs were not a cost-effective intervention in advanced HCC. Although ICIs can significantly enhance the survival of patients with advanced HCC, decision-makers should consider the findings of economic evaluations and affordability before adoption of new therapies.

Abstract Background In this study, we investigated the relationship between the risk of postoperative progressive disease (PD) in breast cancer and depression and sleep disorders in order to develop and validate a suitable risk prevention model. Methods A total of 750 postoperative patients with breast cancer were selected from the First People’s Hospital of LianYunGang, and the indices of two groups (an event group and a non-event group) were compared to develop and validate a risk prediction model. The relationship between depression, sleep disorders, and PD events was investigated using the follow-up data of the 750 patients. Results SAS, SDS, and AIS scores differed in the group of patients who experienced postoperative disease progression versus those who did not; the differences were statistically significant and the ability to differentiate prognosis was high. The area under the receiver operating characteristic (ROC) curves (AUC) were: 0.8049 (0.7685–0.8613), 0.768 (0.727–0.809), and 0.7661 (0.724-–0.808), with cut-off values of 43.5, 48.5, and 4.5, respectively. Significant variables were screened by single-factor analysis and multi-factor analysis to create model 1, by lasso regression and cross-lasso regression analysis to create model 2, by random forest calculation method to create model 3, by stepwise regression method (backward method) to create model 4, and by including all variables for Cox regression to include significant variables to create model 5. The AUC of model 2 was 0.883 (0.848–0.918) and 0.937 (0.893–0.981) in the training set and validation set, respectively. The clinical efficacy of the model was evaluated using decision curve analysis and clinical impact curve, and then the model 2 variables were transformed into scores, which were validated in two datasets, the training and validation sets, with AUCs of 0.884 (0.848–0.919) and 0.885 (0.818–0.951), respectively. Conclusion We established and verified a model including SAS, SDS and AIS to predict the prognosis of breast cancer patients, and simplified it by scoring, making it convenient for clinical use, providing a theoretical basis for precise intervention in these patients. However, further research is needed to verify the generalization ability of our model.

Purpose: The present study aimed to analyze the influence of muscle activation on lumbar injury under a specific +Gz load. Methods: A hybrid finite element human body model with detailed lumbar anatomy and lumbar muscle activation capabilities was developed. Using the specific +Gz loading acceleration as input, the kinematic and biomechanical responses of the occupant's lower back were studied for both activated and deactivated states of the lumbar muscles. Results: The results indicated that activating the major lumbar muscles enhanced the stability of the occupant's torso, which delayed the contact between the occupant's head and the headrest. Lumbar muscle activation led to higher strain and stress output in the lumbar spine under +Gz load, such as the maximum Von Mises stress of the vertebrae and intervertebral discs increased by 177.9% and 161.8%, respectively, and the damage response index increased by 84.5%. Conclusion: In both simulations, the occupant's risk of lumbar injury does not exceed 10% probability. Therefore, the activation of muscles could provide good protection for maintaining the lumbar spine and reduce the effect of acceleration in vehicle travel direction.

Abstract Microglia are important players in surveillance and repair of the brain. Implanting an electrode into the cortex activates microglia, produces an inflammatory cascade, triggers the foreign body response, and opens the blood-brain barrier. These changes can impede intracortical brain-computer interfaces performance. Using two-photon imaging of implanted microelectrodes, we test the hypothesis that low-intensity pulsed ultrasound stimulation can reduce microglia-mediated neuroinflammation following the implantation of microelectrodes. In the first week of treatment, we found that low-intensity pulsed ultrasound stimulation increased microglia migration speed by 128%, enhanced microglia expansion area by 109%, and a reduction in microglial activation by 17%, indicating improved tissue healing and surveillance. Microglial coverage of the microelectrode was reduced by 50% and astrocytic scarring by 36% resulting in an increase in recording performance at chronic time. The data indicate that low-intensity pulsed ultrasound stimulation helps reduce the foreign body response around chronic intracortical microelectrodes.

Abstract Background Prior research has highlighted the involvement of a transcriptional complex comprising C-terminal binding protein 2 (CtBP2), histone acetyltransferase p300, and nuclear factor kappa B (NF-κB) in the transactivation of proinflammatory cytokine genes, contributing to inflammation in mice with acute respiratory distress syndrome (ARDS). Nonetheless, it remains uncertain whether the therapeutic targeting of the CtBP2-p300-NF-κB complex holds potential for ARDS suppression. Methods An ARDS mouse model was established using lipopolysaccharide (LPS) exposure. RNA-Sequencing (RNA-Seq) was performed on ARDS mice and LPS-treated cells with CtBP2, p300, and p65 knockdown. Small molecules inhibiting the CtBP2-p300 interaction were identified through AlphaScreen. Gene and protein expression levels were quantified using RT-qPCR and immunoblots. Tissue damage was assessed via histological staining. Key findings We elucidated the specific role of the CtBP2-p300-NF-κB complex in proinflammatory gene regulation. RNA-seq analysis in LPS-challenged ARDS mice and LPS-treated CtBP2-knockdown (CtBP2KD), p300KD, and p65KD cells revealed its significant impact on proinflammatory genes with minimal effects on other NF-κB targets. Commercial inhibitors for CtBP2, p300, or NF-κB exhibited moderate cytotoxicity in vitro and in vivo, affecting both proinflammatory genes and other targets. We identified a potent inhibitor, PNSC928, for the CtBP2-p300 interaction using AlphaScreen. PNSC928 treatment hindered the assembly of the CtBP2-p300-NF-κB complex, substantially downregulating proinflammatory cytokine gene expression without observable cytotoxicity in normal cells. In vivo administration of PNSC928 significantly reduced CtBP2-driven proinflammatory gene expression in ARDS mice, alleviating inflammation and lung injury, ultimately improving ARDS prognosis. Conclusion Our results position PNSC928 as a promising therapeutic candidate to specifically target the CtBP2-p300 interaction and mitigate inflammation in ARDS management.

Abstract Hydrogen energy storage plays an important role in improving the operation efficiency and reliability of power systems with high wind energy penetration. Hydrogen to power (HtP) system is the key link of hydrogen applications. However, the single HtP equipment is limited in power output range and efficiency. Hybrid HtP system is an important scheme to realize the performance complementary. A wider power output range can enrich the application scenarios of hydrogen energy storage and provide flexible and reliable energy scheduling in larger and more complex energy systems. In this study, first, a power system including traditional units, wind power generation and hybrid HtP system is established. Second, a bi‐layer hybrid HtP system optimal configuration model considering planning and operation is constructed. Then, a bi‐layer optimal configuration method based on the improved PSO algorithm is proposed. Finally, the optimization model and its solution method are applied to IEEE RTS‐96. The discussions based on the optimization results show that the hybrid HtP system has significant contributions in optimizing the output cost of traditional units, improving the utilization of wind energy, and reducing load shedding losses.

Abstract Corrosion of electrocatalysts during electrochemical operations, such as low potential - high potential cyclic swapping, can cause significant performance degradation. However, the electrochemical corrosion dynamics, including structural changes, especially site and composition specific ones, and their correlation with electrochemical processes are hidden due to the insufficient spatial-temporal resolution characterization methods. Using electrochemical liquid cell transmission electron microscopy, we visualize the electrochemical corrosion of Pd@Pt core-shell octahedral nanoparticles towards a Pt nanoframe. The potential-dependent surface reconstruction during multiple continuous in-situ cyclic voltammetry with clear redox peaks is captured, revealing an etching and deposition process of Pd that results in internal Pd atoms being relocated to external surface, followed by subsequent preferential corrosion of Pt (111) terraces rather than the edges or corners, simultaneously capturing the structure evolution also allows to attribute the site-specific Pt and Pd atomic dynamics to individual oxidation and reduction events. This work provides profound insights into the surface reconstruction of nanoparticles during complex electrochemical processes.

Maternal age has significantly increased among Chinese women, thereby posing risk of pregnancy-related complications. Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality, and coagulation analysis in conjunction with clinical signs and symptoms are generally used for its diagnosis with limited efficacy. Sonoclot coagulation analyzer is effective in assessing coagulation function used during cerebral surgery and cardiovascular surgery. However, its use has not been explored in preeclampsia. Here, we investigated the potential use of Sonoclot in diagnosing preeclampsia in obstetrics cases. Subjects meeting the screening criteria were divided either into a test group or a control group, according to whether they were preeclamptic or not. We recorded the Sonoclot-derived coagulation and the routine coagulation parameters including platelet function (PF), activated clotting time (ACT) and clot rate (CR), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), and platelet count. Regression analysis was done on the relevant parameters to assess the feasibility of Sonoclot analyzer in preeclampsia diagnosis. In parallel, changes in preeclampsia lncRNAs was also evaluated. Significant differences were recorded in PT and ACT between the two groups. In the monovariant logistic regression, PT and ACT appeared to be reliable predictor variables. In the multinomial logistic regression, a total of five regression steps were performed with decreasing AIC values. The K-fold cross validation resulted in an accuracy rate (ACC) of 77.5%, a false positive rate of 16.4%, and a false negative rate of 33.2%. lncRNAs ANRIL and HOXD-AS1 were found deregulated. Our findings indicate that Sonoclot may be useful for diagnosis of preeclampsia in obstetrics.

Abstract Neoadjuvant immunochemotherapy (NAIC) achieves superior clinical benefits over neoadjuvant chemotherapy (NAC) in multiple types of human cancers, including gastric adenocarcinoma (GAC). However, it is poorly understood how the malignant epithelial cells and tumor immune microenvironment (TIME) might respond distinctly to NAIC and NAC that underlies therapeutic efficacy. Here treatment‐naive and paired tumor tissues from multiple centers were subjected to pathological, immunological, and transcriptomic analysis. NAIC demonstrated significantly increased rate of pathological complete response compared to NAC (pCR: 25% vs. 4%, p

Dynamic beam scanning with a dynamically tunable beam number, beam direction, and beam polarization remains a challenge in the terahertz gap, which is urgently needed for terahertz radar, next-generation wireless communication, and imaging applications. Different from programmable metasurfaces with element-level phase control, the beam direction is dynamically controlled by two cascaded all-dielectric metasurfaces during in-plane rotation. For a pair of circularly polarized beams with opposite handedness, the scanning field of view (FOV) can be the same or different according to the independent phase modulation in both layers and for both polarization states. Switchable single-beam and dual-beam scanning is achieved by controlling the incident polarization, which covers the ±60° FOV at 0.291 THz with an angular step of 1° and an average gain of 16.2 dBi. The output beam is quasi-circular polarized with an average ellipticity of 0.83. Single beam scanning along a Fibonacci spiral trajectory and dual beam scanning along symmetric and asymmetric trajectories are experimentally validated. Different beam scanning processes are recorded using a terahertz camera, which show good agreement with the theoretical prediction. The wide field-of-view continuous beam scanning with a switchable number of beams and a flexible FOV may have a significant impact on the development of terahertz radar and terahertz intelligent antennas.

BackgroundPeripartum respiratory complications are a major reason for pregnant women’s admission to the ICU, even endangers the maternal life. This bibliometric analysis was designed to elucidate the spectrum of diseases and risk factors for various respiratory complications during the peripartum period, as well as the future research directions in this field.MethodsRelevant publications were downloaded from the Web of Science Core Collection on November 1, 2023. CiteSpace was utilized for conducting the scientometric study.ResultsA total of 2,331 articles and reviews on respiratory complications during pregnancy published between 2004 and 2023 were retrieved, comprising 87,244 co-cited references, originating from 568 institutions across 104 countries/regions. The United States emerged as the leading country in this domain, with Harvard University standing out as the most actively engaged institution. Bibliometric analysis reveals that the current research hotspots include “COVID-19 pandemic,” “venous thromboembolism,” “respiratory distress syndrome” and “cardiovascular diseases.” Meanwhile, “venous thromboembolism,” cytokine storm” and supportive management such as “extracorporeal membrane oxygenation” might represent potential future research directions.ConclusionOver the past two decades, research on respiratory system complications in pregnancy has continually evolved. This study contributes to enabling researchers in the related field to understand future research hotspots and trends, providing information on potential collaborators, institutions, countries, and citation references.

Incorporating medical text annotations compensates for the quality deficiencies of image data, effectively overcoming the limitations of medical image segmentation. Many existing approaches achieve high-quality segmentation results by integrating text into the image modality. However, these approaches require matched image-text pairs during inference to maintain their performance, and the absence of corresponding text annotations results in degraded model performance. Additionally, these methods often assume that the input text annotations are ideal, overlooking the impact of poor-quality text on model performance in practical scenarios. To address these issues, we propose a novel generative medical image segmentation model, Cap2Seg (Leveraging Caption Generation for Enhanced Segmentation of COVID-19 Medical Images). Cap2Seg not only segments lesion areas but also generates related medical text descriptions, guiding the segmentation process. This design enables the model to perform optimal segmentation without requiring text input during inference. To mitigate the impact of inaccurate text on model performance, we consider the consistency between generated textual features and visual features and introduce the Scale-aware Textual Attention Module (SATaM), which reduces the model’s dependency on irrelevant or misleading text information. Subsequently, we design a word-pixel fusion decoding mechanism that effectively integrates textual features into visual features, ensuring that the text information effectively supplements and enhances the image segmentation task. Extensive experiments on two public datasets, MosMedData+ and QaTa-COV19, demonstrate that our method outperforms the current state-of-the-art models under the same conditions. Additionally, ablation studies have been conducted to demonstrate the effectiveness of each proposed module. The code is available at https://github.com/AllenZzzzzzzz/Cap2Seg.

BackgroundHigh-fat diet (HFD)-induced hyperlipidemia, which is associated with gut microbiota disturbances, remains a major public health challenge. Glycerolipid metabolism is responsible for lipid synthesis and is thus involved in the development of hyperlipidemia. However, possible association between the HFD-modulated gut microbiome and the glycerolipid metabolism pathway remains unclear.MethodsHamsters were fed a HFD for 4 weeks to establish a hyperlipidemia model. Fecal, plasma and liver samples collected from hamsters fed a HFD or a normal chow diet (NCD) were used for integrative metagenomic and untargeted metabolomic analyses to explore changes in the composition and functions of the gut microbiota, and relevant metabolites. Spearman rank correlation analysis was used to explore correlations between gut microbes and circulating glycerolipid metabolites, gut microbes and lipids, and circulating glycerolipid metabolites and lipids.ResultsThe gut microbial composition of HFD hamsters showed significant alterations at the phylum, genus, and species levels that were skewed toward metabolic disorders compared with that of NCD hamsters. Functional characterization by KEGG analysis identified enrichment of the glycerolipid metabolism pathway in the gut microbiome of HFD hamsters. Plasma and liver metabolomics further indicated the upregulation and enrichment of glycerolipid metabolites in HFD hamsters. The Faecalibaculum, Allobaculum, and Eubacterium genera were positively correlated with plasma glycerolipid metabolites and lipid indices.ConclusionThe findings of this study suggest an association between glycerolipid metabolism and the HFD-modulated gut microbiome that is involved in the development of hyperlipidemia.

IntroductionPredicting TCR–peptide binding is a complex and significant computational problem in systems immunology. During the past decade, a series of computational methods have been developed for better predicting TCR–peptide binding from amino acid sequences. However, the performance of sequence-based methods appears to have hit a bottleneck. Considering the 3D structures of TCR–peptide complexes, which provide much more information, could potentially lead to better prediction outcomes.MethodsIn this study, we developed TCRcost, a deep learning method, to predict TCR–peptide binding by incorporating 3D structures. TCRcost overcomes two significant challenges: acquiring a sufficient number of high-quality TCR–peptide structures and effectively extracting information from these structures for binding prediction. TCRcost corrects TCR 3D structures generated by protein structure tools, significantly extending the available datasets. The main and side chains of a TCR structure are separately corrected using a long short-term memory (LSTM) model. This approach prevents interference between the chains and accurately extracts interactions among both adjacent and global atoms. A 3D convolutional neural network (CNN) is designed to extract the atomic features relevant to TCR–peptide binding. The spatial features extracted by the 3DCNN are then processed through a fully connected layer to estimate the probability of TCR–peptide binding.ResultsTest results demonstrated that predicting TCR–peptide binding from 3D TCR structures is both efficient and highly accurate with an average accuracy of 0.974 on precise structures. Furthermore, the average accuracy on corrected structures was 0.762, significantly higher than the average accuracy of 0.375 on uncorrected original structures. Additionally, the average root mean square distance (RMSD) to precise structures was significantly reduced from 12.753 Å for predicted structures to 8.785 Å for corrected structures.DiscussionThus, utilizing structural information of TCR–peptide complexes is a promising approach to improve the accuracy of binding predictions.

Estimating the cooling load is essential for cooling systems’ energy efficiency, affecting chiller optimization and air conditioning control. Regression analysis and other conventional techniques are insufficient, but AI and ML have superior capabilities. AI and ML models are able to independently capture complicated patterns, adapt to changing settings, and scale with data efficiently to anticipate cooling loads that are impacted by variables such as weather, building materials, and occupancy. The dynamic, responsive predictions that result from this adaptability improve energy optimization and effective building management. This study delves deep into the intricate landscape of cooling load systems, where energy optimization complexities present challenges requiring thorough investigation and innovative problemsolving approaches. The Least Square Support Vector Regression (LSSVR) model is seamlessly combined with 2 meta-heuristic methods, the Dandelion Optimizer (DO) and the Electric Charged Particles Optimisation (ECPO), for improving precision and correctness. These algorithms use cooling load data that has undergone extensive validation through previous stability tests. 3 different models, LSDO, LSECH, and an independent LSSVR, are introduced in the study, each of which provides insightful information for accurate cooling load prediction. With an impressive R^2 of 0.990 and an incredibly low RMSE of 0.927 , the LSECH stands out as a standout performer. These outstanding outcomes demonstrate the LSECH model’s ability to accurately predict cooling load outcomes, emphasizing its potential for use in actual building management scenarios.

BackgroundThe relationship between selenium and renal function has always attracted widespread attention. Increased selenium level has been found to cause impaired renal function in our previous study, but the mechanism is not clear. In this study, we evaluate the potential mediating effects of plasma proteome in the association of selenium level and renal function to understand the mechanisms of selenium’s effect on renal function.MethodsUtilizing two-sample two-step mediating mendelian randomization (MR) methodology to investigate the genetically causal relationship between selenium level and renal function as well as the role of the plasma proteome in mediating them. Additionally, the mediating proteins were enriched and analyzed through bioinformatics to understand the potential mechanisms of selenium effects on renal function.ResultsIn the MR analysis, an increase in selenium level was found to decrease estimated glomerular filtration rate (eGFR). Specifically, for each standard deviation (SD) increase in selenium levels, eGFR levels are reduced by 0.003 SD [Beta (95% CI): -0.003 (-0.004 ~ -0.001), P=0.001, with no observed heterogeneity and pleiotropy]. Through mediation analysis, 35 proteins have been determined mediating the genetically causal effects of selenium on the levels of eGFR, including Fibroblast growth factor receptor 4 (FGFR4), Fibulin-1, Cilia- and flagella-associated protein 45, Mothers against decapentaplegic homolog 2 (SMAD2), and E3 ubiquitin-protein ligase ZNRF3, and the mediation effect rates of these proteins ranged from 1.59% to 23.70%. In the enrichment analysis, 13 signal transduction pathways, including FGFR4 mutant receptor activation and Defective SLC5A5 causing thyroid dyshormonogenesis 1, were involved in the effect of selenium on eGFR levels.ConclusionOur finding has revealed the underlying mechanism by which increased selenium level lead to deterioration of renal function, effectively guiding the prevention of chronic kidney disease and paving the way for future studies.

BackgroundLong-term heat stress (HS) severely restricts the growth performance of beef cattle and causes various health problems. The gut microbiota plays a crucial role in HS-associated inflammation and immune stress involving lymphocyte function. This study investigated the effects of dietary tea polysaccharide (TPS), a natural acidic glycoprotein, on HS-induced anorexia, inflammation, and gut microbiota dysbiosis in Simmental beef cattle.MethodsThe cattle were divided into two groups, receiving either normal chow or normal chow plus TPS (8 g/kg, 0.8%). Transcriptome sequencing analysis was used to analysis the differential signaling pathway of liver tissue. 16S rDNA sequencing was performed to analysis gut microbiota of beef cattle. Serum metabolite components were detected by untargeted metabolomics analysis.ResultsHepatic transcriptomics analysis revealed that differentially expressed genes in TPS-fed cattle were primarily enriched in immune processes and lymphocyte activation. TPS administration significantly reduced the expression of the TLR4/NF-κB inflammatory signaling pathway, alleviating HS-induced hepatic inflammation. Gut microbiota analysis revealed that TPS improved intestinal homeostasis in HS-affected cattle by increasing bacterial diversity and increasing the relative abundances of Akkermansia and Alistipes while decreasing the Firmicutes-to-Bacteroidetes ratio and the abundance of Agathobacter. Liquid chromatography-tandem mass spectrometry (LC‒MS/MS) analysis indicated that TPS significantly increased the levels of long-chain fatty acids, including stearic acid, linolenic acid, arachidonic acid, and adrenic acid, in the serum of cattle.ConclusionThese findings suggest that long-term consumption of tea polysaccharides can ameliorate heat stress-induced hepatic inflammation and gut microbiota dysbiosis in beef cattle, suggesting a possible liver-gut axis mechanism to mitigate heat stress.

Rubber suspension bushings have mainly been studied under single- or multi-axis load cycling, while research on rubber suspension bushings under random load cycling is not deep enough. This study conducted uniaxial tensile and fatigue tests on N60 rubber dumbbell-shaped plate samples to obtain stress–strain curves and S–N curves. Using the uniaxial tensile test data, a Mooney–Rivlin hyperelastic constitutive model was fitted using Abaqus software, and a finite element model of the rubber suspension bushing was established. A 3D virtual road surface was constructed using Adams software, and characteristic features of typical road surfaces were extracted for statistical analysis, resulting in the generation of a load spectrum showing variations in force over time. Based on the Miner linear damage accumulation theory, finite element fatigue life prediction of the rubber suspension bushing was conducted using pulses from the 232 s region of the load spectrum. The predicted fatigue life was compared to the results from benchtop fatigue testing, resulting in a relative error of less than 6.443 %. The findings suggest that the method is effective in predicting the fatigue life of rubber suspension bushings under random loads.

Some structures or components of coastal buildings are often in an unsaturated state between drying and wetting conditions, and their performance deterioration is extremely serious. This paper mainly studied Cl− diffusion of coral aggregate concrete under the coupled erosion of drying-wetting cycles, sulfate and chloride salts. Based on the microscopic morphology of corroded concrete, the erosion mechanism of the concrete under the coupled erosion of drying-wetting cycles sulfate and chloride salt was elaborated. The results indicated that, under the coupling erosion of sulfate and chloride salts, a large amount of Na2SO4 crystals will precipitate on the surface of concrete. The addition of mineral admixtures can not only improve the relative dynamic elastic modulus and relative compressive strength of coral aggregate concrete, but also improve its resistance to Cl− corrosion. SO42− reacts with cement hydration products to produce ettringite and gypsum, which hinder further Cl− corrosion during the early stage of erosion. However, as the erosion time increases, large numbers of erosion products lead to continuous expansion of cracks and accelerate Cl− transport. Finally, based on the transport mechanism of Cl− in the concrete, machine learning prediction models for Cl− content were established using CART, SVR, and XGBoost, respectively. It was found that the predicted values of the XGBoost model were in good agreement with the measured values, and the goodness of fit of the test set was R2 = 0.98, RMSE = 0.021%, MAE = 0.013%. This work can provide a new method for predicting chloride concentration in concrete under the coupling effect of multiple factors.

Abstract Background PD-L1 overexpression is commonly observed in various malignancies and is strongly correlated with poor prognoses for cancer patients. Moreover, PD-L1 has been shown to play a significant role in promoting angiogenesis and epithelial-mesenchymal transition (EMT) processes across different cancer types. Methods The relationship between PD-L1 and vasculogenic mimicry as well as epithelial-mesenchymal transition (EMT) was explored by bioinformatics approach and immunohistochemistry. The functions of PD-L1 in regulating the expression of ZEB1 and the EMT process were assessed by Western blotting and q-PCR assays. The impact of PD-L1 on the migratory and proliferative capabilities of A549 and H1299 cells was evaluated through wound healing, cell invasion, and CCK8 assays following siRNA-mediated PD-L1 knockdown. Tube formation assay was utilized to evaluate the presence of VM structures. Results In this study, increased PD-L1 expression was observed in A549 and H1299 cells compared to normal lung epithelial cells. Immunohistochemical analysis revealed a higher prevalence of VM structures in the PD-L1-positive group compared to the PD-L1-negative group. Additionally, high PD-L1 expression was also found to be significantly associated with advanced TNM stage and increased metastasis. Following PD-L1 knockdown, NSCLC cells exhibited a notable reduction in their ability to form tube-like structures. Moreover, the levels of key EMT and VM-related markers, including N-cadherin, MMP9, VE-cadherin, and VEGFA, were significantly decreased, while E-cadherin expression was upregulated. In addition, the migration and proliferation capacities of both cell lines were significantly inhibited after PD-L1 or ZEB1 knockdown. Conclusions Knockdown PD-L1 can inhibit ZEB1-mediated EMT, thereby hindering the formation of VM in NSCLC.

Abstract Background Rectal temperature (RT) is an important index of core temperature, which has guiding significance for the diagnosis and treatment of pet diseases. Objectives Development and evaluation of an alternative method based on machine learning to determine the core temperatures of cats and dogs using surface temperatures. Animals 200 cats and 200 dogs treated between March 2022 and May 2022. Methods A group of cats and dogs were included in this study. The core temperatures and surface body temperatures were measured. Multiple machine learning methods were trained using a cross-validation approach and evaluated in one retrospective testing set and one prospective testing set. Results The machine learning models could achieve promising performance in predicting the core temperatures of cats and dogs using surface temperatures. The root mean square errors (RMSE) were 0.25 and 0.15 for cats and dogs in the retrospective testing set, and 0.15 and 0.14 in the prospective testing set. Conclusion The machine learning model could accurately predict core temperatures for companion animals of cats and dogs using easily obtained body surface temperatures.

Abstract This study aimed to investigate the real-world standardisation and adherence of medical treatment regimens in patients with chronic obstructive pulmonary disease (COPD) in the community for making future management strategy. The follow-up data and treatment information of patients with COPD, which were collected through the Management Information Center of COPD (MICCOPD) in 21 community health service centres in Songjiang District, a countryside region of Shanghai. Concordance between the pharmaceutical treatment plan and recommendation of 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) report during the follow-up management period, as well as the medication adherence by patients,were analysed. Out of the 2044 patients diagnosed with COPD, 814 patients (39.8%) who had an initial record of medication use were found to meet the inclusion criteria. The most common medication regimens were long-acting beta-agonist plus inhaled corticosteroids (35.9%) and oral bronchodilators (41.9%). Among these 814 patients, 45.7%, 38.0%, 31.6% and 14.6% adhered to the treatment after 6, 12, 18 and 24 months of follow-up, respectively. The concordance rate with the regimens recommended by the 2017 GOLD guidelines was 35.5% at baseline, 35.5% at 6 months, 32.7% at 12 months, 35.4% at 18 months and 37% at 24 months. The compliance and guideline consistency rates of patients with COPD in the community under the management of general practitioners need to be improved. Enhancing general practitioner proficiency in the prevention and management of COPD and increasing patient awareness of the condition, are crucial standardising and improving adherence to initial and follow-up COPD treatments.