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Students with disabilities are an increasing subpopulation in higher education. Recently, research has put an emphasis on students' voices to explore their academic learning experiences, as well as the learning strategies they use to overcome learning barriers. This study aimed to investigate the academic learning experiences of students with disabilities in college or graduate studies and the learning strategies they used when faced with insufficient or delayed support. This study used interpretative phenomenological analysis to gather data from three online focus groups, with a total of 10 participants. The results demonstrated three themes: experiences or issues related to university resources and accommodations, building influence through advocacy and education, and being an independent learner. Some participants continued to face academic learning challenges despite their active seeking of accommodations and support. Some participants utilized study strategies, especially when support was inadequate or not immediately provided. This study highlighted the urgent need for higher education institutions to establish support services and resources for all students. Related discussions and implications are presented.

With the rapid advancement of information technologies, automated writing evaluation technologies have developed so fast that they can be applied to writing assessments. However, scanty studies have pooled the effects of automated writing evaluation on writing performance. Through a PRISMA protocol-based meta-analysis, this study concludes that automated writing evaluation technologies can significantly reduce anxiety such as writing anxiety and computer anxiety compared with those without the assistance of automated writing evaluation. Automated writing evaluation can also significantly improve writing motivation and second language (L2) writing skills. Educators and designers should highlight how to combine automated writing evaluation with human rating methods and maximize the improvements in L2 writing skills. In the future, artificial intelligence may be integrated into automated writing evaluation to develop advanced automated writing evaluation to address higher-level issues in writing practice.

There is a growing awareness of the importance of financial management skills. However, few studies have systematically examined this topic in China's current higher education (HE) system. In this study, we examine whether enrolling in a finance-related program, either as a degree program or as an elective, improves students' financial literacy and habits. We conducted a mixed-method study with a sample of 1334 students from seven universities in central China. Multivariate regression, matching methods, and the inverse-probability-weighting methods were used for quantitative analysis. The results indicate that college students are generally dissatisfied with their financial situation. Enrolling in finance-related majors has little effect on improving students' financial habits, despite a substantial improvement in their financial literacy. In the current HE system, there is a significant lack of personal finance management training. Therefore, curriculum design and field practices regarding students' personal finance management skills should be introduced to enhance their financial habits.

BACKGROUND: Tau is aberrantly acetylated in various neurodegenerative conditions, including Alzheimers disease, frontotemporal lobar degeneration (FTLD), and traumatic brain injury (TBI). Previously, we reported that reducing acetylated tau by pharmacologically inhibiting p300-mediated tau acetylation at lysine 174 reduces tau pathology and improves cognitive function in animal models. METHODS: We investigated the therapeutic efficacy of two different antibodies that specifically target acetylated lysine 174 on tau (ac-tauK174). We treated PS19 mice, which harbor the P301S tauopathy mutation that causes FTLD, with anti-ac-tauK174 and measured effects on tau pathology, neurodegeneration, and neurobehavioral outcomes. Furthermore, PS19 mice received treatment post-TBI to evaluate the ability of the immunotherapy to prevent TBI-induced exacerbation of tauopathy phenotypes. Ac-tauK174 measurements in human plasma following TBI were also collected to establish a link between trauma and acetylated tau levels, and single nuclei RNA-sequencing of post-TBI brain tissues from treated mice provided insights into the molecular mechanisms underlying the observed treatment effects. RESULTS: Anti-ac-tauK174 treatment mitigates neurobehavioral impairment and reduces tau pathology in PS19 mice. Ac-tauK174 increases significantly in human plasma 24 h after TBI, and anti-ac-tauK174 treatment of PS19 mice blocked TBI-induced neurodegeneration and preserved memory functions. Anti-ac-tauK174 treatment rescues alterations of microglial and oligodendrocyte transcriptomic states following TBI in PS19 mice. CONCLUSIONS: The ability of anti-ac-tauK174 treatment to rescue neurobehavioral impairment, reduce tau pathology, and rescue glial responses demonstrates that targeting tau acetylation at K174 is a promising neuroprotective therapeutic approach to human tauopathies resulting from TBI or genetic disease.

Based on the theoretical approaches to interlanguage and discourse cohesiveness, this study examines international students' growth in discourse awareness and discourse competence in the teaching of elementary Chinese reading and writing, and explores a set of assessment methods for teaching discourse. The learners' knowledge and production of Chinese conjunctive words were assessed with multiple test methods, including the sentence sequencing test for testing learners' cognitive understanding of discourse cohesiveness, the elicitation tasks for assessing learners' production of conjunctive words, the tests of picture-based sentence writing and essay writing for evaluating learners' discourse awareness of the cohesiveness in form and meaning. 13 students were recruited by us to participate in these tests. A comprehensive discussion of the data supports that appropriate reading and writing instruction can develop learners' discourse competence and enhance their discourse awareness to a certain extent.

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 Recurrent spontaneous abortion (RSA) has a complex pathogenesis with an increasing prevalence and is one of the most intractable clinical challenges in the field of reproductive medicine. Quercetin (QCT) is an effective active ingredient extracted from Semen Cuscutae and Herba Taxilli used in traditional Chinese medicine for tonifyng the kidneys and promoting fetal restoration. Although QCT helps improve adverse pregnancy outcomes, the specific mechanism remains unclear. The trophoblast cell line HTR‐8/SVneo cultured in vitro was treated with different concentrations of QCT, and the cell counting kit‐8 assay, wound healing assay, transwell assay, and western blotting were used to evaluate the effects and mechanisms of QCT on the proliferation, migration, and invasion of HTR‐8/SVneo cells, respectively. To assess the expression levels of miR‐149‐3p and AKT serine/threonine kinase 1 (AKT1), quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blotting analysis were performed. A dual‐luciferase reporter assay was used to investigate the potential regulatory relationship between miR‐149‐3p and AKT1. Our results showed that QCT promoted the proliferation, migration, and invasion of trophoblast cells, promoted the expression of MMP2, MMP9, and vimentin, and downregulated the expression of E‐cadherin. Mechanistically, QCT downregulated the expression of miR‐149‐3p and upregulated the expression of AKT1, and miR‐149‐3p directly targets AKT1, negatively regulating its expression. Overexpression of miR‐149‐3p and silencing of AKT1 counteracted the promotional effects of QCT on trophoblast proliferation, migration, and invasion. Taken together, QCT regulates the migration and invasion abilities of HTR‐8/SVneo cells through the miR‐149‐3p/AKT1 axis, which may provide a promising therapeutic approach for RSA.

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