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Concepts related to molecular structure are often challenging for students to visualize and comprehend. Augmented reality has emerged as a promising solution to this problem, providing students with opportunities to manipulate and visualize chemical molecular structures to improve their understanding. Furthermore, collaborative learning environments have the potential to enhance student learning by fostering knowledge sharing and collaborative authoring. However, there is a dearth of research exploring students' acceptance of augmented reality in a collaborative learning context. Therefore, this study aims to investigate the technology acceptance of a wearable collaborative augmented reality system in chemistry education among junior high school students. Specifically, 124 students used "Microsoft® HoloLens 2" device to learn about chemical molecular structure. Data was collected using the Extended Technology Acceptance Questionnaire after participants used the system and analyzed using Partial Least Squares Structural Equation Modeling. The extended model takes knowledge sharing, collaborating learning, and collaborative authoring as exogenous variables with perceived ease of use and perceived usability and finally produces a structural model that leads to behavioral usage intentions. The hypotheses tested in this study were accepted as the relationships were significant. Knowledge sharing, collaborative learning, and collaborative authoring have a positive impact on perceived usefulness and perceived ease of use respectively; and perceived usefulness and perceived ease of use have significant effects on behavioral intention to use respectively. This study conclusively demonstrated the hypothesized relationships. Evidence from these results provides comprehensive insights that can help policymakers and educators better understand the factors influencing the adoption of wearable collaborative augmented reality.

Abstract Akt (also known as protein kinase B) belongs to the multifunctional serine/threonine kinase family and is an important component of the insulin signaling pathway that plays a key role in many biological processes such as cell growth, proliferation, and survival. However, few studies have reported the effect of Akt on reproduction in Hemiptera. In this study, we cloned and characterized the Akt gene from Coridius chinensis (CcAkt). The open reading frame of CcAkt has a length of 1,563 bp and encodes 520 amino acids. It has a conserved pleckstrin homology domain (PH), catalytic domain of serine/threonine protein kinases (S_TKc), and extension of Ser/Thr-type protein kinases (S_TK_X). Phylogenetic analysis showed that CcAkt and HhAkt of Halyomorpha halys had the highest similarity. Analysis of temporal and spatial expression patterns revealed that CcAkt is expressed throughout development and in various tissues of C. chinensis adults. CcAkt was highly expressed in the female adult and the fourth-instar nymph, as well as in the testis and ovary of C. chinensis. Injection of bovine insulin and methoprene induced the CcAkt expression, whereas that of 20-hydroxyecdysone significantly reduced the CcAkt expression. These three hormones, however, induced the expression of vitellogenin (Vg) and vitellogenin receptor (VgR). In unmated females, knockdown of CcAkt resulted in decreased expression of CcVg and CcVgR, stunted the development of the ovarioles, decreased the number of eggs and hatching rate. These findings from RNA interference experiment suggested that CcAkt may be involved in regulating the reproduction of C. chinensis.

Abstract Background Respiratory disease outbreaks frequently occur in settings where individuals are in close contact, for example, schools and factories. However, the transmission patterns of oropharyngeal microbiota among healthy individuals living in clusters are unclear. Therefore, we aimed to investigate the respiratory tract bacteria distribution and transmission patterns among individuals in close contact. Methods A total of 36 freshmen from Peking University Medical School participated in the study. We collected pharyngeal swabs on the first day of enrollment, 15, 30, and 60 days after cohabitation. DNA was extracted from the swabs and subjected to high-throughput sequencing to profile the microbial composition. Statistical analyses were performed to assess diversity and significance. Results Neisseriaceae, Prevotellaceae, and Streptococcaceae were the most abundant bacterial families detected. Over time, changes were observed in the bacterial communities, with a tendency for increased similarity between dormitory room members. By day 60 of cohabitation, the bacterial communities appeared to be more similar compared to the baseline (prior to cohabitation). The transmission patterns included spreading with colonization, spreading without colonization, and non-spreading. Bacteria belonging to the core genera are most likely to spread and colonize easily. Conclusion The risk of healthy cohabitants acquiring respiratory pathogens through close contact may be overestimated in epidemiological studies. Therefore, monitoring the spread of core genera that are easily transmitted and colonized is crucial for effective prevention of respiratory pathogen transmission.

Abstract Background Mobile phone addiction (MPA) has numerous deleterious effects on college students, including depression, anxiety, cognitive impairments, and sleep disorders. Undergraduate nursing students play a crucial role as a significant reserve workforce in clinical nursing practice, and their compromised mental health status significantly influences the quality of nursing work and nurse-patient relationships in the future. Objectives This study aims to investigate the associations between neuroticism and MPA among undergraduate nursing students, the mediating effect of self-control and the moderating effect of psychological capital. Methods A total of 900 undergraduate nursing students participated in the survey, wherein the Eysenck Personality Questionnaire Short Form Scale China Version-Neuroticism Subscale (EPQ-RSC-N), Self-Control Scale (SCS), Positive Psychological Capital Questionnaire (PPQ), and Mobile Phone Addiction Tendency Scale (MPATS) were employed for assessment. To analyze the available data, various statistical methods were utilized, including common method bias test examination, descriptive statistics, chi-square tests, independent samples t-tests, Pearson’s correlation analyses, as well as the Hayes’ PROCESS Macro models 4 and 14. Results (1) The prevalence of MPA in this study was found to be 34.89%. (2) The MPA was positively correlated with neuroticism (r = 0.287, p

Abstract Tackling the shortcomings of slow convergence, imprecision, and entrapment in local optima inherent in traditional meta-heuristic algorithms, this study presents the enhanced artificial hummingbird algorithm with chaotic traversal flight (CEAHA), which employs chaotic ergodicity within the foundational framework of the conventional artificial hummingbird algorithm. This approach implements chaotic motion within local regions of the solution space, ensuring a thorough exploration of potential optima and preventing algorithmic stagnation at local maxima by guaranteeing a non-repetitive traversal of all search states. This study also analyzes the intrinsic mechanisms by which eight different chaotic mappings affect optimization performance, from the perspectives of invariant measures and traversal efficiency of ergodic chaotic motion. In comparative tests with 21 meta-heuristic algorithms on the CEC2014, CEC2019, and CEC2022 benchmark suites across various dimensions, CEAHA demonstrates superior optimization performance. Furthermore, the practicability and robustness of CEAHA have been confirmed in mechanical design optimization problems through 4 engineering instances: pressure vessel, gear trains, speed reducers, and piston levers.

Abstract Objectives To develop and validate a quantitative model for predicting serosal invasion based on multi-parameters in preoperative dual-energy CT (DECT). Materials and methods A total of 342 LAGC patients who underwent gastrectomy and DECT from six centers were divided into one training cohort (TC), and two validation cohorts (VCs). Dual-phase enhanced DECT-derived iodine concentration (IC), water concentration, and monochromatic attenuation of lesions, along with clinical information, were measured and collected. The independent predictors among these characteristics for serosal invasion were screened with Spearman correlation analysis and logistic regression (LR) analysis. A quantitative model was developed based on LR classifier with fivefold cross-validation for predicting the serosal invasion in LAGC. We comprehensively tested the model and investigated its value in survival analysis. Results A quantitative model was established using IC, 70 keV, 100 keV monochromatic attenuations in the venous phase, and CT-reported T4a, which were independent predictors of serosal invasion. The proposed model had the area-under-the-curve (AUC) values of 0.889 for TC and 0.860 and 0.837 for VCs. Subgroup analysis showed that the model could well discriminate T3 from T4a groups, and T2 from T4a groups in all cohorts (all p

Abstract The identification of predictors for immunotherapy is often hampered by the absence of control groups in many studies, making it difficult to distinguish between prognostic and predictive biomarkers. This study presents biomarker analyses from the phase 3 CONTINUUM trial (NCT03700476), the first to show that adding anti-PD-1 (aPD1) to chemoradiotherapy (CRT) improves event-free survival (EFS) in patients with locoregionally advanced nasopharyngeal carcinoma. A dynamic single-cell atlas was profiled using mass cytometry on peripheral blood mononuclear cell samples from 12 pairs of matched relapsing and non-relapsing patients in the aPD1-CRT arm. Using a supervised representation learning algorithm, we identified a Ki67+ proliferating regulatory T cells (Tregs) population expressing high levels of activated and immunosuppressive molecules including FOXP3, CD38, HLA-DR, CD39, and PD-1, whose abundance correlated with treatment outcome. The frequency of these Ki67+ Tregs was significantly higher at baseline and increased during treatment in patients who relapsed compared to non-relapsers. Further validation through flow cytometry (n = 120) confirmed the predictive value of this Treg subset. Multiplex immunohistochemistry (n = 249) demonstrated that Ki67+ Tregs in tumors could predict immunotherapy benefit, with aPD1 improving EFS only in patients with low baseline levels of Ki67+ Tregs. These findings were further validated in the multicenter phase 3 DIPPER trial (n = 262, NCT03427827) and the phase 3 OAK trial of anti-PD-L1 immunotherapy in NSCLC, underscoring the predictive value of Ki67+ Treg frequency in identifying the beneficiaries of immunotherapy and potentially guiding personalized treatment strategies.

Abstract The serine/threonine/tyrosine kinase 1 (STYK1) is a receptor protein-tyrosine kinase (RPTK)-like molecule that is detected in several human organs. STYK1 plays an important role in promoting tumorigenesis and metastasis in various cancers. By analyzing the expression of RTKs in immune cells in the database of 2013 Immunological Genome Project, we found that STYK1 was principally expressed in NK cells. In order to investigate the function of STYK1, we used CRISPR/Cas9 technology to generate STYK1-deleted mice, we found STYK1 deletion mice have normal number, development, and function of NK cells in spleen and bone marrow in tumor-free resting state. To examine the tumor surveillance of STYK1 in vivo, we utilized a variety of tumor models, including NK cell-specific target cell (ß2M and RMA-S) clearance experiments in vivo, subcutaneous and intravenous injection of B16F10 melanoma model, and the spontaneous breast cancer model MMTV-PyMT. Surprisingly, we discovered that deletion of the oncogenic STYK1 promoted the four-model tumor progression, and we observed a reduction of NK cell accumulation in the tumor tissues of STYK1 deletion mice compared to WT mice. In order to study the mechanism of STYK1 in NK, RNA sequence of STYK1−/− and WT NK have unveiled a disparity in the signaling pathways linked to migration and adhesion in STYK1−/− NK cells. Further analysis of chemokine receptors associated with NK cell migration revealed that STYK1-deficient NK cells exhibited a significant reduction in CCR2 expression. The STYK1 expression was negatively associated with tumor progression in glioma patients. Overall, our study found the expression of STYK1 in NK cell mediates NK cell anti-tumor response through regulating CCR2 and infiltrating into tumor tissue.

Abstract Background We aimed to evaluate the predictors for early and interim culture conversion within 2 months and 6 months of treatment in multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) patients in China. Methods This study included adult MDR/RR-TB patients with a positive baseline sputum culture from 8 institutions located in different cities in China from May 2018 to January 2022. We mainly used logistic regression model to derive possible predictors of early and interim culture conversion. Results A total of 813 patients were enrolled and 28.5% of them received multidrug-resistant treatment regimens containing bedaquiline. Of these, 362 (44.5%) patients experienced culture conversion within 2 months of treatment, and 649 (79.8%) within 6 months. The results of the multivariable logistic regression analysis revealed that acid-fast bacilli smear positive (adjusted odds ratio [aOR] = 1.637, 95% confidence interval [CI] = 1.197–2.238), cavities (aOR = 1.539, 95% CI = 1.132–2.092), bilateral disease (aOR = 1.638, 95% CI = 1.183–2.269), and viral hepatitis (aOR = 2.585, 95% CI = 1.189–5.622) were identified as risk factors for early culture un-conversion within 2 months of treatment. Additionally, smoking history (aOR = 2.197, 95% CI = 1.475–3.273), previous treatment for tuberculosis (aOR = 1.909, 95% CI = 1.282–2.844), bilateral disease (aOR = 2.201, 95% CI = 1.369–3.537), viral hepatitis (aOR = 2.329, 95% CI = 1.094–4.962) were identified as risk factors for interim culture un-conversion within 6 months of treatment, while patients with regimen containing bedaquiline (aOR = 0.310, 95% CI = 0.191–0.502) was a protective factor. Conclusions A history of smoking, a baseline sputum AFB smear positive, lung cavities, bilateral disease, previous anti-tuberculosis treatment, or a comorbidity of viral hepatitis can be used as the predictors for early and interim culture un-conversion in MDR/RR-TB patients, while bedaquiline was a protective factor .

Abstract Background Burnout affects the quality of work and health, increases the rate of turnover of newly graduated nurses, and leads to a shortage of nurse resources. Perceived organizational support (POS) can mitigate burnout, but the exact mechanism is unclear. The purpose of this study was to explore the mediating roles of psychological capital (PsyCap) and work engagement (WE) in the relationship between POS and burnout. Methods This is a cross-sectional study. An anonymous investigation with a convenience sampling of nurses was conducted in Sichuan province, southwest China between October 2023 and November 2023. The Perceived Organizational Support Scale, Maslach’s Burnout Inventory General Survey, the Psychological Capital questionnaire, and the Utrecht Work Engagement Scale were used to collect data. SPSS 26.0 and AMOS 26.0 were applied for statistical analysis. Results A total of 995 newly graduated nurses participated in this study. The average burnout score of the nurses was 2.45 (1.06) and the incidence of burnout was 82.6%. Burnout was negatively correlated with POS (r=-0.624, p

Abstract Autoimmune hepatitis(AIH) is a chronic progressive inflammatory liver disease induced by loss of immune tolerance. The role of circulating metabolites in disease pathogenesis is unclear. This study aimed to investigate potential causal links between plasma metabolites and AIH risk by employing a two-sample Mendelian randomization approach. A comprehensive bidirectional two-sample Mendelian randomization analysis was conducted using genome-wide significant variant-metabolite and variant-AIH associations in European ancestry individuals. Various methods assessed causal relationships among 1400 metabolites and AIH, incorporating sensitivity analyses to evaluate pleiotropy and heterogeneity. Fifty-eight metabolites displayed possible associations, including increased AIH risk with genetically predicted higher kynurenine (p = 2.79 × 10− 5, OR: 1.64, 95% CI 1.30–2.07) and a protective effect for the dopamine sulfate ratio (p = 1.06 × 10− 5,OR: 0.62, 95% CI 0.49–0.79). Reciprocal analysis revealed a causal effect of AIH on kynurenine( p = 2.79 × 10− 5, OR: 1.64, 95% CI 1.30–2.07), but not on the dopamine sulfate ratio(p = 0.691, OR: 1.05, 95% CI 0.67–1.64). Our genetics-based approach provides evidence supporting a causal role for specific metabolite levels in AIH risk. The results deliver evidence supporting a causal effect of a specific metabolite ratio(dopamine 4-sulfate/dopamine 3-O-sulfate) on AIH risk. Experimental validation and mechanistic examinations are warranted to confirm findings.

Abstract Oligosaccharins, widely recognized as plant immunity inducers, have been applied and studied for enhancing antiviral defenses in rice over the years. However, due to the complex induction mechanism in rice, further studies are needed. In this study, we demonstrated that oligosaccharins enhanced rice resistance to southern rice black-streaked dwarf virus (SRBSDV) at both the symptomatic and molecular levels. RNA-seq analysis revealed that oligosaccharins enhanced rice antiviral defense by activating multiple defense pathways. Among them, the jasmonic acid (JA) signaling pathway, a crucial antiviral pathway in rice, was investigated in detail. Interestingly, RNA-seq data showed that genes related to JA signaling pathway were significantly induced after 1 h but not after 24 h of oligosaccharins treatment, suggesting that JA induction by oligosaccharins was rapid and sensitive. Furthermore, JA levels and sensitivity analysis showed that oligosaccharins induced JA accumulation, making treated rice plants more sensitive to methyl jasmonate (MeJA). Additionally, oligosaccharins treatment also induced a burst of reactive oxygen species (ROS) in rice. Notably, oligosaccharins demonstrated a low-dose effect, within a certain dilution range from 6000-fold to 1000-fold diluted solution of 5% oligosaccharins, with the 4000-fold diluted solution exhibiting a stronger ability to induce elevated production of JA and ROS. Moreover, the application of low-dose oligosaccharins also enhanced rice resistance to SRBSDV. These data suggest that low-dose of oligosaccharins can enhance rice antiviral defense by inducing multiple defense pathways, including the JA signaling pathway and ROS production.

Abstract Background We concurrently developed a prospective study to assess clinical outcomes among patients receiving 9-month bedaquiline (BDQ)-containing regimens, aiming to provide valuable data on the use of this short-course regimen in China. Methods This open-label, randomized, controlled, multicenter, non-inferiority trial was conducted at sixteen hospitals, and enrolled participants aged 18 years and older with pulmonary rifampicin/multidrug tuberculosis. Participants were randomly assigned, in a 1:1 ratio. Individuals within the standard-regimen group received 6 months of BDQ, linezolid, levofloxacin, clofazimine, and cycloserine plus 12 months of levofloxacin, and any three potentially effective drugs from clofazimine, cycloserine pyrazinamide, ethambutol and protionamide, whereas individuals within shorter-regimen group received 9 months of BDQ, linezolid, levofloxacin, clofazimine and cycloserine. The primary outcome was the percentage of participants with a composite unfavorable outcome (treatment failure, death, treatment discontinuation, or loss to follow-up) by the end of the treatment course after randomization in the modified intention-to-treat population. The noninferiority margin was 10%. This trial was registered with www.chictr.org.cn , ChiCTR2000029012. Results Between Jan 1, 2020, and Dec 31, 2023, 264 were screened and randomly assigned, 132 of 264 participants were assigned to the standard-regimen group and 132 were assigned to the shorter-regimen. Thirty-three (12.55%) of 264 participants were excluded from the modified intention-to-treat analysis. As a result, 231 participants were included in the modified intention-to-treat analysis (116 in the standard-regimen group and 115 in the shorter-regimen group).In the modified intention-to-treat population, unfavorable outcomes were reported in 19 (16.5%) of 115 participants for whom the outcome was assessable in the shorter-regimen group and 26 (22.4%) of 116 participants in the standard care group (risk difference 5.9 percentage points (97.5% CI − 5.8 to 17.5)). One death was reported in the standard-regimen group. The incidence of QTcF prolongation in the shorter-regimen group (22.6%, 26/115) was similar to the standard-regimen group (24.1%, 28/116). Conclusions The 9-month, all-oral regimen is safe and efficacious for the treatment of pulmonary rifampicin/multidrug-resistant tuberculosis. The high incidence of QTc prolongation associated with the use of BDQ highlights the urgent need of routine electrocardiogram monitoring under treatment with BDQ-containing regimens in the Chinese population.

Abstract Background Infectious diseases persistently pose global threats, and it is imperative to accelerate the professionalization of public health workforce. This study aimed to develop and validate the infectious disease control competency scale (IDCCS) for public health professionals to fill a theoretical gap and elevate practical capabilities by informing public health professionals’ development goals. Methods The initial item pool was generated through a literature review, and categorized into three dimensions (knowledge, practical skills, and leadership) based on the competency iceberg model and public health leadership framework. A two-round Delphi process was conducted to determine indicators within the scale. A pilot survey was utilized for item analysis and exploratory factor analysis (EFA). A formal survey was employed for confirmatory factor analysis (CFA). The weight value of each indicator was calculated using the analytic hierarchy process. Results An initial scale with three primary items, 14 secondary items, and 81 tertiary items was generated. Twenty experts participated in the two rounds of the Delphi process. Authority coefficients exceeded 0.9 in both rounds. Kendall's W was 0.29 and 0.19, respectively (both P

Abstract Selecting appropriate global climate models (GCMs) is crucial for minimizing uncertainty in regional climate projections under future scenarios. Previous studies have predominantly assessed the modeling capability of GCMs for regional precipitation climatology and its long-term patterns based on annual and seasonal precipitation data. Building upon these, we primally evaluated the performance of five GCMs from phase 3b of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP3b) in simulating precipitation concentration and its variations in the Southwest River Basin (SWRB) of China using the precipitation concentration index (PCI). The results indicate that: (1) The 5 GCMs generally capture the spatial distribution of annual average precipitation in the SWRB but significantly overestimate its magnitude, with a maximum regional average deviation of 207.80 mm. Furthermore, all models tend to overestimate the overall drying trend in the SWRB and show limited capability in simulating interdecadal variations of annual precipitation. (2) While the 5 GCMs reasonably simulate the spatial distribution of annual average PCI in the SWRB, they tend to overestimate its values, with a maximum regional average deviation of 1.54. Additionally, their simulation performance in capturing PCI trends and interdecadal variations is also limited. (3) The 5 GCMs tend to overestimate seasonal precipitation in the SWRB, with the best simulation performance for the distribution of autumn precipitation, followed by spring and summer, and the poorest for winter. Significant differences exist in the simulation performance of the models for seasonal precipitation proportions, which result in discrepancies in the models’ representation of PCI. Moreover, the models’ poor simulation performance of PCI trends is partly due to their inadequate modeling of trends in seasonal precipitation proportions. The findings will contribute to laying the foundation for meteorological hydrological research and water resource management in the SWRB.

Abstract Background Diapause, a pivotal phase in the insect life cycle, enables survival during harsh environmental conditions. Unraveling the gene expression profiles of the diapause process helps uncover the molecular mechanisms that underlying diapause, which is crucial for understanding physiological adaptations. In this study, we utilize RNA-seq and Ribo-seq data to examine differentially expressed genes (DEGs) and translational efficiency during diapause of Asian corn borer (Ostrinia furnacalis, ACB). Results Our results unveil genes classified as “forwarded”, “exclusive”, “intensified”, or “buffered” during diapause, shedding light on their transcription and translation regulation patterns. Furthermore, we explore the landscape of lncRNAs (long non-coding RNAs) during diapause and identify differentially expressed lncRNAs, suggesting their roles in diapause regulation. Comparative analysis of different types of diapause in insects uncovers shared and unique KEGG pathways. While shared pathways highlight energy balance, exclusive pathways in the ACB larvae indicate insect-specific adaptations related to nutrient utilization and stress response. Interestingly, our study also reveals dynamic changes in the HSP70 gene family and proteasome pathway during diapause. Manipulating HSP protein levels and proteasome pathway by HSP activator or inhibitor and proteasome inhibitor affects diapause, indicating their vital role in the process. Conclusions In summary, these findings enhance our knowledge of how insects navigate challenging conditions through intricate molecular mechanisms.

Cu–15Ni–8Sn-xNb alloys (x = 0, 0.2, 0.6 wt%) were prepared using a medium-frequency induction melting furnace. The effect of Nb addition on grain refinement and inhibition of discontinuous precipitation (DP) in Cu–15Ni–8Sn alloys was systematically studied to elucidate the mechanism by which microstructural characteristics contribute to strength improvement. The results indicate that the increase the Nb content from 0 to 0.6 wt% reduces the average grain size of the as-cast alloy from approximately 524.8 μm to approximately 81.3 μm, and significantly decreases the lamellar transition structure region (α+γ). During solution treatment, dispersed needle-like NbNi3 phases were observed in the Cu–15Ni–8Sn-0.2Nb alloy. After aging, the DP growth rate in the Cu–15Ni–8Sn-0.2Nb alloy was notably slower than those of the other alloys. This was attributed to NbNi3 phases at the grain boundaries hindering DP nucleation, with intragranular NbNi3 phases inhibiting DP growth. The phase transformation order of the solid solution Cu–15Ni–8Sn-0.2Nb at 673 K aging is: spinodal structure → D022 ordered phase → L12 ordered phase → DP. The hardness and tensile strength of the Cu–15Ni–8Sn-0.2Nb alloy peaked at 338.3 HV and 725.42 MPa, respectively, after aging for 120 min. Using the Johnson–Mehl–Avrami–Kolmogorov (JMAK) and Arrhenius equations, the activation energies of DP in Cu–15Ni–8Sn-xNb (x = 0, 0.2, 0.6 wt%) alloys were calculated to be 93.19, 148.64, and 98.33 kJ/mol, respectively. These values suggest that the diffusion of DP atoms in the Nb-containing alloys is hindered, which effectively inhibits DP formation.

The Three River Headwaters （TRH） region， known as the “Water Tower of China”， is a crucial freshwater source and an ecological barrier in China.Changes in precipitation concentration， seasonal precipitation amount， frequency， and intensity is a key process of water cycle in the context of global warming， holding significant implications for vegetation growth and water resource management in the TRH region.In this study， utilizing the CN05.1 daily precipitation gridded dataset from 1961 to 2020 prepared by the China Meteorological Administration， the Precipitation Concentration Index （PCI） were calculated， and the evolving patterns of precipitation concentration and intra-annual distribution in the TRH region were clarified.The climatology， relative interannual variability， long-term trends， and anomalies of annual and seasonal precipitation amount， frequency， and intensity were investigated.The results find that： （1） Precipitation in the TRH region exhibits a certain degree of concentration with PCI of 17.5.PCI increased from southeast to northwest， suggesting an increased precipitation concentration.Over the past 60 years， PCI has declined at a rate of -1.71% per decade， indicating a trend towards more evenly distributed monthly precipitation throughout the year.It’s noteworthy that the reduction in the proportion of precipitation during the growing season may have ramifications for agricultural production and ecosystem maintenance in the TRH region.（2） Over the past six decades， there has been a significant overall increase in precipitation amount and intensity during different seasons.However， precipitation frequency decreased during summer while increasing in other seasons.Enhanced precipitation intensity has predominantly contributed to the rise in precipitation amount during spring， summer， and autumn， while increased precipitation frequency has played a dominant role in elevating precipitation amount during winter.The increase rate in humidity during winter and spring was higher than that during summer and autumn.In spring， precipitation amount and intensity increased by 8.09% and 6.94% per decade respectively， while winter saw snowfall amount and frequency grow by 7.27% and 4.4% per decade.Also noteworthy is the distribution of droughts and floods in parts of the Yangtze River source area tends towards extreme， exacerbating the ecosystem vulnerability.（3） The regional average precipitation amount， frequency， and intensity in the TRH region have shown an increase of 1.36 mm， 0.024%， and 0.0056 mm·d-1 per year over the past 60 years.The cumulative anomalies of precipitation amount， frequency， and intensity in the last 60 years were negative， with abrupt changes occurring in 2003， 1989， and 2003， respectively.There has been a significant decrease in precipitation frequency during the rainy season， coupled with a substantial increase in precipitation intensity.In contrast， both precipitation frequency and intensity during the dry season have experienced significant increases.These changes have been particularly pronounced in the past decade.This study can serve as a valuable reference for research concerning soil erosion， agricultural production， water resource management， and climate change in the TRH region.

Abstract Background Retinol binding protein 4 (RBP4) is a mediator of inflammation and related to skin lesion formation, which suggests its engagement in psoriasis pathology and progression. This study intended to explore the change in RBP4 after systemic treatments, and its ability to predict treatment response in psoriasis patients. Methods This prospective study enrolled 85 psoriasis patients and 20 healthy subjects. Plasma RBP4 was detected by enzyme-linked immunosorbent assay at baseline and 12th week (W12) after systemic treatments in psoriasis patients, as well as after enrollment in healthy subjects. Psoriasis Area and Severity Index (PASI) 75 and PASI 90 were evaluated at W12 in psoriasis patients. Results RBP4 at baseline was higher in psoriasis patients than in healthy subjects [median (interquartile range): 13.39 (9.71–22.92) versus 9.59 (6.57–13.72) µg/mL] (P = 0.003). In psoriasis patients, 50 (58.8%) patients achieved PASI 75 at W12, and 25 (29.4%) patients achieved PASI 90 at W12. RBP4 was decreased at W12 compared to its level at baseline (P 0.7. Conclusion Plasma RBP4 is decreased after systemic treatments, and its low baseline level and greater decline after treatments predict good treatment response in psoriasis patients.

Abstract Background The composition of the vaginal microbiota during the menstrual cycle is dynamic, with some women remaining eu- or dysbiotic and others transitioning between these states. What defines these dynamics, and whether these differences are microbiome-intrinsic or mostly driven by the host is unknown. To address this, we characterized 49 healthy, young women by metagenomic sequencing of daily vaginal swabs during a menstrual cycle. We classified the dynamics of the vaginal microbiome and assessed the impact of host behavior as well as microbiome differences at the species, strain, gene, and phage levels. Results Based on the daily shifts in community state types (CSTs) during a menstrual cycle, the vaginal microbiome was classified into four Vaginal Community Dynamics (VCDs) and reported in a classification tool, named VALODY: constant eubiotic, constant dysbiotic, menses-related, and unstable dysbiotic. The abundance of bacteria, phages, and bacterial gene content was compared between the four VCDs. Women with different VCDs showed significant differences in relative phage abundance and bacterial composition even when assigned to the same CST. Women with unstable VCDs had higher phage counts and were more likely dominated by L. iners. Their Gardnerella spp. strains were also more likely to harbor bacteriocin-coding genes. Conclusions The VCDs present a novel time series classification that highlights the complexity of varying degrees of vaginal dysbiosis. Knowing the differences in phage gene abundances and the genomic strains present allows a deeper understanding of the initiation and maintenance of permanent dysbiosis. Applying the VCDs to further characterize the different types of microbiome dynamics qualifies the investigation of disease and enables comparisons at individual and population levels. Based on our data, to be able to classify a dysbiotic sample into the accurate VCD, clinicians would need two to three mid-cycle samples and two samples during menses. In the future, it will be important to address whether transient VCDs pose a similar risk profile to persistent dysbiosis with similar clinical outcomes. This framework may aid interdisciplinary translational teams in deciphering the role of the vaginal microbiome in women’s health and reproduction. Video Abstract

Abstract Background The function of hematopoietic stem cells (HSC) is regulated by HSC internal signaling pathways and their microenvironment. Chemokines and chemokine ligands play important roles in the regulation of HSC function. Yet, their functions in HSC are not fully understood. Methods We established Cxcr3 and Cxcl10 knockout mouse models (Cxcr3 −/− and Cxcl10 −/− ) to analyze the roles of Cxcr3 or Cxcl10 in regulating HSC function. The cell cycle distribution of LT-HSC was assessed via flow cytometry. Cxcr3 −/− and Cxcl10 −/− stem/progenitor cells showed reduced self-renewal capacity as measured in serial transplantation assays. To study the effects of Cxcr3 or Cxcl10 deficient bone marrow microenvironment, we transplanted CD45.1 donor cells into Cxcr3 −/− or Cxcl10 −/− recipient mice (CD45.2) and examined donor-contributed hematopoiesis. Results Deficiency of Cxcl10 and its receptor Cxcr3 led to decreased BM cellularity in mice, with a significantly increased proportion of LT-HSC. Cxcl10 −/− stem/progenitor cells showed reduced self-renewal capacity in the secondary transplantation assay. Notably, Cxcl10 −/− donor-derived cells preferentially differentiated into B lymphocytes, with skewed myeloid differentiation ability. Meanwhile, Cxcr3-deficient HSCs demonstrated a reconstitution disadvantage in secondary transplantation, but the lineage bias was not significant. Interestingly, the absence of Cxcl10 or Cxcr3 in bone marrow microenvironment did not affect HSC function. Conclusions The Cxcl10 and Cxcr3 regulate the function of HSC, including self-renewal and differentiation, adding to the understanding of the roles of chemokines in the regulation of HSC function.

Abstract Background The aim of this study is to explore the influence of GPs’information, motivation and behavior skills on EM prescribing behavior in urban and suburban districts. Method A cross-sectional study was conducted from June to November 2022 cross 3 urban districts and 4 suburban districts in Beijing. The structural equation model was used to analyze the factors influencing the essential medicine prescription behavior among general practitioners in urban and suburban districts. Results A total of 511 valid questionnaires were collected. There was a statistically significant difference in mean scores for personal motivation and behavioral skills between urban GPs and suburban GPs. For urban GPs, the path analysis revealed that the social motivation had a direct effect on the essential medicine prescribing behavior (β = 0.225, p

Abstract Glycyrrhiza stems and leaves (GSL) are waste products of Glycyrrhiza; however, it has been considered a potential source of flavonoid compounds. In this study, GSL was processed by solid-state fermentation (SSF) to improve the flavonoid content and antioxidant activity. Firstly, a near-infrared (NIR) prediction model for flavonoid content in fermented Glycyrrhiza stems and leaves (FGSL) was established. Next, the effects of SSF on the antioxidant activity and metabolite profile of GSL were investigated. Finally, the possible mechanism of ferment release of flavonoids was explored based on enzyme activity, thermogravimetric analysis, and FTIR spectroscopy. The results revealed that NIR spectroscopy can efficiently analyze flavonoid contents in GSL, with predicted determination coefficient (Rp2) and root mean square error (RMSEP) of 0.9874 and 0.125, respectively. SSF significantly increased the levels of flavonoids, and enhanced the scavenging activities of DPPH radical and hydroxyl radical and reducing power of FGSL. Widely targeted metabolomic analysis showed the detection of 461 differential metabolites were identified after SSF, with 141 metabolites remarkably up-regulated and 320 metabolites of FGSL down-regulated during fermentation. The main types of differential metabolites were phenolic acids and flavonoids, and the destruction of cellulose by SFF was crucial to the release of flavonoids. In conclusion, our study revealed that SSF remarkably improved the phytochemical components of FGSL by increasing enzyme activity and destroying cellulose structure, thereby contributing to the enhancement of antioxidant activity. This study provided a scientific basis for the production of high-value flavonoids from plant materials and offered a novel approach to elucidate the release and conversion of flavonoids. Graphical Abstract

Static corrosion tests in LBE under oxygen-saturated and –depleted conditions at 500 °C for 1000 h were conducted to investigate the corrosion-induced diffusion layers on T91 and SS316L steels subject to dissolution and oxidation corrosion. Following nano-indentation experiments examined the variations of local mechanical properties within the corrosion layers. Under the present conditions, T91 steel showed better resistance to dissolution corrosion while higher susceptibility to oxidation corrosion against SS316L. For both steels, nano-indentation results showed a gradual decrease in mechanical properties from steel matrix to the corrosion side after dissolution corrosion. When subject to oxidation corrosion, the oxide scale formed on T91 steel showed lower Er-modulus and enhanced hardness in comparison with those of the steel matrix. An obvious decrease in both modulus and hardness was found at the interface between steel matrix and oxide scale.

ObjectiveTo systematically review research of integrated dementia care models in primary care abroad, summarize the main dimensions and key elements of the models, and provide a reference for the construction of community-based integrated dementia care models in China. MethodsFollowing the scoping review methodology, literature on integrated dementia care models in primary care published from database inception through July 1, 2023, was searched in Medline, Embase, and Web of Science databases. The literature was screened and characteristics extracted and synthesized. ResultsA total of 3 357 articles were retrieved and 25 were finally included. The integrated dementia care models were categorized into collaborative care plans, memory clinics and care networks. The dimensions of integration focused mainly on the service and professional levels, with the least emphasis on the system, functional and normative levels. Effectiveness was mainly reflected in improved health outcomes for patients, caregiver burden, and accessibility of services, but was related to the form of implementation. The main barriers to the implementation of integrated care models included lack of funding, inconsistent payment methods, short of common information technology platforms, insufficient human resource development, and inadequate skills among general practitioners. The relationship between the models and the local primary care system was mainly embedded. ConclusionThe types of integrated dementia care models in primary care abroad are diverse and their effects vary. They provide a reference for building community-based integrated care models for older adults with dementia in China.

Abstract Background Gibberella ear rot (GER) is one of the most devastating diseases in maize growing areas, which directly reduces grain yield and quality. However, the underlying defense response of maize to pathogens infection is largely unknown. Results To gain a comprehensive understanding of the defense response in GER resistance, two contrasting inbred lines ‘Nov-82’ and ‘H10’ were used to explore transcriptomic profiles and defense-related phytohormonal alterations during Fusarium graminearum infection. Transcriptomic analysis revealed 4,417 and 4,313 differentially expressed genes (DEGs) from the Nov-82 and H10, respectively, and 647 common DEGs between the two lines. More DEGs were obviously enriched in phenylpropanoid biosynthesis, secondary metabolites biosynthesis, metabolic process and defense-related pathways. In addition, the concentration of the defense-related phytohormones, jasmonates (JAs) and salicylates (SAs), was greatly induced after the pathogen infection. The level of JAs in H10 was more higher than in Nov-82, whereas an opposite pattern for the SA between the both lines. Integrated analysis of the DEGs and the phytohormones revealed five vital modules based on co-expression network analysis according to their correlation. A total of 12 hub genes encoding fatty acid desaturase, subtilisin-like protease, ethylene-responsive transcription factor, 1-aminocyclopropane-1-carboxylate oxidase, and sugar transport protein were captured from the key modules, indicating that these genes might play unique roles in response to pathogen infection, Conclusions Overall, our results indicate that large number DEGs related to plant disease resistance and different alteration of defensive phytohormones were activated during F. graminearum infection, providing new insight into the defense response against pathogen invasion, in addition to the identified hub genes that can be further investigated for enhancing maize GER resistance.

Abstract Chenopodium album L. (CAL) has many bioactive compounds and pharmacological activities. Fermentation is the preferred modification method of releasing target bioactive. We prepared two crude polysaccharides: SLC (the polysaccharide from the unfermented stem and leaves of CAL) and FSLC (the polysaccharide from the fermented stem and leaves of CAL). In vitro antioxidant and composition of SLC and FSLC were compared, and the effects of FSLC on antioxidant activity in the IPEC-J2 cells model and development-promoting activity in the zebrafish model were evaluated. The results revealed that FSLC possesses stronger DPPH, hydroxyl radical scavenging, and reducing power than SLC. The levels of total polysaccharide, polyphenol, and flavonoid, as well as the molar ratio of glucuronic acid increased in FSLC. Compared with SLC, the relative contents of protocatechuic acid, protocatechualdehyde, gentisic acid, vanillic acid, p-coumaric acid, quercetin, ferulic acid methyl ester, hispidulin, diosmetin, cinnamic acid, isorhamnetin, syringic acid and kaempferol in FSLC increased. In IPEC-J2 cells, antioxidant enzyme activities and GSH levels were significantly increased, while the MDA level was reduced by treatment with 0.25 mg/mL FSLC. In the zebrafish model, treatment with 25 ~ 300 μg/mL of FSLC had no harmful impact on the morphology and viability of embryos at 12 ~72 hpf. At 48 and 60 hpf, treatment with 100 ~ 300 μg/mL FSLC increased the hatching rate of embryos. At 72hpf, treatment with 100 ~ 300 μg/mL FSLC could relieve morphological abnormalities caused by LPS in zebrafish and improve the hatching rate of embryos. Together, these results provide useful information on the potential for applying polysaccharides from the stems and leaves of CAL as natural feed additives to exert its antioxidant and development-promoting functions. Graphical Abstract

Abstract Background The heart can be involved in immunoglobulin (Ig)-G4-related disease (IgG4-RD). This study aimed to summarize the clinical features and efficacy of treatment for IgG4-RD patients with heart involvement. Methods We conducted a retrospective study enrolling 42 IgG4-RD patients with heart involvement from the IgG4-RD cohorts of the Peking Union Medical College Hospital and Beijing An Zhen Hospital, from 2010 to 2022. Clinical, laboratory, radiological data were collected, and treatment responses to glucocorticoids and immunosuppressants were analyzed. Results IgG4-related cardiac involvement is a rare part of the IgG4-RD spectrum. The incidences of coronary periarteritis and pericarditis were 1.2%(13/1075) and 3.1%(33/1075), respectively in our cohort. Valvular disease possibly related to IgG4-RD was detected in two patients. None of the patients with myocardial involvement were identified. The average age was 58.2 ± 12.8 years, with a male predominance (76.7%). Coronary artery CT revealed that mass-like and diffuse wall-thickening lesions were the most frequently observed type of coronary periarteritis. Pericarditis presented as pericardial effusion, localized thickening, calcification and mass. After treatment with glucocorticoid and immunosuppressants, all patients achieved a reduced IgG4-RD responder index score and achieved radiological remission. Two patients with coronary peri-arteritis experienced clinical relapses during the maintenance period. Conclusions Cardiac involvement in IgG4-RD is rare and easily overlooked since many patients are asymptomatic, and the diagnosis relies on imaging. Patients showed a satisfactory response to glucocorticoid based treatment.

Highlights This review systematically summarizes the source of electricity, the key choice of catalyst, and the potentiality of electrolyte for prospective hydrogen generation. Each section provides comprehensive overview, detailed comparison and obvious advantages in these system configurations. The problems of hydrogen generation from electrolytic water splitting and directions of next-generation green hydrogen in the future are discussed and outlooked.

Abstract Background Indoor residual spraying (IRS) has been implemented to prevent malaria in Zambia for several decades, but its effectiveness has not been evaluated long term and in Vubwi District yet. This study aimed to assess the association between IRS and the malaria burden in Zambia and Vubwi District and to explore the factors associated with refusing IRS. Methods A retrospective study was used to analyze the association between IRS and malaria incidence in Zambia in 2001–2020 and in Vubwi District in 2014–2020 by Spearman correlation analysis. A case-control study was used to explore the factors associated with IRS refusals by households in Vubwi District in 2021. A logistic regression model was performed to identify factors associated with IRS refusals. Results The malaria incidence reached its peak (391/1000) in 2001 and dropped to the lowest (154/1000) in 2019. The annual percentage change in 2001–2003, 2003–2008, 2008–2014, 2014–2018 and 2018–2020 was − 6.54%, − 13.24%, 5.04%, − 10.28% and 18.61%, respectively. A significantly negative correlation between the percentage of population protected by the IRS against the total population in Zambia (coverage) and the average malaria incidence in the whole population was observed in 2005–2020 (r = − 0.685, P = 0.003) and 2005–2019 (r = − 0.818, P

Abstract Metastatic pancreatic cancer (mPC) has a dismal prognosis. Herein, we conducted a prospective, multicentre, single-arm, phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine (PAAG) in patients with first-line mPC (NCT05493995). The primary endpoints included the objective response rate (ORR) and disease control rate (DCR), while secondary endpoints encompassed progression-free survival (PFS), overall survival (OS), and safety. In 66 patients analysed for efficacy, the best response, indicated by the ORR, was recorded at 50.0% (33/66) (95% CI, 37.4–62.6%), with 33 patients achieving partial response (PR). Notably, the DCR was 95.5% (63/66, 95% CI, 87.3–99.1%). The median PFS (mPFS) and OS (mOS) were 8.8 (95% CI, 8.1–11.6), and 13.7 (95% CI, 12.4 to not reached) months, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 39.4% of patients (26/66). In prespecified exploratory analysis, patients with altered SWI/SNF complex had a poorer PFS. Additionally, low serum CA724 level, high T-cell recruitment, low Th17 cell recruitment, and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable efficacy. In conclusion, PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for mPC. The biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.

Background: Takayasu arteritis (TA) is associated with an increased risk of developing complicated comorbidities, which can bring both psychological and physical burdens to the patients. Objective: TA is found to carry a high risk of developing depression. This research aimed to investigate the risk factors and prognosis of depression in TA patients. Design: A longitudinal observation cohort was conducted on TA patients with or without depression to explore the clinical characteristics. Methods: In this cohort study, 90 TA patients were split into two groups with or without depression. Depression was evaluated by the Hospital Anxiety and Depression Scale (HADS) in TA patients. TA patients with depression were followed up for at least 3 months. We used multivariate logistic regression analysis to find the risk factors and Kaplan–Meier curve analysis to determine the prognosis. Results: We concluded 90 TA patients in this research, 29 of whom were in depression. Indian Takayasu’s Arteritis Activity Score (ITAS2010) ⩾2 (odds ratio (OR) (95% confidence interval, CI) 26.664 (2.004–354.741), p = 0.013), interleukin-6 (IL-6) (OR (95% CI) 1.070 (1.022–1.121), p = 0.004), prednisone equivalents (OR (95% CI) 1.101 (1.030–1.177), p = 0.005), and carotidynia (OR (95% CI) 5.829 (1.142–29.751), p = 0.034) have been shown independent risk factors for depression in TA patients. We also identified the association between disease remission with the improvement of HADS-D score (Log-rank p = 0.005, hazard ratio (HR) 0.25) and depression (Log-rank p = 0.043, HR 0.28). Conclusion: Aggressive treatment to achieve remission can promote improvement of depression in patients with TA. Screening for depression should also be performed in patients with elevated disease activity, IL-6, glucocorticoid use, and carotidynia.

Background: 5-Fluorouracil (5-FU) is a cornerstone in colorectal cancer therapy, but resistance has compromised its efficacy, necessitating detailed research into resistance mechanisms. Traditional methods for developing 5-FU-resistant cell lines are lengthy, unstable, and often unrepresentative of clinical scenarios. Methods: We devised a rapid approach to create 5-FU-resistant colorectal cancer cells using an integrated in vivo/in vitro methodology. HCT116 cells were pretreated with 5-FU, then implanted into nude mice. Tumor growth was monitored, and cells from the tumors were cultured to establish the HCT116-Tumor cell line. Cells from 5-FU-exposed tumors received increasing 5-FU doses to induce resistance, creating the tumor-derived resistant (TR) cell line. Cells cultured without 5-FU were termed tumor-derived parental (TP) cells. An in vitro 5-FU resistance model, CR, served as a benchmark. Resistance metrics were evaluated using CCK-8 assays, Western Blotting, flow cytometry, and in vivo studies. Proteomics identified resistance-related differentially expressed proteins (DEPs). Results: Low-dose 5-FU pretreatment accelerated tumor growth. Combining in vivo and in vitro methods, we developed 5-FU-resistant TR cells within two and a half months, faster than the ten-month conventional protocol. TR cells showed stronger and more durable 5-FU resistance than CR cells, with inhibited apoptosis, autophagy, and ferroptosis, and activation of MDR1. Proteomic analysis indicated more DEPs in TR cells, suggesting unique resistance mechanisms. Animal studies confirmed enhanced drug resistance in TR cells. Conclusions: Our integrated approach rapidly develops colorectal cancer cells with robust 5-FU resistance, offering a potent model for exploring multiple resistance pathways and counter-resistance strategies.

Constrictive pericarditis can lead to compromised diastolic ventricular filling due to pericardial inflammation and fibrosis. A diagnosis of constrictive pericarditis was established by identifying structural and hemodynamic features through echocardiography. We present a case of constrictive pericarditis, which manifested in the form of gradually worsening dyspnea and lower-extremity edema over a 7 years period. The patient was diagnosed with constrictive pericarditis using echocardiography, and underwent a pericardiectomy.

Gastrointestinal (GI) cancers are the most common malignancies, while surgical intervention remains the sole therapeutic approach offering the possibility of a definite cure for cancer. Perioperative anxiety negatively impacts the recovery of GI cancers. Recently, mounting studies have demonstrated that proper nursing interventions may alleviative perioperative anxious illnesses in patients with GI cancers. We conducted a first comprehensive review to summarize all the current evidence on this topic. After a systematically search in the six common databases, eighteen relevant studies were included for further analysis. The present review highlighted that there is a high prevalence of perioperative anxiety in patients with GI cancers (e.g., colorectal cancer, gastric/stomach cancer, hepatocellular carcinoma, gallbladder cancer, and esophageal cancer), while specific nursing interventions are the reliable methods to reduce postoperative anxiety. These nursing strategies include, but are not limited to, therapeutic listening intervention, implementing perioperative music, predictive nursing, progressive relaxation exercises, psychological interventions in the nursing care, comprehensive nursing, continuous nursing care, video-based nursing education, multidisciplinary cooperative continuous care, accelerated rehabilitation nursing, TCM nursing, evidence-based early warning nursing, target nursing care, and high-quality nursing. Since several limitations existed in the eligible studies as well as in this review, a well-designed multicenter RCT with large sample size is still warranted for the confirmation of nursing intervention for managing perioperative anxiety in patients with GI cancers. Also, future studies should focus on the long-term effects of relevant interventions, specific patient populations, multidisciplinary approaches, technological innovations, and educational programs.

Abstract Inflammatory bowel disease (IBD) is a recurring chronic inflammatory disease. Current treatment strategies are aimed at alleviating clinical symptoms and are associated with gastrointestinal or systemic adverse effects. New delivery strategies are needed for the treatment of IBD. Bacteria are promising biocarriers, which can produce drugs in situ and sense the gut in real time. Herein, we focus on recent studies of engineered bacteria used for IBD treatment and introduce the application of engineered bacteria in the diagnosis. On this basis, the current dilemmas and future developments of bacterial delivery systems are discussed.

A healthy vaginal microbiome (VMB) is dominated by Lactobacillus spp. and provides the first line of defense against invading pathogens. Vaginal dysbiosis, characterized by the loss of Lactobacillus dominance and increase of microbial diversity, has been linked to an increased risk of adverse genital tract diseases, including bacterial vaginosis, aerobic vaginitis, vulvovaginal candidiasis, sexually transmitted infections, and pregnancy complications such as preterm birth. Currently, antibiotics and antifungals are recommended first-line treatments with high cure rates, but they also can lead to high recurrence and resistance development. As an alternative, lactobacilli have been utilized to restore the vaginal microbiota. In this review article, we discuss vaginal dysbiosis in various gynecological infections and potential interventions based on Live Biotherapeutic Products (LBPs) with a focus on those that use intravaginal treatment modalities to modulate the VMB. Based on these, we provide insights on key factors to consider in designing phenotypic and genotypic screens for selecting bacterial strains for use as vaginally administered microbiome-directed therapeutics. Lastly, to highlight current progress within this field, we provide an overview of LBPs currently being developed with published clinical trial completion for recurrent BV, VVC, and UTI. We also discuss regulatory challenges in the drug development process to harmonize future research efforts in VMB therapy.

Summary: Lysosomal function and activity are essential to support cellular adaptation to multiple stresses. For example, certain drugs can induce increased lysosomal membrane permeability to exert their anti-cancer effects. Here, we present a protocol to evaluate the lysosome alterations induced by drug treatment. We first describe the steps for inducing lysosomal alterations in cultured cells. We then show how to quantify the number of lysosomes, assess the integrity of lysosomal membranes, and determine lysosomal membrane permeabilization by using galectin puncta assay.For complete details on the use and execution of this protocol, please refer to Jiang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

A numerical simulation of the heat dissipation performance in photovoltaic (PV) cells with phase change material (PCM) for cooling is performed by COMSOL Multiphysics. A comparative analysis of two T-shaped fin designs in PCM heat sinks is conducted to evaluate their impact on the cooling performance of PV panels. The findings indicate that a 180° T-shaped fin design substantially outperforms a cavity without fin design, reducing the PV cell average temperature by up to 15.1 K and enhancing electrical efficiency by 1.36 %. Further optimization of distal fin distance and secondary length reveals that temperature uniformity and photovoltaic efficiency can be improved, achieving a maximum electrical efficiency increase of 1.40 % and a temperature uniformity enhancement of 71.0 %. Detailed analysis underscores the critical role of the distal fin distance (Scheme 1) in temperature control and PCM convection, highlighting its importance in the design process. In contrast, numerical results of the alternative fin layout (Scheme 2) reveal its unsuitability for PV cooling applications.

In general, gearbox is prone to occur compound fault frequently because of its harsh working environment, its fault vibration signal often contains polymorphic-oscillatory components and is corrupted by heavy background noise, which brings great difficulty to diagnose fault. Sparse decomposition is often utilized to extract weak fault feature among heavy background noise. In order to solve the problems of traditional sparse decomposition method, such as lacking signal fidelity, causing local optimal solution by using the non-convex objective function, and presenting poor universality, a multi-source sparse optimization objective function with convexity is constructed based on the generalized mini-max concave penalty function. By using forward–backward splitting algorithm combination with Laplace wavelet dictionary, Morlet wavelet dictionary and DFT dictionary, the sparse coefficients corresponding to polymorphic-oscillatory components can be computed efficiently and each oscillatory component can be extracted accurately. Finally, simulation and experimental signal validate that the proposed method can decompose fault signal according to oscillatory property and diagnose gearbox compound fault without the prior knowledge of specific fault numbers.

The mechanical tensile properties of T91 steel after being oxidized in liquid LBE saturated by oxygen at 350–500 °C for up to 1000 h are studied. Duplex oxide scales are found on T91 steels after the LBE exposure, and the thickness evolution is revealed. Oxidized T91 steels with surface oxide scale yield enhanced toughness and ductility, which is mainly attributed to the inner oxide layer. We show that the enhancing effect relies on the presence of the oxide scale, not its thickness. The possible enhancing effect of the oxide scale on the toughness of T91 steel by impeding the dislocation from emitting out of the steel surfaces is discussed and qualitatively verified by micro-scale elastoplastic simulations based on a newly proposed discrete dislocation dynamics and peridynamics superposition scheme.

Abstract Hepatocellular carcinoma (HCC) is associated with a poor prognosis. Our previous study demonstrated that Pleomorphic adenoma gene like-2 (PLAGL2) was a potential therapeutic target in HCC. However, the mechanisms that lead to the upregulation of PLAGL2 in HCC remain unclear. The present study revealed that stress-induced epinephrine increased the expression of PLAGL2, thereby promoting the progression of HCC. Furthermore, PLAGL2 knockdown inhibited epinephrine-induced HCC development. Mechanistically, epinephrine upregulated ubiquitin-specific protease 10 (USP10) to stabilize PLAGL2 via the adrenergic β-receptor-2-c-Myc (ADRB2-c-Myc) axis. Furthermore, PLAGL2 acted as a transcriptional regulator of USP10, forming a signaling loop. Taken together, these results reveal that stress-induced epinephrine activates the PLAGL2-USP10 signaling loop to enhance HCC progression. Furthermore, PLAGL2 plays a crucial role in psychological stress-mediated promotion of HCC progression.

Abstract The aim of this study was to determine the role of lncRNA PART1 and downstream FUT6 in tumorigenesis and progression of head and neck cancer (HNC). Bioinformatics analysis and qRT-PCR revealed that lncRNA PART1 was expressed at low levels in HNC patients. The proliferation, apoptosis, migration and flow cytometry results showed that low expression of lncRNA PART1 inhibited apoptosis and promoted HNC cell migration and proliferation. In addition, animal experiments have also shown that low expression of lncRNA PART1 can promote tumor growth. LncRNA PART1 overexpression promoted apoptosis and inhibited HNC cell migration and proliferation. Through bioinformatics analysis, FUT6 was found to be expressed at low levels in HNC and to be correlated with patient survival. Immunohistochemical and qRT-PCR results revealed that FUT6 was underexpressed in tumour tissues and HNC cells. Cell and animal experiments showed that overexpression of FUT6 could inhibit tumour proliferation and migration. Bioinformatics analysis revealed that lncRNA PART1 was positively correlated with FUT6. By qRT-PCR and western blot, we observed that after knockdown of lncRNA PART1, both the mRNA and protein expression levels of FUT6 were reduced. The above results indicated that lncRNA PART1 and FUT6 play an important role in HNC, and that lncRNA PART1 affected the development of tumor by downstream FUT6.

Abstract Objective To describe how mental health and sleep status influence the health-related quality of life (HRQOL) of people living with HIV/AIDS (PLWHA) during the novel coronavirus disease 2019 (COVID-19) pandemic, and to apply targeted interventions to improve the HRQOL. Methods A web-based online questionnaire survey was administered. Descriptive analysis was used to depict the mental health and sleep status. Correlation analysis and the structural equation model (SEM) method were used to analyze the influence of mental health and sleep status on HRQOL in PLWHA. Results After excluding 24 unqualified questionnaires, a total of 490 participants in this survey were included in the statistical analysis. Of the participants, 66.1% and 55.1% reported mild or worse symptoms of depression and anxiety, respectively. Overall, 70.0% had varying degrees of sleep problems. Correlation analysis showed that anxiety had the strongest correlation with sleep disturbances and sleep quality (R = 0.588 and 0.551, respectively), while depression had the strongest correlation with the HRQOL psychological and physical domains (R = − 0.759 and − 0.682, respectively). SEM analysis showed that depression, sleep quality, and psychological domains had the greatest item load on mental health, sleep status, and HRQOL (093, 0.82, and 0.89, respectively). Mental health had a more significant influence than sleep status on HRQOL, as indicated by factor loading (− 0.75 and − 0.15, respectively). Conclusions There were more severe mental health and sleep problems among PLWHA during the COVID-19 pandemic, thus, mental health intervention, especially to relieve depression symptoms, may be the most important approach to improve the HRQOL among PLWHA.

Abstract Alterations in the vaginal microbiota, including both species composition and functional pathways, have been associated with HPV infection and progression of dysplasia to cervical cancer. To further explore this, shotgun metagenomic sequencing was used to taxonomically and functionally characterize the vaginal microbiota of women with and without cervical dysplasia. Women with histologically verified dysplasia (n = 177; low grade dysplasia (LSIL) n = 81, high-grade dysplasia (HSIL) n = 94, cancer n = 2) were compared with healthy controls recruited from the cervical screening programme (n = 177). Women with dysplasia had a higher vaginal microbial diversity, and higher abundances of Gardnerella vaginalis, Aerococcus christensenii, Peptoniphilus lacrimalis and Fannyhessea vaginae, while healthy controls had higher relative abundance of Lactobacillus crispatus. Genes involved in e.g. nucleotide biosynthesis and peptidoglycan biosynthesis were more abundant in women with dysplasia. Healthy controls showed higher abundance of genes important for e.g. amino acid biosynthesis, (especially L-lysine) and sugar degradation. These findings suggest that the microbiota may have a role in creating a pro-oncogenic environment in women with dysplasia. Its role and potential interactions with other components in the microenvironment deserve further exploration.

Abstract Lung adenocarcinoma (LUAD) is a malignancy with an abysmal survival rate. High metastasis is the leading cause of the low survival rate of LUAD. NCAPH, an oncogene, is involved in the carcinogenesis of LUAD. However, the regulation of NCAPH in LUAD remains controversial. In this work, we identified an up-regulation of NCAPH in LUAD tissues. Patients who expressed more NCAPH had shorter overall survival (OS). Furthermore, NCAPH overexpression promoted LUAD cell migration while inhibiting apoptosis. MiR-1976 and miR-133b were predicted to target NCAPH expression by searching TargetScan and linkedomics databases. Following that, we confirmed that miR-1976 suppressed NCAPH by directly targeting a 7-bp region of NCAPH 3′ untranslated regions (UTR). In addition, increased expression of miR-1976 decreased the proliferation & migration and promoted apoptosis of LUAD cells, and the re-introduction of NCAPH reversed these influences. Furthermore, the xenograft and metastasis mouse models also confirmed that miR-1976 inhibited tumor growth and metastasis in vivo by targeting NCAPH. Finally, we found that MiR-1976 targeting NCAPH blocked the activation of NF-κB. In conclusion, miR-1976 inhibits NCAPH activity in LUAD and acts as a tumor suppressor. The miR-1976/NCAPH/NF-κB axis may, in the future, represent crucial diagnostic and prognostic biomarkers and promising therapeutic options.

Abstract Background As the number of elderly migrants in China continues to grow, it is necessary to pay closer attention to their health and health services. Some studies have confirmed that social capital plays a significant role in the utilization of health services. Therefore, an in-depth exploration of the relationship between social capital and the utilization of essential public health services (EPHS) by elderly migrants will not only contribute to improving their overall health but also facilitate a more balanced development of public health service system in China. Methods Based on the cross-sectional data from the 2017 China Migrants Dynamic Survey (CMDS), this study examined the impact of social capital on the utilization of EPHS among elderly migrants. We evaluated social capital at two distinct levels: the individual and the community, and considered two dimensions of social capital: structural social capital (SSC) and cognitive social capital (CSC). The study aimed to delve into the impact of these forms of social capital on the utilization of EPHS among elderly migrants, and whether the migration range moderates this impact by multilevel logistic regression analysis. Results A total of 5,728 migrant elderly individuals were selected. The health records establishment rate and health education acceptance rate were approximately 33.0% and 58.6%, respectively. Social capital influenceed the utilization of EPHS among elderly migrants. Specifically, individual-level SSC and CSC have impacts on both the establishment of health records (OR = 1.598, 95%CI 1.366–1.869; OR = 1.705, 95%CI 1.433–2.028) and the acceptance of health education (OR = 1.345, 95%CI 1.154–1.567; OR = 2.297, 95%CI 1.906–2.768) among elderly migrants, while community-level SSC only affected the acceptance of health education (OR = 3.838, 95%CI 1.328–11.097). There were significant differences in individual-level SSC, health records, and health education among different migration range subgroups among elderly migrants. Migration range moderated the effect of social capital on the utilization of EPHS, crossing provinces could weaken the relationship between SSC and health education. Conclusions Social capital is associated with a higher utilization rate of EPHS among elderly migrants. It is necessary to encourage them to actively participate in social activities, strengthen public services and infrastructure construction in the area, and improve their sense of belonging and identity.

Abstract Background Chronic lung and heart diseases are more likely to lead an intensive end point after stroke onset. We aimed to investigate characteristics and outcomes of endovascular thrombectomy (EVT) in patients with acute large vessel occlusion stroke (ALVOS) and identify the role of comorbid chronic cardiopulmonary diseases in ALVOS pathogenesis. Methods In this single-center retrospective study, 191 consecutive patients who underwent EVT due to large vessel occlusion stroke in neurological intensive care unit were included. The chronic cardiopulmonary comorbidities and several conventional stroke risk factors were assessed. The primary efficacy outcome was functional independence (defined as a mRS of 0 to 2) at day 90. The primary safety outcomes were death within 90 days and the occurrence of symptomatic intracranial hemorrhage(sICH). Univariate analysis was applied to evaluate the relationship between factors and clinical outcomes, and logistic regression model were developed to predict the prognosis of ALVOS. Results Endovascular therapy in ALVOS patients with chronic cardiopulmonary diseases, as compared with those without comorbidity, was associated with an unfavorable shift in the NHISS 24 h after EVT [8(4,15.25) versus 12(7.5,18.5), P = 0.005] and the lower percentage of patients who were functionally independent at 90 days, defined as a score on the modified Rankin scale of 0 to 2 (51.6% versus 25.4%, P = 0.000). There was no significant between-group difference in the frequency of mortality (12.1% versus 14.9%, P = 0.580) and symptomatic intracranial hemorrhage (13.7% versus 19.4%, P = 0.302) or of serious adverse events. Moreover, a prediction model showed that existence of cardiopulmonary comorbidities (OR = 0.456, 95%CI 0.209 to 0.992, P = 0.048) was independently associated with functional independence at day 90. Conclusions EVT was safe in ALVOS patients with chronic cardiopulmonary diseases, whereas the unfavorable outcomes were achieved in such patients. Moreover, cardiopulmonary comorbidity had certain clinical predictive value for worse stroke prognosis.

Reliable precipitation information is particularly important for understanding the water balance and water cycle processes in the Qinghai-Xizang Plateau.As a new generation of satellite precipitation data， IMERG （Integrated Multi-satellitE Retrievals for Global Precipitation Measurement） represents an advanced iteration in satellite precipitation data， characterized by expanded coverage and heightened spatiotemporal resolution.However， due to the complex terrain in the Qinghai-Xizang Plateau， IMERG still has great uncertainty in the plateau region.In view of this， this study performs bias correction of IMERG daily precipitation data based on the Quantile Delta Mapping （QDM） method.The transfer function is established seasonally using CMFD （China Meteorological Forcing Dataset） precipitation and IMERG daily precipitation data during 2001 -2010 to correct IMERG daily precipitation during 2011 -2014.The results show that： （1） The QDM method can effectively correct the frequency， value， and spatial distribution of IMERG precipitation products， and the corrections are more effective for extreme precipitation and large negative deviation regions.The probability distribution of corrected IMERG daily precipitation is closer to that of the observations， and the precipitation deviation is more in line with the normal distribution.Monthly precipitation and the spatial distribution characteristics of annual and seasonal precipitation are improved.（2） The root mean square error of the corrected daily precipitation is reduced from 1.49 mm·d-1 to 1.26 mm·d-1 with an improvement by 15.44%.The critical success index CSI， probability of detection POD， false alarm rate FAR， precision rate， and Fscore of the corrected daily precipitation in different precipitation intensities are improved， and the Bias score of tiny and torrential precipitation is enhanced.（3） After correction， the extreme precipitation is significantly improved， and the mean values of the simple daily intensity index （SDII） and percentile-based threshold indices （R95p and R99p） are closer to the observed values.The spatial distribution of extreme precipitation is effectively displayed， and the bias of extreme precipitation is reduced from over 30% to within 5%.The root mean square error of SDII， R95p， and R99p is reduced from 1.59， 6.54， and 14.89 mm·d-1 to 0.65， 3.01， and 8.99 mm·d-1 with the accuracy improved by 59.12%， 53.98%， and 39.62%， respectively.This study verifies the applicability of the Quantile Delta Mapping method in the Tibetan Plateau， which is beneficial for obtaining more accurate precipitation data for meteorological and hydrological studies in the region.