Search

Objective: To observe the clinical efficacy of transcutaneous electrical acupoint stimulation (TEAS) at Changqiang (GV 1) based on the modulation of electro-oculogram (EOG) signal for children with mental retardation, and explore the evaluation effect of the goal attainment scale (GAS) in children with mental retardation., Methods: Sixty children with mental retardation were randomly divided into a treatment group and a control group, with 30 cases in each one. The children in the control group were treated with conventional rehabilitation, 5 times a week. On the basis of the control group, TEAS at Changqiang (GV 1) under the modulation of EOG signal was adopted in the treatment group. When the similarity between the collected EOG signal and the template was within the range of EOG threshold, one electric stimulation was triggered at Changqiang (GV 1) for 20 s (continuous wave, 70-100 Hz in frequency, 0.1-0.2 ms in pulse width), lasting 30 min in each treatment, the intervention was given twice a week. One course of treatment was composed of 4 weeks, and 3 courses were required in total in the two groups. The infant-junior high school student's social living ability scale (S-M) and GAS were scored and compared before and after treatment in the two groups., Results: After treatment, the scores of self-living ability in the treatment group and communication ability in the control group were higher than those before treatment ( P <0.01, P <0.05). The scores of collective activity and motor ability in the treatment group were higher than those in the control group ( P <0.05). After treatment, GAS scores were higher than before treatment in both groups ( P <0.001), and the score in the treatment group was higher than the control group ( P <0.05)., Conclusion: TEAS under the modulation of EOG signal is conductive to improving the collective, motor and self-living abilities of the children with mental retardation and promoting children's individual goals. Compared with the standard score of S-M, the T value of GAS can better reflect the subtle progress of individual.

Negotiating a resource package as a potential new department chair is common practice in academic medicine. The foundations for this negotiation include the historical presence of the department in relation to the broader institution, projections for future growth, accounting for mission/vision, resource needs (space, personnel, finances, etc), faculty and staff development, and external partnerships within and outside the institution. Despite similarities in this process across departments, many nuances influence the development of a specific new chair package, such as, department size; desires, perspectives and talents of the incoming chair, the department faculty, the medical school and dean; prevailing agendas and mission imperatives; and the overall priorities of the institution. With strategy and forethought, a new chair package can promote a successful chair tenure and departmental growth. Assembled through the Association of Departments of Family Medicine with input from several dozen department chairs and senior leaders, this is intended to serve as a practical guide to new chair packages for chair candidates., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Abstract Invasion and metastasis are the main reasons for the poor prognosis of patients with cervical cancer(CC). SYK is closely related to tumor development. However, the functions of its two isoforms, SYK (L) or SYK (S), are not fully understood to date. In this study, we investigated their biologic functions and possible prognostic values in CC. qRT-PCR was performed to detect the expression of SYK and two variant isoforms in cervical cancer tissues and cells. The association of SYK(L) and SYK(S) with Clinical pathological parameters were evaluated. The migration and invasion was detected by scratch assay and transwell. Western blot was conducted to measure the changes of epithelial mesenchymal transition (EMT)-related markers and PI3K/AKT signaling pathway proteins in cervical cancer cells. LY294002 (inhibitor of PI3K/AKT pathway) and IGF-1 (activator of PI3K/AKT pathway) were applied to evaluate the contribution of PI3K/AKT signaling pathway in cervical cancer cells. The expression of SYK(S) in cervical cancer tissues was significantly higher than that of SYK(L). SYK(L) and SYK(S) were correlated with muscular infiltration, SYK(L) high expression had a better prognosis, whereas SYK(S) high expression predicted a worse disease outcome. Cox multivariate regression analysis demonstrated that SYK(L) expression was an independent prognostic factor. SYK(L) significantly inhibited the proliferation, migration and invasion, while SYK(S) showed the opposite effects. LY294002 blocked SYK (L) knockdown-induced enhancement of migration and invasion as well as the expression EMT-related markers, whereas IGF-1 rescued the decreased migration, invasion and EMT induced by SYK (S) knockdown. The results suggest that SYK(L) and SYK(S) are involved in the progression of cervical cancer through PI3K/AKT signaling pathway, and may serve as potential targets for clinical treatment of advanced cervical cancer.

Abstract FAR-RED IMPAIRED RESPONSE 1 (FAR1) is a class of transposase-derived transcription factors that play a very important role in the initiation of the photosensitive pigment A (phyA) signaling pathway. Despite their importance, the understanding of the function of FAR1 genes in quinoa is still limited, especially regarding how they affect the spike sprouting response. Quinoa has gained global attention in recent years for its health benefits and potential for sustainable agriculture. In our study, the CqFAR1 gene set in quinoa was characterized using HMMER (PF03101) and BLAST analyses, and 87 genes were identified. The 87 CqFAR1 genes were systematically classified into five groups that showed a high degree of conservation in gene structure and motif composition. Tissue expression profiles of the CqFAR1 gene indicated that the CqFAR1 gene plays a key role throughout the growth and development of quinoa, especially at mid (leaf) and end (spike) stages. By RT-qPCR analysis, we observed significant differences in the expression of the CqFAR1 gene at different developmental stages. Notably, the CqFAR1 gene showed significant expression enhancement at the early stage of quinoa spike sprouting. The results are useful for understanding the role of the CqFAR1 gene in quinoa growth and development and provide theoretical support for quinoa breeding.

Abstract Acute-on-chronic liver failure (ACLF) is a syndrome characterized by the acute decompensation of chronic liver disease, resulting in organ failure and high short-term mortality. The progression of ACLF is dynamic and reversible in a considerable proportion of patients during hospitalization. Early detection and accurate assessment of ACLF are essential; however, ideal methods for this purpose are still lacking. Therefore, this study aimed to develop a new score for predicting the onset of ACLF in patients with various chronic liver diseases.A total of 6,188 patients with various chronic liver diseases were included in the study. Clinical and laboratory data were collected, and the occurrence of ACLF within 28 days was recorded. The Lasso-Cox regression method was employed to develop prediction models for the onset of ACLF at 7, 14, and 28 days. Among 5,221 patients without ACLF, 477 progressed to ACLF within 28 days. Seven predictors were identified as significantly associated with the occurrence of ACLF at 7, 14, and 28 days. A new scoring system was developed as follows: [NEUT ≥ 7, 109/L; 1 or 0] × 0.49 + [PLT 7, mmol/L; 1 or 0] × 0.51 + Ln[INR] × 0.87 + 3.40. This new score demonstrated superior discrimination, with the C-indexes of 0.958, 0.944, and 0.938 at 7, 14, and 28 days, respectively, outperforming those of four other scores (CLIF-C-ACLF-Ds, MELD, MELD-Na, and CLIF-C-ADs score; all P

Abstract The long-term health impacts of niacin are still debated, and the association between dietary niacin and mortality risk in populations hasn’t been extensively explored. This study included 26,746 US adults aged 20 years or older from the National Health and Nutrition Examination Survey 2003–2018, with a median follow-up of 9.17 years. During this period, there were 3,551 all-cause deaths, including 1,096 cardiovascular deaths. Cox models were used to compare hazard ratios (HRs) for mortality among participants grouped into different dietary niacin intake quartiles. Participants with the highest dietary niacin intake had a lower risk of all-cause mortality (HR 0.74, 95%CI 0.63–0.86) compared to those in the lowest intake quartile. For cardiovascular mortality, the HR was 0.73 (95%CI 0.57–0.95) in the highest niacin intake quartile. A dose-response relationship was revealed between dietary niacin intake and mortality by restricted cubic spline. Subgroup analysis showed a significant interaction between dietary niacin intake and diabetes concerning all-cause mortality (P = 0.046). In this population-based cohort study, higher dietary niacin intake correlates with lower risk of all-cause and cardiovascular mortality among US adults. The influence of niacin intake on all-cause mortality appears to be more significant in non-diabetic individuals compared to those with diabetes.

Abstract Phosphorylation of Ser32 and Ser36 controls the degradation of IκBα is the conserved cascade mechanisms of immune core signaling pathway, NF-κB pathway in metazoans, but it’s response to abiotic stress and the presence of novel phosphorylation mechanisms in other species remain unclear. Herein, we reported a novel heat-induced phosphorylation site (Ser74) at oysters’ major IκBα, which independently regulated ubiquitination-proteasome degradation without the requirement of phosphorylation at S32 and S36. And this site was phosphorylated by ERK/MAPK pathway, which then promoted REL nuclear translocation to activate cell survival related genes to defend heat-stress. The MAPK-NF-κB cascade exhibited divergent thermal responses and adaptation patterns between two congeneric oyster species with differential habitat temperatures, indicating its involvement in shaping temperature adaptation. This study demonstrated that the existence of complex and unique phosphorylation-mediated signaling transduction mechanism in marine invertebrates, and expanded our understanding of the evolution and function of established classical pathway crosstalk mechanisms.

Abstract Background: Neoadjuvant chemoradiotherapy combined with immunotherapy (NICRT) is a new neoadjuvant treatment approach that has raised concerns regarding potential challenges in surgery and postoperative complications. This study aimed to compare the efficacy and safety of neoadjuvant chemoradiotherapy (NCRT) and NICRT for the treatment of resectable locally advanced esophageal squamous cell carcinoma (ESCC). Methods: We retrospectively analyzed 291 patients with locally advanced ESCC who underwent neoadjuvant therapy and esophagectomy at three centers between January 2019 and September 2023 and added the data from PALACE-1 for the analysis, Among these patients, 248 and 61 patients received NCRT and NICRT, respectively. Propensity score matching (PSM) was used to balance the potential bias. Results: After the PSM,the rate of a pathological complete response (pCR) in the NCRT group was not significantly different from that in the NICRT group (46.90% vs 36.36%, P = 0.180). There were no significant differences in the tumor regression grade (TRG) and positive lymph node pCR rates between the two groups (P = 0.233 and P = 0.354, respectively). Treatment-related toxicities and postoperative complications were not significantly different between the NCRT group and the NICRT group (P = 0.199, P = 0.284). Conclusion: Compared with NCRT, NICRT did not lead to the better treatment efficacy. There were no significant differences was observed in the incidence of treatment-related toxicities and postoperative complications.

Abstract Vaccination plays a crucial role in preventing and controlling SARS-CoV-2 infections as well as their associated adverse outcomes. But there is a notable lack of research on the effectiveness of COVID-19 vaccination in children, particularly those young preterm-born children, who are more vulnerable to severe outcomes from SARS-CoV-2 infection. We aimed to determine the effect of vaccination with inactivated vaccines BBIBP-CorV and CoronaVac on symptomatic COVID-19 infection and related symptoms in preterm-born children aged 3–7 years after relaxation of the COVID-19 prevention and control measures in December 2022 in China. We performed a retrospective cohort study involving 242 preterm-born children aged 3–7 years and the data were collected in March 2023. Logistic regression models and modified Poisson regression models combined with entropy balancing were used to explore the associations of vaccination against SARS-CoV-2 with symptomatic COVID-19, specific symptoms, and persistent symptoms one month after recovery from COVID-19. Of the 242 recruited preterm-born children, 156 (64.5%) were vaccinated with inactivated vaccines BBIBP‐CorV and CoronaVac. After entropy balancing, the covariates were balanced between the vaccinated and the unvaccinated groups, with standardized mean difference

Abstract Group 2 innate lymphocytes (ILC2) have an important role in orchestrating sepsis-induced immune response. However, the impact of LC2 on sepsis-induced cardiac injury is still not fully understood. This study investigated the mechanisms governing ILC2 activation within the cardiac tissue after sepsis. In vivo experiments using wild-type and IL-33 deficient mice indicated that the presence of interleukin (IL)-33, which participates in expanding and activating ILC2 cells, was correlated with higher ILC2 levels (246 ± 34 vs. 66 ± 18, p

Abstract Purpose This randomized controlled study aims to compare the effects of cluster training versus traditional plyometric lower limb training on vertical and horizontal jump performance, as well as the reactive strength index, in young female artistic gymnasts. Methods: A total of 54 female artistic gymnasts (15.4 ± 1.2 years) participated voluntarily this study. Participants were assigned to one of three groups: (i) cluster training (PLYct); (ii) traditional training (PLYtr); and (iii) a control group (not exposed to plyometric training). The intervention spanned 8 weeks, with evaluations conducted before and after the intervention period for the following variables: (i) squat jump; (ii) countermovement jump; and (iii) reactive strength index in a drop jump test. Results: Significant interactions time × group were found in SJ (p

Abstract Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, immune dysregulation, and systemic fibrosis. Research on SSc has been hindered largely by lack of relevant models to study the progressive nature of the disease and to recapitulate the cell plasticity that is observed in this disease context. Generation of models for fibrotic disease using pluripotent stem cells is important for recapitulating the heterogeneity of the fibrotic tissue and are a potential platform for screening anti-fibrotic drugs. We previously reported a novel in-vitro model for fibrosis using induced pluripotent stem cell-derived mesenchymal cells (iSCAR). Here we report the generation of a “scar-like phenotype” when iPSC derived mesenchymal cells are cultured on hydrogel that mimicks a wound healing/scarring response (iSCAR). First, we performed RNA sequencing (RNA-seq) based transcriptome profiling of iSCAR culture at 48 h and 13 days to characterize early and latestage scarring phenotypes. The next generation RNA-seq of these iSCAR culture at different timepoints detected expression 92% of early “scar associated” genes and 85% late “scar associated” genes, respectively. Comparative transcriptomic analysis of a gene level SSc compendium matrix to the iSCAR wound associated model revealed genes common in both data sets. Early scar formation genes showed biological processes of hypoxia (27.5%), vascular development (13.7%) and glycolysis (27.5), while late scar formation showed genes associated with senescence (22.6%). Next we show the effects of two different antifibrotic compounds to validate the utility of the model as a screening tool to study early and late-stagelate-stage fibrosis. An autotaxin inhibitor was used to validate the iSCAR late stage fibrotic model (iSCAR-T) and an antifibrotic tool screening compound of unknown mechanism (EX00015097) was used to study and validate both early (iSCAR-P) and late-stage (iSCAR-T) fibrosis in the iSCAR model.

Abstract. Background:. Breast cancer is ranked among the most prevalent malignancies in the Chinese female population. However, comprehensive reports detailing the latest epidemiological data and attributable disease burden have not been extensively documented. Methods:. In 2018, high-quality cancer surveillance data were recorded in 700 population-based cancer registries in China. We extracted data on female breast cancers (International Classification of Diseases, Tenth Revision [ICD-10]: C50) and estimated the incidence and mortality in 2022 according to the baseline data and corresponding trends from 2010 to 2018. Pathological types were classified according to the ICD for Oncology, 3rd Edition codes. Disability-adjusted life years (DALYs) were calculated as the sum of the years of life lost (YLLs) and years lived with disability (YLDs). Results:. In 2022, approximately 357,200 new female breast cancer cases and 75,000 deaths occurred in China, accounting for 15.59% and 7.94% of total new cancer cases and deaths, respectively. The age-standardized incidence rate (ASIR) was 33.04 per 100,000. When analyzed by pathological type, the ASIRs for papillary neoplasms, invasive breast carcinoma, rare and salivary gland-type tumors, and other types were 1.13, 29.79, 0.24, and 1.88 per 100,000, respectively. The age-standardized mortality rate (ASMR) was 6.10 per 100,000. A total of 2,628,000 DALYs were found to be attributable to female breast cancer in China, comprising 2,278,300 YLLs and 349,700 YLDs. The ASIR, ASMR, and age-standardized rate (ASR) for DALYs in urban areas were consistently higher than those in rural areas. We observed a four-fold increase in the ASIR and ASR for DALYs and an eight-fold increase in the ASMR among females over 55 years compared with those aged under 55 years. Conclusion:. These data provide invaluable insights into the latest epidemiology of female breast cancer in China and highlight the urgency for disease prevention and control strategy formulation.

Abstract Ensuring the traceability of agricultural products is essential for quality control and food safety. Recent technological advances have provided new ways to enhance traceability systems. This study aims to use blockchain technology, centralized database and RFID tags to develop a secure agricultural product traceability system, retain the detailed information of agricultural products traceability, ensure that the summary information of agricultural products on the chain cannot be modified, and optimize the SM3 algorithm to effectively summarize the traceability data and improve the efficiency of the system. The aggregated data is time-stamped, recorded on the blockchain, and written into an RFID tag. The optimization of the SM3 algorithm improved the efficiency by 30% and reduced the execution time of 192-byte messages to 210µs. The system ensures accurate linking of traceability data through secure data retention and unalterable summaries on the blockchain. The integrated use of blockchain, centralized database and RFID technology, as well as the enhanced SM3 algorithm, allows the system to meet the standards for data accuracy and performance requirements in agricultural traceability applications.

Abstract Functional dyspepsia (FD) is known to be influenced by gut microbiota (GM) and circulating inflammatory proteins (CIPs), however, the causal relationship between GM, CIPs and FD haven’t been investigated. This study employed two-sample Mendelian Randomization (TSMR) to investigate their associations using data from Genome-Wide Association Studies (GWAS). In this study, Inverse-variance weighted (IVW) method was employed as the primary analysis, with supplementary approaches including weighted median, weighted mode, simple mode, and MR-Egger. Heterogeneity and pleiotropy were assessed using the Cochrane Q test, MR-Egger intercept test, and MR-PRESSO global test. Totally, 196 GM traits and 91 CIPs were analyzed, and the results uncovered the causal impact of 12 GM taxa and 5 proteins on functional dyspepsia (FD). 9 GM genera were linked to a reduced risk of FD, while 3 GM genera were associated with an increased risk of FD.Additionally, reverse analysis revealed no FD-GM causation. Furthermore, IL-12, IL-10, CXCL10, CXCL9 and VEGFA were significantly correlated with FD, with CXCL9 and VEGFA acting as mediators in the association between GM traits and FD. Taken together, our findings established a link between specific GM and CIPs in the pathogenesis of FD, offering novel insights for its diagnosis and treatment.

Abstract Metabolism, including glycolysis, oxidative phosphorylation, fatty acid oxidation, and other metabolic pathways, impacts the phenotypes and functions of immune cells. The metabolic regulation of the immune system is important in the pathogenesis and progression of numerous diseases, such as cancers, autoimmune diseases and metabolic diseases. The concept of immunometabolism was introduced over a decade ago to elucidate the intricate interplay between metabolism and immunity. The definition of immunometabolism has expanded from chronic low-grade inflammation in metabolic diseases to metabolic reprogramming of immune cells in various diseases. With immunometabolism being proposed and developed, the metabolic regulation of the immune system can be gradually summarized and becomes more and more clearer. In the context of many diseases including cancer, autoimmune diseases, metabolic diseases, and many other disease, metabolic reprogramming occurs in immune cells inducing proinflammatory or anti-inflammatory effects. The phenotypic and functional changes of immune cells caused by metabolic regulation further affect and development of diseases. Based on experimental results, targeting cellular metabolism of immune cells becomes a promising therapy. In this review, we focus on immune cells to introduce their metabolic pathways and metabolic reprogramming, and summarize how these metabolic pathways affect immune effects in the context of diseases. We thoroughly explore targets and treatments based on immunometabolism in existing studies. The challenges of translating experimental results into clinical applications in the field of immunometabolism are also summarized. We believe that a better understanding of immune regulation in health and diseases will improve the management of most diseases.

Abstract Objectives To assess the efficacy of the Chinese herbal medication Shugan Hewei formula (SHF) combined with rabeprazole in patients with refractory gastroesophageal reflux disease (rGERD). Method A total of 264 participants were randomly assigned to the treatment group (n = 132) receiving SHF granules (20 mg) combined with rabeprazole (10 mg) and the control group (n = 132) receiving placebo SHF granules (20 mg) combined with rabeprazole (20 mg). Both groups undergo 8 weeks of treatment and 2 weeks of follow-up. Results The treatment group showed higher total clinical symptom efficacy and lower total symptom scores compared to the control group. The treatment group was superior to the control group in reducing rGERD major symptom scores, including heartburn, retrosternal pain, regurgitation and belching, and acid regurgitation. Additionally, treatment group (Z = 8.169, P

Abstract The impact of vitamin B2 (riboflavin) intake on cognitive performance among older adults in the United States (US) remains inadequately understood. This study aimed to explore the association between vitamin B2 intake and cognitive performance among non-institutionalized elderly people in the US. Weighted logistic regression was used to evaluate the association between vitamin B2 intake and cognitive performance. Vitamin B2 intake was determined from the mean of two 24-hour dietary recall interviews. Three cognitive ability assessment tests, namely the Immediate Recall Test (IRT), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST), were performed. Participants included all older adults over 60 who underwent cognitive scoring, with cut-offs defined based on the lowest quartile (25th percentile) for each test (the cut-offs for the three scores were 15.625, 12, and 33, respectively). Sensitivity analysis, including dose-response curves, subgroup analyses, interaction effects, per 1 standard deviation (SD), recommended dietary allowance (RDA), and residual energy model analysis, were performed to solidify the solid association between vitamin B2 and cognitive performance. A total of 2893 individuals aged over 60 were included, with a mean age of 69 (7) years, and 46% were men. There was a significant association between vitamin B2 intake and all three cognitive scores (IRT, Odds Ratio = 0.77, 95% confidence interval: [0.65,0.92]; AFT, 0.75, [0.64,0.88]; DSST, 0.72, [0.59,0.88]). Moreover, vitamin B2 intake above the RDA reduced the risk of low cognitive performance (IRT, 0.66, [0.46,0.93]; AFT, 0.83, [0.62,1.11]; DSST, 0.65, [0.45,0.92]) compared to intake below the RDA. Dose-response curves indicated that higher vitamin B2 intake was negatively associated with the risk of low cognitive performance. Physical activity may modify the association between vitamin B2 and cognitive performance. Vitamin B2 intake was positively associated with cognitive performance among older adults. Adequate vitamin B2 intake could help protect cognitive function.

Abstract Lactoferrin is a natural multifunctional glycoprotein with potential antidepressant-like effects. However, the mechanism of its antidepressant effect has not been explored from the perspective of gut flora metabolism. Therefore, we employed both 16S rDNA gene sequencing and LC–MS metabolomics analysis to investigate the regulatory effects and mechanisms of lactoferrin in a rat model of depression. After one week of acclimatization, twenty-four 7-week-old male Sprague–Dawley rats were randomly and equally assigned into three groups: the control group, the model group, and the lactoferrin intervention group. The control group rats were housed under standard conditions, while the rats in the model and lactoferrin intervention groups were individually housed and exposed to chronic unpredictable mild stress for 44 days simultaneously. The lactoferrin intervention group was provided with water containing 2% lactoferrin (2 g/100 ml). Behavioural tests were conducted at week 7. Upon completion of the behavioral tests, the rats were anesthetized with isoflurane, humanely euthanized using a rat guillotine, and tissue samples were collected for further experiments. The results indicated that lactoferrin intervention led to an increase in sucrose solution consumption, horizontal movement distance, number of cross platforms, and residence time in the target quadrant. Additionally, it resulted in an increase in jejunal tight junction protein ZO-1 expression and a suppression of serum expression of inflammatory factors, Lipopolysaccharide and Diamine oxidase. In summary, lactoferrin can regulate the metabolic disorder of intestinal flora, reduce intestinal permeability, and further regulate the metabolic balance of hippocampal tissues through the microbiota-gut-brain axis. This process ultimately alleviates the depression-like behavior in rats.

Abstract Background Nursing literature suggested that patient mistreatment has significant impacts on nurses’ emotions and job burnout. Yet, further research is needed to understand the underlying mechanism and the spillover effect on nurses’ families. Leveraging the goal progress theory, this study aimed to examine the association between patient mistreatment, nurses’ emotional exhaustion, and work-family conflict, as well as the mediating role of social sharing of negative work events and the moderating role of perceived organizational support. Methods During the COVID-19 pandemic in China, a cross-sectional study was conducted with a sample of 1627 nurses from the Hematology Specialist Alliance of Chongqing from October to November 2022. Questionnaires were administered to measure patient mistreatment, perceived organizational support, social sharing of negative work events, emotional exhaustion, and work-family conflict. Hierarchical linear regression and conditional processes were used for statistical analyses. Results Patient mistreatment was positively associated with emotional exhaustion (β = 0.354, p

Abstract Mortise and tenon joint is a key connecting component in timber-framed architecture. Accurately assessing the damage to joints is crucial for the structural design of wooden buildings. This study conducted fatigue tests at three stress levels (70%, 100%, and 130%) based on the maximum stress from static bending tests to analyze the impact of different stress levels on the fatigue performance of mortise and tenon joints. The results showed that the deformation increased as the stress level increased. The energy loss per cycle de-creased and then increased at 130% stress level, and remained essentially constant at 70% and 100% levels. Then, micro-CT scanning was performed on the specimens after fatigue testing. The ambient occlusion algorithm was used to identify the outer boundaries of the tenon, which can distinguish internal cracks from outside air. The sphericity index was used to differentiate between pores and cracks. Three-dimensional visualization analysis was performed on the specimens, and the obtained information on pores and cracks was quantitatively analyzed. The results indicated that deformation and fracture of the tenon were the primary causes of joint damage. The layer-by-layer porosity of the undeformed portion of the tenon remained essentially constant and was lower than that of the fractured region and higher than that of the deformed region. This study analyzed the damage behavior of mortise and tenon joints under different stress levels, contributing to the design and protection of wooden structure buildings.

Abstract Acute lung injury (ALI) is a severe clinical respiratory condition characterized by high rates of mortality and morbidity, for which effective treatments are currently lacking. In this study, lipopolysaccharide (LPS) was used to induce ALI mice, demonstrating the efficacy of tetramethylpyrazine (TMP) in ameliorating ALI. Subsequent we perfored high-throughput sequencing analysis and used Targetscan 8.0 and miRWalk 3.0 databases to predict the interaction between microRNAs and destrin (DSTN), ultimately identifying miR-369-3p as the focus of the investigation. The adenovirus carrying miR-369-3p was administered one week prior to LPS-induced in order to assess its potential efficacy in ameliorating ALI in mice. The findings indicated that the overexpression of miR-369-3p resulted in enhanced lung function, reduced pulmonary edema, inflammation, and permeability in LPS-induced ALI mice, while the suppression of miR-369-3p exacerbated the damage in these mice. Furthermore, the beneficial effects of TMP on LPS-induced ALI were negated by the downregulation of miR-369-3p. The results of our study demonstrate that TMP mitigates LPS-induced ALI through upregulation of miR-369-3p. Consequently, the findings of this study advocate for the clinical utilization of TMP in ALI treatment, with miR-369-3p emerging as a promising target for future ALI interventions.

Abstract While previous observational studies have suggested a link between leukocyte counts and vascular dementia (VD), the causal relationship between leukocyte counts and various subtypes of VD remains elusive. This study aimed to investigate the causal relationship between five types of leukocyte counts and VD, with the goal of improving prevention and treatment strategies. In this study, leukocyte counts were used as the exposure variable, with genome-wide association study (GWAS) data sourced from both the UK Biobank and the Blood Cell Consortium. Additionally, GWAS data for five subtypes of vascular dementia were obtained from the FinnGen database. We conducted rigorous statistical analysis and visualization using Mendelian randomization (MR) to elucidate the potential causal relationship between leukocyte counts and vascular dementia. This study, utilizing MR analysis with data from the UK Biobank and Blood Cell Consortium, identified significant causal associations between increased lymphocyte counts and VD. Specifically, lymphocyte counts were found to be causally related to multiple and mixed VD subtypes. Sensitivity analyses, including MR-Egger regression and MR-PRESSO tests, confirmed the robustness of these findings, with no evidence of reverse causality or significant horizontal pleiotropy detected. The results underscore a potential inflammatory or immunological mechanism in the pathogenesis of VD, highlighting lymphocytes as a key component in their etiology. This investigation establishes a robust association between elevated lymphocyte and leukocyte counts and an increased risk of VD, emphasizing the roles of inflammation, immune activation, and hematological factors in disease pathogenesis.

Abstract Cardiac myxoma is a commonly encountered tumor within the heart that has the potential to be life-threatening. However, the cellular composition of this condition is still not well understood. To fill this gap, we analyzed 75,641 cells from cardiac myxoma tissues based on single-cell sequencing. We defined a population of myxoma cells, which exhibited a resemblance to fibroblasts, yet they were distinguished by an increased expression of phosphodiesterases and genes associated with cell proliferation, differentiation, and adhesion. The clinical relevance of the cell populations indicated a higher proportion of myxoma cells and M2-like macrophage infiltration, along with their enhanced spatial interaction, were found to significantly contribute to the occurrence of embolism. The immune cells surrounding the myxoma exhibit inhibitory characteristics, with impaired function of T cells characterized by the expression of GZMK and TOX, along with a substantial infiltration of tumor-promoting macrophages expressed growth factors such as PDGFC. Furthermore, in vitro co-culture experiments showed that macrophages promoted the growth of myxoma cells significantly. In summary, this study presents a comprehensive single-cell atlas of cardiac myxoma, highlighting the heterogeneity of myxoma cells and their collaborative impact on immune cells. These findings shed light on the complex pathobiology of cardiac myxoma and present potential targets for intervention.

Abstract Background Uterine corpus endometrial carcinoma (UCEC) is a prevalent gynecologic malignancy with a favorable prognosis if detected early. However, there is a lack of accurate and reliable early detection tests for UCEC. This study aims to develop a precise and non-invasive diagnostic method for UCEC using circulating cell-free DNA (cfDNA) fragmentomics. Methods Peripheral blood samples were collected from all participants, and cfDNA was extracted for analysis. Low-coverage whole-genome sequencing was performed to obtain cfDNA fragmentomics data. A robust machine learning model was developed using these features to differentiate between UCEC and healthy conditions. Results The cfDNA fragmentomics-based model showed high predictive power for UCEC detection in training (n = 133; AUC 0.991) and validation cohorts (n = 89; AUC 0.994). The model manifested a specificity of 95.5% and a sensitivity of 98.5% in the training cohort, and a specificity of 95.5% and a sensitivity of 97.8% in the validation cohort. Physiological variables and preanalytical procedures had no significant impact on the classifier’s outcomes. In terms of clinical benefit, our model would identify 99% of Chinese UCEC patients at stage I, compared to 21% under standard care, potentially raising the 5-year survival rate from 84 to 95%. Conclusion This study presents a novel approach for the early detection of UCEC using cfDNA fragmentomics and machine learning showing promising sensitivity and specificity. Using this model in clinical practice could significantly improve UCEC management and control, enabling early intervention and better patient outcomes. Further optimization and validation of this approach are warranted to establish its clinical utility.

Abstract This study aimed to develop and internally validate a nomogram model for assessing the risk of intraoperative hypothermia in patients undergoing video-assisted thoracoscopic (VATS) lobectomy. This study is a retrospective study. A total of 530 patients who undergoing VATS lobectomy from January 2022 to December 2023 in a tertiary hospital in Wuhan were selected. Patients were divided into hypothermia group (n = 346) and non-hypothermia group (n = 184) according to whether hypothermia occurred during the operation. Lasso regression was used to screen the independent variables. Logistic regression was used to analyze the risk factors of hypothermia during operation, and a nomogram model was established. Bootstrap method was used to internally verify the nomogram model. Receiver operating characteristic (ROC) curve was used to evaluate the discrimination of the model. Calibration curve and Hosmer Lemeshow test were used to evaluate the accuracy of the model. Decision curve analysis (DCA) was used to evaluate the clinical utility of the model. Intraoperative hypothermia occurred in 346 of 530 patients undergoing VATS lobectomy (65.28%). Logistic regression analysis showed that age, serum total bilirubin, inhaled desflurane, anesthesia duration, intraoperative infusion volume, intraoperative blood loss and body mass index were risk factors for intraoperative hypothermia in patients undergoing VATS lobectomy (P

Abstract Objective In this study, we added laboratory animal ethics education into both didactic sessions and practical sessions the general surgery laboratory course, with the didactic sessions focus on teaching the fundamental principles of laboratory animal ethics, while the practical sessions emphasize the application of these principles in laboratory classes and have assessed the changes in medical students' perception of laboratory animal ethics following medical students exposure to such education. Methods One hundred and eighty-nine third-year medical students from Wuhan University's Second Clinical College completed a laboratory animal ethics awareness questionnaire and a laboratory animal ethics written examination before and after laboratory animal ethics education. Results After receiving laboratory animal ethics education, the percentage of students who supported euthanasia for the execution of animals and humane treatment of laboratory animals were 95.2% and 98.8%, respectively, which did not differ from the 94.9% and 96.4% observed before the education. Moreover, there was a notable increase in the proportion of students who knew about regulations related to laboratory animals (from 39.9% to 57.1%), welfare issues (from 31.9% to 50.0%), and the 3R principle (from 30.4% to 58.9%) post-education, all statistically significant at P

ObjectiveTo investigate the impact of technique of sling exercise with Tuina therapy on improving paravertebral muscle asymmetry in patients with adolescent idiopathic scoliosis (AIS).MethodsA total of 88 patients with AIS who met the inclusion criteria and received treatment at the Rehabilitation Department of the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine from October 2021 to August 2023 were recruited for this study. They were randomly divided into control group and experimental group, with 44 cases in each group. Routine rehabilitation training was performed in the control group with reference to the German Schroth scoliosis three-dimensional corrective therapy, including manipulation to relax the concave side of the paraspinal muscles, "hip bridge", and "small swallow fly" and other strength exercises. Schroth gymnastics included "muscle column", "rotational sitting movement", "stretching exercise" with angular breathing. The experimental group was treated with sling Tuina exercise technique which mainly included adjusting the position of the spine to restore the neutral position, the methods of plucking, pressing and pushing and other techniques to act back and forth on the Governor vessel, bladder meridian and the convex-concave side of the paravertebral muscle dialectical tonifying and reducing therapy, neutral position control training in supine, prone and lateral position, trunk flexion, extension, rotation and lateral flexion closed chain movement training with the assistance of sling equipment. Before treatment and after 4 weeks of treatment, the surface electromyography (sEMG) was used to measure the paraspinal muscles of the patients during standing weight-bearing position, and the root mean square (RMS) was calculated and analyzed through the included software, and the paraspinal muscle symmetry index was calculated (PMSI=RMSconvex/RMSconcave); Cobb's angle was used to assess the severity of the patients' scoliosis; and the angle of trunk rotation (ATR) was used to assess the degree of rotation of the trunk.ResultsBefore treatment, the PMSI values, Cobb's angle, and ATR values of the two groups were compared, and the differences were not statistically significant (P>0.05). After 4 weeks of treatment, the PMSI values of the experimental group was 1.08 (1.04, 1.14), the Cobb's angle was 5 (2, 9)°, and the ATR value was 2 (1, 3)°, while the PMSI value of the control group was 1.12 (1.09, 1.17), the Cobb's angle was 8.5 (6, 10)°, and the ATR value was 2 (2, 3)°. The intra-group comparison results showed that the Cobb's angle and ATR values decreased in both groups after treatment (PPPPP>0.05).Conclusiontechnique of sling exercise with Tuina therapy can effectively improve the asymmetry of paravertebral muscles and achieve the orthopedic purpose of reducing the Cobb's angle and trunk rotation angle of patients, which is recommended for clinical application.

Abstract To investigate the characteristics of destabilization damage in coal-rock complexes. Mechanical property tests were conducted on coal, rock, and their complexes. An infrared thermal camera was employed to real-time monitor the infrared (IR) radiation response signals during the destabilization damage process. A numerical model of coal-rock destabilization damage was developed, and its validity was verified. Deformed stress fields and displacement contours were obtained during the destabilization damage process. Upon destabilization, numerous cracks form at the base of the “coal” section, extending towards the interface, resulting in the formation of a wave-like deformation region. The differentiation in infrared thermal images is more pronounced in the “coal” section compared to the “rock” section. A high-stress region is evident at the interface, resulting in an area of high stress differentials. However, the bottom of the “coal” section also exhibits a region with high stress differentials and a more pronounced tendency towards destabilization damage. Displacement contours revealed that numerous units at the bottom of the “coal” section had slipped and misaligned, leading to the accumulation of damage and an elevation in the local damage level. It is a crucial factor contributing to the notable phenomenon of IR thermal image differentiation.

Background We aimed to investigate the value of phase angle (PhA) as a prognostic marker for mortality in elderly patients with multimorbidity using a matched case-control study. Methods This study was conducted with patients 70 years of age or older with multimorbidity at Beijing Geriatric Hospital. The body composition parameters including PhA were determined using bioelectrical impedance analysis. Common hematological indices were determined using blood tests. The outcome was mortality 1 year after admission. A multivariate logistic regression analysis was employed to identify independent risk factors for death. A receiver-operating characteristic (ROC) curve analysis was used to evaluate the performance of risk factors in predicting death. Results A total of 30 deceased patients were included in the death group. The living patients were matched 1:1 with the deceased patients in age, gender, and Cumulative Illness Rating Scale-Geriatric score to generate a survival group of 30. The death group exhibited higher levels of blood urea nitrogen and extracellular water to total body water ratio and lower levels of PhA and prealbumin than the survival group. The multivariate logistic regression analysis identified PhA as the only independent risk factor for mortality (OR = 3.296, 95% CI [1.201–9.044], P < 0.05). For the ROC curve analysis, PhA had an area of 0.854 (95% CI [0.755–0.955], P = 000). The Youden index was 0.700, and the optimal cutoff value associated with the Youden index was 2.45°. Conclusion PhA serves as a good prognostic marker for mortality in elderly patients with multimorbidity.

To construct and verify an easy-to-use nomogram for predicting the risk of infectious diseases in pediatric kidney transplant recipients. Clinical data of hospitalized pediatric kidney transplant recipients were retrospectively analyzed. Meaningful variables identified from the multivariate stepwise logistic regression analysis were used to construct the nomogram. Internal validation was performed using Bootstrap resampling 1,000 times. The nomogram was evaluated using calibration, decision and receiver operating characteristic (ROC) curves. A total of 297 pediatric kidney transplant recipients were included (164 infected, 133 non-infected). Multivariate stepwise regression analysis identified white blood cell count (WBC), lymphocyte to monocyte ratio (MLR), platelet to neutrophil ratio (PNR), red cell distribution width-standard deviation (RDW-SD), and albumin (ALB) as significant predictors of postoperative infection. The nomogram, based on the five indicators, showed strong discrimination ability (AUC = 0.756; 95% CI [0.702–0.811]), with a sensitivity of 88.0% and a specificity of 54.3%. The calibration curve and decision curve further demonstrated good consistency and clinical practicality between the predicted and actual values. WBC, MLR, PNR, RDW-SD, and ALB are effective indicators for predicting postoperative infection in pediatric kidney transplant recipients. The nomogram constructed from these indicators can effectively predict and evaluate the early risk of infection in these patients.

Abstract Pharmacological agents regarding the most optimal treatments of acute pancreatitis remain. One‐carbon metabolism nutrients as therapeutic agents in many diseases might be involved in acute pancreatitis. The roles are acquired exploration in acute pancreatitis. We utilized Mendelian randomization to assess the causal impact of folate, homocysteine, and vitamin B12 (VB12) on acute pancreatitis. Wild‐type and corresponding genetically modified mouse models were used to verify the genetic correlating findings. A negative association between genetically predicted serum VB12 levels and risks of acute pancreatitis was identified in human population. The transcobalamin receptor (TCblR)/CD320 gene ablation that decreased cellular VB12 uptake and ATP production in pancreatic tissues promoted necrosis, resulting in much severe pathological changes of induced acute pancreatitis in mice. VB12 pretreatment and posttreatment dramatically increased ATP levels in pancreatic tissues and reduced the necrosis, then the elevated levels of amylase in serum, the levels of CK‐19, the activity of trypsin, and T lymphocyte infiltration in pancreatic tissues, prevented the pancreatic gross loss and ameliorated histopathological changes of mouse pancreases with induced acute pancreatitis. The results reveal that VB12 is potential as a therapeutic agent to inhibit tissue injuries and adaptive inflammatory responses in the pancreas in patients with acute pancreatitis.

Introduction Critically ill patients are at a heightened risk for post-traumatic stress disorder (PTSD). While the intensive care unit (ICU) diary has been shown to improve the mental health and quality of life of ICU patients, the handwritten version still has some limitations such as a lack of support for multimedia content and writing by remote family members, as well as being time-consuming and labour-intensive. We hypothesise that constructing an ICU electronic diary platform based on a co-design approach and verifying its applicability could alleviate these limitations, making the ICU diary more convenient for users.Methods and analysis This sequential exploratory mixed-methods study will consist of four consecutive phases: understanding the ICU diary research content and implementation, developing an ICU electronic diary platform after conducting qualitative interviews with stakeholders, verifying the applicability of the platform and verifying its effectiveness.Ethics and dissemination Ethics approval was obtained from the Biomedical Research Ethics Committee of the Affiliated Hospital of Zunyi Medical University (approval number: KLL-2023–602). The results of this study will be distributed through peer-reviewed journals.Trial registration number Chinese Clinical Trial Register (ChiCTR2400079903).

Abstract Magnesium imbalances commonly exist in septic patients. However, the association of serum magnesium levels with mortality in septic patients remains uncertain. Herein, we elucidated the association between serum magnesium and all‐cause mortality in septic patients from American and Chinese cohorts by analyzing data from 9099 patients in the Medical Information Mart for Intensive Care‐IV (MIMIC‐IV) database and 1727 patients from a university‐affiliated hospital’ intensive care unit in China. Patients in both cohorts were categorized into five groups based on serum magnesium quintiles from the MIMIC‐IV dataset. Patients with higher serum magnesium levels exhibited an increased risk of 28‐day mortality in both cohorts. The restricted cubic spline (RCS) curves revealed a progressively elevated risk of 28‐day mortality with increasing serum magnesium in MIMIC‐IV cohort, while a J‐shaped correlation was observed in institutional cohort. Our findings have validated the association between high serum magnesium and high mortality in sepsis across different races and medical conditions. Serum magnesium levels might be useful in identifying septic patients at higher mortality risk.

Background: An increase in opioid-related overdoses, notably from potent synthetic opioids like fentanyl, prompted this consideration of characteristics of emergency department (ED) patients with evidence for illicit fentanyl use or exposure, the correlation with intentional opioid misuse, and subsequent ED management. Methods: A retrospective review was performed of patients presenting to an urban academic medical center ED with evidence for illicit fentanyl use, determined by positive urine drug screens (UDS), from 6/2021 through 11/2021. Participant demographics, comorbidities, ED chief complaint and disposition, and evidence of intentional opioid misuse were considered. Secondary outcomes included provision of buprenorphine/naloxone and/or naloxone kits at discharge, ED recidivism, and six-month mortality. Bivariate comparisons and logistic regression models were performed. Results: Among 409 unique patients, most were white and male with a mean age of 39.4. Approximately half presented with opioid-related complaints. Evidence of intentional opioid misuse was identified in 72.6 % of patients. Black patients had 79 % lower odds of intentional opioid misuse compared to white patients. Regarding ED management, 28.8 % were discharged with buprenorphine/naloxone and 14.0 % with a naloxone kit. Black patients had 63 % lower odds of receiving buprenorphine/naloxone compared to white patients after controlling for covariates. Nearly 6 % of the study population died within six months of the initial ED visit. Conclusion: This fentanyl-focused review describes patient characteristics which largely mirror the epidemiology of the current opioid epidemic; however, despite evidence of objective exposure, it also suggests that Black patients may be less likely to use fentanyl intentionally. It also highlights potential disparities related to ED-based opioid misuse patient management.

Abstract Due to global warming and the disturbance of the interannual variability of precipitation, the frequency of extreme drought events has increased. The impact of global climate change on water resources is becoming increasingly apparent, then it is particularly necessary to explore the carrying capacity of water ecological environment under extreme drought conditions, which can guarantee the ecological water security in river basins. This study takes the Guanzhong area of the Wei River Basin as an example, calculating the water environment carrying capacity of 40 areas in the Weihe Guanzhong area in different levels of years under extreme drought conditions by comprehensive evaluation model of carrying capacity and using geographic information system GIS to display the spatial distribution of water environment carrying capacity in 40 regions. According to the results of the spatial distribution of water environmental bearing capacity, four different schemes are designed to improve the bearing capacity. The first plan reduces the industrial water consumption and irrigation quota by 5%, the second plan increases the industrial water and sewage treatment rate on this basis. the third plan further improves the development and utilization rate of surface and groundwater, and the fourth plan, on the basis of the first three plans, supplies 600 million cubic meters of industrial and agricultural water to Guanzhong region. Through comparative analysis, without taking any measures, under the extreme drought conditions, the water environment carrying capacity of the 40 areas in Guanzhong is all in an unbearable state. Overall, plan 4 has the most significant improvement in the water environment-carrying capacity, especially the Dong zhuang Reservoir of the Jing River which has played a very important role in enhancing the water ecological environment carrying capacity of the downstream water of the Wei River.

Abstract Callicarpa kwangtungensis Chun (CK) is a common remedy exhibits anti-inflammatory properties and has been used in Chinese herbal formulations, such as KangGongYan tablets. It is the main component of KangGongYan tablets, which has been used to treat chronic cervicitis caused by damp heat, red and white bands, cervical erosion, and bleeding. However, the anti-inflammatory effects of CK water extract remains unknown. This study assessed the anti-inflammatory effects of CK in vivo and in vitro, characterized its main components in the serum of rats and verified the anti-inflammatory effects of serum containing CK. Nitric oxide (NO), tumour necrosis factor α (TNF-α) and interleukin-6 (IL-6) release by RAW264.7 cells was examined by ELISA and Griess reagents. Inflammation-related protein expression in LPS-stimulated RAW264.7 cells was measured by western blotting. Furthermore, rat model of foot swelling induced by λ-carrageenan and a collagen-induced arthritis (CIA) rat model were used to explore the anti-inflammatory effects of CK. The components of CK were characterized by LC–MS, and the effects of CK-containing serum on proinflammatory factors levels and the expression of inflammation-related proteins were examined by ELISA, Griess reagents and Western blotting. CK suppressed IL-6, TNF-α, and NO production, and iNOS protein expression in LPS-stimulated RAW264.7 cells. Mechanistic studies showed that CK inhibited the phosphorylation of ERK, P38 and JNK in the MAPK signaling pathway, promoted the expression of IκBα in the NF-κB signaling pathway, and subsequently inhibited the expression of iNOS, thereby exerting anti-inflammatory effects. Moreover, CK reduced the swelling rates with λ-carrageenan induced foot swelling, and reduced the arthritis score and incidence in the collagen-induced arthritis (CIA) rat model. A total of 68 compounds in CK water extract and 31 components in rat serum after intragastric administration of CK were characterized. Serum pharmacological analysis showed that CK-containing serum suppressed iNOS protein expression and NO, TNF-α, and IL-6 release. CK may be an anti-inflammatory agent with therapeutic potential for acute and chronic inflammatory diseases, especially inflammatory diseases associated with MAPK activation.

Abstract The difference in the survival of obese patients and normal-weight/lean patients with diabetic MAFLD remains unclear. Therefore, we aimed to describe the long-term survival of individuals with diabetic MAFLD and overweight/obesity (OT2M), diabetic MAFLD with lean/normal weight (LT2M), MAFLD with overweight/obesity and without T2DM (OM), and MAFLD with lean/normal weight and without T2DM (LM). Using the NHANESIII database, participants with MAFLD were divided into four groups. Hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cardiovascular disease (CVD)-related, and cancer-related mortalities for different MAFLD subtypes were evaluated using Cox proportional hazards models. Of the 3539 participants, 1618 participants (42.61%) died during a mean follow-up period of 274.41 ± 2.35 months. LT2M and OT2M had higher risks of all-cause mortality (adjusted HR, 2.14; 95% CI 1.82–2.51; p

Abstract Background With over 7000 Mendelian disorders, identifying children with a specific rare genetic disorder diagnosis through structured electronic medical record data is challenging given incompleteness of records, inaccurate medical diagnosis coding, as well as heterogeneity in clinical symptoms and procedures for specific disorders. We sought to develop a digital phenotyping algorithm (PheIndex) using electronic medical records to identify children aged 0–3 diagnosed with genetic disorders or who present with illness with an increased risk for genetic disorders. Results Through expert opinion, we established 13 criteria for the algorithm and derived a score and a classification. The performance of each criterion and the classification were validated by chart review. PheIndex identified 1,088 children out of 93,154 live births who may be at an increased risk for genetic disorders. Chart review demonstrated that the algorithm achieved 90% sensitivity, 97% specificity, and 94% accuracy. Conclusions The PheIndex algorithm can help identify when a rare genetic disorder may be present, alerting providers to consider ordering a diagnostic genetic test and/or referring a patient to a medical geneticist.

Abstract Accumulation landslides are prone to occur during the continuous infiltration of heavy rainfall, which seriously threatens the lives and property safety of local residents. In this paper, based on the Green-Ampt (GA) infiltration model, a new slope rainfall infiltration function is derived by combining the effect of air resistance and lateral seepage of saturated zone. Considering that when the soil layer continues to infiltrate after the saturation zone is formed, the air involvement cannot be discharged in time, which delays the infiltration process. Therefore, the influence of air resistance factor in soil pores is added. According to the infiltration characteristics of finite long slope, the lateral seepage of saturated zone is introduced, which makes up for the deficiency that GA model is only applicable to infinite long slope. Finally, based on the seepage characteristics of the previous analysis, the overall shear strength criterion is used to evaluate the stability of the slope. The results show that the safety factor decreases slowly with the increase of size and is inversely correlated with the slope angle and initial moisture content. The time of infiltration at the same depth increases with the increase of size and slope angle, and is inversely correlated with the initial moisture content, but is less affected by rainfall intensity. By comparing with the results of experimental data and other methods, the results of the proposed method are more consistent with the experimental results than other methods.

Abstract Bacterial infections triggered by patient or healthcare worker contact with surfaces are a major cause of medically acquired infections. By controlling the kinetics of tetrabutyl titanate hydrolysis and condensation during the sol–gel process, it is possible to regulate the content of Ti3+ and oxygen vacancies (OVs) in TiO2, and adjust the associated visible light-induced photocatalytic performance and anti-bacterial adhesion properties. The results have shown that the Ti3+ content in TiO2 was 9.87% at the calcination temperature of the reaction system was 300 °C and pH was 1.0, corresponding to optimal photocatalytic and hydrophilic properties. The formation of a hydrated layer on the superhydrophilic surface provided resistance to bacterial adhesion, preventing cross-contamination on high-touch surfaces. The excellent photocatalytic self-cleaning performance and anti-bacterial adhesion properties can be attributed to synergistic effects associated with the high specific surface area of TiO2 nanoparticles, the mesoporous structure, and the presence of Ti3+ and OVs. The formation of superhydrophilic self-cleaning surfaces under visible light can serve as the basis for the development of a new class of anti-bacterial adhesion materials.

Abstract Temporary neurological dysfunction (TND), a common complication following surgical repair of Type A Aortic Dissection (TAAD), is closely associated with increased mortality and long-term cognitive impairment. Currently, effective treatment options for TND remain elusive. Therefore, we sought to investigate the potential of postoperative relative band power (RBP) in predicting the occurrence of postoperative TND, with the aim of identifying high-risk patients prior to the onset of TND. We conducted a prospective observational study between February and December 2022, involving 165 patients who underwent surgical repair for TAAD at our institution. Bedside Quantitative electroencephalography (QEEG) was utilized to monitor the post-operative brain electrical activity of each participant, recording changes in RBP (RBP Delta, RBP Theta, RBP Beta and RBP Alpha), and analyzing their correlation with TND. Univariate and multivariate analyses were employed to identify independent risk factors for TND. Subsequently, line graphs were generated to estimate the incidence of TND. The primary outcome of interest was the development of TND, while secondary outcomes included intensive care unit (ICU) admission and length of hospital stay. A total of 165 patients were included in the study, among whom 68 (41.2%) experienced TND. To further investigate the independent risk factors for postoperative TND, we conducted both univariate and multivariate logistic regression analyses on all variables. In the univariate regression analysis, we identified age (Odds Ratio [OR], 1.025; 95% CI, 1.002–1.049), age ≥ 60 years (OR, 2.588; 95% CI, 1.250–5.475), hemopericardium (OR, 2.767; 95% CI, 1.150–7.009), cardiopulmonary bypass (CPB) (OR, 1.007; 95% CI, 1.001–1.014), RBP Delta (OR, 1.047; 95% CI, 1.020–1.077), RBP Alpha (OR, 0.853; 95% CI, 0.794–0.907), and Beta (OR, 0.755; 95% CI, 0.649–0.855) as independent risk factors for postoperative TND. Further multivariate regression analyses, we discovered that CPB time ≥ 180 min (OR, 1.021; 95% CI, 1.011–1.032), RBP Delta (OR, 1.168; 95% CI, 1.105–1.245), and RBP Theta (OR, 1.227; 95% CI, 1.135–1.342) emerged as independent risk factors. TND patients had significantly longer ICU stays (p

Abstract 5-Methylcytosine (m5C) is a common RNA modification that modulates gene expression at the posttranscriptional level, but the crosstalk between m5C RNA modification and biomolecule condensation, as well as transcription factor-mediated transcriptional regulation, in ovarian cancer, is poorly understood. In this study, we revealed that the RNA methyltransferase NSUN2 facilitates mRNA m5C modification and forms a positive feedback regulatory loop with the transcription factor E2F1 in ovarian cancer. Specifically, NSUN2 promotes m5C modification of E2F1 mRNA and increases its stability, and E2F1 binds to the NSUN2 promoter, subsequently reciprocally activating NSUN2 transcription. The RNA binding protein YBX1 functions as the m5C reader and is involved in NSUN2-mediated E2F1 regulation. m5C modification promotes YBX1 phase separation, which upregulates E2F1 expression. In ovarian cancer, NSUN2 and YBX1 are amplified and upregulated, and higher expression of NSUN2 and YBX1 predicts a worse prognosis for ovarian cancer patients. Moreover, E2F1 transcriptionally regulates the expression of the oncogenes MYBL2 and RAD54L, driving ovarian cancer progression. Thus, our study delineates a NSUN2-E2F1-NSUN2 loop regulated by m5C modification in a manner dependent on YBX1 phase separation, and this previously unidentified pathway could be a promising target for ovarian cancer treatment.

Abstract To investigate the safety and effect of Tubridge flow diverter deployment for the treatment of intracranial aneurysms, 85 patients with intracranial aneurysms treated with the Tubridge flow diverter were retrospectively enrolled. The clinical data including the baseline data, aneurysm parameters before and after treatment, and follow-up outcomes were assessed. Among 85 patients, there were 35 (41.2%) males and 50 females (58.8%) aged 17–77 (mean 56.7 ± 11.1) years with 110 aneurysms. Five (5.9%) patients initially presented with subarachnoid hemorrhage from aneurysm rupture. The aneurysm size was 2–30 (mean 8.6) mm, and the aneurysm neck was 2–10.6 (mean 5.7 ± 2.3) mm. Ninety-three Tubridge stents were deployed. Twenty-five (29.4%) patients experienced adjunctive loose coiling. Blood flow was significantly reduced from entering the aneurysm after stent deployment. Periprocedural complications occurred in three (3.5%) patients, including in-stent thrombosis during embolization in one patient (1.2%), conjunctiva edema on the right in one patient (1.2%), and acute multiple cerebral infarctions in one patient (1.2%). Angiographic follow-up was conducted in 67 (78.8%) patients 3–36 (mean 15.3 ± 5.6) months later. In 11 (16.4% or 11/67) patients, blood flow still entered the aneurysm with the O’Kelly-Marotta (OKM) grade B in two (3.0%) patients and grade C in nine (13.4%), whereas complete occlusion (OKM grade D) was achieved in the other 56 (83.6% or 56/67) aneurysms. In-stent stenosis was present in five (7.5%) patients with approximately 25% stenosis in three (4.5%) patients and 50% in two (3.0%). In conclusion, the Tubridge flow diverter can be safely and efficiently applied in the treatment of small and large intracranial aneurysms, with a low periprocedural complication rate, a high occlusion degree, and a low in-stent stenosis rate at follow-up even though large aneurysms may necessitate a longer surgical time and adjunctive coiling.

Abstract The incidence of acute kidney injury (AKI) due to ischemia–reperfusion (IR) injury is increasing. There is no effective treatment for AKI, and because of this clinical challenge, AKI often progresses to chronic kidney disease, which is closely associated with poor patient outcomes and high mortality rates. Small extracellular vesicles from human umbilical cord mesenchymal stem cells (hUCMSC-sEVs) play increasingly vital roles in protecting tissue function from the effects of various harmful stimuli owing to their specific biological features. In this study, we found that miR-100-5p was enriched in hUCMSC-sEVs, and miR-100-5p targeted FKBP5 and inhibited HK-2 cell apoptosis by activating the AKT pathway. HK-2 cells that were exposed to IR injury were cocultured with hUCMSC-sEVs, leading to an increase in miR-100-5p levels, a decrease in FKBP5 levels, and an increase in AKT phosphorylation at Ser 473 (AKT-473 phosphorylation). Notably, these effects were significantly reversed by transfecting hUCMSCs with an miR-100-5p inhibitor. Moreover, miR-100-5p targeted FKBP5, as confirmed by a dual luciferase reporter assay. In vivo, intravenous infusion of hUCMSC-sEVs into mice suffering from IR injury resulted in significant apoptosis inhibition, functional maintenance and renal histological protection, which in turn decreased FKBP5 expression levels. Overall, this study revealed an effect of hUCMSC-sEVs on inhibiting apoptosis; hUCMSC-sEVs reduced renal IR injury by delivering miR-100-5p to HK-2 cells, targeting FKBP5 and thereby promoting AKT-473 phosphorylation to activate the AKT pathway. This study provides novel insights into the role of hUCMSC-sEVs in the treatment of AKI.

Abstract The upper tropospheric water vapor is a key component of Earth's climate. Understanding variations in upper tropospheric water vapor and identifying its influencing factors is crucial for enhancing our comprehension of global climate change. While many studies have shown the impact of El Niño-Southern Oscillation (ENSO) and global warming on water vapor, how they affect the upper tropospheric water vapor remains unclear. Long-term, high-precision ERA5 specific humidity data from the European Centre for Medium-Range Weather Forecasts (ECMWF) provided the data foundation for this study. On this basis, we successfully obtained the patterns of global warming (Independent Component 1, IC1) and ENSO (Independent Component 2, IC2) by employing the strategy of independent component analysis (ICA) combined with non-parametric optimal dimension selection to investigate the upper tropospheric water vapor variations and responses to ENSO and global warming. The results indicate that global warming and ENSO are the primary factors contributing to water vapor variations in the upper troposphere, achieving the significant correlations of 0.87 and 0.61 with water vapor anomalies respectively. Together, they account for 86% of the global interannual variations in water vapor. Consistent with previous studies, our findings also find positive anomalies in upper tropospheric water vapor during El Niño years and negative anomalies during La Niña years. Moreover, the influence extent of ENSO on upper tropospheric water vapor varies with the changing seasons.

Abstract Beyond its economic value, copper (Cu) serves as a valuable tracer of deep magmatic processes due to its close relationship with magmatic sulfide evolution and sensitivity to oxygen fugacity (fO2). However, determining Cu’s oxidation state (+ 1 or + 2) in silicate melts, crucial for interpreting its behavior and reconstructing fO2 in the Earth’s interior, has long been a challenge. This study utilizes X-ray Absorption Near Edge Structure spectroscopy to investigate the Cu oxidation state in hydrous mafic silicate melts equilibrated under diverse fO2 (− 1.8 to 3.1 log units relative to the Fayalite–Magnetite–Quartz buffer), temperature (1150–1300 °C), and pressure (1.0–2.5 GPa) conditions. Our results reveal that Cu predominantly exists as Cu+ across all fO2 conditions, with a minor Cu2+ component. This dominance of Cu+ persists even in relatively oxidized melts, highlighting its limited sensitivity to fO2 under upper mantle conditions. This significantly constrains the utility of Cu as an oxybarometer in hydrous silicate melts in the deep Earth. However, our findings suggest that Cu isotopes primarily reflect the interplay of sulfide segregation/accumulation during magmatic differentiation, shedding light on these fundamental processes in Earth’s interior.

Abstract Background The effectiveness of anti-programmed cell death protein 1(PD-1)/programmed cell death 1 ligand 1(PD-L1) therapy in treating certain types of cancer is associated with the level of PD-L1. However, this relationship has not been observed in colorectal cancer (CRC), and the underlying regulatory mechanism of PD-L1 in CRC remains unclear. Methods Binding of TMEM160 to PD-L1 was determined by co-immunoprecipitation (Co-IP) and GST pull-down assay.The ubiquitination levels of PD-L1 were verified using the ubiquitination assay. Phenotypic experiments were conducted to assess the role of TMEM160 in CRC cells. Animal models were employed to investigate how TMEM160 contributes to tumor growth.The expression and clinical significance of TMEM160 and PD-L1 in CRC tissues were evaluated by immunohistochemistry(IHC). Results In our study, we made a discovery that TMEM160 interacts with PD-L1 and plays a role in stabilizing its expression within a CRC model. Furthermore, we demonstrated that TMEM160 hinders the ubiquitination-dependent degradation of PD-L1 by competing with SPOP for binding to PD-L1 in CRC cells. Regarding functionality, the absence of TMEM160 significantly inhibited the proliferation, invasion, metastasis, clonogenicity, and radioresistance of CRC cells, while simultaneously enhancing the cytotoxic effect of CD8 + T cells on tumor cells. Conversely, the upregulation of TMEM160 substantially increased these capabilities. In severely immunodeficient mice, tumor growth derived from lentiviral vector shTMEM160 cells was lower compared with that derived from shNC control cells. Furthermore, the downregulation of TMEM160 significantly restricted tumor growth in immune-competent BALB/c mice. In clinical samples from patients with CRC, we observed a strong positive correlation between TMEM160 expression and PD-L1 expression, as well as a negative correlation with CD8A expression. Importantly, patients with high TMEM160 expression exhibited a worse prognosis compared with those with low or no TMEM160 expression. Conclusions Our study reveals that TMEM160 inhibits the ubiquitination-dependent degradation of PD-L1 that is mediated by SPOP, thereby stabilizing PD-L1 expression to foster the malignant progress, radioresistance, and immune evasion of CRC cells. These findings suggest that TMEM160 holds potential as a target for the treatment of patients with CRC.

Abstract Background Although hepatitis B virus (HBV) infection is a major risk factor for hepatic cancer, the majority of HBV carriers do not develop this lethal disease. Additional molecular alterations are thus implicated in the process of liver tumorigenesis. Since phosphatase and tensin homolog (PTEN) is decreased in approximately half of liver cancers, we investigated the significance of PTEN deficiency in HBV-related hepatocarcinogenesis. Methods HBV-positive human liver cancer tissues were checked for PTEN expression. Transgenic HBV, Alb-Cre and Pten fl/fl mice were inter-crossed to generate WT, HBV, Pten −/− and HBV; Pten −/− mice. Immunoblotting, histological analysis and qRT-PCR were used to study these livers. Gp73 −/− mice were then mated with HBV; Pten −/− mice to illustrate the role of hepatic tumor biomarker golgi membrane protein 73 (GP73)/ golgi membrane protein 1 (GOLM1) in hepatic oncogenesis. Results Pten deletion and HBV transgene synergistically aggravated liver injury, inflammation, fibrosis and development of mixed hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). GP73 was augmented in HBV; Pten −/− livers. Knockout of GP73 blunted the synergistic effect of deficient Pten and transgenic HBV on liver injury, inflammation, fibrosis and cancer development. Conclusions This mixed HCC-ICC mouse model mimics liver cancer patients harboring HBV infection and PTEN/AKT signaling pathway alteration. Targeting GP73 is a promising therapeutic strategy for cancer patients with HBV infection and PTEN alteration.