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Abstract Sodium-ion batteries (SIBs) are emerging as a promising alternative to conventional lithium-ion technology, due to the abundance of sodium resources. The major drawbacks for the commercial application of SIBs lie in the slow kinetic processes and poor energy density of the devices. Molybdenum sulfide (MoS2), a graphene-like material, is becoming a promising anode material for SIBs, because of its high theoretical capacity (670 mAh g–1) and layered structure that suitable for Na+ intercalation/extraction. However, the intrinsic properties of MoS2, such as low conductivity, slow Na+ diffusion kinetics and large volume change during charging/discharging, restrict its rate capability and cycle stability. Here, molybdenum disulfide and graphene oxide (3D MoS2/GO) with excellent conductivity were fabricated through layer-by-layer method using amino-functionalized SiO2 nanospheres as templates. The 3D MoS2/GO composite demonstrates excellent cycling stability and capacity of 525 mA h g–1 at 500 mA g–1 after 100 cycles, which mainly due to the integrated MoS2/GO components and unique 3D macroporous structure, facilitating the material conductivity and Na+ diffusion rate, while tolerating the volume expansion of MoS2 during the charge/discharge processes.

Abstract We aimed to build a deep learning-based pathomics model to predict the early recurrence of non-muscle-infiltrating bladder cancer (NMIBC) in this work. A total of 147 patients from Xuzhou Central Hospital were enrolled as the training cohort, and 63 patients from Suqian Affiliated Hospital of Xuzhou Medical University were enrolled as the test cohort. Based on two consecutive phases of patch level prediction and WSI-level predictione, we built a pathomics model, with the initial model developed in the training cohort and subjected to transfer learning, and then the test cohort was validated for generalization. The features extracted from the visualization model were used for model interpretation. After migration learning, the area under the receiver operating characteristic curve for the deep learning-based pathomics model in the test cohort was 0.860 (95% CI 0.752–0.969), with good agreement between the migration training cohort and the test cohort in predicting recurrence, and the predicted values matched well with the observed values, with p values of 0.667766 and 0.140233 for the Hosmer–Lemeshow test, respectively. The good clinical application was observed using a decision curve analysis method. We developed a deep learning-based pathomics model showed promising performance in predicting recurrence within one year in NMIBC patients. Including 10 state prediction NMIBC recurrence group pathology features be visualized, which may be used to facilitate personalized management of NMIBC patients to avoid ineffective or unnecessary treatment for the benefit of patients.

Abstract Infections by drug-resistant microorganisms are a threat to global health and antimicrobial peptides are considered to be a new hope for their treatment. Temporin-WY2 was identified from the cutaneous secretion of the Ranidae frog, Amolops wuyiensis. It presented with a potent anti-Gram-positive bacterial efficacy, but its activity against Gram-negative bacteria and cancer cell lines was unremarkable. Also, it produced a relatively high lytic effect on horse erythrocytes. For further improvement of its functions, a perfect amphipathic analogue, QUB-1426, and two lysine-clustered analogues, 6K-WY2 and 6K-1426, were synthesised and investigated. The modified peptides were found to be between 8- and 64-fold more potent against Gram-negative bacteria than the original peptide. Additionally, the 6K analogues showed a rapid killing rate. Also, their antiproliferation activities were more than 100-fold more potent than the parent peptide. All of the peptides that were examined demonstrated considerable biofilm inhibition activity. Moreover, QUB-1426, 6K-WY2 and 6K-1426, demonstrated in vivo antimicrobial activity against MRSA and E. coli in an insect larvae model. Despite observing a slight increase in the hemolytic activity and cytotoxicity of the modified peptides, they still demonstrated a improved therapeutic index. Overall, QUB-1426, 6K-WY2 and 6K-1426, with dual antimicrobial and anticancer functions, are proposed as putative drug candidates for the future.

Abstract The coronavirus disease-2019 (COVID-19) pandemic has impaired the quality of life (QoL) for many due to its extensive impacts. However, few studies have addressed the specific impact of COVID-19 on the mental health of adolescents, particularly post-traumatic stress disorder (PTSD). This study considered the impact of COVID-19-related PTSD on the QoL of adolescents in China, the mediating effects of insomnia, and the moderating effects of resilience. Participants included 50,666 adolescents aged 12–18 years selected using a comprehensive sampling method. We performed data collection from January 8th to January 18th, 2023, using the Children’s Revised Impact of Event Scale, Pittsburgh Sleep Quality Index, Ten-item Connor-Davidson Resilience Scale, and Screening for and Promotion of Health-related QoL in Children and Adolescents Questionnaire for data collection. Male adolescents exhibited significantly lower levels of PTSD and insomnia compared to females and scored significantly higher in psychological resilience and overall QoL. Insomnia played a mediating role between PTSD and QoL. Psychological resilience moderated the impact of COVID-19-related stress on adolescents’ QoL through its influence on insomnia. PTSD resulting from the COVID-19 pandemic affects the QoL of adolescents through the presence of insomnia. Psychological resilience plays a moderating role in this process. Cultivating psychological resilience in adolescents can effectively enhance their ability to cope with the impacts of sudden public events.

Abstract In order to analyze the stability of the bridge above the goaf, the disturbance influence of goaf residual deformation on the bridge is studied. Firstly, an equivalent numerical simulation method of goaf residual deformation evolution process is studied by quantitative analysis the sensitivity of residual subsidence to the rock parameters using the OAT (one-variable-at-a-time). Then, the collaborative deformation of ground, pile, and bridge floor is studied under the condition of a simply-supported beam bridge above the goaf center. Finally, the mechanism of collaborative deformation of ground, pile, and bridge floor is revealed. The results show that the goaf residual deformation process can be obtained by weakening the elastic modulus of fractured rock in the caving zone. At the final residual deformation stage, the subsidence ratio of ground to pile is about 10, and the subsidence ratio of pile to bridge floor is about 2, while the ground horizontal movement ratio of ground to pile is about 7, and the bridge floor horizontal movement can be ignored. The bridge floor is always in the positive curvature influence zone, and the pile has an inhibitory effect on the curvature deformation of the bridge floor. The compression deformation occurs between the piles locations, while the tensile deformation occurs at the pile location. The evolution of negative frictional resistance derived from goaf residual deformation is the main reason for the change in the collaborative deformation law among the ground, pile and bridge floor. This research can provide scientific support and theoretical basis for the design, construction, and protection of the bridge above the goaf center, and can also provide reference for the stability evaluation of bridge above goaf under other conditions.

Abstract Thyroid hormones are metabolic indicators to evaluate the physical condition of emergency hospitalized patients, while the relationship between total triiodothyronine and the severity of emergency inpatients is still unclear. To explore the thyroid function levels of inpatients in emergency ward and the status of combined Nonthyroidal illness syndrome (NTIS), and to emphasize the importance of thyroid hormone examination for non-endocrinology inpatients. According to thyroid function of inpatients in emergency ward, they were divided into NTIS group and non-NTIS group, the hematological characteristics and TH levels of each group were analyzed. Based on clinical diagnoses, the hospitalized patients were divided into three major groups, namely infection group, non-infection group and impaired organ function group. Among them, infection group was further divided into sepsis group, lung infection group and local infection group, altogether five groups. The thyroid function levels and low values in each group were evaluated, and the correlation between hormone levels and inflammatory factors, nutritional indicators and the relationship with the risk of death was discussed. The inpatient rate in emergency ward complicated with NTIS was 62.29%, T3 was the most sensitive index of NTIS, followed by FT3. Compared to non-NTIS group, the NTIS group had an increased risk of death. The sepsis group and impaired organ function group had the highest rates of complicated NTIS, reaching 83.33% and 78.12% respectively. Spearman's correlation analysis implied T3/T4/FT3 levels were positively correlated with ALb and PLT (except T4), and negatively correlated with CRP, D-Dimer, IL-6 and Fer. The Receiver Operating Curve (ROC) and Area under the curve (AUC) showed T3 levels alone were strongly associated with the risk of death (AUC 0.750; 95% CI 0.673–0.828; P

Abstract Tuberculosis caused by Mycobacterium tuberculosis (M. tb) is a major public health problem with high morbidity and mortality worldwide. In our previous study, we found that a fermentation product of Streptomyces flavofungini TRM90047 exhibited anti-M. tb activity and decreased the expression level of several genes, including rpsL, Rplc and ClpC1. Guided by heteronuclear single quantum correlation-total correlation spectroscopy (HSQC-TOCSY) fingerprints and genome mining, we isolated two new 44-membered macrolides, desertomycin 44-1 (1) and desertomycin 44-2 (2), together with known desertomycin A (3) from S. flavofungini TRM90047. Three desertomycins showed anti-M. tb activity. The EC50 values of desertomycin A, desertomycin 44-1 and desertomycin 44-2 were 25 µg/mL, 25 µg/mL and 50 µg/mL, respectively. Molecular docking analyses revealed that the isolated desertomycins bound well to the RPSL, RPLC and CLPC1 proteins. In the present study, we describe the discovery of new anti-M. tb compounds guided by genome mining, HSQC-TOCSY and anti-M. tb bioassays.

Abstract Background The key step in evaluating the quality of clinical nursing practice education lies in establishing a scientific, objective, and feasible index system. Current assessments of clinical teaching typically measure hospital learning environments, classroom teaching, teaching competency, or the internship quality of nursing students. As a result, clinical evaluations are often insufficient to provide focused feedback, guide faculty development, or identify specific areas for clinical teachers to implement change and improvement. Therefore, the purpose of our study was to to construct a scientific, systematic, and clinically applicable evaluation index system of clinical nursing practice teaching quality and determine each indicator’s weight to provide references for the scientific and objective evaluation of clinical nursing practice teaching quality. Methods Based on the “Structure-Process-Outcome” theoretical model, a literature review and Delphi surveys were conducted to establish the evaluation index system of clinical nursing practice teaching quality. Analytic Hierarchy Process (AHP) was employed to determine the weight of each indicator. Results The effective response rate for the two rounds of expert surveys was 100%. The expert authority coefficients were 0.961 and 0.975, respectively. The coefficient of variation for the indicators at each level ranged from 0 to 0.25 and 0 to 0.21, and the Kendall harmony coefficients were 0.209 and 0.135, respectively, with statistically significant differences (P

Abstract Background New daily persistent headache (NDPH) is a rare primary headache with unclear pathogenesis. Neuroimaging studies of NDPH are limited, and controversy still exists. Diffusion tensor imaging (DTI) is commonly used to study the white matter. However, lacking specificity, the potential pathological mechanisms of white matter microstructural changes remain poorly understood. In addition, the intricacy of gray matter structures impedes the application of the DTI model. Here, we applied an advanced diffusion model of neurite orientation dispersion and density imaging (NODDI) to study the white matter and cortical gray matter microstructure in patients with NDPH. Methods This study assessed brain microstructure, including 27 patients with NDPH, and matched 28 healthy controls (HCs) by NODDI. The differences between the two groups were assessed by tract-based spatial statistics (TBSS) and surface-based analysis (SBA), focusing on the NODDI metrics (neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF)). Furthermore, we performed Pearson’s correlation analysis between the NODDI indicators and clinical characteristics. Results Compared to HCs, patients with NDPH had a reduction of density and complexity in several fiber tracts. For robust results, the fiber tracts were defined as comprising more than 100 voxels, including bilateral inferior fronto-occipital fasciculus (IFOF), left superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), as well as right corticospinal tract (CST). Moreover, the reduction of neurite density was uncovered in the left superior and middle frontal cortex, left precentral cortex, and right lateral orbitofrontal cortex and insula. There was no correlation between the NODDI metrics of these brain regions and clinical variables or scales of relevance after the Bonferroni correction. Conclusions Our research indicated that neurite loss was detected in both white matter and cortical gray matter of patients with NDPH.

Abstract Bladder urothelial carcinoma (BLCA) presents a persistent challenge in clinical management. Despite recent advancements demonstrating the BLCA efficacy of immune checkpoint inhibitors (ICI) in BLCA patients, there remains a critical need to identify and expand the subset of individuals who benefit from this treatment. Mitochondria, as pivotal regulators of various cell death pathways in eukaryotic cells, exert significant influence over tumor cell fate and survival. In this study, our objective was to investigate biomarkers centered around mitochondrial function and cell death mechanisms to facilitate prognostic prediction and guide therapeutic decision-making in BLCA. Utilizing ssGSEA and LASSO regression, we developed a prognostic signature termed mitochondrial function and cell death (mtPCD). Subsequently, we evaluated the associations between mtPCD score and diverse clinical outcomes, including prognosis, functional pathway enrichment, immune cell infiltration, immunotherapy response analysis and drug sensitivity, within high- and low-risk subgroups. Additionally, we employed single-cell level functional assays, RT-qPCR, and immunohistochemistry to validate the differential expression of genes comprising the mtPCD signature. The mtPCD signature comprises a panel of 10 highly influential genes, strongly correlated with survival outcomes in BLCA patients and exhibiting robust predictive capabilities. Importantly, individuals classified as high-risk according to mtPCD score displayed a subdued overall immune response, characterized by diminished immunotherapeutic efficacy. In summary, our findings highlight the development of a novel prognostic signature, which not only holds promise as a biomarker for BLCA prognosis but also offers insights into the immune landscape of BLCA. This paradigm may pave the way for personalized treatment strategies in BLCA management.

Abstract This study aimed to perform the first external validation of the modified Child-Turcotte-Pugh score based on plasma ammonia (aCTP) and compare it with other risk scoring systems to predict survival in patients with cirrhosis after transjugular intrahepatic portosystemic shunt (TIPS) placement. We retrospectively reviewed 473 patients from three cohorts between January 2016 and June 2022 and compared the aCTP score with the Child-Turcotte-Pugh (CTP) score, albumin-bilirubin (ALBI), model for end-stage liver disease (MELD) and sodium MELD (MELD-Na) in predicting transplant-free survival by the concordance index (C-index), area under the receiver operating characteristic curve, calibration plot, and decision curve analysis (DCA) curve. The median follow-up time was 29 months, during which a total of 62 (20.74%) patients died or underwent liver transplantation. The survival curves for the three aCTP grades differed significantly. Patients with aCTP grade C had a shorter expected lifespan than patients with aCTP grades A and B (P

Abstract. Background:. Intrauterine valvuloplasty is an innovative therapy, which promotes ventricular growth and function in some congenital heart diseases (CHDs). The technique remains challenging and can only be performed in a few centers. This study aimed to assess the feasibility and mid-term outcomes of fetal cardiac intervention (FCI) in fetuses with critical CHD in an experienced tertiary center. Methods:. Five fetal aortic valvuloplasty (FAV) or fetal pulmonary valvuloplasty (FPV) procedures were performed in our fetal heart center between August 2018 and May 2022. Technical success was defined as crossing the aortic or pulmonary valve and balloon inflation, followed by evidence of increased blood flow across the valve and/or new regurgitation. Follow-up clinical records and echocardiography were obtained during the prenatal and postnatal periods. Results:. Five fetuses received FAV or FPV, including critical aortic stenosis ( n = 2) and pulmonary atresia with intact ventricular septum ( n = 3). The mean maternal age was 33.0 ± 2.6 years. The median gestational age (GA) at diagnosis was 24 weeks (range, 22–26 weeks). The median GA at intervention was 29 weeks (range, 28–32 weeks). All five cases underwent successful or partially successful procedures. One patient had pulmonary valve perforation without balloon dilation. No procedure-related deaths or significant complications occurred. However, one neonatal death occurred due to heart and renal failure. The median follow-up period was 29.5 months (range, 8.0–48.0 months). The four surviving patients had achieved biventricular circulation, exhibited improved valve, and ventricular development at the last follow-up visit. Conclusion:. Intrauterine FCI could be performed safely with good prognosis in critical CHD.

Abstract This study presents a comprehensive investigation into the optimization of PID control parameters for marine dual-fuel engines using an improved particle swarm algorithm. Through the development of a Matlab/Simulink simulation model, the thermodynamic behavior of the engine and the functionality of its control system are analyzed. The PID control parameters for air–fuel ratio control and mode switching control systems are fine-tuned utilizing the improved particle swarm algorithm (PSO). Simulation results demonstrate that the proposed improved PID-PSO approach outperforms traditional PID and traditional PSO-PID control methods in terms of reduced overshoot, minimized steady-state error, faster response times, and improved stability across various operating conditions and response modes. In comparison to traditional PID and PSO-PID controllers, the improved PSO-PID controller reduces the response time by 0.47 s and 0.21 s, the maximum overshoot by 98.43% and 96.05%, and decreases the absolute errors by 87.42% and 90.55%, respectively, in air–fuel ratio control using the step response method. The study's findings offer valuable insights into enhancing the performance and efficiency of marine dual-fuel engines through advanced control strategies.

Abstract Retained placenta is a common health issue, and appropriate prevention strategies are effective in postpartum health management. This study aimed to evaluate whether early intervention using GYS can prevent retained placenta and puerperal metritis, as well as enhance reproductive outcomes in cows. Each bovine in the GYS group (n = 591) received a single prophylactic dose of GYS (0.5 g/kg body weight) orally within 2 h after parturition, while those in the control group (n = 598) received no intervention. GYS treatment was associated with a decreased incidence of retained placenta (4.6% vs. 12.0%, P

Background The rapid development of healthcare social work in policy and practice in Beijing, especially since the COVID-19 epidemic, urgently calls for a competence-based evaluation system. Objective This study is to develop a competence-based index system for the training and evaluation of professional healthcare social workers at an institutional and regional level from an interdisciplinary perspective. Methods From August to November 2022, a one-to-one half structured interview was conducted with snowball sampling among 21 members of an interdisciplinary healthcare social work team in T hospital and surrounding communities in Beijing, a focus interview was conducted among the healthcare social workers, and the interview outlines were formulated based on the Spencers' Iceberg Model. Subject analysis method was used to analyze the data, extract the themes of competency for construction of evaluation index system of T hospital. From November to December 2022, a total of 10 experts in healthcare social work practice were invited by using purposive sampling method to imolement the Fuzzy Delphi and form the Beijing competency evaluation system of healthcare social workers. Results (1) A evaluation index system for competency of healthcare social workers in T hospital was formed through qualitive method, including 4 first-level indexes, 16 second-level indexes and 97 third-level indexes. (2) A total of 2 rounds of Fuzzy Delphi were conducted. The enthusiasm coefficient was 100%. According to S1=8.30 and S2=7.00, a revised index system of T hospital and Beijing were respectively formed. Conclusion This study has constructed an evaluation index system for competency of healthcare social workers in Beijing, which covers 4 first-level indexes, 14 second-level indexes and 73 third-level indexes, from the perspective of interdisciplinary including social work, medicine, nursing and community governance.

Abstract Introduction Post-stroke depression (PSD) is a prevalent complication that has been shown to have a negative impact on rehabilitation outcomes and quality of life and poses a significant risk for suicidal intention. However, models for discriminating and predicting PSD in stroke survivors for effective secondary prevention strategies are inadequate as the pathogenesis of PSD remains unknown. Prognostic prediction models that exhibit greater rule-in capacity have the potential to mitigate the issue of underdiagnosis and undertreatment of PSD. Thus, the planned study aims to systematically review and critically evaluate published studies on prognostic prediction models for PSD. Methods and analysis A systematic literature search will be conducted in PubMed and Embase through Ovid. Two reviewers will complete study screening, data extraction, and quality assessment utilizing appropriate tools. Qualitative data on the characteristics of the included studies, methodological quality, and the appraisal of the clinical applicability of models will be summarized in the form of narrative comments and tables or figures. The predictive performance of the same model involving multiple studies will be synthesized with a random effects meta-analysis model or meta-regression, taking into account heterogeneity. Ethics and dissemination Ethical approval is considered not applicable for this systematic review. Findings will be shared through dissemination at academic conferences and/or publication in peer-reviewed academic journals. Systematic review registration PROSPERO CRD42023388548.

Abstract Although endoscopic necrosectomy (EN) is more frequently used to manage walled-off necrosis (WON), there is still debate over how much time should pass between the initial stent placement and the first necrosectomy. This study aims to determine the effect of performing EN within different timings after placing the initial stent on clinical outcomes for WON. A retrospective study on infected WON patients compared an early necrosectomy within one week after the initial stent placement with a necrosectomy that was postponed after a week. The primary outcomes compared the rate of clinical success and the need for additional intervention after EN to achieve WON resolution. 77 patients were divided into early and postponed necrosectomy groups. The complete resolution of WON within six months of follow-up was attained in 73.7% and 74.3% of patients in both the early and postponed groups. The early group tended to a greater need for additional intervention after EN (26.8% early necrosectomy vs. 8.3% postponed necrosectomy, P = 0.036). Our study does not demonstrate that early necrosectomy is superior to postponed necrosectomy in terms of clinical success rate, total count of necrosectomy procedures, procedure-related complications, length of hospitalization and prognosis. Conversely, patients in the postponed group received fewer additional interventions.

Abstract Background Diabetic retinopathy (DR) is the leading cause of blinding eye disease among working adults and is primarily attributed to the excessive proliferation of microvessels, which leads to vitreous hemorrhage and retinal traction, thereby significantly impairing patient vision. NSUN2-mediated RNA m5C methylation is implicated in various diseases, and in this investigation, we focused on elucidating the impact of NSUN2 on the regulation of the expression of the downstream gene MUC1, specifically through RNA m5C methylation, on the progression of DR. Method Utilizing Microarray analysis, we examined patient vitreous fluid to pinpoint potential therapeutic targets for DR. Differential expression of NSUN2 was validated through qRT-PCR, Western blot, and immunofluorescence in human tissue, animal tissue, and cell model of DR. The relationship between NSUN2 and DR was explored in vitro and in vivo through gene knockdown and overexpression. Various techniques, such as MeRIP-qPCR and dot blot, were applied to reveal the downstream targets and mechanism of action of NSUN2. Results The levels of both NSUN2 and RNA m5C methylation were significantly elevated in the DR model. Knockdown of NSUN2 mitigated DR lesion formation both in vitro and in vivo. Mechanistically, NSUN2 promoted MUC1 expression by binding to the RNA m5C reader ALYREF. Knockdown of ALYREF resulted in DR lesion alterations similar to those observed with NSUN2 knockdown. Moreover, MUC1 overexpression successfully reversed a series of DR alterations induced by NSUN2 silencing. Conclusions NSUN2 regulates the expression of MUC1 through ALYREF-mediated RNA m5C methylation, thereby regulating the progression of DR and providing a new option for the treatment of DR in the future.

Abstract Coagulation alterations manifest early after severe burns and are closely linked to mortality outcomes. Nevertheless, the precise characterization of coagulation changes associated with early mortality remains elusive. We examined alterations in indicators linked to mortality outcomes at both the transcriptomic and clinical characteristic levels. At the transcriptomic level, we pinpointed 28 differentially expressed coagulation-related genes (DECRGs) following burn injuries and endeavored to validate their causal relationships through Mendelian randomization. DECRGs tied to survival exhibit a significant association with neutrophil function, wherein the expression of CYP4F2 and P2RX1 serves as robust predictors of fatal outcomes. In terms of clinical indicators, early levels of D-dimer and alterations in serum calcium show a strong correlation with mortality outcomes. Coagulation depletion and fibrinolytic activation, stemming from the hyperactivation of coagulation pathways post-severe burns, are strongly linked to patient mortality. Monitoring these early coagulation markers with predictive value can effectively identify individuals necessitating priority critical care.

Abstract Background Chronic migraine (CM) is a debilitating neurofunctional disorder primarily affecting females, characterized by central sensitization. Central sensitization refers to the enhanced response to sensory stimulation, which involves changes in neuronal excitability, synaptic plasticity, and neurotransmitter release. Environmental enrichment (EE) can increase the movement, exploration, socialization and other behaviors of mice. EE has shown promising effects in various neurological disorders, but its impact on CM and the underlying mechanism remains poorly understood. Therefore, the purpose of this study was to determine whether EE has the potential to serve as a cost-effective intervention strategy for CM. Methods A mouse CM model was successfully established by repeated administration of nitroglycerin (NTG). We selected adult female mice around 8 weeks old, exposed them to EE for 2 months, and then induced the CM model. Nociceptive threshold tests were measured using Von Frey filaments and a hot plate. The expression of c-Fos, calcitonin gene-related peptide (CGRP) and inflammatory response were measured using WB and immunofluorescence to evaluate central sensitization. RNA sequencing was used to find differentially expressed genes and signaling pathways. Finally, the expression of the target differential gene was investigated. Results Repeated administration of NTG can induce hyperalgesia in female mice and increase the expression of c-Fos and CGRP in the trigeminal nucleus caudalis (TNC). Early exposure of mice to EE reduced NTG-induced hyperalgesia in CM mice. WB and immunofluorescence revealed that EE inhibited the overexpression of c-Fos and CGRP in the TNC of CM mice and alleviated the inflammatory response of microglia activation. RNA sequencing analysis identified that several central sensitization-related signaling pathways were altered by EE. VGluT1, a key gene involved in behavior, internal stimulus response, and ion channel activity, was found to be downregulated in mice exposed to EE. Conclusion EE can significantly ameliorate hyperalgesia in the NTG-induced CM model. The mechanisms may be to modulate central sensitization by reducing the expression of CGRP, attenuating the inflammatory response, and downregulating the expression of VGluT1, etc., suggesting that EE can serve as an effective preventive strategy for CM.

Background The family doctor contract service is being vigorously promoted. Compared with the individual performance appraisal scheme, the performance appraisal scheme based on the family doctor team including the two processes of "first distribution" and "secondary distribution" is more capable of mobilizing the work motivation of family doctor team members, thus improving service efficiency and quality. Objective To develop the "first distribution" indicator system of family doctor team performance based on contract service fee. Methods The draft of the "first distribution" indicator system of family doctor team performance was preliminarily formulated through literature analysis and semi-structured interviews. On the basis of the draft, an expert consultation questionnaire was designed, and two rounds of expert consultation were implemented and completed from October 2021 to April 2022 to develop the "first distribution" indicator system of family doctor team performance based on contract service fee. Results The recovery rate of the two rounds of expert consultation questionnaires was 100.0%. The authority coefficient of the first round of correspondence was 0.761 6, and the Kendall coordination coefficients of the two rounds of consultations were 0.067 (P

Abstract REBCO has been used extensively as coated conductors applied to superconducting magnets due to its exceptional superconducting properties. As a REBCO superconductor, YbBa2Cu3O7−y (Yb123) has a low melting temperature, making it suitable for use as an intermediate medium connector while preparing the superconducting joint. However, there is still uncertainty about the formation mechanism of Yb123 and the synthesis of this superconductor has not been fully understood. Therefore, this study systematically investigated the phase transformation process of Yb123 during heat treatment in flowing oxygen. The results indicated that Yb123 sample with the highest phase purity could be obtained by annealing at 927 °C or 937 °C but not in between, respectively. Furthermore, a quantitative phase analysis revealed that the sample annealed at 937 °C had a phase purity greater than 80 wt%. Additionally, a strong c-axis texture was observed in the bulk Yb123 superconductor prepared at 937 °C. Meanwhile, the superconducting results revealed that the bulk sample’s Tc was 89.9 K, and its self-field critical current densities at 4.2 K and 77 K were 1.3 × 105 A/cm2 and 5.0 × 103 A/cm2, respectively. Based on the results mentioned above, the phase transformation process and formation mechanism of Yb123 in flowing oxygen were elaborated.

Abstract Strain-specific probiotics can present antioxidant activity and reduce damage caused by oxidation. Streptococcus alactolyticus strain FGM (S. alactolyticus strain FGM) isolated from the chicken cecum shows potential probiotic properties which have been previously demonstrated. However, the antioxidant properties of S. alactolyticus strain FGM remain unknown. In this view, cell-free supernatant (CFS), intact cells (IC) and intracellular extracts (CFE) of strain FGM and 3 strains of Lactobacillus (LAB) were prepared, and their scavenging capacities against DPPH, hydroxyl radicals and linoleic acid peroxidation inhibitory were compared in this study. The effects of strain FGM cell-free supernatant (FCFS) on NO production, activity of SOD and GSH-Px in RAW264.7 cells and LPS-induced RAW264.7 cells were analyzed. The metabolites in the supernatant were quantitated by N300 Quantitative Metabolome. It was shown that the physicochemical characteristics of CFS to scavenge DPPH, hydroxyl radicals, and linoleic acid peroxidation inhibitory were significantly stronger than that of IC and CFE in the strain FGM (P

Abstract With a significant number of mechanical products approaching the retirement phase, the batch recycling of discarded mechanical parts necessitates a preliminary assessment of their surface condition. However, the presence of surface rust poses a challenge to defect identification. Therefore, this paper proposes a method for detecting heavily rusted surface defects based on an improved YOLOv8n network. In the Backbone, the C2f-DBB module of re-parameterized deep feature extraction was introduced, and the attention module was designed to improve the accuracy of information extraction. In the Neck part, a Bi-Afpn multiscale feature fusion strategy is designed to facilitate information exchange between features at different scales. Finally, Focal-CIoU is employed as the bounding box loss function to enhance the network’s localization performance and accuracy for defects. Experimentally, it is proved that the improved network in this paper improves the Recall, Precision, and mAP0.5 by 1.2%, 2.1%, and 1.9%, respectively, on the original basis, which is better than other network models.

Abstract Background Regulatory T cells (Tregs) are crucial in maintaining immune homeostasis and preventing autoimmunity and inflammation. A proportion of Treg cells can lose Foxp3 expression and become unstable under inflammation conditions. The precise mechanisms underlying this phenomenon remain unclear. Methods The PI16 gene knockout mice (PI16fl/flFoxp3Cre) in Treg were constructed, and the genotypes were identified. The proportion and phenotypic differences of immune cells in 8-week-old mice were detected by cell counter and flow cytometry. Two groups of mouse Naïve CD4+T cells were induced to differentiate into iTreg cells to observe the effect of PI16 on the differentiation and proliferation of iTreg cells, CD4+CD25+Treg and CD4+CD25− effector T cells (Teff) were selected and co-cultured with antigen presenting cells (APC) to observe the effect of PI16 on the inhibitory ability of Treg cells in vitro. The effects of directed knockout of PI16 in Treg cells on inflammatory symptoms, histopathological changes and immune cell expression in mice with enteritis and autoimmune arthritis were observed by constructing the model of antigen-induced arthritis (AIA) and colitis induced by dextran sulfate sodium salt (DSS). Results We identified peptidase inhibitor 16 (PI16) as a negative regulator of Treg cells. Our findings demonstrate that conditional knock-out of PI16 in Tregs significantly enhances their differentiation and suppressive functions. The conditional knockout of the PI16 gene resulted in a significantly higher abundance of Foxp3 expression (35.12 ± 5.71% vs. 20.00 ± 1.61%, p = 0.034) in iTreg cells induced in vitro compared to wild-type mice. Mice with Treg cell-specific PI16 ablation are protected from autoimmune arthritis (AIA) and dextran sulfate sodium (DSS)-induced colitis development. The AIA model of PI16CKO is characterized by the reduction of joint structure and the attenuation of synovial inflammation and in DSS-induced colitis model, conditional knockout of the PI16 reduce intestinal structural damage. Additionally, we found that the deletion of the PI16 gene in Treg can increase the proportion of Treg (1.46 ± 0.14% vs. 0.64 ± 0.07%, p

Abstract The feed-forward loop between the transcription factors Ppar-gamma and C/ebp-alpha is critical for lineage commitment during adipocytic differentiation. Ppar-gamma interacts with epigenetic cofactors to activate C/ebp-alpha and the downstream adipocytic gene expression program. Therefore, knowledge of the epigenetic cofactors associated with Ppar-gamma, is central to understanding adipocyte differentiation in normal differentiation and disease. We found that Prmt6 is present with Ppar-gamma on the Ppar-gamma and C/ebp-alpha promoter. It contributes to the repression of C/ebp-alpha expression, in part through its ability to induce H3R2me2a. During adipocyte differentiation, Prmt6 expression is reduced and the methyltransferase leaves the promoters. As a result, the expression of Ppar-gamma and C/ebp-alpha is upregulated and the adipocytic gene expression program is established. Inhibition of Prmt6 by a small molecule enhances adipogenesis, opening up the possibility of epigenetic manipulation of differentiation. Our data provide detailed information on the molecular mechanism controlling the Ppar-gamma–C/ebp-alpha feed-forward loop. Thus, they advance our understanding of adipogenesis in normal and aberrant adipogenesis.

Abstract Objectives To evaluate whether the urinary continence (UC) recovery after robotic-assisted radical prostatectomy (RARP) relates to the membranous urethral length (MUL) and the membranous urethral complex volume (MUV). Materials and methods 120 patients who underwent RARP were enrolled according to the different times of UC recovery and examined using prostate magnetic resonance imaging (MRI) before surgery. The membranous urethral (MU) parameters were measured using the three-Dimensional (3D) model reconstructed by holographic technology, such as total MUV (tMUV), exposed MUV (eMUV), full MUL (fMUL) and exposed MUL (eMUL). Statistical software SPSS 26.0 was used to analyze the data and compare the MU parameters and baseline data in different groups. Results Patients with larger tMUV (p = 0.038), eMUV (p = 0.003), longer fMUL (p = 0.025), eMUL (p = 0.044) had better UC after removal of the catheter, and eMUV (OR = 1.002, 95%CI = 1.001–1.004, p = 0.004) was a predictor; the patients with younger age (p = 0.021), lower VPSS score (p = 0.004) and larger eMUV (p = 0.012) and longer eMUL (p = 0.049) had better UC recovery one month after RARP while eMUV (OR = 1.002, 95% CI = 1.000–1.003, p = 0.008) and VPSS score (OR = 0.886, 95% CI = 0.806–0.973, p = 0.011) were independent risk factors; The patients with younger age (p = 0.018), larger tMUV (p = 0.029), eMUV (p = 0.016) had better UC recovery three months after RARP. eMUV (OR = 1.002, 95% CI = 1.000–1.004, p = 0.042) and age (OR = 0.904, 95% CI = 0.818–0.998, p = 0.046) were independent risk factors. Conclusion This clinical study shows that patients with larger MUV and longer MUL can return to UC earlier after surgery. Among that, eMUV is a better predictor.

Abstract The mining of the protective coal seam usually produces different pressure relief effects on the different areas of protected coal seam, the reason is that the stress paths of protected seam coal body in different areas caused by mining effect are different. In order to explore the differential pressure relief damage effect of coal body under different pressure relief conditions, the stress evolution path of coal body in different areas of the protected coal seam is obtianed by using theoretical analysis and the macro–micro damage characteristics of coal body under different stress paths by using numerical simulation in this paper. The results show that: The damage characteristics of the sample models are basically the same in the in-situ stress recovery stage and the mining disturbance stage of the two stress paths. With ith the sequence of stress stages experienced by the sample model, the distribution of acoustic emission events concentrates in the high-intensity area and the porosity continues to decrease. The number of cracks increases slowly in the stage of in-situ stress recovery stage, most of which are tensile cracks, while the number of cracks increases sharply in the mining disturbance stage, most of which are shear cracks. The difference of the deformation and macro meso damage characteristics of the sample models under the two stress paths is mainly reflected in the post mining pressure relief stage. At the post mining pressure relief stage of path 1, the number of cracks in the sample has little growth, and most of them are small energy tensile cracks, and the porosity increases, which verifies its obvious pressure relief activation antireflection effect; At this stage of path 2, the crack growth of the sample is obvious, and most of them are high-energy shear cracks, and the porosity continues to decrease. Compared with path 1, the pressure relief expansion effect of the sample model is suppressed and the compression damage continues to develop in this stage of path 2.

Background Intrapartum fever is a common clinical manifestation in obstetrics, which increases the rates of cesarean section, vaginal instrumental delivery and neonatal asphyxia. The influencing factors of intrapartum fever include pregnancy comorbidities and complications, labor induction duration, labor analgesia, trial delivery time, temperature of delivery room, and number of pelvic examination. These factors can exist independently or be causal. Is it true that the higher maximum body temperature correlates with worse maternal and neonatal outcomes in women with intrapartum fever? The study on it is useful to guide the clinical prognosis and management strategies of pregnant women with intrapartum fever. Objective To investigate the effect of intrapartum fever and its severity on maternal and fetal outcomes during trial delivery of full-term singleton primipara. Methods A total of 994 full-term singleton primiparas who delivered in 2019 in Beijing Obstetrics and Gynecology Hospital, Capital Medical University and diagnosed with intrapartum fever during labor were included as fever group, the full-term singleton primiparas without intrapartum fever who met the criteria were enrolled in a 1∶1 ratio as the control group during the same period. The general situation, complications, labor induction, delivery mode, and maternal and infant outcomes were compared between the fever group and control group. The fever group was further divided into 4 subgroups according to the degree of body temperature at delivery, including 142 cases in subgroup 1 with temperature of 37.3 to 0.05) . There was no statistically significant difference in the rates of labor induction, proportion of induced labor≥3 days and incidence of premature rupture of fetal membranes, gestational hypertension and gestational diabetes among the subgroups (P>0.05) . The differences were not statistically significant when comparing the rates of cesarean delivery, puerperal infection, neonatal asphyxia, amniotic fluid contamination and neonatal NICU transfer among the subgroups (P>0.05) . Conclusion The incidence of maternal complications, labor induction, cesarean section, puerperal infection and neonatal asphyxia increased in patients with fever during labor, the severity of fever was not related to the mode of delivery and maternal and infant outcomes.

Abstract To explore the mechanism of inhibiting spontaneous combustion of coal by mixed gases, the low-temperature oxidation characteristics of coal under different components of mixed gases were analyzed. ESR and FTIR experiments were used to investigate the effects of different gas mixtures on the activity of coal during low-temperature oxidation and the oxidation reaction of coal surface functional groups. The mechanism of chemical oxygen inhibition of mixed gas was studied by density functional theory. The results show that the larger the CO2 component in the mixed gas, the higher the ability to inhibit coal oxidation. The concentration of free radicals in coal under dry air condition is higher than that under inert mixed gas condition during oxidation heating at 30–230 °C. The oxidation ability of –CH3, –OH and oxygen-containing functional groups in the mixed gas reaction is inhibited. Through quantum chemistry calculation, it is found that the mixed gas increases the activation energy of free radicals and reduces the heat release of the reaction. This study provides theoretical reference for coal mine thermal disaster.

Abstract At present, clinical outcomes of pancreatic cancer patients are still poor. New therapeutic targets for pancreatic cancer are urgently needed. Previous studies have indicated that Microtubule Associated Monooxygenase, Calponin and LIM Domain Containing 2 (MICAL2) is highly expressed in many tumors and promotes tumor progression. However, the role played by MICAL2 in pancreatic cancer remains unclear. Based on gene expression and clinical information from multiple datasets, we used comprehensive bioinformatics analysis in combination with tissue microarray to explore the function and clinical value of MICAL2. The results showed that MICAL2 was highly expressed in pancreatic cancer tissue and exhibited potential diagnostic capability. High expression of MICAL2 was also associated with poor prognosis and acted as an independent prognostic factor. MICAL2, mainly expressed in fibroblasts of pancreatic cancer, was closely related to metastasis and immune-related features, such as epithelial-mesenchymal transformation, extracellular cell matrix degradation, and inflammatory response. Furthermore, higher MICAL2 expression in pancreatic cancer was also associated with an increase in cancer-associated fibroblasts as well as M2 macrophage infiltration, and a reduction in CD8 + T cell infiltration, thereby facilitating the formation of an immunosuppressive microenvironment. Our results helped elucidate the clinical value and function in metastasis and immunity of MICAL2 in pancreatic cancer. These findings provided potential clinical strategies for diagnosis, targeted therapy combination immunotherapy, and prognosis in patients with pancreatic cancer.

Abstract This study is nationwide multicenter epidemiological research, aimed at investigating the distribution changes and seasonal patterns of various airborne allergens among preschool children with allergic rhinitis (AR) in different regions of China, and analyzing the clinical correlation between sensitization to various airborne allergens and AR symptoms in children. Information on children was collected through standard questionnaires, and total IgE (tIgE) and specific IgE (sIgE) for 11 inhalant allergens were tested. The results showed that dust mites are the primary allergens for preschool AR children (39%). Among pollen allergens, Amb a had the highest positivity rate (8.1%), followed by Art v (7.8%). The sensitization rates for two mites peaked in May (46.9% and 40.6%). Art v peaked in August (21.5%), while Amb a had peaks in May (12.7%) and August (17.8%). The sensitization peaks for various tree pollens mainly occurred in August. In the Eastern monsoon region, the sensitization rate to mites was significantly higher than in the Northwest arid and semi-arid regions; whereas, for pollen allergens, the sensitization rates to Amb a, Pla a, Pin a, Pop d, and Bet v were significantly higher in the Northwest arid and semi-arid regions than in the Eastern monsoon region. The correlation among various tree pollens, specifically between Pla a, Pin r, Pop d, and Bet v was strong (0.63 ~ 0.79), with a cross-overlapping percentage of 53.9%. Children with multiple pollen sensitizations had higher cumulative nasal symptom scores than those negative for pollen (P

Abstract Doxorubicin (DOX) is an effective anticancer drug with potent antitumour activity. However, the application of DOX is limited by its adverse reactions, such as depression. Taurine can alleviate depression induced by multiple factors. However, it is still unclear whether and how taurine improves DOX-induced depression. To address this question, the aim of this study was to explore the potential mechanism by which taurine protects against DOX-induced depression. Mice were randomly divided into three groups (n = 8): (1) the control group, (2) the DOX group, and (3) the DOX + taurine group. The open field test (OFT), elevated plus maze test, and forced swim test (FST) were first performed to assess the effects of DOX and taurine on the behaviour of mice. Next, a combined transcriptomic and metabolomic analysis was performed to analyse the possible antidepressive effect of taurine. Taurine pretreatment increased the total distance travelled and speed of mice in the OFT, increased the number of entries into the open arm and the time spent in the open arm, and reduced the immobility time in the FST. In addition, 179 differential genes and 51 differentially abundant metabolites were detected in the DOX + taurine group compared to the DOX group. Furthermore, differential genes and differentially abundant metabolites were found to be jointly involved in 21 pathways, which may be closely related to the antidepressant effect of taurine. Taurine alleviated DOX-induced depressive behaviour. The various pathways identified in this study, such as the serotonergic synapse and the inflammatory mediator regulation of TRP channels, may be key regulatory pathways related to depression and antidepressant effects.

Abstract Guangxi, China, is one of the world's largest karst regions where potential toxic elements tend to accumulate, resulting in high soil background values. This study explores the ecological risk, elemental baseline values, and sources of potential toxic elements in karst regions, expanding the research to include 21 common elements. The significance of this research lies in its implications for the management of potential toxic element pollution, the formulation of environmental quality standards, and soil remediation in karst areas. In this study, 12,547 topsoil samples (0–20 cm) were collected in the study area. Pollution assessment and ecological risk evaluation of eight potential toxic elements (Zn, Ni, Cu, Pb, Cd, Hg, Cr, and As) were conducted using the geo-accumulation index method and potential ecological risk index method. Multivariate statistical analysis was applied to analyze the total content of 21 common elements (Zn, Ni, Cu, Pb, P, Cd, Hg, Co, Mn, Cr, V, I, S, As, pH, Se, N, CaO, Corg, Mo, and F). Additionally, the potential sources of 21 soil elements were preliminarily quantitatively analyzed using the principal component analysis-absolute principal component scores-multiple linear regression receptor model. The results showed that (1) Zn, Ni, Cu, Pb, Cd, Cr, V, and As were enriched in the research area and Ca, Cd, Mn, Mo, Hg, As, and Cu might have been influenced by human activities; (2) Cr, Pb, As, and Zn were generally lightly polluted, with Hg having a moderate potential ecological risk level; and (3) Ni and Zn have contributions of 37.99% and 35.07% from geological sources, agricultural fertilization, and pesticides. Mo, V, Cr, Se, Hg, and As exhibit contributions ranging from 39.44 to 59.22% originating from geological backgrounds and human activities. Corg, S, N, and P show contributions of 45.39% to 80.33% from surface vegetation. F, Co, Mn, and Pb have contributions ranging from 31.63 to 47.93% from acidic rocks in the soil parent material, mining activities, and transportation. Cd and CaO derive 31.67% and 40.23%, respectively, from soil parent material and industrial sources. I has 31.94% from geological background and human activities, and 31.95% from soil parent material and atmospheric sources. Cu has 30.56% from geological sources. The study results can serve as a scientific basis for element research in karst areas domestically and internationally.

Abstract The prediction of potential microbe–drug associations is of great value for drug research and development, especially, methods, based on deep learning, have been achieved significant improvement in bio-medicine. In this manuscript, we proposed a novel computational model named NMGMDA based on the nuclear norm minimization and graph attention network to infer latent microbe–drug associations. Firstly, we created a heterogeneous microbe–drug network in NMGMDA by fusing the drug and microbe similarities with the established drug–microbe associations. After this, by using GAT and NNM to calculate the predict scores. Lastly, we created a fivefold cross validation framework to assess the new model NMGMDA's progressiveness. According to the simulation results, NMGMDA outperforms some of the most advanced methods, with a reliable AUC of 0.9946 on both MDAD and aBioflm databases. Furthermore, case studies on Ciprofloxacin, Moxifoxacin, HIV-1 and Mycobacterium tuberculosis were carried out in order to assess the effectiveness of NMGMDA even more. The experimental results demonstrated that, following the removal of known correlations from the database, 16 and 14 medications as well as 19 and 17 microbes in the top 20 predictions were validated by pertinent literature. This demonstrates the potential of our new model, NMGMDA, to reach acceptable prediction performance.

Abstract Biochar has shown potential as a sorbent for reducing Cd levels in water. Euhalophytes, which thrive in saline-alkali soils containing high concentrations of metal ions and anions, present an intriguing opportunity for producing biochar with inherent metal adsorption properties. This study focused on biochar derived from the euhalophyte Salicornia europaea and aimed to investigate its Cd adsorption capacity through adsorption kinetics and isotherm experiments. The results demonstrated that S. europaea biochar exhibited a high specific surface area, substantial base cation content, and a low negative surface charge, making it a highly effective adsorbent for Cd. The adsorption data fit well with the Langmuir isotherm model, revealing a maximum adsorption capacity of 108.54 mg g−1 at 25 °C. The adsorption process involved both surface adsorption and intraparticle diffusion. The Cd adsorption mechanism on the biochar encompassed precipitation, ion exchange, functional group complexation, and cation-π interactions. Notably, the precipitation of Cd2+ with CO3 2− in the biochar played a dominant role, accounting for 73.7% of the overall removal mechanism. These findings underscore the potential of euhalophytes such as S. europaea as a promising solution for remediating Cd contamination in aquatic environments.

Objective To explore the predictive value of preoperative liver function for massive blood transfusion (MBT) in patients undergoing ascending aorta surgery. Methods Data from 238 patients undergoing ascending aorta surgery in the Department of Cardiovascular Surgery at The Affiliated Lihuili Hospital of Ningbo University were collected. Preoperative liver function tests were performed for all patients. Based on the perioperative transfusion volumes of red blood cell suspension, patients were divided into the MBT group, non-MBT group, and no blood transfusion (NBT) group. Clinical data during the perioperative period were compared among different groups. Receiver operating characteristic curve (ROC curve) analysis was used to assess the predictive value of liver function indicators for MBT and determine cut-off values. Results Compared with the non-MBT group and NBT group, the MBT group showed statistically significant differences in preoperative levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), direct bilirubin (DBIL), and serum albumin (SA) (P28.50 U/L, ALT >40.00 U/L, SA ≤34.55 g/L, and DBIL >4.25 μmol/L, there was a significant increase in the transfusion volume of various blood components and the incidence of MBT. Conclusion Preoperative liver function indicators (AST, ALT, SA, DBIL) have a moderate predictive value for MBT in patients undergoing ascending aorta surgery.

Abstract In this paper, a thick plate structural mechanical model was established for the hard-thick rock strata in the Ordos region, which was characterized by the occurrence of high-energy strong earthquakes caused by the fracture of hard-thick rock strata. Subsequently, based on Vlasov's theory, the evolution process of hard-thick rock strata was analyzed. And the paper validated the analysis results using high-energy mine earthquake and surface subsidence data. The following conclusions were drawn: (1) The hard-thick strata in the cretaceous system will not be broken during the advancing and mining process of the test panel of the Shilawusu coal mine. (2) When the test panel is mined to a distance of two panel widths, no fracture occurred in the lower part of the hard-thick strata, because no separated space was formed. (3) When the test panel was advanced to about 856 m, the hard-thick strata have fractured in a vertical direction. (4) No high-energy mine earthquake event has occurred during mining at test panel, and the amount of surface subsidence is approximately 200 mm. (5) In the mining at test panel, two high-energy mining earthquakes occurred at 837 m, 1153 m away from the initial position of the panel, respectively, and the maximum amount of surface subsidence increased to 1397 mm, which accords with the results of the first and periodic breaks calculated by theory. The research results of this paper are of guiding significance for the study of the breaking law of hard-thick strata under similar engineering geological conditions and disaster pre-control.

Abstract The importance of uncommon/rare oncogenic drivers in non‐small cell lung cancer (NSCLC) was underscored during the 20th China Lung Cancer Summit. These drivers, while present in a significant proportion of NSCLC patients, remain a challenge for diagnosis and therapeutic targeting. In the never‐smokers/low smokers category with mutations such as EGFR and HER2, the efficacy of immune checkpoint inhibitors (ICIs) remains suboptimal, attributed to lower PD‐L1 expression and tumor mutation burden (TMB). However, heavy smokers, often with mutations like KRAS, may derive benefits from ICIs, as supported by trials like CheckMate‐057. With the complex landscape of these drivers and their clinical implications, the summit culminated in six pivotal consensus points, aiming to guide future research and clinical decisions. Despite the advancements, the detection, interpretation, and therapeutic strategies involving these drivers necessitate further exploration and standardization.

Abstract Adenotonsillectomy is the most common daytime surgery performed on children. Anesthesiologists must select the optimal combination of drugs to ensure effective anesthesia effect and prompt recovery in children. The optimal induction dose of ciprofol in children is unclear. In this study, we aim to investigate the effect of different doses of ciprofol on anesthesia induction in children undergoing daytime adenotonsillectomy and provide a reference for clinical use. 144 children aged 3–12 years, ASA I-II, undergoing daytime adenotonsillectomy, were included in this clinical trial. The children were randomly divided into three groups and given 0.4 mg/kg (C4), 0.6 mg/kg (C6), or 0.8 mg/kg (C8) of ciprofol for anesthesia induction. The primary outcome was intubation conditions. Vital signs and injection pain were also recorded. The rates of unacceptable intubation conditions were 30.6%, 8.7%, and 8.2% in the C4, C6, and C8 groups (P value

Abstract Background Immune dysregulation is a feature of sepsis. However, a comprehensive analysis of the immune landscapes in septic patients has not been conducted. Objectives This study aims to explore the abundance ratios of immune cells in sepsis and investigate their clinical value. Methods Sepsis transcriptome data sets were downloaded from the NCBI GEO database. The immunedeconv R package was employed to analyze the abundance of immune cells in sepsis patients and calculate the ratios of different immune cell types. Differential analysis of immune cell ratios was performed using the t test. The Spearman rank correlation coefficient was utilized to find the relationships between immune cell abundance and pathways. The prognostic significance of immune cell ratios for patient survival probability was assessed using the log-rank test. In addition, differential gene expression was performed using the limma package, and gene co-expression analysis was executed using the WGCNA package. Results We found significant changes in immune cell ratios between sepsis patients and healthy controls. Some of these ratios were associated with 28-day survival. Certain pathways showed significant correlations with immune cell ratios. Notably, six immune cell ratios demonstrated discriminative ability for patients with systemic inflammatory response syndrome (SIRS), bacterial sepsis, and viral sepsis, with an Area Under the Curve (AUC) larger than 0.84. Patients with a high eosinophil/B.cell.memory ratio exhibited poor survival outcomes. A total of 774 differential genes were identified in sepsis patients with a high eosinophil/B.cell.memory ratio compared to those with a low ratio. These genes were organized into seven co-expression modules associated with relevant pathways, including interferon signaling, T-cell receptor signaling, and specific granule pathways. Conclusions Immune cell ratios eosinophil/B.cell.memory and NK.cell.activated/NK.cell.resting in sepsis patients can be utilized for disease subtyping, prognosis, and diagnosis. The proposed cell ratios may have higher prognostic values than the neutrophil-to-lymphocyte ratio (NLR).

Abstract Background Gout pain seriously affects the quality of patients' life. There is still no effective treatment. The inflammatory response is the main mechanism of gout. Here, we found that ozone can reduce the inflammatory reaction in the joints of gouty mice and relieve gout pain, and we further explore its protective mechanism. Methods MSU was used to establish the gouty mice model. Nociception was assessed by Von Frey hairs. Cell signaling assays were performed by western blotting and immunohistochemistry. The mouse leukemia cells of monocyte macrophage line RAW264.7 were cultured to investigate the effects of ozone administration on macrophage. Results Ozone reduced inflammation, relieved gout pain and improved the paw mean intensity and duty cycle of the gouty mice. Ozone increased the phosphorylation of AMP-activated protein kinase (AMPK), induced suppressor of cytokine signaling 3 (SOCS3) expression and inhibited metallopeptidase 9 (MMP9) expression. In vivo, ozone activated AMPK to induce Gas6 release, and upregulated MerTK/SOCS3 signaling pathway to reduce inflammation in mouse macrophage line RAW264.7. Inhibitors of AMPK and MerTK, respectively abolished the analgesic and anti-inflammatory effects of ozone in vivo and in vitro. Gas6 knockout cancelled the protectively effects of ozone on gout pain and the paw mean intensity and duty cycle of gouty mice. Additionally, the level of Gas6 and protein S in plasma of patients with hyperuricemia was significantly higher than that of healthy contrast group. Conclusion Ozone reduces inflammation and alleviates gout pain by activating AMPK to up-regulate Gas6/MerTK/SOCS3 signaling pathway.

AbstractBackground Venetoclax monotherapy is an effective option for patients with acute myeloid leukemia (AML). Venetoclax has also been used in non-myeloablative conditioning allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk AML with a tolerable toxicity profile. However, the efficacy and safety of a venetoclax-containing myeloablative conditioning (MAC) allo-HSCT regimen for high-risk AML have not been evaluated.Objective To evaluate the safety and efficacy of a MAC regimen containing venetoclax for high-risk AML.Study design From 25 February 2021 to 4 September 2022, a total of 31 patients with high-risk AML who underwent allo-HSCT and a MAC regimen with venetoclax were analyzed.Results At the time of transplantation, 21 patients were in first complete remission (CR1), 4 were in a second complete remission (CR2), and 6 in non-remission (NR). Twenty-four patients (77.4%) were minimal residual disease (MRD)-positive before transplant. The FLT3-ITD gene mutation was present in 51.6% of patients. NUP98 rearrangement, MLL rearrangement or MLL-PTD and DEK::CAN fusion genes were found in 5 (16.1%), 7(22.6%) and 2 (6.5%) patients, respectively. Twenty-nine (93.6%) patients underwent haploidentical allo-HSCT. The median follow-up time was 278 days (range: 52–632 days). The 100-day cumulative incidence of grade 3 to 4 acute graft-versus-host disease (aGVHD) was 16.1% (95%CI, 7.2–36.0%). The 180-day cumulative incidence of moderate to severe chronic graft-versus-host disease (cGVHD) was 7.1% (95%CI, 1.9–26.9%). Cumulative incidence of 100-day cytomegalovirus (CMV) viraemia and 100-day Epstein-Barr virus (EBV) viraemia was 61.6% (95%CI, 46.5–81.4%) and 3.2% (95%CI, 0.4–22.2%), respectively. The 600-day overall survival (OS) and leukemia-free survival (LFS) were 80.9% (95%CI, 63.5–93.6%) and 81.3% (95%CI, 64.2–93.7%), respectively. The 600-day relapse incidence (RI) and non-relapse mortality (NRM) was 6.9% (95%CI, 1.8–26.3%) and 11.7% (95%CI, 3.9–35.0%).Conclusion Our study shows that the addition of venetoclax to a MAC allo-HSCT was feasible, safe and effective for high-risk AML patients.

Summary: Background: Poly(ADP-ribose) polymerase (PARP) inhibitors have emerged as promising chemotherapeutic drugs primarily against BRCA1/2-associated tumours, known as synthetic lethality. However, recent clinical trials reported patients’ survival benefits from PARP inhibitor treatments, irrelevant to homologous recombination deficiency. Therefore, revealing the therapeutic mechanism of PARP inhibitors beyond DNA damage repair is urgently needed, which can facilitate precision medicine. Methods: A CRISPR-based knock-in technology was used to establish stable BRCA1 mutant cancer cells. The effects of PARP inhibitors on BRCA1 mutant cancer cells were evaluated by biochemical and cell biological experiments. Finally, we validated its in vivo effects in xenograft and patient-derived xenograft (PDX) tumour mice. Findings: In this study, we uncovered that the majority of clinical BRCA1 mutations in breast cancers were in and near the middle of the gene, rather than in essential regions for DNA damage repair. Representative mutations such as R1085I and E1222Q caused transient extra spindle poles during mitosis in cancer cells. PAR, which is synthesized by PARP2 but not PARP1 at mitotic centrosomes, clustered these transient extra poles, independent of DNA damage response. Common PARP inhibitors could effectively suppress PARP2-synthesized PAR and induce cell senescence by abrogating the correction of mitotic extra-pole error. Interpretation: Our findings uncover an alternative mechanism by which PARP inhibitors efficiently suppress tumours, thereby pointing to a potential new therapeutic strategy for centrosome error-related tumours. Funding: Funded by National Natural Science Foundation of China (NSFC) (T2225006, 82272948, 82103106), Beijing Municipal Natural Science Foundation (Key program Z220011), and the National Clinical Key Specialty Construction Program, P. R. China (2023).

Abstract Hydrogen sulfide for wound healing has drawn a lot of attention recently. In this research, the S‐propargyl‐cysteine (SPRC), an endogenous H2S donor, was loaded on carbomer hydrogel, and a copper sheet rat burn model was developed. Pathological changes in rat skin tissue were examined using hematoxylin–eosin (HE) and Masson staining. The immunohistochemistry (IHC) staining was performed to detect the expression of Collagen I (Col I) and Collagen III (Col III). The mRNA levels of interleukin (IL)‐6, Col Iα2, Col IIIα1, tissue inhibitors of metalloproteinase (TIMP)‐1, matrix metalloproteinase (MMP)‐9, vascular endothelial growth factor (VEGF), and transforming growth factor (TGF)‐β1 were examined by quantitative real‐time chain polymerase reaction. The findings demonstrated that the collagen layer was thicker in the SPRC group during the proliferative phase, SPRC hydrogel promoted VEGF expression. In the late stage of wound healing, the expression of IL‐6, TIMP‐1, MMP‐9, and TGF‐β1 was inhibited, and the Col I content was closer to that of normal tissue. These results surface that SPRC hydrogel can promote wound healing and play a positive role in reducing scar formation. Our results imply that SPRC can facilitate wound healing and play a positive role in reducing scar formation.

Abstract Shallow landslides of expensive soil slopes occur from time to time, and most engineering geological problems are directly or indirectly caused by soil structure cracks. The existence of tensile cracks can significantly affect the hydro-mechanical properties of soils. In this paper, the mechanism of expansive soil landslide formation is explored, and swelling pressures, and drying and wetting cycles are introduced into the discrete element method (DEM), and the landslide process of expansive soils is studied by the numerical simulation mothed. The relationship between the crack development and the instability of expansive soil slopes was investigated. The results show that under the condition of seasonal dry and wet alternation, the cracks of the expansive soil slope gradually develop, the rainwater infiltrates rapidly, the mechanical properties gradually deteriorate, and under the effect of such adverse cycle, the soil gradually softens and the stability decreases. Under the influence of human activities, vehicle loads and other factors, the slope body slides. These findings are helpful for the design and construction of expansive soil slopes and foundations.

Abstract Intestinal symbiotic microorganisms have a strong capacity to regulate the physiological functions of their host, and Drosophila serves as a useful model. Enterococcus faecium (E. faecium) is a member of the normal intestinal flora of animals. Lactic acid bacteria (LAB) such as E. faecium can promote the growth and development of Drosophila, but the mechanism of regulation of Drosophila is poorly understood. In this study, we found that E. faecium used a carbon source to produce probiotic acids. E. faecium is a symbiotic bacterium for Drosophila, and adult flies passed on parental flora to offspring. E. faecium promoted the growth and development of Drosophila, especially under poor nutritional conditions. E. faecium shortened the developmental process for Drosophila and accelerated the transformation from larva to pupa. Finally, E. faecium promoted the growth and development of Drosophila through TOR and insulin signalling pathways.