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Abstract Background Primary health-care workers (PHWs) managed increased workloads and pressure during the COVID-19 pandemic. This study conducted a national survey examining burnout among PHWs at the end of the COVID-19 pandemic, and identifies related factors. By doing so, it addresses the gap in understanding the burnout situation among PHWs at a national level, taking into account urban-rural disparities. Methods We conducted a nationwide cross-sectional survey of PHWs in China from May to October 2022, covering 31 provinces. The MBI-HSS was used to measure overall burnout and emotional exhaustion (EE), depersonalization (DP), and reduced personal accomplishment (PA). We used multivariable logistic regression to identify risk factors, and subgroup analyses to identify differences between rural and urban areas. Results 3769 PHWs from 44 primary health-care institutions completed the survey. Overall, 16.6% reported overall burnout, and the prevalence of EE, DP, and reduced PA was 29.7%, 28.0%, and 62.9%, respectively. The prevalence of overall burnout (17.6% vs. 13.7%, P = 0.004) and EE (31.5% vs. 24.8%, P

Abstract The aim of this study was to examine the effect of a positive emotion‐based exercise intervention on quality of life (QOL), fatigue, and mental health status in patients with lung cancer undergoing chemotherapy. A total of 80 patients with lung cancer undergoing chemotherapy were selected and divided into an observation group and a control group, with 40 patients in each group. Patients in the control group received routine care and were educated about the benefits of exercise, while patients in the experimental group received an additional exercise intervention based on positive emotions. We assessed patients' quality of life, fatigue, and mental health at the time of recruitment and 12 weeks after the exercise intervention. After the intervention, patients in the experimental group had a higher overall QOL score than those in the control group, with statistically significant differences in body, role, and emotions (p

Abstract Observational and genetic studies have reported the relationship between dyslexia and Alzheimer’s disease (AD). Until now, the causal effect of dyslexia on AD risk has remained unclear. We conducted a two-sample univariable Mendelian randomization (MR) analysis to determine the causal association between dyslexia and the risk of AD, vascular dementia (VD), Lewy body dementia (LBD), and frontotemporal dementia (FTD) and its four subtypes. First, we selected 42 dyslexia genetic variants from a large-scale genome-wide association studies (GWAS) dataset and extracted their corresponding GWAS summary statistics from AD, VD, LBD, and FTD. Second, we selected four MR methods, including inverse-variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO. Heterogeneity, horizontal pleiotropy, and leave-one-out sensitivity analysis were then used to evaluate the reliability of all causal estimates. We also conducted multivariable MR (MVMR) and mediation analysis to assess the potential mediating role of cognitive performance (CP) or educational achievement (EA) on the causal association between dyslexia and AD. Two MVMR methods, including MV IVW and MV-Egger, and two-step MR were used to perform the analysis. Using IVW, we found a significant causal association between increased dyslexia and increased risk of AD (OR = 1.15, 95% CI: 1.04–1.28, P = 0.006), but not VD, LBD, FTD, or its four subtypes. MR-PRESSO further supported the statistically significant association between dyslexia and AD (OR = 1.15, 95% CI: 1.05–1.27, P = 0.006). All sensitivity analyses confirmed the reliability of causal estimates. Using MV IVW and mediation analysis, we found no causal relationship between dyslexia and AD after adjusting for CP but not EA, CP mediated the total effect of dyslexia on AD with a proportion of 46.32%. We provide genetic evidence to support a causal effect of increased dyslexia on increased risk of AD, which was largely mediated by CP. Reading activity may be a potential intervention strategy for AD by improving cognitive function.

It is necessary to confirm the appropriate processing parameters for recycled-Be/2024Al composites before hot processing. Therefore, hot compression experiments were conducted on 40 and 50 vol% recycled-Be/2024Al composites prepared by pressure infiltration method. Meanwhile, the constitutive equations were established. The activation energy increased with the volume fraction of reinforcement, which means the increasing difficulty for composites to deform. However, different from ceramic reinforcements, Be is able to deform with matrix coordinately. This characteristic makes recycled-Be/2024Al composites more prone to deformation than ceramic reinforced Al composites with the same volume fraction of reinforcements. The processing maps of 40 and 50 vol% recycled-Be/2024Al composites have been drawn, and the appropriate processing parameters for 40 and 50 vol% recycled-Be/2024Al composites were determined as 495–525 °C,0.0006–0.0016 s−1 and 500–530 °C,0.016–0.04 s−1, respectively. The microstructures of samples hot compressed with various parameters were observed to identify the accuracy of processing maps.

The reconstruction of neural function and recovery of chronic damage following traumatic brain injury (TBI) remain significant clinical challenges. Exosomes derived from neural stem cells (NSCs) offer various benefits in TBI treatment. Numerous studies confirmed that appropriate preconditioning methods enhanced the targeted efficacy of exosome therapy. Interferon-gamma (IFN-γ) possesses immunomodulatory capabilities and is widely involved in neurological disorders. In this study, IFN-γ was employed for preconditioning NSCs to enhance the efficacy of exosome (IFN-Exo, IE) for TBI. miRNA sequencing revealed the potential of IFN-Exo in promoting neural differentiation and modulating inflammatory responses. Through low-temperature 3D printing, IFN-Exo was combined with collagen/chitosan (3D-CC-IE) to preserve the biological activity of the exosome. The delivery of exosomes via biomaterial scaffolds benefited the retention and therapeutic potential of exosomes, ensuring that they could exert long-term effects at the injury site. The 3D-CC-IE scaffold exhibited excellent biocompatibility and mechanical properties. Subsequently, 3D-CC-IE scaffold significantly improved impaired motor and cognitive functions after TBI in rat. Histological results showed that 3D-CC-IE scaffold markedly facilitated the reconstruction of damaged neural tissue and promoted endogenous neurogenesis. Further mechanistic validation suggested that IFN-Exo alleviated neuroinflammation by modulating the MAPK/mTOR signaling pathway. In summary, the results of this study indicated that 3D-CC-IE scaffold engaged in long-term pathophysiological processes, fostering neural function recovery after TBI, offering a promising regenerative therapy avenue.

Abstract There is a relative scarcity of large-scale population studies investigating the relationship between the insulin resistance index of homeostasis model assessment (HOMA-IR) and vascular damage. Therefore, we assessed the association between HOMA-IR and vascular damage in adults aged 18 years and older in China. A total of 17,985 research subjects were included. Vascular damage markers and relevant laboratory tests were measured. HOMA-IR was calculated as (fasting insulin * fasting blood glucose)/22.5. Vascular damage included arteriosclerosis (ba-PWV > 1800 cm/s), peripheral artery disease (ABI 30 mg/g). The relationship between HOMA-IR and vascular damage was analyzed using the RCS. The restricted cubic spline (RCS) analysis suggested that HOMA-IR was nonlinearly associated with arteriosclerosis (P for no-liner

Abstract Inherited non-hemolytic anemia is a group of rare bone marrow disorders characterized by erythroid defects. Although concerted efforts have been made to explore the underlying pathogenetic mechanisms of these diseases, the understanding of the causative mutations are still incomplete. Here we identify in a diseased pedigree that a gain-of-function mutation in toll-like receptor 8 (TLR8) is implicated in inherited non-hemolytic anemia. TLR8 is expressed in erythroid lineage and erythropoiesis is impaired by TLR8 activation whereas enhanced by TLR8 inhibition from erythroid progenitor stage. Mechanistically, TLR8 activation blocks annexin A2 (ANXA2)-mediated plasma membrane localization of STAT5 and disrupts EPO signaling in HuDEP2 cells. TLR8 inhibition improves erythropoiesis in RPS19 +/− HuDEP2 cells and CD34+ cells from healthy donors and inherited non-hemolytic anemic patients. Collectively, we identify a gene implicated in inherited anemia and a previously undescribed role for TLR8 in erythropoiesis, which could potentially be explored for therapeutic benefit in inherited anemia.

Replant diseases (RDs), intraspecific negative plant–soil feedback, often stem from nutrient deficiency, allelopathy, or pathogen accumulation. However, the RDs of certain crops are long-lasting and their causes remain unknown. We examined Panax quinquefolius RD in a space-for-time soil sequence representing crop rotation restoration over 1, 10, and 20 years using multiomics and bioassays. Compared with the soils with no ginseng cultivation history, we found 110 significant potential factors related to RD, surprisingly, 53 of which remained unrestored after 20 years. Soil pH and the levels of organic nutrients (amino acids, carbohydrates, and alditols), allelopathic-promoting metabolites (phenolic acids, amines, pyridines, etc.), and beneficial bacteria (Sphingomonas, Burkholderia-Caballeronia-Paraburkholderia, and Terrabacter) and fungi (Acremonium, Penicillium, and Naganishia) decreased, while the levels of allelochemicals (pyruvic and fatty acids) increased. The expression of all metabolic pathways was significantly down-regulated, with the exception of the up-regulated fatty acid-related metabolic pathways. We confirmed that decreased organic nutrient levels and increased levels of allelochemicals impaired P. quinquefolius growth. Soil metabolic factors rather than microbial factors were dominant by network analysis. In conclusion, we found that the overall changes in nutrient levels and metabolic and microbial factors contributed to short-term RD (1–10 year) persistence, whereas long-term RD (after 20 years) primarily resulted from disordered soil metabolite levels and pathways. This research will help deepen our understanding of the relationship between RD and potential changes in the factors influencing RD that are caused by soil legacy effects of valuable plants and provide theoretical guidance for effective soil quality improvement.

BackgroundInadequate levels of vitamin D (VitD) have been linked to increased rates of various health conditions and mortality. However, little is known about the relationship between mortality outcomes and 25-hydroxyvitamin D [25(OH)D] levels in individuals with rheumatoid arthritis (RA). This study aimed to examine this association using data from the National Health and Nutrition Examination Survey.MethodsA cohort of 2,290 individuals aged 20 to 85 years with RA was analyzed. Lower 25(OH)D levels were inversely associated with all-cause mortality, with a hazard ratio (HR) of 0.91 (0.87 to 0.96) per 10 nmol/L increase. Comparatively, the HR for the VitD insufficiency group was 0.64 (0.50 to 0.83), and for the VitD sufficiency group, it was 0.60 (0.44 to 0.80), both compared to the VitD deficiency group. Cause-specific analysis showed that higher 25(OH)D levels were associated with reduced mortality from heart disease (HR: 0.88, 0.82 to 0.95) and malignant neoplasms (HR: 0.86, 0.79 to 0.94). No significant correlation was found between 25(OH)D levels and cause-specific mortalities for other conditions.ResultsStratified by gender, the HR for males was 0.92 (0.85 to 0.99) and for females was 0.91 (0.86 to 0.98) per 10 nmol/L increase in 25(OH)D levels. Among individuals aged 20-59 years, no significant correlation was observed, while for those aged 60 years and older, the HR was 0.86 (0.82 to 0.90) per 10 nmol/L increase. Nonlinear analysis identified a sharp increase in HR below 59.95 nmol/L, while HR remained below 1 for 25(OH)D levels above 59.95 nmol/L.ConclusionThis study reveals a strong negative correlation between 25(OH)D levels and overall mortality in individuals with RA. Notably, this association is particularly significant for mortality related to heart disease and malignant neoplasms. Targeted VitD supplementation should be emphasized, especially in individuals aged 60 years and older with RA. The proposed minimum threshold for adequate 25(OH)D levels in the RA population is 60 nmol/L.

BackgroundCognitive impairment is one of the major diseases facing the aging population. The progressive decline of cognitive function can lead to declining health or even the loss of life, work, and social ability. Exercise and behavioral stimulation can increase neurotransmitters in the brain and improve overall health and cognitive function. Reactivity training can mobilize neuromuscular function and induce changes in brain plasticity, which may effectively improve cognitive dysfunction and delay the occurrence and development of Alzheimer disease; however, the evidence supporting its effectiveness is still limited. ObjectiveThis study aims to explore the effectiveness and reliability of visual-motor reaction training in improving cognitive function, thereby promoting the application of novel nonpharmacological therapies. MethodsThis study is a single-center, open-label, controlled clinical trial. A total of 78 participants will be recruited for the study, including an equal number of athletes, ordinary healthy college students, and ordinary older adults in the community. Participants will receive 2 weeks of visual-motor response training. The primary outcome of this study is to assess differences in functional magnetic resonance imaging (fMRI) at 2 weeks. The secondary outcomes were the following: acousto-optic response time, Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Mini Mental State Examination (MMSE), Activity of Daily Living (ADL) Scale, Subjective Cognitive Decline Questionnaire–9 (SCD-Q9), a 10-word memory test, and safety. ResultsThe study was approved by the Shanghai Clinical Research Ethics Committee on January 2, 2024 (SECCR/2023-162-01). As of September 11, 2024, we have completed the recruitment of all 3 groups of volunteers. We expect to complete data collection and analysis by February 2025. ConclusionsThe purpose of this study is to compare improvements in brain perceptual motor functions and cognitive levels across different populations through response ability training and to explore the efficacy and safety of exercise-based nonpharmacological therapies in improving cognitive function. Other potential benefits include understanding the functional differences and perceptual characteristics of the brain’s perceptual-motor system between athletes and the general population and exploring the adaptability of the brain in acquiring skills during competitive sports training. This could provide an evidence base for early sports talent development and broader youth development. Trial RegistrationChinese Clinical Trial Registry ChiCTR2400079602; https://tinyurl.com/23fbbndw International Registered Report Identifier (IRRID)DERR1-10.2196/56424

ObjectivesThe aim of this study is to assess the risk factors associated with thrombotic events in obstetric antiphospholipid syndrome (OAPS) patients and to develop a predictive model specifically tailored to predict the risk of postpartum thrombosis in OAPS patients without prior thrombotic events. This research seeks to enhance clinician’s awareness regarding the postpartum care and monitoring of OAPS patients.MethodsA retrospective study was conducted at the First Affiliated Hospital of the Fourth Military Medical University including 269 consecutive inpatients diagnosed with antiphospholipid syndrome (APS) from July 1, 2008 to July 31, 2022. All participants met the 2006 Sydney APS classification criteria or the “non-criteria OAPS classification”. Out of 98 candidate clinical and laboratory parameters considered, 40 potential variables were selected for analysis based on expert opinion. The logistic regression mode with the Least Absolute Shrinkage and Selection Operator (LASSO) were used to identify optimal predictive characteristics. All samples were included in the model building and a nomogram was generated based on these characteristics. The differentiation, calibration, and clinical utility of the predictive model were evaluated using the area under the curve (AUC), calibration curve, and decision curve analysis. The model was also validated by a 1000 bootstrap tests.Results126 patients with OAPS were enrolled, and a total of 89 OAPS patients who had never experienced thrombosis were retrospectively analyzed. After 3 years follow-up, 32.58% of the patients (29/89) developed thrombosis. In order to create, LASSO logistic regression identified three optimal variables: the platelet count less than 125×109/L, more than one positive aPLs (antiphospholipid antibody), and the use of low molecular weight heparin (LMWH) or low dose aspirin (LDA) after delivery. A predictive model was conducted using these three predictive indicators for patients with OAPS who experience thrombosis for the first-time. This prediction model has good distinction, good calibration, and fair clinical practicality.ConclusionOur model has good predictive ability in assessing the risk of thrombosis in patients with OAPS without prior thrombotic events. This model is easy to predict, has good discriminability and calibration, and can be utilized as a routine tool for thrombus screening in OAPS patients.

Abstract Therapeutic agents targeting cytokine-cytokine receptor (CK-CKR) interactions lead to the disruption in cellular signaling and are effective in treating many diseases including tumors. However, a lack of universal and quick access to annotated structural surface regions on CK/CKR has limited the progress of a structure-driven approach in developing targeted macromolecular drugs and precision medicine therapeutics. Herein we develop CytoSIP (Single nucleotide polymorphisms (SNPs), Interface, and Phenotype), a rich internet application based on a database of atomic interactions around hotspots in experimentally determined CK/CKR structural complexes. CytoSIP contains: (1) SNPs on CK/CKR; (2) interactions involving CK/CKR domains, including CK/CKR interfaces, oligomeric interfaces, epitopes, or other drug targeting surfaces; and (3) diseases and phenotypes associated with CK/CKR or SNPs. The database framework introduces a unique tri-level SIP data model to bridge genetic variants (atomic level) to disease phenotypes (organism level) using protein structure (complexes) as an underlying framework (molecule level). Customized screening tools are implemented to retrieve relevant CK/CKR subset, which reduces the time and resources needed to interrogate large datasets involving CK/CKR surface hotspots and associated pathologies. CytoSIP portal is publicly accessible at https://CytoSIP.biocloud.top , facilitating the panoramic investigation of the context-dependent crosstalk between CK/CKR and the development of targeted therapeutic agents.

Abstract Background Currently, different guidelines recommend using different methods to determine whether deduplication is necessary when determining the detection rates of multidrug-resistant organisms (MDROs). However, few studies have investigated the effect of deduplication on MDRO monitoring data. In this study, we aimed to investigate the influence of deduplication on the detection rates of MDROs in different specimens to assess its impact on infection surveillance outcomes. Methods Samples were collected from hospitalized patients admitted between January 2022 and December 2022; four types of specimens were collected from key monitored MDROs, including sputum samples, urine samples, blood samples, and bronchoalveolar lavage fluid (BALF) samples. In this study, we compared and analysed the detection rates of carbapenem-resistant Klebsiella pneumoniae (CRKP), carbapenem-resistant Escherichia coli (CRECO), carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and methicillin-resistant Staphylococcus aureus (MRSA) under two conditions: with and without deduplication. Results When all specimens were included, the detection rates of CRKP, CRAB, CRPA, and MRSA without deduplication (33.52%, 77.24%, 44.56%, and 56.58%, respectively) were significantly greater than those with deduplication (24.78%, 66.25%, 36.24%, and 50.83%, respectively) (all P

The steel and aluminum alloy tubes were successfully joined by magnetic pulse welding (MPW). Part of the joints fractured at the interface, yet part of them fractured at the base metal (BM) of aluminum alloy. The tensile test results revealed a fluctuation of the mechanical properties of the steel/Al MPW joints, demonstrating the microstructure inhomogeneity of the MPW joints. The typical wavy interfacial morphology could be observed at the interface of the MPW joints. The element transition zone composed of elements Fe and Al were detected while no obvious intermetallic compound (IMC) layer could be traced. The good mechanical properties of steel/Al MPW joints could be attributed to the longer effective bonding length and larger element transition area. Besides, the grain refinement was observed at the interface of the MPW joint, which explained its microhardness increase.

Abstract Background The neutrophil-lymphocyte ratio (NLR) is a novel hematological parameter to assess systemic inflammation. Prior investigations have indicated that an increased NLR may serve as a potential marker for pathological states such as cancer and atherosclerosis. However, there exists a dearth of research investigating the correlation between NLR levels and mortality in individuals with diabetes and prediabetes. Consequently, this study aims to examine the connection between NLR and all-cause as well as cardiovascular mortality in the population of the United States (US) with hyperglycemia status. Methods Data were collected from a total of 20,270 eligible individuals enrolled for analysis, spanning ten cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. The subjects were categorized into three groups based on tertiles of NLR levels. The association of NLR with both all-cause and cardiovascular mortality was evaluated using Kaplan-Meier curves and Cox proportional hazards regression models. Restricted cubic splines were used to visualize the nonlinear relationship between NLR levels and all-cause and cardiovascular mortality in subjects with diabetes after accounting for all relevant factors. Results Over a median follow-up period of 8.6 years, a total of 1909 subjects with diabetes died, with 671 deaths attributed to cardiovascular disease (CVD). And over a period of 8.46 years, 1974 subjects with prediabetes died, with 616 cases due to CVD. The multivariable-adjusted hazard ratios (HRs) comparing high to low tertile of NLR in diabetes subjects were found to be 1.37 (95% CI, 1.19–1.58) for all-cause mortality and 1.63 (95% CI, 1.29–2.05) for CVD mortality. And the correlation between high to low NLR tertile and heightened susceptibility to mortality from any cause (HR, 1.21; 95% CI, 1.03–1.43) and CVD mortality (HR, 1.49; 95% CI, 1.08–2.04) remained statistically significant (both p-values for trend

ObjectiveTo understand the impact of vaccine hesitancy on coronavirus disease 2019 (COVID-19) vaccination status among the elderly population in Beijing, and to provide policy recommendations for the implementation of the national strategy to promote COVID-19 vaccination among the elderly. MethodsA stratified random sampling method was used to recruit 800 residents aged ≥ 60 years for a face-to-face survey in October 2020. A self-designed questionnaire was used to collect relevant information, and the 5C scale was used to capture relevant predictors of vaccination behavior among participants. Unconditional multivariate logistic regression models were used to analyze the effect of vaccine hesitancy on COVID-19 vaccination. ResultsOf the 720 eligible participants included in the analysis, 541 (75.14%) had received the first dose of COVID-19 vaccine. Participants′ total score on the 5C scale was 4.84 ± 1.06 after positive and negative conversion, with dimensional scores of 8.94 ± 1.39 for confidence, 1.92 ± 2.26 for complacency, 1.46 ± 1.94 for constraints, 7.44 ± 2.63 for calculation, and 8.10 ± 1.68 for collective responsibility. The numbers (percentages) of participants classified as having high, moderate, and low vaccine hesitancy were 240 (33.33%), 232 (32.22%), and 248 (34.44%), respectively. After adjustment for sex, age, education, marital status, monthly household income per capita, smoking, alcohol consumption, social activities in the previous month, and chronic disease, the results of multivariable logistic regression indicated that participants with a higher collective responsibility score were more likely to have a higher COVID-19 vaccination rate (odds ratio [OR] = 1.21, 95% confidence interval [CI]: 1.00 – 1.46). In contrast, higher levels of complacency (OR = 0.76, 95%CI: 0.64 – 0.92), constraints (OR = 0.83, 95%CI: 0.69 – 0.99), and calculation (OR = 0.72, 95%CI: 0.58 – 0.89) were associated with lower vaccination rates. Participants with moderate and low vaccine hesitancy were more likely to be vaccinated, with an OR (95%CI) of 2.19 (1.44 – 3.33) and 4.03 (2.51 – 6.45), respectively. ConclusionThe COVID-19 vaccination rate among the elderly in Beijing is relatively low, with higher vaccination rates observed among those with lower levels of vaccine hesitancy.

Abstract Background The triglyceride glucose (TyG) index and triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio are recognized as simple non-insulin-based insulin resistance indices. Our study aimed to explore the relationship between these two indicators and heart failure (HF) in overweight or obesity individuals without diabetes. Methods This cross-sectional study selected 13,473 participants from the National Health and Nutrition Examination Survey (NHANES) 2001–2018 dataset. Weighted multivariable logistic regression and subgroup analysis were employed to evaluate the relationships between TyG index, TG/HDL-C ratio, and HF prevalence, respectively. Additionally, smooth curve fitting was utilized to analyze the dose–response relationships. Results A total of 13,473 obesity or overweight people without diabetes were included in this study through screening, among whom 291 (2.16%) had comorbid HF. The results of multivariable logistic regression suggested that the highest TyG index (OR = 2.4, 95% CI = 1.4–4.2, p = 0.002) and the highest TG/HDL-C ratio (OR = 1.2, 95% CI = 1.1–1.3, p

Abstract Background There is an urgent clinical need for developing novel immunoprophylaxis and immunotherapy strategies against Staphylococcus aureus (S. aureus). In our previous work, immunization with a tetra-branched multiple antigenic peptide, named MAP2-3 that mimics lipoteichoic acid, a cell wall component of S. aureus, successfully induced a humoral immune response and protected BALB/c mice against S. aureus systemic infection. In this study, we further investigated whether vaccination with MAP2-3 can elicit immunologic memory. Methods BALB/c mice were immunized with MAP2-3 five times. After one month of the last vaccination, mice were challenged with heat-killed S. aureus via intraperitoneal injection. After a 7-day inoculation, the percentage of plasma cells, memory B cells, effector memory T cells, and follicular helper T cells were detected by flow cytometry. The levels of IL-6, IL-21, IL-2, and IFN-γ were measured by real-time PCR and ELISA. Flow cytometry results were compared by using one-way ANOVA or Mann-Whitney test, real-time PCR results were compared by using one-way ANOVA, and ELISA results were compared by using one-way ANOVA or student’s t-test. Results The percentage of plasma cells and memory B cells in the spleen and bone marrow from the MAP2-3 immunized mice was significantly higher than that from the control mice. The percentage of effector memory T cells in spleens and lymphoid nodes as well as follicular helper T cells in spleens from the MAP2-3 immunized mice were also higher. Moreover, the levels of IL-6 and IL-21, two critical cytokines for the development of memory B cells, were significantly higher in the isolated splenocytes from immunized mice after lipoteichoic acid stimulation. Conclusions Immunization with MAP2-3 can efficiently induce memory B cells and memory T cells.

Abstract Background Sleep-disordered breathing (SDB) during childhood is common and includes a range of breathing abnormalities that range from primary snoring (PS) to obstructive sleep apnea syndrome (OSAS).Studies have shown that not only OSAS, but also PS, which is originally considered harmless, could cause cardiovascular, cognitive, behavioral, and psychosocial problems. Many researches are focused on the relation of OSA and serum lipid levels. However, little studies are focused on PS and serum lipid levels in children.We evaluated whether serum lipid (total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C)) concentrations were associated with specific components of SDB, including indices of oxygen reduction index, lowest oxygen saturation, mean oxygen saturation. And we explored whether serum lipid levels were associated with different degree sleep disordered (PS and OSA group) and obese. Methods This was a cross-sectional study. Children who were complained by their guardians with habitual snoring and(or) mouth breathing were collected in the SDB group. Normal children without sleep problem were matched in the control group. Subjects in the SDB group underwent polysomnography. The serum lipid profiles of all the children included TC, TG, HDL-C and LDL-C concentrations were measured by appropriate enzymatic assays. Results A total of 241 with Apnea/Hypopnea Index ≥ 5 (AHI) were assigned to the OSAS group and the remaining 155 with normal AHI were assigned to the PS group. The values of TC, TG, LDL-C and LDL/HDL were significantly higher in the OSAS group than in the PS group, and the values in the PS group were significantly higher than the control group. Multiple regression analysis revealed serum TG only correlated negatively with lowest oxygen saturation. Body mass index-z score has a positive effect on TG in all the 1310 children (P = 0.031) and in SDB 396 children(P = 0.012). The level of serum TG in obese group was significantly higher than that in non-obese group. Conclusions SDB had a very obvious effect on blood lipids, whereas PS without apnea and hypoxia. Obese only affects the aggregation of TG. Trial registration ChiCTR1900026807(2019.10.23).

Abstract Soil organic carbon (SOC) has various pools with different stabilization mechanisms. It is unclear how these SOC pools respond to various mineral and organic amendments depending on a large climate-soil gradient. Here, we studied in three zonal soils: Ferralic Cambisol (subtropic), Calcaric Cambisol (warm-temperate) and Luvic Phaeozem (mid-temperate) under 23-year mineral, straw and manure amendments. Six SOC sub-pools were isolated: unprotected, physically, chemically, biochemically, physico-chemically and physico-biochemically protected pools. Compared to initial level, SOC and most sub-pools increased in the three soils under manure application (p

Abstract Background Current research has been focusing on non-suicidal self-injury (NSSI) behaviors among adolescents with depression. Although family intimacy and adaptability are considered protective factors for NSSI, evidence supporting this relationship is lacking. Objective This study aims to examine the mechanisms operating in the relationship between family intimacy and adaptability and NSSI behaviors among adolescents. Methods A self-administered general demographic information questionnaire, the Behavioral Functional Assessment Scale for Non-Suicidal Self-Injury, the Family Intimacy and Adaptability Scale, the Connor-Davidson Resilience Scale, and the Self-Assessment of Depression Scale were distributed among adolescents with depression in three tertiary hospitals in Jiangsu Province. Results The relationship between family intimacy and adaptability and NSSI was assessed among 596 adolescents with depression. The results revealed the following: (1) Family intimacy and adaptability were negatively correlated with NSSI behavior. (2) Psychological resilience and depression levels acted as chain mediators in the relationship between family intimacy and adaptability and NSSI behavior. Conclusions Enhancing psychological resilience, controlling depressive symptoms, and reducing depression severity among adolescents by improving their family intimacy and adaptability are conducive to preventing and mitigating their NSSI behaviors.

Abstract Aims To investigate effects of repetitive transcranial magnetic stimulation (rTMS) on the prospective memory (PM) in patients with schizophrenia (SCZ). Methods Fifty of 71 patients completed this double‐blind placebo‐controlled randomized trial and compared with 18 healthy controls' (HCs) PM outcomes. Bilateral 20 Hz rTMS to the dorsolateral prefrontal cortex at 90% RMT administered 5 weekdays for 4 weeks for a total of 20 treatments. The Positive and Negative Symptom Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS), and PM test were assessed before and after treatment. Results Both Event‐based PM (EBPM) and Time‐based PM (TBPM) scores at baseline were significantly lower in patients with SCZ than that in HCs. After rTMS treatments, the scores of EBPM in patients with SCZ was significantly improved and had no differences from that in HCs, while the scores of TBPM did not improved. The negative symptom scores on PANSS and the scores of almost all subscales and total scores of SANS were significantly improved in both groups. Conclusions Our findings indicated that bilateral high‐frequency rTMS treatment can alleviate EBPM but not TBPM in patients with SCZ, as well as improve the negative symptoms. Significance: Our results provide one therapeutic option for PM in patients with SCZ.

Abstract Soil fungi participate in various ecosystem processes and are important factors driving the restoration of degraded forests. However, little is known about the changes in fungal diversity and potential functions under the development of different vegetation types during natural (secondary forest succession) and anthropogenic (reforestation) forest restoration. In this study, we selected typical forest succession sequences (including Pinus densiflora Siebold & Zucc., pine‐broadleaf mixed forest of P. densiflora and Quercus acutissima Carruth., and Q. acutissima), as well as natural secondary deciduous broadleaved mixed forests and planted forests of Robinia pseudoacacia on Kunyu Mountain for analysis. We used ITS rRNA gene sequencing to characterize fungal communities and used the FUNGuild database to predict fungal functional groups. The results showed that forest succession affected fungal β‐diversity, but not the α‐diversity. There was a significant increase in Basidiomycota and a decrease in Ascomycota in the later successional stage, accompanied by an increase in the functional groups of ectomycorrhizal fungi (ECM). Conversely, planted forests exhibited decreased fungal α‐diversity and altered community compositions, characterized by fewer Basidiomycota and more Ascomycota and Mucoromycota. Planted forests led to a decrease in the relative abundances of ECM and an increase in animal pathogens. The TK content was the major factor explaining the distinction in fungal communities among the three successional stages, whereas pH, AP, and NH4+ were the major factors explaining community variations between natural and planted forests. Changes in vegetation types significantly affected the diversity and functional groups of soil fungal communities during forest succession and reforestation, providing key insights for forest ecosystem management in temperate forests.

Abstract Immunosuppression is a major hallmark of tumor progression in non‐small cell lung cancer (NSCLC). Cluster of differentiation 147 (CD147), an important pro‐tumorigenic factor, is closely linked to NSCLC immunosuppression. However, the role of CD147 di‐methylation in the immunosuppressive tumor microenvironment (TME) remains unclear. Here, di‐methylation of CD147 at Lys148 (CD147‐K148me2) is identified as a common post‐translational modification (PTM) in NSCLC that is significantly associated with unsatisfying survival outcomes among NSCLC sufferers, especially those in the advanced stages of the disease. The methyltransferase NSD2 catalyzes CD147 to generate CD147‐K148me2. Further analysis demonstrates that CD147‐K148me2 reestablishes the immunosuppressive TME and promotes NSCLC progression. Mechanistically, this modification promotes the interaction between cyclophilin A (CyPA) and CD147, and in turn, increases CCL5 gene transcription by activating p38‐ZBTB32 signaling, leading to increased NSCLC cell‐derived CCL5 secretion. Subsequently, CD147‐K148me2‐mediated CCL5 upregulation facilitates M2‐like tumor‐associated macrophage (TAM) infiltration in NSCLC tissues via CCL5/CCR5 axis‐dependent intercellular crosstalk between tumor cells and macrophages, which is inhibited by blocking CD147‐K148me2 with the targeted antibody 12C8. Overall, this study reveals the role of CD147‐K148me2‐driven intercellular crosstalk in the development of NSCLC immunosuppression, and provides a potential interventional strategy for PTM‐targeted NSCLC therapy.

Serological detection of hepatitis B virus markers plays a vital role in the diagnosis, treatment, prognosis, and therapeutic surveillance of hepatitis B. To compare the diagnostic performance of Autolumo A2000Plus and Abbott Architect i2000 systems in the detection of hepatitis B infection markers. A total of 6 HBV seroconversion panels and 743 participants were enrolled in this study, including 383 HBV-infected patients and 360 healthy adults. Clinical diagnostic information, laboratory results, and HBV genotyping were collected to evaluate the diagnostic performance of the A2000Plus and i2000 systems in detecting HBV infection markers. The results showed that the total percent agreement of HBV markers was all >90 % in both detection systems among the six seroconversion panels and 743 serum samples from the population. The χ2 values of the Chi-square test among hepatitis B virus serological markers in both analyzers were between 550.7 and 743.0, p

DNA methylation plays a critical role in hematopoietic differentiation. Epimutation is a stochastic variation in DNA methylation that induces epigenetic heterogeneity. However, the effects of epimutations on normal hematopoiesis and hematopoietic diseases remain unclear. In this study, we developed a Julia package called EpiMut that enabled rapid and accurate quantification of epimutations. EpiMut was used to evaluate and provide an epimutation landscape in steady-state hematopoietic differentiation involving 13 types of blood cells ranging from hematopoietic stem/progenitor cells to mature cells. We showed that substantial genomic regions exhibited epigenetic variations rather than significant differences in DNA methylation levels between the myeloid and lymphoid lineages. Stepwise dynamics of epimutations were observed during the differentiation of each lineage. Importantly, we found that epimutation significantly enriched signals associated with lineage differentiation. Furthermore, epimutations in hematopoietic stem cells (HSCs) derived from various sources and acute myeloid leukemia were related to the function of HSCs and malignant cell disorders. Taken together, our study comprehensively documented an epimutation map and uncovered its important roles in human hematopoiesis, thereby offering insights into hematopoietic regulation.

Este artículo examina un grupo de artistas que destacaron en múltiples campos entre los estudiantes chinos de ultramar a principios del siglo XX, con el objetivo de explorar las polifacéticas razones que subyacen a la aparición de estos "eruditos". En primer lugar, a finales de la dinastía Qing y principios de la República de China, los estudiantes de ultramar introdujeron el arte occidental en China, marcando el comienzo de la transformación moderna del arte chino. A principios del siglo XX, marcado por la mezcla del "nuevo aprendizaje" y el "viejo aprendizaje", permitió a los estudiantes extranjeros comprender en profundidad los diversos sistemas de conocimiento de las culturas china y extranjera. En segundo lugar, la influencia del modelo de educación artística fue significativa. Anteriormente, bajo la influencia del modelo educativo japonés normal y los conceptos artísticos orientales, se hacía hincapié en lo común de la música, las bellas artes y la literatura. Sin embargo, con la introducción del modelo europeo de educación artística, el fenómeno del "polímata" disminuyó gradualmente. Por último, el ambiente educativo dentro de las propias familias de los artistas y sus intereses personales también influyeron significativamente en el desarrollo de sus diversos talentos. Este grupo de "polímatas" artísticos representa un fenómeno distintivo en el periodo de intercambio cultural y transformación de la sociedad china moderna.

Abstract Background It is controversial whether antibiotic should be used prophylactically 48 h after pancreatic surgery. Hence, the association of antibiotic prophylaxis (AP) after 48 h postoperatively with the incidence of surgical site infections (SSIs) and other healthcare-associated infections (HAIs) in patients receiving pancreatic surgery was evaluated. Methods A retrospective cohort analysis was performed on 1073 patients who underwent pancreatic surgery. These patients were categorized into the non-AP after 48 h postoperatively group (n = 963) and the AP after 48 h postoperatively group (n = 110) based on whether or not they obtained AP from 48 h to 30 days after surgery. Outcomes included SSIs and other HAIs. Results The incidence of SSIs in the non-AP after 48 h postoperatively group (98/963, 10.2%) was notably lower than that in the AP after 48 h postoperatively group (22/110, 20.0%) (P = 0.002). Other HAIs incidence was not significantly different between the non-AP after 48 h postoperatively group (77/963, 8.0%) and the AP after 48 h postoperatively group (11/110, 10.0%) (P = 0.468). Multiple regression analysis demonstrated that AP after 48 h postoperatively was a risk factor for SSIs (OR = 2.14, 95% CI 1.28–3.59) but not for other HAIs (OR = 1.24, 95% CI 0.63–2.42) after adjustment for age, gender, and diabetes. Subsequent to adjustment for all confounding factors, AP after 48 h postoperatively was not a influence factor for SSIs (OR = 2.13, 95% CI 0.76–5.99) and other HAIs (OR = 3.69, 95% CI 0.99–13.81). Conclusions AP after 48 h postoperatively following pancreatic surgery was not associated with the lower morbidity rate of SSIs and other HAIs. Nonetheless, this study may facilitate further development of strategies towards standardization of the duration of AP management of pancreatic surgery.

Drawing on Karl Marx’s ecological concepts of the “metabolic rift” and the “emancipation of senses”, this paper explores an alternative ecocinema that integrates the ecological with the social and the economic. Early Hollywood films, such as Sunrise: A Song of Two Humans (1927) and The Good Earth (1937), represent the metabolic rift in human relationships as a byproduct of the metabolic rift with nature created in the process of urbanization; hence, they can be regarded as precursors to an alternative ecocinema, which I refer to as “metabolic cinema”. The Story of the Golden Bell (Jinling Zhuan), a comedy film produced during the Chinese Great Leap Forward in 1958, offers an intriguing case for socialist metabolic cinema as a multisensory medianature that participates in and facilitates the metabolic process between humans and nature, as well as the social metabolism among humans, despite the period’s notorious ecological record. The film not only consciously moves away from the visual-centric model associated with capitalist consumerism by using the aural to rectify the once-aberrant visual but also demonstrates how romantic love, as one of the human senses, must be emancipated along with other senses through denouncing utilitarianism and commercialism and, subsequently, returning to need-based labor as the universal condition for the metabolic interaction between humans and nature.

Numerical experiments using the WRF model were conducted to analyze the sensitivity of Typhoon Mangkhut intensification simulations to seven widely used planetary boundary layer (PBL) parameterization schemes, including YSU, MYJ, QNSE, MYNN2, MYNN3, ACM2, and BouLac. The results showed that all simulations generally reproduced the tropical cyclone (TC) track and intensity, with YSU, QNSE, and BouLac schemes better capturing intensification processes and closely matching observed TC intensity. In terms of surface layer parameterization, the QNSE scheme produced the highest Ck/Cd ratio, resulting in stronger TC intensity based on Emanuel’s potential intensity theory. In terms of PBL parameterization, the YSU and BouLac schemes, with the same revised MM5 surface layer scheme, simulated weaker turbulent diffusivity Km and shallower mixing height, leading to stronger TC intensity. During the intensification period, the BouLac, YSU, and QNSE PBL schemes exhibited stronger tangential wind, radial inflow within the boundary layer, and updraft around the eye wall, consistent with TC intensity results. Both PBL and surface layer parameterization significantly influenced simulated TC intensity. The QNSE scheme, with the largest Ck/Cd ratio, and the YSU and BouLac schemes, with weaker turbulent diffusivity, generated stronger radial inflow, updraft, and warm core structures, contributing to higher storm intensity.

BackgroundLong-term skill learning can lead to structure and function changes in the brain. Different sports can trigger neuroplasticity in distinct brain regions. Volleyball, as one of the most popular team sports, heavily relies on individual abilities such as perception and prediction for high-level athletes to excel. However, the specific brain mechanisms that contribute to the superior performance of volleyball athletes compared to non-athletes remain unclear.MethodWe conducted a study involving the recruitment of ten female volleyball athletes and ten regular female college students, forming the athlete and novice groups, respectively. Comprehensive behavioral assessments, including Functional Movement Screen and audio-visual reaction time tests, were administered to both groups. Additionally, resting-state magnetic resonance imaging (MRI) data were acquired for both groups. Subsequently, we conducted in-depth analyses, focusing on the amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) in the brain for both the athlete and novice groups.ResultsNo significant differences were observed in the behavioral data between the two groups. However, the athlete group exhibited noteworthy enhancements in both the ALFF and ReHo within the visual cortex compared to the novice group. Moreover, the functional connectivity between the visual cortex and key brain regions, including the left primary sensory cortex, left supplementary motor cortex, right insula, left superior temporal gyrus, and left inferior parietal lobule, was notably stronger in the athlete group than in the novice group.ConclusionThis study has unveiled the remarkable impact of volleyball athletes on various brain functions related to vision, movement, and cognition. It indicates that volleyball, as a team-based competitive activity, fosters the advancement of visual, cognitive, and motor skills. These findings lend additional support to the early cultivation of sports talents and the comprehensive development of adolescents. Furthermore, they offer fresh perspectives on preventing and treating movement-related disorders. Trial registrationRegistration number: ChiCTR2400079602. Date of Registration: January 8, 2024.

Hematopoietic stem cells (HSCs) have been considered to progressively lose their self-renewal and differentiation potentials prior to the commitment to each blood lineage. However, recent studies have suggested that megakaryocyte progenitors (MkPs) are generated at the level of HSCs. In this study, we newly identified early megakaryocyte lineage-committed progenitors (MgPs) mainly in CD201−CD48− cells and CD48+ cells separated from the CD150+CD34−Kit+Sca-1+Lin− HSC population of the bone marrow in adult mice. Single-cell colony assay and single-cell transplantation showed that MgPs, unlike platelet-biased HSCs, had little repopulating potential in vivo, but formed larger megakaryocyte colonies in vitro (on average 8 megakaryocytes per colony) than did previously reported MkPs. Single-cell RNA sequencing supported that HSCs give rise to MkPs through MgPs along a Mk differentiation pathway. Single-cell reverse transcription polymerase chain reaction (RT-PCR) analysis showed that MgPs expressed Mk-related genes, but were transcriptionally heterogenous. Clonal culture of HSCs suggested that MgPs are not direct progeny of HSCs. We propose a differentiation model in which HSCs give rise to MgPs which then give rise to MkPs, supporting a classic model in which Mk-lineage commitment takes place at a late stage of differentiation.

BackgroundThe influencing factors of the process from latent tuberculosis infection (LTBI) to the onset of active tuberculosis (TB) remain unknown among different population groups, especially among older individuals in high-incidence areas. This study aimed to investigate the development of active TB among older adults with LTBI and identify groups in greatest need of improved prevention and control strategies for TB.MethodsIn 2021, we implemented an investigation among older individuals (≥ 65 years old) in two towns in Zhejiang Province with the highest incidence of TB. All participants underwent assessment using standardized questionnaires, physical examinations, interferon-gamma release assays, and chest radiography. All the participants with suspected TB based on the clinical symptoms or abnormal chest radiography results, as well as those with LTBI, were referred for diagnostic investigation in accordance with the national guidelines. Those with an initial diagnosis of TB were then excluded, whereas those with LTBI were included in a follow-up at baseline. Incident patients with active TB were identified from the Chinese Tuberculosis Management Information System, and a multivariate Cox regression model was used to estimate the incidence and risk of TB among those with LTBI.ResultsIn total, 667 participants with LTBI were followed up for 1,315.3 person-years, revealing a disease density of 1,292.5 individuals/100,000 person-years (17/1,315.3). For those with LTBI, chest radiograph abnormalities had adjusted hazard ratios for active TB of 4.9 (1.6–15.3).ConclusionsThe presence of abnormal chest radiography findings increased the risk of active TB among older individuals with LTBI in high-epidemic sites in eastern China.

Background and objectiveAccurately predicting the extent of lung tumor infiltration is crucial for improving patient survival and cure rates. This study aims to evaluate the application value of an improved CT index combined with serum biomarkers, obtained through an artificial intelligence recognition system analyzing CT features of pulmonary nodules, in early prediction of lung cancer infiltration using machine learning models.Patients and methodsA retrospective analysis was conducted on clinical data of 803 patients hospitalized for lung cancer treatment from January 2020 to December 2023 at two hospitals: Hospital 1 (Affiliated Changshu Hospital of Soochow University) and Hospital 2 (Nantong Eighth People’s Hospital). Data from Hospital 1 were used for internal training, while data from Hospital 2 were used for external validation. Five algorithms, including traditional logistic regression (LR) and machine learning techniques (generalized linear models [GLM], random forest [RF], gradient boosting machine [GBM], deep neural network [DL], and naive Bayes [NB]), were employed to construct models predicting early lung cancer infiltration and were analyzed. The models were comprehensively evaluated through receiver operating characteristic curve (AUC) analysis based on LR, calibration curves, decision curve analysis (DCA), as well as global and individual interpretative analyses using variable feature importance and SHapley additive explanations (SHAP) plots.ResultsA total of 560 patients were used for model development in the training dataset, while a dataset comprising 243 patients was used for external validation. The GBM model exhibited the best performance among the five algorithms, with AUCs of 0.931 and 0.99 in the validation and test sets, respectively, and accuracies of 0.857 and 0.955 in the validation and test groups, respectively, outperforming other models. Additionally, the study found that nodule diameter and average CT value were the most significant features for predicting lung cancer infiltration using machine learning models.ConclusionThe GBM model established in this study can effectively predict the risk of infiltration in early-stage lung cancer patients, thereby improving the accuracy of lung cancer screening and facilitating timely intervention for infiltrative lung cancer patients by clinicians, leading to early diagnosis and treatment of lung cancer, and ultimately reducing lung cancer-related mortality.

This study investigated the associations between gestational weight gain (GWG), pre-pregnancy body mass index (BMI), and prenatal diet quality in pregnant women from Shandong, China. We analyzed a sample of 532 early-stage pregnant women registered at an outpatient clinic. Diet quality was evaluated using the Chinese Healthy Dietary Index for Pregnancy (CHDI-P), encompassing three dimensions: diversity, adequacy, and limitation, with an overall score out of 100. Dietary intake was documented via 24-h dietary recalls spanning three consecutive days and subsequently translated to a CHDI-P score. At the time of enrollment, BMI was measured on-site and classified as underweight (

Summary: Background: Azvudine and nirmatrelvir/ritonavir are approved to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in adults with a high risk for progression to severe infection. We sought to compare the antiviral effectiveness and clinical outcomes of elderly severe patients with COVID-19 receiving these two antiviral agents. Methods: In this observational study, we identified 249 elderly patients with severe COVID-19 infection who were admitted to the Second Medical Center of the People's Liberation Army General Hospital from December 2022 to January 2023, including 128 azvudine recipients, 66 nirmatrelvir/ritonavir recipients and 55 patients not received antiviral treatments. We compared the cycle threshold (Ct) value dynamic change of all three groups. The primary outcome was a composite outcome of disease progression, including all-cause death, intensive care unit admission, and initiation of invasive mechanical ventilation. The outcomes of all enrolled patients were followed up from the electronic medical record system. Kaplan–Meier and Cox risk proportional regression analyses were used to compare the clinical outcomes of all three groups. To more directly compare the effectiveness of the two antiviral drugs, we performed propensity-score matching between the two antiviral groups and compared antiviral efficacy and clinical outcomes in the matched population. Findings: Among 249 patients (mean age, 91.41 years), 77 patients died during the follow-up period. When compared to patients who did not receive any antivirals, neither nirmatrelvir/ritonavir nor azvudine demonstrated a survival benefit. The Cox analysis of the all-cause death of the three groups showed that the risk of death was 0.730 (0.423–1.262) in the azvudine group 0.802 (0.435–1.480) and in the nirmatrelvir/ritonavir group compared with the non-antiviral group. After propensity score matching, we included 58 azvudine recipients and 58 nirmatrelvir/ritonavir recipients. The fitted curve of the Ct value after matching illustrated that the rate of viral decline in the early stage of nirmatrelvir/ritonavir treatment seems to surpass that of azvudine, but there was no statistical significance. Azvudine was seemly associated with a lower risk of composite outcomes (HR:1.676, 95% CI:0.805–3.488) and short-term all-cause death (HR: 1.291, 95%CI: 0.546–3.051). Interpretation: Patients who received azvudine have a similar antiviral effectiveness and survival curve trend compared to nirmatrelvir/ritonavir. In this limited series, antiviral treatment was not associated with a significant clinical benefit. This lack of clinical benefit might be attributed to potential bias. Funding: This study was supported by the “National Key R&D Program of China” (Funding No. 2020YFC2008900) and the National Defense Science and Technology Innovation Special Zone Project (223-CXCY-N101-07-18-01).

Background: The irreversible progression of autosomal dominant polycystic kidney disease (ADPKD) to end-stage renal disease (ESRD) is delayed by tolvaptan. Therefore, we aim to systematically estimate and evaluate the efficacy and safety of tolvaptan in the treatment of ADPKD. Methods: Two reviewers independently searched all published randomized controlled trials studies in PubMed, EMBASE, Web of Science and Cochrane databases, extracted data, assessed bias risk and rated the quality of evidence. Data were analyzed by the RevMan software. Results: We identified 8 trials including 2135 patients. Both of the decline of estimated glomerular filtration rate (eGFR) [MD = 1.89, 95% CI (0.74, 3.04), P = 0.001] and total kidney volume (TKV) [MD = −3.32, 95% CI (−4.57, −2.07), P

Using heterogeneous catalysts to promote the construction of the C–N bond between amines and CO2 under mild conditions is a challenge yet. Herein, we synthesized a novel zwitterionic polymer (PDDC) with a cellular structure via self-complexation of copolymer bearing both quaternary ammonium cation and carboxylate anion. PDDC was employed as a recyclable catalyst for N-methylation of atmospheric CO2 and various amines with hydrosilane as a reductant, affording more than 17 ​N-methylamines in good to excellent yields (up to 99%) under mild conditions. The behavior of PDDC in the reaction medium was disclosed by using a dynamic light scattering study, revealing that the decreased hydraulic radius of particle size contributes to exposing more active sites and increasing reaction activity. Utilizing a series of designed experiments and density functional theory calculations uncovered the crucial role of the prepared zwitterionic polymer during the reaction procedure of CO2 conversion.

Abstract Bacterial σI factors of the σ70-family are widespread in Bacilli and Clostridia and are involved in the heat shock response, iron metabolism, virulence, and carbohydrate sensing. A multiplicity of σI paralogues in some cellulolytic bacteria have been shown to be responsible for the regulation of the cellulosome, a multienzyme complex that mediates efficient cellulose degradation. Here, we report two structures at 3.0 Å and 3.3 Å of two transcription open complexes formed by two σI factors, SigI1 and SigI6, respectively, from the thermophilic, cellulolytic bacterium, Clostridium thermocellum. These structures reveal a unique, hitherto-unknown recognition mode of bacterial transcriptional promoters, both with respect to domain organization and binding to promoter DNA. The key characteristics that determine the specificities of the σI paralogues were further revealed by comparison of the two structures. Consequently, the σI factors represent a distinct set of the σ70-family σ factors, thus highlighting the diversity of bacterial transcription.

Abstract Pyroptosis is a kind of programmed cell death triggered by the inflammasome. Growing evidence has revealed the crucial utility of pyroptosis in tumors. However, the potential mechanism of pyroptosis in clear cell renal cell carcinoma (ccRCC) is still unclear. In this research, we systematically analyze the genetic and transcriptional alterations of pyroptosis-related genes (PRGs) in ccRCC, identify pyroptosis-related subtypes, analyze the clinical and microenvironmental differences among different subtypes, develop a corresponding prognostic model to predict the prognosis of patients, and interpret the effect of pyroptosis on ccRCC microenvironment. This study provides a new perspective for a comprehensive understanding of the role of pyroptosis in ccRCC and its impact on the immune microenvironment, and a reliable scoring system was established to predict patients’ prognosis.

Abstract Background Older people with hypertension may have more complex multisystem problems and a higher risk of morbidity and mortality. We aimed to examine the association of cognitive impairment (CI) and diabetes mellitus (DM) on all-cause mortality in the aged with hypertension (HTN). Methods This is a prospective cohort study with a sample of 1017 older people with hypertension aged 60 years or older who completed baseline examinations in 2009–2010 and followed up for ten years in 2020. The endpoint was death from any cause. Subjects were categorized as HTN only, HTN + DM, HTN + CI, and HTN + DM + CI. Cox regression model was used to determine the association of comorbidities on all-cause mortality. Results During the 10-year follow-up period, 196 deaths occurred. After adjusted for covariates, risk of death from any cause was significantly increased in the older people with increased comorbidities (P = 0.003). Compared with the HTN only, with HTN + CI, and HTN + DM + CI, the HRs (95% confidence intervals) for all-cause mortality were 1.61(1.13–2.30) and 1.79(1.07–2.99), respectively. In stratified analyses, the relationship between comorbidities level and the risk of all-cause mortality persisted. Conclusion All-cause mortality risks increased with increasing the comorbidities. This study emphasizes the importance of comprehensive management of the older people with HTN in clinical practice and public health policy.

Abstract Background Pulmonary arterial hypertension is a major cause of death in systemic lupus erythematosus, but there are no tools specialized for predicting survival in systemic lupus erythematosus-associated pulmonary arterial hypertension. Research question To develop a practical model for predicting long-term prognosis in patients with systemic lupus erythematosus-associated pulmonary arterial hypertension. Methods A prognostic model was developed from a multicenter, longitudinal national cohort of consecutively evaluated patients with systemic lupus erythematosus-associated pulmonary arterial hypertension. The study was conducted between November 2006 and February 2020. All-cause death was defined as the endpoint. Cox regression and least absolute shrinkage and selection operators were used to fit the model. Internal validation of the model was assessed by discrimination and calibration using bootstrapping. Results Of 310 patients included in the study, 81 (26.1%) died within a median follow-up of 5.94 years (interquartile range 4.67–7.46). The final prognostic model included eight variables: modified World Health Organization functional class, 6-min walking distance, pulmonary vascular resistance, estimated glomerular filtration rate, thrombocytopenia, mild interstitial lung disease, N-terminal pro-brain natriuretic peptide/brain natriuretic peptide level, and direct bilirubin level. A 5-year death probability predictive algorithm was established and validated using the C-index (0.77) and a satisfactory calibration curve. Risk stratification was performed based on the predicted probability to improve clinical decision-making. Conclusions This new risk stratification model for systemic lupus erythematosus-associated pulmonary arterial hypertension may provide individualized prognostic probability using readily obtained clinical risk factors. External validation is required to demonstrate the accuracy of this model's predictions in diverse patient populations.

The microstructure and mechanical properties of Sn–Bi solder alloys with various Ag and In addition are comparatively investigated. The results illustrate that the tensile strength and ductility of the solder alloy could be dramatically enhanced with negligible loss of the plasticity. Especially, the Sn–Bi solder alloy with 0.4 wt. % Ag and 1.5 wt. % In exhibits the maximum tensile strength and elongation of 79.7 MPa and 45.9%, respectively. The microstructure of the Sn–Bi solder alloys is mainly composed of Bi-rich and β-Sn phases. With the addition of elements Ag and In, the microstructure is significantly refined, and the lamellar eutectic structure with thinner interlayer spacing could be detected. Element Ag tends to form Ag3Sn phase while element In solutes in the Sn matrix. The mechanical properties of the as-prepared Sn–Bi solder alloy are improved attributed to the precipitated-phase strengthening of the fined Ag3Sn phase and the refinement effect of In on coarse Bi-rich phase.

Base editing represents a cutting-edge genome editing technique that utilizes the CRISPR system to guide base deaminases with high precision to specific genomic sites, facilitating the targeted alteration of individual nucleotides. Unlike traditional gene editing approaches, base editing does not require DNA double-strand breaks or donor templates. It functions independently of the cellular DNA repair machinery, offering significant advantages in terms of both efficiency and accuracy. In this review, we summarize the core design principles of various DNA base editors, their distinctive editing characteristics, and tactics to refine their efficacy. We also summarize their applications in crop genetic improvement and explore their potential contributions to forest genetic engineering.

This report involves a 54-year-old female patient diagnosed with diffuse large B-cell lymphoma who developed interstitial pneumonia (IP) during treatment. The patient presented to the ward with enlarged lymph nodes in the neck and was treated with the standard regimen, which included rituximab, cyclophosphamide, doxorubicin liposomes, vincristine, and prednisone (R-CDOP regimen). After 3 cycles, the treatment was assessed as effective. However, following the 4th cycle, the patient experience shortness of breath after physical activity. A repeat lung computer tomography indicated IP, which completely recovered after receiving “full coverage” treatment. Subsequently, the patient underwent 2 cycles of cyclophosphamide, doxorubicin liposomes, vincristine, and prednisone (CDOP), followed by local radiotherapy. Currently, the patient is now being followed up with regular reviews.

Abstract Mesenchymal stem cells (MSCs) possess potent immunomodulatory activity and have been extensively investigated for their therapeutic potential in treating inflammatory disorders. However, the mechanisms underlying the immunosuppressive function of MSCs are not fully understood, hindering the development of standardized MSC-based therapies for clinical use. In this study, we profile the single-cell transcriptomes of MSCs isolated from adipose tissue (AD), bone marrow (BM), placental chorionic membrane (PM), and umbilical cord (UC). Our results demonstrate that MSCs undergo a progressive aging process and that the cellular senescence state influences their immunosuppressive activity by downregulating PD-L1 expression. Through integrated analysis of single-cell transcriptomic and proteomic data, we identify GATA2 as a regulator of MSC senescence and PD-L1 expression. Overall, our findings highlight the roles of cell aging and PD-L1 expression in modulating the immunosuppressive efficacy of MSCs and implicating perinatal MSC therapy for clinical applications in inflammatory disorders.

Abstract Background Sedentary behavior is prevalent among people with diabetes and is associated with unfavorable cardiometabolic health. However, there is limited evidence regarding the impact of replacing sedentary time (ST) with physical activity on mortality in people with prediabetes and diabetes. We prospectively examined the association between accelerometer-measured ST and mortality among people with prediabetes and diabetes after adjusting for demographic characteristics, lifestyle factors, and moderate- to vigorous-intensity PA (MVPA). We further determined the effect of replacing ST with equal time of different types of physical activities on all-cause mortality. Methods We included 1242 adults with prediabetes and 1037 with diabetes from the National Health and Nutrition Examination Survey. Restricted cubic splines were fitted to determine the dose–response association between ST and overall mortality. Isotemporal substitution modeling was used to explore the hazard ratio (HR) effects of ST replacement. Results During a median follow-up of 14.1 years, 424 adults with prediabetes and 493 with diabetes died. Compared with the lowest tertile of ST, the multivariable-adjusted HRs for all-cause mortality in the highest tertile were 1.76 (95% confidence interval [CI] 1.19, 2.60) for participants with prediabetes and 1.76 (1.17, 2.65) for those with diabetes. Additionally, a linear association between ST and all-cause mortality was observed in adults with prediabetes and diabetes, with HRs for each 60 min/day increment in ST of 1.19 (1.10, 1.30) and 1.25 (1.12, 1.40), respectively. Isotemporal substitution results indicated that individuals with prediabetes whose ST was replaced by 30 min of light-intensity physical activity (LPA) and MVPA had 9% and 40% lower all-cause mortality, respectively. In people with diabetes, replacing sedentary behavior with an equivalent time of LPA and MVPA was also associated with mortality risk reduction (HR 0.89; 95% CI 0.84, 0.95 for LPA; HR 0.73; 95% CI 0.49, 1.11 for MVPA). Conclusions Higher ST was associated in a dose–response manner with an increased risk of premature mortality among adults with prediabetes and diabetes. Statistically replacing ST with LPA was potentially beneficial for health in this high-risk population.

Abstract Salmonella Typhimurium creates an intracellular niche for its replication by utilizing a large cohort of effectors, including several that function to interfere with host ubiquitin signaling. Although the mechanism of action of many such effectors has been elucidated, how the interplay between the host ubiquitin network and bacterial virulence factors dictates the outcome of infection largely remains undefined. In this study, we found that the SPI‐2 effector SseK3 inhibits SNARE pairing to promote the formation of a Salmonella‐induced filament by Arg‐GlcNAcylation of SNARE proteins, including SNAP25, VAMP8, and Syntaxin. Further study reveals that host cells counteract the activity of SseK3 by inducing the expression of the E3 ubiquitin ligase TRIM32, which catalyzes K48‐linked ubiquitination on SseK3 and targets its membrane‐associated portion for degradation. Hence, TRIM32 antagonizes SNAP25 Arg‐GlcNAcylation induced by SseK3 to restrict Salmonella‐induced filament biogenesis and Salmonella replication. Our study reveals a mechanism by which host cells inhibit bacterial replication by eliminating specific virulence factors.

Glioblastoma (GBM) is a lethal cancer with limited therapeutic options. Dendritic cell (DC)-based cancer vaccines provide a promising approach for GBM treatment. Clinical studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor activity. Here, we report a GBM case with combination immunotherapy consisting of DC vaccines, anti-programmed death-1 (anti-PD-1) and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy, and the patient remained disease-free for 69 months. The patient received DC vaccines loaded with multiple forms of tumor antigens, including mRNA-tumor associated antigens (TAA), mRNA-neoantigens, and hypochlorous acid (HOCl)-oxidized tumor lysates. Furthermore, mRNA-TAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histocompatibility complex (MHC) class I and II antigen presentation. The treatment consisted of 42 DC cancer vaccine infusions, 26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions. The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells. No immunotherapy-related adverse events were observed during the treatment. Robust antitumor CD4+ and CD8+ T-cell responses were detected. The patient remains free of disease progression. This is the first case report on the combination of the above three agents to treat glioblastoma patients. Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient. A large-scale trial to validate these findings is warranted.