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Abstract Background In this study, we aimed to explore the association between baseline and early changes in the neutrophil-to-lymphocyte ratio (NLR) and the 30-day mortality rate in patients having anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis with interstitial lung disease (DM-ILD). Methods Overall, 263 patients with anti-MDA5 DM-ILD from four centers in China were analyzed. Multivariate logistic regression analysis was used to evaluate the impact of baseline NLR on the 30-day mortality rate in patients with anti-MDA5-positive DM-ILD. Furthermore, a generalized additive mixed model (GAMM) was applied to compare the NLR variations over time between 30-day survival group and non-survival group. Results Two hundred sixty-three patients with anti-MDA5-positive DM-ILD were divided into different groups based on their NLR and whether they survived or not within 30 days. The multivariate logistic regression analysis, accounting for confounding factors, identified an elevated baseline NLR as a prognostic indicator for 30-day mortality in patients with anti-MDA5-positive DM-ILD (hazard ratio 2.68, 95% confidence interval [CI] 1.18,6.00, P = 0.019). Furthermore, the GAMM results indicated that the NLR gradually increased more in the non-survival group compared with the survival group within 14 days of admission, with a daily average increase of 1.03 (β = 1.03; 95% CI, 0.75–1.31; P

Abstract Background Diabetes mellitus (DM) is a major risk factor for tuberculosis (TB), However, limited research exists on their clinical and strain characteristics. This study aims to investigate the correlation between these factors in TB-DM patients in Changping District. Methods Whole genome sequencing (WGS) and drug susceptibility tests (DST) were performed on culture-positive strains. Spearman correlation analysis was used to examine risk factors and the correlation between lineage, cavities, and hemoptysis in the TB-DM population. The specificity, sensitivity, and confidence intervals for predicting phenotypic drug resistance based on genotypic resistance were calculated. Results Among the 3924 TB patients, 292 had DM, showing a doubling in the proportion of TB patients with DM over seven years. Among the 144 etiologically positive TB-DM cases treated at the Changping Institute for Tuberculosis Prevention and Treatment, 75% (108/144) of the patients exhibited tuberculosis lesions that formed cavities and 12.5% (18/144) with hemoptysis. A statistically significant difference in cavity formation across different age groups was observed (r = -0.198, P

Abstract The aim of this study is to investigate the effect of cardiometabolic diseases (CMDs) on the development of depressive symptoms and to determine whether socioeconomic status (SES) moderates this effect. A total of 6,455 individual free from depressive symptoms were selected from the China Health and Retirement Longitudinal Study (CHARLS). CMDs and SES were self-reported. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CESD-10). Cox proportional hazards regression models were employed to examine the association between baseline CMDs and subsequent depressive symptoms. Stratified analysis were conducted to explore the moderating effect of SES on this association.Participants with any CMDs exhibited a higher risk of developing depressive symptoms compared to those without CMDs, with a hazard ratio (HR) of 1.10 (95% CI: 1.01, 1.20). Individuals with one CMD (HR = 1.08, 95% CI: 1.00, 1.20) or cardiometabolic multimorbidity (HR = 1.13, 95% CI: 1.02, 1.26) also demonstrated an increased risk. The effect of CMDs on depressive symptoms was observed primarily in adults aged 60 years and older with lower education attainment (HR = 1.28, 95%CI: 1.12, 1.46), lower income (HR = 1.29, 95%CI: 1.11, 1.50) and rural residency (HR = 1.29, 95%CI: 1.12,1.51). These findings emphasize the importance of closely monitoring the mental status of patients with CMDs and considering routine screening and evaluation for depressive symptoms, especially in individuals with low SES.

Abstract The Cox-Maze IV (CMIV) procedure is the mainstay in surgical treatment of atrial fibrillation (AF), but the rate of AF recurrence after the CMIV procedure in patients with persistent AF is difficult to accurately evaluate. In this study, we aimed to develop and validate a risk prediction model of AF recurrence within 1 year after undergoing the Cox-Maze IV procedure. We retrospectively enrolled 303 consecutive patients who underwent the Cox-Maze IV procedure for persistent AF concomitant with other cardiac procedures at our institute between 2019 and 2021. A nomogram was developed using multivariate logistic regression analysis, and the concordance statistic (C-statistic) was computed. Differentiation, calibration, clinical suitability, and bootstrapping were performed to verify the model. Among the 303 patients, 71 developed recurrent AF within 1 year of CMIV. Factors predictive of postoperative AF recurrence included age, left ventricular hypertrophy (LVH), early atrial tachyarrhythmias (ATAs), and congenital heart disease surgery (namely, ventricular septal defect repair and atrial septal defect repair). Based on the training dataset, the nomogram had a C-statistic of 0.864 (95% CI 0.811–0.918) for predicting AF recurrence. According to the receiver operating characteristic curve, (ROC curve), the cutoff value of the model was 0.293, and the specificity and sensitivity were 0.841 and 0.789, respectively. This model can predict the risk of AF recurrence after the CMIV procedure. Its discrimination, calibration, and clinical applicability are strong, and its clinical application is simple and easy to promote.

Abstract Bacterial transcription activator-like effectors (TALEs) promote pathogenicity by activating host susceptibility (S) genes. To understand the pathogenicity and host adaptation of Xanthomonas citri pv. malvacearum (Xcm), we assemble the genome and the TALE repertoire of three recent Xcm Texas isolates. A newly evolved TALE, Tal7b, activates GhSWEET14a and GhSWEET14b, different from GhSWEET10 targeted by a TALE in an early Xcm isolate. Activation of GhSWEET14a and GhSWEET14b results in water-soaked lesions. Transcriptome profiling coupled with TALE-binding element prediction identify a pectin lyase gene as an additional Tal7b target, quantitatively contributing to Xcm virulence alongside GhSWEET14a/b. CRISPR-Cas9 gene editing supports the function of GhSWEETs in cotton bacterial blight and the promise of disrupting the TALE-binding site in S genes for disease management. Collectively, our findings elucidate the rapid evolution of TALEs in Xanthomonas field isolates and highlight the virulence mechanism wherein TALEs induce multiple S genes to promote pathogenicity.

Abstract Background To assess the therapeutic effects of mesenchymal stem cell (MSC)-derived exosome therapy on periodontal regeneration and identify treatment factors associated with enhanced periodontal regeneration in recent preclinical studies. Methods Searches were conducted in PubMed, Cochrane Library, EMBASE, and Web of Science databases until October 10, 2024. A risk of bias (ROB) assessment was performed using the SYRCLE tool. Osteogenic-related parameters were used as the primary outcome measures. Results In total, 1360 articles were identified, of which 17 preclinical studies were based on MSC-derived exosome therapy, and they demonstrated a beneficial effect on BV/TV (SMD = 13.99; 95% Cl = 10.50, 17.48; p

Abstract Background The multi-biological barriers present in the inflammatory microenvironment severely limit the targeted aggregation of anti-inflammatory drugs in the lesion area. However, conventional responsive drug carriers inevitably come into contact with several pro-responsive stimulatory mediators simultaneously, leading to premature drug release and loss of most therapeutic effects. Breaking through the multi-level barriers of the inflammatory microenvironment is essential to improve the enrichment and bioavailability of drugs. Results In this study, we propose a novel two-stage structural strategy to build shielded cascades of targeted nanocarriers (FA-PTP@Que) through inflammatory mediators, using cascade structures to cross multiple environmental barriers. The cascade structure of FA-PTP@Que is responsive to inflammatory mediators and exhibits ideal pathological microenvironmental response and drug release properties. FA-PTP@Que has shown good macrophage regulation and anti-inflammatory effects by efficiently targeting macrophages, scavenging intracellular reactive oxygen species (ROS), and down-regulating the secretion of pro-inflammatory factors. Significantly, in mice with arthritis and colitis, FA-PTP@Que enriches and targets macrophages at the sites of arthritis and colitis, showing significant anti-inflammatory effects. Conclusion FA-PTP@Que combines active chemotaxis of nanocarriers to inflammatory tissues and active targeting of effector cells, acting precisely at each barrier level in different microenvironments by responding to inflammatory mediators and overcoming the multiple barriers in the inflammatory microenvironment. This innovative strategy can effectively break through various inflammatory microenvironments and has the potential application to other inflammatory diseases.

Abstract Objective The aim of this study is to explore the clinicopathological features, radiographic manifestations, treatment options, and prognosis of primary pulmonary angiosarcoma (PPAS). Method We summarized and analyzed the clinical data of 11 patients with primary pulmonary angiosarcoma treated at the First Affiliated Hospital of Guangzhou Medical University between January 2018 and January 2024. A retrospective analysis was conducted in conjunction with a review of the relevant literature. Results Among the 11 cases, the primary symptoms were nonspecific respiratory issues, with chest pain, cough, and shortness of breath being the most common. Initial diagnosis was correct in only 2 cases, while the remaining 9 cases were misdiagnosed as other conditions, such as lung nodules, infections, or pulmonary embolism. All patients were ultimately diagnosed via pathology, with CD31 and CD34 showing a high positivity rate of 60%. Of the 11 patients, 9 have died, and 2 remain alive. The average survival period was 13.2 months.Based on the number of lesions, PPAS was categorized into three types: solitary, multiple, and invasive pulmonary artery. The average survival period for the solitary type (2 cases) was 15.5 months, for the multiple type (5 cases) was 6.6 months, and for the pulmonary artery type (4 cases) was 20.5 months. Among the 3 patients who underwent surgery, the median overall survival (OS) was 23.0 months, whereas for the 8 non-surgical patients, the median OS was 9.7 months. Conclusion Primary pulmonary angiosarcoma is a rare, highly aggressive vascular malignancy characterized by nonspecific clinical symptoms and a tendency for metastasis and pulmonary artery embolism. Currently, no effective treatment exists, and the overall prognosis is poor.

Summary: Objectives: Intraoperative frozen section (FS) analysis is pivotal in guiding surgical interventions for early-stage lung adenocarcinoma. However, the challenge arises when distinguishing between Minimally Invasive Adenocarcinoma (MIA) and Invasive Adenocarcinoma (IAC) poses diagnostic difficulties. This study investigates the prognosis and clinicopathological characteristics of patients encountering this diagnostic challenge. Methods: We conducted a retrospective analysis of 7082 intraoperative FSs from early-stage lung adenocarcinoma cases. The cases with pulmonary nodules within 3 cm and diagnosed as indeterminate FSs were included. We analyzed baseline data, computed tomography (CT) findings, and pathological characteristics. Prognostic data were obtained from patients with confirmed IAC diagnoses through final pathological examination. Results: Out of 7082 FSs, 551 cases presented challenges in distinguishing between MIA and IAC. Upon final pathological examination, 233 cases were identified as IAC, while 314 were classified as MIA. The median invasive pathological size in the IAC group was larger than that in the MIA group (0.6 cm vs 0.3 cm). 131 cases (56.2 %) with IAC underwent lobectomy, while 102 cases (43.8 %) underwent sub-lobar resection.Among the MIA cases, 220 cases (69.8 %) underwent sub-lobar resection, while 95 cases (30.2 %) underwent lobectomy. No recurrence and disease specific death was observed during the follow-up period, regardless of surgical strategy. Conclusions: Indeterminate intraoperative FSs, posing diagnostic challenges in distinguishing between MIA and IAC. Sub-lobar resection presented the same long term survival benefit compared with the lobectomy for indeterminate lung adenocarcinoma within 3 cm during intraoperative FSs.

Abstract Objectives To evaluate the association between toothbrushing behavior and cardiometabolic multimorbidity (CMM) among middle-aged and older adults. Methods Data from the Beijing Health Service Survey were used to estimate the association between toothbrushing behavior and the risk of CMM using multilevel logistic models (N = 18,158). Results There were 554 patients with CMM, with a prevalence of 3.05%. We found a higher risk of CMM for those with toothbrushing once or less (OR = 2.16, 95%CI: 1.80, 2.59) compared with those brushed two or more times per day in the crude model. After adjusting for confounding factors, the association between the two remained significant (OR = 1.68, 95%CI: 1.39, 2.04). The effect size was higher in adults with a higher education level (OR = 2.32) compared to those with a lower education level (OR = 1.39, P for interaction

Abstract Suicidal ideation (SI) is a significant precursor and risk marker for suicide behaviors in major depressive disorder (MDD). Exploration of SI trajectory from a longitudinal framework are essential for treatment guidelines and clinical management of suicide risk. This study sought to explore SI trajectories and its associated clinical, sociodemographic characteristics, and initial treatment among patients with MDD. We used data from a non-interventional, national multi-centered prospective cohort study. 1 461 patients with MDD were included in the growth mixture modeling using SI at baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks, and 6 months, 9 months, and 12 months as the indicator. A multinomial regression was employed with SI trajectory as the outcome and anhedonia, depressive symptoms, atypical depressive symptoms, pharmacological treatments, and other covariates as the predictors. Four distinct SI trajectories were identified: a consistently low SI trajectory(50.7%), a persistently mild SI trajectory(20.6%), a fast declined SI trajectory(8.9%), and a slowly declined trajectory(19.8%). Compared to those with a consistently low SI trajectory, a higher score of anhedonia was associated with an increased risk of experiencing persistently mild (RRR = 1.20, 95%CI: 1.05, 1.38) and slowly declined SI (1.54, 95%CI: 1.32, 1.80). Severity of depressive symptom was also positively associated with the risk of experiencing persistently mild (1.15, 95%CI: 1.13, 1.18) and slowly declined SI (1.17, 95%CI: 1.14, 1.21). And the risk of experiencing slowly declined SI was higher for those use SSRI(1.49, 95%CI: 1.02, 2.31), and for those use antidepressant and antipsychotic/mood stabilizer combined therapy (3.78, 95%CI: 1.48, 9.61). The findings of this study are potentially useful for clinical practice as critical indicators of profiles and interventions for prognosis among patients with MDD. Further research is warranted to explore potential modifiable factors and the association between SI trajectories and suicide behavior.

Abstract Objectives Observe the effect of integrated care for older people on intrinsic capacity in elderly patients. Methods Sixty elderly patients from department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between June 2021 and December 2021 were selected and divided into control group and intervention group with 30 patients in each group using random sampling method. Two groups implement routine care, and the intervention group implement integrated care by a “hospital-community-family” multidisciplinary team. After 12 weeks of intervention, the differences in frailty, cognition, depression scores, comprehension social support scores, and World Quality of Life Scale scores were compared between the two groups. Results Before intervention, there was no significant difference in the grip strength, step speed, frailty scores, cognition, depression scores, social support and quality of survival between the control group and the intervention group. After intervention, grip strength and depression scores improved both in the control group and the intervention group, but there was no difference between the two groups. Cognitive scores, comprehension social support and quality of survival scores improved only in the intervention group, while only the cognitive ability showed significant differences between the intervention group and the control group after 12 weeks of intervention (P

Obesity is a metabolic disorder due to over-accumulation of adipose tissue and ultimately becomes a “disease”. Brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning emerge as a potential strategy of anti-obesity by dissipating energy as heat. However, drugs based on adipose tissue thermogenesis have not been successfully approved yet. In current study, we found that black tea extract (BTE) obtained by patent-authorized manufacturing process prevented body weight gain as novel thermogenic activator with reduction of adiposity, improvement of adipose distribution, and glucose metabolism improvement in diet-induced obesity mice. Mechanismly, anti-obesity effect of BTE depends on promoting BAT thermogenesis and WAT browning with upregulation of uncoupling protein 1 (UCP1), especially visceral adipose tissue (VAT) with browning resistance. Specifically, utilizing in silico approach of network pharmacology and molecular docking, we identified carbonic anhydrase 2 (CA2) in nitrogen metabolism as anti-obesity target of BTE and further elucidated that protein kinase B (AKT) signaling pathway linked CA2 and UCP1. Meanwhile gut microbiota regulation may prompt the CA2-dependent thermogenesis activation. Our findings demonstrated anti-obesity effect of BTE as thermogenic activator through CA2-mediated BAT thermogenesis and WAT browning via CA2-AKT-UCP1 signaling pathway, which could be developed as promising anti-obesity agent with good safety and efficacy.

In recent years, the incidence of cosmetic injection-induced botulism has remarkably increased due to the frequent usage of botulinum neurotoxin type A (BoNT/A). To mimic and investigate this new clinical type of botulism, we established a novel animal model and evaluated the therapeutic potential of a new drug. Firstly, we injected BoNT/A into the gastrocnemius of rats to induce partial paralysis of the remaining limbs. Then, the intoxicated rats were treated with 3,4-diaminopyridine (3,4-DAP) at different stages of the disease and the forelimbs grasping strength (FGS) was evaluated. We showed that, at the sublethal dose, the FGS began to decrease at 6.00 ​± ​1.86 ​h after injection in rats, from 2.28 ​± ​0.19 ​N to 1.51 ​± ​0.18 ​N, while the FGS declined appeared earlier (4.29 ​± ​0.42 ​h) at the lethal dose, from 2.30 ​± ​0.20 ​N to 1.20 ​± ​0.16 ​N. Treatment with 3,4-DAP respectively at the time of the symptoms onset or 7 days after injection both can temporarily reverse the symptoms of muscle paralysis, indicating that 3,4-DAP may be an effective approach to relieve botulism. Overall, this study provides an available rat model and a promising therapeutic strategy for cosmetic injection-induced botulism.

Abstract Background This study assessed the global trends and burden of severe chest injury, including rib fractures, lung contusions, and heart injuries from 1990 to 2019. Herein, we predicted the burden patterns and temporal trends of severe chest injuries to provide epidemiological evidence globally and in China. Methods In our analysis, the age-standardized incidence rate (ASIR), prevalence rate (ASPR), and years lived with disability rate (ASYR) of severe chest injury were analyzed by gender, age, sociodemographic index, and geographical region between 1990 and 2019 using data from the Global Burden of Disease study 2019. Trends were depicted by calculating the estimated annual percentage changes (EAPCs). The impact of age, period, and cohort factors was assessed using an Age-Period-Cohort model. Autoregressive integrated moving average (ARIMA) model was employed to predict severe chest injury trends from 2020 to 2050. Results In 2019, the global number of severe chest injury cases reached 7.95 million, with the highest incidence rate observed in Central Europe (209.61). Afghanistan had the highest ASIRs at 277.52, while North Korea had the lowest ASIRs at 41.02. From 1990 to 2019, the Syrian Arab Republic saw significant increases in ASIR, ASPR, and ASYR, with EAPCs of 10.4%, 9.31%, and 10.3%, respectively. Burundi experienced a decrease in ASIR with an EAPC of − 6.85% (95% confidence interval [CI] − 11.11, − 2.37), while Liberia’s ASPR and ASYR declined with EAPCs of − 3.22% (95% CI − 4.73, − 1.69) and − 5.67% (95% CI − 8.00, − 3.28), respectively. Falls and road injuries remained the most common causes. The relative risk of severe chest injury by age, period, and cohort demonstrated a complex effect globally and in China. The ARIMA model forecasted a steady increase in global numbers from 2020 to 2050, while in China, it forecasted an increase in incidence, a decrease in ASIR and ASYR, and an increase in ASPR. Conclusions This study provides a groundbreaking analysis of global severe chest injury, shedding light on its measures and impact. These findings highlight the need for timely, specialized care and addressing regional disparities to mitigate the severe chest injury burden.

Critical-size bone defects (CSDs), which are those that do not self-repair in a given period, are essential for evaluating bone-regeneration strategies. We established CSDs models in the rabbit cranium and ulna, and the bone-regeneration capacities of porous calcium phosphate (CaP) ceramics were assessed. A 12.6-mm cranial defect was confirmed as a CSDs after 12 weeks, with submicron surface-structured biphasic calcium-phosphate (BCP) implants [consisting of 20% hydroxyapatite and 80% tricalcium phosphate (TCP)] demonstrating significantly higher bone formation (32.2% ± 10.6%) than micron surface-structured TCP (TCP-B) implants (17.8% ± 4.6%, p = 0.0121). Ulna defects (15.0 mm in length) failed to heal spontaneously within 24 weeks when the periosteum was removed from both the ulna and radius, and the radius was covered with an expanded polytetrafluoroethylene (ePTFE) membrane. No bone bridging (i.e., union) was observed in the BCP implants at 12 weeks, whereas 80% of BCP implants (four out of five) achieved union by 24 weeks. Furthermore, the bone area within the available space of BCP implants increased significantly from 19.3% ± 7.3% at 12 weeks to 37.7% ± 8.5% at 24 weeks (p = 0.0063), accompanied by significant BCP resorption (14.8% at 12 weeks and 30.2% at 24 weeks). This study offers two rabbit CSDs models for evaluating bone-regeneration strategies (including bone substitution), and the overall data obtained in the current study indicate the possibility of repairing CSDs with CaP ceramics demonstrating improved bone-forming ability given adequate implantation time.

Introduction Lung cancer is the leading cause of cancer-related mortality globally, with non-small cell lung cancer (NSCLC) comprising the majority of cases. For advanced NSCLC, immunotherapy offers substantial survival benefits but is often accompanied by severe immune-related adverse events symptoms, significantly affecting health-related quality of life (HRQoL). Routinely collection of patient-reported outcomes (PROs) followed by automated alerts has been shown to improve overall survival and HRQoL for cancers. However, there is limited evidence for PRO-based symptom monitoring on advanced NSCLC during immunotherapy. This study proposes an electronic PRO-based symptom tracking intervention, integrated with reactive alerts and nudges (PRO-NET) to improve HRQoL for advanced NSCLC patients receiving immunotherapy in China. Secondary objectives include assessing the effect of PRO-symptom monitoring on survival, physical function, symptom control, mental health, cost-effectiveness and implementation fidelity.Methods and analysis The PRO-NET study is a two-arm, parallel randomised controlled trial. The study will enrol at least 300 advanced NSCLC patients undergoing immunotherapy in China. Participants will be randomly assigned to either the intervention or control group in a ratio of 1:1 via PRO-NET programme. The intervention involves weekly electronic collection of immune-related PROs and reactive alerts sent directly to patients, combined with nudges over a 6-month period. Patients in the control group will follow usual care and will not trigger the alerts. Both the intervention and control groups will receive outcome assessments at baseline, 3 months and 6 months. Primary outcome focuses on HRQoL, while secondary outcomes include survival, physical function, symptom burden, mental health, cost-effectiveness and implementation fidelity. Differences in HRQoL between the groups will be compared using general linear mixed model, accounting for potential confounding.Ethics and dissemination The study was approved by the Institutional Review Board of the Peking University protocol on 21 July 2024 (No. IRB 00001052-24066). This protocol is based on V2.0, 6 July 2024 of the protocol. The results of this study will be disseminated through peer-reviewed publications and academic conferences.Trials registration number ChiCTR2400088408.

This paper aims to establish an intelligent delivery system integrated with track logistics and explores its impact on the clinical transportation of goods. The study analyzed hospital delivery items before and after the implementation of an intelligent delivery system combined with automated track logistics in 2023. Delivery conditions prior to the system’s activation served as the control group, while those post-implementation formed the observation group. This research assesses the effects on transportation efficiency, resource allocation, transport safety, and satisfaction among medical staff. The average delivery time of goods significantly decreased following the adoption of the intelligent delivery system combined with automated track logistics ( P

Summary: As an opportunistic pathogen, Pseudomonas aeruginosa can cause both acute and chronic infections that are notoriously difficult to treat. However, the mechanism underlying acute or chronic P. aeruginosa infection remains unclear. Here, we identify a mutation in a transcriptional regulator PA5438 (named GavR). This mutation causes a 3-amino-acid absence in GavR and is strongly associated with chronic P. aeruginosa infection. Mechanistically, the deletion in GavR directly downregulates the transcription of the aceEF operon and leads to an accumulation of intracellular pyruvate, which can promote bacterial survival in neutrophils. Notably, P. aeruginosa with 9-bp-deleted or full-length gavR composes a mixed population in most patients with chronic or acute infections. Overall, the mutation in gavR attenuates P. aeruginosa virulence and enhances innate immune evasion by reprogramming pyruvate metabolism and the glyoxylate cycle. This work reveals a molecular mechanism of transition control from acute to chronic infection in P. aeruginosa.

BackgroundAlthough immunoglobulin (Ig) alleles play a pivotal role in the antibody response to pathogens, research to understand their role in the humoral immune response is still limited.MethodsWe retrieved the germline sequences for the IGHV from the IMGT database to illustrate the amino acid polymorphism present within germline sequences of IGHV genes. We aassembled the sequences of IgM and IgD repertoire from 130 people to investigate the genetic variations in the population. A dataset comprising 10,643 SARS-CoV-2 spike-specific antibodies, obtained from COV-AbDab, was compiled to assess the impact of SARS-CoV-2 infection on allelic gene utilization. Binding affinity and neutralizing activity were determined using bio-layer interferometry and pseudovirus neutralization assays. Primary docking was performed using ZDOCK (3.0.2) to generate the initial conformation of the antigen-antibody complex, followed by simulations of the complete conformations using Rosetta SnugDock software. The original and simulated structural conformations were visualized and presented using ChimeraX (v1.5).ResultsWe present an allelic atlas of immunoglobulin heavy chain (IgH) variable regions, illustrating the diversity of allelic variants across 33 IGHV family germline sequences by sequencing the IgH repertoire of in the population. Our comprehensive analysis of SARS-CoV-2 spike-specific antibodies revealed the preferential use of specific Ig alleles among these antibodies. We observed an association between Ig alleles and antibody binding epitopes. Different allelic genotypes binding to the same RBD epitope on the spike show different neutralizing potency and breadth. We found that antibodies carrying the IGHV1-69*02 allele tended to bind to the RBD E2.2 epitope. The antibodies carrying G50 and L55 amino acid residues exhibit potential enhancements in binding affinity and neutralizing potency to SARS-CoV-2 variants containing the L452R mutation on RBD, whereas R50 and F55 amino acid residues tend to have reduced binding affinity and neutralizing potency. IGHV2-5*02 antibodies using the D56 allele bind to the RBD D2 epitope with greater binding and neutralizing potency due to the interaction between D56 on HCDR2 and K444 on RBD of most Omicron subvariants. In contrast, IGHV2-5*01 antibodies using the N56 allele show increased binding resistance to the K444T mutation on RBD.DiscussionThis study provides valuable insights into humoral immune responses from the perspective of Ig alleles and population genetics. These findings underscore the importance of Ig alleles in vaccine design and therapeutic antibody development.

The subcellular localization of Yes-associated protein (YAP) is dynamically regulated by post-transcriptional modifications, critically influencing cardiac function. Despite its significance, the precise mechanism controlling YAP nuclear sequestration and its role in cardiac hypertrophy remain poorly defined. In this study, utilizing immunoprecipitation-mass spectrometry, we identified potential acetylation sites and interacting proteins of YAP. Co-immunoprecipitation and immunofluorescence assays were used to elucidate the protein interactions and subcellular colocalization. We found that YAP protected against ISO-induced pathological cardiac hypertrophy both in vivo and in vitro. During cardiac hypertrophy YAP acetylation increased while its nuclear accumulation reduced without altering Ser127 phosphorylation. Notably, lysine 236 was identified as a novel acetylation site on YAP. Acetylation at K236 facilitated YAP’s nucleic export, suppressed the expression of target genes such as NRF1 and Cox IV, and counteracted YAP's anti-hypertrophic effects. Importantly, deacetylase SIRT6 was identified as a regulator of YAP deacetylation, disrupting the YAP with chaperone protein 14–3–3 interaction and inhibiting YAP’s nuclear export, thereby facilitating cardiac protective role of YAP. This study identified YAP K236 acetylation as a key regulator of its nuclear retention in cardiomyocytes, with SIRT6-mediated deacetylation facilitating YAP’s protective effects against cardiac hypertrophy. Targeting YAP acetylation may offer a promising therapeutic strategy for cardiac hypertrophy.

Background Chronic respiratory diseases (CRDs) have been shown to be associated with frailty, but these findings have not yet reached a consensus. The aim of this study was to investigate the association between CRDs and frailty in the elderly using a nationally representative data from China.Methods Data from the China Health and Retirement Longitudinal Study (CHARLS) were analysed, including 3309 frailty-free participants followed for three waves from 2011. Frailty was assessed using the physical frailty phenotype scale, and CRDs were conformed by self-reported physician diagnoses. Cox proportional hazard models were used to examine the association between baseline CRDs and subsequent frailty.Results Among participants (mean age 67.07 years, 51.53% male), 497 (15.02%) had CRDs. During a mean follow-up of 46 months, 273 (8.25%) participants developed frailty. The incidence rate of frailty was significantly higher in the CRDs group (37.17% per 1000 person-years vs 18.41% per 1000 person-years, p

BackgroundSepsis is a systemic inflammatory response syndrome, with sepsis-associated acute kidney injury (SA-AKI) being a common complication. Insulin resistance (IR) is closely related to the stress response, inflammatory response, and severity of critical illness. The triglyceride-glucose body mass index (TyG-BMI) is a valuable tool for assessing IR. However, the relationships between TyG-BMI and clinical outcomes in patients with SA-AKI remain unclear.MethodsWe conducted a retrospective analysis of ICU patients with SA-AKI using data from the MIMIC-IV database. The Boruta algorithm was employed to select significant features for predicting short-term mortality in SA-AKI patients. Multivariate Cox proportional hazards regression, sensitivity analysis, restricted cubic spline (RCS) models, and Kaplan–Meier (K–M) survival analysis were used to assess the relationship between TyG-BMI and short-term mortality in SA-AKI patients. Subgroup analyses considered the effects of age, sex, ethnicity, comorbidities and septic shock.ResultsThis study included 3,349 patients, with males accounting for 60.5% of the patients. The Boruta analysis identified the TyG-BMI as an important clinical feature. Higher TyG-BMI values were significantly associated with reduced short-term mortality rates (28, 90, and 180 days) in patients with SA-AKI; for each standard deviation increase in TyG-BMI, the risk of all-cause death decreased by 0.2% (p

Neutralizing antibodies are a key component in protective humoral immunity against SARS-CoV-2. Currently, available technologies cannot track epitope-specific antibodies in global antibody repertoires. Thus, the comprehensive repertoire of spike-specific neutralizing antibodies elicited by SARS-CoV-2 infection is not fully understood. We therefore combined high-throughput immunoglobulin heavy chain (IgH) repertoire sequencing, and structural and bioinformatics analysis to establish an antibodyomics pipeline, which enables tracking spike-specific antibody lineages that target certain neutralizing epitopes. We mapped the neutralizing epitopes on the spike and determined the epitope-preferential antibody lineages. This analysis also revealed numerous overlaps between immunodominant neutralizing antibody-binding sites and mutation hotspots on spikes as observed so far in SARS-CoV-2 variants. By clustering 2677 spike-specific antibodies with 360 million IgH sequences that we sequenced, a total of 329 shared spike-specific antibody clonotypes were identified from 33 COVID-19 convalescents and 24 SARS-CoV-2-naïve individuals. Epitope mapping showed that the shared antibody responses target not only neutralizing epitopes on RBD and NTD but also non-neutralizing epitopes on S2. The immunodominance of neutralizing antibody response is determined by the occurrence of specific precursors in human naïve B-cell repertoires. We identified that only 28 out of the 329 shared spike-specific antibody clonotypes persisted for at least 12 months. Among them, long-lived IGHV3-53 antibodies are likely to evolve cross-reactivity to Omicron variants through accumulating somatic hypermutations. Altogether, we created a comprehensive atlas of spike-targeting antibody lineages in COVID-19 convalescents and antibody precursors in human naïve B cell repertoires, providing a valuable reference for future vaccine design and evaluation.

China, with the third largest share of global tuberculosis cases, faces a substantial challenge in its healthcare system as a result of the high burden of multidrug-resistant and rifampicin-resistant tuberculosis (MDR/RR-TB). This study employs a genomic epidemiological approach to assess recent tuberculosis transmissions between individuals, identifying potential risk factors and discerning the role of transmitted resistant isolates in the emergence of drug-resistant tuberculosis in China. We conducted a population-based retrospective study on 5052 Mycobacterium tuberculosis (MTB) isolates from 70 surveillance sites using whole genome sequencing (WGS). Minimum spanning tree analysis identified resistance mutations, while epidemiological data analysis pinpointed transmission risk factors. Of the 5052 isolates, 23% (1160) formed 452 genomic clusters, with 85.6% (387) of the transmissions occurring within the same counties. Individuals with younger age, larger family size, new cases, smear positive, and MDR/RR were at higher odds for recent transmission, while higher education (university and above) and occupation as a non-physical workers emerged as protective factors. At least 61.4% (251/409) of MDR/RR-TB were likely a result of recent transmission of MDR/RR isolates, with previous treatment (crude OR = 2.77), smear-positive (cOR = 2.07) and larger family population (cOR = 1.13) established as risk factors. Our findings highlight that local transmission remains the predominant form of TB transmission in China. Correspondingly, drug-resistant tuberculosis is primarily driven by the transmission of resistant tuberculosis isolates. Targeted interventions for high-risk populations to interrupt transmission within the country will likely provide an opportunity to reduce the prevalence of both tuberculosis and drug-resistant tuberculosis.

Background To use the three-dimensional (3D) ultrasound for assessment of pelvic floor muscle function in non-diabetic females with insulin resistance (IR), and to evaluate its functional relationship with insulin levels.Methods From October 2022 to November 2023, 216 non-diabetic females with insulin-resistant (IR group) and 118 normal females (control group) were sequentially recruited from our hospital for our study. The 3D ultrasound was used to assess the levator hiatus in resting state for all females regarding diameter lines, perimeters and areas; as well as the Valsalva manoeuvre (VM). The t-test and linear regression model were used to analyse the collected data.Results The analysis indicates that there were significant differences in the resting state of the levator hiatus between the IR and the control groups (14.8 ± 5.8 cm2 and 11.6 ± 2.7 cm2, p

The continuous emergence of highly immune-evasive SARS-CoV-2 variants has challenged vaccine efficacy. A vaccine that can provide broad protection is desirable. We evaluated the immunogenicity of a series of monovalent and bivalent adenovirus-vectored vaccines containing the spikes of Wildtype (WT), Beta, Delta, Omicron subvariants BA.1, BA.2, BA.2.12.1, BA.2.13, BA.3, BA.5, BQ.1.1, and XBB. Vaccination in mice using monovalent vaccines elicited the highest neutralizing titers against each self-matched strain, but against other variants were reduced 2− to 73-fold. A bivalent vaccine consisting of WT and BA.5 broadened the neutralizing breadth against pre-Omicron and Omicron subvariants except XBB. Among bivalent vaccines based on the strains before the emergence of XBB, a bivalent vaccine consisting of BA.2 and BA.5 elicited the most potent neutralizing antibodies against Omicron subvariants, including XBB. In mice primed with injected WT vaccine, intranasal booster with a bivalent vaccine containing XBB and BA.5 could elicit broad serum and respiratory mucosal neutralizing antibodies against all late Omicron subvariants, including XBB. In mice that had been sequentially vaccinated with WT and BA.5, intranasal booster with a monovalent XBB vaccine elicited greater serum and mucosal XBB neutralizing antibodies than bivalent vaccines containing XBB. Both monovalent and bivalent XBB vaccines induced neutralizing antibodies against EG.5. Unlike the antibody response, which is highly variant-specific, mice receiving either monovalent or bivalent vaccines elicited comparable T-cell responses against all variants. Furthermore, intranasal but not intramuscular booster induced antigen-specific lung resident T cells. This study provides insights into the design of the COVID-19 vaccine and vaccination strategies.

Abstract Introduction Based on the data from the China Health and Retirement longitudinal study (CHARLS), we aimed to investigate the bidirectional relationship between depressive symptoms and functional disability. Methods Data were collected across 3 waves from 2013 to 2018. The activities of daily living (ADLs) and the instrumental activities of daily living (IADLs) scales were used to measure functional disability and the CESD-10 was used to measure depressive symptoms. Cross-lagged models were performed to examine cross effect between depressive symptoms and functional disability across three waves. Results Data on 10,092(mean [SD] age, 61.98[8.44] years; 3764 females [37.30%]) and 10,180 participants (mean [SD] age, 62.01[8.46] years; 3788 females [37.21%]) in IADL sample and ADL sample were included in the analyses. For IADL disability, the cross-lagged model shows a bidirectional association across three waves; the multivariable GEE model revealed that changes in CESD-10 score across waves were associated with worse IADL disability (β ranges: 0.08–0.10) and vice versa, worsen of IADL disability ascending developing of CESD-10 score (β ranges: 0.09–0.10). For ADL disability, the cross-lagged model shows a bidirectional association across three waves; the multivariable GEE model revealed that changes of CESD-10 score across waves were associated with worse IADL disability (β ranges: 0.08–0.10) and vice versa, worsen of IADL disability ascending developing of CESD-10 score (β ranges: 0.09–0.10). Discussion Study findings underscore a significant bidirectional between depressive symptoms and functional disability in older adults. Thus, simultaneous intervention should be taken to manage the mutual development of functional disability and depression.

Abstract Continued evolution of SARS-CoV-2 generates variants to challenge antibody immunity established by infection and vaccination. A connection between population immunity and genesis of virus variants has long been suggested but its molecular basis remains poorly understood. Here, we identify a class of SARS-CoV-2 neutralizing public antibodies defined by their shared usage of VL6-57 light chains. Although heavy chains of diverse genotypes are utilized, convergent HCDR3 rearrangements have been observed among these public antibodies to cooperate with germline VL6-57 LCDRs to target a convergent epitope defined by RBD residues S371-S373-S375. Antibody repertoire analysis identifies that this class of VL6-57 antibodies is present in SARS-CoV-2-naive individuals and is clonally expanded in most COVID-19 patients. We confirm that Omicron-specific substitutions at S371, S373 and S375 mediate escape of antibodies of the VL6-57 class. These findings support that this class of public antibodies constitutes a potential immune pressure promoting the introduction of S371L/F-S373P-S375F in Omicron variants. The results provide further molecular evidence to support that antigenic evolution of SARS-CoV-2 is driven by antibody mediated population immunity.

Small cell lung cancer (SCLC), one of the histological subtypes of lung cancer, is characterized by high proliferation, early metastasis, susceptibility to drug resistance and recurrence. For several years, SCLC has always been regarded as a homogeneous disease, treated with a unified radiotherapy and chemotherapy strategy. Despite significant early therapeutic effects, drug resistance and recurrence occur quickly, and there is a lack of satisfactory treatment results, which may be due to insufficient understanding of the tumor heterogeneity of SCLC at present. Recently, the concept of SCLC molecular subtype based on the definition of relatively high expression of lineage transcription factors has been proposed in preclinical studies. This article mainly elaborates on the current status and latest findings of SCLC molecular subtype, emphasizing the potential problems that molecular typing may encounter in clinical practice, aiming to promote understanding of the research progress of molecular subtype in SCLC.

Abstract To optimally harness the adjustable capabilities of reactive power sources for voltage control, a dynamic partitioning method that uses reactive power flow tracking for branch cutting through Binary Particle Swarm Optimisation (BPSO) is proposed for Active Distribution Networks (ADNs). Initially, the limitations of existing Voltage/Var Sensitivity (VVS) calculation methods are analysed, leading to the proposition of a novel VVS calculation method capable of capturing variations in source‐load timing characteristics. Subsequently, the fuzzification of the VVS matrix between nodes is used to derive the membership degree matrix. Next, based on the membership relationship between reactive power source nodes, these nodes are pre‐partitioned, and the number of leading nodes and zones alongside are preliminarily determined. Then, the range of the branch to be cut is established, guided by the reactive power flow direction of the branch. Employing the zonal comprehensive coupling degree as the objective function of the BPSO facilitates the identification of optimal branch cutting points, thereby determining the partitioning outcome. Finally, a reactive power reserve check is executed to rectify any non‐compliant zones. In this study, numerical simulations are conducted using the enhanced IEEE 33‐node power system to demonstrate the efficacy of the proposed method.

Purpose This study aimed to evaluate changes in ultrafast pulse wave velocity (ufPWV) in individuals with arterial stiffness and subclinical atherosclerosis (subAS), and to provide cutoff values. Methods This retrospective study recruited 231 participants, including 67 patients with subAS. The pulse wave velocity was measured at the beginning and end of systole (PWV-BS and PWVES, respectively) using ultrafast ultrasonography to assess arterial stiffness. The right and left common carotid arteries were measured separately, and laboratory metabolic parameters were also collected. Participants were balanced between groups using propensity score matching (PSM) at a 1:1 ratio, adjusting for age, sex, and waist-to-hip ratio as potential confounders. Cutoff values of ufPWV for monitoring subAS were determined via receiver operating characteristic (ROC) curve analysis. Results PWV-ES, unlike PWV-BS, was higher in the subAS subgroup than in the subAS-free group after PSM (all P0.05). Conclusion PWV-ES measured using ultrafast ultrasonography was significantly higher in individuals with subAS than in those without. Specific PWV-ES cutoff values showed potential for predicting an increased risk of subAS.

Abstract The upper respiratory tract is the initial site of SARS-CoV-2 infection. Nasal spike-specific secretory immunoglobulin A (sIgA) correlates with protection against Omicron breakthrough infection. We report that intranasal vaccination using human adenovirus serotype 5 (Ad5) vectored Omicron spike in people who previously vaccinated with ancestral vaccine could induce robust neutralizing sIgA in the nasal passage. Nasal sIgA was predominantly present in dimeric and multimeric forms and accounted for nearly 40% of total proteins in nasal mucosal lining fluids (NMLFs). A low-level IgG could also be detected in NMLFs but not IgM, IgD, and IgE. After a complete nasal wash, sIgA in the nasal passage could be replenished rapidly within a few hours. A comparison of purified paired serum IgA, serum IgG, and nasal sIgA from the same individuals showed that sIgA was up to 3-logs more potent than serum antibodies in binding to spikes and in neutralizing Omicron subvariants. Serum IgG and IgA failed to neutralize XBB and BA.2.86, while nasal sIgA retained potent neutralization against these newly emerged variants. Further analysis showed that sIgA was more effective than IgG or IgA in blocking spike-mediated cell-to-cell transmission and protecting hACE2 mice from XBB challenge. Using a sIgA monoclonal antibody as a reference, we estimated that the total nasal sIgA contains about 2.6–3.9% spike-specific sIgA in NMLFs collected approximately one month after intranasal vaccination. Our study provided insights for developing intranasal vaccines that can induce sIgA to build an effective and mutation-resistant first-line immune barrier against constantly emerging variants.

Abstract Tumor-draining lymph nodes (TDLNs) are usually the first station of tumor metastasis in lung cancer. TDLNs+ have distinct pathomorphologic and tumor microenvironment (TME)-compositional patterns, which still need to be thoroughly investigated in lung adenocarcinoma (LUAD). Here, we enrolled 312 LUAD patients with TDLNs+ from our institution between 2015 and 2019. 3DHISTECH was used to scan all of the TDLNs+. Based on morphologic features, TDLNs+ patterns were classified as polarized-type or scattered-type, and TME-compositional patterns were classified as colloid-type, necrosis-type, specific-type, and common-type. Multivariate analysis revealed an increased risk of early recurrence associated with scattered-type (HR 2.37, 95% CI: 1.06–5.28), colloid-type (HR 1.95, 95% CI: 1.03–3.67), and necrosis-type (HR 2.21, 95% CI: 1.13–4.89). NanoString transcriptional analysis revealed an immunosuppression and vascular invasion hallmark in scattered and necrosis patterns and an immunoactivated hallmark in polarized and common patterns. According to imaging mass cytometry (IMC), the scattered and necrosis patterns revealed that germinal centers (GC) were compromised, GCB cell and T cell proliferation were deficient, tumor cells had the potential for proliferation, and the immune attack may be weaker. In this study, we present evidence that LUAD patients have distinct patterns and immune hallmarks of TDLNs+ related to their prognosis.

Background: Annual influenza vaccination is crucially recommended for the elderly to maintain humoral immunity. Insufficient coverage requires us to understand the determinants of their influenza behaviors and how these patterns impact vaccination choices. Methods: Data from 540 Beijing residents aged over 65 were collected through interviews, capturing vaccination history and sociodemographic details. Individual influenza vaccination records from 2016 to 2020 were obtained from China’s Immunization Information Systems. A latent class model identified three vaccination patterns. Multinomial logistic regression assessed relative risk ratios (RRRs) for vaccination based on sociodemographic factors. Vaccination patterns were used to predict future vaccination likelihood. Results: The analysis revealed three groups: sporadically vaccinated (63.33%), occasionally vaccinated (18.71%), and frequently vaccinated (17.96%). Factors associated with frequent vaccination included age over 70 (RRR = 2.81), lower income (RRR = 0.39), higher vaccine hesitancy (RRR = 3.10), multiple chronic conditions (RRR = 2.72), and rural residence (RRR = 2.48). The frequently vaccinated group was more likely to sustain regular vaccination habits in subsequent years compared to the occasionally vaccinated group. Conclusions: Only 17.96% of Beijing’s older population exhibited a consistent influenza vaccination pattern. Older age, rural residency, and chronic diseases correlated with repeated influenza vaccination. Segmenting the population based on past vaccination behavior can aid in designing targeted interventions to improve vaccination rates.

Abstract This study investigates the role of school principals’ instructional leadership as a predictor of teachers’ professional development. The research sample comprised 304 secondary school teachers and 19 principals in Awka South, Anambra State, Nigeria. The study adopts Hallinger and Murphy’s (1985) Instructional Leadership Model. Data were collected using the “Principal’s Instructional Leadership Practices and Teachers’ Professional Development” (PILPTPD) tool. Correlation analysis was utilized to explore the relationship between school principals’ instructional leadership and teachers’ professional development, while multiple regression analysis was employed to ascertain the predictive capacity of instructional leadership on teacher professional development. The results reveal significant associations between instructional leadership and teacher professional development and growth. Ultimately, instructional leadership emerges as a significant predictor of teacher professional development. This study contributes to the expanding literature emphasizing the nexus between principal instructional leadership and teacher professional development, shedding light on the mediating role of principals’ leadership in influencing teachers’ professional development and instructional practices.

Abstract Gut microbiota can regulate the metabolic and immunological aspects of ischemic stroke and modulate the treatment effects. The present study aimed to identify specific changes in gut microbiota in patients with large vessel occlusion (LVO) ischemic stroke and assess the potential association between gut microbiota and clinical features of ischemic stroke. A total of 63 CSVD patients, 64 cerebral small vessel disease (CSVD) patients, and 36 matching normal controls (NCs) were included in this study. The fecal samples were collected for all participants and analyzed for gut microbiota using 16S rRNA gene sequencing technology. The abundances of five gut microbiota, including genera Bifidobacterium, Butyricimonas, Blautia, and Dorea and species Bifidobacterium_longum, showed significant changes with high specificity in the LVO patients as compared to the NCs and CSVD patients. In LVO patients, the genera Bifidobacterium and Blautia and species Bifidobacterium_longum were significantly correlated with the National Institutes of Health Stroke Scale (NIHSS) scores at the admission and discharge of the patients. Serum triglyceride levels could significantly affect the association of the abundance of genus Bifidobacterium and species Bifidobacterium_longum with the NIHSS scores at admission and modified Rankin Scale (mRS) at discharge in LVO patients. The identification of five gut microbiota with high specificity were identified in the early stage of LVO stroke, which contributed to performed an effective clinical management for LVO ischemic stroke.

The daily precipitation data of Kunming Station for nearly 30 years from 1991 to 2020 were used to calculate the beginning and ending periods of Kunming rainy season （May-October）， further determine the length of the rainy season in Kunming.Additionally， statistical yearbook data for Yunnan Province and Kunming City were used， including year-end total population， urban built-up area， urbanization rate， per capita GDP， and other urban development factors， to determine the urban development process in Kunming.This process divided Kunming's urban development into a slow period （1991 -2003） and a fast period （2004 -2020）.The characteristics and differences in the length of the rainy season in Kunming City during these two periods were then analyzed and compared.Various analytical methods， including statistical analysis， wavelet analysis， and Mann-Kendall （M-K） mutation test， were employed to systematically analyze the temporal changes in the length of the rainy season in Kunming City.Additionally， the grey correlation analysis method was used to assess the correlation between the length of the rainy season and urban development in Kunming City.The results indicate that from 1991 to 2020， the start date of Kunming City's rainy season gradually became later， while the end date gradually became earlier， resulting in an overall trend of the rainy season getting shorter.Wavelet coefficient analysis revealed that there was no obvious regularity in the variation of the rainy season's length on time scales below 8 years， but on a 17-year time scale， there was a noticeable cycle of short-long-short-long-short variations， The rainy seasons from 2003 to 2008 and from 2014 to 2017 were relatively long， while the rainy seasons from 1991 to 2002， 2009 to 2012， and 2018 to 2020 were relatively short.The unclosed contour lines from 2018 to 2020 indicate a further trend of shortening.The M-K test showed that the length of the rainy season in Kunming City experienced four abrupt changes between 1991 and 2020， Occurring in 2002， 2008， 2012 and 2017.Regarding the relationship between Kunming's urban development and the length of the rainy season， the variation trend of the rainy season length during the slow urban development period remained relatively stable.However， after 2004， during the rapid urban development period， there was a significant reduction in the length of the rainy season in Kunming City， Extreme volatility became more pronounced as the urban development process accelerated.The SPSS （Statistical Product and Service Solutions） was used to predict the duration of rainy season in the next 10 years in Kunming City， The results show that the rainy season will continue to be shorter in the next 10 years in Kunming.When the grey correlation resolution was set at 0.5， four factors representing the urban development process had varying degrees of influence on the length of the rainy season in Kunming City， with correlation coefficients all exceeding 0.70， the results show that there is a significant correlation between the urban development and the length of rainy season in Kunming.Among these factors， the most influential one was the year-end total population， while the least influential was per capita GDP， with grey correlation coefficients of 0.88 and 0.70， respectively， signifying a high and significant correlation.The order of correlation coefficients for the four factors is as follows： year-end total population > urbanization rate > urban built-up area > per capita GDP.

Empowering leadership has been widely recognized as an effective approach to enhancing new product development performance in Western countries. However, it was not so prevalent in Chinese R&D team management. This study reported here examined the relationship between empowering leadership and new product development performance (i.e., new product creativity, and new product development speed) by focusing on the mediating effect of job autonomy, direct and moderating effects of error aversion culture to find out the reasons. Data collected from a two-wave survey involving 107 superiors and 387 subordinates in 107 R&D teams in China was used to conduct analysis of hierarchical multiple regression. The results revealed two key findings. Firstly, empowering leadership was found to have no significant association with new product development speed which was the primary performance target for Chinese R&D teams. Secondly, while empowering leadership was positively associated with new product creativity when mediated by job autonomy, the widespread presence of an error aversion culture in China significantly reduced job autonomy within R&D teams and negatively moderated the relationship between empowering leadership and job autonomy. Consequently, empowering leadership had no impact on new product creativity when error aversion culture was high. The implications of these findings were discussed in the context of Chinese R&D teams, aiming to highlight potential avenues for improving new product development performance through leadership interventions.

Many inflammatory disorders, including diabetic kidney disease (DKD), are associated with pyroptosis, a type of inflammation-regulated cell death. The purpose of this work was to ascertain the effects of apabetalone, which targets BRD4, a specific inhibitor of the bromodomain (BRD) and extra-terminal (BET) proteins that target bromodomain 2, on kidney injury in DKD. This study utilized pharmacological and genetic approaches to investigate the effects of apabetalone on pyroptosis in db/db mice and human tubular epithelial cells (HK-2). BRD4 levels were elevated in HK-2 cells exposed to high glucose and in db/db mice. Modulating BRD4 levels led to changes in the generation of inflammatory cytokines and cell pyroptosis linked to NLRP3 inflammasome in HK-2 cells and db/db mice. Likewise, these cellular processes were mitigated by apabetalone through inhibition BRD4. Apabetalone or BRD4 siRNA suppressed PLK1 expression in HK-2 cells under high glucose by P300-dependent H3K27 acetylation on the PLK1 gene promoter, as demonstrated through chromatin immunoprecipitation and immunoprecipitation assays. To summarize, apabetalone relieves renal proptosis and fibrosis in DKD. BRD4 regulates the P300/H3K27ac/PLK1 axis, leading to the activation of the NLRP3 inflammasome and subsequent cell pyroptosis, inflammation, and fibrosis. These results may provide new perspectives on DKD treatment.

BackgroundThe diagnosis of major depressive disorder (MDD) mainly depends on subjective clinical symptoms, without an acceptable objective biomarker for the clinical application of MDD. Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) showed a high specificity as biomarker for the diagnosis and treatment of MDD. The present study aimed to investigate differences in plasma ITIH4 in two different aged MDD patients and underlying pathological mechanisms of plasma ITIH4 in the occurrence and development of MDD.MethodsSixty-five adult MDD patients, 51 adolescent MDD patients, and 64 healthy controls (HCs) were included in the present study. A 14-days’ antidepressive treatment was conducted in all MDD patients. Psychological assessments were performed and plasma ITIH4 and astrocyte-related markers were detected for all participants.Results(1) Plasma levels of ITIH4 in adult MDD patients were significantly higher than adolescent MDD patients and HCs, and significantly increased plasma ITIH4 levels was observed in adolescent MDD patients compared with HCs (2). There were positive correlations between plasma ITIH4 levels and 24-item Hamilton Depression Scale (HAMD-24) scores and plasma glial fibrillary acidic protein (GFAP) levels in MDD patients, however, plasma ITIH4 levels were significantly correlated with age just in adult MDD patients (3). Plasma ITIH4 showed area under the curve values of 0.824 and 0.729 to differentiate adult MDD patients and adolescent MDD patients from HCs, respectively (4). There was significant decrease in plasma levels of ITIH4 between before and after antidepressive treatment in adult MDD patients, but not in adolescent MDD patients (5). Changed value of ITIH4 levels were correlated with the changed value of GFAP levels and changed rate of HAMD-24 scores in adult MDD patients following antidepressive treatment.ConclusionPlasma ITIH4 may be potential plasma biomarkers of MDD with age-related specificity, which was associated with depressive symptoms astrocyte-related pathologic changes, and antidepressive treatment efficacy.

Determining the fertilization rate plays a pivotal role in agronomic practices as they directly impact yield targets, soil fertility, and environmental risks. In this study, we proposed a method that utilizes allowed ranges of partial nutrient balance and yield to estimate the threshold of nitrogen (N), phosphorus (P), and potassium (K) fertilizer applied to rice (Oryza sativa L.) fields in China. Based on a dataset of 6792 observations from rice fields, we determined the minimum and maximum rates of N, P and K suggested for single (mono-season rice), middle (summer-season rice rotated with winter-season upland crop), early and late (double-season rice cropping system) rice, ranging between 114−146 and 220−292 kg N ha−1 per season, 56−74 and 112−149 kg P2O5 ha−1 per season, and 170−230 and 329−347 kg K2O ha−1 per season, respectively. These values serve as the lower and upper fertilization thresholds, guiding yield goals and environmental protection. Furthermore, if rice straw is returned to fields, the demand for K fertilizer can theoretically decrease by 183 kg K2O ha−1, with corresponding decreases of 50 kg N ha−1 and 26 kg P2O5 ha−1, respectively. A recommended fertilization approach, excluding returned straw nutrients from the upper fertilization thresholds, suggested average application rates of 194 kg N ha−1, 105 kg P2O5 ha−1, and 157 kg K2O ha−1, which align well with the nutrient requirements of rice. Additionally, substituting organic N for chemical N is an effective approach to conserve chemical fertilizer N, potentially reducing chemical N usage by 20%−40%. Utilizing slow-release N is also a favorable option to enhance N use efficiency and optimize N balance. This study offers valuable insights into the development of fertilization restriction indicators, aiming to achieve a delicate balance between environmental impact and agricultural productivity through the adoption of balanced fertilization rates and utilization of organic residues.

Abstract Phase transition is a fundamental phenomenon in condensed matter physics, in which states of matter transform to each other with various critical behaviors under different conditions. The magnetic martensitic transformation features significant multi‐caloric effects that benefit the solid‐state cooling or heat pumping. Meanwhile, the electronic topological transition (ETT) driven by pressure has been rarely reported in martensitic systems. Here, the modulation effects of hydrostatic pressure on phase transitions in a magnetic martensitic alloy are reported. Owing to the huge volume expansion during the transition, the martensitic transition temperature is driven from 339 to 273 K by pressure within 1 GPa, resulting in highly tunable giant baro‐ and magneto‐caloric effects (BCE and MCE) in a wide working temperature range. Interestingly, an ETT is further induced by pressure in the martensite phase, with a sudden drop of the measured saturation magnetization around 0.6 GPa. First‐principles calculations reveal a sharp change in the density of states (DOS) due to the orbit shift around the Fermi level at the same pressure and reproduce the experimental observation of magnetization. Besides, the ETT is accompanied by remarkable changes in the lattice parameters and the unit‐cell orthorhombicity. The study provides insight into pressure‐modulated exotic phase‐transition phenomena in magnetic martensitic systems.

Abstract Objective To create a deep‐learning automatic segmentation model for esophageal cancer (EC), metastatic lymph nodes (MLNs) and their adjacent structures using the UperNet Swin network and computed tomography angiography (CTA) images and to improve the effectiveness and precision of EC automatic segmentation and TN stage diagnosis. Methods Attention U‐Net, UperNet Swin, UNet++ and UNet were used to train the EC segmentation model to automatically segment the EC, esophagus, pericardium, aorta and MLN from CTA images of 182 patients with postoperative pathologically proven EC. The Dice similarity coefficient (DSC), sensitivity, and positive predictive value (PPV) were used to assess their segmentation effectiveness. The volume of EC was calculated using the segmentation results, and the outcomes and times of automatic and human segmentation were compared. All statistical analyses were completed using SPSS 25.0 software. Results Among the four EC autosegmentation models, the UperNet Swin had the best autosegmentation results with a DSC of 0.7820 and the highest values of EC sensitivity and PPV. The esophagus, pericardium, aorta and MLN had DSCs of 0.7298, 0.9664, 0.9496 and 0.5091. The DSCs of the UperNet Swin were 0.6164, 0.7842, 0.8190, and 0.7259 for T1‐4 EC. The volume of EC and its adjacent structures between the ground truth and UperNet Swin model were not significantly different. Conclusions The UperNet Swin showed excellent efficiency in autosegmentation and volume measurement of EC, MLN and its adjacent structures in different T stage, which can help to T and N stage diagnose EC and will save clinicians time and energy.

Abstract Background Nitrogen (N) is essential for plant growth and development. In Lithocarpus polystachyus Rehd., a species known for its medicinal and food value, phlorizin is the major bioactive compound with pharmacological activity. Research has revealed a positive correlation between plant nitrogen (N) content and phlorizin synthesis in this species. However, no study has analyzed the effect of N fertilization on phlorizin content and elucidated the molecular mechanisms underlying phlorizin synthesis in L. polystachyus. Results A comparison of the L. polystachyus plants grown without (0 mg/plant) and with N fertilization (25, 75, 125, 175, 225, and 275 mg/plant) revealed that 75 mg N/plant fertilization resulted in the greatest seedling height, ground diameter, crown width, and total phlorizin content. Subsequent analysis of the leaves using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) detected 150 metabolites, including 42 flavonoids, that were differentially accumulated between the plants grown without and with 75 mg/plant N fertilization. Transcriptomic analysis of the L. polystachyus plants via RNA sequencing revealed 162 genes involved in flavonoid biosynthesis, among which 53 significantly differed between the N-treated and untreated plants. Fertilization (75 mg N/plant) specifically upregulated the expression of the genes phenylalanine ammonia-lyase (PAL), 4-coumarate-CoA ligase (4CL), and phlorizin synthase (PGT1) but downregulated the expression of trans-cinnamate 4-monooxygenase (C4H), shikimate O-hydroxycinnamoyltransferase (HCT), and chalcone isomerase (CHI), which are related to phlorizin synthesis. Finally, an integrated analysis of the transcriptome and metabolome revealed that the increase in phlorizin after N fertilization was consistent with the upregulation of phlorizin biosynthetic genes. Quantitative real-time PCR (qRT‒PCR) was used to validate the RNA sequencing data. Thus, our results indicated that N fertilization increased phlorizin metabolism in L. polystachyus by regulating the expression levels of the PAL, PGT1, 5-O-(4-coumaroyl)-D-quinate 3’-monooxygenase (C3’H), C4H, and HCT genes. Conclusions Our results demonstrated that the addition of 75 mg/plant N to L. polystachyus significantly promoted the accumulation of flavonoids, including phlorizin, and the expression of flavonoid synthesis-related genes. Under these conditions, the genes PAL, 4CL, and PGT1 were positively correlated with phlorizin accumulation, while C4H, CHI, and HCT were negatively correlated with phlorizin accumulation. Therefore, we speculate that PAL, 4CL, and PGT1 participate in the phlorizin pathway under an optimal N environment, regulating phlorizin biosynthesis. These findings provide a basis for improving plant bioactive constituents and serve as a reference for further pharmacological studies.

Abstract Background Genital infection with Chlamydia trachomatis (C. trachomatis) is a major public health issue worldwide. It can lead to cervicitis, urethritis, and infertility. This study was conducted to determine the characteristics of genital C. trachomatis infection among women attending to the infertility and gynecology clinics. Methods Endocervical swabs were collected from 8,221 women for C. trachomatis nucleotide screening and genotyping, while serum samples were collected for C. trachomatis pgp3 antibody determination using luciferase immunosorbent assays. Results High C. trachomatis DNA prevalence (3.76%) and seroprevalence (47.46%) rates were found, with genotype E (27.5%) being the most prevalent. C. trachomatis omp1 sense mutation was associated with cervical intraepithelial neoplasia (CIN) (odds ratio [OR] = 6.033, 95% confidence interval [CI] = 1.219–39.185, p = 0.045). No significant differences in C. trachomatis seroprevalence rates were observed between women with detectable C. trachomatis DNA in the infertility and routine physical examination groups (86.67% vs. 95%, p > 0.05); however, among women with negative C. trachomatis DNA, the former group had a markedly higher seroprevalence than the latter group (56.74% vs. 20.17%, p

Abstract Hard carbons are emerging as the most viable anodes to support the commercialization of sodium-ion (Na-ion) batteries due to their competitive performance. However, the hard carbon anode suffers from low initial Coulombic efficiency (ICE), and the ambiguous Na-ion (Na+) storage mechanism and interfacial chemistry fail to give a reasonable interpretation. Here, we have identified the time-dependent ion pre-desolvation on the nanopore of hard carbons, which significantly affects the Na+ storage efficiency by altering the solvation structure of electrolytes. Consummating the pre-desolvation by extending the aging time, generates a highly aggregated electrolyte configuration inside the nanopore, resulting in negligible reductive decomposition of electrolytes. When applying the above insights, the hard carbon anodes achieve a high average ICE of 98.21% in the absence of any Na supplementation techniques. Therefore, the negative-to-positive capacity ratio can be reduced to 1.02 for full cells, which enables an improved energy density. The insight into hard carbons and related interphases may be extended to other battery systems and support the continued development of battery technology.

Abstract Two-dimensional metal-organic frameworks (MOFs) have a wide variety of applications in molecular separation and other emerging technologies, including atomically thin electronics. However, due to the inherent fragility and strong interlayer interactions, high-quality MOF crystals of atomic thickness, especially isolated MOF crystal monolayers, have not been easy to prepare. Here, we report the self-condensation-assisted chemical vapour deposition growth of atomically thin MOF single-crystals, yielding monolayer single-crystals of poly[Fe(benzimidazole)2] up to 62 μm in grain sizes. By using transmission electron microscopy and high-resolution atomic force microscopy, high crystallinity and atomic-scale single-crystal structure are verified in the atomically MOF flakes. Moreover, integrating such MOFs with MoS2 to construct ultrathin van der Waals heterostructures is achieved by direct growth of atomically MOF single-crystals onto monolayer MoS2, and enables a highly selective ammonia sensing. These demonstrations signify the great potential of the method in facilitating the development of the fabrication and application of atomically thin MOF crystals.

Abstract The cosmic-ray spectrum structures help to study the acceleration and propagation mechanism of ultra-high energy cosmic rays, and these structures were predicted to culminate in a cut-off, named the Greisen–Zatsepin–Kuzmin (GZK) cut-off, near $$5\times 10^{19}~\textrm{eV}$$ 5 × 10 19 eV as a result of the inelastic interaction of protons with the $$2.73~\textrm{K}$$ 2.73 K black body radiation. The confirmation of the existence of GZK cut-off was tortuous, leading to activities to explore new physics, such as the cosmic-ray new components, unidentified cosmic-ray origins, unknown propagation mechanism and the modification of fundamental physics concepts like the tiny Lorentz invariance violation (LV). The confirmation of the GZK cut-off provides an opportunity to constrain the LV effect. We use a phenomenological framework to restudy the GZK mechanism under the Planck scale deformation of the proton and pion dispersion relations. Restudying the photon induced pion production of the proton $$\textrm{p}+\gamma \rightarrow \textrm{p}+\pi ^0$$ p + γ → p + π 0 , we predict abnormal threshold behaviors of this reaction under different LV modifications. Therefore we can study the LV effects not only from the conventional GZK cut-off, but also from potentially threshold anomalies of the pion production process. We divide the LV parameter space into three regions, and analyze the constraints from current observations in each region. The current observations have set strict restrictions on a certain LV region. However, for others LV regions, further experimental observations and theoretical researches are still needed, and we also find survival space for some theoretical explorations that permit specific LV effects.

Abstract In plant immunity, a well-orchestrated cascade is initiated by the dimerization of receptor-like kinases (RLKs), followed by the phosphorylation of receptor-like cytoplasmic kinases (RLCKs) and subsequent activation of NADPH oxidases for ROS generation. Recent findings by Zhong et al. illustrated that a maize signaling module comprising ZmWAKL-ZmWIK-ZmBLK1-ZmRBOH4 governs quantitative disease resistance to grey leaf spot, a pervasive fungal disease in maize worldwide, unveiling the conservation of this signaling quartet in plant immunity.