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Background Heart failure (HF) is a serious condition with increasing prevalence, high morbidity, and increased mortality. Obesity is an established risk factor for HF. Fluctuation in body mass index (BMI) has shown a higher risk of cardiovascular outcomes. We investigated the association between BMI variability and incident HF. Methods and Results In the UK Biobank, we established a prospective cohort after excluding participants with prevalent HF or cancer at enrollment. A total of 99 368 White participants with ≥3 BMI measures during >2 years preceding enrollment were included, with a median follow‐up of 12.5 years. The within‐participant variability of BMI was evaluated using standardized SD and coefficient of variation. The association of BMI variability with incident HF was assessed using Fine and Gray's competing risk model, adjusting for confounding factors and participant‐specific rate of BMI change. Higher BMI variability measured in both SD and coefficient of variation was significantly associated with higher risk in HF incidence (SD: hazard ratio [HR], 1.05 [95% CI, 1.03–1.08], P

Abstract Allogeneic Vγ9Vδ2 (Vδ2) T cells have emerged as attractive candidates for developing cancer therapy due to their established safety in allogeneic contexts and inherent tumor-fighting capabilities. Nonetheless, the limited clinical success of Vδ2 T cell-based treatments may be attributed to donor variability, short-lived persistence, and tumor immune evasion. To address these constraints, we engineer Vδ2 T cells with enhanced attributes. By employing CD16 as a donor selection biomarker, we harness Vδ2 T cells characterized by heightened cytotoxicity and potent antibody-dependent cell-mediated cytotoxicity (ADCC) functionality. RNA sequencing analysis supports the augmented effector potential of Vδ2 T cells derived from CD16 high (CD16Hi) donors. Substantial enhancements are further achieved through CAR and IL-15 engineering methodologies. Preclinical investigations in two ovarian cancer models substantiate the effectiveness and safety of engineered CD16Hi Vδ2 T cells. These cells target tumors through multiple mechanisms, exhibit sustained in vivo persistence, and do not elicit graft-versus-host disease. These findings underscore the promise of engineered CD16Hi Vδ2 T cells as a viable therapeutic option for cancer treatment.

Summary: Ovarian cancer (OC) is highly lethal due to late detection and frequent recurrence. Initial treatments, comprising surgery and chemotherapy, lead to disease remission but are invariably associated with subsequent relapse. The identification of novel therapies and an improved understanding of the molecular and cellular characteristics of OC are urgently needed. Here, we conducted a comprehensive analysis of primary tumor cells and their microenvironment from 16 chemonaive and 10 recurrent OC patient samples. Profiling OC tumor biomarkers allowed for the identification of potential molecular targets for developing immunotherapies, while profiling the microenvironment yielded insights into its cellular composition and property changes between chemonaive and recurrent samples. Notably, we identified CD1d as a biomarker of the OC microenvironment and demonstrated its targeting by invariant natural killer T (iNKT) cells. Overall, our study presents a comprehensive immuno-profiling of OC tumor and microenvironment during disease progression, guiding the development of immunotherapies for OC treatment, especially for recurrent disease.

Abstract Aims Low C-peptide levels, indicating beta-cell dysfunction, are associated with increased within-day glucose variation and hypoglycemia. In advanced type 2 diabetes, severe hypoglycemia and increased glucose variation predict cardiovascular (CVD) risk. The present study examined the association between C-peptide levels and CVD risk and whether it can be explained by visit-to-visit glucose variation and severe hypoglycemia. Materials and methods Fasting C-peptide levels at baseline, composite CVD outcome, severe hypoglycemia, and visit-to-visit fasting glucose coefficient of variation (CV) and average real variability (ARV) were assessed in 1565 Veterans Affairs Diabetes Trial participants. Results There was a U-shaped relationship between C-peptide and CVD risk with increased risk with declining levels in the low range ( 1.23 nmol/l, 1.27 [1.00–1.63], p = 0.05). C-peptide levels were inversely associated with the risk of severe hypoglycemia (OR 0.68 [0.60–0.77]) and visit-to-visit glucose variation (CV, standardized beta-estimate − 0.12 [SE 0.01]; ARV, − 0.10 [0.01]) (p

Abstract One unmet challenge in lung cancer diagnosis is to accurately differentiate lung cancer from other lung diseases with similar clinical symptoms and radiological features, such as pulmonary tuberculosis (TB). To identify reliable biomarkers for lung cancer screening, we leverage the recently discovered non-canonical small non-coding RNAs (i.e., tRNA-derived small RNAs [tsRNAs], rRNA-derived small RNAs [rsRNAs], and YRNA-derived small RNAs [ysRNAs]) in human peripheral blood mononuclear cells and develop a molecular signature composed of distinct ts/rs/ysRNAs (TRY-RNA). Our TRY-RNA signature precisely discriminates between control, lung cancer, and pulmonary TB subjects in both the discovery and validation cohorts and outperforms microRNA-based biomarkers, which bears the diagnostic potential for lung cancer screening.

SARS-CoV-2 has caused symptomatic COVID-19 and widespread death across the globe. We sought to determine genetic variants contributing to COVID-19 susceptibility and hospitalization in a large biobank linked to a national United States health system. We identified 19,168 (3.7%) lab-confirmed COVID-19 cases among Million Veteran Program participants between March 1, 2020, and February 2, 2021, including 11,778 Whites, 4,893 Blacks, and 2,497 Hispanics. A multi-population genome-wide association study (GWAS) for COVID-19 outcomes identified four independent genetic variants (rs8176719, rs73062389, rs60870724, and rs73910904) contributing to COVID-19 positivity, including one novel locus found exclusively among Hispanics. We replicated eight of nine previously reported genetic associations at an alpha of 0.05 in at least one population-specific or the multi-population meta-analysis for one of the four MVP COVID-19 outcomes. We used rs8176719 and three additional variants to accurately infer ABO blood types. We found that A, AB, and B blood types were associated with testing positive for COVID-19 compared with O blood type with the highest risk for the A blood group. We did not observe any genome-wide significant associations for COVID-19 severity outcomes among those testing positive. Our study replicates prior GWAS findings associated with testing positive for COVID-19 among mostly White samples and extends findings at three loci to Black and Hispanic individuals. We also report a new locus among Hispanics requiring further investigation. These findings may aid in the identification of novel therapeutic agents to decrease the morbidity and mortality of COVID-19 across all major ancestral populations.

High-throughput sequencing technology has enabled population-based studies of the role of the human microbiome in disease etiology and exposure response. Microbiome data are summarized as counts or composition of the bacterial taxa at different taxonomic levels. An important problem is to identify the bacterial taxa that are associated with a response. One method is to test the association of specific taxon with phenotypes in a linear mixed effect model, which incorporates phylogenetic information among bacterial communities. Another type of approaches consider all taxa in a joint model and achieves selection via penalization method, which ignores phylogenetic information. In this paper, we consider regression analysis by treating bacterial taxa at different level as multiple random effects. For each taxon, a kernel matrix is calculated based on distance measures in the phylogenetic tree and acts as one variance component in the joint model. Then taxonomic selection is achieved by the lasso (least absolute shrinkage and selection operator) penalty on variance components. Our method integrates biological information into the variable selection problem and greatly improves selection accuracies. Simulation studies demonstrate the superiority of our methods versus existing methods, for example, group-lasso. Finally, we apply our method to a longitudinal microbiome study of Human Immunodeficiency Virus (HIV) infected patients. We implement our method using the high performance computing language Julia. Software and detailed documentation are freely available at https://github.com/JingZhai63/VCselection.

Aims: The association of glycemic variability with microvascular disease complications in type 2 diabetes (T2D) has been under-studied and remains unclear. We investigated this relationship using both Action to Control Cardiovascular Risk in Diabetes (ACCORD) and the Veteran Affairs Diabetes Trial (VADT).Methods: In ACCORD, fasting plasma glucose (FPG) was measured 1 to 3 times/year for up to 84 months in 10 251 individuals. In the VADT, FPG was measured every 3 months for up to 87 months in 1791 individuals. Variability measures included coefficient of variation (CV) and average real variability (ARV) for fasting glucose. The primary composite outcome was time to either severe nephropathy or retinopathy event and secondary outcomes included each outcome individually. To assess the association, we considered variability measures as time-dependent covariates in Cox proportional hazard models. We conducted a meta-analysis across the 2 trials to estimate the risk of fasting glucose variability as well as to assess the heterogenous effects of FPG variability across treatment arms.Results: In both ACCORD and the VADT, the CV and ARV of FPG were associated with development of future microvascular outcomes even after adjusting for other risk factors, including measures of average glycemic control (ie, cumulative average of HbA1c). Meta-analyses of these 2 trials confirmed these findings and indicated FPG variation may be more harmful in those with less intensive glucose control.Conclusions: This post hoc analysis indicates that variability of FPG plays a role in, and/or is an independent and readily available marker of, development of microvascular complications in T2D. [ABSTRACT FROM AUTHOR]

Objective To assess the uptake of second line antihyperglycaemic drugs among patients with type 2 diabetes mellitus who are receiving metformin.Design Federated pharmacoepidemiological evaluation in LEGEND-T2DM.Setting 10 US and seven non-US electronic health record and administrative claims databases in the Observational Health Data Sciences and Informatics network in eight countries from 2011 to the end of 2021.Participants 4.8 million patients (≥18 years) across US and non-US based databases with type 2 diabetes mellitus who had received metformin monotherapy and had initiated second line treatments.Exposure The exposure used to evaluate each database was calendar year trends, with the years in the study that were specific to each cohort.Main outcomes measures The outcome was the incidence of second line antihyperglycaemic drug use (ie, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, and sulfonylureas) among individuals who were already receiving treatment with metformin. The relative drug class level uptake across cardiovascular risk groups was also evaluated.Results 4.6 million patients were identified in US databases, 61 382 from Spain, 32 442 from Germany, 25 173 from the UK, 13 270 from France, 5580 from Scotland, 4614 from Hong Kong, and 2322 from Australia. During 2011-21, the combined proportional initiation of the cardioprotective antihyperglycaemic drugs (glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors) increased across all data sources, with the combined initiation of these drugs as second line drugs in 2021 ranging from 35.2% to 68.2% in the US databases, 15.4% in France, 34.7% in Spain, 50.1% in Germany, and 54.8% in Scotland. From 2016 to 2021, in some US and non-US databases, uptake of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors increased more significantly among populations with no cardiovascular disease compared with patients with established cardiovascular disease. No data source provided evidence of a greater increase in the uptake of these two drug classes in populations with cardiovascular disease compared with no cardiovascular disease.Conclusions Despite the increase in overall uptake of cardioprotective antihyperglycaemic drugs as second line treatments for type 2 diabetes mellitus, their uptake was lower in patients with cardiovascular disease than in people with no cardiovascular disease over the past decade. A strategy is needed to ensure that medication use is concordant with guideline recommendations to improve outcomes of patients with type 2 diabetes mellitus.

Introduction Studies have reported that antidiabetic medications (ADMs) were associated with lower risk of dementia, but current findings are inconsistent. This study compared the risk of dementia onset in patients with type 2 diabetes (T2D) treated with sulfonylurea (SU) or thiazolidinedione (TZD) to patients with T2D treated with metformin (MET).Research design and methods This is a prospective observational study within a T2D population using electronic medical records from all sites of the Veterans Affairs Healthcare System. Patients with T2D who initiated ADM from January 1, 2001, to December 31, 2017, were aged ≥60 years at the initiation, and were dementia-free were identified. A SU monotherapy group, a TZD monotherapy group, and a control group (MET monotherapy) were assembled based on prescription records. Participants were required to take the assigned treatment for at least 1 year. The primary outcome was all-cause dementia, and the two secondary outcomes were Alzheimer’s disease and vascular dementia, defined by International Classification of Diseases (ICD), 9th Revision, or ICD, 10th Revision, codes. The risks of developing outcomes were compared using propensity score weighted Cox proportional hazard models.Results Among 559 106 eligible veterans (mean age 65.7 (SD 8.7) years), the all-cause dementia rate was 8.2 cases per 1000 person-years (95% CI 6.0 to 13.7). After at least 1 year of treatment, TZD monotherapy was associated with a 22% lower risk of all-cause dementia onset (HR 0.78, 95% CI 0.75 to 0.81), compared with MET monotherapy, and 11% lower for MET and TZD dual therapy (HR 0.89, 95% CI 0.86 to 0.93), whereas the risk was 12% higher for SU monotherapy (HR 1.12 95% CI 1.09 to 1.15).Conclusions Among patients with T2D, TZD use was associated with a lower risk of dementia, and SU use was associated with a higher risk compared with MET use. Supplementing SU with either MET or TZD may partially offset its prodementia effects. These findings may help inform medication selection for elderly patients with T2D at high risk of dementia.

Background: Early recognition of sepsis, a common life-threatening condition in intensive care units (ICUs), is beneficial for improving patient outcomes. However, most sepsis prediction models were trained and assessed in the ICU, which might not apply to emergency department (ED) settings., Aims: To establish an early predictive model based on basic but essential information collected upon ED presentation for the follow-up diagnosis of sepsis observed in the ICU., Study Design: This study developed and validated a reliable model of sepsis prediction among ED patients by comparing 10 different methods based on retrospective electronic health record data from the MIMIC-IV database. In-ICU sepsis was identified as the primary outcome. The potential predictors encompassed baseline demographics, vital signs, pain scale, chief complaints and Emergency Severity Index (ESI). 80% and 20% of the total of 425 737 ED visit records were randomly selected for the train set and the test set for model development and validation, respectively., Results: Among the methods evaluated, XGBoost demonstrated an optimal predictive performance with an area under the curve (AUC) of 0.90 (95% CI: 0.90-0.91). Logistic regression exhibited a comparable predictive ability to XGBoost, with an AUC of 0.89 (95% CI: 0.89-0.90), along with a sensitivity and specificity of 85% (95% CI: 0.83-0.86) and 78% (95% CI: 0.77-0.80), respectively. Neither of the five commonly used severity scoring systems demonstrated satisfactory performance for sepsis prediction. The predictive ability of using ESI as the sole predictor (AUC: 0.79, 95% CI: 0.78-0.80) was also inferior to the model integrating ESI and other basic information., Conclusions: The use of ESI combined with basic clinical information upon ED presentation accurately predicted sepsis among ED patients, strengthening its application in ED., Relevance to Clinical Practice: The proposed model may assist nurses in risk stratification management and prioritize interventions for potential sepsis patients, even in low-resource settings., (© 2024 British Association of Critical Care Nurses.)

Background: The combination of anti-PD-1 antibody serplulimab and chemotherapy is considered standard first-line therapy for advanced esophageal squamous cell carcinoma (ESCC), but few later-line treatments are available. Here we evaluated the therapeutic efficacy of the recombinant, humanized anti-EGFR antibody HLX07 when used alone or together with serplulimab and chemotherapy against advanced ESCC., Methods: This open-label, non-randomized, two-cohort, phase 2 trial involved patients 18-75 years old with histologically or cytologically confirmed locally advanced, unresectable, or metastatic ESCC, and an Eastern Cooperative Oncology Group performance status of 0-1. Patients who had failed first-line immuno-chemotherapy or at least two lines of other systemic therapy received HLX07 monotherapy intravenously at a dose of 1,000 mg once every 2 weeks (Q2W). Patients with no prior systemic therapy received HLX07 (1,000 mg, day 1) and serplulimab (200 mg, day 1) intravenously Q2W for up to 2 years, concurrently with cisplatin (50 mg/m 2 , day 1) for up to 8 cycles and 5-fluorouracil (1,200 mg/m 2 , days 1-2) for up to 12 cycles intravenously Q2W. The primary endpoints were progression-free survival (PFS) and objective response rate (ORR)., Results: Overall, 50 patients were enrolled. In the HLX07 monotherapy group, ORR was 15.0% (3/20), and the median PFS was 1.5 months (95% confidence interval [CI], 1.3 to 3.7). The median duration of response was not reached, and the rate of patients showing an objective response lasting at least 6 months was 66.7% (95% CI, 5.4 to 94.5). Two (10.0%, 2/20) patients experienced grade 3-4 treatment-related adverse events (TRAEs), including hypomagnesemia, hypocalcemia, and fatigue. No patient experienced grade 5 TRAEs. In the HLX07 combination group, the ORR was 60.0% (18/30), and the median PFS was 7.8 months (95% CI, 3.3 to 9.1). Fourteen (46.7%, 14/30) patients experienced grade 3-4 TRAEs, and one (3.3%, 1/30) patient died due to serplulimab-related pneumonitis., Conclusions: HLX07 monotherapy and its combination with serplulimab and chemotherapy showed manageable toxicity and promising antitumor activity in patients with recurrent or metastatic ESCC. Randomized controlled trials are warranted to further establish the safety and efficacy of HLX07 against ESCC., Trial Registration: This trial was registered at Clinicaltrials.gov (NCT05221658)., (© 2024 The Author(s). Cancer Communications published by John Wiley & Sons Australia, Ltd on behalf of Sun Yat‐sen University Cancer Center.)

Background: It remains unclear whether chronic obstructive pulmonary disease (COPD) is an independent risk factor for lung cancer after excluding confounding factors such as smoking, age, sex, body mass index (BMI), comorbidities, etc., Methods: Data from 11,440 participants (≥ 40 years old) in the National Health and Nutrition Examination Survey (NHANES) 2013-2018 were analyzed. Weighted multivariable logistic regression models were used to assess the association between COPD and lung cancer risk. Subgroup analyses were based on age, sex, BMI, and smoking., Results: This study included 660 patients with COPD and 10,780 participants without COPD. The prevalence of lung cancer was significantly higher in patients with COPD compared to participants without COPD (3.39% vs 0.14%). After adjusting for confounding factors, COPD was associated with a significantly increased risk of lung cancer (OR, 12.24, 95% CI, 4.99-30.06, p < 0.001). This association remained significant in all subgroups, particularly in individuals aged > 65 years (OR, 20.05, 95% CI, 6.85-58.72, p < 0.001), smokers (OR, 19.38, 95% CI, 2.02-185.66, p = 0.010), males (OR, 17.39, 95% CI, 5.28-57.31, p < 0.001), individuals who quit smoking within 10 years (OR, 12.86, 95% CI, 2.59, 63.99, p = 0.002), and individuals with a BMI > 25 kg/m2 (OR, 14.56, 95% CI, 3.88-54.69, p < 0.001)., Conclusions: COPD is an independent risk factor for lung cancer, especially in certain subgroups. The combination of COPD and smoking greatly amplifies the lung cancer risk. These findings highlight the importance of early lung cancer screening in patients with COPD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: While laparoscopic splenectomy (LS) has been widely used in benign splenic tumor, more concerns have been raised for postoperatively short-term and long-term complications. Laparoscopic partial splenectomy (LPS) is a surgical option, to preserve splenic function, and reduce postoperative complications. The aim of our study was to retrospectively identify the safety and feasibility of LPS compared with LS in patients with splenic benign tumor., Materials and Methods: From 2014 to 2024, a total of 165 patients diagnosed with occupational splenic lesions underwent splenectomy, of whom 87 underwent LPS and 78 underwent LS. We compare the perioperative parameters and long term follow up between these two groups., Results: The etiology of splenic space-occupying lesions was nonparasitic splenic cysts, followed by splenic lymphangioma and splenic hemangioma. Of the patients with LPS, 55 underwent conventional surgery with blockage of the splenic arterial branch and resection along the ischemic line (RAIL), and 32 underwent with our modified total splenic blood supply blockade followed by resection alone the tumor edge (RATE). The tumor size, the operative time and estimated blood loss were comparable between the LPS and LS groups. One patient developed abnormal signs during the LPS procedure and was promptly referred for LS. The LPS group had fewer pancreatic leakage, incision infection, and pulmonary infection. As for different vascular types, patients with LS under all branches of the splenic artery had a longer time to resume postoperative feeding. As for the comparison of RAIL and RATE, estimated blood and operative time were significantly reduced in patients receiving RATE. Postoperative complications were the same in patients underwent each surgical procedures., Conclusion: LPS is a viable approach for patients with splenic benign tumor. We introduce the tumor artery supply types to indicate the resection region. Our RATE technique has proven to be clinically effective and safety., (© 2024. The Author(s).)

Developing lightweight, high-performance electromagnetic wave (EMW) absorbing materials those can absorb the adverse electromagnetic radiation or waves are of great significance. Transition metal carbides and/or nitrides (MXenes) are a novel type of 2D nanosheets associated with a large aspect ratio, abundant polar functional groups, adjustable conductivity, and remarkable mechanical properties. This contributes to the high-efficiency assembly of MXene-based aerogels possessing the ultra-low density, large specific surface area, tunable conductivity, and unique 3D porous microstructure, which is beneficial for promoting the EMW absorption. Therefore, MXene-based aerogels for EMW absorption have attracted widespread attention. This review provides an overview of the research progress on MXene-based aerogels for EMW absorption, focusing on the recent advances in component and structure design strategies, and summarizes the main strategies for constructing EMW absorbing MXene-based aerogels. In addition, based on EMW absorption mechanisms and structure regulation strategies, the preparation methods and properties of MXene-based aerogels with varieties of components and pore structures are detailed to advance understanding the relationships of composition-structure-performance. Furthermore, the future development and challenges faced by MXene-based aerogels for EMW absorption are summarized and prospected., (© 2024 Wiley‐VCH GmbH.)

Objective: To observe the clinical efficacy of medical education combined with extended care in patients with bronchial asthma and its effect on adherence to inhaled glucocorticoids., Methods: Ninety-eight patients with bronchial asthma were divided into the control group and the experimental group, n  = 49, by utilizing the random number table method. The control group was given routine education and care as well as routine out-of-hospital instructions, and the experimental group was given medical education and extended care based on the control group. Asthma disease knowledge mastery, asthma control, quality of life, medication adherence and lung function were compared between both groups, and the number of asthma attacks and re-hospitalizations were recorded., Results: The experimental group performed higher scores of health knowledge, asthma control test and quality of life, rate of complete adherence, forced expiratory volume in one second (FEV 1 ), peak expiratory flow rate, and FEV 1 /forced vital capacity. The number of asthma attacks and the times of re-hospitalizations were lower in the experimental group (all p  < 0.05)., Conclusion: Medical education combined with extended care can improve bronchial asthma patients' mastery of asthma disease knowledge, effectively control patients' conditions, enhance patients' quality of life and lung function, increase patients' adherence to inhaled glucocorticoids, and reduce the recurrence of bronchial asthma patients.

Thermal-induced coral bleaching has received substantial research attention; however, the dynamics of symbiotic coral-associated bacterial communities are underexplored and the roles of coral with intermediate health status remain unclear. Using high-throughput sequencing and biochemical analyses, we found that the symbiotic zooxanthellae number gradually decreased with the increase of bleaching degree (non-bleached, semi-bleached, and fully-bleached) in the coral Acropora pruinosa. The semi-bleached host exhibited a relatively more complex microbial interaction network. For the carbon metabolic profiles, relatively higher carbon-fixing abilities observed in non-bleached coral symbiotic bacteria, followed by semi-bleached host, and lowest values appeared in fully-bleached coral. Partial least-squares pathway modeling revealed that bacterial community features and carbon metabolic function were directly related with health status, while temperature exerted a strong influence on the bleaching resilience. These findings can help us better understand the coral microecological feature and carbon metabolic potential under changing environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: The primary aim of this study is to investigate the mediating role of school adaptation in the impact of adolescent bullying victimization on mental health, as well as the gender differences therein. These findings offer a novel perspective for parents and educators, aiding bullied adolescents in managing and addressing mental health concerns., Methods: The primary data source for this study was the 2020/2021 Adolescent Health Theme Database from the China Population Health Data Center (PHDA). The research sample consisted of high school students from 16 cities in Shandong Province. Descriptive statistics, reliability and validity testing, structural equation modeling, as well as mediation analysis and multiple group analysis were conducted using SPSS 26.0 and AMOS 26.0., Results: School adaptation serves as a mediating variable between adolescent bullying and mental health. The model fit indices are as follows: GFI=0.946, AGFI=0.922, RMSEA=0.070, NFI=0.978, IFI=0.979, CFI=0.97. Even when considering gender, the model still demonstrates good fit. School bullying has significant negative effects on the mental health of both male and female victims (p<0.05). For female victims, the mitigating effect of school adaptation on mental health is slightly lower than that for males (-2.256). Regarding cyberbullying, male victims face a greater threat to mental health (-3.234), with a impact of -0.109 from cyberbullying on male mental health and -0.065 from school bullying on female mental health., Conclusion: The school is found to mediate between school bullying, cyberbullying, and mental health. Schools may play a greater role in improving female mental health than male mental health. The impact of campus bullying on female mental health is greater than that of cyberbullying, whereas the opposite is true for males. Enhancing adolescents' school adaptation levels helps mitigate the adverse effects of school and cyberbullying on adolescent mental health., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Zhang et al.)

A method for detecting methamphetamine (MET), ketamine (KET), and morphine (MOP) molecules is presented using a reusable substrate based on SERS. The SERS substrate was prepared by etching the Au/Ag alloy film to synthesize a nanoporous Au membrane (AuNPM). By optimizing the preparation conditions and using rhodamine 6G (R6G) as an analyte, the AuNPM exhibited good SERS performance with a limit of detection (LOD) of 10 -9  mol L -1 . A competitive immunoassay category has been applied to the detection of MET, KET, and MOP. The MET, KET, and MOP antigens were functionalized on the surface of the AuNPM to specifically bind to the related drug antibodies. The Au nanoparticles (AuNPs) modified with 4-mercaptobenzoic acid (4-MBA) and antibodies against MET, KET, and MOP were used as nanotags. The 4-MBA served as the reporting molecule and drug antibodies were used to bind to free drug molecules in the target solution. The mixture of nanotags and target solution was dropped onto the antigen-modified AuNPM (antigen/AuNPM), and the free nanotags bind to the antigen/AuNPM. By comparing the SERS intensity of 4-MBA with the presence or absence of drug molecules, the drugs were qualitatively and quantitatively identified. Through this category, the LODs for detecting MET, KET, and MOP were 0.1, 1, and 1 ng mL -1 , respectively. This study proposes an effective method for constructing SERS-based detection of drug molecules with good potential for practical applications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Phaeocystis globosa is among the dominant microalgae associated with harmful algal blooms. P. globosa has a polymorphic life cycle and its ecological success has been attributed to algal colony formation, however, few studies have assessed differences in microbial communities and their functional profiles between intra- and extra-colonies during P. globosa blooms. To address this, environmental and metagenomics tools were used to conduct a time-series analysis of the bacterial composition and metabolic characteristics of intra- and extra-colonies during a natural P. globosa bloom. The results show that bacterial composition, biodiversity, and network interactions differed significantly between intra- and extra-colonies. Dominant extra-colonial bacteria were Bacteroidia and Saccharimonadis, while dominant intra-colonial bacteria included Alphaproteobacteria and Gammaproteobacteria. Despite the lower richness and diversity observed in the intra-colonial bacterial community, relative to extra-colonies, the complexity and interconnectedness of the intra-colonial networks were higher. Regarding bacterial function, more functional genes were enriched in substance metabolism (polysaccharides, iron element and dimethylsulfoniopropionate) and signal communication (quorum sensing, indoleacetic acid-IAA) pathways in intra- than in extra-colonies. Conceptual model construction showed that microbial cooperative synthesis of ammonium, vitamin B 12 , IAA, and siderophores were strongly related to the P. globosa bloom, particularly in the intra-colonial environment. Overall, our data highlight the differences in bacterial structure and functions within and outside the colony during P. globosa blooms. These findings represent fundamental information indicating that phenotypic heterogeneity is a selective strategy that improves microbial population competitiveness and environmental adaptation, benefiting P. globosa bloom formation and persistence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Patients with lung cancer face a heightened risk of developing sarcopenia. Despite this known risk, the impact of sarcopenia on the long-term prognosis of lung cancer patients, specifically concerning progression-free survival (PFS) and overall survival (OS), remains unclear. The primary objective of our study was to examine the correlation between metabolic parameters derived from 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) and sarcopenia, as well as the prognostic value of sarcopenia in patients with surgically resected early-stage non-small cell lung cancer (NSCLC)., Methods: In this retrospective cross-sectional study, we analyzed 187 NSCLC patients who underwent 18 F-FDG PET/CT at the First Affiliated Hospital of Soochow University between March 2019 and October 2023. Patients were divided into two groups based on the presence (n=46) or absence (n=141) of sarcopenia. The correlation between sarcopenia, metabolic parameters, and patient characteristics was evaluated using chi-square and Mann-Whitney U tests. Survival analyses, including PFS and OS, were conducted using Kaplan-Meier analysis and Cox proportional hazards regression. Based on sarcopenia, metabolic parameters and patient characteristics, patients were classified into high-risk (n=28), intermediate-risk (n=121), and low-risk (n=38) groups., Results: Our analysis identified gender, body mass index (BMI), psoas Hounsfield unit (HU), and maximum standardized uptake value of the psoas major muscle (SUV max -Muscle) as independent predictors of sarcopenia (P<0.05 for all). A nomogram model, utilizing these parameters, was constructed to predict sarcopenia. Survival analysis further demonstrated that total lesion glycolysis [hazard ratio (HR) =2.499; 95% confidence interval (CI): 2.014-3.267; P=0.016], sarcopenia (HR =3.323; 95% CI: 1.748-6.316; P<0.001), and programmed death ligand-1 (PD-L1) expression (HR =0.093; 95% CI: 0.012-0.698; P=0.021) emerged as independent predictors of OS in early-stage NSCLC. Notably, patients categorized as high-risk, characterized by elevated total lesion glycolysis, presence of sarcopenia, and PD-L1 positivity, exhibited a significantly poorer prognosis compared to the intermediate-risk (P<0.05) and low-risk groups (P<0.05)., Conclusions: Our findings indicated an inverse relationship between SUV max -Muscle or psoas HU with the incidence of sarcopenia in NSCLC patients. Additionally, total lesion glycolysis, sarcopenia, and PD-L1 expression were identified as independent prognostic factors for OS in early-stage NSCLC. The risk stratification model, incorporating total lesion glycolysis, sarcopenia, and PD-L1 expression, assumed a pivotal role in guiding personalized therapy decisions and post-treatment monitoring., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-852/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

China is the largest mariculture country, and shellfish and algae output ranks first, showing high carbon sink capacity. In recent years, the single cultivation of macroalgae (Pyropia yezoensis) has been changed to macroalgae-shellfish mariculture in Haizhou Bay to increase the yield of P. yezoensis and improve the water environment quality. In this study, four surveys were carried out in July 2022 during the monoculture period of oyster (Magallana gigas), as well as at different stages of P. yezoensis culture (head-crop period, November 2022, peak growing season, January 2023, and end of harvesting, March 2023) in the mariculture and the surrounding waters of Haizhou Bay. The effects of different stages of culture on the seawater environment and seasonal and spatial variations in the carbonate system were analyzed, and the carbon sink capacity was preliminarily estimated. The results showed that in summer, the calcification of M. gigas and the primary production process of phytoplankton effectively reduced the dissolved inorganic carbon (DIC) level in the culture area. The culture area acts as a CO 2 sink, with an average air-sea CO 2 flux of -4.5 mmol m -2 d -1 . During the polyculture period, the P. yezoensis culture activities maintained the stability of the seawater carbonate system, and the culture area shows strong CO 2 sinks, with the average air-sea CO 2 flux of -24.10 mmol m -2 d -1 , -37.68 mmol m -2 d -1 , and -38.99 mmol m -2 d -1 , respectively. The absorption of CO 2 by large-scale cultured P. yezoensis through the "biological pump" effect is the main factor affecting the CO 2 exchange process at the air-sea interface, and the absorption rate of CO 2 by P. yezoensis at the mature stage is higher than that at the growth stage before harvesting. The study revealed that macroalgae-shellfish mariculture could promote mutual growth, alleviate environmental pressure, and enhance the carbon sink of the culture area. The relationship between mariculture and the carbon cycle of a mariculture ecosystem is very complicated, and its biochemical process should be given great attention for further study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Hair dyes (HDs) are mainly composed of various benzene series, amines, and phenolic compounds. These ingredients are well known to have allergenic, teratogenic, and carcinogenic properties. As such, the presence of these ingredients in HDs has received increased attention in recent years. At present, the applications of traditional analytical and detection methods and commercial chromatographic columns are limited by problems such as poor qualitative analysis and inaccurate quantification. Thus, the development of new analytical and detection technologies and stationary phases is an urgent endeavor. Moreover, HDs contain complex compounds and exhibit significant matrix interference. Hence, appropriate sample pretreatment methods are necessary to analyze HDs. In this study, the 3D nonpolar rigid structure of triptycene (TP) was combined with the polar flexible chains of polyethylene glycol (PEG) to design and synthesize a TP derivative, TP-PEG, as a stationary phase for chromatographic columns. The stationary phase enabled the expansion of the selection range for polar and nonpolar analytes. Subsequently, gas chromatography-mass spectrometry (GC-MS) was used to quantitatively analyze 22 ingredients in HDs. The experimental results demonstrated that analytes with different polarities exhibited sharp and symmetrical peak shapes on the stationary phase, and all 22 analytes achieved baseline separation on the chromatographic column. The 22 ingredients in HDs showed good linear relationships within their respective ranges, with correlation coefficients greater than 0.9985. The average recovery rates at three spiked levels were in the range of 89.2%-103.2%, and RSDs were less than 5%. Compared with traditional methods, the proposed method has higher efficiency and better accuracy, thus verifying the excellent separation performance of the new stationary phase and the effectiveness of the established GC-MS detection method. The findings indicated the applicability of the developed method to the detection and analysis of various compounds in HDs.

Septic cardiomyopathy (SCM) is the main cause of death in critically ill patients with sepsis. However, its definitive pathogenic mechanisms remain to be elucidated. Lipid droplets (LDs) are important sub-organelles that store lipids and participate in intracellular lipid metabolism. Abnormal aggregation and altered polarity of LDs are associated with the development of several cardiac diseases. To date, visualization of abnormal polarity in models of SCM has not been achieved. Herein, we designed and synthesized the probe BDP-551, a polarity-sensitive probe possessing a donor-π-acceptor (D-π-A) structure. BDP-551 exhibits excellent photostability, high LDs targeting, near-infrared (NIR) emission (up to 678 nm) and strong polarity sensitivity. With the help of confocal imaging microscopy, the BDP-551 was able to detect the polarity changes induced in the SCM model cells and visualize the yolk sac region in hypoxic as well as inflamed living zebrafish. In addition, the BDP-551 has been successfully applied to visualize the polarity changes of mice hearts with SCM, proving a decrease of microenvironmental polarity in the development of SCM. Therefore, BDP-551 in this study can be used as a reliable tool to investigate polarity fluctuations and provide new insights into the associated pathogenic and therapeutic mechanisms on SCM., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Short-term exposure to ozone has been linked to multiple allergic diseases, but the relationship between ozone exposure and allergic conjunctivitis (AC) remains unclear. This study aimed to investigate the association between short-term exposure to ozone and the risk of AC. We conducted a time-stratified case-crossover study across five Chinese cities from 2014 to 2022. Daily outpatient visit records for AC were identified in five hospitals using either the diagnosis name or ICD-10 code H10.1. Data on air pollution and meteorological conditions were also collected. We first examined the city-specific association between short-term ozone exposure and AC using conditional logistic regression. A random-effects meta-analysis was then conducted to obtain overall estimates. During the study period, 130,093 outpatient visits for AC occurred, with 58.8% (76,482) being male and 41.2% (53,611) female. A one-standard-deviation (SD) increase in ozone was associated with an 8.3% increase (95% CI: 3.8%, 13.0%) in AC outpatient visits. Similar positive associations were observed when adjusting for other pollutants (PM 2.5 , CO, SO 2 and NO 2 ) in two-pollutant and multi-pollutant models. Furthermore, the positive association remained consistent when using mixed-effects regression models or further adjusting for meteorological conditions. In addition, no effect modification of the AC-ozone association by sex, age and season was apparent. This study provides evidence supporting a positive association between short-term ozone exposure and AC risk in China. This highlights the potential value of mitigating ozone pollution to reduce the risk of ocular surface disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Ammonia-oxidizing archaea (AOA) play crucial roles in marine carbon and nitrogen cycles by fixing inorganic carbon and performing the initial step of nitrification. Evaluation of carbon and nitrogen metabolism popularly relies on functional genes such as amoA and accA . Increasing studies suggest that quorum sensing (QS) mainly studied in biofilms for bacteria may serve as a universal communication and regulatory mechanism among prokaryotes; however, this has yet to be demonstrated in marine planktonic archaea. To bridge this knowledge gap, we employed a combination of metabolic activity markers ( amoA , accA , and grs ) to elucidate the regulation of AOA-mediated nitrogen, carbon processes, and their interactions with the surrounding heterotrophic population. Through co-transcription investigations linking metabolic markers to potential key QS genes, we discovered that QS molecules could regulate AOA's carbon, nitrogen, and lipid metabolisms under different conditions. Interestingly, specific AOA ecotypes showed a preference for employing distinct QS systems and a distinct QS circuit involving a typical population. Overall, our data demonstrate that QS orchestrates nitrogen and carbon metabolism, including the exchange of organic metabolites between AOA and surrounding heterotrophic bacteria, which has been previously overlooked in marine AOA research., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). mLife published by John Wiley & Sons Australia, Ltd on behalf of Institute of Microbiology, Chinese Academy of Sciences.)

In this study, we synthesized mesoporous polydopamine nanoparticles (MPDA NPs) using an emulsion-induced interface assembly strategy and loaded epigallocatechin gallate (EGCG) into MPDA NPs via electrostatic attraction to form EGCG@MPDA NPs. In the post myocardial infarction (MI) environment, these interventions specifically aimed to eliminate reactive oxygen species (ROS) and facilitate the repair of MI. We further combined them with a thermosensitive chitosan (CS) hydrogel to construct an injectable composite hydrogel (EGCG@MPDA/CS hydrogel). Utilizing in vitro experiments, the EGCG@MPDA/CS hydrogel exhibited excellent ROS-scavenging ability of H9C2 cells under the oxidative stress environment and also could inhibit their apoptosis. The EGCG@MPDA/CS hydrogel significantly promoted left ventricular ejection fraction (LVEF) in infarcted rat models post injection for 28 days compared to the PBS group (51.25 ± 1.73% vs 29.31 ± 0.78%, P < 0.05). In comparison to the PBS group, histological analysis revealed a substantial increase in left ventricular (LV) wall thickness in the EGCG@MPDA/CS hydrogel group (from 0.58 ± 0.03 to 1.39 ± 1.11 mm, P < 0.05). This work presents a novel approach to enhance MI repair by employing the EGCG@MPDA/CS hydrogel. This hydrogel effectively reduces local oxidative stress by ROS and stimulates the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway.

Cancer immunotherapies are ineffective in nonresponding patients due to absence of immune responses. Here, we identified that dihydroartemisinin (DHA) induced immunogenic cell death (ICD) in hepatocellular carcinoma (HCC), proved by release or surface expose of damage-associated molecular patterns and in vivo protective vaccine activity. Mechanistically, DHA can inhibit cyclin-dependent kinases (CDKs), leading to a buildup of intracellular reactive oxygen species (ROS), which induces immunogenic cell death. In both Hepa1-6 and H22 tumor bearing mice, DHA exerted anti-tumor activity through increasing tumor-infiltrating CD8 + T cells with expression of activation makers (CD25 and CD69), secretion of intracellular cytokines (IFN-γ and TNF-α) and activated dendritic cells expressing MHCⅡ, CD80 and CD86. In hepa1-6 tumor bearing mice, DHA decreased immunosuppressive myeloid-derived suppressor cells. Furthermore, DHA enhanced the anti-PD-1 antibody and chimeric antigen receptor (CAR) T cell-mediated tumor suppression through recruitment and activation of endogenous CD8 + T cells. Overall, we demonstrated that by inhibiting CDKs, DHA can remodel tumor micro-environment to amplify anti-tumor immune responses in HCC. These findings provide a promising therapy option for HCC patients., (Copyright © 2024. Published by Elsevier B.V.)