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Abstract This phase 3, observer-blinded, non-inferiority randomized trial (ClinicalTrials.gov: NCT05517642), conducted from September 2022 to May 2023 at three Malaysian sites, involved 540 adults previously vaccinated with three COVID-19 doses. Participants were randomized 1:1 to receive either one dose of inhaled Recombinant COVID-19 Vaccine (Ad5-nCoV-IH) or intramuscular tozinameran (BNT-IM). The study assessed safety, vaccine efficacy (VE) and immunogenicity against SARS-CoV-2 variants. The primary outcome was the non-inferiority of anti-spike protein receptor-binding domain (S-RBD IgG) antibodies, with a 97.5% confidence interval lower limit for the geometric mean concentration (GMC) ratio >0.67. Ad5-nCoV-IH showed lower immunogenicity than BNT-IM, with a GMC ratio of 0.22 and a seroconversion rate difference of -71.91%. Adverse drug reactions (ADRs) were less frequent with Ad5-nCoV-IH (39.26%) compared to BNT-IM (64.68%). No serious vaccine-related adverse events were reported. Both vaccines had comparable efficacy against COVID-19 variants. This study was funded by Tianjin Biomedical Science and Technology Major Project.

Abstract Background Lung cancer is the most common cause of cancer-related death worldwide. The most prevalent histological subtype of lung cancer is lung adenocarcinoma (LUAD), with incidence rising each year. Treating LUAD remains a significant issue due to a lack of early diagnosis and poor therapy outcomes. YKT6 is a member of the SNARE protein family, whose clinical value and biological function in LUAD has yet to be established. Methods TCGA, HPA and UALCAN were used to analyze YKT6 mRNA and protein levels, the correlation between YKT6 expression and clinicopathological features and prognosis. YKT6 mRNA and protein expression were verified by qRT-PCR, immunohistochemistry (IHC) and tissue microarrays (TMA). Additionally, lung cancer cell lines were chosen for YKT6 silencing to explore the effects on cell proliferation and migration. The cBioPortal was used to select YKT6-related genes. Protein-protein interaction (PPI) network was created based on STRING database and hub genes were screened, with their expression levels and prognosis values in LUAD analyzed accordingly. YKT6-related genes were enriched by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses. Results In LUAD, YKT6 was distinctly highly expressed with relation to clinical features of staging, smoking, lymph node metastasis, and TP53 mutation. Elevated YKT6 expression was linked to adverse prognosis, serving as an independent unfavorable prognostic factor. Moreover, YKT6 presented high diagnostic value in LUAD patients (AUC = 0.856). Experimental validation indicated that freshly collected LUAD tissues showed significantly high mRNA expression of YKT6. IHC and TMA verified increased YKT6 protein level in LUAD. Knockdown of YKT6 inhibited cell proliferation and promoted apoptosis, with mitigated capability of migration and invasion. The top ten hub genes screened by PPI network were highly expressed in LUAD, and significantly associated with poor prognosis. GO and KEGG analyses showed that YKT6-related genes were mainly involved in cell cycle. Conclusion Elevated YKT6 expression is related to poor prognosis of LUAD patients. YKT6 can serve as a novel biomarker for LUAD diagnosis and prognosis. Cell proliferation, migration and invasion was impaired with increased apoptosis upon YKT6 silencing in lung cancer cells. In summary, this study comprehensively uncovered that YKT6 could be identified as a potential prognostic and diagnostic biomarker in LUAD.

Abstract The pathogenesis of Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) remains unclear, though increasing evidence suggests inflammatory processes play key roles. In this study, single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) was used to decipher the immunometabolic profile in 4 ME/CFS patients and 4 heathy controls. We analyzed changes in the composition of major PBMC subpopulations and observed an increased frequency of total T cells and a significant reduction in NKs, monocytes, cDCs and pDCs. Further investigation revealed even more complex changes in the proportions of cell subpopulations within each subpopulation. Gene expression patterns revealed upregulated transcription factors related to immune regulation, as well as genes associated with viral infections and neurodegenerative diseases.CD4+ and CD8+ T cells in ME/CFS patients show different differentiation states and altered trajectories, indicating a possible suppression of differentiation. Memory B cells in ME/CFS patients are found early in the pseudotime, indicating a unique subtype specific to ME/CFS, with increased differentiation to plasma cells suggesting B cell overactivity. NK cells in ME/CFS patients exhibit reduced cytotoxicity and impaired responses, with reduced expression of perforin and CD107a upon stimulation. Pseudotime analysis showed abnormal development of adaptive immune cells and an enhanced cell-cell communication network converging on monocytes in particular. Our analysis also identified the estrogen-related receptor alpha (ESRRA)-APP-CD74 signaling pathway as a potential biomarker for ME/CFS in peripheral blood. In addition, data from the GSE214284 database confirmed higher ESRRA expression in the monocyte cell types of male ME/CFS patients. These results suggest a link between immune and neurological symptoms. The results support a disease model of immune dysfunction ranging from autoimmunity to immunodeficiency and point to amyloidotic neurodegenerative signaling pathways in the pathogenesis of ME/CFS. While the study provides important insights, limitations include the modest sample size and the evaluation of peripheral blood only. These findings highlight potential targets for diagnostic biomarkers and therapeutic interventions. Further research is needed to validate these biomarkers and explore their clinical applications in managing ME/CFS.

Abstract Inflammation plays an important role in depression, and the neutrophil-to-albumin ratio (NPAR) is a cost-effective and readily available novel biomarker of inflammation. The association between NPAR and depression is unclear; therefore, to assess the relationship between NPAR and depression, we conducted a cross-sectional study of 33,768 participants ≥ 18 years of age from the 2005–2018 NHANES database. NPAR was calculated as Neutrophil percentage (in total WBC count) (%) × 100/Albumin (g/dL). Multivariate logistic regression models were used to test the independent association between NPAR and depression, adjusting for demographic factors, education, smoking status, alcohol consumption, hypertension, diabetes mellitus, body mass index, the ratio of income to poverty, and history of cardiovascular disease. Results showed that NPAR was significantly and positively associated with depression. When NPAR were analyzed as a categorical variable, there was a 20% increase in the prevalence of depression in the quartile with the highest NPAR compared to the quartile with the lowest NPAR (OR 1.20[95% CI 1.06, 1.36]). Smoothed curve fitting and threshold effect analyses also showed a positive association between NPAR and depression, with an inflection point for threshold and saturation effects of 12.65. NPAR was positively associated with the likelihood of developing depression when NPAR > 12.65 (OR 1.06[95% CI 1.04, 1.09]). The results of subgroup analyses and interaction tests indicated that smoking status had a significant effect on the relationship between NPAR and depression (P

Abstract Addressing levodopa-unresponsive freezing of gait (FOG) in Parkinson’s disease (PD) presents a significant challenge. A randomized double-blinded trial evaluated the effects of repetitive transcranial magnetic stimulation (rTMS) in conjunction with transcutaneous magnetic spinal cord stimulation among 57 PD individuals experiencing levodopa-unresponsive FOG. Patients were randomized to receive dual-site stimulation involving bilateral primary motor cortex of the lower leg (M1-LL) and the lumbar spinal cord, single-site stimulation targeting bilateral M1-LL alone, or sham stimulation for 10 sessions. Low-frequency rTMS induced remarkable improvements in FOG, gait, and motor functions compared to sham at 1 day and 1 month postintervention. Notably, the dual-site protocol demonstrated superior efficacy in mitigating FOG and improving gait compared to the single-site approach, which correlated with a pronounced increase in short-interval intracortical inhibition of the abductor pollicis brevis. These findings underscore the potential of the cerebrospinal dual-site regimen as a promising approach for levodopa-unresponsive FOG and gait in PD.

Abstract The treatment of cognitive impairment in schizophrenia is an unaddressed need due to the absence of novel treatments. Recent studies demonstrated that fingolimod and siponimod have neuroprotective effects in several neuropsychiatric disorders; however, their pharmacological mechanisms are unclear. The objective of this study was to identify potential molecular mechanisms of fingolimod and siponimod for improving cognition of schizophrenia through network pharmacology and molecular docking. The putative target genes of ingredients, schizophrenia, and impaired cognition were obtained from online databases, including SwissTargetPrediction, PharmMapper, GeneCards, CTD, DisGeNET, and OMIM. A protein–protein interaction network was constructed to identify core targets. The DAVID database was used for GO and KEGG pathway enrichment analyses. An ingredient–target–pathway–disease network was constructed using Cytoscape. Finally, the interactions between ingredients and core targets were assessed with molecular docking. The analysis revealed 260 targets shared by fingolimod and siponimod, 257 unique targets for fingolimod, and 88 unique targets for siponimod. Two signaling pathways were involved in fingolimod-mediated improvements in the cognition of schizophrenia, including the PI3K-Akt and MAPK signaling pathways. The core targets that regulated these two pathways included IL1B, AKT1, TNF, IL6, INS, BCL2, and BDNF. The MAPK signaling pathway was involved in siponimod-mediated improvement in the cognition of schizophrenia. The MAPK pathway was regulated by three core targets, namely TNF, AKT1, and CASP3. Docking scores ranged from −5.0 to −10.4 kcal/mol. Our analysis revealed that fingolimod regulates the PI3K-Akt and MAPK signaling pathways via the core targets IL1B, AKT1, TNF, IL6, INS, BCL2, and BDNF, and siponimod regulates the MAPK signaling pathways via the core targets AKT1, TNF, and CASP3 to improve the cognition of schizophrenia. Our results provide potential targets and a theoretical basis for the design of new drugs to treat the impaired cognition of schizophrenia.

Diabetic wounds can occur as a prevalent complication among people diagnosed with diabetes, frequently resulting in the necessity for amputation. The cause and effect of diabetic foot ulcer is complex, involving multiple factors. In the present study, wound healing strategies utilizing nanomaterials have proven to be effective in battling bacterial infections and improve wound regeneration. Poloxamers (PLX) exhibit extensive potential as a viable option for the development of nanomedicines owing to their inherent characteristics of self-assembly and encapsulation. This study aims to design and develop a PLX/ZnO nanocomposite incorporated with Centella Asiatica extract (CAE) for the multi-functional action in the diabetic wound healing treatment. Subsequently physico-chemical characterizations, such as XRD, FTIR, and TEM observations, demonstrated that the ZnO were evenly distributed through the PLX framework. The developed nanocomposite was biocompatible with mouse fibroblast cell line (L929), and it had multiple beneficial characteristics, such as a rapid self-healing process and effective antibacterial action against G+ and G− bacterial pathogens. After being treated with the developed formulation, skin fibroblast cell line and HUVECs demonstrated a substantial increase in their in vitro cell proliferation ability, migration, and tube-forming abilities. The utilization of a CAE@PLX/ZnO nanoformulation presents a viable strategy and a distinctive, encouraging composite for diabetic wound healing treatment.

Summary: Purpose: To identify the relationship between emotional intelligence, occupational well-being, and work engagement among Chinese clinical nurses. Methods: This cross-sectional study is based on survey responses provided by 1744 registered nurses from a Chinese hospital. The survey utilized emotional intelligence, occupational well-being, and work engagement scales. Results: A questionnaire was distributed to nurses, and among them, 1744 filled it in. Work engagement was related to demographic characteristics. The nurses' work engagement score was 28.99±5.46. Work engagement was positively correlated with emotional intelligence (r=.94, p < .01) and occupational well-being (r=.96, p < .01). Conclusions: The current work engagement of nurses in China is at a medium level. It is influenced by emotional intelligence and occupational well-being.

Abstract Background Due to the increasing emergence of antibiotic resistance in Enterococcus faecalis (E. faecalis), it indicated as potentially opportunistic pathogen causing various healthcare-associated and life-threatening diseases around the world. Objective The aim of this meta-analysis was to evaluate the weighted pooled resistance rates in clinical E. faecalis isolates based on over time, areas, antimicrobial susceptibility testing (AST), and infection source. Methods We searched the studies in PubMed, Scopus, and Web of Science (November 30, 2022). All statistical analyses were carried out using the statistical package R. Results The analysis encompassed a total of 74 studies conducted in 28 countries. According to the meta-regression, the chloramphenicol, fosfomycin, imipenem, linezolid, minocycline, norfloxacin, quinupristin-dalfopristin, and tetracycline resistance rate increased over time. Analysis revealed statistically significant differences in antibiotic resistance rates for ampicillin, chloramphenicol, erythromycin, gentamicin, penicillin, rifampicin, teicoplanin, tetracycline, and vancomycin across various countries. Conclusions Globally, the prevalence of drug resistant E. faecalis strains are on the increase over time. Daptomycin and tigecycline can be an effective agent for the treatment of clinical E. faecalis infections. Considering the low prevalence of antibiotic resistance in continents of Europe and Australia, it is suggested to take advantage of their preventive strategies in order to obtain efficient results in other places with high prevalence of resistance.

Abstract Purpose The objective of this study is to assess the impact of smoking on stroke prevalence and to delineate the relationship between smoking-related factors and the risk of stroke, incorporating an analysis of demographic variations influencing this association. Methods Our analysis encompassed 9,176 participants, evaluating clinical attributes alongside smoking-related characteristics such as duration of cigarette consumption, and levels of nicotine, tar, and carbon monoxide. We employed weighted univariate logistic regression and restricted cubic splines to examine the association between smoking indicators and stroke risk, complemented by subgroup analyses for demographic differentiation. Results The overall prevalence of stroke in our cohort was 3.4%. Statistically significant associations were found between stroke incidence and factors such as age, gender, education, and marital status (p

Abstract In order for full utilization of the switching devices and safe continued operation of the power converter at the same time, the junction temperature of the switching devices needs to be accurately monitored without shutting down the motor drive. This paper derives an analytical junction temperature calculation method by using Laplace transformation and thermal network theory. Based on an actual motor drive, a simulation model is established using platform for power electronic systems (PLECS). Through comparison, the derived method is proven to be able to calculate junction temperature accurately.

Abstract Ataxin-2 (ATXN2) was originally discovered in the context of spinocerebellar ataxia type 2 (SCA2), but it has become a key player in various neurodegenerative diseases. This review delves into the multifaceted roles of ATXN2 in human diseases, revealing its diverse molecular and cellular pathways. The impact of ATXN2 on diseases extends beyond functional outcomes; it mainly interacts with various RNA-binding proteins (RBPs) to regulate different stages of post-transcriptional gene expression in diseases. With the progress of research, ATXN2 has also been found to play an important role in the development of various cancers, including breast cancer, gastric cancer, pancreatic cancer, colon cancer, and esophageal cancer. This comprehensive exploration underscores the crucial role of ATXN2 in the pathogenesis of diseases and warrants further investigation by the scientific community. By reviewing the latest discoveries on the regulatory functions of ATXN2 in diseases, this article helps us understand the complex molecular mechanisms of a series of human diseases related to this intriguing protein.

Abstract Background Delirium is a common disorder affecting patients’ psychiatric illness, characterized by a high rate of underdiagnosis, misdiagnosis, and high risks. However, previous studies frequently excluded patients with psychiatric illness, leading to limited knowledge about risk factors and optimal assessment tools for delirium in psychiatric settings. Objectives The scoping review was carried out to (1) identify the risk factors associated with delirium in patients with psychiatric illness; (2) synthesize the performance of assessment tools for detecting delirium in patients with psychiatric illness in psychiatric settings. Design Scoping review. Data sources PubMed, Web of Science, and Embase were searched to identify primary studies on delirium in psychiatric settings from inception to Dec 2023 inclusive. Two independent reviewers screened eligible studies against inclusion criteria. A narrative synthesis of the included studies was conducted. Results A final set of 36 articles meeting the inclusion criteria, two main themes were extracted: risk factors associated with delirium in patients with psychiatric illness and assessment tools for detecting delirium in psychiatric settings. The risk factors associated with delirium primarily included advanced age, physical comorbid, types of psychiatric illness, antipsychotics, anticholinergic drug, Electroconvulsive therapy, and the combination of lithium and Electroconvulsive therapy. Delirium Rating Scale-Revised-98, Memorial Delirium Assessment Scale, and Delirium Diagnostic Tool-Provisional might be valuable for delirium assessment in patients with psychiatric illness in psychiatric settings. Conclusions Delirium diagnosis in psychiatric settings is complex due to the overlapping clinical manifestations between psychiatric illness and delirium, as well as their potential co-occurrence. It is imperative to understand the risk factors and assessment methods related to delirium in this population to address diagnostic delays, establish effective prevention and screening strategies. Future research should focus on designing, implementing, and evaluating interventions that target modifiable risk factors, to prevent and manage delirium in patients with psychiatric illness.

Abstract Background Associations between perceived and actual risk of HIV infection and HIV prevention services uptake are inconclusive. This study aimed to evaluate the discrepancy between the perceived and actual HIV risk, and quantify the associations between perceived and actual risk of HIV infection and three HIV prevention services utilization among men who have sex with men (MSM) in Shandong province, China. Methods A cross-sectional study was conducted in Shandong province in June 2021. Participants were eligible if they were born biologically male, aged 18 years or older, had negative or unknown HIV status, and had sex with men in the past year. Participants were recruited online. The discrepancy between their perceived and actual risk of HIV infection was evaluated by calculating the Kappa value. Bayesian model averaging was used to assess the associations between perceived and actual risk of HIV infection and HIV prevention services uptake. Results A total of 1136 MSM were recruited, most of them were 30 years old or younger (59.9%), single (79.5%), with at least college education level (74.7%). Most participants (97.4%) perceived that they had low risk of HIV infection, and 14.1% were assessed with high actual risk. The discrepancy between their perceived and actual risk of HIV infection was evaluated with a Kappa value of 0.076 (P

Fat content is an important trait in pig production. Adipose tissue and muscle are important sites for fat deposition and affect production efficiency and quality. To regulate the fat content in these tissues, we need to understand the mechanisms behind fat deposition. Laiwu pigs, a Chinese indigenous breed, have significantly higher fat content in both adipose tissue and muscle than commercial breeds such as Duroc. In this study, we analyzed the transcriptomes in adipose tissue and muscle of 21-d-old Laiwu and Duroc piglets. Results showed that there were 828 and 671 differentially expressed genes (DEG) in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), respectively. Functional enrichment analysis showed that these DEG were enriched in metabolic pathways, especially carbohydrate and lipid metabolism. Additionally, in the longissimus muscle (LM) and psoas muscle (PM), 312 and 335 DEG were identified, demonstrating enrichment in the cell cycle and metabolic pathways. The protein–protein interaction (PPI) networks of these DEG were analyzed and potential hub genes were identified, such as FBP1 and SCD in adipose tissues and RRM2 and GADL1 in muscles. Meanwhile, results showed that there were common DEG between adipose tissue and muscle, such as LDHB, THRSP, and DGAT2. These findings showed that there are significant differences in the transcriptomes of the adipose tissue and muscle between Laiwu and Duroc piglets (P

Glycosylation is a post-transcriptional modification that can influence protein structure and function, yet the glycosylation of the major shellfish allergen, sarcoplasmic calcium-binding protein (SCP), remains poorly understood. In this study, we characterized the glycosylation profile of SCP and explored the role of N-glycans in its allergenicity. Tandem mass spectrometry (MSn) revealed seven distinct N-glycans conjugated to SCP and provided detailed structural identification. ELISA and mast cell degranulation assay using sera from allergic individuals demonstrated that SCP exhibits significant allergenicity, which was markedly reduced following deglycosylation. Additionally, through the integration of various bioinformatics approaches, seven potential epitopes of SCP were predicted, and two glycosylated conformational epitopes were identified. In summary, this study elucidated the detailed glycosylation pattern and allergenic properties of SCP, offering a theoretical foundation for future research on the impact of glycosylation on allergenicity and contributing to the development of hypoallergenic products.

BackgroundTo examine the associations of serum sodium and frailty with the risk of mild cognitive impairment (MCI) among hospitalized older adults with chronic diseases.MethodsA cross-sectional study was conducted in 403 hospitalized older adults with chronic diseases. Serum sodium concentration was assessed by the ion-selective electrode method, frailty status was evaluated by the FRAIL scale, and MCI was determined by the Montreal Cognitive Assessment (MoCA). Multiple logistic regression models were used to estimate the associations of serum sodium and frailty with MCI.ResultsParticipants with the lowest tertile of serum sodium had a higher risk of MCI than those in the middle tertile group (OR = 1.75, 95% CI: 1.01–3.04). Below 143 mmol/L, the risk of MCI was 1.38 (95% CI: 1.03–1.84) for per 1 SD decrease in serum sodium. Compared with the robust group, frailty was significantly associated with an increased risk of MCI (OR = 3.94, 95% CI: 1.92–8.10). Moreover, in comparison with participants with the middle tertile of serum sodium and who were robust/prefrail, those with frailty and either the lowest (OR = 5.53, 95% CI: 2.08–14.67) or the highest tertile of serum sodium (OR = 3.48, 95% CI: 1.20–10.05) had higher risks of MCI.ConclusionBoth lower and higher serum sodium impose a significantly higher risk for MCI in older adults with frailty. This could inform the design of clinical trials and the development of guidelines and recommendations for correcting serum sodium and frailty in hospitalized older adults with chronic diseases.

BackgroundGrowing evidence emphasizes the importance of xanthophyll carotenoids and omega-3 fatty acids in eye health. However, the beneficial effects of such supplementation have not been thoroughly discussed among adults with high screen exposure. Current trial evidence on lutein bioavailability is contradictory, and the interactions of dietary intervention with host-related factors remain elusive. This study aims to investigate the comparative effectiveness of supplementation with macular xanthophylls and omega-3 fatty acids on macular pigment optical density (MPOD) and visual function, access the bioavailability of free lutein and lutein ester, and explore the complex interplay between genetic variations, intestinal microbiota, and the dietary intervention in Chinese adults with long-term exposure to digital devices.MethodsThe Lutein, Zeaxanthin, and Omega-3 (LZO) clinical trial is a 24-week multicenter, randomized, double-blind, placebo-controlled trial of 600 participants recruited from research centers, universities, and communities. Individuals are eligible to participate if they are aged over 18 years and use digital devices for over 8 h daily in the last 2 years, and will be randomized to six arms. A total of three visits will be scheduled at baseline, 12 and 24 weeks. The primary outcome is the change in MPOD over the 24-week intervention. The secondary outcomes are changes in visual function (visual acuity, best-corrected visual acuity, contrast and glare sensitivity, critical flicker fusion, reaction time, visuognosis persistence, symptoms and signs of dry eye, retinal thickness, and optical quality), and changes in serum lutein and zeaxanthin concentrations, and erythrocyte membrane omega-3 fatty acids. Genetic variations will be determined using genome-wide genotyping at baseline. 16S rRNA gene sequencing will be utilized to assess microbiome compositional changes before and after intervention.DiscussionThe trial is anticipated to establish early interventions to prevent photochemical ocular damage and delay the onset of vision impairment in young adults with long-term repeated exposure to screen-based electronic devices, and provide valuable insights for the development of precision nutrition strategies for maintaining eye health.Clinical trial registrationwww.clinicaltrials.in.th, Identifier, TCTR20220904002.

Background Mental health issues are highly prevalent in older adults with mild cognitive impairment (MCI). Digital Health Interventions (DHIs) for individuals with MCI have proven effective in improving cognitive function, but their impact on mental health has received less attention. Objective Reporting a protocol for a systematic review and meta-analysis to evaluate the effectiveness of DHIs for older adults with MCI, focusing on mental health outcomes both overall and within homogeneous subgroups. Methods A systematic review and meta-analysis of randomized controlled trials will be conducted, with searches performed in the Cochrane Library, PubMed, Embase, Web of Science, CINAHL, CNKI, and WanFang date from inception to March 2024. Mental health outcomes are the primary outcome. Risk of bias will be assessed with the Cochrane Collaboration tool, and evidence quality will be evaluated with Grading of Recommendations Assessment, Development, and Evaluation. If sufficient studies are available, subgroup analysis will assess variations based on population and intervention characteristics, including types and modalities of DHIs, intervention settings, session frequency, and duration, focusing on specific mental health outcomes and both short- and long-term effects. Additionally, sensitivity analysis and meta-regression analysis will identify sources of other potential heterogeneity. Conclusion The protocol will guide a systematic review and meta-analysis to determine the effectiveness of DHIs in improving mental health of older adults with MCI. This effort will enhance understanding and optimization of DHIs, vital for reducing mental health disparities and improving psychotherapy access for older adults with MCI. PROSPERO registration number CRD42024522342

The study of extrachromosomal DNA (ecDNA), an element existing beyond classical chromosomes, contributes to creating a more comprehensive map of the cancer genome. In hematological malignancies, research on ecDNA has lacked comprehensive investigation into its frequency, structure, function, and mechanisms of formation. We re-analyzed WGS data from 208 hematological cancer samples across 11 types, focusing on ecDNA characteristics. Amplification of ecDNA was observed in 7 of these cancer types, with no instances found in normal blood cells. Patients with leukemia carrying ecDNA showed a low induction therapy remission rate (

Abstract Inflammatory bowel disease (IBD) is a chronic and unspecific inflammatory disorder of the gastrointestinal tract, and current treatment options often fail to maintain long‐term remission. Studies have shown that propionate level is reduced in fecal samples from patients with IBD. Propionate can ameliorate IBD through intestinal epithelial cells and immune regulation, but its effects on the inflammatory microenvironment and macrophage differentiation have not been widely studied. To address this, we constructed an engineered propionate‐producing probiotic (EcNP3) to achieve sustained restoration of propionate levels in the gut and increase its bioavailability. DSS‐induced experimental intestinal inflammation model was used to evaluate the effect of EcNP3 on improving the intestinal mucosal barrier and increasing the proportion of anti‐inflammatory macrophages. It was found that EcNP3 exhibited a restorative effect on the depletion of peritoneal anti‐inflammatory macrophages (F4/80hiCD11bhi) and significantly improved the expression level of IL‐10. Simultaneously, the expression of IL‐1β, IL‐6, and CXCL1 was downregulated while inhibiting apoptosis of tissue‐resident macrophages ex vivo. Further investigation revealed that EcNP3 regulates IL‐10 expression through G protein‐coupled receptor 43 and histone deacetylase. Furthermore, EcNP3 significantly inhibited the protein expression of HDAC1 and promoted the histone acetylation level of cells. Finally, EcNP3 significantly improved DSS‐induced colitis in mice by increasing mucus production and reducing inflammatory infiltration. Our results suggest that the engineered live biotherapeutic product EcNP3 is a safe and potently efficacious treatment for IBD, which defines a novel strategy in IBD therapy through macrophage IL‐10 signaling.

ObjectiveWork engagement significantly influences both the quality of nursing care and nurses’ job performance. In this study, we aimed to explore the mediating effects of negative emotions on the relationship between self-compassion and work engagement among Chinese nurses.MethodA cross-sectional study was performed on nurses in a tertiary A hospital located in Henan province from September, 2023 to December, 2023. Custom-designed digital surveys were disseminated to gather pertinent data. Structural Equation Modelling (SEM) were utilised to analyse the data and determine relationships among self-compassion, negative emotions and work engagement.ResultsA total of 1,201 nurses were included. According to the statistical model, self-compassion (β = 0.116, CI: −0.036 to −0.008, p

Background: With the development of nursing positions and nursing disciplines in China's tertiary hospitals, the number of people applying for the master's degree in nursing is also increasing year by year. Postgraduate examinations are held during internship, so nursing students face the dual pressure of testing and internship, which brings varying degrees of negative experiences and emotional fluctuations. Objective: To explore the psychological experiences and influencing factors of undergraduate nursing students under the dual pressures of clinical nursing internships and postgraduate examination preparations. Design: Descriptive qualitative study. Method: Purposeful sampling was used to recruit 18 participants from eight tertiary hospitals in China between October and December 2023. Semi-structured in-depth interviews were conducted, with interview recordings transcribed verbatim. Thematic analysis was then applied to the data. Results: Four themes were identified: negative experiences under dual pressures, coping mechanisms for negative experiences, motivational effects under dual pressures, and evaluations of significant individuals. Nursing students improved their overall abilities through internships and exam preparations, gaining a clear understanding of themselves and certain hospital roles. However, at this stage, students also experienced adverse psychological experiences for various reasons. Thus, they employed several methods to alleviate their psychological stress, aiming for a better state to face internships and exam preparations. Conclusion: Schools and hospitals should pay more attention to the needs of nursing students under dual pressures, monitoring their emotional states, and providing psychological support to enhance their stress-coping abilities. It is important to ensure the overall well-being of students while strengthening the motivational effects of internships and learning experiences.

Revealing alpine plant diversity patterns can contribute to conserving mountain plant diversity. However, the spatial variation in the ecological niche and diversity patterns of the plant community and the mechanism by which it maintains itself in alpine desert grasslands remain poorly understood. Here, we conducted a field investigation across altitudinal gradients (3093, 3296, 3549, and 3790 m) in the northern Tibetan Plateau and compared species composition, diversity indices, Levins' niche breadth, and Pianka's niche overlap. The results showed that perennial herbs replaced semi-shrubs and xermesophytes and mesophytes replaced xerophytes with increasing altitude. The plant community heights decreased with altitude. The cover of the herb layer increased with altitude, whereas that of the shrub layer was hump-shaped. Species diversity indices (Patrick, Pielou, Shannon-Wiener, and Simpson) increased with increasing altitude. Sympegma regelii (1.05), Leymus chinensis (1.03), and Reaumuria kaschgarica (0.94) had larger niche breadths and were widespread. Species with a high niche overlap occupied a considerable proportion at higher altitudes, indicating strong interactions among species. The redundancy analysis revealed that altitude, soil water content, soil organic matter content, and pH were the main factors driving changes in plant diversity (P = 0.036, F = 3.7). Our study illustrated that environmental filtering and biotic interactions jointly shape plant composition and diversity in alpine desert grasslands along altitudinal gradients.

Malignant insulinomas are rare neuroendocrine tumors that require management for both symptomatic control and tumor reduction. It is clinically challenging to optimize treatment strategies for refractory malignant insulinoma. We report a case of metastatic grade 3 insulinoma presented with recurrent hypoglycemia in a 23-year-old female with RAD51D p.Q192 germline mutation. During the disease course of 5 years, the tumor has continuously progressed despite locoregional therapy and multiple lines of systemic treatment. However, oxaliplatin-based chemotherapy achieved a partial response, which was maintained for 2 years. The hypoglycemic symptoms were controlled after the treatment response and did not recur. The platinum-based regimen could be a feasible therapeutic strategy for malignant insulinoma. The relationship between germline mutation in the DNA damage repair pathway and treatment response to platinum-based regimens in neuroendocrine tumors warrants further investigation.

ObjectiveTo explore the intervention effects of different social media platforms on improving the knowledge of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) diagnosis and treatment among HIV-positive men who have sex with men (MSM). MethodsA total of 288 HIV-positive MSM were recruited at the Shandong Provincial Public Health Clinical Center from October to December 2020, and according to their preference, the MSM were divided into three groups to receive information on the knowledge and practice of HIV/AIDS diagnosis and treatment via short message service (SMS), WeChat, and the combination of WeChat and QQ group in six months. The generalized estimating equation used to analyze and compare the intervention effects of the interventions via different social media on the overall knowledge score of HIV/AIDS diagnosis and treatment among the all and subgroups of the participants. ResultsThe mean age of the participants was 34.67 ± 9.22 years. Six-month follow-up showed that the total score of HIV/AIDS diagnosis and treatment knowledge in the WeChat intervention group was 0.38 points higher than that in the SMS intervention group (P = 0.01), and there was no significant difference between the results of the other intervention groups (P > 0.05); in the subgroup with high school education and below, WeChat intervention (P = 0.018), WeChat and QQ group intervention (P = 0.002) were better than SMS intervention in improving the total score of AIDS diagnosis and treatment knowledge. ConclusionCompared with SMS intervention, WeChat intervention significantly improved the HIV/AIDS diagnosis and treatment knowledge score of HIV-positive MSM, and WeChat can be used as the main media for HIV-positive MSM to popularize HIV/AIDS knowledge in the future.

Abstract Generating genetic diversity lies at the heart of directed evolution which has been widely used to engineer genetic parts and gene circuits in synthetic biology. With the ever-expanding application of directed evolution, different approaches of generating genetic diversity are required to enrich the traditional toolbox. Here we show in vitro generation of genetic diversity for directed evolution by error-prone artificial DNA synthesis (epADS). This approach comprises a three-step process which incorporates base errors randomly generated during chemical synthesis of oligonucleotides under specific conditions into the target DNA. Through this method, 200 ~ 4000 folds of diversification in fluorescent strength have been achieved in genes encoding fluorescent proteins. EpADS has also been successfully used to diversify regulatory genetic parts, synthetic gene circuits and even increase microbial tolerance to carbenicillin in a short time period. EpADS would be an alternative tool for directed evolution which may have useful applications in synthetic biology.

Abstract Background The absence of heterozygosity (AOH) is a kind of genomic change characterized by a long contiguous region of homozygous alleles in a chromosome, which may cause human genetic disorders. However, no method of low-pass whole genome sequencing (LP-WGS) has been reported for the detection of AOH in a low-pass setting of less than onefold. We developed a method, termed CNVseq-AOH, for predicting the absence of heterozygosity using LP-WGS with ultra-low sequencing data, which overcomes the sparse nature of typical LP-WGS data by combing population-based haplotype information, adjustable sliding windows, and recurrent neural network (RNN). We tested the feasibility of CNVseq-AOH for the detection of AOH in 409 cases (11 AOH regions for model training and 863 AOH regions for validation) from the 1000 Genomes Project (1KGP). AOH detection using CNVseq-AOH was also performed on 6 clinical cases with previously ascertained AOHs by whole exome sequencing (WES). Results Using SNP-based microarray results as reference (AOHs detected by CNVseq-AOH with at least a 50% overlap with the AOHs detected by chromosomal microarray analysis), 409 samples (863 AOH regions) in the 1KGP were used for concordant analysis. For 784 AOHs on autosomes and 79 AOHs on the X chromosome, CNVseq-AOH can predict AOHs with a concordant rate of 96.23% and 59.49% respectively based on the analysis of 0.1-fold LP-WGS data, which is far lower than the current standard in the field. Using 0.1-fold LP-WGS data, CNVseq-AOH revealed 5 additional AOHs (larger than 10 Mb in size) in the 409 samples. We further analyzed AOHs larger than 10 Mb, which is recommended for reporting the possibility of UPD. For the 291 AOH regions larger than 10 Mb, CNVseq-AOH can predict AOHs with a concordant rate of 99.66% with only 0.1-fold LP-WGS data. In the 6 clinical cases, CNVseq-AOH revealed all 15 known AOH regions. Conclusions Here we reported a method for analyzing LP-WGS data to accurately identify regions of AOH, which possesses great potential to improve genetic testing of AOH.

BackgroundCooking oil fumes are closely related to immune response, and adipose tissue also plays an important role in immune regulation. At present, the biological effect and mechanism of inflammation of adipose tissue induced by oil fume exposure are not clear yet.ObjectiveTo investigate the inflammatory effect of different exposure duration of cooking fumes on adipose tissue in mice and explore the role of Nod-like receptor pyrin domain 3 (NLRP3)/cysteinyl aspartate specific proteinase 1 (Caspase 1)/interleukin (IL)-1β signaling pathway.MethodsForty 8-week-old female C57BL/6J mice were randomly divided into 3-day control group (CON3 group), 7-day control group (CON7 group), 3-day oil fume exposure group (COF3 group), and 7-day oil fume exposure group (COF7 group), with 10 mice in each group. The mice were exposed to oil fumes in a cooking oil fume formation and exposure equipment (COFFEE) for 20 min, followed by a 10-min pause, 1 h a day for consecutive 3 d or 7 d. General condition of mice was observed and body weight was measured every day. After exposure, blood was sampled from the eyeball. Serum levels of IL-6, IL-27, and IL-1β were detected by enzyme-linked immunosorbent assay (ELISA). The adipose tissue of mice was collected and observed after hematoxylin-eosin (HE) staining. The percentages of CD4+ and CD8+T cells in adipose tissue were detected by flow cytometry. Real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of nuclear factor-κB (NF-κB), NLRP3, Caspase 1, and IL-1β in adipose tissue. Western blot was used to detect the expression levels of NLRP3, Caspase 1, and IL-1β in adipose.ResultsCompared with the corresponding control group, serum IL-6, IL-27, and IL-1β contents in the COF3 group and the COF7 group were significantly increased (P

Abstract Understanding both positive and negative impacts of climate change is essential for comprehensively assessing and well adapting to the impacts of changing climate. Conventionally, climate warming is revealed to negatively impact human activities. Here, we reveal that human beings’ performance in anaerobic sports may benefit from climate warming. Using global weather observation and athletes’ performance datasets, we show that world-top athletes’ performances in nearly all athletics anaerobic events (i.e., sprints, jumps and throws) substantially improve as ambient temperature rises. For example, 100 m performance monotonically improves by 0.26 s as ambient temperature rises from 11.8° to 36.4 °C. Using Coupled Model Intercomparison Project Phase 6 datasets, we further show that global warming can substantially improve world-top athletes’ performance in eleven of the thirteen Olympics athletics anaerobic events by 0.27%–0.88% and 0.14–0.48% under high-emission and medium-emission scenarios, respectively, during 1979–2100. Among them, the improvements for 100 m are 0.59% (0.063 s) and 0.32% (0.034 s), respectively. Mechanism analysis shows that the warmed ambient atmosphere can improve competitors’ performance through expanding the air and thus reducing the air resistance to the competitors and throwing implements for hummer throw and all the sprints, hurdling and jumps. Quantitative analysis estimates that this thermodynamic process is essential for the impacts of warmed ambient atmosphere on the performances in these events as physiological processes are.

Radiotherapy (RT) is one of the most feasible and routinely used therapeutic modalities for treating malignant tumors. In particular, immune responses triggered by RT, known as radio-immunotherapy, can partially inhibit the growth of distantly spreading tumors and recurrent tumors. However, the safety and efficacy of radio-immunotherapy is impeded by the radio-resistance and poor immunogenicity of tumor. Herein, we report oxaliplatin (IV)-iron bimetallic nanoparticles (OXA/Fe NPs) as cascade sensitizing amplifiers for low-dose and robust radio-immunotherapy. The OXA/Fe NPs exhibit tumor-specific accumulation and activation of OXA (II) and Fe2+ in response to the reductive and acidic microenvironment within tumor cells. The cascade reactions of the released metallic drugs can sensitize RT by inducing DNA damage, increasing ROS and O2 levels, and amplifying the immunogenic cell death (ICD) effect after RT to facilitate potent immune activation. As a result, OXA/Fe NPs-based low-dose RT triggered a robust immune response and inhibited the distant and metastatic tumors effectively by a strong abscopal effect. Moreover, a long-term immunological memory effect to protect mice from tumor rechallenging is observed. Overall, the bimetallic NPs-based cascade sensitizing amplifier system offers an efficient radio-immunotherapy regimen that addresses the key challenges.

Abstract Dilated perivascular spaces (PVS) have emerged as a pathological hallmark in various neurological conditions, including Parkinson’s disease (PD). Levodopa-induced dyskinesia (LID), an intractable motor complication of PD, remains enigmatic regarding the distribution patterns of PVS. Our objective was to scrutinize the percent PVS (pPVS) changes within PD patients with LID (PD-LID). In total, 132 individuals were enrolled, including PD-LID (n = 42), PD patients without LID (PD-nLID, n = 45), and healthy controls (HCs, n = 45). Employing an automated approach for PVS quantification based on structural magnetic resonance imaging, we comprehensively evaluated total pPVS in subcortical white matter globally and regionally. A significant increase in global pPVS was observed in PD patients versus HCs, particularly evident in PD-LID relative to HCs. Within the PD-LID group, elevated pPVS was discerned in the right inferior frontal gyrus region (rIFG) (pars opercularis), contrasting with PD-nLID and HCs. Moreover, PD patients exhibited increased pPVS in bilateral superior temporal regions compared to HCs. Notably, pPVS in the rIFG positively correlated with dyskinetic symptoms and could well identify LID. Our findings unveiled PVS alternations in subcortical white matter in PD-LID at both global and regional levels, highlighting the increased pPVS in rIFG as a prospective imaging marker for LID.

Arginine (Arg), a safe basic amino acid, modulates interprotein interactions and impacts the processing characteristics of myofibrillar proteins (MP) in meat products, as numerous studies have demonstrated. This study aimed to explore the effects of varying concentrations of Arg (0.025, 0.050, 0.100, 0.200 %) on the physicochemical properties and gel behavior of yak MP. Utilizing yak MP as the substrate, we assessed and analyzed the physicochemical attributes and gel performance of the MP-Arg composite system. The findings revealed that Arg facilitates MP unfolding and internal group exposure, effectively mitigating oxidative tertiary structure alterations. Arg exerts potent antioxidant activity on MP, augmenting their water-holding capacity, which ameliorates gel properties. In this experiment, 0.05 % Arg maximally inhibited oxidative damage to MP, with protection being concentration-dependent. Collectively, these findings suggest that Arg effectively inhibits the oxidative degradation of MP structure and promotes the formation of enhanced gel characteristics.

DNA and RNA methylation are essential epigenetic modifications that play a pivotal role in various physiological processes by modulating gene expression at the post-transcriptional level. Abnormal DNA/RNA methylation is closely linked to a range of human diseases, including cancer and neurological disorders. Therefore, the accurate and sensitive detection of DNA/RNA methylation is of great importance in both epigenetic biology research and disease diagnosis. Technological advancements have led to the comprehensive development of methylation detection methods. Among these, electrochemical techniques have garnered significant attention owing to their simplicity and effectiveness in detection. This review provides an overview of methylation detection technologies based on electrochemical principles developed over the past five years, including electrochemical, photoelectrochemical, electrochemiluminescence, and fluorescence methodologies. Additionally, it discusses the advantages and disadvantages of these approaches, challenges and advancements in methylation detection.

Antibiotic residues resulting from the misuse of veterinary antibiotics pose a serious threat to global food safety and the ecological environment. Regulating the use of antibiotics is currently a major concern; however, existing literature on this issue remains insufficient. Therefore, to advance research in this area, this study utilizes data from 988 questionnaires collected across 9 provinces in China and employs the 3SLS systematic estimation method. It constructs an analytical framework to explore the mechanisms through which policy advocacy (PA) influences regulating antibiotics use (RAU) among meat duck farmers. Specifically, the study examines two pathways: “ PA - public opinion pressure perception (POPP) - RAU” and “ PA - moral responsibility (MR) - RAU.” Additionally, it explores the potential mechanisms through which PA impacts RAU among farmers. The results show that PA (Coef = 0.070, SE = 0.014) can promote RAU by increasing the level of POPP (Coef = 0.173, SE = 0.091). PA (Coef = 0.351, SE = 0.028) can also promote RAU by enhancing MR (Coef = 0.239, SE = 0.035). Meanwhile, this study introduces Internet use (IU) and reputational incentives (RI) as moderating variables to analyze their role in moderating the impact of PA on RAU. It was demonstrated that IU (Coef = 0.088, SE = 0.016) significantly enhances farmers' awareness of the value of RAU and amplifies the impact of PA on MR. However, IU (Coef = −0.017, SE = 0.008) was found to inhibit the effect of PA on POPP. RI fully satisfies farmers' need for “ honor “ and enhances the effectiveness of PA in promoting both POPP (Coef = 0.009, SE = 0.002) and MR (Coef = 0.058, SE = 0.004). Finally, the study proposes that the government expand PA channels, innovate methods, and combine online outreach with demonstrations to improve farmers' awareness of antibiotic use and address their reputational needs.

To fully understand the safety of DTaP-IPV/Hib vaccination, we evaluated the differences between DTaP-IPV/Hib co-administration and separate administration of the DTaP, IPV and Hib vaccines (DTaP+IPV+Hib) based on adverse events following immunization (AEFI). All AEFI reported in Hebei Province, China, between 2020 and 2022 were included in this study. The risk difference (RD%), relative risk (RR), and Chi-square value were used to compare the differences in reported rates of AEFI between the DTaP-IPV/Hib and DTaP+IPV+Hib groups. From 2020 to 2022, 130 AEFI cases were reported in Hebei Province after DTaP-IPV/Hib vaccination, corresponding to an AEFI reported rate of 66.9/million doses, which was significantly lower than that for DTaP+IPV+Hib (9836 AEFI with a reported rate of 637.8/million doses). The overall reported rate of non-severe AEFI for DTaP+IPV+Hib vaccines was 9.5 times that of DTaP-IPV/Hib vaccination [95% confidence interval (CI): 8.0, 11.3]. Meanwhile, the reported rate of AEFI among infants aged 0–1 y was 9.8 times higher for DTaP+IPV+Hib than for DTaP-IPV/Hib (95% CI: 8.2, 11.7). DTaP+IPV+Hib vaccination also resulted in higher risks of high fever, localized redness and swelling, localized induration, and allergic rash compared with DTaP-IPV/Hib vaccination. The risk of AEFI, which were mostly mild reaction, was higher after vaccination with DTaP+IPV+Hib than after DTaP-IPV/Hib vaccination.

ABSTRACTIntestinal microbiota dysbiosis and metabolic disruption are considered essential characteristics in inflammatory bowel disorders (IBD). Reasonable butyrate supplementation can help patients regulate intestinal flora structure and promote mucosal repair. Here, to restore microbiota homeostasis and butyrate levels in the patient’s intestines, we modified the genome of Saccharomyces cerevisiae to produce butyrate. We precisely regulated the relevant metabolic pathways to enable the yeast to produce sufficient butyrate in the intestine with uneven oxygen distribution. A series of engineered strains with different butyrate synthesis abilities was constructed to meet the needs of different patients, and the strongest can reach 1.8 g/L title of butyrate. Next, this series of strains was used to co-cultivate with gut microbiota collected from patients with mild-to-moderate ulcerative colitis. After receiving treatment with engineered strains, the gut microbiota and the butyrate content have been regulated to varying degrees depending on the synthetic ability of the strain. The abundance of probiotics such as Bifidobacterium and Lactobacillus increased, while the abundance of harmful bacteria like Candidatus Bacilloplasma decreased. Meanwhile, the series of butyrate-producing yeast significantly improved trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice by restoring butyrate content. Among the series of engineered yeasts, the strain with the second-highest butyrate synthesis ability showed the most significant regulatory and the best therapeutic effect on the gut microbiota from IBD patients and the colitis mouse model. This study confirmed the existence of a therapeutic window for IBD treatment by supplementing butyrate, and it is necessary to restore butyrate levels according to the actual situation of patients to restore intestinal flora.

ABSTRACTConstructing synthetic microbial consortia is a challenging task but holds enormous potential for various applications. Our previous droplet-based microfluidic approach allowed for the isolation of bacteria that could utilize metabolites from an engineered bacterium BsS-RS06551 with anti-obesity potential, facilitating the construction of synthetic microbial consortia. Here, we identified a strain of Bifidobacterium pseudocatenulatum JJ3 that interacted with BsS-RS06551, and in vitro coculture showed that BsS-RS06551 was likely to interact with JJ3 through five dipeptides. Pathway analysis revealed that the vitamin B6 metabolism pathway was enriched in the coculture of BsS-RS06551 and JJ3 compared with the individual culture of BsS-RS06551. Additionally, we confirmed that the administration of JJ3 significantly alleviated obesity and related disorders in mice fed a high-fat diet. Notably, continuous ingestion of the synthetic microbial consortium comprising BsS-RS06551 and JJ3 not only exhibited a more pronounced impact on alleviating obesity compared to the individual administration of BsS-RS06551 or JJ3 but also enriched the population of Bifidobacterium longum and perturbed the vitamin B6 metabolism pathway in the gut. Synthetic microbial consortia represent a promising frontier for synthetic biology, and our strategy provides guidance for constructing and applying such consortia.

Background: Lung cancer is one of the malignant tumors with the highest rates of morbidity and mortality worldwide. One of the most common histological types of lung cancer is lung adenocarcinoma (LUAD). Despite the fact that development in medicine has significantly improved some patients’ prognoses, the overall survival (OS) rate is still very low. In glucose-deficient SLC7A11-overexpressed cancer cells, the accumulation of disulfide molecules leads to abnormal disulfide bonding between actin cytoskeletal proteins, interferes with their tissues, and eventually leads to actin network collapse and cell death. This mode of cell death is called disulfidptosis. Studies have shown that disulfidptosis may be a new target for cancer treatment. However, the role of disulfidptosis in LUAD is still unknown. Methods: LUAD transcriptome and clinical information from The Cancer Genome Atlas (TCGA) was downloaded. The co-expression analysis, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and Cox regression analysis was performed to screen the disulfidptosis-related lncRNAs (DRLs) and build the prognostic model. Kaplan-Meier curve, Cox regression analysis, and receiver operating characteristic (ROC) curve was used to validate the model. Then a nomogram is made to predict the prognosis of LUAD patients. Finally, fresh-collected clinical samples were used to verify the expression of DRLs in LUAD. Results: The prognostic model with six DRLs was developed to predict the prognosis of LUAD, with superior prognosis value compared to other clinical variables. The Cox regression analysis revealed that T stage, N stage and the risk score were identified as independent variables that affected LUAD prognosis. ROC curve revealed that the model has a moderate diagnostic value, with an AUC of 1-year 0.684, 3-year 0.664, and 5-year 0.588. Moreover, nine medications connected to LUAD treatment were acquired through drug sensitivity analysis. LUAD tissue validation showed that AC012073.1, AC012615.1, EMSLR, and SNHG12 were highly expressed, while AL606834.1 and AL365181.2 with low expression. Conclusion: Six DRLs were screened and verified to construct the prognostic model, which can accurately predict the LUAD prognosis. It establishes a basis for further exploration into the molecular mechanisms underlying LUAD and identification of potential biomarkers for diagnosis, prognosis, and therapeutic targets.

Actin depolymerizing factors (ADFs), as the important actin-binding proteins (ABPs) with depolymerizing/severing actin filaments, play a critical role in plant growth and development, and in response to biotic and abiotic stresses. However, the information and function of the ADF family in melon remains unclear. In this study, 9 melon ADF genes (CmADFs) were identified, distributed in 4 subfamilies, and located on 6 chromosomes respectively. Promoter analysis revealed that the CmADFs contained a large number of cis-acting elements related to hormones and stresses. The similarity of CmADFs with their Arabidopsis homologue AtADFs in sequence, structure, important sites and tissue expression confirmed that ADFs were conserved. Gene expression analysis showed that CmADFs responded to low and high temperature stresses, as well as ABA and SA signals. In particular, CmADF1 was significantly up-regulated under above all stress and hormone treatments, indicating that CmADF1 plays a key role in stress and hormone signaling responses, so CmADF1 was selected to further study the mechanism in plant tolerance low temperature. Under low temperature, virus-induced gene silencing (VIGS) of CmADF1 in oriental melon plants showed increased sensitivity to low temperature stress. Consistently, the stable genetic overexpression of CmADF1 in Arabidopsis improved their low temperature tolerance, possibly due to the role of CmADF1 in the depolymerization of actin filaments. Overall, our findings indicated that CmADF genes, especially CmADF1, function in response to abiotic stresses in melon.

Background: Adolescents diagnosed with depression are particularly susceptible to anxiety and depressive symptoms, this vulnerability often diminishes their future expectations and overall outlook on life. The objective of this research was to scrutinize the associated risk factors of adolescent depression and delineated the interplay between anxiety and depressive symptoms. Concurrently, it sought to ascertain the latent mediating effects of hope levels and coping strategies within this framework. Methods: A mixed-methods research approach was employed. For the qualitative component, 18 adolescents with depression were interviewed following a semi-structured interview guide, with sessions audio-recorded. The data were subsequently transcribed and subjected to thematic content analysis. In the quantitative phase, a cross-sectional online survey was administered to 210 adolescents diagnosed with depression using Questionnaire Star, with data analysis performed using SPSS25.0 and AMOS 24.0. Results: The qualitative analysis identified three major themes and nine categories as key risk factors influencing the onset of adolescent depression. Three major themes were generated: school factors, family factors, and other factors. Nine categories were generated: heavy academic load, strained peer, and teacher-student relationships; unstable family structures, internal familial conflicts, and high parental expectations; a strong sense of social isolation, insufficient sexual education, and prevalent suicidal ideation or attempts. A nurturing and supportive school environment significantly bolsters adolescents' sense of hope and coping abilities, while a warm and encouraging family setting effectively mitigates psychological stress. Conversely, heightened loneliness and the onset of suicidal ideation are frequently linked to diminished hope and the adoption of maladaptive coping strategies. Hence, to comprehensively understand the intricate interplay of these factors, this study concentrated on the levels of hope and coping mechanisms, investigating their potential mediating role in adolescent anxiety and depression. Quantitative analysis revealed a positive correlation between anxiety and depression (r = 0.767, p＜0.01). Additionally, it was found that hope levels and coping strategies mediated the relationship between anxiety and depressive symptoms (β = −0.24–0.84 = 0.20, p

ObjectiveSclerodermus wasps are important biocontrol agents of a class of wood borers. Bacterial symbionts influence the ecology and biology of their hosts in a variety of ways, including the formation of life-long beneficial or detrimental parasitic infections. However, only a few studies have explored the species and content of the symbionts in the Sclerodermus species.MethodsHere, a high-throughput sequencing study of the V3-V4 region of the 16S ribosomal RNA gene revealed a high level of microbial variety in four Sclerodermus waps, and their diversities and functions were also predictedResultsThe three most prevalent phyla of microorganisms in the sample were Firmicutes, Bacteroides, and Proteus. The KEEG pathways prediction results indicated that the three pathways with the highest relative abundances in the S. sichuanensis species were translation, membrane transport, and nucleotide metabolism. These pathways differed from those observed in S. guani, S. pupariae, and S. alternatusi, which exhibited carbohydrate metabolism, membrane transport, and amino acid metabolism, respectively. Bacteroides were found to be abundant in several species, whereas Wolbachia was the most abundant among S. sichuanensis, with a significant negative correlation between temperature and carriage rate.ConclusionsThese results offer insights into the microbial communities associated with the bethylid wasps, which is crucial for understanding how to increase the reproductive capacity of wasps, enhance their parasitic effects, and lower cost in biocontrol.

Objectives The blood urea nitrogen to creatinine (BUN/Cr) ratio is associated with early neurological deterioration in acute ischaemic stroke (AIS). However, the predictive value of the BUN/Cr ratio for the AIS prognosis remains unclear. Therefore, we evaluated the correlation between the BUN/Cr ratio and the 3-month outcome in patients with AIS, further testing their dose–response relationship.Design This retrospective cohort study enrolled patients with AIS who were admitted between 1 January 2013 and 31 May 2022. Poor clinical outcome was defined as 3-month Modified Rankin Scale (mRS) >2. Cox proportional HR was used to evaluate the correlation between the BUN/Cr ratio and 3-month outcome. Restricted cubic spline and robust locally weighted regression analyses were conducted to determine the dose–response relationship between the BUN/Cr ratio and the 3-month outcome.Results A total of 4952 eligible patients were included in the study. The patients were divided into three groups according to the tertiles of BUN/Cr ratio (T1, 0.093). After logistic regression adjustment for demographic and clinical characteristics, the BUN/Cr ratio was found to be independently associated with the 3-month outcome in patients with AIS. The restricted cubic spline and locally regression smoothing scatterplot graph showed a strong dose–response relationship between the BUN/Cr ratio and the 3-month outcome in patients with AIS.Conclusion A dose–response relationship was observed between the BUN/Cr ratio and the 3-month outcome in patients with AIS, suggesting that the BUN/Cr ratio could serve as a reliable predictor for the AIS prognosis.

In the context of accelerating ecological fragmentation, it is urgent to enhance the interconnectivity of urban ecological patches to form a resilient ecological network (EN). The construction of a Natural Protected Area (NPA) system proposed in 2019 is the latest strategy implemented by China in protecting ecological spaces. However, the effectiveness of this strategy has not been adequately demonstrated. This study specifically analyzes the concrete impacts of the natural protected area system on the resilience of ecological networks (ENs). The economically developed Urban Agglomeration around Hangzhou Bay (UAHB) was chosen as an example for the argumentation. Firstly, we utilized circuit theory to construct an EN consisting of 173 ecological sources and 401 ecological corridors. Secondly, the ecological sources were categorized into three levels based on their connectivity values. Finally, a dynamic disturbance scenario simulation framework was constructed to evaluate the impact of NPA on the resilience of EN. The results indicated that: (1) The preceding 47% of ecological sources are crucial for maintaining the resilience of the EN; (2) Compared with other ecological spaces, NPAs have a 38% and 1100% greater effect on the resilience of the EN in first and second-level ecological sources, respectively, while its impact in third-level is 118% lower. This study innovatively investigates the differential impacts of hierarchical natural protected areas and natural unprotected areas on the ecological environment.

BackgroundWuhan is located in the hinterland of China, in the east of Hubei Province, at the intersection of the Yangtze River and Hanshui River. It is a national historical and cultural city, an important industrial, scientific, and educational base, and a key transportation hub. There are many schools in Wuhan, with nearly a thousand of all kinds. The number of students is ~2.2 million, accounting for nearly one-fifth of the resident population; college or university students account for ~60% of the total student population. The geographical location of these colleges is relatively concentrated, and the population density is relatively high, making it prone to tuberculosis cluster epidemic.ObjectiveThis study analyzed the epidemiological characteristics and influencing factors of tuberculosis aggregation in schools in Wuhan, China, during 2017–2022 to provide the basis for the scientific development of tuberculosis prevention and control strategies and measures in schools.MethodsThis study adopted the methods of descriptive epidemiology to analyze the epidemic characteristics of tuberculosis aggregation in schools in Wuhan from January 2017 to December 2022, collecting the relevant data on tuberculosis prevention and control in all kinds of schools in the city using Questionnaire Star, an application of the China network questionnaire survey, and analyze the influencing factors of tuberculosis aggregation by using multifactor logistic regression analysis.ResultsFrom 2017 to 2022, 54 outbreaks of pulmonary tuberculosis aggregation in schools were reported in Wuhan, which involved 37 different schools, including 32 colleges or universities and five senior high schools; 176 cases were reported, among which 73 were positive for pathogens and 18 were rifampicin or izoniazid resistant. The median duration of a single cluster epidemic was 46 (26,368) days. Universities were more prone to cluster outbreaks than middle schools (χ2 = 105.160, P = 0.001), and the incidence rate among male students was higher than that of female students in cluster epidemics (χ2 = 12.970, P = 0.001). The multivariate logistic regression analysis results showed that boarding in school (OR = 7.60) is the risk factor for a tuberculosis cluster epidemic in schools. The small number of students (OR = 0.50), the location of the school in the city (OR = 0.60), carry out physical examinations for freshmen (OR = 0.44), carry out illness absence and cause tracking (OR = 0.05), dormitories and classrooms are regularly ventilated with open windows (OR = 0.16), strict implement the management of sick student's suspension from school (OR = 0.36), and seeking timely medical consultation (OR = 0.32) were the protective factors for a tuberculosis cluster epidemic in schools.ConclusionWe successfully identified the epidemiological characteristics and influencing factors of tuberculosis aggregation in schools in Wuhan. The results revealed the influence and status of various factors and indicated ways for schools to improve their TB prevention and control measures in their daily activities. These measures can effectively help curb the cluster epidemic of tuberculosis in schools.

This case report describes a patient initially diagnosed with Gaucher disease (GD) with type I with homozygous mutation c.1448T > C p. (Leu483Pro) at age of 2, presenting with hepatosplenomegaly and cytopenia. Imiglucerase replacement therapy was initiated. At age 17, bilateral hearing loss developed, with subsequent Cranial MRI revealing thalamic damage, leading to a reclassification as type 3 GD. By age of 20, the patient presented with a range of symptoms, including abdominal pain, diarrhea, hypoproteinemia, multiple lymphadenopathy, edema, and Gaucher cell infiltration in the lymph nodes. Comprehensive diagnosis identifies Gaucher tumor and protein-losing enteropathy. Imiglucerase therapy at 90‐120 U/kg every 2 weeks significantly improved clinical symptoms, emphasizing the importance of tailored interventions for managing GD manifestations.

Low-earth orbit (LEO) satellite networks are an important part of the sixth-generation mobile communication system (6G) network, which overcomes the blind spots in ground-based station coverage. However, the limited onboard computing capability and battery capacity cause the problems of extended mission duration and high-energy consumption; therefore, edge computing is introduced in LEO satellite networks, and its key technology is computational offloading. To address the problems of dynamic changes in the intersatellite environment and high-dimensional action space during computational offloading, we propose a genetic algorithm (GA) and deep deterministic policy gradient (DDPG)-based offloading algorithm for edge computing in space-based LEO satellite networks—the GA-DDPG algorithm. The constant change in a satellite edge computing environment will result in sparse rewards (system overhead) and a lack of DDPG exploration. In this study, a GA is introduced into the DDPG algorithm. First, the selection operator of the GA is used to enable the DDPG algorithm to adapt to a changing satellite environment. Second, to address the problem of unstable convergence of the DDPG algorithm owing to the increasing dimension of the action space, the diversity exploration and redundancy of the GA population are used to improve the stability of the convergence of the DDPG algorithm. In this study, a system model, including a space-based LEO satellite constellation structure, mission model, computational model, and load model, is constructed; in addition, a system overhead, weighted by the residual rate of battery energy of edge satellites, is designed to model the problems of minimization of mission delay, minimization of mission energy consumption, and optimization of computational resource allocation as a Markov process. First, the offloading algorithm obtains edge satellites that are visible to the local satellites by analyzing the constraints for establishing links between the satellites. Second, the channel is modeled, and the intersatellite path loss and Doppler shift are modeled, following which the intersatellite transmission rate is obtained. Subsequently, information on the computational capacity and battery energy remaining of each satellite is obtained through the intersatellite link, and a monitoring cycle is set to timely correct the satellite network topology structure. Third, the intersatellite link parameters and mission information are transmitted to the GA-DDPG computational offloading algorithm; various strategies are generated using the GA; elite strategies are input into the replay buffer of the DDPG algorithm; the less adapted strategies are input into the actor network of the DDPG algorithm; the strategies in the replay buffer are used to train their strategies, and the strategies with improved adaptation after training are inserted into the GA population, following which the optimal strategy is determined from the strategy population, and the strategy is updated using the GA to generate the next generation strategy population. The simulation results demonstrate that the GA-DDPG unloading algorithm reduces the computational load of space-based low-orbit satellite networks, and the algorithm confirms its stability (low volatility) through the variance of the computational load. The delay and energy consumption are lower than those of the DDPG and GA unloading algorithms, respectively, increasing the convergence speed and stability of the algorithm compared with the DDPG unloading algorithm.

As the country has loosened its family planning policy and living standards have improved, postnatal obesity has become a social problem seriously threatening public health in China, which has attracted widespread attention from all walks of life. Therefore, a method for improving postpartum obesity urgently needs to be explored. Intestinal microecology is critical to the health of mothers and children, and plays an important role in the occurrence and development of obesity. Improving intestinal microecology as an effective way to improve obesity has attracted more and more attention. This article focuses on the relationship between postnatal obesity and intestinal microecology and summarizes the mechanisms of action of probiotics and prebiotics in regulating intestinal microecology to suppress postpartum obesity. The purpose of this article is to provide a theoretical basis for probiotic-prebiotic intervention based on intestinal microecology to suppress postpartum obesity.