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Microbial phospholipase D (PLD) showed a more competent potential for phospholipids production due to its higher catalytic activity and broader substrate specificity. In this study, the PLD from Acinetobacter sp. DUT-2 (ADPLD) was used as the research object. Firstly, bioinformatics was used to examine the protein sequence characteristics. Then, the recombinant plasmid was generated and heterologously expressed in Escherichia coli. The enzyme protein was purified further, and the substrate selectivity of ADPLD to phosphatidylcholine (PC) with various acyl chains was investigated. Finally, the substrate recognition mechanism of ADPLD was investigated using molecular docking and molecular dynamics simulation. Multiple sequence alignment and phylogenetic tree analysis of ADPLD and other microbial-derived PLDs revealed that the sequence similarity between ADPLD and Streptomyces-derived PLDs was less than 30%, and there was only one conserved HKD motif, indicating that the catalytic mechanism of ADPLD might differ from the reaction mechanism in traditional cognition, which required two HKD motifs to complete the PLD catalytic process. ADPLD was mostly produced as a soluble protein, and a relatively uniform protein could be purified using Ni2+ affinity chromatography at a low concentration of 50 mmol/L imidazole. When soybean PC was utilized as a substrate, the specific activity of ADPLD was about 4.09 U/mg. ADPLD showed relatively high activity in neutralizing short-chain PC (C6~C14), with a specific activity of 13.2 U/mg for 8:0/8:0-PC, which was higher than that of other PC substrates with long acyl chains. The activity of ADPLD on PC reduced dramatically when the acyl chain length of PC grew from C14 to C16. Molecular dynamics simulation and molecular docking experiments revealed that the ADPLD amino acid residues Thr205, Pro209, Phe293, Ala324, Lys329, and Phe453 might form hydrophobic interactions with PC. Arg383 and Gly326 could form hydrogen bonds with PC when the distance between Arg383 (N), Gly326 (N), and PC (P) was

Soybean (Glycine max) is a short-day crop whose flowering time is regulated by photoperiod. The long-juvenile trait extends its vegetative phase and increases yield under short-day conditions. Natural variation in J, the major locus controlling this trait, modulates flowering time. We report that the three J-family genes influence soybean flowering time, with the triple mutant Guangzhou Mammoth-2 flowering late under short days by inhibiting transcription of E1-family genes. J-family genes offer promising allelic combinations for breeding.

Abstract High-quality ocean in situ profile observations are fundamental for ocean and climate research and operational oceanographic applications. Here we describe a new global ocean subsurface temperature profile database named the Chinese Academy of Science (CAS) Oceanography Data Center version 1 (CODC-v1). This database contains over 17 million temperature profiles between 1940–2023 from all available instruments. The major data source is the World Ocean Database (WOD), but CODC-v1 also includes some data from some Chinese institutes which are not available in WOD. The data are quality-controlled (QC-ed) by a new QC system that considers the skewness of local temperature distributions, topographic barriers, and the shift of temperature distributions due to climate change. Biases in Mechanical Bathythermographs (MBTs), eXpendable Bathythermographs (XBTs), and Bottle data (OSD) are all corrected using recently proposed correction schemes, which makes CODC-v1 a bias-corrected dataset. These aspects ensure the data quality of the CODC-v1 database, making it suitable for a wide spectrum of ocean and climate research and applications.

Abstract Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children and the elderly. There are currently no approved RSV-specific therapeutic small molecules available. Using high-throughput antiviral screening, we identified an oral drug, the prenylation inhibitor lonafarnib, which showed potent inhibition of the RSV fusion process. Lonafarnib exhibited antiviral activity against both the RSV A and B genotypes and showed low cytotoxicity in HEp-2 and human primary bronchial epithelial cells (HBEC). Time-of-addition and pseudovirus assays demonstrated that lonafarnib inhibits RSV entry, but has farnesyltransferase-independent antiviral efficacy. Cryo-electron microscopy revealed that lonafarnib binds to a triple-symmetric pocket within the central cavity of the RSV F metastable pre-fusion conformation. Mutants at the RSV F sites interacting with lonafarnib showed resistance to lonafarnib but remained fully sensitive to the neutralizing monoclonal antibody palivizumab. Furthermore, lonafarnib dose-dependently reduced the replication of RSV in BALB/c mice. Collectively, lonafarnib could be a potential fusion inhibitor for RSV infection.

Abstract The long non-coding RNA (lncRNA) Small Nucleolar RNA Host Gene 4 (SNHG4) has been demonstrated to be significantly downregulated in various inflammatory conditions, yet its role in chronic obstructive pulmonary disease (COPD) remains elusive. This study aims to elucidate the biological function of SNHG4 in COPD and to unveil its potential molecular targets. Our findings reveal that both SNHG4 and Four and a Half LIM Domains 1 (FHL1) were markedly downregulated in COPD, whereas microRNA-409-3p (miR-409-3p) was upregulated. Importantly, SNHG4 exhibited a negative correlation with inflammatory markers in patients with COPD, but a positive correlation with forced expiratory volume in 1s percentage (FEV1%). SNHG4 distinguished COPD patients from non-smokers with high sensitivity, specificity, and accuracy. Overexpression of SNHG4 ameliorated cigarette smoke extract (CSE)-mediated inflammation, apoptosis, oxidative stress, and airway remodeling in 16HBE bronchial epithelial cells. These beneficial effects of SNHG4 overexpression were reversed by the overexpression of miR-409-3p or the silencing of FHL1. Mechanistically, SNHG4 competitively bound to miR-409-3p, mediating the expression of FHL1, and consequently improving inflammation, apoptosis, oxidative stress, and airway remodeling in 16HBE cells. Additionally, SNHG4 regulated the miR-409-3p/FHL1 axis to inhibit the activation of the mitogen-activated protein kinase (MAPK) pathway induced by CSE. In a murine model of COPD, knockdown of SNHG4 exacerbated CSE-induced pulmonary inflammation, apoptosis, and oxidative stress. In summary, our data affirm that SNHG4 mitigates pulmonary inflammation, apoptosis, and oxidative damage mediated by COPD through the regulation of the miR-409-3p/FHL1 axis. Graphical Abstract

Abstract Precise neurostimulation can revolutionize therapies for neurological disorders. Electrode-based stimulation devices face challenges in achieving precise and consistent targeting due to the immune response and the limited penetration of electrical fields. Ultrasound can aid in energy propagation, but transcranial ultrasound stimulation in the deep brain has limited spatial resolution caused by bone and tissue scattering. Here, we report an implantable piezoelectric ultrasound stimulator (ImPULS) that generates an ultrasonic focal pressure of 100 kPa to modulate the activity of neurons. ImPULS is a fully-encapsulated, flexible piezoelectric micromachined ultrasound transducer that incorporates a biocompatible piezoceramic, potassium sodium niobate [(K,Na)NbO3]. The absence of electrochemically active elements poses a new strategy for achieving long-term stability. We demonstrated that ImPULS can i) excite neurons in a mouse hippocampal slice ex vivo, ii) activate cells in the hippocampus of an anesthetized mouse to induce expression of activity-dependent gene c-Fos, and iii) stimulate dopaminergic neurons in the substantia nigra pars compacta to elicit time-locked modulation of nigrostriatal dopamine release. This work introduces a non-genetic ultrasound platform for spatially-localized neural stimulation and exploration of basic functions in the deep brain.

This paper proposes an efficient method for quantifying the stratigraphic uncertainties and modeling the geological formations based on boreholes. Two Markov chains are used to describe the soil transitions along different directions, and the transition probability matrices (TPMs) of the Markov chains are analytically expressed by copulas. This copula expression is efficient since it can represent a large TPM by a few unknown parameters. Due to the analytical expression of the TPMs, the likelihood function of the Markov chain model is given in an explicit form. The estimation of the TPMs is then re-casted as a multi-objective constrained optimization problem that aims to maximize the likelihoods of two independent Markov chains subject to a set of parameter constraints. Unlike the method which determines the TPMs by counting the number of transitions between soil types, the proposed method is more statistically sound. Moreover, a random path sampling method is presented to avoid the directional effect problem in simulations. The soil type at a location is inferred from its nearest known neighbors along the cardinal directions. A general form of the conditional probability, based on Pickard's theorem and Bayes rule, is presented for the soil type generation. The proposed stratigraphic characterization and simulation method is applied to real borehole data collected from a construction site in Wuhan, China. It is illustrated that the proposed method is accurate in prediction and does not show an inclination during simulation.

Abstract The wet bulb temperature (Tw) has gained considerable attention as a crucial indicator of heat-related health risks. Here we report south-to-north spatially heterogeneous trends of Tw in China over 1979-2018. We find that actual water vapor pressure (Ea) changes play a dominant role in determining the different trend of Tw in southern and northern China, which is attributed to the faster warming of high-latitude regions of East Asia as a response to climate change. This warming effect regulates large-scale atmospheric features and leads to extended impacts of the South Asia high (SAH) and the western Pacific subtropical high (WPSH) over southern China and to suppressed moisture transport. Attribution analysis using climate model simulations confirms these findings. We further find that the entire eastern China, that accommodates 94% of the country’s population, is likely to experience widespread and uniform elevated thermal stress the end of this century. Our findings highlight the necessity for development of adaptation measures in eastern China to avoid adverse impacts of heat stress, suggesting similar implications for other regions as well.

Objective: This study aimed to reveal associations between metabolic hormones in cerebral spinal fluid (CSF) and cigarette smoking-induced weight gain and to explore the underlying mechanism. Methods: A total of 156 adult men were included, comprising active smokers and nonsmokers. In addition to demographic information and body mass index (BMI), plasma levels of ApoA1 and ApoB, high-density lipoprotein, low-density lipoprotein, cholesterol, triglyceride, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase in the participants were measured. Moreover, the metabolic hormones adiponectin, fibroblast growth factor 21 (FGF21), ghrelin, leptin, and orexin A, as well as the trace elements iron and zinc in CSF, were assessed. Results: Compared to nonsmokers, active smokers showed higher BMI, and elevated CSF levels of FGF21, Zn, and Fe, but decreased levels of metabolic hormones adiponectin, ghrelin, leptin, and orexin A. Negative correlations existed between CSF FGF21 and ghrelin, between CSF Zn and ghrelin, as well as between CSF Fe and orexin A in active smokers. Furthermore, elevated CSF FGF21 and Zn predicted ghrelin level decrease in the smokers. Conclusion: These data relate smoking-induced weight gain to its neurotoxic effect on the neurons that synthesize metabolic hormones such as adiponectin, ghrelin, leptin, or orexin A in the brain, by disrupting mitochondrial function and causing oxidative stress in the neurons.

Abstract The homogeneity hypothesis is a common assumption in classic measurement. However, the item response theory model assumes that different respondents with same ability have the same option probabilities, which may not hold. The aim of this study is to propose a new individual random effect model that accounts for the differences in option probabilities among respondents with same latent traits by using within-person variance. The performance of the new model is evaluated through simulation studies and real data using the PRESUPP scale of PISA. The model parameters are estimated by the MCMC method. The results show that the individual random effect model can provide more accurate parameter estimates and obtain a scale parameter to describe the distribution of respondents’ abilities, under different within-person variances. The new model has lower RMSE and better model fit than the classic IRT model.

Abstract Objective Alcohol withdrawal syndrome (AWS) is a complex condition associated with alcohol use disorder (AUD), characterized by significant variations in symptom severity among patients. The psychological and emotional symptoms accompanying AWS significantly contribute to withdrawal distress and relapse risk. Despite the importance of neural adaptation processes in AWS, limited genetic investigations have been conducted. This study primarily focuses on exploring the single and interaction effects of single-nucleotide polymorphisms in the ANK3 and ZNF804A genes on anxiety and aggression severity manifested in AWS. By examining genetic associations with withdrawal-related psychopathology, we ultimately aim to advance understanding the genetic underpinnings that modulate AWS severity. Methods The study involved 449 male patients diagnosed with alcohol use disorder. The Self-Rating Anxiety Scale (SAS) and Buss-Perry Aggression Questionnaire (BPAQ) were used to assess emotional and behavioral symptoms related to AWS. Genomic DNA was extracted from peripheral blood, and genotyping was performed using PCR. Results Single-gene analysis revealed that naturally occurring allelic variants in ANK3 rs10994336 (CC homozygous vs. T allele carriers) were associated with mood and behavioral symptoms related to AWS. Furthermore, the interaction between ANK3 and ZNF804A was significantly associated with the severity of psychiatric symptoms related to AWS, as indicated by MANOVA. Two-way ANOVA further demonstrated a significant interaction effect between ANK3 rs10994336 and ZNF804A rs7597593 on anxiety, physical aggression, verbal aggression, anger, and hostility. Hierarchical regression analyses confirmed these findings. Additionally, simple effects analysis and multiple comparisons revealed that carriers of the ANK3 rs10994336 T allele experienced more severe AWS, while the ZNF804A rs7597593 T allele appeared to provide protection against the risk associated with the ANK3 rs10994336 mutation. Conclusion This study highlights the gene-gene interaction between ANK3 and ZNF804A, which plays a crucial role in modulating emotional and behavioral symptoms related to AWS. The ANK3 rs10994336 T allele is identified as a risk allele, while the ZNF804A rs7597593 T allele offers protection against the risk associated with the ANK3 rs10994336 mutation. These findings provide initial support for gene-gene interactions as an explanation for psychiatric risk, offering valuable insights into the pathophysiological mechanisms involved in AWS.

Abstract Various studies have focused on the application of fibrin sealants (FS) in thyroid surgery. Utilizing a meta-analysis, this systematic review analyzed the findings of recent randomized controlled trials on the safety and efficacy of FS in patients who underwent thyroidectomy. The Cochrane Library, Web of Science, Embase, PubMed, and Medline databases were searched for relevant studies, without any language restrictions. Seven randomized controlled trials were included in the originally identified 69 studies. Overall, 652 patients received FS during thyroid surgery; their outcomes were compared with those of conventionally treated patients. The primary outcomes were total volume of wound drainage, length of hospitalization, and operative time. Significant differences were observed in the total volume of wound drainage (mean deviation (MD): -29.75, 95% confidence interval (CI): -55.39 to -4.11, P = 0.02), length of hospitalization (MD: -0.84, 95% CI: -1.02 to -0.66, P

Abstract Suicide is prevalent among young adults, and epidemiological studies indicate that insomnia, nightmares, and depression are significantly associated with a high incidence of suicidal ideation (SI). However, the causal relationship between these factors and SI remains unclear. Therefore, the purpose of this study was to examine the association between nightmares and depression and insomnia and SI in young adults, as well as to develop a mediation model to investigate the causal relationship between insomnia, nightmare, depression, and SI. We assessed insomnia, nightmares, depression, and SI in 546 young adults using the Insomnia Severity Scale (ISI), Disturbing Dream and Nightmare Severity Scale (DDNSI), Depression Study Scale (CESD-20), and Columbia-Suicide Severity Rating Scale (C-SSRS). Using the Bootstrap method, the mediation effects of nightmares and depression between insomnia and SI were calculated. The results demonstrated that nightmares and depression fully mediated the relationship between insomnia and SI, including the chain-mediation of insomnia and SI between nightmare and depression with an effect value of 0.02, 95% CI 0.01–0.04, and depression as a mediator between insomnia and SI with an effect value of 0.22, 95% CI 0.15–0.29. This study found that depression and nightmares may be risk and predictive factors between insomnia and SI, which implies that the assessment and treatment of depression and the simple or linked effect of nightmares play crucial roles in preventing SI in young adults.

Abstract Diquat (DQ) is among the most widely used herbicides, and its intake can cause severe systemic toxicity that manifests rapidly. The resultant symptoms can cause the dysfunction of a range of tissues and organs,. As there is no specific antidote for diquat poisoning and the efficacy of extant treatments is suboptimal, physicians must acquire a more comprehensive understanding of the most effective approaches to managing affected patients. Relative few studies have been published to date focused on diquat poisoning in pediatric patients. In this report, we compare two similar cases of juvenile diquat poisoning with dynamic changes in clinical manifestations, laboratory values, and imaging results. For the first time, the difference in whether to perform blood flow perfusion and the time difference of initiation of hemoperfusion had a clear clinical difference in the subsequent effects of diquat poisoning in children with diquat poisoning. Limited evidence is available regarding the efficacy of early hemoperfusion for diquat poisoning; however, the differences in clinical outcomes articulated here highlight the benefits of early and timely hemoperfusion therapy in the treatment of DQ toxicity in children, in conjunction with primary supportive care in the management of DQ poisoning in children.

Most coal mine accidents are caused by people’s unsafe behavior, and people’s unsafe behavior is caused by the low level of coal miners’ safety information cognition. In order to prevent and control coal mine safety accidents caused by coal miners’ failure of safety information cognition, through the analysis of typical coal mine accident cases in China in recent years, three first-level indicators and 15 second-level indicators affecting coal miners’ safety information cognition are determined, and the social network analysis method is used to construct the coal miners’ safety information cognition network. Through the overall network density analysis, individual network density analysis, node degree centrality analysis, node intermediate centrality analysis, key influencing factor analysis and important influencing path analysis of safety information cognitive factors, five key influencing factors such as identification understanding ability and safety knowledge are obtained, and the key influencing path is identified.

Abstract This article introduces two transmissive metasurfaces applied to normal windows, aiming to improve the 5G outdoor-to-indoor (O2I) coverage. These windows can be utilized in various settings, such as vehicles or buildings. The proposed unit cells, designed to be wide-incident angle and polarization insensitive, are implemented in both single-glazing and double-glazing glasses, arranged in a periodic structure to form the transmission surfaces. Both metasurfaces maintain optical transparency by incorporating Indium Tin Oxide (ITO) as the conductive element in each unit cell. These engineered transmission surfaces enhance the 5G signal indoor coverage at the 3.5 GHz band across a broad range of incident angles. While multi-layer structures typically exhibit heightened sensitivity to the angle of incidence, the proposed two-layered transmissive surfaces demonstrate substantial angular stability, reaching up to 65 and 75 degrees for double- and single-glazed glass, respectively. To achieve this wide and stable angular response, evolutionary optimization techniques were employed to fine-tune the proposed unit cells. Both designs exhibit a high transmission coefficient across the operating frequency for a variety of incident angles, surpassing those reported in the existing literature. Experimental evaluations of the fabricated prototypes indicate that both metasurfaces hold significant potential for enhancing signal propagation into buildings and vehicles.

Abstract Multimode fibers (MMFs) are gaining renewed interest for nonlinear effects due to their high-dimensional spatiotemporal nonlinear dynamics and scalability for high power. High-brightness MMF sources with effective control of the nonlinear processes would offer possibilities in many areas from high-power fiber lasers, to bioimaging and chemical sensing, and to intriguing physics phenomena. Here we present a simple yet effective way of controlling nonlinear effects at high peak power levels. This is achieved by leveraging not only the spatial but also the temporal degrees of freedom during multimodal nonlinear pulse propagation in step-index MMFs, using a programmable fiber shaper that introduces time-dependent disorders. We achieve high tunability in MMF output fields, resulting in a broadband high-peak-power source. Its potential as a nonlinear imaging source is further demonstrated through widely tunable two-photon and three-photon microscopy. These demonstrations provide possibilities for technology advances in nonlinear optics, bioimaging, spectroscopy, optical computing, and material processing.

Abstract To address the problems of low efficacy and low microbial activity in low-temperature municipal wastewater treatment, this study utilized an air-lift micro-pressure internal circulation integrated reactor (AMICIR). Through controlling the amount of aeration and dissolved oxygen (DO) in the reactor, AMICIR creates alternating aerobic and anaerobic environments, explores the enrichment conditions of aerobic denitrifying bacteria, examines the changes in pollutant removal efficiency and the characteristics of bacterial colony structure during the process of enrichment of aerobic denitrifying bacteria in the system, and reveals the mechanism of nitrogen removal by aerobic denitrifying bacteria cooperating with anaerobic denitrifying bacteria in the low-temperature municipal wastewater treatment system. Experimental results showed average removal rates of NH4 +-N, chemical oxygen demand (COD), total phosphorus (TP), and total nitrogen (TN) reaching 93.85%, 89.30%, 92.75%, and 75.4%, respectively. The microorganisms secreted large amounts of proteins and polysaccharides, forming zoogloea and anaerobic microenvironments conducive to traditional denitrification reactions. IlluminaMiSeq sequencing analysis revealed the presence of anaerobic phyla. The system was enriched with a large number of microorganisms, and aerobic denitrifying bacteria (Flavobacterium, Rhodoferax, and Pseudomonas) were successfully cultured. Flavobacterium emerged as the dominant species, with relative abundance ranging from 18.56% to 22.60%. Functional gene prediction indicated high abundance of aerobic denitrification genes, such as napA. Aerobic denitrifying bacteria were successfully enriched in the system to improve nitrogen removal from municipal wastewater at low temperatures.

Abstract As the largest transporter family impacting on tumor genesis and development, the prognostic value of solute carrier (SLC) members has not been elucidated in colorectal cancer (CRC). We aimed to identify a prognostic signature from the SLC members and comprehensively analyze their roles in CRC. Firstly, we downloaded transcriptome data and clinical information of CRC samples from GEO (GSE39582) and TCGA as training and testing dataset, respectively. We extracted the expression matrix of SLC genes and established a prognostic model by univariate and multivariate Cox regression. Afterwards, the low-risk and high-risk group were identified. Then, the differences of prognosis traits, transcriptome features, clinical characteristics, immune infiltration and drug sensitivity between the two groups were explored. Furthermore, molecular subtyping was also implemented by non-negative matrix factorization (NMF). Finally, we studied the expression of the screened SLC genes in CRC tumor tissues and normal tissues as well as investigated the role of SLC12A2 by loss of function and gain of function. As a result, we developed a prognostic risk model based on the screened 6-SLC genes (SLC39A8, SLC2A3, SLC39A13, SLC35B1, SLC4A3, SLC12A2). Both in the training and testing sets, CRC patients in the high-risk group had the poorer prognosis and were in the more advanced pathological stage. What’s more, the high-risk group were enriched with CRC progression signatures and immune infiltration. Two groups showed different drug sensitivity. On the other hand, two distinct subclasses (C1 and C2) were identified based on the 6 SLC genes. CRC patients in the high-risk group and C1 subtype had a worse prognosis. Furthermore, we found and validated that SLC12A2 was steadily upregulated in CRC. A loss-of-function study showed that knockdown of SLC12A2 expression restrained proliferation and stemness of CRC cells while a gain-of-function study showed the contrary results. Hence, we provided a 6-SLC gene signature for prognosis prediction of CRC patients. At the same time, we identified that SLC12A2 could promote tumor progression in CRC, which may serve as a potential therapeutic target.

Abstract Chronic Eosinophilic Leukemia (CEL), a rare and intricate hematological disorder characterized by uncontrolled eosinophilic proliferation, presents clinical challenges owing to its infrequency. This study aimed to investigate epidemiology and develop a prognostic nomogram for CEL patients. Utilizing the Surveillance, Epidemiology and End Results database, CEL cases diagnosed between 2001 and 2020 were analyzed for incidence rates, clinical profiles, and survival outcomes. Patients were randomly divided into training and validation cohorts (7:3 ratio). LASSO regression analysis and Cox regression analysis were performed to screen the prognostic factors for overall survival. A nomogram was then constructed and validated to predict the 3- and 5-year overall survival probability of CEL patients by incorporating these factors. The incidence rate of CEL was very low, with an average of 0.033 per 100,000 person-years from 2001 to 2020. The incidence rate significantly increased with age and was higher in males than females. The mean age at diagnosis was 57 years. Prognostic analysis identified advanced age, specific marital statuses, and secondary CEL as independent and adverse predictors of overall survival. To facilitate personalized prognostication, a nomogram was developed incorporating these factors, demonstrating good calibration and discrimination. Risk stratification using the nomogram effectively differentiated patients into low- and high-risk groups. This study enhances our understanding of CEL, offering novel insights into its epidemiology, demographics, and prognostic determinants, while providing a possible prognostication tool for clinical use. However, further research is warranted to elucidate molecular mechanisms and optimize therapeutic strategies for CEL.

Abstract Background Current studies have shown that longer observation time can improve neoplastic detection rate. This study aimed to clarify whether endoscopists with longer observation times can detect more focal lesions. Methods Based on the mean examination time for Esophagogastroduodenoscopy (EGD) without biopsy, endoscopists were divided into fast and slow groups, and the detection rate of focal lesions was compared between the two groups. Univariate analysis, multivariate analysis and restricted cubic spline were used to explore the factors of focal lesion detection rate. Results Mean examination time of EGD without biopsy was 4.5 min. The cut-off times used were 5 min. 17 endoscopists were classified into the fast (4.7 ± 3.6 min), and 16 into the slow (7.11 ± 4.6 min) groups. Compared with fast endoscopists, slow endoscopists had a higher detection rate of focal lesions (47.2% vs. 51.4%, P

Abstract Background Human discs large-associated protein 5 (DLGAP5) is reported to play a pivotal role in regulating the cell cycle and implicate in tumorigenesis and progression of various cancers. Our current research endeavored to explore the prognostic value, immune implication, biological function and targeting strategy of DLGAP5 in LUAD through approaches including bioinformatics, network pharmacology analysis and experimental study. Methods Multiple databases, including TCGA, GEO, CPTAC and Human Protein Atlas, were utilized to explore the expression and clinical significance of DLGAP5 in LUAD. The genetic alterations of DLGAP5 were assessed through cBioPortal and COSMIC databases. The relationship between DLGAP5 expression and genetic abnormalities of driver genes in LUAD was analyzed through TIMER2.0 database. CancerSEA database was utilized to explore the function of DLGAP5 in 14 different states in LUAD at single-cell resolution. GDSC database was utilized to analyze the impact of DLGAP5 on IC50 of frequently-used anti-LUAD drugs. CIBERSORT method and TIMER2.0 database was utilized to explore the relationship between DLGAP5 and tumor immune infiltration. Network pharmacology was applied to screen potential DLGAP5 inhibitor. In vitro and in vivo experiments were utilized to evaluate biological function and downstream targets of DLGAP5, and the effect of screened DLGAP5 inhibitor on LUAD growth. Results High DLGAP5 expression was commonly observed in LUAD and associated with mutation of major driver genes, poor prognosis, high IC50 values of frequently-used anti-LUAD drugs, increasing immune infiltration and elevated immune checkpoint blockade-related genes in LUAD. PLK1 was revealed as a potential DLGAP5 downstream target in LUAD. DLGAP5 overexpression or knockdown significantly promoted or inhibited LUAD cell proliferation and PLK1 expression. PLK1 overexpression well rescued DLGAP5 knockdown-induced cell proliferation inhibition, or vice versa. Furthermore, by virtual screening of an investigational drug library from the DrugBank database, AT9283 was screened and identified as a novel DLGAP5 inhibitor. AT9283 effectively suppressed growth of LUAD cells both in vitro and in vivo. DLGAP5 overexpression significantly reversed AT9283-induced proliferation inhibition. Moreover, AT9283 significantly suppressed DLGAP5 and PLK1 expression, while DLGAP5 overexpression significantly reversed AT9283-induced PLK1 suppression. Conclusion Our research has demonstrated that DLGAP5 is upregulated in LUAD and exhibits a strong correlation with unfavorable prognosis. Furthermore, DLGAP5 assumes a significant function in the regulation of tumor immunity and treatment outcome of immune checkpoint inhibitors. Of note, we found that DLGAP5 promotes cell proliferation of LUAD via upregulating PLK1. Targeting DLGAP5 by AT9283, our newly identified DLGAP5 inhibitor, suppresses LUAD growth. DLGAP5 may become a promising prognostic biomarker and therapeutic target for patients with LUAD.

IntroductionYouth e-cigarette (EC) use has rapidly increased in the last few years. It is crucial to identify the susceptible youth and prevent them from EC uptake. This study was conducted to investigate factors that affect youth susceptibility to EC use.MethodsThis study employed a cross-sectional survey design, utilizing multi-center stratified cluster sampling method to select two junior high schools and two senior high schools in Shanghai, Guangzhou, and Chengdu. One-third of classes of each grade in the selected schools were involved in this survey. After obtaining the informed consent of parents, an anonymous and self-administered questionnaire was distributed to students. Questionnaire was designed based on the Ecological Models of Health Behavior. Associations between EC susceptibility and covariates were identified using multivariate logistic regression.ResultsAmong 2,270 students who had never vaped, 38.0% were susceptible to ECs. Logistic regression analysis identified factors on different levels affecting the susceptibility. Individual factors included senior high school students (OR = 1.34, 95% CI: 1.08–1.65), sensation seeker (OR = 1.11, 95%CI: 1.08–1.14), poor academic performance (OR = 1.24, 95% CI: 1.01–1.54), ever cigarette user (OR = 2.27, 95% CI: 1.29–4.01), unaware of the second-hand smoke from vaping (OR = 1.56, 95% CI: 1.25–1.96), agreeable with “I do not want to hang around vapers” (OR = 0.79, 95% CI: 0.64–0.97), agreeable with “ECs are more fashionable than cigarette” (OR = 2.50, 95% CI: 1.72–3.62) and favorable attitudes toward vaping (OR = 5.09, 95% CI: 3.78–6.85) were significantly associated with susceptibility to ECs. At interpersonal level, students who believe they would not be punished by parents for vaping increased susceptibility (OR = 1.27, 95% CI:1.01–1.59). At community level, exposure of EC advertising (OR = 1.81, 95% CI:1.46–2.25), exposure to hazard information (OR = 0.76, 95% CI: 0.59–0.97) and seeing vaping in daily life (OR = 2.11, 95% CI: 1.62–2.74), were statistically significantly associated with youth susceptibility to ECs.ConclusionEC susceptibility was observed in a substantial proportion of adolescents who had never vaped, influenced by factors on different levels. This research underscores the urgent need for comprehensive intervention strategies to prevent the youth susceptibility to ECs.

Biosynthesis and biodegradation of microorganisms critically underpin the development of biotechnology, new drugs and therapies, and environmental remediation. However, most uncultured microbial species along with their metabolic capacities in extreme environments, remain obscured. Here we unravel the metabolic potential of microbial dark matters (MDMs) in four deep-inland hypersaline lakes in Xinjiang, China. Utilizing metagenomic binning, we uncovered a rich diversity of 3030 metagenome-assembled genomes (MAGs) across 82 phyla, revealing a substantial portion, 2363 MAGs, as previously unclassified at the genus level. These unknown MAGs displayed unique distribution patterns across different lakes, indicating a strong correlation with varied physicochemical conditions. Our analysis revealed an extensive array of 9635 biosynthesis gene clusters (BGCs), with a remarkable 9403 being novel, suggesting untapped biotechnological potential. Notably, some MAGs from potentially new phyla exhibited a high density of these BGCs. Beyond biosynthesis, our study also identified novel biodegradation pathways, including dehalogenation, anaerobic ammonium oxidation (Anammox), and degradation of polycyclic aromatic hydrocarbons (PAHs) and plastics, in previously unknown microbial clades. These findings significantly enrich our understanding of biosynthesis and biodegradation processes and open new avenues for biotechnological innovation, emphasizing the untapped potential of microbial diversity in hypersaline environments.

Background and aims The immunosuppressive tumor microenvironment (TME) plays an essential role in cancer progression and immunotherapy response. Despite the considerable advancements in cancer immunotherapy, the limited response to immune checkpoint blockade (ICB) therapies in patients with hepatocellular carcinoma (HCC) remains a major challenge for its clinical implications. Here, we investigated the molecular basis of the protein O-fucosyltransferase 1 (POFUT1) that drives HCC immune evasion and explored a potential therapeutic strategy for enhancing ICB efficacy.Methods De novo MYC/Trp53−/− liver tumor and the xenograft tumor models were used to evaluate the function of POFUT1 in immune evasion. Biochemical assays were performed to elucidate the underlying mechanism of POFUT1-mediated immune evasion.Results We identified POFUT1 as a crucial promoter of immune evasion in liver cancer. Notably, POFUT1 promoted HCC progression and inhibited T-cell infiltration in the xenograft tumor and de novo MYC/Trp53−/− mouse liver tumor models. Mechanistically, we demonstrated that POFUT1 stabilized programmed death ligand 1 (PD-L1) protein by preventing tripartite motif containing 21-mediated PD-L1 ubiquitination and degradation independently of its protein-O-fucosyltransferase activity. In addition, we further demonstrated that PD-L1 was required for the tumor-promoting and immune evasion effects of POFUT1 in HCC. Importantly, inhibition of POFUT1 could synergize with anti-programmed death receptor 1 therapy by remodeling TME in the xenograft tumor mouse model. Clinically, POFUT1 high expression displayed a lower response rate and worse clinical outcome to ICB therapies.Conclusions Our findings demonstrate that POFUT1 functions as a novel regulator of tumor immune evasion and inhibition of POFUT1 may be a potential therapeutic strategy to enhance the efficacy of immune therapy in HCC.

Abstract Cell mechanotransduction signals are important targets for physical therapy. However, current physiotherapy heavily relies on ultrasound, which is generated by high‐power equipment or amplified by auxiliary drugs, potentially causing undesired side effects. To address current limitations, a robotic actuation‐mediated therapy is developed that utilizes gentle mechanical loads to activate mechanosensitive ion channels. The resulting calcium influx precisely regulated the expression of recombinant tumor suppressor protein and death‐associated protein kinase, leading to programmed apoptosis of cancer cell line through caspase‐dependent pathway. In stark contrast to traditional gene therapy, the complete elimination of early‐ and middle‐stage tumors (volume ≤ 100 mm3) and significant growth inhibition of late‐stage tumor (500 mm3) are realized in tumor‐bearing mice by transfecting mechanogenetic circuits and treating daily with quantitative robotic actuation in a form of 5 min treatment over the course of 14 days. Thus, this massage‐derived therapy represents a quantitative strategy for cancer treatment.

Abstract The climate benefit of blue carbon sequestered by mangrove forests can be partially offset by CH4 emission, but this offset is rarely assessed using multi‐year high‐frequency measurements. Here, four‐year eddy covariance measurements were used to examine temporal patterns of CH4 flux and its blue carbon offset (i.e., reduced climate benefit) in a subtropical estuarine mangrove in China. We found both diel and seasonal CH4 fluxes were mainly driven by soil temperature and tidal activities, showing greater nighttime emission. On average, one‐tenth of CO2 uptake was offset by CH4 emission using the sustained‐flux global warming potential metric at a 20‐year time horizon, while this offset could vary over an order of magnitude due to asynchronous fluxes of CH4 and CO2 across diel and seasonal cycles. These results highlight the significant contribution of nighttime emission to mangrove CH4 budget and the importance of asynchronous flux variations in assessing mangrove's climate benefit.

Although brain-computer interface (BCI) is considered a revolutionary advancement in human-computer interaction and has achieved significant progress, a considerable gap remains between the current technological capabilities and their practical applications. To promote the translation of BCI into practical applications, the gold standard for online evaluation for classification algorithms of BCI has been proposed in some studies. However, few studies have proposed a more comprehensive evaluation method for the entire online BCI system, and it has not yet received sufficient attention from the BCI research and development community. Therefore, the qualitative leap from analyzing and modeling for offline BCI data to the construction of online BCI systems and optimizing their performance is elaborated, and then user-centred is emphasized, and then the comprehensive evaluation methods for translating BCI into practical applications are detailed and reviewed in the article, including the evaluation of the usability (including effectiveness and efficiency of systems), the evaluation of the user satisfaction (including BCI-related aspects, etc.), and the evaluation of the usage (including the match between the system and user, etc.) of online BCI systems. Finally, the challenges faced in the evaluation of the usability and user satisfaction of online BCI systems, the efficacy of online BCI systems, and the integration of BCI and artificial intelligence (AI) and/or virtual reality (VR) and other technologies to enhance the intelligence and user experience of the system are discussed. It is expected that the evaluation methods for online BCI systems elaborated in this review will promote the translation of BCI into practical applications.

Background: Borrelia miyamotoi is a spirochete species transmitted via hard ticks. Following its discovery in Japan, this pathogen has been detected around the world, and is increasingly confirmed as a human pathogen causing febrile disease, namely relapsing fever. Its presence has been confirmed in the Northeast China. However, there is little information regarding the presence of B. miyamotoi and other hard-tick-borne relapsing fever spirochetes in southern China including Yunnan province, where tick and animal species are abundant and many people both inhabit and visit for recreation. Methods: For the present study, we collected samples of ticks, wildlife, and domestic animal hosts from different counties in Yunnan province. Nucleic acids from samples were extracted, and the presence of B. miyamotoi and other relapsing fever spirochetes was confirmed using polymerase chain reaction (PCR) for the 16S rRNA specific target gene fragment. The positive samples were then amplified for partial genome of the flaB and glpQ genes. Statistical differences in its distribution were analyzed by SPSS 20 software. Sequence of partial 16S rRNA, flaB and glpQ genome were analyzed and phylogenetic trees were constructed. Results: A total of 8260 samples including 2304 ticks, 4120 small mammals and 1836 blood of domestic animal hosts were collected for screening for infection of B. miyamotoi and other relapsing fever spirochetes. Cattle and sheep act as the main hosts and Rhipicephalus microplus, Haemaphysalis nepalensis, H. kolonini and Ixodes ovatus were identified as the important vector host with high prevalence or wide distribution. Only one Mus caroli (mouse) and one Sorex alpinus (shrew) were confirmed positive for relapsing fever spirochetes. Evidence of vertical transmission in ticks was also confirmed. Two known strains of B. miyamotoi and one novel relapsing fever spirochetes, B. theileri-like agent, were confirmed and described with their host adaptation, mutation, and potential risk of spreading and spillover for human beings. Conclusions: Our results provide new evidence of relapsing fever spirochetes in vector and animal hosts in Yunnan province based on large sample sizes, and offer guidance on further investigation, surveillance and monitoring of this pathogen.

Osteoarthritis (OA) is characterized by progressive and irreversible damage to the articular cartilage and a consecutive inflammatory response. However, the majority of clinical drugs for OA treatment only alleviate symptoms without addressing the fundamental pathology. To mitigate this issue, we developed an inflammation-responsive carrier and encapsulated bioactive material, namely, LDH@TAGel. The LDH@TAGel was designed with anti-inflammatory and antioxidative abilities, aiming to directly address the pathology of cartilage damage. In particular, LDH was confirmed to restore the ECM secretion function of damaged chondrocytes and attenuate the expression of catabolic matrix metalloproteinases (Mmps). While TAGel showed antioxidant properties by scavenging ROS directly. In vitro evaluation revealed that the LDH@TAGel could protect chondrocytes from inflammation-induced oxidative stress and apoptosis via the Nrf2/Keap1 system and Pi3k-Akt pathway. In vivo experiments demonstrated that the LDH@TAGel could alleviated the degeneration and degradation of cartilage induced by anterior cruciate ligament transection (ACLT). The OARSI scores indicating OA severity decreased significantly after three weeks of intervention. Moreover, the IVIS image revealed that LDH@TAGel enhances the controlled release of LDH in a manner that can be customized according to the severity of OA, allowing adaptive, precise treatment. In summary, this novel design effectively alleviates the underlying pathological causes of OA-related cartilage damage and has emerged as a promising biomaterial for adaptive, cause-targeted OA therapies.

ABSTRACT: Salmonella, which is widely distributed in nature, is an important zoonotic pathogen affecting humans, livestock, and other animals. Salmonella infection not only hinders the development of livestock and poultry-related industries but also poses a great threat to human health. In this study, we collected 1,537 samples including weak chicks, dead embryos, fecal samples and environmental samples from 2020 to 2023 (for a period of 1 to 2 months per year) to keep a long-term monitor the prevalence of Salmonella in an intensive laying hen farm, 105 Salmonella strains were isolated with an isolation rate of 6.83% (105/1,537). It revealed a significant decrease in prevalence rates of Salmonella over time (P < 0.001). Before 2020, the predominant serotype was S. Enteritidis. S. Kentucky was first detected in November 2020 and its proportion was gradually found to exceed that of S. Enteritidis since then. S. Kentucky isolates were distributed in various links of the four regions in the poultry farm. A total of 55 S. Kentucky strains, were assigned to ST198 based on whole genome sequencing. Among them, 54 strains were resistant to 12 to 16 antibiotics, indicating that they were extensively drug-resistant (XDR). Seventeen antimicrobial resistance genes were detected in 55 S. Kentucky isolates. For most of these isolates, antibiotic resistance phenotypes were concordant with their genotypes. All S. Kentucky strains isolated from this farm in 2020 to 2023 showed a high similarity based on their core-genome SNP-based phylogeny. The traceability analysis revealed that S. Kentucky was introduced to the farm through newly purchased flocks. The long-term existence of XDR S. Kentucky ST198 poses a substantial risk because of the multiage management and circulation of workers in this poultry farm. Thus, this study is the first to report extensively drug-resistant S. Kentucky ST198 detected in this intensive poultry farm in China.

Abstract Background Human dermal fibroblasts (HDFs) are essential in the processes of skin ageing and wound healing. However, the underlying mechanism of HDFs in skin healing of the elderly has not been well defined. This study aims to elucidate the mechanisms of HDFs senescence and how senescent HDFs affect wound healing in aged skin. Methods The expression and function of sperm equatorial segment protein 1 (SPESP1) in skin ageing were evaluated via in vivo and in vitro experiments. To delve into the potential molecular mechanisms by which SPESP1 influences skin ageing, a combination of techniques was employed, including proteomics, RNA sequencing, immunoprecipitation, chromatin immunoprecipitation and liquid chromatography‐mass spectrometry analyses. Clearance of senescent cells by dasatinib plus quercetin (D+Q) was investigated to explore the role of SPESP1‐induced senescent HDFs in wound healing. Results Here, we define the critical role of SPESP1 in ameliorating HDFs senescence and retarding the skin ageing process. Mechanistic studies demonstrate that SPESP1 directly binds to methyl‐binding protein, leading to Decorin demethylation and subsequently upregulation of its expression. Moreover, SPESP1 knockdown delays wound healing in young mice and SPESP1 overexpression induces wound healing in old mice. Notably, pharmacogenetic clearance of senescent cells by D+Q improved wound healing in SPESP1 knockdown skin. Conclusions Taken together, these findings reveal the critical role of SPESP1 in skin ageing and wound healing, expecting to facilitate the development of anti‐ageing strategies and improve wound healing in the elderly.

ObjectivePrevious research indicates associations between cigarette smoking, insulin-like growth factor-1 (IGF1), and sleep disturbances. This study aimed to examine the association between smoking and sleep quality and investigate the moderating role of IGF1.MethodsThis case-control study involved 146 Chinese adult males (53 active smokers and 93 non-smokers) from September 2014 to January 2016. Sleep quality and disturbances were evaluated using the Pittsburgh Sleep Quality Index (PSQI), which includes seven scales. Pearson correlation analysis and logistic regression analysis were utilized to examine the link between IGF1 levels in cerebrospinal fluid (CSF) and PSQI scores. The effect of IGF1 was assessed using the moderation effect and simple slope analysis, with adjustments made for potential confounders.ResultsActive smokers exhibited significantly higher global PSQI scores and lower IGF1 levels in CSF compared to non-smokers. A significant negative correlation was observed between IGF1 and PSQI scores (â = -0.28, P < 0.001), with a stronger association in non-smokers (Pearson r = -0.30) compared to smokers (Pearson r = -0.01). Smoking was associated with higher global PSQI scores (â = 0.282, P < 0.001), and this association was moderated by IGF1 levels in CSF (â = 0.145, P < 0.05), with a stronger effect at high IGF1 levels (Bsimple = 0.402, p < 0.001) compared to low IGF1 levels (Bsimple = 0.112, p = 0.268). Four subgroup analysis revealed similar results for sleep disturbances (Bsimple = 0.628, P < 0.001), with a marginal moderation effect observed on subjective sleep quality (Bsimple = 0.150, P = 0.070). However, independent associations rather than moderating effects were observed between IGF1 and sleep efficiency and daytime disturbance.ConclusionWe provided evidence to demonstrate the moderation effect of IGF1 on the relationship between smoking and sleep in CSF among Chinese adult males.

Osteoarthritis (OA) is characterized by cartilage degradation, inflammatory responses, and osteophyte formation. Matrix metalloproteinase 13 (MMP13) is a hallmark of OA development, and increased MMP13 expression is closely associated with extracellular matrix degradation. MMP13 expression varies significantly at different stages of OA progression. While cyclooxygenase 2 (COX-2) inhibitors are commonly used to treat OA, their long-term systemic administration increases the risks of adverse effects. Therefore, with the aim of achieving localized and responsive delivery of the COX-2 inhibitor celecoxib, the current study investigated an innovative MMP13-responsive micro-nano hydrogel microsphere system. Celecoxib-loaded cationic liposomes are non-covalently attached within the microsphere, enabling controlled drug release for OA treatment. In an OA environment with elevated MMP13 expression, the system is degraded via the action of MMP13 substrate peptide (MMP13sp), facilitating accelerated release of drug-loaded liposomes to improve the inflammatory microenvironment and treat OA rapidly. Compared to a phosphate-buffered saline solution with hyaluronidase (HAase), the prepared hyaluronic acid methacrylate microspheres HAMA/MMP13sp/Lipo@celecoxib exhibited rapid degradation in a solution containing a physiological concentration of MMP13/HAase, demonstrating specific enzyme responsiveness for precise anti-inflammatory drug release. The MMP13-responsive hydrogel microsphere system achieves intelligent and controllable drug release in OA, effectively decelerating disease progression and promoting articular cartilage repair.

Abstract Background The problem of suicide has become increasingly common in individuals with major depressive disorder (MDD). Transcranial direct current stimulation (tDCS) is an effective treatment for MDD with 2 milliamperes (mA) for at least 30 min per day for 2 weeks. This study aims to investigate the efficacy of daily duration-doubled tDCS as an adjunctive intervention for rapidly reducing suicidal ideation and improving depression in MDD patients. Methods In this double-blind, randomized, sham-controlled study, 76 MDD patients with suicidal ideation are randomly assigned to either active (n=38) or sham (n=38) tDCS group. The anode and cathode are placed over the scalp areas corresponding to left and right dorsolateral prefrontal cortex (DLPFC), respectively, and each stimulation lasts for 60 min. The primary outcome is defined as change of Beck Scale for Suicide Ideation (BSI) after 5 and 10 sessions. The change of other clinical assessments, blood biomarkers related to suicidal ideation and depressive sumptoms are defined as secondary outcomes. Blood biomarkers related to suicidal ideation are collected at baseline and after 10 sessions. Discussion This study suggests the adjunctive duration-doubled tDCS might be a novel method to rapidly reduce suicidal ideation and improve depressive symptom. The variation of biomarkers could be potential predictive models of suicide risk. Trial registration The trial protocol is registered with ClinicalTrials.gov under protocol registration number NCT05555927. Registered on September 25, 2022.

Abstract Droughts or floods are usually attributed to precipitation deficits or surpluses, both of which may become more frequent and severe under continued global warming. Concurring large-scale droughts in the Southwest and flooding in the Southeast of China in recent decades have attracted considerable attention, but their causes and interrelations are not well understood. Here, we examine spatiotemporal changes in hydrometeorological variables and investigate the mechanism underlying contrasting soil dryness/wetness patterns over a 54-year period (1965–2018) across a representative mega-watershed in South China—the West River Basin. We demonstrate that increasing rainfall intensity leads to severe drying upstream with decreases in soil water storage, water yield, and baseflow, versus increases therein downstream. Our study highlights a simultaneous occurrence of increased drought and flooding risks due to contrasting interactions between rainfall intensification and topography across the river basin, implying increasingly vulnerable water and food security under continued climate change.

Due to the crucial role of photovoltaic power prediction in the integration, scheduling and operation of intelligent grid systems, the accuracy of prediction has garnered increasing attention from both the research and industry sectors. Addressing the challenges posed by the nonlinearity and inherent unpredictability of photovoltaic (PV) power generation sequences, this paper introduced a novel PV prediction model known as the dilated causal convolutional network and stacked long short-term memory (DSLSTM). The methodology begins by incorporating physical constraints to mitigate the limitations associated with machine learning algorithms, thereby ensuring that the predictions remain within reasonable bounds. Subsequently, a dilated causal convolutional network is employed to extract salient features from historical PV power generation data. Finally, the model adopts a stacked network structure to effectively enhance the prediction accuracy of the LSTM component. To validate the efficacy of the proposed model, comprehensive experiments were conducted using a real PV power generation dataset. These experiments involved comparing the predictive performance of the DSLSTM model against several popular existing models, including multilayer perceptron (MLP), recurrent neural network (RNN), long short-term memory (LSTM), gated recurrent unit (GRU), stacked LSTM and stacked GRU. Evaluation was performed using four key performance metrics: Mean absolute error (MAE), mean squared error (MSE), root mean squared error (RMSE) and R-squared (R2). The empirical results demonstrate that the DSLSTM model outperforms other models in terms of both prediction accuracy and stability.

Abstract Oxidative stress is the primary cause of ischaemic stroke and is closely related to circadian rhythm. However, the mechanism by which circadian rhythm regulates oxidative stress in ischaemic stroke remains elusive. The Silent Information Regulator 1 (SIRT1) controls circadian rhythm by activating the transcription of the circadian clock core protein Basic Helix-Loop-Helix ARNT Like 1 (BMAL1) through deacetylation. Studies have shown that the SIRT1-BMAL1 pathway can regulate oxidative stress. To investigate its correlation with oxidative stress, we examined the expression levels and influencing factors of SIRT1-BMAL1 at different times in ischaemic stroke patients and analyzed their clinical indexes, oxidative stress, and inflammatory factor indicators. The expression levels of oxidative stress and inflammatory factor indicators, including malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-α), SIRT1, and BMAL1, were detected in ischaemic stroke patients within 4.5 h of onset and in non-stroke patients. Patients were divided into four subgroups based on onset time: subgroup 1 (0:00–05:59); subgroup 2 (06:00–11:59); subgroup 3 (12:00–17: 59); and subgroup 4 (18:00–23:59). Our results showed higher MDA, IL-6, and TNF-α levels, and lower SOD, SIRT1, and BMAL1 levels in ischaemic stroke patients compared to control patients (P 0.05). Our findings suggest that the SIRT1-BMAL1 pathway may be involved in early oxidative stress in ischaemic stroke, which may be related to MPO.

This study focuses on the analytical prediction of subsurface settlement induced by shield tunnelling in sandy cobble stratum considering the volumetric deformation modes of the soil above the tunnel crown. A series of numerical analyses is performed to examine the effects of cover depth ratio (C/D), tunnel volume loss rate (ηt) and volumetric block proportion (VBP) on the characteristics of subsurface settlement trough and soil volume loss. Considering the ground loss variation with depth, three modes are deduced from the volumetric deformation responses of the soil above the tunnel crown. Then, analytical solutions to predict subsurface settlement for each mode are presented using stochastic medium theory. The influences of C/D, ηt and VBP on the key parameters (i.e. B and N) in the analytical expressions are discussed to determine the fitting formulae of B and N. Finally, the proposed analytical solutions are validated by the comparisons with the results of model test and numerical simulation. Results show that the fitting formulae provide a convenient and reliable way to evaluate the key parameters. Besides, the analytical solutions are reasonable and available in predicting the subsurface settlement induced by shield tunnelling in sandy cobble stratum.

Abstract Aim Human immunodeficiency virus (HIV) nursing has become more prominent with the increase in chronic HIV infections. This study examined articles related to HIV nursing to determine how the profession has developed and its future direction. Design A bibliometric analysis was conducted. Methods HIV nursing‐related articles published in the Web of Science core collection between 1999 and 2022 were searched. VOSviewer was used to identify the contributions of countries, institutions and authors in HIV‐related care. Collaborative maps, hot topics and keywords trends were analysed using VOSviewer and CiteSpace. Results A total of 1513 publications were extracted. An increase in articles published between 1999 and 2012 was observed. After 2012, the increase in the number of publications was relatively stable. Since 2016, a downward trend in the number of publications has occurred. The USA, South Africa and the UK were the leading contributors to publications related to HIV nursing. The focus of the HIV nursing research has gradually shifted from “HIV infection”, “risk factors”, and “transmission routes” to “social support”, “depression”, and “public health”. The result shows that increased collaboration among countries/regions can improve the development of HIV nursing and effectively reduce the global HIV infection rate. The mental health of patients has become a research centre in the field of HIV nursing. This study provides direction in clinical practice and future research areas in this field.

Abstract Aim To evaluate the psychometric properties of the Advance Care Planning Readiness Scale (ACPRS‐C) within the context of community‐dwelling older adults with chronic diseases residing in suburban counties in China. Design Descriptive, cross‐sectional survey. Methods The research method employed in this study is characterized as a methodological study. Self‐reported survey data were collected among community‐dwelling older adults with chronic diseases residing in suburban counties in China. Including the following psychometric characteristics, item analysis was performed using the decision value method and Pearson's correlation analysis. Content validity was assessed through expert panel evaluation. The internal consistency of the questionnaire was determined by calculating Cronbach's alpha coefficient and corrected item‐total correlation. Additionally, confirmatory factor analysis (CFA) was utilized to assess the construct validity of the ACPRS‐C. Results A total of 228 older adults participated in this psychometric study from August to October 2023. The item content validity index ranged from 0.80 to 1.00, while the scale content validity index was 0.945. The scale demonstrated excellent internal consistency (Cronbach's alpha = 0.931), and the correlation between items and total score was satisfactory. The structural validity was deemed robust (CFA model fit: chi‐square/df = 1.121, comparative fit index = 0.992). Conclusion The ACPRS‐C is a scale with strong psychometric properties to assess the ACP readiness within the context of community‐dwelling older adults with chronic diseases residing in suburban counties in China. Its reliability and validity hold considerable significance for both research and clinical practice.

IntroductionPatients with alcohol use disorder (AUD) often experience repeated withdrawal. Impulsivity is the most relevant factor influencing successful withdrawal. Brain-derived neurotrophic factor (BNDF) and fibroblast growth factor 21 (FGF21) are associated with impulsivity. Previous studies on the differential effects of BDNF or FGF21 on impulsivity have focused on single-gene effects and have inconsistent results. We aim to investigate the effects of BDNF rs6265 and FGF21 rs11665896, individually and together, on impulsivity during alcohol withdrawal in patients with AUD.MethodsWe recruited 482 adult Han Chinese males with AUD and assessed their impulsivity using the Barratt Impulsivity Scale. Genomic DNA was extracted and genotyped from peripheral blood samples. Statistical analysis was conducted on the data.ResultsThe T-test and 2 × 2 analysis of variance were used to investigate the effects of the genes on impulsivity. There was a significant BDNF × FGF21 interaction on no-planning impulsiveness (F = 9.15, p = 0.003, η2p = 0.03). Simple main effects analyses and planned comparisons showed that BDNF rs6265 A allele × FGF21 rs11665896 T allele was associated with higher no-planning impulsiveness. Finally, hierarchical regression analyses revealed that only the interaction of BDNF and FGF21 accounted for a significant portion of the variance in no-planning impulsiveness.Conclusion and significanceThe combination of BDNF rs6265 A allele and FGF21 rs11665896 T allele may increase impulsivity and discourage alcohol withdrawal. Our study provides a possible genetic explanation for the effects of associated impulsivity in patients with AUD from the perspective of gene-gene interactions.

Objective: Preventing adverse events due to unstable oxygen saturation (SpO2) at night in pregnant women is of utmost importance. Poor sleep has been demonstrated to impact SpO2 levels. Nowadays, many gravida have a habit of prolonged exposure to light before sleep, which can disrupt their sleep. Therefore, this study aimed at investigate the relationship between lights-out time, sleep parameters and SpO2, exploring the underlying mechanisms. Methods: The data of 2881 eligible subjects from the Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be and Sleep Disordered Breathing (nuMOM2b-SDB) database were analyzed. Multiple linear regression models were used to investigate the relationship between lights-out time and SpO2. In addition, restricted cubic splines (RCS) were employed to fit the nonlinear correlation between the two variables. The smoothing curve method was further utilized to depict the relationship between lights-out time and SpO2 based on various subgroup variables. Results: All participants were categorized according to race/ethnicity. A negative correlation was observed between nighttime lights-out time and average value of SpO2 (Avg-SpO2) (β = −0.05, p = 0.010). RCS revealed a U-shaped relationship between lights-out time and Avg-SpO2, with the turning point at 22:00. The subcomponent stratification results indicated that the Avg-SpO2 and minimum value of SpO2(Min-SpO2) of advanced maternal age decreased as the lights-out time was delayed. Furthermore, overweight and obese gravida showed lower Avg-SpO2 and Min-SpO2 levels than normal weight. Conclusions: A U-shaped relationship was identified between lights-out time and nocturnal Avg-SpO2 during early pregnancy, with the inflection at 22:00. Notably, later lights-out times are associated with lower levels of Min-SpO2 for advanced maternal age. The findings suggest that appropriately adjusting the duration of light exposure before sleep and maintaining a relatively restful state may be more beneficial for the stability of SpO2 in pregnant women. Conversely, deviations from these practices could potentially lead to pathological alterations in SpO2 levels.

BackgroundWhile antibiotics are commonly used to treat inflammatory bowel disease (IBD), their widespread application can disturb the gut microbiota and foster the emergence and spread of antibiotic resistance. However, the dynamic changes to the human gut microbiota and direction of resistance gene transmission under antibiotic effects have not been clearly elucidated.MethodsBased on the Human Microbiome Project, a total of 90 fecal samples were collected from 30 IBD patients before, during and after antibiotic treatment. Through the analysis workflow of metagenomics, we described the dynamic process of changes in bacterial communities and resistance genes pre-treatment, during and post-treatment. We explored potential consistent relationships between gut microbiota and resistance genes, and established gene transmission networks among species before and after antibiotic use.ResultsExposure to antibiotics can induce alterations in the composition of the gut microbiota in IBD patients, particularly a reduction in probiotics, which gradually recovers to a new steady state after cessation of antibiotics. Network analyses revealed intra-phylum transfers of resistance genes, predominantly between taxonomically close organisms. Specific resistance genes showed increased prevalence and inter-species mobility after antibiotic cessation.ConclusionThis study demonstrates that antibiotics shape the gut resistome through selective enrichment and promotion of horizontal gene transfer. The findings provide insights into ecological processes governing resistance gene dynamics and dissemination upon antibiotic perturbation of the microbiota. Optimizing antibiotic usage may help limit unintended consequences like increased resistance in gut bacteria during IBD management.

Personal health data sharing can facilitate value co-creation between multiple stakeholders, including individuals, public organisations, private companies, research institutes, and policymakers. Yet, when companies are involved in sharing health data to develop health-related solutions, it can lead to conflicts and contradictions between stakeholders. We apply a qualitative research approach over two cases in the Finnish healthcare sector to explore the tensions and contradictions in sharing personal health data that companies can utilise in the development of new products/or services in the healthcare sector. We identify the tensions and paradoxes from multiple stakeholders’ perspectives and provide management approaches on three levels: (I) The micro-level focusing on individuals as users, (II) The meso-level concerns businesses operating within the digital health ecosystem. (III) The macro-level addresses broader societal impact and policies governing the secondary use of health data.

This study aimed to investigate whether there is a causal relationship between educational attainment and delirium at the genetic level using the Mendelian randomization method, and provide new evidence for studies in this field. We found a causal relationship between educational attainment and delirium at the genetic level after excluding confounders using Mendelian randomization. The inverse variance weighting method of random effects was the main analysis method. The weighted median and Mendelian Randomization-Egger methods, as well as simple, and weighted modes were used as supplementary analysis methods. Additionally, horizontal pleiotropy tests were conducted, including the Mendelian Randomization-Egger intercept test and Mendelian Randomization Pleiotropy RESidual Sum and Outlier. Cochran's Q statistic was used to assess the size of heterogeneity. We retrieved all second single nucleotide polymorphism features and performed multivariate Mendelian randomization to adjust for the effect of potential confounders on our results. The inverse variance weighting suggested a negative correlation between genetically predicted educational attainment and delirium (0.67[0.49–0.92], p = 0.013); Mendelian Randomization Pleiotropy RESidual Sum and Outlier (0.67[0.49–0.92], p = 0.013) and multivariate Mendelian randomization (0.52[0.33–0.82], p = 0.005) results were generally consistent with the inverse variance weighting method. The Mendelian Randomization-Egger, simple, and weighted mode results were consistent with the inverse variance weighting results. Our results were not affected by pleiotropy or heterogeneity (p > 0.05, for both pleiotropy and heterogeneity). In addition, the “leave-one-out” analysis showed that the results of our Mendelian randomization analysis were not influenced by individual single nucleotide polymorphisms. Studies have found a causal relationship between educational attainment and delirium at the genetic level; higher educational attainment may be a protective factor against delirium. Clinically, more attention should be paid to patients at a high risk of delirium with low educational attainment.

Objective: To investigate the association between particulate matter and the incidence, disability, and mortality of stroke, we reported the burden of stroke attributable to particulate matter (PM2.5) pollution, including ambient particulate matter pollution (APMP) and household air pollution from solid fuels (HAP), from 1990 to 2019. Methods: We retrieved the detailed data on the burden of stroke attributable to PM2.5 from the Global Burden of Disease (GBD) 2019. The number of disability-adjusted life-years (DALYs) and deaths, age-standardized death rates (ASMR), and age-standardized disability-adjusted life-years rates (ASDR) attributable to PM2.5 were estimated by age, sex, geographical location, socio-demographic index (SDI), and stroke subtypes (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage). The estimated annual percentage change (EAPC) was calculated to assess the trends in ASDR and ASMR during the period 1990–2019. Results: Regarding stroke subtypes, the proportion of ischemic stroke burden is increasing, while intracerebral hemorrhage carries the heaviest burden. Both APMP and HAP contributed the most to stroke-related deaths and DALYs of stroke among the elderly populations and males. The highest ASDR and ASMR of stroke attributable to APMP were in the middle SDI regions, especially in East Asia. For HAP, the highest ASDR and ASMR were in the low SDI regions, mainly in Oceania. From 1990–2019, in terms of the EAPC results, APMP caused an increased burden of stroke, whereas the impact of HAP significantly fell. The most pronounced increase in ASDR and ASMR for strokes attributed to APMP were in the low-middle SDI and low SDI regions, particularly among the 25–35 age group. Conclusions: Stroke attributed to PM2.5 is a global health problem, and the patterns and trends were heterogeneous across APMP and HAP. Targeted interventions should be formulated for APMP and HAP.

Abstract The Maritime Continent (MC), a critical region for inter‐basin climate interaction, harbors the world's highest marine biodiversity. Ocean warming in the MC, although with notable impacts on regional climate and marine ecosystems, remains poorly constrained by observations. By applying a volume‐correction algorithm to existing gridded observational data sets, this study provides an estimate for the ocean heat content (OHC) change of the MC. The results suggest a substantial OHC increase of 2.65 ± 0.46 Zettajoules during 1990–2015 (1.08 ± 0.17 W m−2) and limited changes before and after. This increase primarily arose from the enhanced Pacific Walker circulation, which drove a convergence of upper‐layer warm water toward the MC. A potential heat storage “hotspot” with enhanced warming below 500 m emerges within the Sulu Sea, which is supported by analysis of profile data collected in boreal winter but not in other seasons.