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BackgroundWith the events reporting on odors in drinking water, odorous substances in water have become a hot topic in water quality analysis. Due to the low concentration of the odor threshold and the complexity of the odor components in water, it is difficult to make accurate qualitative and quantitative analysis. So it is necessary to develop a highly sensitive and accurate qualitative and quantitative analysis method. ObjectiveTo establish a method for simultaneous determination of four odorous substances, including dimethyl disulfide, dimethyl trisulfide, 2-methylisoborneol, and geosmin in water by purge and trap-gas chromatography-tandem mass spectrometry. MethodsA certain amount of water sample was stored in the sample vial of a purge and trapinstrument. Through nitrogen purging, the odorous substances in water were purged out and enriched in the trap. Subsequently, the odorous substances were rapidly released at high temperatures after heating the trap, and then carried by carrier gas into gas chromatograph. After temperature programming, the substances were separated by an Agilent DB-624 capillary chromatographic column (30 m×0.25 mm, 1.4 μm) and determined by tandem mass spectrometry in multiple reaction monitoring modes, with internal standard method for quantification. The current project optimized purge time, sodium chloride concentration in water sample, desorption temperature, desorption time, and split ratio during the experimental process. Under the optimized experimental conditions, the standard curve, detection limit, and quantification limit were validated. Recovery tests with spiking concentrations of 5.0, 10.0, 30.0, 80.0 ng·L−1 and precision tests were conducted on water samples. Finally, the established method was applied to detect odorous substances in source water, finished water, and pipeline water in Deqing County of Huzhou City. ResultAfter the optimization, the purge time was 20 min, the desorption temperature was 280 ℃, the desorption time was 2 min, the split ratio was 10∶1, and no sodium chloride was added during the purge process. Under the optimized experimental conditions, the calibration curves for the four odorous substances showed an excellent linearity in the range of 1 to 100 ng·L−1 (R>0.999), with 0.3 ng·L−1 limit of detection and 1.0 ng·L−1 limit of quantitation. The average recoveries were from 85.5% to 102.4% and relative standard deviations (RSD) from 1.6% to 5.2%. After applying this method to detect local source water, finished water, and pipeline water, it was found that the positive rates of 2-methylisoborneo, and geosmin were relatively high, while the positive rates of dimethyl disulfide and dimethyl trisulfide were relatively low. Only one sample of source water tested positive for dimethyl disulfide, and all samples were negative for dimethyl trisulfide. ConclusionCombined with the superiority of purge and trap and tandem mass spectrometry, the method has the advantages of easy to perform, strong anti-interference ability, good accuracy and precision, which meet the limit requirements of the four odorous substances in the expanded indices and reference indices of Hygienic standards for drinking water (GB 5749-2022). It also provides technical support for water quality assessment and analysis of odorous substances.

Abstract Adiposity is an established risk factor for multiple diseases, but the causal relationships of different adiposity types with circulating protein biomarkers have not been systematically investigated. We examine the causal associations of general and central adiposity with 2923 plasma proteins among 3977 Chinese adults (mean BMI = 23.9 kg/m²). Genetically-predicted body mass index (BMI), body fat percentage (BF%), waist circumference (WC), and waist-to-hip ratio (WHR) are significantly (FDR

Abstract Inflammatory bowel diseases (IBD) are a group of chronic, non-specific intestinal diseases that could comorbid with varieties of negative emotional constructs, including pain-related negative emotions and trait negative emotions; however, the link between brain functions and different dimensions of negative emotions remains largely unknown. Ninety-eight patients with IBD and forty-six healthy subjects were scanned using a 3.0-T functional magnetic resonance imaging scanner. The amplitudes of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) were used to assess resting-state brain activity. Partial least squares (PLS) correlation was employed to assess the relationship among abnormal brain activities, pain-related and trait negative emotions. Compared to controls, patients with IBD exhibited higher values of ALFF in the right anterior cingulate cortex (ACC), lower values of ALFF in the left postcentral gyrus, and higher values of DC in the bilateral ACC. Multivariate PLS correlation analysis revealed the brain scores of the ACC were correlated with pain-related negative emotions, the brain salience in the left postcentral gyrus was associated with the higher-order trait depression. These findings can enhance our comprehension of how pain-related negative emotion and trait negative emotion affect the brains of patients with IBD in distinct ways.

Abstract Objective In the present study, we aimed to explore the association between left atrial appendage emptying velocity (LAAEV) measured by transesophageal echocardiography and atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA) in patients with early persistent atrial fibrillation (PeAF). Methods We retrospectively analyzed patients with early PeAF who underwent their initial ablation procedure. The echocardiographic and clinical data of the enrolled patients were collected and recorded prior to the operation. Following adjustment for confounding factors, we investigated the relationship between the LAAEV and AF recurrence in patients with early PeAF after radiofrequency ablation. Results The proportions of AF recurrence in the low, medium, and high LAAEV groups were 48.8%, 16.0%, and 13.1%, respectively. After adjusting for potential confounding factors, we observed a gradual decrease in the risk of AF recurrence with increasing LAAEV (odds ratio: 0.882, 95% confidence interval: 0.842—0.924, p

Abstract Background There is no consensus on the cause and effect of systemic chronic inflammation (SCI) regarding chronic obstructive pulmonary disease (COPD). The impact of second-hand smoke (SHS) on COPD has reached inconsistent conclusions. Methods The China Kadoorie Biobank cohort was followed up from the 2004–08 baseline survey to 31 December 2018. Among the selected 445,523 participants in the final analysis, Cox and linear regressions were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of tobacco exposure with COPD risk and baseline levels of log-transformed inflammatory factors [βs (95% CIs)], respectively. Results Participants were followed up for a median of 12.1 years and 11,825 incident COPD events were documented. Ever-smokers were associated with a higher risk of COPD than non-smokers with non-weekly SHS exposure. A younger age to start smoking, a greater amount of daily tobacco consumption, and deeper inhalation were associated with increased risk of COPD and correlated with elevated levels of plasma high-sensitivity C-reactive protein (hs-CRP, all P trend

Abstract Little is known about the prospective association between autosomal mosaic chromosomal alterations (mCAs), a group of large-scale somatic mutations on autosomes, and bladder cancer. Here we utilized data from 99,877 participants who were free of physician-diagnosed cancer at baseline (2004–2008) of the China Kadoorie Biobank to estimate the associations between autosomal mCAs and bladder cancer (ICD-10: C67). A total of 2874 autosomal mCAs events among 2612 carriers (2.6%) were detected. After a median follow-up of 12.4 years, we discovered that participants with all autosomal mCAs exhibited higher risks of bladder cancer, with a multivariable-adjusted hazard ratio (HR) (95% confidence interval [CI]) of 2.60 (1.44, 4.70). The estimate of such association was even stronger for mosaic loss events (HR [95% CI]: 6.68 [2.92, 15.30]), while it was not significant for CN-LOH events. Both expanded (cell fraction ≥10%) and non-expanded autosomal mCAs, as well as mosaic loss, were associated with increased risks of bladder cancer. Of interest, physical activity (PA) significantly modified the associations of autosomal mCAs and mosaic loss (P interaction = 0.038 and 0.012, respectively) with bladder cancer. The increased risks of bladder cancer were only observed with mCAs and mosaic loss among participants with a lower level of PA (HR [95% CI]: 5.11 [2.36, 11.09] and 16.30 [6.06, 43.81]), but not among participants with a higher level of PA. Our findings suggest that peripheral leukocyte autosomal mCAs may represent a novel risk factor for bladder cancer, and PA may serve as a potential intervention target for mCAs carriers.

Abstract Researchers and policymakers hold diverse opinions about the impact of globalization on environmental degradation. Over the past three decades, increased economic, social, and political interconnections have fueled this debate. However, prior studies have largely overlooked these facets of globalization concerning environmental implications, particularly carbon emissions in developing countries. We contribute to this discourse by examining how various aspects of globalization (economic, social, and political) and two specific measures, de facto and de jure trade, influenced carbon emissions in four selected South Asian countries from 1996 to 2019. The results obtained through feasible generalized least squares (FGLS) reveal that economic globalization increases carbon emissions while social and political globalization reduces them. These results further confirm that, in South Asia, the pollution haven hypothesis is associated only with economic globalization. In contrast, social and political globalization support the world polity theory, indicating potential for positive change. The results also show that both de facto and de jure measures of disaggregated globalization equally influence carbon emissions, suggesting a significant impact from policy interventions. For future environmental sustainability, the governments of these nations should intensify their efforts to strengthen social and political globalization. Meanwhile, the adverse effects of economic globalization can be mitigated by reducing reliance on fossil fuels and providing financial assistance to businesses to encourage the use of renewable energy and modern technology in production.

Abstract Background The AGEs levels in tissues of diabetics and elderly tend to be higher than in normal individuals. This study aims to determine the effects of AGEs on Achilles tendon repair. Materials and methods Thirty-six male eight-week-old Sprague Dawley rats were selected in this study. The rats were randomly divided into two experimental groups and a control group after the transection of the Achilles tendon. During the tendon repair, the experimental groups were injected around the Achilles tendon with 350mmol/L (low dose group) and 1000mmol/L (high dose group) D-ribose 0.2 ml respectively to increase the AGEs level, while in the control group were given the same amount of PBS. The injections were given twice a week for six weeks. Collagen-I, TNF-α, and IL-6 expression in the healed Achilles tendon was assessed. Additionally, macroscopic, pathological, and biomechanical evaluations of Achilles tendon repair were conducted. Results The repaired Achilles tendons in the high dose group showed severe swelling and distinctive adhesions. The histological score went up with the increase of the AGEs in the Achilles tendon (p

Abstract Molecular targeted therapy resistance remains a major challenge in treating lung adenocarcinoma (LUAD). The resistance of Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs, epidermal growth factor receptor-tyrosine kinase inhibitor) plays a dominant role in molecular targeted therapy. Our previous research demonstrated the role of MALAT-1 (Metastasis-associated lung adenocarcinoma transcript 1) in the formation of Erlotinib-resistant LUAD cells. This study aims to uncover the mechanism of MALAT-1 overexpression in Erlotinib-resistant LUAD cells. The RT2 LncRNA PCR array system was used to explore MALAT-1 regulation in Erlotinib-resistant LUAD cells through patient serum analysis. Dual luciferase reporter experiments confirmed the binding between MALAT-1 and miR-125, leading to regulation of miR-125 expression. Functional assays were performed to elucidate the impact of MALAT1 on modulating drug resistance, growth, and Epithelial-mesenchymal transition (EMT, Epithelial-mesenchymal transition) in both parental and Erlotinib-resistant LUAD cells. The investigation unveiled the mechanism underlying the competing endogenous RNA (ceRNA, competing endogenouse RNA) pathway. MALAT1 exerted its regulatory effect on miR-125 as a competing endogenous RNA (ceRNA). Moreover, MALAT1 played a role in modulating the sensitivity of LUAD cells to Erlotinib. Rab25 was identified as the direct target of miR-125 and mediated the functional effects of MALAT1 in Erlotinib-resistant LUAD cells. In conclusion, our study reveals overexpress MALAT-1 cause the drug resistance of EGFR-TKIs in non-small cell lung cancer (NSCLC) through the MALAT-1/miR-125/Rab25 axis. These findings present a potential novel therapeutic target and perspective for the treatment of LUAD.

Abstract Research on the severity and prognosis of sepsis with or without progressive delirium is relatively insufficient. We constructed a prediction model of the risk factors for 28-day mortality in patients who developed sepsis or sepsis-associated delirium. The modeling group of patients diagnosed with Sepsis-3 and patients with progressive delirium of related indicators were selected from the MIMIC-IV database. Relevant independent risk factors were determined and integrated into the prediction model. Receiver operating characteristic (ROC) curves and the Hosmer–Lemeshow (HL) test were used to evaluate the prediction accuracy and goodness-of-fit of the model. Relevant indicators of patients with sepsis or progressive delirium admitted to the intensive care unit (ICU) of a 3A hospital in Xinjiang were collected and included in the verification group for comparative analysis and clinical validation of the prediction model. The total length of stay in the ICU, hemoglobin levels, albumin levels, activated partial thrombin time, and total bilirubin level were the five independent risk factors in constructing a prediction model. The area under the ROC curve of the predictive model (0.904) and the HL test result (χ2 = 8.518) indicate a good fit. This model is valuable for clinical diagnosis and treatment and auxiliary clinical decision-making.

Abstract Background Congenital heart disease (CHD) is the most prevalent congenital anomaly, but its underlying causes are still not fully understood. It is believed that multiple rare genetic mutations may contribute to the development of CHD. Methods In this study, we aimed to identify novel genetic risk factors for CHD using an ENU-based dominant genetic screen in mice. We analyzed fetuses with malformed hearts and compared them to control littermates by whole exome or whole genome sequencing (WES/WGS). The differences in mutation rates between observed and expected values were tested using the Poisson and Binomial distribution. Additionally, we compared WES data from human CHD probands obtained from the Pediatric Cardiac Genomics Consortium with control subjects from the 1000 Genomes Project using Fisher’s exact test to evaluate the burden of rare inherited damaging mutations in patients. Results By screening 10,285 fetuses, we identified 1109 cases with various heart defects, with ventricular septal defects and bicuspid aortic valves being the most common types. WES/WGS analysis of 598 cases and 532 control littermates revealed a higher number of ENU-induced damaging mutations in cases compared to controls. GO term and KEGG pathway enrichment analysis showed that pathways related to cardiac contraction and neuronal development and functions were enriched in cases. Further analysis of 1457 human CHD probands and 2675 control subjects also revealed an enrichment of genes associated with muscle and nervous system development in patients. By combining the mice and human data, we identified a list of 101 candidate digenic genesets, from which each geneset was co-mutated in at least one mouse and two human probands with CHD but not in control mouse and control human subjects. Conclusions Our findings suggest that gene mutations affecting early hemodynamic perturbations in the developing heart may play a significant role as a genetic risk factor for CHD. Further validation of the candidate gene set identified in this study could enhance our understanding of the complex genetics underlying CHD and potentially lead to the development of new diagnostic and therapeutic approaches.

Abstract Background It is known that the neurodevelopmental disorder associated gene, Satb2, plays important roles in determining the upper layer neuron specification. However, it is not well known how this gene regulates other neocortical regions during the development. It is also lack of comprehensive delineation of its spatially regulatory pathways in neocortical development. Results In this work, we utilized spatial transcriptomics and immuno-staining to systematically investigate the region-specific gene regulation of Satb2 by comparing the Satb2 +/+ and Satb2 −/− mice at embryonic stages, including the ventricle zone (VZ) or subventricle zone (SVZ), intermediate zone (IZ) and cortical plate (CP) respectively. The staining result reveals that these three regions become moderately or significantly thinner in the Satb2 −/− mice. In the cellular level, the cell number increases in the VZ/SVZ, whereas the cell number decreases in the CP. The spatial transcriptomics data show that many important genes and relevant pathways are dysregulated in Satb2 −/− mice in a region-specific manner. In the VZ/SVZ, the key genes involved in neural precursor cell proliferation, including the intermediate progenitor marker Tbr2 and the lactate production related gene Ldha, are up-regulated in Satb2 −/− mice. In the IZ, the key genes in regulating neuronal differentiation and migration, such as Rnd2, exhibit ectopic expressions in the Satb2 −/− mice. In the CP, the lineage-specific genes, Tbr1 and Bcl11b, are abnormally expressed. The neuropeptide related gene Npy is down-regulated in Satb2 −/− mice. Finally, we validated the abnormal expressions of key regulators by using immunofluorescence or qPCR. Conclusions In summary, our work provides insights on the region-specific genes and pathways which are regulated by Satb2 in neocortical development.

Objective Embryonic interferon-tau (IFNT) and progesterone affect expression of interferon-stimulated genes (ISGs), progesterone receptor (PGR) and progesterone-induced blocking factor (PIBF) in the ovine thyroid. Methods Thyroids of ewes were sampled at day 16 of nonpregnancy, days 13, 16, and 25 of pregnancy, and real-time quantitative polymerase chain reaction assay, western blot and immunohistochemistry were used to detect expression of ISGs, PGR, and PIBF. Results Free ISG15 protein was undetected, but ISG15 conjugated proteins upregulated at day 16 of pregnancy, and expression levels of ISG15 conjugated proteins, PGR isoform (70 kDa), PIBF, interferon-gamma-inducible protein 10 and myxovirusresistance protein 1 peaked, but expression level of signal transducer and activator of transcription 1 was the lowest at day 16 of pregnancy. In addition, the expression levels of PGR isoform (70 kDa) and signal transducer and activator of transcription 1 (STAT1) decreased, but levels of PGR isoform (43 kDa), 2′,5′-oligoadenylate synthetase, IP-10 and MX1 increased at day 25 of pregnancy comparing with day 16 of the estrous cycle. Conclusion Early pregnancy affects expression of ISGs, PGR, and PIBF in maternal thyroid through IFNT and progesterone, which may regulate thyroid autoimmunity and thyroid hormone secretion in ewes.

Abstract Elevated blood pressure (BP) is major risk factor for cardiovascular diseases (CVD). Genome-wide association studies (GWAS) conducted predominantly in populations of European ancestry have identified >2,000 BP-associated loci, but other ancestries have been less well-studied. We conducted GWAS of systolic, diastolic, pulse, and mean arterial BP in 100,453 Chinese adults. We identified 128 non-overlapping loci associated with one or more BP traits, including 74 newly-reported associations. Despite strong genetic correlations between populations, we identified appreciably higher heritability and larger variant effect sizes in Chinese compared with European or Japanese ancestry populations. Using instruments derived from these GWAS, multivariable Mendelian randomisation demonstrated that BP traits contribute differently to the causal associations of BP with CVD. In particular, only pulse pressure was independently causally associated with carotid plaque. These findings reinforce the need for studies in diverse populations to understand the genetic determinants of BP traits and their roles in disease risk.

Abstract Objective In this study, we explored the determinants of ventricular aneurysm development following acute myocardial infarction (AMI), thereby prompting timely interventions to enhance patient prognosis. Methods In this retrospective cohort analysis, we evaluated 297 AMI patients admitted to the First People’s Hospital of Changzhou. The study was structured as follows. Comprehensive baseline data collection included hematological evaluations, ECG, echocardiography, and coronary angiography upon admission. Within 3 months post-AMI, cardiac ultrasounds were administered to detect ventricular aneurysm development. Univariate and multivariate logistic regression analysis were employed to pinpoint the determinants of ventricular aneurysm formation. Subsequently, a predictive model was formulated for ventricular aneurysm post-AMI. Moreover, the diagnostic efficacy of this model was appraised using the ROC curves. Results In our analysis of 291 AMI patients, spanning an age range of 32–91 years, 247 were male (84.9%). At the conclusion of a 3-month observational period, the cohort bifurcated into two subsets: 278 patients without ventricular aneurysm and 13 with evident ventricular aneurysm. Distinguishing features of the ventricular aneurysm subgroup were markedly higher values for age, B-type natriuretic peptide(BNP), Left atrium(LA), Left ventricular end-diastolic dimension (LEVDD), left ventricular end systolic diameter (LVEWD), E-wave velocity (E), Left atrial volume (LAV), E/A ratio (E/A), E/e ratio (E/e), ECG with elevated adjacent four leads(4 ST-Elevation), and anterior wall myocardial infarction(AWMI) compared to their counterparts (p

Abstract News media play an indispensable role in disseminating information and shaping public perception during times of crisis. This study, integrating sentiment, emotion, discourse, and timeline analyses together, conducts a corpus-based sentiment analysis of the news articles on unemployment from the New York Times in 2020 to capture the emotional dynamics conveyed by the newspaper as the pandemic-induced unemployment developed in the US. The results reveal that positive sentiment in the news articles on unemployment is significantly higher than negative sentiment. In emotion analysis, “trust” and “anticipation” rank the first and second among the eight emotions, while “fear” and “sadness” top the negative emotions. Complemented with a discourse analysis approach, the study reveals that the change of the sentiments and emotions over time is linked with the evolution of the pandemic and unemployment, the policy response as well as the protests against ethnic inequalities. This study highlights the important role mainstream news media play in information dissemination and solution-focused reportage at the time of severe crisis.

Abstract Background The incidence of lung cancer combined with pulmonary tuberculosis has been increasing, but there is relatively limited published literature on the topic of lung cancer combined with tuberculosis (LC‐PTB) from a bibliometric perspective. Therefore, in this study, we aimed to quantitatively analyze the LC‐PTB‐related literature to better understand the current status of this field and identify future research trends. Methods We searched for articles related to LC‐PTB using the Web of Science Core Collection (SCI‐E) and conducted a visual analysis of publication quantity, countries, institutions, authors, journals, references, and keywords using bibliometric software (CiteSpace, VOSviewer, and Scimago Graphica). Results As of January 8, 2024, a total of 460 publications related to LC‐PTB were included for analysis from 3705 retrieved records. The number of publications has been increasing almost yearly, with most from China (n = 123), followed by the United States (n = 77). Taipei Medical University contributed the most publications (n = 11). Jing‐Yang Huang and Yung‐Po Liaw (eight documents each) ranked first among the included authors. The Journal of Thoracic Oncology was the most productive academic journal on LC‐PTB. The aggregation of key nodes in the co‐citation network and the chronological sequence indicated that LC‐PTB research has shifted from initial hotspots such as lung diseases, bronchitis, and exposure to recent areas, including immunotherapy, immune checkpoint inhibitors, and nivolumab. Conclusion In this study, we visualized the current status of LC‐PTB research as well as future trends using bibliometric methods, providing new insights into the differential diagnosis of LC‐PTB and its related promoting mechanisms.

Abstract Objective High‐power ablation has been widely used in atrial fibrillation (AF). However, there were many studies observed the outcomes of the short‐term follow‐up. This study aims to the long‐term results of high‐power ablation guided by ablation index (AI) in patients with AF. Methods Analysis of patients with AF, who first received high‐power (40–50 W) ablation, to pulmonary vein isolation (PVI) in the Second Hospital of Shanxi Medical University from May 2020 to March 2022. All patients were managed perioperatively according to the routine treatment procedures. High‐power ablation was conducted under the guidance of our conventional power AI and baseline data, first‐pass PVI rate, ablation time, operative time, and long‐term surgical success rate were analyzed. Results A total of 83 patients with atrial fibrillation were enrolled in the study, with an average age of 61.62 ± 9.04 years, 47 male patients, and 49 paroxysmal atrial fibrillation. All patients achieved PVI, and the rate of first pass was 82%. The ablation time of the left atrial was 28.54 ± 9.11 min. There were no serious complications related to ablation, and only a small amount of pericardial effusion was found in 4 patients. During the follow‐up period of 26.36 ± 6.11 months, 8 patients were lost to follow‐up and the overall success rate was 84%, including 91% for paroxysmal AF and 71% for persistent AF. Conclusion High‐power ablation long‐term results appear a high freedom atrial arrhythmia, but further expanded samples are needed for controlled studies.

Abstract Background Rose myrtle (Rhodomyrtus tomentosa (Ait.) Hassk), is an evergreen shrub species belonging to the family Myrtaceae, which is enriched with bioactive volatiles (α-pinene and β-caryophyllene) with medicinal and industrial applications. However, the mechanism underlying the volatile accumulation in the rose myrtle is still unclear. Results Here, we present a chromosome-level genomic assembly of rose myrtle (genome size = 466 Mb, scaffold N50 = 43.7 Mb) with 35,554 protein-coding genes predicted. Through comparative genomic analysis, we found that gene expansion and duplication had a potential contribution to the accumulation of volatile substances. We proposed that the action of positive selection was significantly involved in volatile accumulation. We identified 43 TPS genes in R. tomentosa. Further transcriptomic and TPS gene family analyses demonstrated that the distinct gene subgroups of TPS may contribute greatly to the biosynthesis and accumulation of different volatiles in the Myrtle family of shrubs and trees. The results suggested that the diversity of TPS-a subgroups led to the accumulation of special sesquiterpenes in different plants of the Myrtaceae family. Conclusions The high quality chromosome-level rose myrtle genome and the comparative analysis of TPS gene family open new avenues for obtaining a higher commercial value of essential oils in medical plants.

IntroductionVirtual reality (VR) games, propelled by advancements in VR and artificial intelligence technologies, offer a level of realism and interactivity that traditional games cannot match. However, despite their immersive potential, VR games have not yet reached the widespread popularity of their conventional counterparts. While VR can craft the illusion of a parallel reality, users often remain cognizant of the delineation between the virtual and the real.MethodsIn this paper, we employ a blend of qualitative and quantitative research methods to explore the impact of familiarity with virtual environments and interactive elements on users sense of embodiment, flow experience, and their intention to continue playing VR games. Additionally, we examine the moderating influence of perceived cost within this framework.Results and discussionsOur analysis of 307 collected responses, facilitated by PLS-SEM, reveals that familiarity with interactivity is positively associated with both sense of embodiment and flow experience, whereas familiarity with the virtual scene primarily influences sense of embodiment. Interestingly, perceived cost exerts a positive moderating effect on the relationship between flow experience and the intention to persist with VR gaming, while it negatively moderates the impact of sense of embodiment on this intention. This study offers theoretical insights that can guide future research in the domain of VR gaming, as well as practical takeaways for companies in the VR game industry, shedding light on how to enhance user engagement and sustain long-term interest in VR gaming experiences.

IntroductionCodonopsis pilosula is a significant plant in traditional Chinese medicine, valued for its edible and medicinal properties. However, the lack of available genomic resources has hindered further research.MethodsThis study presents the first chromosome-scale genome assembly of C. pilosula using PacBio CLR reads and Hi-C scaffolding technology. Additionally, Ks analysis and syntenic depth analysis were performed to elucidate its evolutionary history.ResultsThe final assembly yielded a high-quality genome of 679.20 Mb, which was anchored to 8 pseudo-chromosomes with an anchoring rate of 96.5% and a scaffold N50 of 80.50 Mb. The genome assembly showed a high completeness of 97.6% based on Benchmarking with Universal Single-Copy Orthologs (BUSCO) analysis. Repetitive elements constituted approximately 76.8% of the genome, with long terminal repeat retrotransposons (LTRs) accounting for about 39.17%. Ks and syntenic depth analyses revealed that the polyploidization history of three platycodonoid clade species involved only the γ-WGT event. Karyotype evolutionary analysis identified an ancestral karyotype with 9 protochromosomes for the three platycodonoid clade species. Moreover, non-WGD genes, particularly those arising from tandem duplications, were found to contribute significantly to gene family expansion.DiscussionThese findings provide essential insights into the genetic diversity and evolutionary biology of C. pilosula, aiding its conservation and sustainable use.

Abstract The coexistence of diabetes mellitus (DM) and tuberculosis (TB) presents a significant global burden, with DM being recognized as a major risk factor for TB. This review comprehensively analyzes the immunological aspects of DM‐TB comorbidity, shedding light on the impact of DM on TB pathogenesis and immune responses. It reveals that high blood glucose levels in TB patients contribute to reduced innate immune cell count, compromised phagocytic function, and delayed antigen presentation. These factors ultimately impair the clearance of Mycobacterium tuberculosis (MTB) and delay adaptive immune responses. With the interaction between TB and DM, there is an increase in inflammation and elevated secretion of pro‐inflammatory cytokines by immune cells. This exacerbates the inflammatory response and contributes to poor treatment outcomes in TB. Moreover, the review explores the effects of DM on TB prevention, diagnosis, and treatment. It highlights how poor glycemic control, insulin resistance (IR), DM complications, and genetic factors increase the risk of MTB infection in individuals with DM. Additionally, DM‐related immune suppression adversely affects the sensitivity of traditional diagnostic tests for TB, potentially resulting in underdiagnosis and delayed intervention. To mitigate the burden of TB in DM patients, the review emphasizes the need for further research on the mechanisms underlying DM reactivation in latent TB infection (LTBI). It shows how important it is to find and treat LTBI in DM patients as soon as possible and suggests looking into biomarkers that are specific to DM to make diagnosis more accurate.

Accurate recognition of nutritional components in food is crucial for dietary management and health monitoring. Current methods often rely on traditional chemical analysis techniques, which are time-consuming, require destructive sampling, and are not suitable for large-scale or real-time applications. Therefore, there is a pressing need for efficient, non-destructive, and accurate methods to identify and quantify nutrients in food. In this study, we propose a novel deep learning model that integrates EfficientNet, Swin Transformer, and Feature Pyramid Network (FPN) to enhance the accuracy and efficiency of food nutrient recognition. Our model combines the strengths of EfficientNet for feature extraction, Swin Transformer for capturing long-range dependencies, and FPN for multi-scale feature fusion. Experimental results demonstrate that our model significantly outperforms existing methods. On the Nutrition5k dataset, it achieves a Top-1 accuracy of 79.50% and a Mean Absolute Percentage Error (MAPE) for calorie prediction of 14.72%. On the ChinaMartFood109 dataset, the model achieves a Top-1 accuracy of 80.25% and a calorie MAPE of 15.21%. These results highlight the model's robustness and adaptability across diverse food images, providing a reliable and efficient tool for rapid, non-destructive nutrient detection. This advancement supports better dietary management and enhances the understanding of food nutrition, potentially leading to more effective health monitoring applications.

α‐ketoglutarate (AKG), a key component of the tricarboxylic acid cycle, has attracted attention for its antiaging properties. In the recent study, it is indicated that locally delivered cell‐permeable AKG significantly promotes osteogenic differentiation and mouse bone regeneration. However, the cytotoxicity and rapid hydrolysis of the metabolite limit its application. In this study, novel AKG‐based polymeric microparticles (PAKG MPs) are synthesized for sustained release. In vitro data suggest that the chemical components, hydrophilicity, and size of the MPs can significantly affect their cytotoxicity and pro‐osteogenic activity. Excitingly, these biodegradable PAKG MPs are highly phagocytosable for nonphagocytic pre‐osteoblasts MC3T3‐E1 and primary bone marrow mesenchymal stem cells, significantly promoting their osteoblastic differentiation. RNA‐Sequencing (RNA‐Seq) data suggest that PAKG MPs strongly activate Wnt/β‐catenin and PI3K–Akt pathways for osteogenic differentiation. Moreover, PAKG enables poly(L‐lactic acid) and poly(lactic‐co‐glycolic acid) MPs (PLGA MPs) for efficient phagocytosis. In this data, it is indicated that PLGA–PAKG‐MPs‐mediated intracellular drug delivery can significantly promote stronger osteoblastic differentiation compared to PLGA‐MPs‐delivered phenamil. Notably, PAKG MPs significantly improve large bone regeneration in a mouse cranial bone defect model. Thus, the novel PAKG‐based MPs show great promise to improve osteogenic differentiation and bone regeneration and enable efficient intracellular drug delivery for broad regenerative medicine.

Triboelectric nanogenerators (TENGs) are promising self‐powering supplies for various intelligent sensing and monitoring devices, especially because they can harvest electric energy from low frequency and small‐scale mechanical motions. Despite the fact that contact‐separation mode TENGs with smaller contact areas harvest higher electrical outputs due to fringing effect, the impact of fringing effect on TENGs’ electrical outputs is rarely investigated quantitatively. Herein, in this study, the influence of fringing effect on the electrical outputs of contact‐separation mode TENGs by introducing discontinuity on the tribo‐negative side manually is investigated. In the results, it is revealed that the TENGs with more discontinuities show higher overall electric performance. Compared to pristine TENGs, the TENGs with discontinuity increased significantly, improving the surface charge by 50% and the power density by 114% when cross discontinuities are applied. However, one should generate discontinuities on tribo‐negative side of TENGs using ceramic blade instead of metal blade within a positive‐ion atmosphere due to the neutralization through the electrically conductive metal blade. The computational simulation validates that the TENGs with discontinuities obtain higher electrical outputs, and further investigates the effect of discontinuity gap size and array distance on TENGs performance. In this study, a promising method is provided for the future design of TENGs using discontinuous structures.

PurposeThis research aimed to create a machine learning model for clinical-radiomics that utilizes unenhanced computed tomography images to assess the likelihood of malignant cerebral edema (MCE) in individuals suffering from acute ischemic stroke (AIS).MethodsThe research included 179 consecutive patients with AIS from two different hospitals. These patients were randomly assigned to training (n = 143) and validation (n = 36) sets with an 8:2 ratio. Using 3DSlicer software, the radiomics features of regions impacted by infarction were derived from unenhanced CT scans. The radiomics features linked to MCE were pinpointed through a consistency test, Student’s t test and the least absolute shrinkage and selection operator (LASSO) method for selecting features. Clinical parameters associated with MCE were also identified. Subsequently, machine learning models were constructed based on clinical, radiomics, and clinical-radiomics. Ultimately, the efficacy of these models was evaluated by measuring the operating characteristics of the subjects through their area under the curve (AUCs).ResultsLogistic regression (LR) was found to be the most effective machine learning algorithm, for forecasting the MCE. In the training and validation cohorts, the AUCs of clinical model were 0.836 and 0.773, respectively, for differentiating MCE patients; the AUCs of radiomics model were 0.849 and 0.818, respectively; the AUCs of clinical and radiomics model were 0.912 and 0.916, respectively.ConclusionThis model can assist in predicting MCE after acute ischemic stroke and can provide guidance for clinical treatment and prognostic assessment.

Endocrine and exocrine functions of the pancreas control nutritional absorption, utilisation and systemic metabolic homeostasis. Under basal conditions, the lysosome is pivotal in regulating intracellular organelles and metabolite turnover. In response to acute or chronic stress, the lysosome senses metabolic flux and inflammatory challenges, thereby initiating the adaptive programme to re-establish cellular homeostasis. A growing body of evidence has demonstrated the pathophysiological relevance of the lysosomal stress response in metabolic diseases in diverse sets of tissues/organs, such as the liver and the heart. In this review, we discuss the pathological relevance of pancreatic lysosome stress in diabetes mellitus. We begin by summarising lysosomal biology, followed by exploring the immune and metabolic functions of lysosomes and finally discussing the interplay between lysosomal stress and the pathogenesis of pancreatic diseases. Ultimately, our review aims to enhance our understanding of lysosomal stress in disease pathogenesis, which could potentially lead to the discovery of innovative treatment methods for these conditions.

Background: Infectious diseases remain a major global health concern, including in China, with an estimated >10 million cases of infectious disease in 2019. We describe the burden of site-specific infectious diseases among Chinese adults. Methods: From 2004 to 2008, the prospective China Kadoorie Biobank enrolled 512,726 adults aged 30-79 years from 10 diverse areas (5 rural, 5 urban) of China. During the 12 years of follow-up, 101,673 participants were hospitalized for any infectious disease. Descriptive analyses examined standardized incidence, mortality and case fatality of infections. Findings: The incidence of any infectious disease was 1856 per 100,000 person-years; respiratory tract infections (1069) were most common. The infectious disease mortality rate was 31.8 per 100,000 person-years (20.3 and 9.4 for respiratory and non-respiratory infections, respectively) and case fatality was 2.2% (2.6% and 1.6% for respiratory and non-respiratory infections, respectively). Infectious disease incidence and mortality rates were higher at older ages and in rural areas. There were no clear sex differences in infectious disease incidence rates, but mortality and case fatality rates were twice as high in men as in women. Interpretation: Infectious diseases were common in Chinese adults. The observed burden of, and disparities in, site-specific infections can inform targeted prevention efforts. Funding: Kadoorie Foundation, Wellcome Trust, MRC, BHF, CR-UK, MoST, NNSF.

PurposeMachine learning (ML) models were constructed according to non-contrast computed tomography (NCCT) images as well as clinical and laboratory information to assess risk stratification for the occurrence of hemorrhagic transformation (HT) in acute ischemic stroke (AIS) patients.MethodsA retrospective cohort was constructed with 180 AIS patients who were diagnosed at two centers between January 2019 and October 2023 and were followed for HT outcomes. Patients were analyzed for clinical risk factors for developing HT, infarct texture features were extracted from NCCT images, and the radiomics score (Rad-score) was calculated. Then, five ML models were established and evaluated, and the optimal ML algorithm was used to construct the clinical, radiomics, and clinical-radiomics models. Receiver operating characteristic (ROC) curves were used to compare the performance of the three models in predicting HT.ResultsBased on the outcomes of the AIS patients, 104 developed HT, and the remaining 76 had no HT. The HT group consisted of 27 hemorrhagic infarction (HI) and 77 parenchymal-hemorrhage (PH). Patients with HT had a greater neutrophil-to-lymphocyte ratio (NLR), baseline National Institutes of Health Stroke Scale (NIHSS) score, infarct volume, and Rad-score and lower Alberta stroke program early CT score (ASPECTS) (all p 0.05), with an overall accuracy of 79.5%. Moreover, this model performed reliably in predicting the PH and HI subcategories, with accuracies of 82.9 and 92.9%, respectively.ConclusionML models based on clinical and NCCT radiomics characteristics can be used for early risk evaluation of HT development in AIS patients and show great potential for clinical precision in treatment and prognostic assessment.

Background: Myokines play vital roles in both stable coronary artery disease (SCAD) and depression. Meanwhile, there is a pressing necessity to find effective biomarkers for early predictor of major adverse cardiovascular events (MACE) in SCAD patients with depressive symptoms. Methods: A single-center, 5-year follow-up study was investigated. MACE was defined as composite end points, including cardiovascular death, non-fatal stroke, non-fatal myocardial infarction, coronary artery revascularization, or hospitalization for unstable angina. Results: A total of 116 SCAD patients were enrolled, consisting of 30 cases (25.9%) without depressive symptoms and 86 cases (74.1%) with depressive symptoms. During the follow-up, 3 patients (2.6%) were lost. Out of 113 patients, 51 (45.1%) experienced MACE. In the subgroup of 84 SCAD patients with depressive symptoms, 44 cases (52.4%) of MACE were observed. Finally, mature brain-derived neurotrophic factor (mBDNF), pro-brain-derived neurotrophic factor, receptor activator of nuclear factor-κB ligand, smoking history, hypertension and cystatin C were incorporated into the predictive model. Conclusions: Depressive symptoms represent an independent risk factor for MACE in patients with SCAD. Additionally, low mBDNF expression may be an important early predictor for MACE in SCAD patients with depressive symptoms. The predictive model may exhibit a commendable predictive performance for MACE in SCAD patients with depressive symptoms.

Objective: This study aimed to investigate the impact of lifelong exercise, including both moderate-intensity continuous training and high-intensity interval training, on blood lipid levels and mental behaviour in naturally ageing mice to identify effective exercise strategies for ageing-related health issues. Methods: Six-week-old male BALB/c mice were randomly assigned to one of four groups: young control (YC), natural ageing control (OC), lifelong moderate-intensity continuous exercise (EM), and lifelong high-intensity interval exercise (EH) groups. The EM group was trained at a speed corresponding to 70 % of the maximum running speed, while the EH group was trained at a running speed alternating between 50 % of the maximum running speed, 70 % of the maximum running speed, and 90 % of the maximum running speed. All exercise sessions were conducted three times per week, with each session lasting 50 min. Behavioural tests and blood sample collection were conducted at 72 weeks of age. Results: Ageing in mice led to changes in muscle and fat mass. Both the EM and EH groups showed greater muscle mass and lower fat mass than did the OC group. Ageing was associated with elevated anxiety (fewer open arm entries, time spent in the central region) and depression (lower sucrose preference) indicators. However, these changes were reversed in both exercise groups, with no differences between the two exercise groups. Blood lipid levels, including total cholesterol (TC), total triglycerides (TGs), low-density lipoprotein (LDL), and free fatty acid (FFA) levels, were greater in the OC group than in the YC group. Additionally, the OC group exhibited lower high-density lipoprotein (HDL) levels. However, both the EM and EH groups exhibited improved lipid profiles compared to those of the YC group. Conclusion: Lifelong exercise, whether moderate-intensity continuous or high-intensity interval training, can preserve body health during ageing, prevent anxiety and depression, and maintain stable blood lipid levels. Both exercise types are equally effective, suggesting that exercise intensity may not be the critical factor underlying these beneficial adaptations.

Abstract Despite advances in active drug targeting for blood-brain barrier penetration, two key challenges persist: first, attachment of a targeting ligand to the drug or drug carrier does not enhance its brain biodistribution; and second, many brain diseases are intricately linked to microcirculation disorders that significantly impede drug accumulation within brain lesions even after they cross the barrier. Inspired by the neuroprotective properties of vinpocetine, which regulates cerebral blood flow, we propose a molecular library design centered on this class of cyclic tertiary amine compounds and develop a self-enhanced brain-targeted nucleic acid delivery system. Our findings reveal that: (i) vinpocetine-derived ionizable-lipidoid nanoparticles efficiently breach the blood-brain barrier; (ii) they have high gene-loading capacity, facilitating endosomal escape and intracellular transport; (iii) their administration is safe with minimal immunogenicity even with prolonged use; and (iv) they have potent pharmacologic brain-protective activity and may synergize with treatments for brain disorders as demonstrated in male APP/PS1 mice.

Background: Nonalcoholic steatohepatitis (NASH) has been the second most common cause of liver transplantation in the United States. To date, NASH pathogenesis has not been fully elucidated but is multifactorial, involving insulin resistance, obesity, metabolic disorders, diet, dysbiosis, and gene polymorphism. An effective and approved therapy for NASH has also not been established. Bile acid is long known to have physiological detergent function in emulsifying and absorbing lipids and lipid-soluble molecules within the intestinal lumen. With more and more in-depth understandings of bile acid, it has been deemed to be a pivotal signaling molecule, which is capable of regulating lipid and glucose metabolism, liver inflammation, and fibrosis. In recent years, a plethora of studies have delineated that disrupted bile acid homeostasis is intimately correlated with NASH disease severity. Aims: The review aims to clarify the role of bile acid in hepatic lipid and glucose metabolism, liver inflammation, as well as liver fibrosis, and discusses the safety and efficacy of some pharmacological agents targeting bile acid and its associated pathways for NASH. Key scientific concepts of review: Bile acid has a salutary effect on hepatic metabolic disorders, which can ameliorate liver fat accumulation and insulin resistance mainly through activating Takeda G-protein coupled receptor 5 and farnesoid X receptor. Moreover, bile acid also exerts anti-inflammation and anti-fibrosis properties. Furthermore, bile acid has great potential in nonalcoholic liver disease stratification and treatment of NASH.

In this work, the phase transition process of β-Ga2O3 thin films under heating and (or) electron irradiation condition was investigated by in-situ transmission electron microscopy. It is found that only under the high temperature, β-Ga2O3 did not undergo phase transition even when the temperature was up to 1000 °C. When under electron irradiation condition, the unconventional phase transition from β-Ga2O3 to δ-Ga2O3 occurred with a slow rate. When electron irradiation was coupled with a thermal field, the initial temperature of phase transition decreased, and the speed of phase transition also greatly accelerated. The new phase maintains crystallography relationship with the β-Ga2O3 parent phase as following: [010]β//[011‾]δ, (200)β//(2‾11)δ, and (402‾)β//(411)δ. The results reveal that electron irradiation can trigger the phase transition process from β-Ga2O3 to δ-Ga2O3, and the high temperature obviously accelerates the rate of phase transition process.

Abstract Tuberculosis (TB) is an infectious disease that significantly threatens human health. However, the differential diagnosis of latent tuberculosis infection (LTBI) and active tuberculosis (ATB) remains a challenge for clinicians in early detection and preventive intervention. In this study, we developed a novel biomarker named HP16118P, utilizing 16 helper T lymphocyte (HTL) epitopes, 11 cytotoxic T lymphocyte (CTL) epitopes, and 8 B cell epitopes identified from 15 antigens associated with LTBI-RD using the IEDB database. We analyzed the physicochemical properties, spatial structure, and immunological characteristics of HP16118P using various tools, which indicated that it is a hydrophilic and relatively stable alkaline protein. Furthermore, HP16118P exhibited good antigenicity and immunogenicity, while being non-toxic and non-allergenic, with the potential to induce immune responses. We observed that HP16118P can stimulate the production of high levels of IFN-γ+ T lymphocytes in individuals with ATB, LTBI, and health controls. IL-5 induced by HP16118P demonstrated potential in distinguishing LTBI individuals and ATB patients (p=0.0372, AUC=0.8214, 95% CI [0.5843 to 1.000]) with a sensitivity of 100% and specificity of 71.43%. Furthermore, we incorporated the GM-CSF, IL-23, IL-5, and MCP-3 induced by HP16118P into 15 machine learning algorithms to construct a model. It was found that the Quadratic discriminant analysis model exhibited the best diagnostic performance for discriminating between LTBI and ATB, with a sensitivity of 1.00, specificity of 0.86, and accuracy of 0.93. In summary, HP16118P has demonstrated strong antigenicity and immunogenicity, with the induction of GM-CSF, IL-23, IL-5, and MCP-3, suggesting their potential for the differential diagnosis of LTBI and ATB.

Abstract High-precision and high-efficiency Semantic segmentation of high-resolution remote sensing images is a challenge. Existing models typically require a significant amount of training data to achieve good classification results and have numerous training parameters. A novel model called MST-DeepLabv3+ was suggested in this paper for remote sensing image classification. It’s based on the DeepLabv3+ and can produce better results with fewer train parameters. MST-DeepLabv3+ made three improvements: (1) Reducing the number of model parameters by substituting MobileNetV2 for the Xception in the DeepLabv3+’s backbone network. (2) Adding the attention mechanism module SENet to increase the precision of semantic segmentation. (3) Increasing Transfer Learning to enhance the model's capacity to recognize features, and raise the segmentation accuracy. MST-DeepLabv3+ was tested on international society for photogrammetry and remote sensing (ISPRS) dataset, Gaofen image dataset (GID), and practically applied to the Taikang cultivated land dataset. On the ISPRS dataset, the mean intersection over union (MIoU), overall accuracy (OA), Precision, Recall, and F1-score are 82.47%, 92.13%, 90.34%, 90.12%, and 90.23%, respectively. On the GID dataset, these values are 73.44%, 85.58%, 84.10%, 84.86%, and 84.48%, respectively. The results were as high as 90.77%, 95.47%, 95.28%, 95.02%, and 95.15% on the Taikang cultivated land dataset. The experimental results indicate that MST-DeepLabv3+ effectively improves the accuracy of semantic segmentation of remote sensing images, recognizes the edge information with more completeness, and significantly reduces the parameter size.

Abstract Background The Auxin Responsive Factor (ARF) family plays a crucial role in mediating auxin signal transduction and is vital for plant growth and development. However, the function of ARF genes in Korean pine (Pinus koraiensis), a conifer species of significant economic value, remains unclear. Results This study utilized the whole genome of Korean pine to conduct bioinformatics analysis, resulting in the identification of 13 ARF genes. A phylogenetic analysis revealed that these 13 PkorARF genes can be classified into 4 subfamilies, indicating the presence of conserved structural characteristics within each subfamily. Protein interaction prediction indicated that Pkor01G00962.1 and Pkor07G00704.1 may have a significant role in regulating plant growth and development as core components of the PkorARFs family. Additionally, the analysis of RNA-seq and RT-qPCR expression patterns suggested that PkorARF genes play a crucial role in the development process of Korean pine. Conclusion Pkor01G00962.1 and Pkor07G00704.1, which are core genes of the PkorARFs family, play a potentially crucial role in regulating the fertilization and developmental process of Korean pine. This study provides a valuable reference for investigating the molecular mechanism of embryonic development in Korean pine and establishes a foundation for cultivating high-quality Korean pine.

Aging is a complex physiological process, accompanied by metabolic and immune disorders leading to aging. The aging process yields dramatic alterations in the gut microbiota. However, there is limited evidence for a mechanistic role of the gut microbiota in aging processes. We conducted fecal microbiota transplantation from either young (4 months) or aged (22 months) donor mice into aged recipient mice (22 months) or young (4 months). Aged mice receiving young donor gut microbiota reversed aging-associated inflammation in serum and issues, and the behavioral characteristics with spontaneous activities, standing times, the number of falls, and the latency time in aged mice were alleviated. Conversely, young mice receiving aged donor gut microbiota promoted the development of inflammation, and the behavioral characteristics of aging were intensified. The relative abundance of Odoribacter, Flexispira, Veillonella, and Prevotellaceae_Prevotella were significantly enriched in aged mice, while changes were reversed in aged mice receiving young donor gut microbiota. The metabolites including indole acrylic acid, LPC (18:1/0:0), LPC (15:0/0:0), LPC (0:0/15:0) were up-regulated, and xanthine, inosine, allopurinol, N6-methyladenosine metabolites were down-regulated. After aged mice receiving young donor gut microbiota, these metabolite changes were reversed too. Analysis of the correlation between the microbiota, metabolites, and inflammatory cytokines showed indoleacrylic acid, LPC (18:1/0:0), LPC (15:0/0:0), and LPC (0:0/15:0) were negatively associated with Adlercreutzia, while positively correlated with Veillonella, Prevotellaceae_Prevotella, Streptococcus, and Odoribacter. 1-methylinosine, L-methyladenosine, allopurinol, and N6-methyladenosine were positively correlated with Desulfovibrio, and negatively correlated with Veillonella and Prevotellaceae_Prevotella. Indoleacrylic acid was negatively correlated with TGF-β. LPC (18:1/0:0), LPC (15:0/0:0), and LPC (0:0/15:0) were positively correlated with IL-10. 1-methylinosine, L-methyladenosine, N6-methyladenosine and inosine were negatively correlated with IL-6 and LPS. Our findings suggest that modulating the gut microbiome may be an appropriate treatment to promote healthy aging.

Abstract Background Lung cancer is the leading cause of cancer mortality among Chinese females despite the low smoking prevalence among this population. This study assessed the roles of reproductive factors in lung cancer development among Chinese female never-smokers. Methods The prospective China Kadoorie Biobank (CKB) recruited over 0.5 million Chinese adults (0.3 million females) from 10 geographical areas in China in 2004–2008 when information on socio-demographic/lifestyle/environmental factors, physical measurements, medical history, and reproductive history collected through interviewer-administered questionnaires. Cox proportional hazard regression was used to estimate adjusted hazard ratios (HRs) of lung cancer by reproductive factors. Subgroup analyses by menopausal status, birth year, and geographical region were performed. Results During a median follow-up of 11 years, 2,284 incident lung cancers occurred among 282,558 female never-smokers. Ever oral contraceptive use was associated with a higher risk of lung cancer (HR = 1.16, 95% CI: 1.02–1.33) with a significant increasing trend associated with longer duration of use (p-trend = 0.03). Longer average breastfeeding duration per child was associated with a decreased risk (0.86, 0.78–0.95) for > 12 months compared with those who breastfed for 7–12 months. No statistically significant association was detected between other reproductive factors and lung cancer risk. Conclusion Oral contraceptive use was associated with an increased risk of lung cancer in Chinese female never-smokers. Further studies are needed to assess lung cancer risk related to different types of oral contraceptives in similar populations.

Abstract In recent years, sparse arrays based on the fourth‐order difference coarray (FODCA) have received increased research attention due to their small number of array elements and large consecutive virtual arrays. The expanding and shift structure based on the nested array (NA) and coprime array (CPA) (EAS‐NA‐CPA) is the representative one. The EAS‐NA‐CPA comprises two sparse subarrays, wherein the NA is expanded and shifted according to the second‐order difference coarray of the CPA. Although the number of consecutive elements is large, there are many redundant elements in the FODCA of the EAS‐NA‐CPA. To decrease the number of redundant elements and increase the number of consecutive elements in the FODCA, the authors proposed the enhanced EAS‐NA‐CPA (EEAS‐NA‐CPA). Compared with the original EAS‐NA‐CPA, the EEAS‐NA‐CPA increases the adjacent physical sensor spacing further by using more fourth‐order cross‐correlation coarrays in the FODCA, which are not considered in the original EAS‐NA‐CPA. By performing a theoretical analysis of the FODCA provided by the proposed EEAS‐NA‐CPA, the sensor spacing in the expanded NA was further increased to obtain a larger number of consecutive elements compared with the original EAS‐NA‐CPA. Furthermore, the relationship between the number of physical sensors and corresponding number of consecutive elements provided by the FODCA was explicitly expressed. Experimental simulations were conducted to verify the effectiveness of the proposed sparse array for the fourth‐order cumulant‐based direction of arrival estimation.

Background: Information on the association between physical activity (PA) and the risk of chronic kidney disease (CKD) is limited. We aimed to explore the associations of total, domain-specific, and intensity-specific PA with CKD and its subtypes in China. Methods: The study included 475,376 adults from the China Kadoorie Biobank aged 30–79 years during 2004–2008 at baseline. An interviewer-administered questionnaire was used to collect the information about PA, which was quantified as metabolic equivalent of task hours per day (MET-h/day) and categorized into 4 groups based on quartiles. Cox regression was used to analyze the association between PA and CKD risk. Results: During a median follow-up of 12.1 years, 5415 incident CKD cases were documented, including 1159 incident diabetic kidney disease (DKD) cases and 362 incident hypertensive nephropathy (HTN) cases. Total PA was inversely associated with CKD risk, with an adjusted hazard ratio (HR, 95% confidence interval (95%CI)) of 0.83 (0.75–0.92) for incident CKD in the highest quartile of total PA as compared with participants in the lowest quartile. Similar results were observed for risk of DKD and HTN, and the corresponding HRs (95%CIs) were 0.75 (0.58–0.97) for DKD risk and 0.56 (0.37–0.85) for HTN risk. Increased nonoccupational PA, low-intensity PA, and moderate-to-vigorous-intensity PA were significantly associated with a decreased risk of CKD, with HRs (95%CIs) of 0.80 (0.73–0.88), 0.85 (0.77–0.94), and 0.85 (0.76–0.95) in the highest quartile, respectively. Conclusion: PA, including nonoccupational PA, low-intensity PA, and moderate-to-vigorous-intensity PA, was inversely associated with the risk of CKD, including DKD, HTN, and other CKD, and such associations were dose dependent.

Abstract Despite the high prevalence of snoring in Asia, little is known about the genetic etiology of snoring and its causal relationships with cardiometabolic traits. Based on 100,626 Chinese individuals, a genome-wide association study on snoring was conducted. Four novel loci were identified for snoring traits mapped on SLC25A21, the intergenic region of WDR11 and FGFR, NAA25, ALDH2, and VTI1A, respectively. The novel loci highlighted the roles of structural abnormality of the upper airway and craniofacial region and dysfunction of metabolic and transport systems in the development of snoring. In the two-sample bi-directional Mendelian randomization analysis, higher body mass index, weight, and elevated blood pressure were causal for snoring, and a reverse causal effect was observed between snoring and diastolic blood pressure. Altogether, our results revealed the possible etiology of snoring in China and indicated that managing cardiometabolic health was essential to snoring prevention, and hypertension should be considered among snorers.

Sepsis-induced acute kidney injury (SI-AKI) is a common clinical syndrome that is associated with high mortality and morbidity. Effective timely detection may improve the outcome of SI-AKI. Kidney-derived cell-free DNA (cfDNA) may provide new insight into understanding and identifying SI-AKI. Plasma cfDNA from 82 healthy individuals, 7 patients with sepsis non-acute kidney injury (SN-AKI), and 9 patients with SI-AKI was subjected to genomic methylation sequencing. We deconstructed the relative contribution of cfDNA from different cell types based on cell-specific methylation markers and focused on exploring the association between kidney-derived cfDNA and SI-AKI.Based on the deconvolution of the cfDNA methylome: SI-AKI patients displayed the elevated cfDNA concentrations with an increased contribution of kidney epithelial cells (kidney-Ep) DNA; kidney-Ep derived cfDNA achieved high accuracy in distinguishing SI-AKI from SN-AKI (AUC = 0.92, 95% CI 0.7801–1); the higher kidney-ep cfDNA concentrations tended to correlate with more advanced stages of SI-AKI; strikingly, SN-AKI patients with potential kidney damage unmet by SI-AKI criteria showed higher levels of kidney-Ep derived cfDNA than healthy individuals. The autonomous screening of kidney-Ep (n = 24) and kidney endothelial (kidney-Endo, n = 12) specific methylation markers indicated the unique identity of kidney-Ep/kidney-Endo compared with other cell types, and its targeted assessment reproduced the main findings of the deconvolution of the cfDNA methylome. Our study first demonstrates that kidney-Ep- and kidney-Endo-specific methylation markers can serve as a novel marker for SI-AKI emergence, supporting further exploration of the utility of kidney-specific cfDNA methylation markers in the study of SI-AKI.

Quinoa is an important economic food crop. However, quinoa seedlings are susceptible to drought stress, and the molecular mechanism of drought tolerance remains unclear. In this study, we compared transcriptomic and physiological analyses of drought-tolerant (L1) and susceptible (HZ1) genotypes exposed to 20% PEG for 3 and 9 days at seedling stage. Compared with HZ1, drought stress had less damage to photosynthetic system, and the contents of SOD, POD and CAT were higher and the contents of H2O2 and O2−were lower in L1 leaves. Based on the RNA-seq method, we identified 2423, 11856, 1138 and 3903 (HZ1-C3-VS-T3, HZ1-C9-vs-T9, L1-C3-vs-T3 and L1-C9-vs-T9) annotated DEGs. Go enrichment was shown in terms of Biological Process: DEGs involved in biological processes such as metabolic process, cellular process, and single-organism process were most abundant in all four comparison treatments. In Molecular Function: the molecular functions of catalytic activity, binding and transporter activity have the most DEGs in all four processes. Cellular Component: membrane, membrane part, and cell have the most DEGs in each of the four processes. These DEGs include AP2/ERF, MYB, bHLH, b-ZIP, WRKY, HD-ZIP, NAC, C3h and MADS, which encode transcription factors. In addition, the MAPK pathway, starch and sucrose metabolism, phenylpropanoid biosynthesis and plant hormone signal transduction were significantly induced under drought stress, among them, G-hydrolases-66, G-hydrolases-81, G-hydrolases-78, Su-synthase-02, Su-synthase-04, Su-synthase-06, BRI1-20 and bHLH17 were all downregulated at two drought stress points in two genotypes, PP2C01, PP2C03, PP2C05-PP2C07, PP2C10, F-box01 and F-box02 were upregulated at two drought stress points in two genotypes. These results agree with the physiological responses and RNA-seq results. Collectively, these findings may lead to a better understanding of drought tolerance, and some of the important DEGs detected in this study could be targeted for future research. And our results will provide a comprehensive basis for the molecular network that mediates drought tolerance in quinoa seedlings and promote the breeding of drought-resistant quinoa varieties.

BackgroundDistal radial artery (DRA) access is an infrequent alternative access for pediatric catheterization. The feasibility of using the DRA for arterial catheterization in children depends on the vessel's size.ObjectivesThis study aims to provide a reference for pediatric catheterization via DRA access by evaluating the diameter of the DRA in the anatomic snuffbox (AS).MethodsWe conducted a retrospective review of clinical and vascular ultrasound data of 412 children (ages 3–12) who were scheduled for arterial blood gas analysis via the DRA due to serious respiratory diseases between June 2023 and October 2023.ResultsThe corrected DRA diameter in the AS was 1.97 ± 0.37 mm overall, with no significant difference between males (1.98 ± 0.38 mm) and females (1.95 ± 0.35 mm) (p = 0.457). The anteroposterior, transverse, and corrected DRA diameters increased significantly with age (p 2.0 mm and >1.5 mm increased significantly with age (p

Summary: Background: In non-high-risk individuals, risk-category-based atherosclerotic cardiovascular disease (ASCVD) screening strategies may be more cost-effective than one-size-fits-all approaches. However, current decisions are constrained by a lack of research evidence. We aimed to explore appropriate risk-category-based screening interval strategies for non-high-risk individuals in ASCVD primary prevention in the Chinese population. Methods: We used data from 28,624 participants in the China Kadoorie Biobank (CKB) who had completed at least two field surveys. The risk assessment tools were the 10-year ASCVD risk prediction models developed based on the CKB cohort. We constructed multistate Markov models to model disease progression and estimate transition probabilities between different risk categories. The total person-years spent unidentified in the high-risk state over a 10-year period were calculated for each screening interval protocol. We also estimated the number of ASCVD events prevented, quality-adjusted life years (QALYs) gained, and costs saved when compared to the 3-yearly screening protocol. Findings: When compared to the uniform 3-yearly protocol, most risk-category-based screening interval protocols would identify more high-risk individuals timely, thus preventing more ASCVD events and gaining QALYs. A few of them would reduce total health-care costs. The protocol, which used 6-year, 3-year, and 2-year screening intervals for low-risk, intermediate-low-risk, and intermediate-high risk individuals, was optimal, and would reduce the person-years spent unidentified in the high-risk category by 17.9% (95% CI: 13.1%–21.9%), thus preventing an estimated 113 thousand (95% CI: 83–138) hard ASCVD events for Chinese adults aged 30–79 over a 10-year period. When using a lower cost of statin therapy, more screening protocols would gain QALYs while saving costs. Interpretation: For the primary prevention of ASCVD, risk-category-based screening protocols outperformed the one-size-fits-all approach in the Chinese population. Funding: This work was supported by National Natural Science Foundation of China (82192904, 82388102, 82192900) and grants (2023YFC2509400) from the National Key R&D Program of China. The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), grants (2016YFC0900500) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 91846303, 81941018), and Chinese Ministry of Science and Technology (2011BAI09B01).

This article proposes a novel energy control strategy for distributed energy storage system (DESS) to solve the problems of slow state of charge (SOC) equalization and slow current sharing. In this strategy, a key part of the presented strategy is the integration of a new parameter virtual current defined from SOC and output current. With the help of virtual current, the characteristic of the arcsinh function has a large slope near the zero point, and three acceleration factors, to realize the fast equalization of SOC and the output current quickly distributed by capacity. In addition, current sharing and voltage restoration can be achieved by designing only one controller, thereby simplifying the control structure. In communication layer, only two variables need to be exchanged between neighboring converters, thus, reducing the communication burden. Then, the stability of the system is analyzed by small signal modeling. Finally, the correctness and effectiveness of the proposed control strategy are verified through the experiments.

The significance of USP11 as a critical regulator in cancer has garnered substantial attention, primarily due to its catalytic activity as a deubiquitinating enzyme. Nonetheless, a thorough evaluation of USP11 across various cancer types in pan-cancer studies remains absent. Our analysis integrates data from a variety of sources, including five immunotherapy cohorts, thirty-three cohorts from The Cancer Genome Atlas (TCGA), and sixteen cohorts from the Gene Expression Omnibus (GEO), two of which involve single-cell transcriptomic data. Our findings indicate that aberrant USP11 expression is predictive of survival outcomes across various cancer types. The highest frequency of genomic alterations was observed in uterine corpus endometrial carcinoma (UCEC), with single-cell transcriptome analysis revealing significantly higher USP11 expression in plasmacytoid dendritic cells and mast cells. Notably, USP11 expression was associated with the infiltration levels of CD8+ T cells and natural killer (NK) activated cells. Additionally, in the skin cutaneous melanoma (SKCM) phs000452 cohort, patients with higher USP11 mRNA levels during immunotherapy experienced a significantly shorter median progression-free survival. USP11 emerges as a promising molecular biomarker with significant potential for predicting patient prognosis and immunoreactivity across various cancer types.

BackgroundInsulin resistance and/or insulin secretion dysfunction are crucial causes of type 2 diabetes mellitus (T2DM). Although some studies have suggested potential roles for vitamins D and K in glucose metabolism and insulin sensitivity, there is limited and inconclusive research on their levels in T2DM patients and their relationship with blood glucose levels and insulin resistance. Additionally, there is a lack of large-scale clinical trials and comprehensive studies investigating the combined effects of vitamins D and K on T2DM.MethodsA total of 195 participants with newly diagnosed T2DM were included in the research group, while 180 volunteers undergoing physical examinations in our hospital served as the control group. Fasting plasma glucose (FPG) was estimated using the glucose-oxidase technique, and fasting serum insulin (FINS) was evaluated by radioimmunoassay. FPG and FINS were used to calculate the homeostasis model assessment-insulin resistance (HOMA-IR). Serum vitamin D levels were measured using 25-hydroxyvitamin D, and vitamin K levels were evaluated using phylloquinone (VK1) and menaquinone (VK2) via ultra-high performance liquid chromatography and tandem mass spectrometry. Receiver operating characteristic (ROC) analysis was performed to assess the predictive value of these vitamins for T2DM.ResultsCirculating levels of 25-hydroxyvitamin D (25.95 ± 10.42 ng/mL), VK1 (1.24 ± 0.89 ng/mL), and VK2 (0.2 ± 0.21 ng/mL) in T2DM patients were significantly lower than in the control group (37.46 ± 13.95 ng/mL for 25-hydroxyvitamin D, 1.99 ± 1.39 ng/mL for VK1, and 0.33 ± 0.22 ng/mL for VK2; p

By replacing and removing defective or infected cells, programmed cell death (PCD) contributes to homeostasis maintenance and body development, which is ubiquitously present in mammals and can occur at any time. Besides apoptosis, more novel modalities of PCD have been described recently, such as necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death. PCD not only regulates multiple physiological processes, but also participates in the pathogenesis of diverse disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD is mainly classified into metabolic dysfunction-associated steatotic liver (MASL) and metabolic dysfunction-associated steatohepatitis (MASH), and the latter putatively progresses to cirrhosis and hepatocellular carcinoma. Owing to increased incidence and obscure etiology of MASH, its management still remains a tremendous challenge. Recently, hepatocyte PCD has been attracted much attention as a potent driver of the pathological progression from MASL to MASH, and some pharmacological agents have been proved to exert their salutary effects on MASH partly via the regulation of the activity of hepatocyte PCD. The current review recapitulates the pathogenesis of different modalities of PCD, clarifies the mechanisms underlying how metabolic disorders in MASLD induce hepatocyte PCD and how hepatocyte PCD contributes to inflammatory and fibrotic progression of MASH, discusses several signaling pathways in hepatocytes governing the execution of PCD, and summarizes some potential pharmacological agents for MASH treatment which exert their therapeutic effects partly via the regulation of hepatocyte PCD. These findings indicate that hepatocyte PCD putatively represents a new therapeutic point of intervention for MASH.