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Abstract IS630/Tc1/mariner (ITm) represents the most widely distributed superfamily of DNA transposons in nature. Currently, bioinformatics research on ITm members primarily involves collecting data of existing and emerging members and organizing them into new groups or families. In the present study, our survey revealed that Tc1 and IS630 members have a broad host range, spanning across all six biological kingdoms (bacteria, fungi, plantae, animalia, archaea and protista) and viruses. The primary discoveries include the first Tn630 member—Tn630-NC1 and the closest homolog of IS630 from viruses—Tc1-C#1. By incorporating our discoveries into existing knowledge, we proposed a model to elucidate the formation of composite transposons. Organization of Tc1 and IS630 members into groups across biological kingdoms facilitates data collection for future research, particularly on their horizontal transfer between different kingdoms. The formation of composite transposons may result from asymmetric of terminal inverted repeats. IS630 should be merged with Tc1 into a single family IS630/Tc1. Furthermore, IS630 and its homologs constitute a valuable resource for studying horizontal gene transfer between gut bacteria and phages, opening up new avenues for research in this field.

Abstract The function of PD-1/PD-L1 axis have been intensively studied for immune escape of various cancers. However, the underlying function of PD-L2 remains poorly understood. Here, we demonstrate that PD-L2 is majorly expressed in exosomes with surface localization by clear cell renal cell carcinoma (ccRCC) cells. Tumor cell-derived exosome PD-L2 (TDE-PD-L2) exhibits high expression compared with TDE-PD-L1 in various cancers. In the absence of adaptive immune, TDE-PD-L2 suppresses tumor growth and metastasis. Under immune competence condition, TDE-PD-L2 is hijacked by immune cells in a PD-1-dependent manner to systematically dampen function of T cells via the increased proportion of the regulatory T cells and the decreased proportion of cytotoxic CD8+ T cells in both tumor-infiltrating T cells and spleen. The effects of TDE-PD-L2 on tumor is restored by antibodies targeting PD-L2. Collectively, we demonstrate that PD-1/TDE-PD-L2 axis systematically suppresses T cell functions, representing a potentially therapeutic strategy for ccRCC treatment.

Abstract Background There is a growing interest in utilizing a combination of brain radiotherapy (RT) and tyrosine kinase inhibitors (TKIs) for patients diagnosed with brain metastases (BM) in epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma (LAC). The current status of this treatment strategy remains a subject of debate. Methods We initiated our study by conducting a comprehensive literature search using the SCI-expanded database of Web of Science Core Collection (WoSCC). We utilized the VOSPviewer software to analyze various aspects of the research, including the year of publication, authorship, keywords, and country.Subsequently, we performed an extensive and systematic literature search on popular online databases. Our primary outcome measures were overall survival (OS) and intracranial progression-free survival (iPFS), both quantified by hazard ratios (HRs). Additionally, for data verification, we included data from patients in non-small cell lung cancer with brain metastasis who underwent therapeutic intervention at the Cancer Prevention and Treatment Center of Sun Yat-sen University and the Radiotherapy Department of Hanzhong Central Hospital between August 2012 and November 2021. Results The bibliometric analysis revealed an increasing trend in research focused on the combination of RT and TKIs for the management of lung cancer brain metastases over the previous decade. Then, nine studies consistent with the research direction were included for meta-analysis. The meta-analysis showed that the OS (HR = 0.81, 95% confidence interval: 0.69–0.94; P = 0.007) and iPFS (HR = 0.71, 95% confidence interval: 0.61–0.82; P

Abstract The immune checkpoint receptor, programmed cell death 1 (PD-1, encoded by PDCD1), mediates the immune escape of cancer, but whether PD-1 splicing isoforms contribute to this process is still unclear. Here, we identify an alternative splicing isoform of human PD-1, which carries a 28-base pairs extension retained from 5′ region of intron 2 (PD-1^28), is expressed in peripheral T cells and tumor infiltrating lymphocytes. PD-1^28 expression is induced on T cells upon activation and is regulated by an RNA binding protein, TAF15. Functionally, PD-1^28 inhibits T cell proliferation, cytokine production, and tumor cell killing in vitro. In vivo, T cell-specific exogenous expression of PD-1^28 promotes tumor growth in both a syngeneic mouse tumor model and humanized NOG mice inoculated with human lung cancer cells. Our study thus demonstrates that PD-1^28 functions as an immune checkpoint, and may contribute to resistance to immune checkpoint blockade therapy.

Potato cyst nematodes (PCNs) are a significant threat to potato production, having caused substantial damage in many countries. Predicting the future distribution of PCN species is crucial to implementing effective biosecurity strategies, especially given the impact of climate change on pest species invasion and distribution. Machine learning (ML), specifically ensemble models, has emerged as a powerful tool in predicting species distributions due to its ability to learn and make predictions based on complex data sets. Thus, this research utilised advanced machine learning techniques to predict the distribution of PCN species under climate change conditions, providing the initial element for invasion risk assessment. We first used Global Climate Models to generate homogeneous climate predictors to mitigate the variation among predictors. Then, five machine learning models were employed to build two groups of ensembles, single-algorithm ensembles (ESA) and multi-algorithm ensembles (EMA), and compared their performances. In this research, the EMA did not always perform better than the ESA, and the ESA of Artificial Neural Network gave the highest performance while being cost-effective. Prediction results indicated that the distribution range of PCNs would shift northward with a decrease in tropical zones and an increase in northern latitudes. However, the total area of suitable regions will not change significantly, occupying 16–20% of the total land surface (18% under current conditions). This research alerts policymakers and practitioners to the risk of PCNs’ incursion into new regions. Additionally, this ML process offers the capability to track changes in the distribution of various species and provides scientifically grounded evidence for formulating long-term biosecurity plans for their control.

Abstract Observational and genetic studies have reported the relationship between dyslexia and Alzheimer’s disease (AD). Until now, the causal effect of dyslexia on AD risk has remained unclear. We conducted a two-sample univariable Mendelian randomization (MR) analysis to determine the causal association between dyslexia and the risk of AD, vascular dementia (VD), Lewy body dementia (LBD), and frontotemporal dementia (FTD) and its four subtypes. First, we selected 42 dyslexia genetic variants from a large-scale genome-wide association studies (GWAS) dataset and extracted their corresponding GWAS summary statistics from AD, VD, LBD, and FTD. Second, we selected four MR methods, including inverse-variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO. Heterogeneity, horizontal pleiotropy, and leave-one-out sensitivity analysis were then used to evaluate the reliability of all causal estimates. We also conducted multivariable MR (MVMR) and mediation analysis to assess the potential mediating role of cognitive performance (CP) or educational achievement (EA) on the causal association between dyslexia and AD. Two MVMR methods, including MV IVW and MV-Egger, and two-step MR were used to perform the analysis. Using IVW, we found a significant causal association between increased dyslexia and increased risk of AD (OR = 1.15, 95% CI: 1.04–1.28, P = 0.006), but not VD, LBD, FTD, or its four subtypes. MR-PRESSO further supported the statistically significant association between dyslexia and AD (OR = 1.15, 95% CI: 1.05–1.27, P = 0.006). All sensitivity analyses confirmed the reliability of causal estimates. Using MV IVW and mediation analysis, we found no causal relationship between dyslexia and AD after adjusting for CP but not EA, CP mediated the total effect of dyslexia on AD with a proportion of 46.32%. We provide genetic evidence to support a causal effect of increased dyslexia on increased risk of AD, which was largely mediated by CP. Reading activity may be a potential intervention strategy for AD by improving cognitive function.

Abstract This study aimed to explore physicians’ and pharmacists’ knowledge, attitudes, and practice (KAP) regarding the prevention and treatment of cardiovascular toxicity associated with cancer treatment. A multicenter cross-sectional study included physicians and pharmacists between April 2023 and June 2023. The study included 918 participants (514 physicians and 404 pharmacists). The average scores of knowledge, attitudes, and practice were 11.6 ± 3.39, 24.7 ± 2.6, and 26.3 ± 6.8 points. Sufficient knowledge was significantly associated with age ≥ 41 years (odds ratio (OR) = 2.745, 95% confidence interval (CI) 1.086–6.941, P = 0.033), male (OR = 2.745, 95% CI 1.150–2.223, P = 0.005), bachelor’s degree (OR = 0.084, 95% CI 0.013–0.533, P = 0.009), master’s degree and above (OR = 0.096, 95% CI 0.015–0.609, P = 0.013), physician occupation (OR = 7.601, 95% CI 1.337–43.207, P = 0.022), pharmacy department (OR = 18.858, 95% CI 3.245–109.57, P = 0.001), oncology department (OR = 4.304, 95% CI 2.426–7.634, P

Abstract Background Osteoarthritis (OA) is the most prevalent type of arthritis and the main reason for progressive disability in middle-aged and older people. Studies of candidate genes may provide a novel insight and treatment strategy for knee osteoarthritis (KOA). The aim of this study was to investigate the relationship between KOA susceptibility and single-nucleotide polymorphism (SNP) of the ADAMTS-5 gene. Materials and methods The case group included 188 patients from Luoyang Orthopedic Hospital with clinically and radiographically diagnosed primary KOA, and the control group included 100 age-matched individuals without KOA. Fifteen ADAMTS-5 SNPs were assayed using MALDI-TOF MS. Allelic and haplotypic frequencies were compared between the groups. The relationship between genotype distribution and risk of KOA was analyzed by multivariate logistic regression. Results The frequency of A allele in rs2249350 site in the KOA group was significantly lower (odds ratio [OR]: 0.761; 95% confidence interval [95% CI]: 0.612–0.947; P = 0.016), while that of C allele was higher than that in the control group (OR: 1.176; 95% CI: 1.025–1.351; P = 0.016). AA genotype and gene model, especially recessive gene model at rs2249350 locus, negatively correlated with KOA risk after adjustment for sex, body mass index, age, and occupation (AA vs. CC: OR: 0.288; 95% CI: 0.124–0.669; P = 0.004; AA vs. CA + CC: OR: 0.348; 95% CI: 0.162–0.749; P = 0.007). Meanwhile, one protective haplotype, GA (rs229054, rs2249350) (OR: 0.763; 95% CI: 0.614–0.949; P = 0.017), and one high-risk haplotype, GC (rs229054, rs2249350) (OR: 1.259; 95% CI: 1.032–1.537; P = 0.019), were found in this study. Conclusion Despite a limited sample size, our study suggests that the rs2249350 polymorphism in the ADAMTS-5 gene is one of the genetic factors influencing the risk of KOA. The A allele and AA genotype of rs2249350 may protect from KOA, whereas C allele and CC genotype increase the risk of KOA. In addition, the GA haplotype (rs229054, rs2249350) might be associated with a decreased risk of KOA, whereas the GC haplotype (rs229054, rs2249350) may be a risk factor for KOA. Additional larger-sized studies in more ethnically diverse populations are needed to confirm these findings.

Abstract Background In recent decades, early rehabilitation after Achilles tendon rupture (ATR) repair has been proposed. The aim of this prospective cohort study was to compare different immobilisation durations in order to determine the optimal duration after open surgery for ATR repair. Methods This study included 1088 patients (mean age, 34.9 ± 5.9 years) who underwent open surgery for acute ATR repair. The patients were categorised into four groups (A, B, C, and D) according to postoperative immobilisation durations of 0, 2, 4, and 6 weeks, respectively. All patients received the same suture technique and a similar rehabilitation protocol after brace removal,; they were clinically examined at 2, 4, 6, 8, 10, 12, 14, and 16 weeks postoperatively, with a final follow-up at a mean of 19.0 months. The primary outcome was the recovery time for the one-leg heel-rise height (OHRH). Secondary outcomes included the time required to return to light exercise (LE) and the recovery times for the range of motion (ROM). Data regarding the surgical duration, complications, the visual analogue scale (VAS) score for pain, the Achilles tendon Total Rupture Score (ATRS), and the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale score were also collected. Results The recovery times for OHRH, LE, and ROM were significantly shorter in groups A and B than in groups C and D (P

Abstract Background and aim Bismuth and non-bismuth quadruple therapy are the guideline-recommended first-line therapy in children with Helicobacter pylori infection in areas with high antibiotic resistance. However, their efficacy in children is uncertain and there are few well-designed studies. Here, we evaluated the eradication rates of standard triple therapy, bismuth-based quadruple therapy and sequential therapy in children with H. pylori infection. Methods A randomised controlled trial was conducted in children infected with H. pylori in West China Second Hospital. They were randomly assigned to 14-day standard triple therapy (omeprazole + amoxicillin + clarithromycin), 14-day bismuth quadruple therapy (bismuth + omeprazole + amoxicillin + clarithromycin) and 10-day sequential therapy (omeprazole + amoxicillin for 5 days followed by omeprazole + clarithromycin + metronidazole for 5 days). The eradication rate was assessed by a 13C-urea breath test 4 to 6 weeks after therapy completion. Symptom improvement and adverse events were compared among the groups. Results In total, 132 patients were enrolled. The eradication rates of 14-day standard triple therapy, 14-day bismuth quadruple therapy and 10-day sequential therapy were 70.0%, 78.9% and 50.0% in per-protocol analysis and 63.6%, 68.2% and 43.2% in intention-to-treat analysis, respectively. Symptom improvement and adverse drug event rates were similar in the three groups. Conclusion The three therapeutic regimens evaluated in this study are equally not recommendable for H. pylori infection treatment due to unsatisfactory eradication rates. The high prevalence of clarithromycin resistance makes the use of clarithromycin-based quadruple therapy not advisable, even in combination with amoxicillin and bismuth salts.

Abstract Background Chronic cough in children is closely related to gastroesophageal reflux (GER). However, this association has not been adequately studied due to a lack of diagnostic tools. Combined esophageal multichannel intraluminal impedance and pH (MII-pH) monitoring is considered the most accurate method for evaluating the association between symptoms and reflux, but data on its use in children with chronic cough are still lacking. We aimed to assess the association between chronic cough and GER in children through MII-pH monitoring. Methods Children with chronic cough (> 4 weeks) who were suspected gastroesophageal reflux disease(GERD) were selected to undergo 24 h MII-pH monitoring at our hospital. Patients were divided into groups according to their age, body position, reflux index (RI) or total reflux events, and the differences between the groups were analyzed. Then the significance and value of 24 h pH and impedance monitoring in chronic cough and the relationship between chronic cough and reflux were discussed. Results Overall, 426 patients were included. The median age was 12 months (interquartile range: 6–39.5 months), 129 (30.3%) patients had RI > 7% detected by pH-metry, and 290 (68.1%) patients had positive diagnosis based on the impedance data. GER predominantly occurred in the upright position and mostly involved weakly acidic reflux and mixed gas–liquid reflux. There were 14.1% of children in non-acid GER group were SAP positive showing no difference in acid GER group 13.2% (P = 0.88), whereas patients with SAP > 95% in MII positive group (47[16.2%]) is higher than in MII negative group (P

Reinforcement configuration of Al composites has recently been at the center of attention. In this study, through the analysis of microstructure and tensile properties, effects of Cu content on the reinforcing behaviors of AlN network were investigated in details. Results indicated that the increasing amount of Cu would form micron Al2Cu which would decorated on the AlN network. With the increasing amount of Cu addition from 1.5% to 6%, the particle size of Al2Cu increased from 1 μm to 10 μm. Besides the micron Al2Cu, Cu elements were also existed in θ′ precipitates in the region where were poor of AlN and segregated on the surface of AlN. Given the microstructure changes with different Cu addition, the tensile properties at room temperature increased with Cu addition while the average tensile strength at 350 °C were decreased from 102 MPa to 85 MPa. The addition of elements would affect the bearing capacity of the 8.2AlN/Al–Cu composites at 350 °C. Firstly, the micron Al2Cu phase would suffer the load and get stress concentration. It would lead to the premature imitation of voids and strongly impair the strengthening behavior of AlN network. Secondly, the nano θ′ precipitates would become coarsen and the hinder effects of dislocation would be enhanced at 350 °C. Finally, the segregated Cu atoms on the AlN surface could increase the deformation coordination of AlN network and help decrease the stress concentration.

Abstract Background Acute thrombotic events play a major role in various cardiovascular diseases. Therefore, direct thrombus imaging can be proved beneficial for early diagnosis and prompt therapy of thrombosis. Our study investigated targeted dual‐modality cyclic arginine‐glycine‐aspartic micro bubbles (cRGD‐MBs) for direct imaging of thrombi by fluorescence and ultrasound. Methods cRGD‐MBs were prepared by mechanical vibration and chemical chelation methods. Results Coulter counter analysis demonstrated that the cRGD‐MBs were well dispersed, with diameters ranging from 1 to 3 μm. They emitted bright red fluorescence under an excitation wavelength of 660 nm. In vivo fluorescence and ultrasound imaging revealed that cRGD‐MBs accumulated at the site of thrombus in the carotid artery with significant fluorescence and ultrasonic signal. Conclusions This study showed that novel microbubble cRGD‐MBs were successfully synthesized, and that these could potentially be used as contrast agents for immediate diagnosis of acute thrombus in vivo.

Abstract Background Ischemic cardio-cerebrovascular disease is the leading cause of mortality worldwide. However, studies focusing on elderly and very elderly patients are scarce. Hence, our study aimed to characterize and investigate the long-term prognostic implications of ischemic cardio-cerebrovascular diseases in elderly Chinese patients. Methods This retrospective cohort study included 1026 patients aged ≥ 65 years who were categorized into the mono ischemic cardio-cerebrovascular disease (MICCD) (either coronary artery disease or ischemic stroke/transient ischemic attack) (n = 912) and the comorbidity of ischemic cardio-cerebrovascular disease (CICCD) (diagnosed with both coronary artery disease and ischemic stroke/transient ischemic attack at admission) (n = 114). The primary outcome was all-cause death. The mortality risk was evaluated using the Cox proportional hazards risk model with multiple adjustments by conventional and propensity-score-based approaches. Results Of the 2494 consecutive elderly patients admitted to the hospital, 1026 (median age 83 years [interquartile range]: 76.5–86.4; 94.4% men) met the inclusion criteria. Patients with CICCD consisted mostly of very elderly (79.2% vs. 66.1%, P

Abstract Objective To evaluate the consistency between doctors and artificial intelligence (AI) software in analysing and diagnosing pulmonary nodules, and assess whether the characteristics of pulmonary nodules derived from the two methods are consistent for the interpretation of carcinomatous nodules. Materials and Methods This retrospective study analysed participants aged 40–74 in the local area from 2011 to 2013. Pulmonary nodules were examined radiologically using a low-dose chest CT scan, evaluated by an expert panel of doctors in radiology, oncology, and thoracic departments, as well as a computer-aided diagnostic(CAD) system based on the three-dimensional(3D) convolutional neural network (CNN) with DenseNet architecture(InferRead CT Lung, IRCL). Consistency tests were employed to assess the uniformity of the radiological characteristics of the pulmonary nodules. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic accuracy. Logistic regression analysis is utilized to determine whether the two methods yield the same predictive factors for cancerous nodules. Results A total of 570 subjects were included in this retrospective study. The AI software demonstrated high consistency with the panel's evaluation in determining the position and diameter of the pulmonary nodules (kappa = 0.883, concordance correlation coefficient (CCC) = 0.809, p = 0.000). The comparison of the solid nodules' attenuation characteristics also showed acceptable consistency (kappa = 0.503). In patients diagnosed with lung cancer, the area under the curve (AUC) for the panel and AI were 0.873 (95%CI: 0.829–0.909) and 0.921 (95%CI: 0.884–0.949), respectively. However, there was no significant difference (p = 0.0950). The maximum diameter, solid nodules, subsolid nodules were the crucial factors for interpreting carcinomatous nodules in the analysis of expert panel and IRCL pulmonary nodule characteristics. Conclusion AI software can assist doctors in diagnosing nodules and is consistent with doctors' evaluations and diagnosis of pulmonary nodules.

Dysbiosis of the intestinal microbiota is prevalent among patients with colorectal cancer (CRC). This study aims to explore the anticancer roles of the fecal microbiota in inhibiting the progression of colorectal cancer and possible mechanisms. The intestinal microbial dysbiosis in CRC mice was significantly ameliorated by fecal microbiota transplantation (FMT), as indicated by the restored ACE index and Shannon index. The diameter and number of cancerous foci were significantly decreased in CRC mice treated with FMT, along with the restoration of the intestinal mucosal structure and the lessening of the gland arrangement disorder. Key factors in oxidative stress (TXN1, TXNRD1, and HIF-1α); cell cycle regulators (IGF-1, BIRC5, CDK8, HDAC2, EGFR, and CTSL); and a critical transcription factor of the innate immune signal pathway (IRF5) were among the repressed oncogenic targets engaged in the FMT treatment of CRC. Correlation analysis revealed that their expressions were positively correlated with uncultured_bacterium_o_Mollicutes_RF39, Rikenellaceae_RC9_gut_group, and negatively correlated with Bacillus, Marvinbryantia, Roseburia, Angelakisella, Enterorhabdus, Bacteroides, Muribaculum, and genera of uncultured_bacterium_f_Eggerthellaceae, uncultured_bacterium_f_Xanthobacteraceae, Prevotellaceae_UCG-001, uncultured_bacterium_f_Erysipelotrichaceae, uncul-tured_bacterium_f_Lachnospiraceae, uncultured_bacterium_f_Ruminococcaceae, Eubacterium_coprostanoligenes_group, Ruminococcaceae_UCG-005, and uncultured_bacterium_f_Peptococcaceae. This study provides more evidence for the application of FMT in the clinical treatment of CRC.

Abstract De novo lipogenesis (DNL), a hallmark of cancer, facilitates tumor growth and metastasis. Therapeutic drugs targeting DNL are being developed. However, how DNL is directly regulated in cancer remains largely unknown. Here, transcription factor sine oculis homeobox 1 (SIX1) is shown to directly increase the expression of DNL‐related genes, including ATP citrate lyase (ACLY), fatty acid synthase (FASN), and stearoyl‐CoA desaturase 1 (SCD1), via histone acetyltransferases amplified in breast cancer 1 (AIB1) and lysine acetyltransferase 7 （HBO1/KAT7）, thus promoting lipogenesis. SIX1 expression is regulated by insulin/lncRNA DGUOK‐AS1/microRNA‐145‐5p axis, which also modulates DNL‐related gene expression as well as DNL. The DGUOK‐AS1/microRNA‐145‐5p/SIX1 axis regulates liver cancer cell proliferation, invasion, and metastasis in vitro and in vivo. In patients with liver cancer, SIX1 expression is positively correlated with DGUOK‐AS1 and SCD1 expression and is negatively correlated with microRNA‐145‐5p expression. DGUOK‐AS1 is a good predictor of prognosis. Thus, the DGUOK‐AS1/microRNA‐145‐5p/SIX1 axis strongly links DNL to tumor growth and metastasis and may become an avenue for liver cancer therapeutic intervention.

BackgroundThe triglyceride-glucose (TyG) index is a surrogate indicator of insulin resistance. Therefore, we aimed to determine the association between TyG index and heart failure (HF) with preserved ejection fraction (HFpEF) in patients with coronary heart disease (CHD) and to explore whether such associations would be modified by different metabolic states.MethodsAmong 107,301 CHD patients, 62,794 were included to analyze the relationship between the TyG index and HF. Among them, 8,606 patients who had undergone echocardiography were included to identify different types of HF, including HF with reduced ejection fraction (HFrEF), HF with intermediate-range ejection fraction (HFmrEF), and HFpEF. Among them, 1896 patients were diagnosed with HFpEF. Logistic regression was used to analyze the relationship between the TyG index and HFpEF in CHD patients. In addition, the association between TyG index and HFpEF according to sex, age, blood lipids, and blood pressure was assessed.ResultsA baseline analysis of CHD patients divided into four groups according to the tertile level of the TyG index showed significant differences in the related parameters between the groups. In the multi-adjusted models, the TyG index was significantly associated with the risk of HFpEF (odds ratio [OR]: 1.17; 95% confidence interval [CI]: 1.09–1.25). After adjustment for multivariates, TyG index levels for T2 (OR: 1.33; 95% CI: 1.16–1.52) and T3 (OR: 1.52; 95% CI: 1.32–1.74) were associated with increased OR in HFpEF. In addition, the TyG index of CHD patients was significantly associated with HFpEF in older adults aged > 60 years (OR: 1.20; 95% CI: 1.11–1.29), hypertension (OR: 1.27; 95% CI: 1.17–1.37), and dyslipidemia (OR: 1.15; 95% CI: 1.08–1.24). Moreover, the OR (OR: 1.23; 95% CI: 1.11–1.36) in women is higher than in men (OR: 1.17; 95% CI: 1.02–1.22, indicating a stronger association between TyG index and HFpEF in women.ConclusionsOur findings demonstrated a significant association between TyG index and HFpEF in CHD patients. Furthermore, TyG index was independently associated with HFpEF in hypertension, dyslipidemia, and older patients (aged > 60 years). In addition, the association between the TyG index and HFpEF in CHD patients differed according to sex.

IntroductionEmerging evidence suggests that the vaginal microbiota is closely associated with cervical cancer. However, little is known about the relationships among the vaginal microbiota, vaginal metabolites, and cervical lesion progression in women undergoing cervical dysplasia.MethodsIn this study, to understand vaginal microbiota signatures and vaginal metabolite changes in women with cervical lesions of different grades and cancer, individuals with normal or cervical dysplasia were recruited and divided into healthy controls (HC) group, low-grade squamous intraepithelial lesions (LSIL) group, high-grade squamous intraepithelial lesions (HSIL) group, and cervical cancer (CC) group. Vaginal secretion samples were collected for 16S rRNA gene sequencing, liquid chromatography coupled with mass spectrometry (LC–MS)-based metabolomics, and integrated analysis.ResultsThe results demonstrated that bacterial richness and diversity were greater in the CC group than the other three groups. Additionally, Lactobacillus was found to be negatively associated with bacterial diversity and bacterial metabolic functions, which increased with the degree of cervical lesions and cancer. Metabolomic analysis revealed that distinct metabolites were enriched in these metabolite pathways, including tryptophan metabolism, retinol metabolism, glutathione metabolism, alanine, aspartate, and glutamate metabolism, as well as citrate cycle (TCA cycle). Correlation analysis revealed positive associations between CC group-decreased Lactobacillus abundance and CC group-decreased metabolites. Lactobacillus iners was both negative to nadB and kynU genes, the predicted abundance of which was significantly higher in the CC group. The linear regression model showed that the combination of the vaginal microbiota and vaginal metabolites has good diagnostic performance for cervical cancer.DiscussionOur results indicated a clear difference in the vaginal microbiota and vaginal metabolites of women with cervical dysplasia. Specifically altered bacteria and metabolites were closely associated with the degree of cervical lesions and cancer, indicating the potential of the vaginal microbiota and vaginal metabolites as modifiable factors and therapeutic targets for preventing cervical cancer.

ObjectivesOropouche virus (OROV) causes systemic infections including the nervous and blood systems, posing a significant and growing public health challenge. However, a comprehensive review of the bibliometric analysis of OROV is still lacking. Therefore, the objective of this study was to provide insight into the research dynamics and current hotspots of OROV.MethodsThis study used bibliometric analysis to explore the current status of research related to OROV. 148 publications from 1961 to 2024 were retrieved from the Scopus database. Countries, authors, institutions, journals, references, and keywords were visualized using VOSviewer, CiteSpace, R studio, and Bibliometrix. Microsoft Excel was used for statistical analysis.ResultsBrazil is the country with the highest number of publications, total cited frequency, and the most extensive international collaboration. The most popular journal in this field is the American Journal of Tropical Medicine and Hygiene. Instituto Evandro Chagas is the institution with the highest number of publications, and Eurico Arruda is involved in the highest number of publications. Keyword co-occurrence analysis showed that Oropouche bunyavirus, virology, bunyavirus, priority journal, and nucleotide sequence are the main research hotspots in this field.ConclusionOur study provides a comprehensive overview of the research trends and key areas of focus in OROV. The field is currently experiencing rapid growth, as evidenced by the rising number of annual publications, which not only highlights increased research activity but also lays a solid foundation for further in-depth investigations. This trend offers valuable insights for developing effective strategies for outbreak prevention and control in public health. Presently, researchers are concentrating on the detailed study of Bunyavirus infections, employing both virological and genetic approaches to elucidate their complex pathogenic mechanisms.

Background: Regulated cell death (RCD) has considerable impact on tumor progress and sensitivity of treatment. Lung adenocarcinoma (LUAD) show a high resistance for conventional radiotherapies and chemotherapies. Currently, regulation of cancer cell death has been emerging as a new promising therapeutic avenue for LUAD patients. However, the crosstalk in each pattern RCD is unclear. Methods: We integrated collected the hub-genes of 12 RCD subroutines and compressively analyzed these hub-genes synergistic effect in LUAD. The characters of RCD genes expression and prognosis were developed in The Cancer Genome Atlas (TCGA)-LUAD data. We developed and validated an RCD risk model based on TCGA and GSE70294 data set, respectively. Functional annotation and tumor immunotherapy based on the risk model were also investigated. Results: 28 RCD-related genes and two LUAD molecular cluster were identified. Survival analysis revealed that the prognosis in high-risk group was worser than those in low-risk group. Functional enrichment analysis indicated that the RCD risk model correlated with immune responses. Further analysis indicated that the high-risk group in RCD risk model exhibited an immunosuppressive microenvironment and a lowly immunotherapy responder ratio. Conclusions: We present an RCD risk model which have a promising ability in predicting LUAD prognosis and immunotherapy response.

The planning of public charging stations is crucial for the growth of electric vehicles (EVs). To improve the accuracy of predicting EV charging demand in urban areas, we propose a charging decision-making model based on fuzzy logic. Meanwhile, the influence of private charging piles is considered to further enhance the accuracy of predicting public charging demand. To address the issue of optimization algorithms easily getting stuck in local optima due to the vast quantity of variables involved in the location and capacity planning process, this paper introduces a two-layer planning method. In specific, the upper-level location model optimizes the locations of charging stations, while the lower-layer capacity model determines the number of charging piles within each station, leading to a reduction in the number of variables for each layer. Moreover, through iterative exchange results between the upper-layer location model and lower-layer capacity model, the optimal solution can be attained. The simulation results demonstrate that the proposed method can simultaneously consider the perspectives of both EV drivers and charging station investors, while also enhancing the utilization rates of public charging piles.

Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide, and endoplasmic reticulum stress (ERS) and mitochondrial Ca2+ overload have been involved in apoptotic cardiomyocyte death during MI. 13-Methylpalmatine (13-Me-PLT) is a natural isoquinoline alkaloid isolated from Coptis chinensis and has not been systematically studied for their potential pharmacological effects in cardiovascular diseases. We conducted the present study to elucidate whether 13-Me-PLT modulates MI pathology in animal MI and cellular hypoxic models, employing state-of-the-art molecular techniques. The results demonstrated that 13-Me-PLT preserved post-ischemic cardiac function and alleviated cardiomyocyte apoptosis. 13-Me-PLT decreased ERS and the communication between ER and mitochondria, which serves as a protective mechanism against mitochondrial Ca2+ overload and structural and functional injuries to mitochondria. Our data revealed mitigating mitochondrial Ca2+ overload and apoptosis by inhibiting CHOP-mediated Ca2+ transfer between inositol 1,4,5-trisphosphate receptor (IP3R) in ER and VDAC1 in mitochondria as an underlying mechanism for 13-Me-PLT action. Furthermore, 13-Me-PLT produced superior effects in alleviating cardiac dysfunction and apoptosis post-MI to diltiazem and palmatine. Collectively, our research suggests that the CHOP/IP3R/VDAC1 signaling pathway mediates ER-mitochondrial Ca2+ transfer and 13-Me-PLT activates this axis to maintain cellular and organellar Ca2+ homeostasis, protecting against ischemic myocardial injury. These findings may offer an opportunity to develop new agents for the therapy of ischemic heart disease.

Shrimp are non-negligible victims of cadmium (Cd) contamination, and there is still a lack of strategies for mitigating Cd toxicity in shrimp. Bacillus cereus, with its significant heavy metal (HM) tolerance and chelating effects, is a representative beneficial bacterium to be investigated for mitigating the toxicity of Cd exposure. This study revealed the effects and potential mechanisms of B. cereus in mitigating chronic Cd toxicity in shrimp by analyzing growth performance, hepatopancreatic Cd accumulation, pathology, as well as comprehensive hepatopancreatic transcriptomics and metabolomics in Litopenaeus vannamei. The results showed that shrimp's growth inhibition, hepatopancreatic Cd accumulation and physiological structure damage in B. cereus+chronic Cd group were effectively alleviated compared with the chronic Cd treatment group. The pathways related to amino acid metabolism, glycolipid metabolism, immune response, and antioxidant stress were significantly activated in the B. cereus+chronic Cd group, including glycolysis, pentose phosphate pathway, oxidative phosphorylation, biosynthesis of amino acids, and biosynthesis of unsaturated fatty acids pathways. The key differentially expressed genes (e.g., macrophage migration inhibitory factor, glycine cleavage system H protein, glycine dehydrogenase, phosphoglucomutase-2, asparaginase, ATP synthase subunit, cytochrome c, and 4-hydroxyphenylpyruvate dioxygenase) and metabolites (e.g., L-leucine, D-ribose, gluconic acid, 6-Phosphogluconic acid, sedoheptulose 7-phosphate, 1-Kestose, glyceric acid, arachidic acid, prostaglandins, 12-Keto-tetrahydro-leukotriene B4, and gamma-glutamylcysteine) associated with the above pathways were significantly altered. This study demonstrated that B. cereus is an effective mitigator for the treatment of chronic Cd poisoning in shrimp. B. cereus may play a role in alleviating the toxicity of Cd by enhancing the antioxidant performance, immune defense ability, metabolic stability, and energy demand regulation of shrimp. The study provides reference materials for the study of B. cereus in alleviating Cd toxicity of shrimp and broadens the application of probiotics in treating HM toxicity.

Tracheobronchomegaly (TBM) is a rare condition characterized by the dilatation of the trachea and bronchi due to severe atrophy of elastic fibers, accompanied by the thinning of the muscularis mucosae and the development of diverticula between cartilaginous rings. The etiology of this condition remains unclear. Tracheobronchopathia osteochondroplastica (TO) is another uncommon airway disease with an unknown etiology. The co-occurrence of these two diseases has not been reported. In this study, we report and discuss a case involving an elderly man with TBM and TO with a history of recurrent pneumonia over the past 6 years.

Despite the associations of dietary patterns and air pollution with human reproductive health have been demonstrated, the interaction of maternal preconception diet and PM2.5 and its components exposure on in vitro fertilization (IVF) treatment outcomes has not been investigated. A total of 2688 couples from an ongoing prospective cohort were included. Principle component analysis with varimax rotation was performed to determine dietary patterns. One-year and 85-day average PM2.5 and its components exposure levels before oocyte retrieval were estimated. Generalized linear regression models were conducted to assess the association of dietary patterns and PM2.5 and its components exposure with IVF outcomes. Interactive effects of dietary patterns on the association between PM2.5 and its components and IVF outcomes were evaluated by stratified analyses based on different dietary patterns. A positive association between the “Fruits-Vegetables-Dairy” pattern and normal fertilization (p-trend = 0.009), Day 3 available embryos (p-trend = 0.048), and top-quality embryos (p-trend = 0.041) was detected. Conversely, women with higher adherence to the “Puffed food-Bakery-Candy” pattern were less likely to achieve Day 3 available embryos (p-trend = 0.042) and top-quality embryos (p-trend = 0.030), clinical pregnancy (p-trend = 0.049), and live birth (p-trend = 0.020). Additionally, increased intake of animal organs and seafood improved the odds of live birth (p-trend = 0.048). Exposure to PM2.5, SO42-, organic matter (OM), and black carbon (BC) had adverse effects on embryo development and pregnancy outcomes. Furthermore, our findings indicated that the effects of PM2.5 components exposure on normal fertilization and embryo quality were modified by the “Grains-Tubers-Legumes”. Moreover, moderate intake of animal organs and seafood appeared to attenuate the effect of NO3- and NH4+ on the risk of early abortion. Our findings provide human evidence of the interaction between dietary patterns and PM2.5 exposure on IVF outcomes during preconception, implicating the potential for dietary interventions in infertile women to improve reproductive outcomes under conditions of unavoidable ambient air-pollutant exposure.

Objectives: The recent surge of Mpox outbreaks in multiple countries has garnered global attention. As of July 12, 2023, there have been 88,288 reported cases of Mpox worldwide. Although genetic variation was not found to be the cause of the epidemic outbreak, the reasons for its rapid spread remain unclear. Methods: Using the niche method, this study identified high-risk regions for Mpox and determined that human factors are the primary contributors to global risks. To further investigate, a travel network resistance surface was created based on various modes of transportation and was combined with sea, airline, highway, and railway routes to construct the least cost path for human travel networks in different risk areas. Results: The results indicated that high-risk regions for Mpox are mainly concentrated in Europe and the United States, with large risk ranges and high-risk values. The least cost path revealed three primary transmission paths rely on developed transportation networks, including internal transmission in North America, Europe-Africa, and Europe-Asia-Africa. These findings suggest that human activities, facilitated by developed travel networks, remain the main contributing factor to the spread. Conclusions: In summary, based on the Mpox epidemic report, this study conducted risk prediction and driving factor analysis on Mpox. The research results indicate that human use of transportation for long-distance activities is a key factor leading to the rapid spread of the virus. Subsequently, we focused on studying the global transmission pathways of Mpox and revealed several transmission pathways with high global population migration rates by constructing the LCPs between different high-risk areas. This study also emphasizes the importance of applying early monitoring data of Mpox to model risk prediction in controlling emerging infectious diseases, providing a new perspective for controlling Mpox and similar diseases.

Abstract Aims This study assessed diabetes (type 1 and type 2) mortality in China and globally from 1990 to 2019, predicting the next decade's trends. Materials and Methods Data came from the Global Burden of Disease (GBD) database. The annual percentage change (AAPC) in age‐standardized mortality rates (ASMR) for diabetes (type 1 and type 2) during 1990–2019 was calculated. A Bayesian age‐period‐cohort (BAPC) model predicted diabetes (type 1 and type 2) mortality from 2020 to 2030. Results In China, type 1 diabetes deaths declined from 6,005 to 4,504 cases (AAPC −2.827), while type 2 diabetes deaths rose from 64,084 to 168,388 cases (AAPC −0.763) from 1990 to 2019. Globally, type 1 diabetes deaths increased from 55,417 to 78,236 cases (AAPC 0.223), and type 2 diabetes deaths increased from 606,407 to 1,472,934 cases (AAPC 0.365). Both China and global trends showed declining type 1 diabetes ASMR. However, female type 2 diabetes ASMR in China initially increased and then decreased, while males had a rebound trend. Peak type 1 diabetes deaths were in the 40–44 age group, and type 2 diabetes peaked in those over 70. BAPC predicted declining diabetes (type 1 and type 2) mortality burden in China and globally over the next 10 years. Conclusions Type 2 diabetes mortality remained high in China and globally despite decreasing type 1 diabetes mortality over 30 years. Predictions suggest a gradual decrease in diabetes mortality over the next decade, highlighting the need for continued focus on type 2 diabetes prevention and treatment.

Chilled meat is favored by consumers because of its fresh, low price and high nutritive value. However, it is susceptible for microbial contamination in slaughtering, processing, marketing and other links, as well as the change of its color, odor and other qualities, which results in short shelf life, even losing its edible value and other problems of chilled meat, restricting the further development of the fresh meat industry. Therefore, the preservative preservation technology is particularly important in China's meat food, and it has a wide range of application prospects in the development of meat food industry. This paper describes the main reasons for the corruption and deterioration of chilled meat, including microbial contamination, lipid oxidation and discoloration of myoglobin. Besides, it elaborates on chemical preservation technologies such as organic acids, microbial metabolites and physical preservation technologies such as packaging technology, irradiation technology, etc., and their anticorrosion mechanisms. In addition to enumerating the status quo of its application in the preservation of meat, analyzing the advantages of preservation technology and its limitations in the development, and making future research proposals for the development of meat food. In addition, it lists the current status of its application in meat preservation, analyzes the advantages of the preservation technology and its limitations in application, and makes prospects for future preservation technologies, with a view to providing a certain theoretical basis for the further in-depth research on the preservation technology for the preservation of the preservation of cold meat as well as the preservation of fresh meat.

Background: Various factors play crucial roles in aneurysm development and prognosis. Macrophages have recently emerged as a major research focus. Despite the numerous studies on the role and function of macrophages in aneurysm pathogenesis, no bibliometric analyses have focused on this topic. Objective: This study aimed to analyze articles related to macrophages and aneurysms to reveal trends, hotspots, and new frontiers in macrophage-related aneurysm research. Methods: We retrieved and incorporated 1211 articles from the Science Citation Index Expanded database of the Web of Science Core Collection between 1999 and 2022. The data were analyzed and visualized using CiteSpace and VOSviewer, and Microsoft Excel 2019 was used to plot the data. Results: The most influential articles were published between 1999 and 2022, with a total citation count of 43870. This study encompassed a comprehensive analysis of 74 research directions. The year with the highest number of publications was 2021 when 109 articles were published. 'ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY' journal has made significant contributions by publishing the highest number of articles (99 articles), while funding support primarily came from the National Institutes of Health and United States Department of Health and Human Services. The United States exerted a substantial influence within this field, with a total publication count of 453 publications and the highest centrality value (0.63). Recent studies have focused on understanding the developmental processes underlying aneurysms and devising preventive measures to effectively impede disease progression. Conclusions: Our analysis demonstrates the rapid growth in research exploring the relationship between macrophages and aneurysms over the past two decades. Continued exploration and collaboration among different specialties and manufacturers will facilitate innovative approaches for effective management strategies that target patients with diverse forms of aneurysms.

Thermal barrier coatings (TBCs) applications of yttria-stabilized (YSZ) are widely utilized on turbine blades of aviation engines due to its low thermal conductivity and high electrical conductivity. Predicting the infrared emissivity aids in monitoring blade operating temperatures, ensuring safe engine operation. This paper innovatively introduces a novel three-dimensional columnar EB-PVD coating model and utilizes the FDTD method to predict emissivity. The model exhibits strong consistency with experimental results for predicted emissivity in the short-wave infrared band (1.4–3 μm). The unique microstructure of the EB-PVD thermal barrier coatings significantly influence the infrared emissivity. The results indicate that vertically uniform arranged feathers exhibit higher emissivity levels compared to feathers with varying densities. Additionally, increasing the thickness of the ceramic top coating and reducing spherical closed porosity also enhance the emissivity levels. This research provides guidance for controlling emissivity at the microscale in the preparation of thermal barrier coatings.

Chemoresistance is a main cause of chemotherapy failure and tumor recurrence. The effects of global protein SUMOylation on chemoresistance in colorectal cancer (CRC) remains to be investigated. Herein, we have proposed that the elevated SUMO2/3-modified proteins confer 5-fluorouracil (5-FU) chemoresistance acquisition in CRC. The SUMOylation levels of global proteins in CRC cell lines were elevated compared with normal colon cell line NCM460. 5-FU treatment obviously reduced SUMOylation of global proteins in 5-FU-sensitive CRC cells including HT29, HCT116 and HCT-8. However, in 5-FU-resistant HCT-8/5-FU cells, the expression level of SUMO2/3-modified proteins was increased under 5-FU exposure in a concentration-dependent manner. 5-FU treatment combined with SUMOylation inhibitor ML-792 significantly increased the sensitivity of 5-FU-resistant cells to 5-FU and reduced colony formation numbers in HCT-8/5-FU cells. And UBC9-mediated SUMOylation elevation contributes to 5-FU resistance in HCT116 cells. Moreover, we also identified RREB1 as a regulator of SUMOylation profiling of global cellular proteins via directly binding to the promoter of UBC9. Overexpression of RREB1 promoted 5-FU resistance in CRC, which was partially abolished by treatment of inhibitor ML-792. In conclusion, RREB1-enhanced protein SUMOylation contributes to 5-FU resistance acquisition in CRC.

Adaptive gradient algorithms have been successfully used in deep learning. Previous work reveals that adaptive gradient algorithms mainly borrow the moving average idea of heavy ball acceleration to estimate the first- and second-order moments of the gradient for accelerating convergence. However, Nesterov acceleration which uses the gradient at extrapolation point can achieve a faster convergence speed than heavy ball acceleration in theory. In this article, a new optimization algorithm which combines adaptive gradient algorithm with Nesterov acceleration by using a look-ahead scheme, called NALA, is proposed for deep learning. NALA iteratively updates two sets of weights, i.e., the ‘fast weights’ in its inner loop and the ‘slow weights’ in its outer loop. Concretely, NALA first updates the fast weights k times using Adam optimizer in the inner loop, and then updates the slow weights once in the direction of Nesterov’s Accelerated Gradient (NAG) in the outer loop. We compare NALA with several popular optimization algorithms on a range of image classification tasks on public datasets. The experimental results show that NALA can achieve faster convergence and higher accuracy than other popular optimization algorithms.

This study aims to examine the effects of various aluminum alloy constitutive models on the behavior of concrete-filled aluminum tubular stub columns under axial compression. The bi-linear model with hardening, the Baehre model, and the Ramberg-Osgood (R-O) model, which follow the European standard (EC9) were analyzed and compared in terms of their ability to describe the stress-strain behavior of aluminum alloy tensile coupons over the full range, and their respective application scenarios were discussed. A total of 74 sets of experimental data results were collected to examine the effects of these three models on the ultimate load of concrete-filled aluminum tubular stub columns. Furthermore, a full-scale model was constructed to analyze the effect of the hardening exponent n in the R-O model on the load-displacement curves. The results show that, apart from the bi-linear model with hardening, the other two aluminum alloy constitutive models are capable of accurately predicting the stress-strain behavior of aluminum alloys throughout the full range. The accuracy of the R-O model is significantly influenced by the calculation methods of n. The Baehre model is found to be more suitable for non-heat-treated aluminum alloys. The simulated ultimate load values obtained from the three constitutive models fall within a deviation range of ±10%, indicating their suitability for practical engineering applications. Among the three models, the R-O model exhibits the highest stability, as changes in the hardening exponent n do not affect the ultimate load but have a significant effect on the load-displacement curves beyond the ultimate load.

BackgroundPrevious observational studies have indicated a potential association between the gut microbiota and multiple myeloma (MM). However, the relationship between the gut microbiota and MM remains unclear. This study aimed to ascertain the existence of a causal link between the gut microbiota and MM.MethodsTo investigate the potential causal relationship between gut microbiota and MM, a two-sample Mendelian randomization (MR) analysis was conducted. Exposure data was obtained from the MiBioGen consortium, which provided genetic variants associated with 211 bacterial traits. MM outcome data was obtained from the FinnGen consortium. The selection of Single nucleotide polymorphisms estimates was performed through meta-analysis using inverse-variance weighting, and sensitivity analyses were conducted using weighted median, MR Egger, Simple mode, and MR-PRESSO.ResultsThe results of the study demonstrated a significant positive correlation between the genus Eubacterium ruminantium group and the risk of MM (OR 1.71, 95% CI 1.21 to 2.39). Conversely, the genus: Dorea (OR 0.46, 95% CI 0.24 to 0.86), Coprococcus1 (OR 0.47, 95% CI 0.22 to 1.00), RuminococcaceaeUCG014 (OR 0.57, 95% CI 0.33 to 0.99), Eubacterium rectale group (OR 0.37, 95% CI 0.18 to 0.77), and order: Victivallales (OR 0.62, 95% CI 0.41–0.94), class: Lentisphaeria (OR 0.62, 95% CI 0.41 to 0.94), exhibited a negative association with MM. The inverse variance weighting analysis provided additional support for these findings.ConclusionThis study represents an inaugural exploration of MR to investigate the connections between gut microbiota and MM, thereby suggesting potential significance for the prevention and treatment of MM.

Small interference RNA (siRNA) is a class of short double-stranded RNA molecules that cause mRNA degradation through an RNA interference mechanism and is a promising therapeutic modality. RBD1016 is a siRNA drug in clinical development for the treatment of chronic Hepatitis B Virus (HBV) infection, which contains a conjugated with N-acetylglucosamine moiety that can facilitate its hepatic delivery. We aimed to construct a semi-mechanistic model of RBD1016 in pre-clinical animals, to elucidate the pharmacokinetic/pharmacodynamic (PK/PD) profiles in mice and PK profiles in monkeys, which can lay the foundation for potential future translation of RBD1016 PK and PD from the pre-clinical stage to the clinic stage. The proposed semi-mechanistic PK/PD model fitted PK and PD data in HBV transgenic mice well and described plasma and liver concentrations in the monkeys well. The simulation results showed that our model has a reasonable predictive ability for Hepatitis B surface antigen (HBsAg) levels after multiple dosing in mice. Further PK and PD data for RBD1016, including clinical data, will assist in refining the model presented here. Our current effort focused on model building for RBD1016, we anticipate that the model could apply to other GalNAc-siRNA drugs.

Abstract To explore the optimal cut-off values of Klotho for predicting all-cause and cardiovascular mortality among chronic kidney disease (CKD) patients. Klotho was measured in 40–79-year-old individuals in the NHANES 2007–2016. A total of 2418 patients with stage 1–4 CKD were included. The optimal cut-off values of Klotho were utilized using receiver operator characteristic (ROC) curves and be verified on the effects of all-cause and cardiovascular mortality. Restricted cubic splines were used to examine the relationship between Klotho and all-cause and cardiovascular mortality with the optimal cutpoints as the reference. After a mean follow-up period of 87.9 months, 535 deaths occurred and 188 died of cardiovascular disease. Cubic splines showed that the risk of all-cause and cardiovascular mortality increased gradually for Klotho

Abstract Background The number and proportion of the elderly population have been continuously increasing in China, leading to the elevated prevalence of chronic diseases and multimorbidity, which ultimately brings heavy burden to society and families. Meanwhile, the status of multimorbidity tends to be more complex in elderly inpatients than community population. In view of the above concerns, this study was designed to investigate the health status of elderly inpatients by analyzing clinical data in Chinese People's Liberation Army (PLA) General Hospital from 2008 to 2019, including the constitution of common diseases, comorbidities, the status of multimorbidity, in-hospital death and polypharmacy among elderly inpatients, so as to better understand the diseases spectrum and multimorbidity of elderly inpatients and also to provide supporting evidence for targeted management of chronic diseases in the elderly. Methods A clinical inpatients database was set up by collecting medical records of elderly inpatients from 2008 to 2019 in Chinese PLA General Hospital, focusing on diseases spectrum and characteristics of elderly inpatients. In this study, we collected data of inpatients aged ≥ 65 years old, and further analyzed the constitution of diseases, multimorbidity rates and mortality causes in the past decade. In addition, the prescriptions were also analyzed to investigate the status of polypharmacy in elderly inpatients. Results A total of 210,169 elderly patients were hospitalized from January 1st, 2008 to December 31st, 2019. The corresponding number of hospitalizations was 290,833. The average age of the study population was 72.67 years old. Of the total population, 73,493 elderly patients were re-admitted within one year, with the re-hospitalization rate of 25.27%. Malignant tumor, hypertension, ischemic heart disease, diabetes mellitus and cerebrovascular disease were the top 5 diseases. Among the study population, the number of patients with two or more long-term health conditions was 267,259, accounting for 91.89%, with an average of 4.68 diseases. In addition, the average number of medications taken by the study population was 5.4, among which, the proportion of patients taking more than 5 types of medications accounted for 55.42%. Conclusions By analyzing the constitution of diseases and multimorbidity, we found that multimorbidity has turned out to be a prominent problem in elderly inpatients, greatly affecting the process of healthy aging and increasing the burden on families and society. Therefore, multidisciplinary treatment should be strengthened to make reasonable preventive and therapeutic strategies to improve the life quality of the elderly. Meanwhile, more attention should be paid to reasonable medications for elderly patients with multimorbidity to avoid preventable side effects caused by irrational medication therapy.

Hyperspectral image (HSI) is pivotal in ground object classification, owing to its rich spatial and spectral information. Recently, convolutional neural networks and graph neural networks have become hotspots in HSI classification. Although various methods have been developed, the problem of detail loss may still exist when extracting complex features within homogenous regions. To solve this issue, in this article, we proposed a double-hop graph attention multiview fusion network. This model is adept at pinpointing precise attention features by integrating a double-hop graph with the graph attention network, thereby enhancing the aggregation of multilevel node information and surmounting the limitations of a restricted receptive field. Furthermore, the spectral-coordinate attention module (SCAM) is presented to seize more nuanced spectral and spatial attention features. SCAM harnesses the coordinate attention mechanism for in-depth pixel-level global spectral–spatial view. Coupled with the multiscale Gabor texture view, we forge a multiview fusion network that meticulously highlights edge details across varying scales and captures beneficial features. Our experimental validation across four renowned benchmark HSI datasets showcases our model's superiority, outstripping comparative methods in classification accuracy with limited labeled samples.

Based on a power supply system, a repairable K-out-of- $N+W$ : G system with c repairmen and warm spares is considered, where each repairman asynchronously takes multiple working vacations and vacation interruption policy. Total load of the system is shared equally by all the operating generators, the failure rate of each operating generator increases with the decreasing of the number of operating generators. Using Markov process and matrix-analytic method, steady-state probabilities and important performance indices are obtained. The mean time to first failure and reliability function are given by using the definition of PH-distribution. Numerical examples are given to illustrate the effect of system parameters on these reliability indices. In addition, machine learning (ML) methods including decision tree regression (DTR), random forest regression (RFR) and multilayer perceptron regression (MLPR) are used to predict the steady-state availability of the system, which shows that RFR is the optimal prediction model, and feature importances of system parameters are also provided.

Abstract Inulin, as a prebiotic, could modulate the gut microbiota. Burn injury leads to gut microbiota disorders and skeletal muscle catabolism. Therefore, whether inulin can improve burn-induced muscle atrophy by regulating microbiota disorders remains unknown. This study aimed to clarify that inulin intake alleviates gut microbiota disorders and skeletal muscle atrophy in burned rats. Rats were divided into the sham group, burn group, prebiotic inulin intervention group, and pseudo-aseptic validation group. A 30% total body surface area (TBSA) third-degree burn wound on dorsal skin was evaluated in all groups except the sham group. Animals in the intervention group received 7 g/L inulin. Animals in the validation group received antibiotic cocktail and inulin treatment. In our study inulin intervention could significantly alleviate the burn-induced skeletal muscle mass decrease and skeletal myoblast cell apoptosis. Inulin intake increased the abundances of Firmicutes and Actinobacteria but decreased the abundance of Proteobacteria. The biosynthesis of amino acids was the most meaningful metabolic pathway distinguishing the inulin intervention group from the burn group, and further mechanistic studies have shown that inulin can promote the phosphorylation of the myogenesis-related proteins PI3K, AKT and P70S6K and activate PI3K/AKT signaling for protein synthesis. In conclusion, inulin alleviated burn induced muscle atrophy through PI3K/AKT signaling and regulated gut microbiota dysbiosis.

Abstract Alagille Syndrome (ALGS) is a complex genetic disorder characterized by cholestasis, congenital cardiac anomalies, and butterfly vertebrae. The variable phenotypic expression of ALGS can lead to challenges in accurately diagnosing affected infants, potentially resulting in misdiagnoses or underdiagnoses. This study highlights novel JAG1 gene mutations in two cases of ALGS. The first case with a novel p.Pro325Leufs*87 variant was diagnosed at 2 months of age and exhibited a favorable prognosis and an unexpected manifestation of congenital hypothyroidism. Before the age of 2, the second patient was incorrectly diagnosed with liver structural abnormalities, necessitating extensive treatment. In addition, he exhibited delays in language acquisition that may have been a result of SNAP25 haploinsufficiency. The identification of ALGS remains challenging, highlighting the importance of early detection and genetic testing for effective patient management. The variant p.Pro325Leufs*87 is distinct from reported variants linked to congenital hypothyroidism in ALGS patients, thereby further confirming the clinical and genetic complexity of ALGS. This emphasizes the critical need for individualized and innovative approaches to diagnosis and medical interventions, uniquely intended to address the complexity of this syndrome.

Abstract Background Cadmium (Cd) pollution in agricultural soils has become a priority environmental concern globally. A reasonable application of passivators is critical to address the problem. In this study, we examined the remediation effects of rice husk biochar (rBC) and sepiolite (Sep) as single and combined (rBC + Sep) treatments on Cd pollution in a weakly alkaline soil using three maize cultivars (Liyu 16, Zhengdan 958, and Sanbei 218) as test crops. We also explained the mechanisms involved in the remediation effects. Results The pseudo-second-order kinetic equation and Langmuir model could well describe the adsorption process of rBC + Sep for Cd2+. Compared with the control treatment (CK), soil available Cd concentration decreased by 29.51–36.34% under rBC + Sep treatment (p 0.05). Conclusions The application of 0.2% rBC + 0.5% Sep composite passivation material to weakly alkaline Cd-contaminated soil can effectively reduce the Cd concentration of soil and maize.

Purpose: Male overweight and obesity could affect sperm quality and reproductive health. However, the impact of body mass index (BMI) on assisted reproductive technology (ART) outcomes in oligospermia and/or asthenospermia patients is yet lacking. This study aims to assess the impact of paternal BMI on ART and neonatal outcomes among oligozoospermia and/or asthenospermia patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Materials and Methods: In this study, 2,075 couples undergoing their first fresh embryo transfer between January 2015 and June 2022 were recruited. Following the World Health Organization’s (WHO’s) categories, couples were stratified into three cohorts based on paternal BMI: normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), and obese (≥30.0 kg/m2). Modified Poisson regression models were used to assess the associations of paternal BMI with fertilization, in vitro embryonic development, and pregnancy outcomes. Logistic regression models were performed to investigate the associations of paternal BMI with pregnancy loss and neonatal outcomes. Furthermore, stratified analyses were performed based on fertilization methods, male infertility cause, and maternal BMI. Results: Higher paternal BMI is associated with a lower likelihood of achieving normal fertilized (p-trend=0.002), Day 3 transferable (p-trend=0.007), and high-quality embryos (p-trend=0.046) in IVF cycles, rather than in ICSI cycles. Paternal BMI of oligospermia or asthenospermia was negatively correlated with day 3 transferable (p-trend=0.013 and 0.030) and highquality embryos (p-trend=0.024 and 0.027). Moreover, for neonatal outcomes, paternal BMI was positively associated with macrosomia (p-trend=0.019), large for gestational age (LGA) (p-trend=0.031), and very LGA (p-trend=0.045). Conclusions: Our data suggested that higher paternal BMI was associated with fetal overgrowth, reduced fertilization, and embryonic development potential. Among males with oligospermia and/or asthenospermia, the impact of overweight and obesity on the choice of fertilization method and the long-term effects on their offspring need to be further investigated.

Abstract Obesity is a metabolic disorder characterized by the hypertrophy expansion of adipose tissue, resulting in dysregulated energy metabolism, and accompanied by chronic low-grade inflammation. Adipose tissue macrophages (ATMs), a principal component of inflammation, respond to microenvironment signals and modulate adipose tissue remodeling and metabolic processes situation-specific. However, the mechanisms governing how the organism maintains equilibrium between its chronic inflammation and metabolism still need to be understood. Here, we describe a novel role of apolipoprotein E (ApoE), which associated with lipid particles, in maintaining fat deposition and system metabolic inflammation. Using human samples and mouse models, we show that ApoE is robustly downregulated in obese individuals, db/db mice, and mice of high-fat diet (HFD) feeding and increased in obese subjects with diabetes. Furthermore, we found that ApoE deficiency mice globally prevented obesity by restraining adipose tissue expansion and improved systemic glucose tolerance and insulin sensitivity. However, macrophage contributed to metabolic inflammation due to increased IL-1β production in adipose tissue from ApoE-/- mice induced by HFD. Our results suggest that the role of ApoE in regulating obesity and obesity-associated glucose dysregulation is inconsistent. Mechanistically, ApoE modulates of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome priming and activation step. Thus, our studies might provide new sights into ApoE, which is required for obesity-induced hyperglycemia, hyperinsulinism, and adaptive inflammation responses but diminishes the tolerance towards a subsequent metabolic inflammatory challenge. Our study shed new light on the integral role of apolipoprotein APOE in immunometabolism and adipose tissue homeostasis.

Chloroplast and mitochondrial DNA (cpDNA and mtDNA) are apart from nuclear DNA (nuDNA) in a eukaryotic cell. The transcription system of chloroplasts differs from those of mitochondria and eukaryotes. In contrast to nuDNA and animal mtDNA, the transcription of cpDNA is still not well understood, primarily due to the unresolved identification of transcription initiation sites (TISs) and transcription termination sites (TTSs) on the genome scale. In the present study, we characterized the transcription of chloroplast (cp) genes with greater accuracy and comprehensive information using PacBio full-length transcriptome data from Arabidopsis thaliana. The major findings included the discovery of four types of artifacts, the validation and correction of cp gene annotations, the exact identification of TISs that start with G, and the discovery of polyA-like sites as TTSs. Notably, we proposed a new model to explain cp transcription initiation and termination at the whole-genome level. Four types of artifacts, degraded RNAs and splicing intermediates deserve the attention from researchers working with PacBio full-length transcriptome data, as these contaminant sequences can lead to incorrect downstream analysis. Cp transcription initiates at multiple promoters and terminates at polyA-like sites. Our study provides new insights into cp transcription and new clues to study the evolution of promoters, TISs, TTSs and polyA tails of eukaryotic genes.

Colon cancer is a common and lethal malignancy, ranking second in global cancer-related mortality, highlighting the urgent need for novel targeted therapies. The sea cucumber (Apostichopus japonicus) is a marine organism known for its medicinal properties. After conducting a bioinformatics analysis of the cDNA library of Apostichopus japonicus, we found and cloned a cDNA sequence encoding histidine-rich peptides, and the recombinant peptide was named rAj-HRP. Human histidine-rich peptides are known for their anti-cancer properties, raising questions as to whether rAj-HRP might exhibit similar effects. To investigate whether rAj-HRP can inhibit colon cancer, we used human colon cancer HCT116 cells as a model and studied the tumor suppressive activity in vitro and in vivo. The results showed that rAj-HRP inhibited HCT116 cell proliferation, migration, and adhesion to extracellular matrix (ECM) proteins in vitro. It also disrupted the cytoskeleton and induced apoptosis in these cells. In vivo, rAj-HRP significantly inhibited the growth of HCT116 tumors in BALB/c mice, reducing tumor volume and weight without affecting the body weight of the tumor-bearing mice. Western blot analysis showed that rAj-HRP inhibited HCT116 cell proliferation and induced apoptosis by upregulating BAX and promoting PARP zymogen degradation. Additionally, rAj-HRP inhibited HCT116 cell adhesion and migration by reducing MMP2 levels. Further research showed that rAj-HRP downregulated EGFR expression in HCT116 cells and inhibited key downstream molecules, including AKT, P-AKT, PLCγ, P38 MAPK, and c-Jun. In conclusion, rAj-HRP exhibits significant inhibitory effects on HCT116 cells in both in vitro and in vivo, primarily through the EGFR and apoptosis pathways. These findings suggest that rAj-HRP has the potential as a novel targeted therapy for colon cancer.