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Abstract Background Catheter ablation has evolved as a safe treatment for atrial flutter (AFL) in patients with pulmonary hypertension (PH), and the recurrence of AFL may accelerate clinical decompensation. The aim of this study was to determine the recurrence rate and risk factors for recurrent AFL in PH patients after ablation. Methods All PH patients who underwent AFL ablation at Fuwai Hospital between May 2015 and December 2020 were followed up. The recurrence rate and risk factors for recurrence were analyzed. Results A total of 68 PH patients (mean age 44.0 ± 13.0 years, 36.8% male) were enrolled. The majority patients diagnosed PH had congenital heart disease-associated PH (63.2%), and 30.9% had idiopathic pulmonary arterial hypertension. At baseline, most patients (80.9%) had only cavotricuspid isthmus (CTI)-related AFL; the occurrence of non-CTI-related AFL among patients was 8.8%, and 10.3% of the patients had both types of AFL. During a median follow-up of 17.5 months, 22 patients developed at least one recurrent AFL episode (AFL-free survival: 76.5% at 1 year). The immediate success of ablation (HR 0.061, 95% CI 0.009 to 0.438; P = 0.005) and the right atrial volume index (RAVi, per 10 ml/m2; HR 1.064, 95% CI 1.011 to 1.120; P = 0.018) were associated with long-term ablation outcomes in PH patients. With 166.64 ml/m2 as a cutoff value, AFL-free survival was significantly greater in patients whose RAVi was < 166.64 ml/m2 (log-rank P = 0.024). Conclusion The immediate success of ablation and the RAVi are associated with recurrent AFL. Patients with a RAVi ≥ 166.64 ml/m2 are likely experience recurrence.

Abstract Seawater direct electrolysis (SDE) using renewable energy provides a sustainable pathway to harness abundant oceanic hydrogen resources. However, the side-reaction of the chlorine electro-oxidation reaction (ClOR) severely decreased direct electrolysis efficiency of seawater and gradually corrodes the anode. In this study, a redox-mediated strategy is introduced to suppress the ClOR, and a decoupled seawater direct electrolysis (DSDE) system incorporating a separate O2 evolution reactor is established. Ferricyanide/ferrocyanide ([Fe(CN)6]3−/4−) serves as an electron-mediator between the cell and the reactor, thereby enabling a more dynamically favorable half-reaction to supplant the traditional oxygen evolution reaction (OER). This alteration involves a straightforward, single-electron-transfer anodic reaction without gas precipitation and effectively eliminates the generation of chlorine-containing byproducts. By operating at low voltages (~1.37 V at 10 mA cm−2 and ~1.57 V at 100 mA cm−2) and maintaining stability even in a Cl−-saturated seawater electrolyte, this system has the potential of undergoing decoupled seawater electrolysis with zero chlorine emissions. Further improvements in the high-performance redox-mediators and catalysts can provide enhanced cost-effectiveness and sustainability of the DSDE system.

Abstract Hydrogels are promising candidates for the delivery of therapeutics in the treatment of human cancers. Regarding to the biocomaptiiblity, high drug and encapsulation efficacy and adjustable physico-chemical features, the hydrogels have been widely utilized for the delivery of chemotherapy drugs. Doxorubicin (DOX) is one of the most common chemotherapy drugs used in cancer therapy through impairing topoisomerase II function and increasing oxidative damage. However, the tumor cells have developed resistance into DOX-mediated cytotoxic impacts, requiring the delivery systems to increase internalization and anti-cancer activity of this drug. The hydrogels can deliver DOX in a sustained manner to maximize its anti-cancer activity, improving cancer elimination and reduction in side effects and drug resistance. The natural-based hydrogels such as chitosan, alginate and gelatin hydrogels have shown favourable biocompatibility and degradability in DOX delivery for tumor suppression. The hydrogels are able to co-deliver DOX with other drugs or genes to enhance drug sensitivity and mediate polychemotherapy, synergistically suppressing cancer progression. The incorporation of nanoparticles in the structure of hydrogels can improve the sustained release of DOX and enhancing intracellular internalization, accelerating DOX’s cytotoxicity. Furthermore, the stimuli-responsive hydrogels including pH-, redox- and thermo-sensitive platforms are able to improve the specific release of DOX at the tumor site. The DOX-loaded hydrogels can be further employed in the clinic for the treatment of cancer patients and improving efficacy of chemotherapy.

Abstract Background Stress urinary incontinence (SUI), the prevalent form of urinary incontinence, significantly impairs women’s quality of life. This study aims to create a visual nomogram to estimate the risk of SUI within one year postpartum for early intervention in high-risk Chinese women. Methods We recruited 1,531 postpartum women who gave birth at two hospitals in Kunshan City from 2021 to 2022. Delivery details were meticulously extracted from the hospitals’ medical records system, while one-year postpartum follow-ups were conducted via phone surveys specifically designed to ascertain SUI status. Utilizing data from one hospital as the training set, logistic regression analysis was performed to pinpoint significant factors and subsequently construct the nomogram. To ensure robustness, an independent dataset sourced from the second hospital served as the external validation cohort. The model’s performance was rigorously evaluated using calibration plots, ROC curves, AUC values, and DCA curves. Results The study population was 1,125 women. The SUI incidence within one year postpartum was 26% (293/1125). According to the regression analysis, height, pre-pregnancy BMI, method of induction, mode of delivery, perineal condition, neonatal weight, SUI during pregnancy, and SUI during the first pregnancy were incorporated into the nomogram. The AUC of the nomogram was 0.829 (95% CI 0.790–0.867), and the external validation set was 0.746 (95% CI 0.689–0.804). Subgroup analysis based on parity showed good discrimination. The calibration curve indicated concordance. The DCA curve showed a significant net benefit. Conclusion Drawing from real-world data, we have successfully developed an SUI predictive model tailored for postpartum Chinese women. Upon successful external validation, this model holds immense potential as an effective screening tool for SUI, enabling timely interventions and ultimately may improve women’s quality of life.

Abstract The central nervous system has been implicated in the age-induced reduction in adipose tissue lipolysis. However, the underlying mechanisms remain unclear. Here, we show the expression of SLC7A14 is reduced in proopiomelanocortin (POMC) neurons of aged mice. Overexpression of SLC7A14 in POMC neurons alleviates the aging-reduced lipolysis, whereas SLC7A14 deletion mimics the age-induced lipolysis impairment. Metabolomics analysis reveals that POMC SLC7A14 increased taurochenodeoxycholic acid (TCDCA) content, which mediates the SLC7A14 knockout- or age-induced WAT lipolysis impairment. Furthermore, SLC7A14-increased TCDCA content is dependent on intestinal apical sodium-dependent bile acid transporter (ASBT), which is regulated by intestinal sympathetic afferent nerves. Finally, SLC7A14 regulates the intestinal sympathetic afferent nerves by inhibiting mTORC1 signaling through inhibiting TSC1 phosphorylation. Collectively, our study suggests the function for central SLC7A14 and an upstream mechanism for the mTORC1 signaling pathway. Moreover, our data provides insights into the brain–gut–adipose tissue crosstalk in age-induced lipolysis impairment.

Abstract Hepatocellular carcinoma (HCC) is a highly heterogeneous disease, making the prognostic prediction challenging. Ferroptosis, an iron-dependent form of cell death, is a key regulator in the initiation, progression, and metastasis of HCC. However, the expression and function of ferroptosis-related genes (FRGs) in HCC remained largely unclear. In this study, we analyzed TCGA datasets and identified 58 survival-related deferentially expressed FRGs (DE-FRGs). Then, based on the results of LASSO analysis, we developed a novel prognostic model based on 12 survival-related DE-FRGs. Survival assays indicated a strong prognostic ability of this new model in predicting clinical prognosis of HCC patients. In addition, we conducted an exploration of molecular subtypes related to HCC and delved into the associated immune characteristics and gene expression patterns. Among the 12 survival-related DE-FRGs, our attention focused on ABHD12 (abhydrolase domain containing 12) which was highly expressed in HCC and associated with advanced clinical stages. Multivariate assays confirmed that ABHD12 was a significant prognostic factor for HCC patients. Immune analysis revealed that ABHD12 may play an important role in tumor microenvironment. Finally, we performed RT-PCR and confirmed that ABHD12 was highly expressed in HCC cells. Functional experiments revealed that ABHD12 knockdown may suppress the proliferation and migration of HCC cells. These findings emphasized the significance of ABHD12 as a potential prognostic marker for HCC and its crucial role in the field of tumor biology. Additionally, the study introduces a novel survival model that holds promise for enhancing prognostic predictions in HCC patients. Overall, this research provided valuable insights for a deeper comprehension of the complexity of HCC and the development of personalized treatment strategies.

Abstract Background The bacterial persistence, responsible for therapeutic failures, can arise from the biofilm formation, which possesses a high tolerance to antibiotics. This threat often occurs when a bone and joint infection is diagnosed after a prosthesis implantation. Understanding the biofilm mechanism is pivotal to enhance prosthesis joint infection (PJI) treatment and prevention. However, little is known on the characteristics of Cutibacterium acnes biofilm formation, whereas this species is frequently involved in prosthesis infections. Methods In this study, we compared the biofilm formation of C. acnes PJI-related strains and non-PJI-related strains on plastic support and textured titanium alloy by (i) counting adherent and viable bacteria, (ii) confocal scanning electronic microscopy observations after biofilm matrix labeling and (iii) RT-qPCR experiments. Results We highlighted material- and strain-dependent modifications of C. acnes biofilm. Non-PJI-related strains formed aggregates on both types of support but with different matrix compositions. While the proportion of polysaccharides signal was higher on plastic, the proportions of polysaccharides and proteins signals were more similar on titanium. The changes in biofilm composition for PJI-related strains was less noticeable. For all tested strains, biofilm formation-related genes were more expressed in biofilm formed on plastic that one formed on titanium. Moreover, the impact of C. acnes internalization in osteoblasts prior to biofilm development was also investigated. After internalization, one of the non-PJI-related strains biofilm characteristics were affected: (i) a lower quantity of adhered bacteria (80.3-fold decrease), (ii) an increase of polysaccharides signal in biofilm and (iii) an activation of biofilm gene expressions on textured titanium disk. Conclusion Taken together, these results evidenced the versatility of C. acnes biofilm, depending on the support used, the bone environment and the strain.

Abstract Background The interplay between atrial fibrillation (AF) and obesity on mortality in critically ill patients warrants detailed exploration, given their individual impacts on patient prognosis. This study aimed to assess the associations between AF, obesity, and 1-year mortality in a critically ill population. Methods Utilizing data from the Medical Information Mart for Intensive Care (MIMIC)-IV database, we conducted a retrospective analysis of adult patients admitted to the intensive care unit. The primary endpoint was 1-year mortality, analyzed through Cox regression with hazard ratio (HR) and Kaplan-Meier survival methods. Results The study included 25,654 patients (median age 67.0 years, 40.6% female), with 39.0% having AF and 36.1% being obese. Multivariate COX regression analysis revealed that AF was associated with a 14.7% increase in the risk of 1-year mortality (p

Abstract Background The molecular mechanisms underlying nonalcoholic fatty liver disease (NAFLD) remain to be fully elucidated. Ubiquitin specific protease 13 (USP13) is a critical participant in inflammation-related signaling pathways, which are linked to NAFLD. Herein, the roles of USP13 in NAFLD and the underlying mechanisms were investigated. Methods L02 cells and mouse primary hepatocytes were subjected to free fatty acid (FFA) to establish an in vitro model reflective of NAFLD. To prepare in vivo model of NAFLD, mice fed a high-fat diet (HFD) for 16 weeks and leptin-deficient (ob/ob) mice were used. USP13 overexpression and knockout (KO) strategies were employed to study the function of USP13 in NAFLD in mice. Results The expression of USP13 was markedly decreased in both in vitro and in vivo models of NAFLD. USP13 overexpression evidently inhibited lipid accumulation and inflammation in FFA-treated L02 cells in vitro. Consistently, the in vivo experiments showed that USP13 overexpression ameliorated hepatic steatosis and metabolic disorders in HFD-fed mice, while its deficiency led to contrary outcomes. Additionally, inflammation was similarly attenuated by USP13 overexpression and aggravated by its deficiency in HFD-fed mice. Notably, overexpressing of USP13 also markedly alleviated hepatic steatosis and inflammation in ob/ob mice. Mechanistically, USP13 bound to transforming growth factor β-activated kinase 1 (TAK1) and inhibited K63 ubiquitination and phosphorylation of TAK1, thereby dampening downstream inflammatory pathways and promoting insulin signaling pathways. Inhibition of TAK1 activation reversed the exacerbation of NAFLD caused by USP13 deficiency in mice. Conclusions Our findings indicate the protective role of USP13 in NAFLD progression through its interaction with TAK1 and inhibition the ubiquitination and phosphorylation of TAK1. Targeting the USP13-TAK1 axis emerges as a promising therapeutic strategy for NAFLD treatment.

Abstract Objective Retinal vascular endothelial cell (RVECs) injury is a major cause of morbidity and mortality among the patients with diabetes. RVECs dysfunction is the predominant pathological manifestation of vascular complication in diabetic retinopathy. N6-methyladenosine (m6A) serves as the most prevalent modification in eukaryotic mRNAs. However, the role of m6A RNA modification in RVECs dysfunction is still unclear. Methods RT-qPCR analysis and western blot were conducted to detect the change of m6A RNA modification in diabetic retinopathy. CCK-8 assay, transwell experiment, wound healing assay, tube formation experiment, m6A-IP-qPCR were performed to determine the role of YTHDC1 in RVECs. Retinal trypsin digestion test and H&E staining were used to evaluate histopathological changes. Results The levels of m6A RNA methylation were significantly up-regulated in HG-induced RVECs, which were caused by increased expression of YTHDC1. YTHDC1 regulated the viability, proliferation, migration and tube formation ability in vitro. YTHDC1 overexpression impaired RVECs function by repressing CDK6 expression, which was mediated by YTHDC1-dependent mRNA decay. Moreover, it showed sh-YTHDC1 inhibited CDK6 nuclear export. Sh-YTHDC1 promotes the mRNA degradation of CDK6 in the nucleus but does not affect the cytoplasmic CDK6 mRNA. In vivo experiments showed that overexpression of CDK6 reversed the protective effect of sh-YTHDC1 on STZ-induced retinal tissue damage. Conclusion YTHDC1-mediated m6A methylation regulates diabetes-induced RVECs dysfunction. YTHDC1-CDK6 signaling axis could be therapeutically targeted for treating DR.

Abstract Background Radioresistance is the leading cause of death in advanced cervical cancer (CC). Dysregulation of RNA modification has recently emerged as a regulatory mechanism in radiation and drug resistance. We aimed to explore the biological function and clinical significance of 5-methylcytosine (m5C) in cervical cancer radiosensitivity. Methods The abundance of RNA modification in radiotherapy-resistant and sensitive CC specimens was quantified by liquid chromatography-tandem mass spectrometry. The essential RNA modification-related genes involved in CC radiosensitivity were screened via RNA sequencing. The effect of NSUN6 on radiosensitivity was verified in CC cell lines, cell-derived xenograft (CDX), and 3D bioprinted patient-derived organoid (PDO). The mechanisms of NSUN6 in regulating CC radiosensitivity were investigated by integrative m5C sequencing, mRNA sequencing, and RNA immunoprecipitation. Results We found a higher abundance of m5C modification in resistant CC samples, and NSUN6 was the essential m5C-regulating gene concerning radiosensitivity. NSUN6 overexpression was clinically correlated with radioresistance and poor prognosis in cervical cancer. Functionally, higher NSUN6 expression was associated with radioresistance in the 3D PDO model of cervical cancer. Moreover, silencing NSUN6 increased CC radiosensitivity in vivo and in vitro. Mechanistically, NDRG1 was one of the downstream target genes of NSUN6 identified by integrated m5C-seq, mRNA-seq, and functional validation. NSUN6 promoted the m5C modification of NDRG1 mRNA, and the m5C reader ALYREF bound explicitly to the m5C-labeled NDRG1 mRNA and enhanced NDRG1 mRNA stability. NDRG1 overexpression promoted homologous recombination-mediated DNA repair, which in turn led to radioresistance in cervical cancer. Conclusions Aberrant m5C hypermethylation and NSUN6 overexpression drive resistance to radiotherapy in cervical cancer. Elevated NSUN6 expression promotes radioresistance in cervical cancer by activating the NSUN6/ALYREF-m5C-NDRG1 pathway. The low expression of NSUN6 in cervical cancer indicates sensitivity to radiotherapy and a better prognosis.

Epidemiological studies have demonstrated exposure to cadmium ion (Cd2+) is significantly associated with the incidence and aggravation of nonalcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH). Cd2+ exposure could alter lipid metabolism, and changed lipid metabolites are significantly associated with NASH. Arachidonic acid (ArA) is an omega-6 polyunsaturated fatty acid. Promotion of ArA synthesis and profile changes by Cd2+ exposure potentially to cause NAFLD. ArA metabolism pathway has been identified to enrich in Cd2+ exposure-facilitated NASH. ArA could be generation an impressive metabolic profile through mainly three pathways, including Cyclooxygenases (COX), Lipoxygenases (LOX) and Cytochrome P450 (CYP450) pathway. However, the functions of these metabolites and underlying mechanism in hepatic inflammation are still not clear. In present study, by integrative transcriptomics and metabolomics analysis, we identified that the fatty acid metabolic process and the pro-inflammatory NF-κB signaling pathway were enriched in Cd2+-regulated differentially expressed genes (DEGs) and Cd2+-altered differential metabolites, such as, fatty acid biosynthesis, degradation, and ArA metabolism. The metabolites levels of LOX pathway products 5-HETE and leukotriene C4 (LTC4), and COX catalytic product prostaglandin D2 (PGD2) were significantly elevated in Cd2+ exposed mouse livers. 5-HETE, LTC4, and PGD2 were significantly positive correlated with NF-κB signaling. In addition, the synthase of 20-Hydroxyeicosatetraenoic acid (20-HETE), CYP450 gene 4 family (CYP4A32), was also involved in NF-κB signaling network. Results from both in vitro and in vivo proved that Cd2+ exposure increased ArA metabolite to PGD2 and 20-HETE, and upregulated the mRNA level of their catalytic enzyme PGDS and CYP4A32. Cd2+-induced ArA metabolite to PGD2 and 20-HETE promoted activation of TLR4/IκBα/NF-κB signaling and pro-inflammatory of hepatocytes. Our study explores novel molecular mechanism of Cd2+ exposure-aggravated liver diseases and provides potential novel targets for in hepatic inflammatory treatments and prevention.

BackgroundSedation-related adverse events not only referred to a cause for morbidity and mortality but also included events that could disrupt routine procedures and thus lead to reduced procedural efficiency or quality. To date, no literature is available to predict the risk factors associated with prolonged recovery in pediatric patients during procedural sedation. Thus, we retrospectively analyzed the two-year sedation data to explore the above questions.MethodsPediatric patients who underwent procedural sedation between January 2022 and January 2024 were retrospectively analyzed. The patients were divided into two groups according to sedation duration

Introduction Atrial fibrillation (AF) is an independent predictor of adverse outcomes in patients with hypertrophic cardiomyopathy (HCM). Although catheter ablation is highly recommended for general AF populations, it is less effective in maintaining sinus rhythm in patients with HCM associated with AF. Hybrid ablation, combining a cosmetic approach with a lower rate of AF relapse, lacks comparative studies to verify its efficacy against CA in HCM. This study aims to assess the rhythm control effectiveness of hybrid versus CA in non-obstructive HCM (non-oHCM) patients with AF.Methods/analysis This prospective, multicentre, randomised trial involves a blinded assessment of outcomes in non-oHCM patients with non-paroxysmal AF. Sixty-six candidates from three centres will be randomised 1:1 to either hybrid or CA, including isthmus addressed lesion sets. Participants will be stratified by left atrial (LA) size (LA diameter ≤50 mm or >50 mm). Follow-ups at the 3rd, 6th and 12th months will evaluate the primary endpoint of freedom from documented atrial tachycardia lasting over 30 s within 12 months post-procedure without antiarrhythmic drugs, along with secondary endpoints of all-cause mortality, cardiovascular-related mortality, cerebral stroke, peripheral vascular embolism, heart failure-related rehospitalisation, all-cause rehospitalisation and quality of life assessments.Ethics and disseminationapproval The central ethics committee at Fuwai Hospital has approved the Hypertrophic CardioMyopathy with Atrial Fibrillation trial (approval number: 2022-1736). Results will be disseminated through publications in peer-reviewed journals and presentations at conferences.Trial registration number NCT05610215.

PurposeTo develop a predictive nomogram based on computed tomography (CT) radiomics to distinguish pulmonary tuberculosis (PTB) from community-acquired pneumonia (CAP).MethodsA total of 195 PTB patients and 163 CAP patients were enrolled from three hospitals. It is divided into a training cohort, a testing cohort and validation cohort. Clinical models were established by using significantly correlated clinical features. Radiomics features were screened by the least absolute shrinkage and selection operator (LASSO) algorithm. Radiomics scores (Radscore) were calculated from the formula of radiomics features. Clinical radiomics conjoint nomogram was established according to Radscore and clinical features, and the diagnostic performance of the model was evaluated by receiver operating characteristic (ROC) curve analysis.ResultsTwo clinical features and 12 radiomic features were selected as optimal predictors for the establishment of clinical radiomics conjoint nomogram. The results showed that the predictive nomogram had an outstanding ability to discriminate between the two diseases, and the AUC of the training cohort was 0.947 (95% CI, 0.916-0.979), testing cohort was 0.888 (95% CI, 0.814-0.961) and that of the validation cohort was 0.850 (95% CI, 0.778-0.922). Decision curve analysis (DCA) indicated that the nomogram has outstanding clinical value.ConclusionsThis study developed a clinical radiomics model that uses radiomics features to identify PTB from CAP. This model provides valuable guidance to clinicians in identifying PTB.

With the expansion of the digital publishing industry, copyright infringement of digital resources has become increasingly rampant. Blockchain technology offers a promising solution for copyright protection of digital resources. However, existing copyright protection methods based on single-chain or consortium blockchains have disadvantages such as low system processing efficiency, poor scalability, and a lack of alignment with real-world business needs. To address the current challenges of blockchain technology in the field of copyright protection and establish a more effective solution for protecting digital resource copyrights, while also expanding the application of blockchain cross-chain technology and promoting its development, leveraging blockchain cross-chain theory, technology, and methods, a digital resource copyright protection scheme based on blockchain cross-chain technology was constructed. It outlines detailed processes for copyright registration, resource transactions, copyright modifications, and copyright enforcement. Furthermore, this copyright protection scheme was analyzed. The findings indicated that the blockchain cross-chain technology is suitable for digital resource copyright protection. The proposed copyright protection scheme can allow various stakeholders to better fulfill their roles, in addition to enhancing the overall maintainability and scalability of the blockchain system.

Abstract Background The relationship between triglyceride glucose-body mass index (TyG-BMI) index and mortality in elderly patients with diabetes mellitus (DM) are still unclear. This study aimed to investigate the association between TyG-BMI with all-cause and cardiovascular mortality among elderly DM patients in the United States (US). Methods Patients aged over 60 years with DM from the National Health and Nutrition Examination Survey (2007–2016) were included in this study. The study endpoints were all-cause and cardiovascular mortality and the morality data were extracted from the National Death Index (NDI) which records up to December 31, 2019. Multivariate Cox proportional hazards regression model was used to explore the association between TyG-BMI index with mortality. Restricted cubic spline was used to model nonlinear relationships. Results A total of 1363 elderly diabetic patients were included, and were categorized into four quartiles. The mean age was 70.0 ± 6.8 years, and 48.6% of them were female. Overall, there were 429 all-cause deaths and 123 cardiovascular deaths were recorded during a median follow-up of 77.3 months. Multivariate Cox regression analyses indicated that compared to the 1st quartile (used as the reference), the 3rd quartile demonstrated a significant association with all-cause mortality (model 2: HR = 0.64, 95% CI 0.46–0.89, P = 0.009; model 3: HR = 0.65, 95% CI 0.43–0.96, P = 0.030). Additionally, the 4th quartile was significantly associated with cardiovascular mortality (model 2: HR = 1.83, 95% CI 1.01–3.30, P = 0.047; model 3: HR = 2.45, 95% CI 1.07–5.57, P = 0.033). The restricted cubic spline revealed a U-shaped association between TyG-BMI index with all-cause mortality and a linear association with cardiovascular mortality, after adjustment for possible confounding factors. Conclusions A U-shaped association was observed between the TyG-BMI index with all-cause mortality and a linear association was observed between the TyG-BMI index with cardiovascular mortality in elderly patients with DM in the US population.

Abstract Glioma, with its heterogeneous microenvironments and genetic subtypes, presents substantial challenges for treatment prediction and development. We integrated 3D bioprinting and multi-algorithm machine learning as a novel approach to enhance the assessment and understanding of glioma treatment responses and microenvironment characteristics. The bioprinted patient-derived glioma tissues successfully recapitulated molecular properties and drug responses of native tumors. We then developed GlioML, a machine learning workflow incorporating nine distinct algorithms and a weighted ensemble model that generated robust gene expression-based predictors, each reflecting the diverse action mechanisms of various compounds and drugs. The ensemble model superseded the performance of all individual algorithms across diverse in vitro systems, including sphere cultures, complex 3D bioprinted multicellular models, and 3D patient-derived tissues. By integrating bioprinting, the evaluative scope of the treatment expanded to T cell-related therapy and anti-angiogenesis targeted therapy. We identified promising compounds and drugs for glioma treatment and revealed distinct immunosuppressive or angiogenic myeloid-infiltrated tumor microenvironments. These insights pave the way for enhanced therapeutic development for glioma and potentially for other cancers, highlighting the broad application potential of this integrative and translational approach.

Abstract Background Renal cell carcinoma (RCC) is a prevalent and extensively immune-infiltrated malignancy of the urinary system. Immune cells play a crucial role in both the progression and therapeutic interventions targeting RCC. Nevertheless, the interplay between RCC and immune cells remains understudied, lacking substantial evidence supporting their causal relationship. Methods For the purpose of investigating the causal connection between RCC and immune cell characteristics, a two-way two-sample Mendelian randomization (MR) analysis was carried out in this study. The aim was to determine whether specific immune cell traits have a causal impact on the risk of RCC. In order to achieve this, publicly accessible genetic data was utilized to examine and establish the potential relationship between 731 immune cell characteristics and the likelihood of developing RCC. Additionally, various techniques were applied to verify the reliability, variability, and presence of horizontal pleiotropy in the outcomes. Results We found a bidirectional causal relationship between RCC and immune cells according to the MR analysis results. It should be noted that CD4-CD8-T cells (OR = 1.61, 95%CI = 1.02–2.55, P = 4.07 × 10–2) pose a risk for RCC, whereas BAFF-R (OR = 0.69, 95%CI = 0.53–0.89, P = 5.74 × 10–3) and CD19 (OR = 0.59, 95%CI = 1.02–2.55, P = 4.07 × 10–2) on B cells act as protective factors. Furthermore, the presence of RCC reduces the levels of B cells (OR = 1.05, 95%CI = 1.01–1.09, P = 1.19 × 10–2) and CD8 + T cells (OR = 1.04, 95%CI = 1.00–1.08, P = 2.83 × 10–2). Conclusions Our research illustrates the intricate correlation between immune cells and RCC, presenting novel insights for the prospective safeguarding against RCC risk and the exploration of fresh therapeutic targets.

Abstract Aims We aimed to evaluate the effects of radiofrequency catheter ablation (RFCA) and the factors influencing mortality after RFCA in patients with pulmonary hypertension (PH) and atrial flutter (AFL). Methods and results Fifty‐eight consecutive PH patients with AFL who underwent an electrophysiological study and RFCA between April 2013 and August 2021 were selected for this study. In the study population, pulmonary arterial hypertension associated with congenital heart disease (PAH‐CHD) was the most common type of PH (n = 34, 59%), followed by idiopathic pulmonary arterial hypertension (IPAH) (n = 19, 33%). Typical atrial flutter was the most common type of atrial flutter (n = 50, 86.2%). Sinus rhythm was restored in 53 (91.4%) patients during RFCA. After a mean follow‐up of 33.8 months, AFL recurred in a total of 22 patients. Nine of them underwent repeat RFCA, and the site of the repeat ablation was not exactly the same as the first. At a median follow‐up of 34.6 months after the last ablation, none of the patients who underwent repeat RFCA experienced AFL recurrence, and all of these patients survived. There were no procedure‐related complications during hospitalization or follow‐up. Univariate Cox regression analysis suggested that AFL recurrence after the last ablation was not associated with all‐cause mortality. NT‐proBNP (HR: 1.00024, 95% CI: 1.00008–1.00041, P = 0.004), pulmonary artery systolic pressure (PASP) (HR: 1.048, 95% CI: 1.020–1.076, P = 0.001), and IPAH (vs. PAH‐CHD, HR: 7.720, 95% CI: 1.437–41.483, P = 0.017) were independent predictors of all‐cause mortality in PH patients with AFL after RFCA. Receiver operating characteristic (ROC) curve analysis revealed that the area under the curve (AUC) of PASP for predicting all‐cause mortality was 0.708. There was no significant difference in the Kaplan–Meier curves for all‐cause mortality between patients with AFL recurrence after the last ablation and those without recurrence (P = 0.851). Patients with higher PASP (≥110 mmHg) and IPAH showed the lower survival rate in Kaplan–Meier curves. Conclusion Repeat ablation was safe and feasible in patients with recurrent AFL and can maintain sinus rhythm. AFL recurrence was not associated with all‐cause mortality, and patients with high PASP or IPAH were at higher risk for adverse outcomes.

With the continuous development of the oblique photography technique, it has been used more and more widely in the field of geological disasters. It can quickly obtain the three-dimensional (3D) real scene model of dangerous mountainous areas under the premise of ensuring the safety of personnel while restoring the real geographic information as much as possible. However, geological disaster areas are often accompanied by many adverse factors such as cliffs and dense vegetation. Based on this, the paper introduced the flight line design of oblique photogrammetry, analyzed the multi-platform data fusion processing, studied the multi-period data dynamic evaluation technology and proposed the application methods of data acquisition, early warning, disaster assessment and decision management suitable for geological disaster identification through the analysis of actual cases, which will help geologists to plan and control geological work more scientifically and rationally, improve work efficiency and reduce the potential personnel safety hazards in the process of geological survey, to offer technical support to the application of oblique photogrammetry in geological disaster identification and decision making and provide the scientific basis for personal and property safety protection and later-stage geological disaster management in disaster areas.

Abstract The growth of newly formed particles through new particle formation (NPF) contributes a significant fraction to the cloud condensation nuclei, yet the driving mechanisms remain unclear, especially for polluted environments. To investigate the potential species contributing for nanoparticle growth in environments with significant anthropogenic influences, we measured the hygroscopicity of newly formed particles at 20–40 nm at a rural observational site in the North China Plain during winter 2018. Our results demonstrate that these particles were not very hygroscopic, with the mean hygroscopicity parameter κ of 0.13 ± 0.09. Clear differences in the inferred κ of the growing material responsible for the growth were observed among different events, indicating that even at the same region, the compounds driving particle growth may not be identical. This may be synergistically influenced by the NPF precursors, oxidants and meteorological conditions, suggesting complex mechanisms might co‐exist behind nanoparticle growth in polluted environments.

ObjectivesNewborns and small infants are unable to cooperate actively during diagnostic procedures; therefore, sedation is often employee to maintain immobilization and obtain high-quality images. However, these procedures are often indicated in sick, vulnerable, or hemodynamically unstable neonates and young infants, which raises the associated risks of sedation. This study summarizes our 4-year of experience with safe and effective procedural sedation in this vulnerable population.Study designThis retrospective study analyzed data on neonates and young infants who underwent non-painful diagnostic procedures from December 2019 to November 2023. Patients were categorized into the neonate (aged≦ 28 days) and the young infant (29 days ≦ aged ≦ 90 days) groups.ResultsNon-pharmacological strategies, including sleeping naturally, swaddling/facilitated tucking, non-nutritive sucking, and skin-to-skin care, can achieve a success rate for sedation about 98.4%. In terms of pharmacological methods, our institution primarily utilizes chloral hydrate for procedural sedation in neonates and young infants undergoing non-painful diagnostic procedures. Midazolam serves as an alternative sedative. Chloral hydrate alone demonstrated a 92.5% success rate on the first attempt, compared to midazolam alone, with an 85.11% success rate. Neonates experienced a higher incidence of adverse events during sedation compared to young infants.ConclusionThis study reviews our 4-year experience with procedural sedation in neonates and young infants. Chloral hydrate demonstrated a high degree of safety and efficacy in this population. However, supervision by skilled medical personnel and extended observation is required. In our institution, the experience with midazolam is limited in this population, and further research is warranted to establish its safety and efficacy. Non-pharmacological strategies can achieve an acceptable rate of sedation success, which can be used based on patient’s tolerance.

Amidst rising global temperatures, chronic heat stress (CHS) is increasingly problematic for the poultry industry. While mammalian CHS responses are well-studied, avian-specific research is lacking. This study uses in-depth transcriptome sequencing to evaluate the pulmonary response of Cherry Valley ducks to CHS at ambient temperatures of 20°C and a heat-stressed 29°C. We detailed the CHS-induced gene expression changes, encompassing mRNAs, lncRNAs, and miRNAs. Through protein–protein interaction network analysis, we identified central genes involved in the heat stress response—TLR7, IGF1, MAP3K1, CIITA, LCP2, PRKCB, and PLCB2. Subsequent functional enrichment analysis of the differentially expressed genes and RNA targets revealed significant engagement in immune responses and regulatory processes. KEGG pathway analysis underscored crucial immune pathways, specifically those related to intestinal IgA production and Toll-like receptor signaling, as well as Salmonella infection and calcium signaling pathways. Importantly, we determined six miRNAs—miR-146, miR-217, miR-29a-3p, miR-10926, miR-146b-5p, and miR-17-1-3p—as potential key regulators within the ceRNA network. These findings enhance our comprehension of the physiological adaptation of ducks to CHS and may provide a foundation for developing strategies to improve duck production under thermal stress.

IntroductionIn goal-directed tasks, visual prompts before the appearance of goals can make people ready in advance, which helps them to complete the movement better, and the presentation type of the visual prompt is very important. In previous studies, it has not been clear how different types of visual prompts guide attention in goal-directed tasks.MethodsAccording to the characteristics of goal-directed tasks, our research designed three different prompts: the cue prompt (featuring static arrow), the preparation prompt (involving dynamic countdown), and the combination prompt of cue and preparation information (simultaneously incorporating arrow and countdown). We used event-related potential components (CNV and P300) and graph theory indicators (clustering coefficient and characteristic path length) under the brain function connection to analyze the attention state of the brain.ResultsThe results showed that the combination prompts better guided the participants’ sustained attention during the prompt stage, making them well prepared for the movement. Thus, after the target appeared, the participants had better executive control and achieved a faster response to the target. However, under the combination prompt, the participants consumed more attention resources during the prompt stage.DiscussionWe believe that for the participants with impaired cognitive function, cue prompts or preparation prompts can be considered, which also play a role in guiding the participants’ attention and helping them make motor preparations when less attention resources are consumed. This study provides a neurophysiological and behavioral foundation for the design of visual prompts in goal-directed tasks.

Abstract Background This study aims to investigate the early kinetics of interleukin 6 (IL‐6), procalcitonin (PCT), and C‐reactive protein (CRP) on initial antibiotic efficacy in hematological disorder patients with febrile neutropenia (FN). Methods A total of 40 patients with 43 episodes of FN were enrolled and divided into initial antibiotic effective group (IAE group, n = 24) and initial antibiotic ineffective group (IAI group, n = 19). The levels of IL‐6, PCT, and CRP before antibacterial treatment (T0), and 12 h (T1), 24 h (T2), 48 h (T3), and 72 h (T4) post‐antibacterial treatment were determined, respectively. Furthermore, the receiver operating characteristic curve (ROC) analysis was performed to evaluate the clinical value of indicators. Results In IAE group, the IL‐6 levels gradually decreased from T0 to T4, and the CRP levels significantly decreased at 48 to 72 h, whereas both IL‐6 and CRP remained at high levels in the IAI group. The PCT levels in both groups increased at the early stage of anti‐infection (T1–T2) and reached to peak at T1–T2 in effective group. ROC curve analysis identified IL‐6 as a predictive biomarker for initial antibiotic efficacy at 12, 48, and 72 h after treatment, with the AUC of 0.698, 0.744, and 0.821, respectively. In addition, CRP demonstrated predictive ability of initial antibiotics against infection at 24, 48, and 72 h after therapy, with the AUC of 0.724, 0.741, and 0.797, respectively. ROC curve analysis of percentage changes demonstrated that IL‐6 percentage change showed predictive ability of antibiotic efficacy at the early stage, and both the IL‐6 and CRP percentage changes showed the predictive ability of antibiotic efficacy 48 or 72 h after antibiotics therapy. Conclusion This study confirmed IL‐6 and CRP levels, and the percentage change in IL‐6 as the biomarkers for initial antibiotic efficacy prediction in hematological disorder patients with FN.

Introduction: and objectives: Extracellular vesicles (EVs) have emerged as key players in intercellular communication within the context of non-alcoholic fatty liver disease (NAFLD). This study aims to explore the intricate crosstalk between hepatocytes and hepatic stellate cells (HSCs) mediated by EVs in NAFLD. Materials and methods: EVs ferritin was detected in hepatocytes stimulated with free fatty acids (FFA) as well as in NAFLD mice. Deferoxamine (DFO) was employed to reduce ferritin levels, while GW4869 was utilized to inhibit EVs. The impact of EVs ferritin on the HSCs activation was evaluated both in vitro and in vivo. Additionally, serum EVs ferritin levels were compared between NAFLD patients and controls. Results: FFA treatment induces the formation and secretion of EVs and facilitates the release of ferritin from hepatocytes via EVs. Subsequently, EVs ferritin is hijacked by HSCs, prompting accelerated HSCs activation. Silencing ferritin with DFO and inhibiting EVs formation and secretion with GW4869 can reverse the effects of FFA treatment and disrupt the communication between hepatocytes and HSCs. Accumulation of ferritin leads to excessive reactive oxygen species (ROS) production, promoting HSCs fibrogenesis. Conversely, depleting EVs ferritin cargo restores liver function, concurrently mitigating NAFLD-associated fibrosis. Notably, NAFLD patients exhibit significantly elevated levels of serum EVs ferritin. Conclusions: This study unveils a previously underestimated role of ferritin in HSCs upon its release from hepatocytes, emphasizing DFO as a promising compound to impede NAFLD advancement.

Epidemiological evidence indicates an association between exposure to toxic metals and the occurrence of cardiometabolic diseases (CMDs). However, the impact of exposure to harmful metallic elements, such as lead (Pb), cadmium (Cd), and mercury (Hg), on mortality in individuals with cardiometabolic multimorbidity (CMM) remains uncertain. Therefore, in this study, we analyzed data from 4139 adults diagnosed with CMM from the National Health and Nutrition Examination Survey 1999–2016. CMM was defined as the presence of at least two CMDs (hypertension, diabetes, stroke, and coronary artery disease). Over an average follow-up period of 9.0 years, 1379 deaths from all causes, 515 deaths related to cardiovascular disease (CVD), and 215 deaths attributable to cancer were recorded. After adjusting for potential covariates, serum Pb concentrations were not associated with all-cause, CVD, or cancer mortality. Participants exposed to Cd had an elevated risk of all-cause mortality (hazard ratio [HR], 1.23; 95 % CI, 1.16–1.30), CVD-related mortality (HR, 1.23; 95 % CI, 1.12–1.35), and cancer-related mortality (HR, 1.29; 95 % CI, 1.13–1.47). Participants with serum Hg levels in the highest quantile had lower risks of all-cause (HR, 0.64; 95 % CI, 0.52–0.80) and CVD-related (HR, 0.62; 95 % CI, 0.44–0.88) mortality than did those in the lowest quantile. Stratified analyses revealed significant interactions between serum Cd concentrations and age for CVD-related mortality (P for interaction =0.011), indicating that CMM participants aged < 60 years who were exposed to Cd were at a greater risk of CVD-related mortality. A nonlinear relationship was observed between serum Cd concentrations and all-cause (P for nonlinear relationship = 0.012) and CVD-related (P for nonlinear relationship < 0.001) mortality. Minimizing Cd exposure in patients with CMM may help prevent premature death.

Introduction Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disorder that arises from complex interactions between genetics, environment and gut microbiota. It encompasses Crohn’s disease, ulcerative colitis and IBD-unclassified. The protracted course of IBD imposes a significant burden on patients’ quality of life, economic productivity, social functioning, as well as treatment, hospitalisation and surgery. This study aims to conduct an umbrella review of meta-analyses to systematically evaluate the methodology’s quality, potential biases and validity of all epidemiological evidence focused on risk factors for IBD while providing an overview of the evidence concerning IBD risk factors.Methods and analysis We will systematically search, extract and analyse data from reported systematic reviews and meta-analyses that specifically focus on the risk factors of IBD, following the guidelines outlined in Preferred Reporting Items for Overviews of Reviews. Our search will encompass PubMed, Embase, Web of Science and the Cochrane Database of Systematic Reviews from the initial period up until April 2023 (last update), targeting systematic reviews and meta-analyses based on non-interventional studies. Inclusion criteria allow for systematic reviews and meta-analyses evaluating IBD risk factors across all countries and settings, regardless of ethnicity or sex. The identified risk factors will be categorised according to the health ecological model into innate personal traits, behavioural lifestyles, interpersonal networks, socioeconomic status and macroenvironments. To assess methodological quality for each meta-analysis included in our study, two authors will employ a measurement tool to assess the methodological quality of systematic reviews (AMSTAR)-2, Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria along with evidence classification criteria.Ethics and dissemination Ethical approval is not required for this umbrella review. We will seek to submit the results for publication in a peer-reviewed journal or present it at conferences.PROSPERO registration number CRD42023417175.

BackgroundPoly (ADP-Ribose) Polymerase (PARP) inhibitors represent a novel class of drugs that hinder DNA repair mechanisms in tumor cells, leading to cell death. This systematic review aims to evaluate the effectiveness, safety, and potential adverse effects of PARP inhibitors (PARPi) in the management of patients with advanced lung cancer.Materials and MethodsWe conducted a comprehensive search for relevant studies in PubMed, Embase, Cochrane, and ClinicalTrials.gov. We extracted primary and secondary outcome measures, including progression-free survival (PFS), overall survival (OS), and adverse events (AEs), from the identified literature for subsequent meta-analysis and systematic review.ResultsThis study encompassed twelve randomized controlled trials, involving 3,132 patients with advanced lung cancer. In comparison to non-PARPi treatments, the administration of PARPi significantly extended OS (hazard ratio (HR) = 0.90, 95% CI = 0.83–0.97, p = 0.006). However, the difference in PFS did not reach statistical significance.ConclusionIn summary, therapies incorporating PARPi provide a degree of benefit by extending OS in patients with advanced lung cancer. Nonetheless, further trials are necessary to furnish additional evidence regarding the efficacy and safety of PARPi in the treatment of lung cancer.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier number: CRD42023424673.

The increasing prevalence and incidence of colorectal cancer (CRC), particularly in young adults, underscore the imperative to comprehend its fundamental mechanisms, discover novel diagnostic and prognostic markers, and enhance therapeutic strategies. Here, we integrated multi-omics data, including gene expression, somatic mutation data and DNA methylation data, to unravel the intricacies of tumor microenvironment (TME) in CRC and search for novel prognostic markers. By calculating the immune score for each patient from the expression profile, we delineated the differential immune cell fraction, constructed an immune-related multi-omics atlas, and identified molecular characteristics. The entire colorectal dataset (n = 343) was randomly divided into training (n = 249) and testing datasets (n = 94). We screened 144 immune-related genes, 6 mutant genes, and 38 methylation probes associated with overall survival (OS). These makers were then incorporated into a 10-gene prognostic model using Lasso and Cox regression in the training dataset, and the model's performance was evaluated in an independent validation dataset. The model exhibited satisfactory results (average concordance index [C-index] = 0.77), with the average 1-year, 3-year, and 5-year AUCs being 0.79, 0.76, and 0.76 in the training dataset and 0.74, 0.80, and 0.90 in the testing dataset. Furthermore, the prognostic model demonstrated applicability in guiding chemotherapy for CRC patients and exhibited a degree of pan-cancer utility in risk stratification. In conclusion, our integrated analysis of multi-omics data revealed immune-related genetic and epigenetic characteristics of the TME. We propose an integrative prognostic model that can stratify risk and guide chemotherapy for CRC patients. The generalizability of the model in risk stratification across different cancer types was validated in Pan-Cancer cohort.

Summary: The clinical success of immune checkpoint inhibitors is compromised by the fact of immune-related adverse events (irAEs), especially for older patients. To identify predictive biomarkers for older patients with irAEs, we used multiplex immunoassay and flow cytometry and liquid chromatography-tandem mass spectrometry to test immune factors and plasma protein and metabolites levels in non-small cell lung cancer (NSCLC) patients. The results showed that older patients with irAEs displayed lower CD28, CD4+ T cell, and B cell and higher interleukin (IL)-10 and CCL2 levels at baseline. Besides, lower aldolase, fructose-bisphosphate B (ALDOB), higher ST6GAL1, and lower lactate/pyruvate ratio at baseline were found in older patients with irAEs. Based on metabolomic markers, predictive models were developed to distinguish patients with grade 2–4 irAEs from grade 0–1 (Area under curve, AUC = 0.831) and to distinguish patients with grade 3–4 irAEs from grade 2 (AUC = 1). Our results confirmed the predictive value of plasma metabolites for irAEs in older patients with NSCLC.

Glioblastoma (GBM) presents a significant therapeutic challenge due to the limited efficacy of existing treatments. Chimeric antigen receptor (CAR) T-cell therapy offers promise, but its potential in solid tumors like GBM is undermined by the physical barrier posed by the extracellular matrix (ECM). To address the inadequacies of traditional 2D cell culture, animal models, and Matrigel-based 3D culture in mimicking the mechanical characteristics of tumor tissues, we employed biomaterials and digital light processing-based 3D bioprinting to fabricate biomimetic tumor models with finely tunable ECM stiffness independent of ECM composition. Our results demonstrated that increased material stiffness markedly impeded CAR-T cell penetration and tumor cell cytotoxicity in GBM models. The 3D bioprinted models enabled us to examine the influence of ECM stiffness on CAR-T cell therapy effectiveness, providing a clinically pertinent evaluation tool for CAR-T cell development in stiff solid tumors. Furthermore, we developed an innovative heat-inducible CAR-T cell therapy, effectively overcoming the challenges posed by the stiff tumor microenvironment.

Abstract Background The Stress hyperglycemia ratio (SHR) is a novel marker reflecting the true acute hyperglycemia status and is associated with clinical adverse events. The relationship between SHR and mortality in patients with diabetes or prediabetes is still unclear. This study aimed to investigate the predictive value of the SHR for all-cause and cardiovascular mortality in patients with diabetes or prediabetes. Methods This study included 11,160 patients diagnosed with diabetes or prediabetes from the National Health and Nutrition Examination Survey (2005–2018). The study endpoints were all-cause and cardiovascular mortality, and morality data were extracted from the National Death Index (NDI) up to December 31, 2019. Patients were divided into SHR quartiles. Cox proportion hazards regression was applied to determine the prognostic value of SHR. Model 1 was not adjusted for any covariates. Model 2 was adjusted for age, sex, and race. Model 3 was adjusted for age, sex, race, BMI, smoking status, alcohol use, hypertension, CHD, CKD, anemia, and TG. Results During a mean follow-up of 84.9 months, a total of 1538 all-cause deaths and 410 cardiovascular deaths were recorded. Kaplan-Meier survival analysis showed the lowest all-cause mortality incidence was in quartile 3 (P

Abstract Liver kinase B1 (LKB1), an evolutionarily conserved serine/threonine kinase, is a master regulator of the AMPK subfamily and controls cellular events such as polarity, proliferation, and energy homeostasis. Functions and mechanisms of the LKB1-AMPK axis at specific subcellular compartments, such as lysosome and mitochondria, have been established. AMPK is known to be activated at the Golgi; however, functions and regulatory mechanisms of the LKB1-AMPK axis at the Golgi apparatus remain elusive. Here, we show that TBC1D23, a Golgi-localized protein that is frequently mutated in the neurodevelopment disorder pontocerebellar hypoplasia (PCH), is specifically required for the LKB1 signaling at the Golgi. TBC1D23 directly interacts with LKB1 and recruits LKB1 to Golgi, promoting Golgi-specific activation of AMPK upon energy stress. Notably, Golgi-targeted expression of LKB1 rescues TBC1D23 deficiency in zebrafish models. Furthermore, the loss of LKB1 causes neurodevelopmental abnormalities in zebrafish, which partially recapitulates defects in TBC1D23-deficient zebrafish, and LKB1 sustains normal neuronal development via TBC1D23 interaction. Our study uncovers a regulatory mechanism of the LKB1 signaling, and reveals that a disrupted Golgi-LKB1 signaling underlies the pathogenesis of PCH.

Abstract Background The association between homeostatic model assessment (HOMA2-IR) and mortality in obese and non-obese populations has not been clearly explained. Methods A total of 7,085 individuals aged ≥ 20 years from the 1999–2006 National Health and Nutrition Examination Survey were included in the study. Study endpoints were all-cause and cardiovascular mortality. Multivariate Cox proportional hazards regression models with restricted cubic spline analysis were used for analysis. Results In the study populations, a total of 1666 all-cause deaths and 555 cardiovascular (CV) deaths were recorded during a mean follow-up of 195.53 months. Notably, a significant difference in obesity was observed in the association between HOMA2-IR and mortality. After adjustment for multiple variables, HOMA2-IR was positively associated with all-cause mortality in all participants, in those with normal BMI, and in those with obesity. Conversely, tertile 2 of HOMA2-IR was associated with a lower risk of all-cause mortality in participants with obesity compared with tertile 1 (adjusted hazard ratio, 0.68; 95% confidence interval, 0.52–0.89; P = 0.005). Results from restricted cubic spline analysis showed a J-shaped association between HOMA2-IR and all-cause and CV mortality. In addition, a nonlinear U-shaped correlation with all-cause (P for nonlinear

The ICASSP 2023 Deep Noise Suppression (DNS) Challenge marks the fifth edition of the DNS challenge series. DNS challenges were organized from 2019 to 2023 to foster research in the field of DNS. Previous DNS challenges were held at INTERSPEECH 2020, ICASSP 2021, INTERSPEECH 2021, and ICASSP 2022. This challenge aims to advance models capable of jointly addressing denoising, dereverberation, and interfering talker suppression, with separate tracks focusing on headset and speakerphone scenarios. The challenge facilitates personalized deep noise suppression by providing accompanying enrollment clips for each test clip, each containing the primary talker only, which can be used to compute a speaker identity feature and disentangle primary and interfering speech. While the majority of models submitted to the challenge were personalized, the same teams emerged as the winners in both tracks. The best models demonstrated improvements of 0.145 and 0.141 in the challenge's score, respectively, when compared to the noisy blind test set. We present additional analysis and draw comparisons to previous challenges.

Objective: We aimed to analyse the risk factors of complications after laparoscopic anterior resection of rectal cancer, and to establish a nomogram prediction model and evaluate its accuracy. Patients and Methods: We retrospectively analysed the clinical data of 180 patients undergoing laparoscopic anterior resection of rectal cancer. Univariate analysis and multivariate logistic regression analysis were used to screen the potential risk factors of post-operative complications of Grade II and establish a nomogram model. The receiver operating characteristic (ROC) curve and Hosmer–Lemeshow goodness-of-fit test were used to evaluate the discrimination and coincidence of the model, and the calibration curve was used to internally verify. Results: A total of 53 patients (29.4%) with rectal cancer had Grade II post-operative complications. Multivariate logistic regression analysis showed that age (odds ratio [OR] =1.085, P < 0.001), body mass index ≥24 kg/m2 (OR = 2. 763, P = 0. 008), tumour diameter ≥5 cm (OR = 3. 572, P = 0.002), tumour distance from anal margin ≤6 cm (OR = 2.729, P = 0.012) and operation time ≥180 min (OR = 2.243, P = 0.032) were independent risk factors for Grade II post-operative complications. The area under the ROC was 0.782 (95% confidence interval: 0.706–0.858, sensitivity: 66.0%, specificity: 76.4%) in the nomogram prediction model. Hosmer–Lemeshow goodness-of-fit test showed χ2 = 9.350, P = 0.314. Conclusion: Based on five independent risk factors, the nomogram prediction model has a good predictive performance for post-operative complications after laparoscopic anterior resection of rectal cancer, which is helpful to early identify high-risk people and formulate clinical intervention measures.

Abstract Abnormal expression of Cylindromatosis (CYLD), a tumor suppressor molecule, plays an important role in tumor development and treatment. In this work, we found that CYLD binds to class I histone deacetylases (HDAC1 and HDAC2) through its N-terminal domain and inhibits HDAC1 activity. RNA sequencing showed that CYLD-HDAC axis regulates cellular antioxidant response via Nrf2 and its target genes. Then we revealed a mechanism that class I HDACs mediate redox abnormalities in CYLD low-expressing tumors. HDACs are central players in the DNA damage signaling. We further confirmed that CYLD regulates radiation-induced DNA damage and repair response through inhibiting class I HDACs. Furthermore, CYLD mediates nasopharyngeal carcinoma cell radiosensitivity through class I HDACs. Thus, we identified the function of the CYLD-HDAC axis in radiotherapy and blocking HDACs by Chidamide can increase the sensitivity of cancer cells and tumors to radiation therapy both in vitro and in vivo. In addition, ChIP and luciferase reporter assays revealed that CYLD could be transcriptionally regulated by zinc finger protein 202 (ZNF202). Our findings offer novel insight into the function of CYLD in tumor and uncover important roles for CYLD-HDAC axis in radiosensitivity, which provide new molecular target and therapeutic strategy for tumor radiotherapy.

In the agricultural sector, farmers and agribusiness are confronted with a multitude of complex choices every day. These selections are influenced by multiple variables that significantly affect their outcomes. The primary source of revenue for a good deal of individuals is derived from the agricultural sector. The provision of precise and punctual predictions on crop yields has significant importance in facilitating informed investment choices and shaping agricultural policies. One of the challenges encountered is the presence of old or incomplete data about the accessibility of resources. This represents a significant obstacle in accurately ascertaining the present state of affairs. The process of evaluating becomes complex as a result of the diverse range of soil conditions and climatic factors. This research introduces a novel approach called Enhanced Gravitational Search Optimized based Gated Recurrent Unit (EGSO-GRU) for the purpose of calculating crop production. The dataset was first gathered and pre-processed using a normalization method. Enhanced independent component analyses (EICA) have been employed for the purpose of extracting features. To determine the suggest method achievement with regard to accuracy (95.89%), specificity (92.4%), MSE (0.071), RMSE (0.210) and MAE (0.199). The proposed method achieved greater crop prediction accuracy, outperforming the majority of the existing models. The necessity of this progress is vital to the successful operation of crops. The concept signifies a technological advancement aimed at optimizing agricultural resources, hence fostering enhanced productivity and long-term sustainability within the farming industry.

In response to the challenge of insufficient trajectory tracking accuracy and low solution efficiency of Mecanum wheel AGV (Automated Guided Vehicle) under complex and constrained working conditions, this paper proposes an efficient Model Predictive Control (MPC) method to achieve superior tracking performance and robustness. Initially, a linear error model of the mobile platform is established based on pose error, serving as the predictive model for the MPC controller. A target function is designed to transform the trajectory tracking control problem into an optimal control problem. To handle inequality constraints, penalty terms are introduced into the objective function, and the resulting constrained problem is subsequently solved to approximate the optimal solution for the original inequalities. To alleviate the computational burden associated with real-time optimization problem-solving, an efficient MPC algorithm. has been developed. To ensure closed-loop stability under the MPC control method, stability constraints are imposed on the new optimization problem. Simulation results demonstrate that, in comparison to traditional MPC methods, the proposed approach reduces the average solution calculation time by 5.1% and the maximum single calculation time by 13.7%, all while maintaining trajectory tracking accuracy. These results validate the algorithm’s feasibility, effectively addressing the challenges associated with solving MPC problems.

【Objective】The effect of exogenous methyl jasmonate on resistance to bacterial leaf stripe (BLS) was studied, which would provide a theoretical basis for the prevention and control of BLS in rice.【Method】With rice BLS-resistant and susceptible near isogenic lines (K9 and G9) as materials, 0.1 mmol/L methyl jasmonate (MeJA) were sprayed on BLS-resistant and susceptible near isogenic lines (K9 and G9) plants respectively at tillering stage, and water spraying was used as control (CK). The inoculation with Xanthomonas oryzae pv. Oryzicola (Xoc) were conducted at 0, 12, 24, 48, 72 h after MeJA treatment, then the symptoms of BLS were investigated. In K9 and G9 plants sprayed with MeJA for 48 h then inoculated with Xoc, the expression changes of hormone-pathway related genes were further analyzed at 0, 6, 12, 24 and 48 h after inoculation.【Result】In K9 plants, the lesion lengths of leaves inoculated at 0, 24, 48, 72h after being sprayed with MeJA were significantly shorter than those in CK; in G9 plants, the lesion lengths of leaves inoculated at 0 h and 12 h after being sprayed with MeJA were significantly longer than those in CK, while inoculated at 72 h after being sprayed with MeJA were significantly shorter than those in CK. Compared with the CK, relative expression levels of jasmonate-pathway related genes LOX2 and AOS2, and pathogenesis-related gene PR10 were upregulated, while relative expression levels of alicylic acid-pathway related genes PAD4 and PAL, ethylene-pathway related genes EIN2 and ERF70, and pathogenesis-related gene PR1a were downregulated in K9 plants inoculated at 48h after being sprayed with MeJA; relative expression levels of jasmonate-pathway related genes LOX2 and AOS2, salicylic acid-pathway related genes PAD4 and PAL and pathogenesis-related genes PR1a and PR10 were upregulated, while relative expression level of ethylene-pathway related gene EIN2 was downregulated in G9 plants inoculated at 48h after being sprayed with MeJA.【Conclusion】Exogenous MeJA affects the BLS-resistance in rice resistant and susceptible near isogenic lines. The resistance responses of resistant and susceptible near isogenic lines to Xoc are different at different inoculation time points after MeJA treatment. Exogenous MeJA involves in the defense response to Xoc infection by inducing the expression changes of jasmonate, salicylic acid and ethylene pathway-related genes and pathogenesis-related genes.

Abstract Objective: Inflammation plays a critical role in the progression of chronic liver diseases, and diet can modulate inflammation. Whether an inflammatory dietary pattern is associated with higher risk of hepatic steatosis or fibrosis remains unclear. We aimed to investigate the associations between inflammatory dietary pattern and the odds of hepatic steatosis and fibrosis. Design: In this nationwide cross-sectional study, diet was measured using two 24-h dietary recalls. Empirical dietary inflammatory pattern (EDIP) score was derived to assess the inflammatory potential of usual diet, which has been validated to highly predict inflammation markers in the study population. Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were derived from FibroScan to define steatosis and fibrosis, respectively. Setting: US National Health and Nutrition Examination Survey. Participants: 4171 participants aged ≥18 years. Results: A total of 1436 participants were diagnosed with S1 steatosis (CAP ≥ 274 dB/m), 255 with advanced fibrosis (LSM ≥ 9·7 kPa). Compared with those in the lowest tertile of EDIP-adherence scores, participants in the highest tertile had 74 % higher odds of steatosis (OR: 1·74, 95 % CI (1·26, 2·41)). Such positive association persisted among never drinkers, or participants who were free of hepatitis B and/or C. Similarly, EDIP was positively associated with CAP in multivariate linear model (P < 0·001). We found a non-significant association of EDIP score with advanced fibrosis or LSM (P = 0·837). Conclusions: Our findings suggest that a diet score that is associated with inflammatory markers is associated with hepatic steatosis. Reducing or avoiding pro-inflammatory diets intake might be an attractive strategy for fatty liver disease prevention.

Betaine aldehyde dehydrogenases (BADHs) are key enzymes in the biosynthesis of glycine betaine, which is an important organic osmolyte that maintains cell structure and improves plant tolerance to abiotic stresses, especially in halotolerant plants. Improving the drought tolerance of crops will greatly increase their yield. In this study, a novel BADH gene named SgBADH from Suaeda glauca was induced by drought stress or abscisic acid. To explore the biological function of SgBADH, the SgBADH gene was transformed into Arabidopsis. Then, we found SgBADH-overexpressing Arabidopsis seedlings showed enhanced tolerance to drought stress. SgBADH transgenic Arabidopsis seedlings also had longer roots compared with controls under drought stress, while SgBADH-overexpressing Arabidopsis exhibited increased glycine betaine accumulation and decreased malondialdehyde (MDA) under drought stress. Our results suggest that SgBADH might be a positive regulator in plants during the response to drought.

Bisphenol F (BPF), a substitute for bisphenol A (BPA), is ubiquitous existed in various environmental media. Exposure to BPF may promote non-alcoholic fatty liver disease (NAFLD), while the potential mechanism is still unknown. In current study, we used in vitro and in vivo model to evaluate its hepatotoxicity and molecular mechanism. Using multi-omics approach, we found that BPF exposure led to changes in hepatic transcriptome, metabolome and chromatin accessible regions that were enriched for binding sites of transcription factors in bZIP family. These alterations were enriched with pathways integral to the endoplasmic reticulum stress and NAFLD. These findings suggested that BPF exposure might reprogram the chromatin accessibility and enhancer landscape in the liver, with downstream effects on genes associated with endoplasmic reticulum stress and lipid metabolism, which relied on bZIP family transcription factors. Overall, our study describes comprehensive molecular alterations in hepatocytes after BPF exposure and provides new insights into the understanding of the hepatoxicity of BPF.

Parkinson’s disease (PD), ranking as the second most prevalent neurodegenerative disorder globally, presents a pressing need for innovative animal models to deepen our understanding of its pathophysiology and explore potential therapeutic interventions. The development of such animal models plays a pivotal role in unraveling the complexities of PD and investigating promising treatment avenues. In this study, we employed transcriptome sequencing on BmN cells treated with 1 μg/ml rotenone, aiming to elucidate the underlying toxicological mechanisms. The investigation brought to light a significant reduction in mitochondrial membrane potential induced by rotenone, subsequently triggering mitophagy. Notably, the PTEN induced putative kinase 1 (PINK1)/Parkin pathway emerged as a key player in the cascade leading to rotenone-induced mitophagy. Furthermore, our exploration extended to silkworms exposed to 50 μg/ml rotenone, revealing distinctive motor dysfunction as well as inhibition of Tyrosine hydroxylase (TH) gene expression. These observed effects not only contribute valuable insights into the impact and intricate mechanisms of rotenone exposure on mitophagy but also provide robust scientific evidence supporting the utilization of rotenone in establishing a PD model in the silkworm. This comprehensive investigation not only enriches our understanding of the toxicological pathways triggered by rotenone but also highlights the potential of silkworms as a valuable model organism for PD research.

IntroductionUpper limb rehabilitation assessment plays a pivotal role in the recovery process of stroke patients. The current clinical assessment tools often rely on subjective judgments of healthcare professionals. Some existing research studies have utilized physiological signals for quantitative assessments. However, most studies used single index to assess the motor functions of upper limb. The fusion of surface electromyography (sEMG) and functional near-infrared spectroscopy (fNIRS) presents an innovative approach, offering simultaneous insights into the central and peripheral nervous systems.MethodsWe concurrently collected sEMG signals and brain hemodynamic signals during bilateral elbow flexion in 15 stroke patients with subacute and chronic stages and 15 healthy control subjects. The sEMG signals were analyzed to obtain muscle synergy based indexes including synergy stability index (SSI), closeness of individual vector (CV) and closeness of time profile (CT). The fNIRS signals were calculated to extract laterality index (LI).ResultsThe primary findings were that CV, SSI and LI in posterior motor cortex (PMC) and primary motor cortex (M1) on the affected hemisphere of stroke patients were significantly lower than those in the control group (p

Mylabris sibirica is a hypermetamorphic insect whose adults feed on oilseed rape. However, due to a shortage of effective and appropriate endogenous references, studies on molecular functional genes in Mylabris sibirica, have been tremendously limited. In this study, ten internal reference genes (ACT, ARF1, AK, EF1α, GAPDH, α-TUB, RPL6, RPL13, RPS3 and RPS18) were tested and assessed under four selected treatments including adult ages, adult tissues, temperatures, and sex by RT-qPCR based on five methods (Ct value, geNorm, NormFinder, BestKeeper and RefFinder). Our findings showed that RPL6 and RPL13 were the most optimal internal reference gene combination for gene expression during various adult ages and under diverse temperatures; The combination of RPL6 and RPS18 was recommended to test gene transcription levels under different adult tissues. AK and RPL6 were the best reference genes in male and female adults. RPL6 and RPL13 were the most appropriate reference gene pair to estimate gene expression levels under four different tested backgrounds. The relative transcript levels of a uridine diphosphate (UDP)-N-acetylglucosamine-pyrophosphorylase (MsUAP), varied greatly according to normalization with the two most- and least-suited reference genes. This study will lay the basis for further molecular physiology and biochemistry studies in M. sibirica, such as development, reproduction, sex differentiation, cold and heat resistance.

Background: Insufficient clinicians' auscultation ability delays the diagnosis and treatment of valvular heart disease (VHD); artificial intelligence provides a solution to compensate for the insufficiency in auscultation ability by distinguishing between heart murmurs and normal heart sounds. However, whether artificial intelligence can automatically diagnose VHD remains unknown. Our objective was to use deep learning to process and compare raw heart sound data to identify patients with VHD requiring intervention. Methods: Heart sounds from patients with VHD and healthy controls were collected using an electronic stethoscope. Echocardiographic findings were used as the gold standard for this study. According to the chronological order of enrollment, the early-enrolled samples were used to train the deep learning model, and the late-enrollment samples were used to validate the results. Results: The final study population comprised 499 patients (354 in the algorithm training group and 145 in the result validation group). The sensitivity, specificity, and accuracy of the deep-learning model for identifying various VHDs ranged from 71.4 to 100.0%, 83.5–100.0%, and 84.1–100.0%, respectively; the best diagnostic performance was observed for mitral stenosis, with a sensitivity of 100.0% (31.0–100.0%), a specificity of 100% (96.7–100.0%), and an accuracy of 100% (97.5–100.0%). Conclusions: Based on raw heart sound data, the deep learning model effectively identifies patients with various types of VHD who require intervention and assists in the screening, diagnosis, and follow-up of VHD.