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To investigate the effects of sacubitril valsartan sodium combined with levosimendan on improving cardiac and renal functions in patients with CRS.ObjectiveTo investigate the effects of sacubitril valsartan sodium combined with levosimendan on improving cardiac and renal functions in patients with CRS.90 patients with the cardiorenal syndrome who were hospitalized in our hospital from February 2020 to February 2022 were selected and divided into two groups, the control group, and the joint group, according to both single and double number methods, with 45 cases in each group. Patients who met the diagnostic criteria for CRS, were older than 18 years of age, had NYHA class II to IV, and had stage 1 or 2 chronic kidney disease were included in the study. Patients with severe hypersensitivity to the drugs used in this test, haemodynamic instability, combined hyperthyroidism, malignancy, severe pulmonary hypertension, cardiogenic shock, malignant arrhythmias and pregnant women were excluded. Among them, the control group was treated with sacubitril valsartan sodium alone, and the joint group was treated with levosimendan supplemented with the treatment method of the control group. The treatment effect, the improvement of cardiac and renal function, and the incidence of adverse reactions were compared between the two groups of CRS patients, and the prognostic effect was followed up 6 months after treatment.Methods90 patients with the cardiorenal syndrome who were hospitalized in our hospital from February 2020 to February 2022 were selected and divided into two groups, the control group, and the joint group, according to both single and double number methods, with 45 cases in each group. Patients who met the diagnostic criteria for CRS, were older than 18 years of age, had NYHA class II to IV, and had stage 1 or 2 chronic kidney disease were included in the study. Patients with severe hypersensitivity to the drugs used in this test, haemodynamic instability, combined hyperthyroidism, malignancy, severe pulmonary hypertension, cardiogenic shock, malignant arrhythmias and pregnant women were excluded. Among them, the control group was treated with sacubitril valsartan sodium alone, and the joint group was treated with levosimendan supplemented with the treatment method of the control group. The treatment effect, the improvement of cardiac and renal function, and the incidence of adverse reactions were compared between the two groups of CRS patients, and the prognostic effect was followed up 6 months after treatment.The total effective rate of treatment in the joint group was 95.56%, which was significantly higher than that in the control group of 80.00%, and the difference was statistically significant by using χ2 test (P < .05). After treatment, LVEF, LVEDD, and NT-proBNP levels in both groups were significantly improved compared with those before treatment (P < .05), and the improvement effect of each index in the joint group was more significant than that in the control group (P < .05). After treatment, the levels of SCr, BUN, and UA in both groups were significantly lower than those before treatment (P < .05), and the levels of each index in the joint group were significantly lower than those in the control group, statistical analyses showed significant differences (P < .05) using t test. The incidence of adverse effects such as tachycardia, premature ventricular contractions, heart failure, and myocardial ischaemia was 22.22% in the combined group, which was significantly lower than 42.22% in the control group, and the difference in the total incidence between the two groups was statistically significant by χ2 test (P < .05). One case of malignant arrhythmia and five cases of recurrence of heart failure occurred 6 months after surgery in the combined group, which were significantly lower than the eight and twelve cases in the control group.ResultsThe total effective rate of treatment in the joint group was 95.56%, which was significantly higher than that in the control group of 80.00%, and the difference was statistically significant by using χ2 test (P < .05). After treatment, LVEF, LVEDD, and NT-proBNP levels in both groups were significantly improved compared with those before treatment (P < .05), and the improvement effect of each index in the joint group was more significant than that in the control group (P < .05). After treatment, the levels of SCr, BUN, and UA in both groups were significantly lower than those before treatment (P < .05), and the levels of each index in the joint group were significantly lower than those in the control group, statistical analyses showed significant differences (P < .05) using t test. The incidence of adverse effects such as tachycardia, premature ventricular contractions, heart failure, and myocardial ischaemia was 22.22% in the combined group, which was significantly lower than 42.22% in the control group, and the difference in the total incidence between the two groups was statistically significant by χ2 test (P < .05). One case of malignant arrhythmia and five cases of recurrence of heart failure occurred 6 months after surgery in the combined group, which were significantly lower than the eight and twelve cases in the control group.Sacubitril valsartan sodium combined with levosimendan can significantly improve the therapeutic effect of CRS, with significant improvement in cardiac and renal function of CRS patients, and its incidence of adverse effects and long-term prognostic effects are lower than those of sacubitril valsartan sodium alone. This combination therapy offers a promising new direction for CRS management, warranting further investigation in larger, multicenter trials.ConclusionSacubitril valsartan sodium combined with levosimendan can significantly improve the therapeutic effect of CRS, with significant improvement in cardiac and renal function of CRS patients, and its incidence of adverse effects and long-term prognostic effects are lower than those of sacubitril valsartan sodium alone. This combination therapy offers a promising new direction for CRS management, warranting further investigation in larger, multicenter trials.

To investigate the effects of sacubitril valsartan sodium combined with levosimendan on improving cardiac and renal functions in patients with CRS. 90 patients with the cardiorenal syndrome who were hospitalized in our hospital from February 2020 to February 2022 were selected and divided into two groups, the control group, and the joint group, according to both single and double number methods, with 45 cases in each group. Patients who met the diagnostic criteria for CRS, were older than 18 years of age, had NYHA class II to IV, and had stage 1 or 2 chronic kidney disease were included in the study. Patients with severe hypersensitivity to the drugs used in this test, haemodynamic instability, combined hyperthyroidism, malignancy, severe pulmonary hypertension, cardiogenic shock, malignant arrhythmias and pregnant women were excluded. Among them, the control group was treated with sacubitril valsartan sodium alone, and the joint group was treated with levosimendan supplemented with the treatment method of the control group. The treatment effect, the improvement of cardiac and renal function, and the incidence of adverse reactions were compared between the two groups of CRS patients, and the prognostic effect was followed up 6 months after treatment. The total effective rate of treatment in the joint group was 95.56%, which was significantly higher than that in the control group of 80.00%, and the difference was statistically significant by using χ2 test (P < .05). After treatment, LVEF, LVEDD, and NT-proBNP levels in both groups were significantly improved compared with those before treatment (P < .05), and the improvement effect of each index in the joint group was more significant than that in the control group (P < .05). After treatment, the levels of SCr, BUN, and UA in both groups were significantly lower than those before treatment (P < .05), and the levels of each index in the joint group were significantly lower than those in the control group, statistical analyses showed significant differences (P < .05) using t test. The incidence of adverse effects such as tachycardia, premature ventricular contractions, heart failure, and myocardial ischaemia was 22.22% in the combined group, which was significantly lower than 42.22% in the control group, and the difference in the total incidence between the two groups was statistically significant by χ2 test (P < .05). One case of malignant arrhythmia and five cases of recurrence of heart failure occurred 6 months after surgery in the combined group, which were significantly lower than the eight and twelve cases in the control group. Sacubitril valsartan sodium combined with levosimendan can significantly improve the therapeutic effect of CRS, with significant improvement in cardiac and renal function of CRS patients, and its incidence of adverse effects and long-term prognostic effects are lower than those of sacubitril valsartan sodium alone. This combination therapy offers a promising new direction for CRS management, warranting further investigation in larger, multicenter trials.

Local genetic correlation quantifies the genetic similarity of complex traits in specific genomic regions. However, accurate estimation of local genetic correlation remains challenging, due to linkage disequilibrium in local genomic regions and sample overlap across studies. We introduce SUPERGNOVA, a statistical framework to estimate local genetic correlations using summary statistics from genome-wide association studies. We demonstrate that SUPERGNOVA outperforms existing methods through simulations and analyses of 30 complex traits. In particular, we show that the positive yet paradoxical genetic correlation between autism spectrum disorder and cognitive performance could be explained by two etiologically distinct genetic signatures with bidirectional local genetic correlations.

The increasing prevalence of pediatric atopic diseases in China poses substantial risks to children's physical health, mental well-being, and quality of life. Cognitive behavioral interventions for caregivers are effective in managing pediatric atopic diseases. Existing interventions are typically siloed and lack integration across the comorbidities of the atopic march. The protection motivation theory (PMT) could provide an integrated cognitive behavioral intervention framework for addressing shared pathophysiological mechanisms and unifying management strategies across atopic diseases, while online interventions offer advantages in accessibility, cost-effectiveness, and scalability, particularly for caregiver-mediated pediatric care. This study aimed to develop and evaluate a PMT-based cognitive behavioral online (PMT-CBO) intervention for caregivers of children with atopic diseases, assessing its effects on caregivers' protective motivation, behavioral intentions, preventive practices, and children's atopic disease outcomes. A quasi-experimental design was conducted in 3 health care institutions in Hangzhou, China, where 2 health care institutions were assigned to the PMT-CBO group (127/243, 52.3%) and 1 health care institution was assigned to the control group (116/243, 47.7%). Caregivers in the PMT-CBO group received a 4-week structured course comprising 16 online modules delivered via a WeChat mini-program, whereas controls received routine care with verbal education. Primary outcomes included caregivers' PMT dimensions (threat appraisal and coping appraisal), behavioral intentions, and preventive behaviors, and secondary outcomes involved children's symptom severity and medication adherence. The primary outcome scales or questionnaires were designed by the research team, while the secondary outcome scales were derived from established studies. All scales demonstrated good reliability and validity. Intention-to-treat analysis was used. Compared to the control group, the PMT-CBO group demonstrated significant improvements in overall PMT scores (Z=-6.289; P<.001) and most subdimensions (response efficacy, self-efficacy, threat severity, and response cost, with P<.05), except susceptibility (Z=-1.321; P=.19) and reward appraisals (Z=-0.989; P=.32). In the intervention group, caregivers exhibited stronger intentions and partial behavioral optimization (eg, environmental allergen control, with Z=-3.025; P=.002) and children showed improved medication adherence (Z=-4.457; P<.001) and alleviated eczema (Z=-3.112; P=.002) and allergic rhinitis symptoms (Z=-3.277; P<.001), although no significant differences emerged in asthma control (Z=-.830; P=.41) or food allergy-related caregiver burden (Z=-1.693; P=.09). The PMT-CBO intervention enhanced caregivers' motivation and intentions and children's medication adherence and eczema and rhinitis outcomes, with a 91.3% (116/127) completion rate via WeChat's scalable platform. Limited improvements in asthma control and food allergy management implied the future need for additional condition-specific plug-ins, beyond the core PMT-CBO modules. Moreover, merging this PMT-CBO intervention with implementation techniques or ecological frameworks could help address intention-behavior gaps and external barriers, thereby promoting equitable and precision-based allergy care.

The wide utilization of gas-fired generation and the rapid development of power-to-gas technologies have led to the intensified integration of electricity and gas systems. The random failures of components in either electricity or gas system may have a considerable impact on the reliabilities of both systems. Therefore, it is necessary to evaluate the reliabilities of electricity and gas systems considering their integration. In this paper, a novel reliability evaluation method for integrated electricity–gas systems (IEGSs) is proposed. First, reliability network equivalents are utilized to represent reliability models of gas-fired generating units, gas sources (GSs), power-to-gas facilities, and other conventional generating units in IEGS. A contingency management schema is then developed considering the coupling between electricity and gas systems based on an optimal power flow technique. Finally, the time-sequential Monte Carlo simulation approach is used to model the chronological characteristics of the corresponding reliability network equivalents. The proposed method is capable to evaluate customers’ reliabilities in IEGS, which is illustrated on an integrated IEEE Reliability Test System and Belgium gas transmission system.

Climate change is expanding vector-borne disease ranges, yet Chikungunya virus (CHIKV) risk projections remain limited by single-model uncertainty and lack of vector integration. CHIKV, transmitted by and , threatens 1.3 billion people globally, necessitating robust spatiotemporal risk assessment. Using hierarchical ensemble modeling in Biomod2, we first projected vector distributions based on 19 bioclimatic variables and elevation, then integrated vector suitability as biological predictors for CHIKV under 16 CMIP6 scenarios (4 SSPs × 4 GCMs, 2021-2100). Eleven algorithms were evaluated and ensembled to minimize uncertainty. Ensemble models achieved excellent performance ( : AUC = 0.949, TSS = 0.773; : AUC = 0.934, TSS = 0.764; CHIKV: AUC = 0.909, TSS = 0.659). distribution was constrained by temperature stability (isothermality, temperature seasonality), while responded to both temperature and precipitation. CHIKV distribution was primarily vector-driven (84% explanatory power), further modulated mainly by the mean temperature of wettest quarter. Currently, 21.26% of global land area (139 countries) faces CHIKV risk, concentrated in tropical/subtropical zones. Future projections reveal northward expansion into temperate regions (northeastern North America, central Europe, East Asia), but extreme warming (SSP585) may contract tropical habitats via thermal stress. Multi-model projections identify region-specific invasion risks, with previously unaffected temperate areas emerging as high-priority surveillance zones by 2100. These findings provide actionable risk maps for targeted vector control and preparedness strategies in 139 at-risk countries, particularly those lacking population immunity. Model heterogeneity underscores the necessity of ensemble approaches for climate-health policy planning.

Swine coronaviruses (CoVs) have been found to cause infection in humans, suggesting that Suiformes might be potential intermediate hosts in CoV transmission from their natural hosts to humans. The present study aims to establish convolutional neural network (CNN) models to predict host adaptation of swine CoVs. Decomposing of each ORF1ab and Spike sequence was performed with dinucleotide composition representation (DCR) and other traits. The relationship between CoVs from different adaptive hosts was analyzed by unsupervised learning, and CNN models based on DCR of ORF1ab and Spike were built to predict the host adaptation of swine CoVs. The rationality of the models was verified with phylogenetic analysis. Unsupervised learning showed that there is a multiple host adaptation of different swine CoVs. According to the adaptation prediction of CNN models, swine acute diarrhea syndrome CoV (SADS-CoV) and porcine epidemic diarrhea virus (PEDV) are adapted to Chiroptera, swine transmissible gastroenteritis virus (TGEV) is adapted to Carnivora, porcine hemagglutinating encephalomyelitis (PHEV) might be adapted to Primate, Rodent, and Lagomorpha, and porcine deltacoronavirus (PDCoV) might be adapted to Chiroptera, Artiodactyla, and Carnivora. In summary, the DCR trait has been confirmed to be representative for the CoV genome, and the DCR-based deep learning model works well to assess the adaptation of swine CoVs to other mammals. Suiformes might be intermediate hosts for human CoVs and other mammalian CoVs. The present study provides a novel approach to assess the risk of adaptation and transmission to humans and other mammals of swine CoVs.

Influenza A virus (IAV) is a leading cause of human respiratory infections and poses a major public health concern. IAV replication can affect the expression of DNA methyltransferases (DNMTs), and the subsequent changes in DNA methylation regulate gene expression and may lead to abnormal gene transcription and translation, yet the underlying mechanisms of virus-induced epigenetic changes from DNA methylation and its role in virus–host interactions remain elusive. Here in this paper, we showed that DNMT1 expression could be suppressed following the inhibition of miR-142-5p or the PI3K/AKT signaling pathway during IAV infection, resulting in demethylation of the promotor region of the 2′-5′-oligoadenylate synthetase-like (OASL) protein and promotion of its expression in A549 cells. OASL expression enhanced RIG-I-mediated interferon induction and then suppressed replication of IAV. Our study elucidated an innate immunity mechanism by which up-regulation of OASL contributes to host antiviral responses via epigenetic modifications in IAV infection, which could provide important insights into the understanding of viral pathogenesis and host antiviral defense.

Recent advances in consortium-scale genome-wide association studies (GWAS) have highlighted the involvement of common genetic variants in autism spectrum disorder (ASD), but our understanding of their etiologic roles, especially the interplay with rare variants, is incomplete. In this work, we introduce an analytical framework to quantify the transmission disequilibrium of genetically regulated gene expression from parents to offspring. We applied this framework to conduct a transcriptome-wide association study (TWAS) on 7,805 ASD proband-parent trios, and replicated our findings using 35,740 independent samples. We identified 31 associations at the transcriptome-wide significance level. In particular, we identified POU3F2 (p = 2.1E-7), a transcription factor mainly expressed in developmental brain. Gene targets regulated by POU3F2 showed a 2.7-fold enrichment for known ASD genes (p = 2.0E-5) and a 2.7-fold enrichment for loss-of-function de novo mutations in ASD probands (p = 7.1E-5). These results provide a novel connection between rare and common variants, whereby ASD genes affected by very rare mutations are regulated by an unlinked transcription factor affected by common genetic variations.

Human adenovirus 55 (HAdV-55) has recently caused outbreaks of acute respiratory disease (ARD), posing a significant public threat to civilians and military trainees. Efforts to develop antiviral inhibitors and quantify neutralizing antibodies require an experimental system to rapidly monitor viral infections, which can be achieved through the use of a plasmid that can produce an infectious virus. Here, we used a bacteria-mediated recombination approach to construct a full-length infectious cDNA clone, pAd55-FL, containing the whole genome of HadV-55. Then, the green fluorescent protein expression cassette was assembled into pAd55-FL to replace the E3 region to obtain a recombinant plasmid of pAd55-dE3-EGFP. The rescued recombinant virus rAdv55-dE3-EGFP is genetically stable and replicates similarly to the wild-type virus in cell culture. The virus rAdv55-dE3-EGFP can be used to quantify neutralizing antibody activity in sera samples, producing results in concordance with the cytopathic effect (CPE)-based microneutralization assay. Using an rAdv55-dE3-EGFP infection of A549 cells, we showed that the assay could be used for antiviral screening. Our findings suggest that the rAdv55-dE3-EGFP-based high-throughput assay provides a reliable tool for rapid neutralization testing and antiviral screening for HAdV-55.