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A cross-study transcriptional patient map of heart failure defines conserved multicellular coordination in cardiac remodeling

Abstract Impaired cardiac function in heart failure (HF) involves tissue remodeling through multicellular coordination. Although individual bulk and single-nucleus transcriptomics studies have offered insights, they have not been integrated to study conserved tissue-wide responses, limiting understanding of multicellular processes in cardiac remodeling necessary for therapeutic translation. Here, we integrate 25 studies of bulk and single-nucleus transcriptomics, spanning 1524 individuals, to define consensus multicellular programs associated with HF. These programs reveal conserved fibrotic, inflammatory, metabolic, and hypertrophic processes, with fibroblast activity consistently predicting cardiomyocyte stress. Our integration revealed that multicellular programs in HF are largely independent of tissue composition, and that fibroblast activation reflects a broad phenotypic shift rather than solely the emergence of discrete subtypes. Projecting external datasets onto these programs showed that clinical recovery aligns with reversion of disease-associated programs. This integrative analysis across studies establishes a public reference for the exploration of multicellular coordination in HF.

Exposure to volatile organic compounds increases the risk of sarcopenia: Insights into association and mechanism

Background Volatile organic compounds (VOCs) are ubiquitous in our environment, and their associations with sarcopenia are unknown. The aim of this study is to evaluate the association between VOCs exposure and sarcopenia. Methods Data from 2429 U.S. adults (aged ≥ 20 years) were extracted from the NHANES (2011–2018). Logistic regression, LASSO, Weighted Quantile Sum (WQS) and Bayesian Kernel Machine regression (BKMR) analyses were used to assess the associations between VOCs and sarcopenia. Mediation analysis tested roles of inflammation and oxidative stress in this association. The underlying mechanisms were further investigated through database enrichment analysis, molecular docking, and molecular dynamics simulations. Results Among the 2429 adults included, 1213 (49.9%) were male, 1216 (50.1%) were female, and the median age was 39 years (interquartile range, 29–49 years), with a prevalence of sarcopenia of 8.03%. According to the logistic analysis, nine mVOCs were significantly associated with sarcopenia, with N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHBMA) identified as a potential independent risk factor (odds ratio [OR], 4.51 [95% CI: 1.7–12.1]). WQS analysis revealed a positive association between LASSO-selected 12 mVOCs and sarcopenia (OR 1.39 [95% CI: 1.17–1.90]). BKMR analysis further confirmed this association, with DHBMA showing a significant contribution. Mediation analysis confirmed that inflammation and oxidative stress exert mediating effects. GO and KEGG enrichment analyses indicated that its effects are exerted through the TNF and PI3K–Akt signaling pathways, and that DHBMA binds stably to AKT1. Conclusion This nationally representative cross-sectional study revealed a positive correlation between exposure to mVOCs and sarcopenia via TNF and PI3K–Akt signaling pathways. DHBMA plays a potentially pivotal role in this association.

Activation of enzymatic catalysis via nucleic acid hybridization affords synergistic coupling of specificity, potency, and signal amplification

The association between the CUN-BAE index and depression mediated by SIRI: A large cross-sectional study

Background Depression is a common global mood disorder problem and one of the major disabling factors. The Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) index is an important composite indicator for measuring fat content in the body. Our goal is to find out the relationship between the CUN-BAE index and depression, as well as the mediating effect of the Systemic Inflammatory Response Index (SIRI) between the two. Methods All participants aged ≥ 20 from the 2005–2020 cycles of the NHANES in the US were included in the research. To assess the relationships between CUN-BAE and SIRI and depression, we used weighted multivariable logistic regression models. Potential nonlinearity was examined using restricted cubic splines (RCS) regression models. We performed mediation analysis with 1000 bootstrap replicates to evaluate the mediating function of SIRI in the relationship of CUN-BAE and depression. Results 31,592 participants were examined for the statistical analysis, of whom 28,825 were classified into the non-depression group and 2,767 were identified as belonging to depression group. Individuals in the depression group were more probable to be female and to have diabetes and hypertension, and higher SIRI and CUN-BAE levels. An incremental rise of one unit in CUN-BAE was connected to a 2% elevation in the odds of developing depression (OR = 1.02; 95% CI: 1.01–1.03; P  < 0.001). The regression analysis revealed a statistically significant non-linear positive relationship between CUN-BAE levels and depressive status ( P for non-linearity = 0.005), alongside a J-shaped curve characterizing the association between log-transformed SIRI and depression ( P for non-linearity = 0.007). The AUC of CUN-BAE for predicting depression was 0.60(0.59,0.61). With a 3% mediating effect, SIRI functioned as a partial mediator in the pathway linking CUN-BAE levels to depression. Conclusions The level of the CUN-BAE index might serve as a potential index for assessing an individual’s risk of developing depression. Monitoring body fat and inflammation levels might be useful for early detection of those who are potentially at risk for depression.

Gene expression signatures from whole blood predict amyotrophic lateral sclerosis case status and survival

Qualitative understandings of the persistent use of traditional contraceptive methods using the socio-ecological model among older reproductive-age women in Khulna, Bangladesh

Background The continued use of Traditional Contraceptive Methods (TCM) among Bangladeshi women of reproductive age (aged 35–49 years) poses a significant public health issue. Existing research in Bangladesh suggests that women in this age group use TCM more than their younger counterparts. However, the reason for the higher TCM use among Bangladeshi women of reproductive age is yet to be explored—the current study aimed to understand the use of TCM among Bangladeshi women aged 35 years. Methods This qualitative study employed purposive sampling from the Khulna district to conduct ten in-depth interviews with women aged 35–49 years and seven key informant interviews with family planning service providers. A socio-ecological model was adopted for this study. Data were collected in January 2024. The interviews were audio-recorded and transcribed verbatim. Thematic data analysis was performed. Results At the individual level, women’s poor knowledge and fear of the side effects of modern contraceptive methods, perceptions related to the effectiveness, risks, and benefits, ease of use, and cost shaped the use of TCM. Interpersonal factors included the influence of spouses, mothers-in-law, and peer groups on the women. Community norms and beliefs are also pivotal in this regard. Institutional factors include providers’ attitudes, health facility-related issues such as distance from the house, waiting in queues, unavailability of products, and policy-level influences, such as the lack of an updated policy that promotes TCM use among older women of reproductive age in Bangladesh. Conclusion The complex interplay of various factors shapes the use of TCM in Bangladesh. Therefore, comprehensive reproductive health education programs should be considered to enable women to make informed choices about contraceptive use and switch from traditional to modern contraceptive methods, such as long-acting methods. This will ultimately lead to improved reproductive health outcomes.

Controlling rotational air lasing lineshape by carrier-envelope offset phase

Health effects of street vended fresh cut fruits: A randomized controlled trial in Bangladesh

Foodborne infections, particularly from street-vended fresh-cut fruits, are a growing public health concern in urban settings of developing countries. This study evaluated the gastrointestinal effects of consuming street-vended fruits in a randomized controlled trial (RCT) in Mymensingh, Bangladesh. A total of 300 participants were recruited and randomized into Treatment (n = 150) and Control (n = 150) groups. Treatment participants consumed guava, pineapple, or watermelon purchased from street vendors, while Control participants avoided street-vended fruits. Microbial analysis of fruits included total viable count (TVC), S. aureus , and E. coli . Participants recorded GI symptoms for 4 days post-intervention, with a 10-day follow-up. At least one GI symptom occurred in 41 (27.3%) treatment participants compared with 15 (10%) controls. Nausea affected 20 (13.3%) versus 2 (1.3%) participants (RR = 10, 95% CI: 2.38–42.03, p < 0.001), abdominal cramps 13 (8.7%) versus 0 (0%) participants (p < 0.001), and diarrhea 7 (4.7%) versus 0 (0%) participants (p = 0.02). Cox modeling indicated a markedly higher hazard of symptom development in the Treatment group (HR = 162.68, 95% CI: 21.53–1229.43, p < 0.001), while higher hygienic practice scores modestly reduced risk (HR = 0.90, 95% CI: 0.82–0.99, p = 0.028). Higher total viable counts (TVC 5.78–5.86 log CFU/ml) were strongly associated with weakness (r = 0.66, p < 0.001, OR=11.28), abdominal cramps (r = 0.56, p < 0.001, OR=6.16), and diarrhea (r = 0.51, p < 0.001, OR=6.73). E. coli (6–10% prevalence) showed the strongest correlations with abdominal cramps, weakness, and diarrhea (ρ = 0.69–0.78, p < 0.001), whereas S. aureus (20–34%) correlated primarily with weakness and abdominal cramps (ρ = 0.44–0.47, p < 0.001). Abdominal cramps, weakness, and diarrhea demonstrated the highest sensitivity to microbial contamination (AUC = 0.801–0.908). These findings provide robust evidence that consumption of street-vended fresh-cut fruits is associated with a significant increase in GI symptoms linked to microbial contamination, supporting behavioral interventions, such as consumer awareness and improved hygiene practices, and informing policy measures to enhance food safety and protect public health.

Mining extreme properties from a large metamaterial database

Bone weathering in a Mediterranean climate region: An experimental case study from Doñana National Park (Spain)

Bone weathering constitutes a highly informative and commonly studied variable in taphonomic analyses. Vertebrate paleontologists, zoo-archeologists and forensic anthropologists have used weathering as a taphonomic clock to ascertain the exposure time of a bone assemblage before burial. Given that climatic conditions largely govern the weathering process, it is essential to investigate the effects of weathering across various climatic settings. This study analyzes the bone weathering process at Doñana National Park (Spain), a Mediterranean climate area. In 2018, we set an experiment in which four bones, three tibias and one skull, belonging to the main ungulates from Doñana (red deer, fallow deer, horse and wild boar) were placed in an enclosure and exposed to the natural environmental conditions. We present here results after almost 6 years of exposure. Over the study period, the most exposed area of the bones reached weathering stages 1 and 2, an intermediate progression between semi-arid tropical savannas, where weathering stages were initially described, and temperate and colder climates. By the final observation, the tibia of the horse, the heaviest taxon in our study, only has reached weathering stage 1, so our study agrees with previous studies in that the rate of weathering differs across body size, being slower in larger animals. The skull of Sus scrofa stands out for exhibiting modifications that differ from those observed in the tibias, probably due to the different structural anatomy of this bone. We have characterized the local meteorological conditions throughout the experiment and the soil composition as they might play a role in the weathering progression. This research constitutes a first attempt to calibrate the weathering scale in a Mediterranean climatic context, a setting that contains abundant and important fossil assemblages but that lacks bone weathering calibration.

Reply to: Is apparent optimum soil moisture equivalent to field capacity?

Reliable evaluation for the AI-enabled intrusion detection system from data perspective

As the primary link in cybersecurity, the intrusion detection system (IDS) is of indispensable importance. Many studies have proposed sophisticated artificial intelligence (AI) models to detect intrusion behavior from a large amount of data, yet they have ignored the fact that poor data quality has a direct impact on the performance of IDS. The poor data quality is mainly attributed to the interference and damage, such as data tampering, poisoning, and corruption, which leads to decision-making deviations, triggering a serious trust crisis of model application. This paper proposes a multi-indicator comprehensive evaluation method (MICEM) to ensure the reliability of AI decision-making from data perspective. First, several evaluation indicators are established to analyze the potential risks that intrusion detection data may face from the different dimensions, and specific quantitative methods are provided. Second, a comprehensive evaluation is conducted based on the results of each indicator to determine the quality of the intrusion detection data as a whole, thus guaranteeing the usability and reliability of AI-enabled IDS. Finally, the effectiveness and practicality of the proposed MICEM are fully verified by evaluating the benchmark-CICIDS2017 dataset and the real intrusion detection dataset.

Is apparent optimum soil moisture equivalent to field capacity?

In-Silico discovery of Pediatric Acute-Myeloid-Leukemia (pAML) causing druggable molecular signatures highlighting their pathogenetic processes and therapeutic agents through single-cell RNA-Seq profile analysis

Pediatric acute-myeloid-leukemia (pAML) is an aggressive malignancy and the second most common blood cancer in children. In spite of significant advances in the frontline therapeutic approaches, approximately 50% of pAML patients show poor prognosis and relapse. Though drugs show positive response against the cancer cells initially, however, it becomes resistant in the long run of treatment, requiring the use of alternative drugs. Therefore, this study aimed to discover pAML-causing druggable molecular signatures highlighting their pathogenetic processes and alternative therapeutic agents. To address these issues, at first, we performed an integrated single-cell RNA sequencing (scRNA-seq) profile analysis of two datasets with accession IDs GSE154109 and GSE235923, which revealed 6 pAML-related key cell types (Erythroid cells, GdT-cells, Naive B-cells, Naive CD4 T-cells, Non-Classical Monocytes, and T-regs) and 198 common differentially expressed genes (cDEGs) between pAML and healthy groups. The protein-protein interaction (PPI) analysis yielded top-ranked eight cDEGs (JUN, MDM2, FOS, SOD2, FBXW7, CHD3, MCL1, and MAP2K1) as common key genes (cKGs) across the key cell types. Disease-cKGs enrichment analysis further confirmed the relevance of these genes to pAML and other leukemic diseases. Regulatory network analysis identified top four transcription factors (FOXC1, GATA2, RELA, and TP53) and three microRNAs (hsa-let-7a-5p, hsa-let-7e-5p, hsa-miR-15a-5p) that regulate these cKGs. Gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis results reflected their potential roles in pAML pathogenesis. Pathway perturbation analysis through gene-set enrichment analysis (GSEA) tool identified significantly perturbed pathways, highlighting how they are altered in pAML environment and how the cKGs are linked in the process. Subsequently, three potential therapeutic candidates (IRINOTECAN HYDROCHLORIDE, IMATINIB and IBRUTINIB) were disclosed through an integrative strategy combining molecular docking, drug-likeness, ADME/T, and DFT analyses. Molecular dynamics (MD) simulation studies for the top three drug-target complexes indicated the stability of complexes. Thus, the findings potentially offer valuable insights for pAML pathogenesis and effective therapeutic candidates for pAML patients.

Chiral metal cluster-mediated chirality transfer in light-harvesting nanoribbons for amplified circularly polarized luminescence

Construction of a prognostic prediction model for concurrent radiotherapy in cervical cancer using GEO and TCGA databases with preliminary validation analysis

Introduction Radiotherapy is a primary treatment for intermediate and advanced cervical cancer (CC). Resistance to radiotherapy is a principal reason for treatment failure in synchronous applications, yet the molecular mechanisms remain poorly understood. Identifying reliable prognostic markers to predict and evaluate patient outcomes is essential for advancing therapeutic strategies. This study aims to address this need by developing a prognostic prediction model for concurrent radiotherapy in CC, utilizing both single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data. Methods The research began by screening for co-expressed genes using samples from two GEO datasets (GSE236738 and GSE56363). To pinpoint target genes that exhibit significant co-expression, both univariate and multivariate Cox regression analyses were conducted, facilitating the development of prognostic prediction models. The clinical significance of these models was confirmed through the analysis of 144 CC samples sourced from the TCGA database, utilizing Kaplan-Meier survival curves, ROC curve analyses, and Spearman’s correlation tests to investigate the relationships between gene expression and the levels of immune cell infiltration. IHC assays were conducted to further validate the prognostic potential of the identified target genes in CC patients. Results Prognostic models for four target genes—MPP5, SNX7, LSM12, and GALNT3—showed significant predictive value for the outcomes of CC patients undergoing radiotherapy, as demonstrated using the GSE236738 and GSE56363 datasets. The prognostic efficacy of the model was illustrated through scatter plots and calibration curves. Additionally, the model exhibited significant associations with tumor immune infiltration, immune checkpoints, and chemotherapeutic drug sensitivity. Immunohistochemistry (IHC) on clinical tumor samples confirmed that the protein expression levels of MPP5, SNX7, LSM12, and GALNT3 were distinctively predictive for CC patients. Conclusion The results indicate that MPP5, SNX7, LSM12, and GALNT3 are significantly associated with radiotherapy sensitivity in CC cells. A prognostic risk model based on these genes demonstrated strong predictive capabilities for patient outcomes in radiotherapy, suggesting these genes as effective predictors and potential therapeutic targets for treating CC.

Spinal interneuron population dynamics underlying flexible pattern generation

Optimizing blood alcohol concentration measurement with breath alcohol meter and its preliminary application in evaluating CYP2E1 activity

Background Ethanol metabolism in vivo is primarily mediated by CYP2E1 and alcohol dehydrogenase, with CYP2E1 playing the predominant role at high ethanol concentrations. However, it is a difficult problem to evaluate CYP2E1 activity with ethanol as a probe, especially in rats. Currently, high-performance liquid chromatography (HPLC)-based detection of chlorzoxazone is the standard method for evaluating CYP2E1 activity. Nevertheless, this method is labor-intensive, time-consuming, costly, and unsuitable for real-time on-site or multipoint noninvasive monitoring. Objectives This study aimed to develop and optimize a noninvasive and rapid method for blood alcohol concentration BAC detection in rats. The optimized approach was subsequently applied to preliminarily assess hepatic CYP2E1 activity. Methods Male Sprague-Dawley rats were randomly divided into two groups: the immune-mediated liver injury (hepatitis) group and the control group. Hepatitis rats was induced by tail vein injection of Bacillus Calmette-Guerin and lipopolysaccharide, whereas the control rats received an equivalent volume of normal saline. On day 14 of the experiment, following intragastric administration of 56% (v/v) alcohol (5 mL·kg ⁻ ¹), BAC in both groups was measured using a breath alcohol meter. The BAC-time curve was segmented at 46 mg·dL ⁻ ¹: the upper portion was used to assess CYP2E1 activity, while the lower portion reflected alcohol dehydrogenase activity. Liver tissues were collected from rats and observed for histopathological changes using hematoxylin and eosin staining. To validate the accuracy of breath alcoholmeter, headspace gas chromatography was employed. Additionally, HPLC was used to determine plasma chlorzoxazone metabolism, serving as an independent measure of CYP2E1 activity. Based on these findings, we further investigated the potential of ethanol as a probe substrate for assessing the activity of CYP2E1. Results The pathological findings demonstrated that BCG successfully induced immune liver injury in rats. Comparative analysis using both breath alcohol meter and gas chromatography revealed significantly reduced alcohol metabolism in the immune-mediated liver injury rats relative to the control. The gas chromatographic measurements of BAC confirmed the accuracy and reproducibility of the breath alcohol detection method. Furthermore, HPLC analysis demonstrated a marked reduction in CYP2E1 activity in the liver injury rats compared to control. Conclusion The breath alcohol detection method offers a simple, non-invasive approach that can serve as a viable alternative for assessing hepatic CYP2E1 metabolic activity.

Proteome atlas for mechanistic discovery and risk prediction of diabetic retinopathy

Comparative mortality outcomes in metabolic dysfunction-associated steatotic liver disease and nonalcoholic fatty liver disease subtypes in the United States

Background In 2023, experts from the European and American regions proposed the concepts of steatotic liver disease (SLD) and metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD was proposed as a replacement for nonalcoholic fatty liver disease (NAFLD). We compared the long-term outcomes of patients with MASLD, NAFLD, and various subtypes of SLD. Methods We conducted a retrospective study using the NHANESIII database. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality and cause-specific mortality among patients with subtypes of SLD, MASLD, and NAFLD. Results During a follow-up period of 31 years (median 25 years), the adjusted risks of all-cause death for patients with MASLD was 1.19 (95% CI 1.06–1.34; P  = 0.006) vs . the non-SLD group. There was a moderate level of consistency between MASLD and NAFLD (Cohen’s kappa coefficient of 0.62545). Advanced fibrosis was the most serious risk factor for all-cause mortality in MASLD, and high C-reactive protein concentration was the most serious risk factor for all-cause mortality in NAFLD, followed by type 2 diabetes. Conclusions MASLD is associated with a higher risk of all-cause mortality, and this association is independent of patients’ demographic or metabolic characteristics, despite a relatively small hazard ratio. Our research findings further support that MASLD is a pathological disease related to liver disease itself. Therefore, redefining NAFLD as MASLD may help improve our understanding of predictive factors that increase the risk of death.