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Bioinformatics analysis of regulatory relationships between long non-coding RNA genes and transcription factor coding genes
Abstract Long non-coding RNAs (lncRNAs) are increasingly recognized as important regulators of gene expression, yet their interactions with transcription factors (TFs) remain poorly understood. While previous studies have identified lncRNA-TF associations in specific biological contexts, a broader perspective on their evolutionary and functional relationships remains necessary. In this study, we systematically analyze the proximity and co-expression patterns of lncRNAs and TF-encoding genes in humans. We reveal consistent spatial associations and tissue-specific co-expression between lncRNAs and TFs using genome-wide annotations and transcriptomic data. Time-series analysis reveals interesting, but not definitive, dynamic correlations suggesting potential functional interactions. Additionally, our evolutionary analysis identified conserved pairs across species, particularly those related to developmental processes such as eye development, highlighting possible avenues for further investigation in evolutionary and developmental contexts. In summary, our findings provide new insights into the spatial and co-expression associations between lncRNAs and TF genes, and suggest directions for future research on the potential roles of lncRNAs in gene regulatory networks.
Evaluation of Curcuma Radix’s protective effects on diabetic retinopathy based on network pharmacology and experimental validation
Abstract The potential protective effects of Curcuma Radix on diabetic retinopathy were investigated through network pharmacology, molecular docking, and cellular experiments. Network pharmacology results identified four primary active ingredients and twenty key target molecules; Protein-protein interaction network analysis revealed that the core targets regulated by Curcuma Radix in DR include AKT2, RAF1, IL6, IRS1 and IGF1R. KEGG enrichment analysis indicated that Curcuma Radix may improve DR through the HIF-1 signaling pathway, FOXO signaling pathway, and VEGF signaling pathway. Molecular docking results indicated that curcumin, demethoxycurcumin, bisdemethoxycurcumin, and naringenin exhibited favorable docking activities with the core targets AKT2, RAF1, MAPK14, IL6, IRS1 and IGF1R.The ARPE-19 cell experiment results indicated that the four active ingredients could enhance cell viability and mitigate oxidative damage. They exhibited significant gene expression regulation effects on AKT2, RAF1, MAPK14, IL6, IRS1 and IGF1R, which were consistent with the molecular docking outcomes.Through the HUVEC endothelial cell model, the protective effects of the two compounds on the cellular barrier were validated. Demethoxycurcumin and bisdemethoxycurcumin demonstrated protective effects on endothelial cells by modulating ICAM-1 and VCAM-1 to improve barrier damage.This study preliminarily revealed, through network pharmacology and experimental validation that four active components in Curcuma Radix modulated high-glucose-induced ARPE-19 cell models by regulating the gene expression of AKT2, RAF1, MAPK14, IL6, IRS1 and IGF1R. Two of these components also mitigated thrombin-induced endothelial cell barrier damage in the HUVEC cell model by regulating VCAM-1 and ICAM-1 expression, thereby providing protection against DR. This study provides a theoretical foundation for investigating the pharmacological basis and mechanisms underlying these effects.
Artificial intelligent modelling of uniaxial compression strength of rock using machine learning algorithms
Not all West Nile virus lineages behave alike: dose-response differences between lineages 1 and 2
Abstract The globally distributed arbovirus West Nile virus (WNV) is expanding across Europe, with rising numbers of human cases and an increasingly broad geographic distribution. Transmitted primarily by Culex mosquitoes, WNV lineages 1 and 2 are pathogenic to humans, yet their differences in transmission dynamics remain unclear. As vertebrate hosts develop varying viremia, mosquitoes encounter a wide range of viral doses, which may influence transmission. Here, we investigated the dose-response differences between the lineages in Cx. pipiens biotype pipiens , Cx. torrentium , and Aedes albopictus . Mosquitoes were fed increasing titers of one strain of either WNV lineage, and infection and transmission were assessed after 14 days at 24 °C. Lineage 2 required lower infectious doses while causing higher transmission. Notably, Cx. torrentium was identified as a highly competent vector for lineage 2. These findings highlight important differences between WNV lineages, improve our understanding of dose-dependent transmission, and therefore support refined risk assessments in Europe.
Change in physical activity after ischemic stroke and risk of new vascular event or death: registry-based long-term follow-up
Abstract Physical activity (PA) is linked to reduced cardiovascular risk. This study investigated whether changes in PA, or lack thereof, after stroke influence long-term cardiovascular risk. The study included 498 first-ever ischemic stroke patients, with PA assessed pre-stroke and 6 months post-stroke via questionnaire. The primary outcome was a composite of new cardiovascular events or death, determined through register-based follow-up. Participants were categorized into PA change groups: consistently above the lowest quartile (reference), decreasing to the lowest quartile, increasing from the lowest quartile, and consistently in the lowest quartile. Cox proportional-hazards models were adjusted for demographics, clinical data, socioeconomic factors, quality-of-life measures, and functional status. The median age was 68 years (interquartile range 58–76), with 35% female. Median follow-up was 6.8 years (interquartile range 5.7–7.6), during which 156 events occurred. Adjusted hazard ratios for cardiovascular events or death were 1.71 (95% CI 0.96–3.06) for decreased PA, 1.75 (95% CI 0.99–3.10) for increased PA, and 2.56 (95% CI 1.37–4.78) for consistently low PA, compared to the reference group. Persistently low PA after stroke was associated with the highest risk of new events, even after adjusting for functional status and stroke severity.
Exonisation of an Alu element in the 3’-UTR contributes to SRD5A2 deficiency
Abstract Steroid 5α-reductase deficiency is a rare autosomal recessive condition caused by mutations in the SRD5A2 gene that leads to a severe virilisation deficit of the external genitalia in individuals with a 46,XY karyotype. Here we report an adult 46,XY person with clinically confirmed steroid 5α-reductase deficiency. Sanger sequencing revealed a compound heterozygous, maternal, pathogenic c.692A > G; p.(His231Arg) variant and a very rare paternal c.*66T > G variant in the 3’-UTR. RT-PCR products of individual’s derived genital skin fibroblasts revealed that only the maternal variant is expressed while the paternal variant could not be detected. PacBio RNA Isosequencing revealed that the variant c.*66T > G introduces a new strong splice donor site 66 nt after the canonical stop codon that is spliced to an inverted Alu sequence located 15 kb downstream. In all paternal, but none of the maternal transcripts, we found a new exon junction 66 nt after the stop codon within the 3’-UTR. Mammalian transcripts with an intron excision site > 55 nt downstream from a termination codon are subject to degradation by the nonsense-mediated decay (NMD) pathway. We conclude that the pathogenic maternal variant, together with the NMD-triggered downregulation of the paternal allele, is causative for the observed SRD5A2 deficiency.
A novel approach to breast cancer detection using modified logistic regression with optimized feature selection
Abstract The World Health Organization (WHO) reports 2.3 million new cases and 670,000 fatalities annually, and breast cancer remains one of the most prevalent and life-threatening diseases on a global scale. These poor outcomes highlight the critical need for new diagnostic techniques that can identify breast cancer in its early stages, allowing for early detection and increasing survival rates. Traditional screening methods, such as mammography, are frequently restricted by their high false-positive rates, despite the fact that early and precise diagnosis is essential for enhancing survival rates. To enhance diagnostic accuracy, we recommend a Modified Logistic Regression (MLR) model that employs different activation functions (sigmoid and modified $$\tanh$$ ). In addition, we employed feature selection techniques to reduce redundancy and eradicate highly correlated features in the Wisconsin Diagnostic Breast Cancer (WDBC) dataset and Wisconsin breast cancer (WBC) dataset. The proposed MLR model was compared using standard machine learning algorithms, including Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), Decision Tree (DT), K-Nearest Neighbors (KNN), XGBoost, LightGBM, CatBoost and these models are integrated into a soft voting classifier (SVC) technique to enhance predictive accuracy. All machine learning models in this study were implemented using the scikit-learn library, except for the modified logistic regression model, which was manually coded without using the LogisticRegression class from sklearn. Each model’s performance is individually evaluated and then compared against MLR. The proposed MLR attains an accuracy that is competitive with the strongest baselines (98.25% on WDBC and 97.81% on WBC); a paired McNemar’s test confirms that this accuracy is statistically on par with standard logistic regression rather than significantly superior. The distinctive benefits of MLR lie elsewhere: it produces better-calibrated probability estimates (consistently lower Brier scores than logistic regression and far below the no-skill prevalence baseline), a lower false-negative rate, and more compact feature attributions with consistent ranking, within a flexible architecture that admits any differentiable activation. We further show analytically that the modified $$\tanh$$ used by MLR is equivalent to a logistic sigmoid evaluated at twice the logit, $$\tfrac{1+\tanh (z)}{2}=\sigma (2z)$$ , so the training objective remains convex in the effective logits and the learnable bias weight introduces no spurious minima. These results position MLR as a reliable, well-calibrated instrument for supporting early breast cancer diagnosis.
Dietary DNA in municipal wastewater reveals signatures of wealth, immigration, and coastal proximity
Public health nutrition lacks scalable, objective tools for real-time dietary surveillance. We developed FoodSeq-FLOW (Food Landscape Observation in Wastewater), a genomic platform that sequences chloroplast trnL and mitochondrial 12SV5 DNA in municipal wastewater. Across 183 samples from 21 North Carolina wastewater treatment plants serving 2.1 million people, we detected 184 plant and 116 animal food taxa at a cost of <US $0.01 per person. Wastewater-derived dietary profiles correlated with paired individual stool dietary data (Spearman ρ = 0.64), and 98% of animal-derived sequences mapped to known food taxa. Temporal sampling revealed seasonal shifts in food taxa consistent with regional food availability patterns. Spatial analysis revealed community-level dietary signatures associated with per capita income and education, beer ingredient abundance with discretionary income, tropical fruits and pulses with foreign-born population size, and local seafood with coastal geography. FoodSeq-FLOW extends wastewater-based epidemiology from pathogens to diet, providing a scalable platform that existing global wastewater surveillance networks can deploy to inform nutrition policy and market analytics.
Design and evaluation of a tendon-and-linkage hybrid-driven humanoid dexterous hand
Integrated DNA- and RNA-based characterization of microbial and resistome communities in a hotel lobby
Innovative assessment of meteorological drought in northern Algeria using the NIFT index
A class-wise quantum relational calibration network for brain tumor diagnosis
Synthesis and computational evaluation of novel indazole-based benzamide derivatives as anti-tubercular agents via DFT, molecular docking studies
Multimodal neural-regulation profiling and task-state recognition of sport-related attention in relation to athletic performance
The role of group attachment security in minority opinion expression in decision making groups
Abstract Minority opinions often generate crucial ideas and knowledge, but it is more challenging to be a minority opinion holder in an ingroup (disagreeing with members of one’s own group) than in an outgroup (disagreeing with members of other groups). This paper extends the group decision-making, knowledge sharing, and minority influence literatures by exploring a psychological condition under which ingroup minority opinion holders can be influential in diverse decision-making groups. Across two experiments, activating group attachment security (vs. neutral condition) increased minority opinion holders’ task focus and the persuasiveness of their expressed dissenting opinions (Study 1), and increased majority members’ willingness to use that dissent while these authentic texts also differed in argument quality (Study 2). Although the predicted omnibus attachment-by-social-category (secure vs. neutral × ingroup vs. outgroup) interactions were generally non-significant, exploratory simple-effects comparisons suggested these effects were more notable among ingroup minorities. These findings suggest that group attachment security can help minority opinion holders be influential in decision-making groups that represent diverse social categories.
Multidrug-resistant and virulence traits in genetically distinct vesicular Leptospira inhabiting farmland and sewage in Southern India
Correction: Reimbursement restrictions reduce liver fibrosis screening in adults with diabetes in Ontario: a population-based interrupted time series analysis
Subjective experience and social support predict exercise persistence in university students via perceived usefulness and behavioral control
Enhanced differentiation potential of pigmented human epidermal equivalents
Abstract Melanocyte-keratinocyte interactions are vital for regulating melanogenesis and maintaining epidermal homeostasis. However, most 3D human skin equivalents lack melanocytes, limiting their relevance for pigmentation studies. To address this, we utilized a pigmented human epidermal equivalent (PmtHEE) that incorporates melanocytes into the epidermis. Using single-cell RNA sequencing (scRNA-seq), we characterized PmtHEE and compared it with neonatal foreskin epidermis (FsEpi) and a fibroblast-containing human skin equivalent model (FibHSE). PmtHEE showed a higher proportion of differentiated cells and model-specific cell state transition paths that reflect possible in vivo trajectories. We further uncovered an inferred L1CAM-EZR-driven external signaling network using exSigNet in FsEpi and PmtHEE that may influence keratinocyte differentiation. Altogether, PmtHEE provides a distinct and physiologically relevant model of pigmented skin, with likely enhanced differentiation potential compared to conventional in vitro systems.