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Background/Objectives: Coronary artery disease (CAD) remains the leading cause of mortality worldwide, with South Asia bearing a disproportionately high and rising burden, particularly at younger ages. The present study aimed to investigate genetic variants associated with premature coronary artery disease (PCAD) using whole-genome sequencing (WGS). Methods: WGS was conducted on 12 people (five PCAD cases, seven matched controls) to assess feasibility and methodology for future large-scale research. High-quality genomic DNA was sequenced at a minimum read depth of 10× with a quality threshold of Q30. Variant calling with stringent quality control identified single-nucleotide polymorphisms (SNPs), followed by annotation against gnomAD for allele frequencies and ClinVar for pathogenicity. Protein-coding variants were filtered, and candidate genes were prioritized for comparative analysis between cases and controls. Results: An average of over 8.8 million SNPs per individual was identified, with comparable overall variant distributions between cases and controls. Initial analyses revealed 120 SNPs exclusively present in PCAD cases. All protein-coding variants were rare (allele frequency < 0.0001), and none were previously classified as pathogenic in ClinVar. After filtration, 87 candidate genes were prioritized. Enriched or unique variants in PCAD cases are mapped to genes involved in lipid metabolism, endothelial dysfunction, inflammatory signaling, immune regulation, thrombosis, vascular remodeling, and metabolic processes. Additional variants were identified in genes related to smooth muscle proliferation, oxidative stress, and other biological pathways. Conclusions: This WGS pilot study provides an initial overview of the genomic landscape of PCAD in a South Asian cohort, highlighting rare variants across multiple biological pathways implicated in atherosclerosis that need validation in a large-scale study.

Cardiovascular disease (CVD) contributes to morbidity and mortality in people with HIV (PWH) receiving antiretroviral therapy (ART). In the REPRIEVE trial, pitavastatin reduced atherosclerotic CVD risk to a magnitude inconsistent with pitavastatin’s impact solely on LDL cholesterol and inflammation. Here, atorvastatin and ART used in REPRIEVE, including tenofovir, emtricitabine, and dolutegravir, ritonavir and darunavir were examined in 2 mouse models: transgenic HIV-Tg26 mice and HIV-PDX mice engrafted with T cells from PWH. HIV-Tg26 and HIV-PDX mice had higher cardiac fibrosis than littermate controls without HIV. Administration of tenofovir, emtricitabine, and dolutegravir or ritonavir, but not darunavir, resulted in an approximately 2-fold increase in fibrosis. Mice depleted of platelet TGF-β1 or treated with atorvastatin were partially protected from HIV- and ART-induced cardiac fibrosis, steatosis, and diastolic dysfunction. Atorvastatin’s effects were independent of changes in inflammatory cytokines, which correlated with reduced platelet activation and TGF-β signaling in cardiac endothelial cells, fibroblasts, and macrophages undergoing mesenchymal transition. Our results indicate that certain ART regimens accelerate HIV-associated CVD characterized by heart failure with preserved ejection fraction via platelet TGF-β1–dependent processes, which were mitigated by atorvastatin. Our findings provide a potential mechanism for the pleiotropic effects of statins in HIV/ART-linked CVD, which could be targeted by antiplatelet agents or inhibition of TGF-β signaling.

Background/ObjectiveVascular smooth muscle cell (VSMC) proliferation and migration play a pronounced role in the pathophysiology of atherosclerosis and neointima formation. microRNAs are short, single stranded, non-coding 22 nucleotide RNAs involved in post transcriptional gene silencing. Increasing evidence has suggested an important role of miRNAs in regulating VSMC functions. However, little is known about the functional involvements of miR-214 in VSMC proliferation/migration and vessel injury-induced neointima formation. In the current study, we aimed to study the functional importance of miR-214 and its target genes in VSMC proliferation, migration and neointima SMC hyperplasia.Methods and ResultsmiR-214 expression was closely associated with VSMC phenotypic modulation in response to different pathological stimuli. miR-214 over-expression in serum-starved VSMCs significantly decreased VSMC proliferation and migration, while knockdown of miR-214 dramatically increased VSMC proliferation and migration, respectively. Proteomic analyses pinpointed that NCK-associated protein 1 (NCKAP1), a major component of the WAVE complex that regulates lamellipodia formation and cell motility, was negatively regulated by miR-214 in VSMCs. NCKAP1 has also been predicted as one of the top targets of miR-214 by using several computational miRNA target prediction tools, and was indeed negatively regulated by miR-214 in VSMCs. Luciferase assay showed miR-214 substantially repressed wild type, but not the miR-214 binding site mutated version of NCKAP1–3’-UTR-luciferase activity in VSMCs, confirming the NCKAP1 is the functional target of miR-214 in VSMCs. Data from co-transfection experiments also revealed that inhibition of NCKAP1 is required for miR-214-mediated lamellipodia formation and cell motility. Importantly, locally enforced expression of miR-214 in the injured vessels significantly reduced NCKAP1 expression levels, inhibited VSMC proliferation, and prevented neointima SMC hyperplasia after injury.Conclusions/implicationsWe have uncovered an important role of miR-214 in modulating VSMC functions and neointima  hyperplasia. Our findings have suggested that miR-214 represents a potential therapeutic target for vascular diseases.

Premature coronary artery disease (PCAD) is a growing public health concern, especially in South Asia, where traditional risk factors fail to fully explain the increasing incidence of early-onset myocardial infarction. To explore its molecular underpinnings, we conducted a pilot study analyzing plasma proteins and lipids to identify potential biomarkers and dysregulated pathways associated with PCAD. Label-free quantitative proteomics revealed distinct molecular signatures separating PCAD patients from age- and sex-matched healthy controls. Key alterations included upregulation of GALE, immunoglobulin genes, and KIF20B, suggesting enhanced inflammatory responses and proliferative activity associated with post-myocardial infarction cellular repair. Similarly, down regulations of various proteins linked to multiple functions, such as myocardial infarction, hemoglobinopathy, complement and coagulation cascade, and fatty acid and lipoprotein transport in hepatocytes, were observed. Untargeted lipidomics further revealed significant elevations in several phosphatidylcholine species (PC 42:5, PC 40:3, and PC 42:7), highlighting disruption of highly unsaturated phospholipid metabolism. Overall, these findings indicate that PCAD is a multifactorial disorder involving metabolic, immune, and vascular dysfunction beyond conventional lipid abnormalities, underscoring the need for larger cohort studies to validate these biomarkers and uncover novel therapeutic targets.

The proliferation of sophisticated generative AI models has significantly escalated the threat of synthetic manipulations in identity documents, particularly through face swapping and text inpainting attacks. This paper presents TwoHead-SwinFPN, a unified deep learning architecture that simultaneously performs binary classification and precise localization of manipulated regions in ID documents. Our approach integrates a Swin Transformer backbone with Feature Pyramid Network (FPN) and UNet-style decoder, enhanced with Convolutional Block Attention Module (CBAM) for improved feature representation. The model employs a dual-head architecture for joint optimization of detection and segmentation tasks, utilizing uncertainty-weighted multi-task learning. Extensive experiments on the FantasyIDiap dataset demonstrate superior performance with 84.31\\% accuracy, 90.78\\% AUC for classification, and 57.24\\% mean Dice score for localization. The proposed method achieves an F1-score of 88.61\\% for binary classification while maintaining computational efficiency suitable for real-world deployment through FastAPI implementation. Our comprehensive evaluation includes ablation studies, cross-device generalization analysis, and detailed performance assessment across 10 languages and 3 acquisition devices.

Cardiovascular disease (CVD) both atherosclerosis-related and heart failure with preserved ejection fraction (HFpEF) and linked to cardiac fibrosis, contributes to morbidity and mortality in people with HIV (PWH) receiving antiretroviral therapy (ART). In the REPRIEVE trial, pitavastatin reduced atherosclerotic CVD risk to a magnitude inconsistent with pitavastatin’s impact solely on LDL-cholesterol and inflammation. We hypothesized that HFpEF in PWH relates to HIV-induced fibrosis mediated by platelet TGFβ1, that it is accelerated by certain contemporary ART, and may also be inhibited by statins. ART drugs used in REPRIEVE, including a nucleoside/nucleotide, integrase inhibitor-based regimen (tenofovir (TDF), emtricitabine (FTC), and dolutegravir (DTG)), and the protease inhibitors ritonavir (RTV) and darunavir (DRV), and the impact of atorvastatin, were examined in two HIV mouse models: transgenic Tg26 mice and HIV-PDX mice engrafted with HIV-infected T cells. Tg26 and HIV-PDX mice had higher cardiac fibrosis than littermate controls without HIV (p<0.05). Administration of TDF-FTC-DTG or RTV, but not DRV, resulted in a further ∼2-fold increase in fibrosis (p<0.01). Higher cardiac fibrosis with intracardiac fat accumulation correlated with reduced diastolic function. Mice depleted of platelet TGFβ1 (TGFβ1Platelet-ΔTg26), or treated with atorvastatin, were partially protected from HIV- and ART-induced cardiac fibrosis, steatosis, and diastolic dysfunction. Atorvastatin effects occurred independently of changes in inflammatory cytokines and total cholesterol. They correlated with reduced platelet activation and TGFβ1 signaling in cardiac endothelial cells, fibroblasts, and macrophages undergoing mesenchymal transition. These results indicate that certain ART regimens accelerate HIV-associated CVD characterized by HFpEF via platelet TGFβ1-dependent processes and mitigated by atorvastatin. They enhance understanding of the pleiotropic effects of statins in HIV/ART CVD and suggest a mechanism that might be targeted by antiplatelet agents or inhibition of TGFβ signaling. Contemporary ART regimens induce release of platelet TGFβ1 and are associated with cardiac fibrosis and diastolic dysfunction with ectopic fat deposition in HIV-infected mice. Depleting platelet TGFβ1 and/or treating with atorvastatin therapy suppresses HIV-ART-induced cardiac fibrosis, suggesting use of anti-platelet strategies to prevent heart failure among PWH.

This paper presents an analytical mode-matching framework to examine acoustic wave propagation in a cylindrical waveguide structure featuring a central porous cavity bounded by flexible membrane discs. Unlike conventional models that consider rigid or purely absorptive boundaries, the proposed approach accounts for the dynamic response of membranes and the coupled behavior of air and porous media, enabling accurate representation of fluid–structure interactions. The acoustic field is decomposed into symmetric and anti-symmetric modal components to capture key physical phenomena such as mode conversion, energy dissipation, and complex reflection–transmission mechanisms. Continuity conditions at the interfaces are applied to determine the interaction of wave modes between subdomains, allowing the calculation of reflected, transmitted, and absorbed acoustic powers. Numerical results demonstrate strong reflection and efficient low-frequency absorption, with negligible transmission. Parametric analysis reveals that increasing the length of the porous cavity enhances sound attenuation by intensifying dissipative effects. These findings highlight the effectiveness of the multilayered configuration as a frequency-selective acoustic filter, offering a tunable and practical solution for silencers and noise control in engineering structures.

In this paper, we propose two different control strategies for the position control of the ball of the ball and beam system (BBS). The first control strategy uses the proportional integral derivative-second derivative with a proportional integrator PIDD 2 -PI. The second control strategy uses the tilt integral derivative with filter (TID-F). The designed controllers employ two distinct metaheuristic computation techniques: grey wolf optimization (GWO) and whale optimization algorithm (WOA) for the parameter tuning. We evaluated the dynamic and steady-state performance of the proposed control strategies using four performance indices. In addition, to analyze the robustness of proposed control strategies, a comprehensive comparison has been performed with a variety of controllers, including tilt integral-derivative (TID), fractional order proportional integral derivative (FOPID), integral–proportional derivative (I-PD), proportional integral-derivative (PI-D), and proportional integral proportional derivative (PI-PD). By comparing different test cases, including the variation in the parameters of the BBS with disturbance, we examine step response, set point tracking, disturbance rejection analysis, and robustness of proposed control strategies. The comprehensive comparison of results shows that WOA-PIDD 2 -PI-ISE and GWO-TID-F- ISE perform superior. Moreover, the proposed control strategies yield oscillation-free, stable, and quick response, which confirms the robustness of the proposed control strategies to the disturbance, parameter variation of BBS, and tracking performance. The practical implementation of the proposed controllers can be in the field of under actuated mechanical systems (UMS), robotics and industrial automation. The proposed control strategies are successfully tested in MATLAB simulation.

Polycyclic aromatic compounds (PACs) are pervasive environmental contaminants derived from diverse sources including pyrogenic (e.g., combustion processes), petrogenic (e.g., crude oil), and biological origins. They are commonly found in gasoline, coal, and crude oil, reflecting their prevalence and varied origins in natural and anthropogenic activities. The aim of this study is to use Bacillus tropicus which is a spore-forming, gram-positive and facultative anaerobic bacteria, containing a gene for PACs degradtion. In this study bacterial sample was collected from women’s vaginal discharge through streaking and spreading techniques. The DNA was extracted from bacterial culture and then the bacterium was identified through 16S rRNA which appeared to be B.tropicus . Then the computational analysis was conducted where the sequence similarity and functional analysis of alcohol dehydrogenase EutG protein from B.tropicus was analyzed through PSI-BLAT and SMART tool, respectively. The PSI-BLAST showed 100% query coverage score and 9 domains of alcohol dehydrogenase EutG protein were predicted through SMART tool. The quality of the protein was also assessed through ProQ server with a predicted LQ score of 8.091, a Maxsub score of − 0.350 and a z score of − 10.76. Then the phylogentic analysis was conducted to know the evolutionary relationship and closely related taxa. The 3D structure of the protein was predicted through SWISS MODEL and its quality was predicted through ERRAT with overall qauality factor of 98.708. The Ramachandran plot also predicted its quality and showed that 93.8% residues were in the most favored region. After this, 3D stucture of PACs were obtained from PubChem and molecular docking of the protein was performed with each of the compound. The lowest energy of − 10.3 was obtained with Indeno[1,2,3-cd] pyrene and the best docked complex was visulaized through discover studio to analyze its binding residues. Lastly, in-silico site-directed mutagenesis studies were performed which showed that the EutG gene (codes for alcoholic dehydrogenase) obtained from B. tropicus, will not get altered or have any decreasing effect on the enzyme’s stability if it goes through any mutations. This suggests that B. tropicus can act as an efficient, non-virulent, and reliable candidate for the eco-friendly and cost-effective bioremediation of PACs.

Cadmium (Cd 2+ ) contamination in aquatic systems poses serious environmental and public health risks, necessitating sustainable and easily recoverable adsorbents. In this study, cellulose was extracted from Cedrus deodara sawdust and magnetically modified through Fe 2+ /Fe 3+ co-precipitation to synthesize a magnetic cellulose adsorbent for Cd 2+ removal from aqueous solutions. The materials were characterized using Fourier transform infrared spectroscopy, X-ray diffraction, dynamic light scattering, scanning electron microscopy, energy-dispersive spectroscopy, and nuclear magnetic resonance to confirm cellulose structure, iron oxide incorporation, particle size and stability, surface morphology, elemental composition, and purity. Batch adsorption experiments assessed the effects of contact time, initial Cd 2+ concentration, pH, adsorbent dose, and temperature, while residual Cd 2+ concentrations were determined by atomic absorption spectrophotometry (AAS). Adsorption capacity increased with contact time and initial Cd 2+ concentration, reaching 488.9 mg g −1 after 60 min at 100 mg L −1 . At higher concentrations (up to 120 mg L −1 ), calculated capacities increased based on mass-balance relationships under the applied conditions. Cd(II) adsorption was favored under alkaline pH and elevated temperatures. Recyclability tests demonstrated stable performance over three cycles with 89% Cd(II) removal. Kinetic data were best described by pseudo-first-order and Ritchie second-order models (R 2  > 0.99), suggesting diffusion-controlled uptake followed by surface interactions. Equilibrium data fitted the Redlich–Peterson isotherm better than the Langmuir model, indicating heterogeneous surface energies and possible multilayer adsorption. Overall, magnetically modified sawdust-derived cellulose shows promising laboratory-scale performance for Cd 2+ removal, warranting further evaluation in complex wastewater systems.