Browse Articles

Integrative computational analysis of plant-derived flavonoids as inhibitors of Listeriolysin O and Internalin A in Listeria monocytogenes

Foodborne pathogen Listeria monocytogenes causes listeriosis, a rare but deadly condition. Internalin A ( InlA ) and Listeriolysin O ( LLO ), its main virulence factors, facilitate adhesion, invasion, intracellular survival, and intercellular spreading, making them interesting therapeutic targets. L. monocytogenes infections are becoming harder to treat because of antibiotic resistance; hence, flavonoids are being considered. An integrated in-silico technique was used to test plant-derived flavonoids’ inhibitory efficacy against these proteins. For both targets, three modes of docking (HTVS, SP, and XP docking) were used for the preliminary screening from a library of 1,254 flavonoids. While CIDs 441667, 15126294, and 187808 showed favorable in-silico profiles for InlA with scores of −8.461, −7.578, and −7.521 kcal/mol, respectively, CIDs 441699, 443648, and 442868 showed the best affinity for LLO with values of −7.446, −5.991, and −5.852 kcal/mol, respectively. Admet analysis predicted the drug-likeness and safety characteristics of the compounds. Subsequently, the QM calculation was employed to examine the interaction of these compounds with the receptor, alongside their MEP and NBO characteristics. The selected ligands and the control ampicillin for both proteins were utilized to build protein-ligand complexes, subsequently assessed via a 100 ns molecular dynamics simulation. Subsequent post-simulation MM-GBSA, PCA and DCCM analysis of the trajectories evaluated their dynamic stability concerning InlA and LLO . CIDs 441667 and 15126294 for InlA , as well as CIDs 441699 and 443648 for LLO , have been identified as potential inhibitors, establishing a basis for future in vivo investigations and experimental validation.

A Missed Signal and a Closed Pathway

Association between carbohydrate quality index and cardiovascular disease: Tehran Lipid and Glucose Study

Beyond temperature: Why climate adaptation in agriculture needs a systems approach

Cadmium exposure as a contributing factor to hepato-renal injury in apparently healthy active cigarette smokers in buea-cameroon

Cigarette smoke contains numerous toxicants, including cadmium, polycyclic aromatic hydrocarbons (PAHs), tobacco-specific nitrosamines (TSNAs), and volatile organic compounds, all of which may contribute to hepato-renal injury. This study, conducted in Buea (Southwest Region, Cameroon), aimed to assess cadmium inhalation exposure from cigarette smoking as a contributing factor to altered liver and kidney function biomarkers in apparently healthy smokers, while acknowledging that combined exposure to multiple co-toxicants may potentiate organ dysfunction. A survey was used to recruit smokers and collect data on their smoking habits. Cadmium contents in the major cigarette brands selected were used to estimate the cadmium Daily Exposure (DE), Weekly Inhalational Exposure (WIE) and the percentage contribution to the Tolerable Weekly Intake (TWI) of cadmium. Serum alanine aminotransferase (ALT) activity, urea, creatinine contents, and urinary albuminuria and glucosuria were measured in blood and urine samples from smokers and nonsmokers. The 102 smokers enrolled were categorized respectively as light (37.3%; 38/102), moderate (38.2%; 39/102), and heavy (24.5%; 25/102) smokers, smoking an average number of 4.7 ± 0.5, 9.1 ± 1.5, and 19.1 ± 3.0 cigarettes/day, respectively. Cadmium levels in cigarette brands ranged from 0.72–1.08 µg Cd per gram of tobacco removed from the cigarette. Heavy smokers exceeded the permitted cadmium No Significant Risk Level (NSRL) by up to 28-fold, contributing 4–8% to the cadmium TWI. Serum ALT activity and creatinine content were significantly higher ( P  < 0.05) in smokers groups compared to non-smokers. Also, moderate and heavy smokers were at a significantly higher risk (relative risk 6.90–13.32; P  < 0.05) of displaying abnormal elevated serum urea content, positive albuminuria and glucosuria. Our findings demonstrate that healthy active smokers are highly exposed to cadmium (and potentially to other cigarette toxicants) and are at significantly higher risk of displaying abnormally elevated levels of biochemical markers of liver and kidney function, suggesting early signs of organ damage.

Implications of Cranial Arterial Stenosis and Dolichoectasia for Cerebral Small-Vessel Disease Etiopathogenesis: Findings From a Prospective Mild Stroke Cohort

BACKGROUND: Stenosis and dolichoectasia of cranial arteries likely reflect distinct mechanisms. Their contributions to lacunar stroke and cerebral small-vessel disease (cSVD) remain contentious. We investigated the associations of large-artery stenosis (LAS) and arterial widening with stroke subtype, cSVD markers, incident infarcts, and clinical outcomes. METHODS: We prospectively recruited patients with lacunar or mild nonlacunar stroke, with demographic, stroke-related, cognitive, functional, and magnetic resonance imaging (index and incident infarcts, cSVD markers) assessments at baseline and 1 year. LAS was defined as ≥50% intracranial or cervical artery stenosis; basilar artery dolichoectasia was defined by basilar artery diameter, bifurcation height, and lateral displacement; and intracranial carotid and middle cerebral artery diameters were also measured. Associations were estimated from multivariable logistic, linear, and proportional odds regression models adjusted for age, sex, and vascular risk factors. We further conducted a systematic literature review to synthesize evidence on relationships between large-artery pathology and cSVD. RESULTS: Among 229 patients (mean age, 65.9±11.1 years; 131 [57.2%] lacunar stroke), LAS and basilar artery dolichoectasia were present in 20.5% and 15.7%, respectively. After adjustment, LAS (odds ratio, 0.49 [95% CI, 0.23–0.99]) and the presence of any embolic source were associated with lower odds of lacunar versus non-lacunar stroke, and not with cSVD markers or incident infarcts. In contrast, basilar artery dolichoectasia was strongly associated with lacunar stroke (odds ratio, 4.67 [95% CI, 1.87–13.14]), higher cSVD scores (ordinal analysis; odds ratio, 2.57 [95% CI, 1.28–5.25]), incident infarcts (75% subcortical; odds ratio, 2.29 [95% CI, 1.01–5.14]), and greater progression of white matter hyperintensities over 1 year (β, 0.15 [95% CI, 0.01–0.29] per log 10 -transformed volume). Similar associations were observed for wider intracranial arteries. The systematic review supported these findings. CONCLUSIONS: cSVD, including lacunar stroke, was unrelated to LAS but strongly associated with dolichoectasia and wider arteries. These findings support a nonatheromatous, intrinsic microvascular pathology, particularly segmental arteriolar disorganization, as the principal mechanism of lacunar stroke and cSVD. Mechanism-specific diagnostic and therapeutic strategies are warranted.

Detecting vegetation anomalies in mediterranean ecosystems in southern Italy using sentinel-2 NDVI time series and principal component analysis

Habitat split drives assembly of less protective host microbiomes

Parameter calibration method for car-following models under snowy weather conditions: Integrating an informer time series encoder and physics-informed neural networks

Under snowy weather conditions, factors such as road conditions and weather conditions significantly affect vehicle car-following behavior. Traditional car-following models struggle to accurately capture driving characteristics on slippery roads. To address this, this paper proposes a parameter calibration method for car-following models under snowy conditions, considering factors including road adhesion coefficient and visibility. Five classical car-following models are selected for analysis: the GM model, the Gipps model, the Intelligent Driver Model (IDM), the Wiedemann model, and the Full Velocity Difference Model (FVDM). A systematic analysis is conducted on the key parameters to be calibrated for each model in snowy environments. To overcome the poor adaptability and low accuracy of traditional calibration methods, an adaptive parameter calibration framework combining an Informer time series encoder and a physics-informed neural network is proposed. This method extracts features of snowy environments using the Informer time series encoder and achieves dynamic optimization of model parameters via the physics-informed neural network algorithm, making it applicable to multiple car-following models simultaneously. Validation results based on the NGSIM dataset and real vehicle test data under snowy conditions show that the proposed method improves calibration accuracy by 12.7% under snowy scenarios compared to the traditional genetic algorithm, and exhibits strong generalization capability across different car-following models. This research can provide fundamental models for traffic simulation systems and enhance simulation accuracy.

The Heart’s Cipher, the Muscle’s Prophecy

LightGastroFormer: a lightweight multi-resolution transformer for gastrointestinal disease classification

HLA micropolymorphisms confine neoantigen conformational adaptability and guide T cell receptor selectivity

T cell receptor (TCR) restriction by highly polymorphic major histocompatibility complex (MHC) proteins is a foundation of cellular immunity. Although the effects of MHC polymorphisms on peptide binding and selection are well established, how micropolymorphisms within MHC supertypes impact immune recognition is poorly understood. Here, we identified a mechanism through which the micropolymorphisms in two closely related HLA-A3 superfamily members govern TCR specificity. We previously showed that TCRs specific for a public neoantigen arising from a PIK3CA oncogenic hotspot mutation restricted by HLA-A*03:01 were unable to recognize the same epitope in the context of HLA-A*03:02 despite equivalent processing and presentation by both alleles. We found here that the two micropolymorphisms distinguishing A*03:02 from A*03:01 prevent TCR binding not by altering peptide binding or static structures, but by altering the conformational ensemble of the neoantigen, preventing it from adopting a binding-permissive state. The effect is rooted in how the two polymorphic sites interact with other covarying, evolutionarily coupled polymorphisms, reflecting a cross-groove network of interactions that controls the conformational adaptability of the peptide/HLA complex. We suggest polymorphism-dependent adaptability reflects an evolved feature of class I MHC proteins, further diversifying epitopes and contributing to how TCRs and other immunoreceptors differentiate between antigens. Beyond this mechanistic insight, our findings emphasize the need for high-resolution HLA typing in efforts across immunology, including antigen-specific immunotherapy.

Risk factors for fecal incontinence after surgery for cryptoglandular anal fistula: Protocol of a meta-analytic study

Introduction Fecal incontinence after anal fistula surgery is a feared functional complication that can impair dignity, social participation, and quality of life. Reported rates vary widely across procedures and fistula phenotypes, and individual studies suggest multiple patient-, disease-, and surgery-related predictors. However, the prognostic evidence remains dispersed, with inconsistent outcome definitions and variable adjustment for confounding. This protocol describes a systematic review and quantitative synthesis to identify factors associated with postoperative fecal incontinence after surgery for cryptoglandular anal fistula. Methods and analysis The study will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidance. PubMed, Embase, Cochrane Library, Web of Science, and grey-literature sources will be searched from inception to January 11, 2026, without language restrictions. Eligible studies will be cohort or case-control studies of adults undergoing surgery for cryptoglandular anal fistula that report new-onset or worsening postoperative fecal incontinence using validated scores or clearly defined clinical criteria at least 3 months after surgery. Two reviewers will independently screen records, extract data, and assess risk of bias using the Quality in Prognosis Studies tool and, where applicable, the Newcastle-Ottawa Scale. Adjusted estimates will be prioritized for random-effects meta-analysis when studies are clinically comparable. Heterogeneity and confounding will be explored by fistula complexity, procedure type, follow-up duration, and baseline continence assessment. Certainty of evidence will be rated using a prognostic-factor approach. Discussion By integrating observational evidence across diverse surgical strategies, this review aims to generate pooled, evidence-based prognostic estimates for postoperative fecal incontinence. The findings may support preoperative counseling, baseline continence assessment, individualized procedure selection, sphincter imaging where appropriate, and targeted strategies to reduce preventable functional harm. Ethics and Dissemination No ethical approval is required as this study uses existing data. Results will be disseminated through peer-reviewed journals and conferences to inform anal fistula management. Registration International Prospective Register of Systematic Reviews (CRD420261283433)

Rethinking the Valsalva Maneuver During Resistance Exercise: Why Transmural Pressure Matters

A time-delayed mathematical framework for analyzing pertussis transmission dynamics

Navigating the unknown: Nanobubbles and the hidden complexity of aerophilic surfaces

Comprehensive reconstruction of the musculoskeletal anatomy in the shoulder using a hybrid 3D ultrasound mosaicking workflow: A pilot study

Background Three-dimensional (3D) ultrasound (US) imaging of complex joints such as the shoulder is limited by a small field of view and shallow imaging depth. As a result, capturing the entire shoulder anatomy in a single scan is not feasible. This study evaluates a hybrid 3D US mosaicking workflow that combines probe pose tracking, image-based alignment, and magnetic resonance imaging (MRI) guidance to reconstruct the full shoulder musculoskeletal anatomy. Methods Five healthy volunteers underwent shoulder imaging using a robot-assisted 3D US probe. Each shoulder was divided into five scan regions, yielding approximately 45 partially overlapping US volumes per trial. Volumes were first positioned using probe pose information and then refined using a hybrid alignment strategy that combined semi-automatic US-US registration with expert manual adjustments guided by subject-specific MRI bone models. Reconstruction performance was assessed by measuring alignment consistency of the humerus across overlapping volumes using Dice similarity coefficients and multimodal overlap metrics. Results The hybrid workflow improved reconstruction accuracy by approximately 17% compared to pose estimation alone. The refined reconstructions showed clearer anatomical continuity and fewer alignment artefacts. Reconstruction accuracy was influenced by the amount of overlap between scans and by differences in shoulder position between US and MRI acquisitions. Weighted mean compounding performed best for regional reconstructions with sufficient overlap, while maximum compounding was more effective for whole-shoulder mosaics. Conclusion This study demonstrates the feasibility of reconstructing the full shoulder anatomy using a hybrid 3D US mosaicking approach. The proposed workflow improves alignment accuracy and anatomical visualisation compared with pose estimation alone and provides a practical reference framework for future large-scale and automated, real-time musculoskeletal US reconstruction.

Total Event Analysis in Cardiovascular Outcome Trials: Approaches and Interpretation

Synthesis and characterization of a new N4-Schiff base its zinc halide/pseudohalide complexes with thermal, antimicrobial, antioxidant, anticancer, DNA cleavage and wound healing properties

Synthetic pectin–cellulose nanofiber capsule recapitulates the mechanical properties of a regenerating plant cell wall

Plant primary cell walls are dynamic supramolecular assemblies composed of layered cellulose, hemicellulose, and pectin, progressively built through synthesis and secretion. However, the specific architectural features and structural components sufficient to endow the mechanical properties of the wall remain unclear. Here, we construct a minimal synthetic spherical shell and compare its structural and mechanical properties to those of a plant single-cell system. To eliminate complexities from intercellular connectivity and developmental history, we exploit the ability of plant protoplasts to regenerate cell walls de novo. Compression tests of regenerating protoplasts between parallel plates reveal that wall stiffness increases with wall thickening over time. Despite differences in assembly pathways, architecture, and composition, the synthetic shell exhibits a similar thickness-dependent modulus and similar material stiffness. The synthetic shell, mainly composed of pectin and cellulose nanofibers, mirrors the mechanical behavior of regenerating primary cell walls, suggesting that these components play a major role in conferring key mechanical properties in the limit of compressive small deformations. Extending this comparative approach should allow similarities and differences in component interactions in controlling wall behavior to be identified.