Search Results (2,350)

Background: Familial Mediterranean fever (FMF) is a chronic autoinflammatory disorder characterized by sustained systemic inflammation that may affect cardiac structure and function. Colchicine is the cornerstone of FMF therapy and has cardiovascular benefits in inflammatory settings. Methods: This cross-sectional study enrolled 106 participants: 53 patients with FMF receiving long-term colchicine therapy and 53 age- and sex-matched controls. Participants underwent transthoracic echocardiography with speckle-tracking imaging. Conventional parameters and strain-derived indices of the left ventricular (LV) and left atrial (LA) function were assessed. Correlation analyses and multivariable linear regression models were used to evaluate the association between FMF presence and cardiac strain parameters. Results: The LV ejection fractions were comparable between the groups. The FMF group showed thinner ventricular walls and larger chamber dimensions than the control group. Patients with FMF exhibited higher LA reservoir strain, while conduit and contractile atrial contributions were reduced, as shown by lower passive and active emptying fractions and reduced LA ejection fraction. LA volumes and stiffness indices were lower in the FMF group, indicating smaller and more compliant atrial structures. Left ventricular global longitudinal strain (LVGLS) was more negative in patients with FMF, indicating preserved LV longitudinal systolic function. FMF was independently associated with LVGLS and LA strain parameters after adjusting for cardiovascular risk factors. Conclusions: In patients with FMF receiving long-term colchicine therapy, cardiac strain imaging showed preserved LV longitudinal function and distinct LA mechanics with preserved reservoir strain but reduced conduit and contractile function. Strain echocardiography may provide insights into cardiac involvement in well-controlled FMF, although prospective studies are needed to clarify the clinical significance of these findings. Full article

Background/Objectives: Bacterial biofilms formed by Escherichia coli pose a significant challenge in veterinary medicine due to their intrinsic resistance to antibiotics. Antimicrobial peptides (AMPs) represent a promising alternative. AMPs exert their bactericidal activity by binding to negatively charged phospholipids in bacterial membranes via electrostatic interactions, leading to membrane disruption and rapid cell lysis. Methods: In vitro assays including MIC determination, biofilm eradication testing (crystal violet, colony counts, and CLSM), swimming motility, and EPS quantification were performed. CRISPR/Cas9 was used to construct and complement a kduD mutant. A transposon mutagenesis library was screened for biofilm-defective mutants. In an in vivo murine excisional wound infection model treated with the mouse cathelicidin-related antimicrobial peptide (CRAMP-34), wound closure and bacterial burden were monitored. Gene expression changes were analyzed via RT-qPCR. Results: CRAMP-34 effectively eradicated pre-formed biofilms of a clinically relevant, porcine-origin E. coli strain and promoted wound healing in the murine infection model. We conducted a genome-wide transposon mutagenesis screen, which identified kduD as a critical gene for robust biofilm formation. Functional characterization revealed that kduD deletion drastically impairs flagellar motility and alters exopolysaccharide production, leading to defective biofilm architecture without affecting growth. Notably, the anti-biofilm activity of CRAMP-34 phenocopied aspects of the kduD deletion, including motility inhibition and transcriptional repression of a common set of biofilm-related genes. Conclusions: This research highlights CRAMP-34 as a potent anti-biofilm agent and unveils kduD as a previously unrecognized regulator of E. coli biofilm development, which is also targeted by CRAMP-34. Full article

Chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) increasingly co-occur in low- and middle-income countries and aging populations. Prior pulmonary TB is a robust, smoking-independent determinant of COPD and is linked to persistent systemic inflammation, endothelial dysfunction, dyslipidemia, and hypercoagulability axes that also amplify cardiovascular disease (CVD) risk. We conducted a targeted narrative non-systematic review (2005–2025) of PubMed/MEDLINE, Embase, Scopus, and Web of Science, selecting studies for clinical relevance across epidemiology, clinical phenotypes, pathobiology, biomarkers, risk scores, sleep-disordered breathing, and management. No quantitative synthesis or formal risk-of-bias assessment was performed. Accordingly, findings should be interpreted as a qualitative synthesis rather than pooled estimates. Prior TB is associated with a distinctive COPD phenotype characterized by mixed obstructive–restrictive defects, reduced diffusing capacity (DLCO), radiographic sequelae, and higher exacerbation/hospitalization burden. Mechanistic insights: Convergent mechanisms chronic immune activation, endothelial injury, prothrombotic remodeling, molecular mimicry, and epigenetic reprogramming provide biologic plausibility for excess CVD, venous thromboembolism, and pulmonary hypertension. Multimarker panels spanning inflammation, endothelial injury, myocardial strain/fibrosis, and coagulation offer incremental prognostic value beyond clinical variables. While QRISK4 now includes COPD, it does not explicitly model prior TB or COPD-TB outcomes, but data specific to post-TB cohorts remain limited. Clinical implications: In resource-constrained settings, pragmatic screening, prioritized PAP access, guideline-concordant pharmacotherapy, and task-shifting are feasible adaptations. A history of TB is a clinically meaningful modifier of cardiopulmonary risk in COPD. An integrated, multimodal assessment history, targeted biomarkers, spirometry/lung volumes, DLCO, 6 min walk test, and focused imaging should guide individualized care while TB-aware prediction models and implementation studies are developed and validated in high-burden settings. Full article

Microbial biosurfactants (mBSs) are bioactive molecules with diverse applications, notably as antimicrobial agents against antibiotic-resistant pathogens. Produced by bacteria and yeasts, mBSs are classified as glycolipids, lipopeptides, polymeric, and particulate types. The global rise in multidrug-resistant organisms, such as Escherichia coli, Klebsiella pneumoniae, Salmonella typhimurium, Pseudomonas aeruginosa, and Acinetobacter baumannii, underscores the urgent need for new antimicrobial strategies. mBSs disrupt microbial growth by interacting with the lipid components of pathogens, offering promising alternatives to conventional antibiotics. This review highlights the sources, chemical structures, and properties of mBSs, their antimicrobial activities, synergistic effects with antibiotics, and structure–activity relationships. Special emphasis is placed on surfactant modification, where targeted changes—such as valine substitution in surfactin—significantly lower critical micelle concentrations (CMC) and enhance antimicrobial potency. Such rational engineering demonstrates how biosurfactants can be tailored for improved biomedical performance while minimizing cytotoxicity. In parallel, artificial intelligence (AI) algorithms, including artificial neural networks and genetic algorithms, optimize yields, predict substrate suitability from agricultural residues, and guide microbial strain engineering. AI models can predict interfacial behavior and synchronize fermentation with purification. Advancing the understanding of mBS interactions with microbial membranes, combined with modification strategies and AI-guided optimization, is essential for developing targeted therapies against resistant infections. Future research should integrate these approaches to engineer novel derivatives, reduce costs, and validate clinical potential through comprehensive in vivo studies. Full article

Hot-fluid injection in thermal-enhanced oil recovery (thermal-EOR, TEOR) imposes temperature-driven volumetric strains that can substantially alter in situ stresses, fracture geometry, and wellbore/reservoir integrity, yet existing TEOR modeling has not fully captured coupled thermo-poroelastic (thermo-hydro-mechanical) effects on fracture aperture, fracture-tip behavior, and stress rotation within a displacement discontinuity method (DDM) framework. This study aims to examine the influence of sustained hot-fluid injection on stress redistribution, hydraulic-fracture deformation, and fracture stability in thermal-EOR by accounting for coupled thermal, hydraulic, and mechanical interactions. This study develops a fully coupled thermo-poroelastic DDM formulation in which fracture-surface normal and shear displacement discontinuities, together with fluid and heat influx, act as boundary sources to compute time-dependent stresses, pore pressure, and temperature, while internal fracture fluid flow (Poiseuille-based volume balance), heat transport (conduction–advection with rock exchange), and mixed-mode propagation criteria are included. A representative scenario considers an initially isothermal hydraulic fracture grown to 32 m, followed by 12 months of hot-fluid injection, with temperature contrasts of ΔT = 0–100 °C and reduced pumping rate. Results show that the hydraulic-fracture aperture increases under isothermal and modest heating (ΔT = 25 °C) and remains nearly stable near ΔT = 50 °C, but progressively narrows for ΔT = 75–100 °C despite continued injection, indicating potential injectivity decline driven by thermally induced compressive stresses. Hot injection also tightens fracture tips, restricting unintended propagation, and produces pronounced near-fracture stress amplification and re-orientation: minimum principal stress increases by 6 MPa for ΔT = 50 °C and 10 MPa for ΔT = 100 °C, with principal-stress rotation reaching 70–90° in regions adjacent to the fracture plane and with markedly elevated shear stresses that may promote natural-fracture activation. These findings show that temperature effects can directly influence injectivity, fracture containment, and the risk of unintended fracture or natural-fracture activation, underscoring the importance of temperature-aware geomechanical planning and injection-strategy design in field operations. Incorporating these effects into project design can help operators anticipate injectivity decline, improve fracture containment, and reduce geomechanical uncertainty during long-term hot-fluid injection. Full article

Obesity is among the top contributing factors for non-communicable chronic disease development and has attained menacing global proportions, affecting approximately one of eight adults. Phytochemicals that support energy metabolism and prevent obesity development have been the subject of intense research endeavors over the past several decades. Cycloastragenol is a natural triterpenoid compound and aglycon of astragaloside IV, known for activating telomerase and mitigating cellular aging. Here, we aim to characterize the effect of cycloastragenol on lipid metabolism in a glucose-induced obesity model in Caenorhabditis elegans. We assessed the changes in the body length, width, and area in C. elegans maintained under elevated glucose through automated WormLab system. Lipid accumulation in the presence of either cycloastragenol (100 μM) or orlistat (12 μM), used as a positive anti-obesity control drug, was quantified through Nile Red fluorescent staining. Furthermore, we evaluated the changes in key energy metabolism molecular players in GFP-reporter transgenic strains. Our results revealed that cycloastragenol treatment decreased mean body area and reduced lipid accumulation in the C. elegans glucose-induced model. The mechanistic data indicated that cycloastragenol suppresses the nuclear hormone receptor family member NHR-49 and the delta(9)-fatty-acid desaturase 7 (FAT-7) enzyme, and activates the 5′-AMP-activated protein kinase catalytic subunit alpha-2 (AAK-2) and the protein skinhead 1 (SKN-1) signaling. Collectively, our findings highlight that cycloastragenol reprograms lipid metabolism by down-regulating the insulin-like receptor (daf-2)/phosphatidylinositol 3-kinase (age-1)/NHR-49 signaling while simultaneously enhancing the activity of the AAK-2/NAD-dependent protein deacetylase (SIR-2.1) pathway. The anti-obesogenic potential of cycloastragenol rationalizes further validation in the context of metabolic diseases and obesity management. Full article

Understanding how strain is transferred across the interior of tectonic plates is fundamental to quantifying lithospheric deformation. The Central Anatolia Transition Zone (CATZ), situated between the North and East Anatolian fault systems, provides a unique natural laboratory for investigating how continental deformation evolves from localized faulting to distributed shear. In this study, we integrate InSAR analysis with Global Navigation Satellite System (GNSS) velocity data, and stress tensor inversion with supporting gravity and seismic datasets to characterize the geometry, kinematics, and geodynamic significance of the CATZ. The combined geodetic and geophysical observations reveal that the CATZ is a persistent, left-lateral deformation corridor (i.e., elongated zone of Earth’s crust that accommodates movement where the landmass on the opposite side of a fault system moves to the left relative to an observer) accommodating ~4 mm/yr of shear between the oppositely moving eastern and western sectors of the Anatolian Plate. Spatial coherence among LiCSAR-derived shear patterns, GNSS velocity gradients, and regional stress-field rotations defines the CATZ as a crustal- to lithospheric-scale transition zone linking the strike-slip domains of central Anatolia with the subduction zones of the Hellenic and Cyprus arcs. Stress inversion analyses delineate four subzones with systematic kinematic transitions: compressional regimes in the north, extensional fields in the central domain, and complex compressional–transtensional deformation toward the south. The CATZ coincides with zones of variable Moho depth, crustal thickness, and inferred lithospheric tearing within the retreating African slab, indicating a deep-seated origin. Its S-shaped curvature and long-term evolution since the late Miocene reflect progressive coupling between upper-crustal faulting and deeper lithospheric reorganization. Recognition of the CATZ as a lithospheric-scale transition zone, rather than a discrete active fault, refines the current understanding of Anatolia’s kinematic framework. This study demonstrates the capability of integrated satellite geodesy and stress modeling to resolve diffuse intra-plate deformation, offering a transferable approach for delineating similar transition zones in other continental regions. Full article

Background/Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the global COVID-19 pandemic, which led to hundreds of millions of human infections and more than seven million deaths worldwide. Major variants of concern, particularly the Omicron variant and its associated subvariants, can escape the vaccines developed so far to target previous strains/subvariants. Therefore, effective vaccines that broadly neutralize different Omicron subvariants and show good protective efficacy are needed to prevent further spread of Omicron. The spike (S) protein, including its receptor-binding domain (RBD), is a key vaccine target. Methods: Here, we designed a unique mRNA vaccine encoding Omicron-KP.3 RBD based on RBD-truncated S protein backbone of an earlier Omicron subvariant EG.5 (KP3 mRNA), and evaluated its stability, immunogenicity, neutralizing activity, and protective efficacy in a mouse model. Results: Our data showed that the nucleoside-modified, lipid nanoparticle-encapsulated mRNA vaccine was stable at various temperatures during the period of detection. In addition, the vaccine elicited potent antibody responses with broadly neutralizing activity against multiple Omicron subvariants, including KP.2, KP.3, XEC, and NB.1.8.1. This mRNA vaccine protected immunized transgenic mice from challenge with SARS-CoV-2 Omicron-KP.3. Immune serum also protected against subsequent virus challenge, with the level of protection associating positively with the serum neutralizing antibody titer. Conclusions: Taken together, the data presented herein suggest that this newly designed mRNA vaccine has potential against current and future Omicron subvariants. Full article

Background/Objectives: Phages show efficacy against multidrug-resistant Pseudomonas aeruginosa, but limited host ranges require combining them in cocktails. In this work, we characterized 25 P. aeruginosa phages, developed therapeutic cocktails active against diverse clinical isolates, and tested phage efficacy in a mouse incisional wound model. Methods/Results: These phages represent seven genera, and genomic and phenotypic analyses indicate that 24/25 are lytic and suitable for phage therapy. Phage host ranges on a diversity panel of 156 P. aeruginosa strains that included 106 sequence types varied from 8% to 54%, and together the 24 lytic phages were active against 133 strains (85%). All of the phages reduced bacterial counts in biofilms. A cocktail of five lytic phages, WRAIR_PAM1, covered 56% of the strain panel, protected 100% of mice from lethal systemic infection (vs. 20% survival in the saline-treated group), and accelerated healing of infected wounds. An improved five-phage cocktail, WRAIR_PAM2, was formulated by a rational design approach (using phages with broader host ranges, more complementing activity, relatively low resistance background, and compatibility in mixes). Conclusions: WRAIR_PAM2 covered 76% of highly diverse clinical isolates and demonstrated significant efficacy against topical and systemic P. aeruginosa infection, indicating that it is a promising therapeutic candidate. Full article

Outcomes of influenza virus infection vary widely across individuals, reflecting not only viral genetics and host factors but also the composition and function of the airway microbiome. Over the past few years, mechanistic work has clarified how specific commensals (for example, Staphylococcus epidermidis and Streptococcus oralis) restrict influenza replication by priming epithelial interferon-λ programs, reshaping intracellular metabolite pools (notably polyamines), dampening host protease activity, and maintaining barrier integrity; meanwhile, pathobionts (notably Staphylococcus aureus and Streptococcus pneumoniae) can enhance viral fitness via secreted proteases and neuraminidases that activate hemagglutinin and remodel sialylated glycoconjugates and mucus, setting the stage for secondary bacterial disease. Recent studies also highlight the gut–lung axis: gut microbiota-derived short-chain fatty acids (SCFAs), especially acetate, protect tight junctions and modulate antiviral immunity in influenza models. Together, these insights motivate translational strategies—from intranasal live biotherapeutics (LBPs) to metabolite sprays and decoy/dual neuraminidase approaches—that complement vaccines and antivirals. We synthesize recent evidence and outline a framework for leveraging the airway microbiome to prevent infection, blunt severity, and reduce transmission. Key priorities include strain-level resolution of commensal effects, timing/dosing windows for metabolites and LBPs, and microbiome-aware clinical pathways for anticipating and averting bacterial coinfection. Overall, the airway microbiome emerges as a tractable lever for influenza control at the site of viral entry, with several candidates moving toward clinical testing. Full article

The olive tree hosts diverse endophytic fungi that may contribute to plant protection and growth. In this study, a preliminary screening of olive-associated fungal endophytes was conducted. A total of 67 fungal endophytes were isolated from the leaves and roots of the Greek cultivars Amfissa and Kalamon and identified using morphological and molecular approaches; 28 representative strains were selected for functional evaluation. Dual culture assays revealed substantial antagonistic activity against major phytopathogens, with growth inhibition ranging from 19.05% to 100%. Notably, strains F.KALl.8 and F.AMFr.15 showed the strongest suppression across pathogens. Interaction phenotyping revealed all major interaction types (A, B, C) and subtype C1/C2, with several strains producing pigmentation zone lines or hyphal ridges at contact sites. The assessment of plant growth-related effects using Arabidopsis thaliana as a model system showed that three strains (F.AMFr.15, F.KALr.4, F.KALr.38A) significantly increased seedling biomass (up to ~16% above the control), whereas nine strains caused severe growth reduction and disease symptoms. Beneficial strains also altered root architecture, inhibiting primary root elongation while inducing extensive lateral root formation. Collectively, these findings highlight the functional diversity of olive-associated fungal endophytes and identify promising candidate strains, particularly F.AMFr.15 (identified as Clonostachys sp.), for further host-specific validation as potential biological control and plant growth-promoting agents. Full article

Transmissible gastroenteritis (TGE), caused by the TGE virus (TGEV), is a highly contagious enteric disease characterized by vomiting, dehydration, and watery diarrhea. It mainly endangers piglets within two weeks of age, with a 100% mortality rate, inflicting severe economic losses on the global swine industry. Since enteric tropism of the virus and mucosa serves as the first line of defense against viral invasion, an oral vaccine inducing sufficient secretory immunoglobulin A (SIgA) antibodies in animals should be developed. Being a generally recognized as safe (GRAS) microorganism, Bacillus subtilis can form endospores under extreme environmental conditions, which confer resistance to the hostile gastric environment and have been widely employed as delivery vehicles for oral vaccines owing to their immunoadjuvant activity and non-specific antidiarrheal effects. In this study, the AD antigenic epitope of the TGEV S protein was selected as the immunogen. The mature peptide of the B subunit of the heat-labile enterotoxin from enterotoxigenic Escherichia coli served as a mucosal adjuvant, and B. subtilis WB800N was used as the delivery host to construct the recombinant strain pHT43-LTB-AD/WB800N. After confirming the successful expression of the target protein, oral immunization was performed using mice as a model. The results demonstrated that this recombinant strain induced robust mucosal, humoral, and cellular immunity, along with considerable levels of neutralizing antibodies. These findings indicate that recombinant B. subtilis could serve as an oral vaccine candidate to combat TGEV infections. Full article

Bacillus velezensis strain G2T39 is an endophytic bacterium previously isolated from Crotalaria retusa L., with evidenced biocontrol activity against Fusarium oxysporum f. sp. Cubense and Fusarium graminearum. In this study, it was shown that this strain also exhibited biocontrol activity against Colletotrichum gloeosporioides and Fusarium oxysporum f. sp. Vasinfectum, two important crop pathogens in tropical zones. Comprehensive phylogenetic and genomic analyses were performed to further characterize this strain. The genome of B. velezensis G2T39 consists of a single circular chromosome of 4,040,830 base pairs, with an average guanine–cytosine (GC) content of 46.35%. Both whole-genome-based phylogeny and average nucleotide identity (ANI) confirmed its identity as B. velezensis, being closely related to biocontrol and plant growth promotion Gram-positive model strains such as B. velezensis FZB42. Whole-genome annotation revealed 216 carbohydrate-active enzymes and 14 gene clusters responsible for secondary metabolite production, including surfactin, macrolactin, bacillaene, fengycin, bacillibactin, bacilysin, and difficidin. Genes involved in plant defense mechanisms were also identified. Additionally, G2T39 genome harbors multiple plant growth-promoting traits, such as genes associated with nitrogen metabolism (nifU, nifS, nifB, fixB, glnK) and a putative phosphate metabolism system (phyC, pst glpQA, ugpB, ugpC). Additional genes linked to biofilm formation, zinc solubilization, stress tolerance, siderophore production and regulation, nitrate reduction, riboflavin and nicotinamide synthesis, lactate metabolism, and homeostasis of potassium and magnesium were also identified. These findings highlight the genetic basis underlying the biocontrol capacity and plant growth-promoting properties of B. velezensis G2T39 and support its potential application as a sustainable bioinoculant in agriculture. Full article

Repeated exposure to low-level blast overpressure (BOP) during controlled detonations is an emerging occupational health concern for military breachers and Special Operations Forces personnel, given accumulating evidence that chronic exposure may produce subtle, subclinical neurotrauma. This study derived a latent neuroinjury construct integrating three complementary domains of brain health—post-concussive symptoms, working-memory performance, and circulating biomarkers—to determine whether breachers exhibit coherent patterns of neurobiological alteration. Symptom severity was assessed using the Rivermead Post-Concussion Questionnaire (RPQ), and working memory was assessed with the N-Back task and a panel of thirteen neuroproteomic biomarkers was measured reflecting astroglial activation, neuronal and axonal injury, oxidative stress, inflammatory signaling, and neurotrophic regulation. Experienced Canadian Armed Forces breachers with extensive occupational BOP exposure were compared with unexposed controls. Bayesian latent-variable modeling provided probabilistic evidence for a chronic, subclinical neurobiological signal, with the strongest contributions arising from self-reported symptoms and smaller but consistent contributions from the biomarker domain. Working-memory performance did not load substantively on the latent factor. Several RPQ items and circulating biomarkers showed robust loadings, and the latent neuroinjury factor was elevated in breachers relative to controls (97% posterior probability). The pattern is broadly consistent with subclinical neurobiological stress in the absence of measurable cognitive impairment, suggesting early or compensated physiological alterations rather than overt dysfunction. This multidomain, biomarker-informed framework provides a mechanistically grounded and scalable approach for identifying subtle neurobiological strain in military personnel routinely exposed to repetitive low-level blast. It may offer value for risk stratification, operational health surveillance, and the longitudinal monitoring of neurobiological change in high-risk occupations. Full article

Microalgae are sustainable sources of bioactive compounds with broad hepato-protective potential. This review synthesizes evidence for five major classes—carotenoids such as astaxanthin and fucoxanthin, polysaccharides such as paramylon and fucoidan, phycobiliproteins such as phycocyanin, omega-3 fatty acids, and phenolic extracts—linking their actions to key liver injury mechanisms. Preclinically, these compounds enhance antioxidant defenses, improve mitochondrial function, suppress inflammatory signaling, regulate lipid metabolism, modulate the gut–liver axis, and inhibit hepatic stellate cell activation, thereby attenuating fibrosis. Consistent benefits are observed in models of non-alcoholic and alcoholic fatty liver disease, drug-induced injury, ischemia–reperfusion, and fibrosis, with marked improvements in liver enzymes, oxidative stress, inflammation, steatosis, and collagen deposition. Emerging evidence also highlights their roles in regulating endoplasmic reticulum stress and ferroptosis. Despite their promise, translational challenges include compositional variability, a lack of standardized quality control, limited safety data, and few rigorous human trials. To address these challenges, we propose a framework integrating multi-omics and AI-assisted strain selection with specification-driven quality control and formulation-aware designs—such as lipid carriers for carotenoids or rational combinations like fucoxanthin with low-molecular-weight fucoidan. Future priorities include composition-defined randomized controlled trials in non-alcoholic fatty liver disease, alcoholic liver disease, and drug-induced liver injury; harmonized material specifications; and multi-constituent interventions that synergistically target oxidative, inflammatory, metabolic, and fibrotic pathways. Full article