Search Results (263)

Antimicrobial resistance (AMR) in foodborne pathogens poses a major threat to global public health and food safety. Using 9393 U.S. isolates of Salmonella enterica, Campylobacter jejuni, and Escherichia coli/Shigella collected from poultry, cattle, and swine between 2015 and 2025 and archived in the NCBI Pathogen Isolates Browser, we applied multivariate statistical analysis to characterize antimicrobial resistance patterns in isolates showing resistance to one to six antimicrobials (AMR-1 to AMR-6). Six antimicrobials—tetracycline, streptomycin, sulfisoxazole, ampicillin, nalidixic acid, and ciprofloxacin—were identified through PCA-guided clustering and frequency profiling as the principal axes of co-resistance across pathogens. Tetracycline emerged as a foundational driver of multidrug resistance, while C. jejuni contributed almost exclusively to single-drug resistance and Salmonella enterica dominated higher-order AMR categories, reflecting species-specific ecological and genomic constraints. Gene analyses revealed a progressive, modular accumulation of resistance determinants, led by efflux pumps (mdsA, mdsB), tetracycline genes (tetA/B/O), aminoglycoside-modifying enzymes, sulfonamide genes (sul1/sul2), quinolone resistance determinants (gyrA, acrF, mdtM), and β-lactamases (bla_EC, bla_OXA, bla_CTX). Together, these results demonstrate that multidrug resistance in U.S. foodborne pathogens evolves through coordinated gene–drug–pathogen interactions rather than isolated events, underscoring the need for integrated surveillance and targeted stewardship strategies focused on the dominant antimicrobials and high-risk foodborne pathogens. Full article

The growing pressure to achieve carbon neutrality has exposed major limitations in current industrial processes, which often operate in isolation, rely on simplified mass-balance assumptions, and struggle to manage increasingly complex material and energy flows. Traditional industrial symbiosis and circular economy strategies have improved resource efficiency, yet they rarely capture molecular-level interactions or enable coordinated optimization across multiple facilities, restricting their ability to support large-scale decarbonization. In this context, Carbon–Hydrogen–Oxygen Symbiosis Networks (CHOSYNs) have emerged as an advanced framework that integrates atomic-level targeting with multi-scale process systems engineering to identify synergies, valorization pathways, and cross-sector exchanges that conventional approaches overlook. This review consolidates the theoretical foundations, historical development, and recent applications of CHOSYNs, illustrating how it can enhance efficiency, reduce emissions, and strengthen resilience in energy systems, chemical industries, and circular resource management. Although the literature remains limited, existing studies demonstrate the promise of CHOSYNs as a unifying methodology for designing low-carbon industrial ecosystems. Key challenges related to scalability, validation, governance, and operational robustness are examined, and a roadmap is proposed to guide the evolution and practical deployment of CHOSYNs toward 2035. Full article

Background: Nosocomial infections represent a significant clinical burden due to high morbidity, mortality and healthcare costs. Invasive fungal infections, particularly those caused by Candida species, are of growing concern due to increasing antifungal resistance, which limits therapeutic options and worsens patient outcomes. This study aimed to characterize the prevalence, species distribution, antifungal susceptibility profiles, and molecular mechanisms of resistance in clinical Candida isolates from hospitalized patients. Methods: A cross-sectional study was conducted involving 55 hospitalized patients, yielding 60 isolates from blood, secretions, fluids, and catheter tips. Species identification was performed using chromogenic media and confirmed by MALDI-TOF MS. Antifungal susceptibility testing followed CLSI M27-A4 broth microdilution guidelines for amphotericin B, fluconazole and 5-flucytosine. Gene expression of ERG2, ERG11 and MDR1 was evaluated by RT-qPCR after exposure to subinhibitory antifungal concentrations using the 2^−∆∆Ct method. Results:Candida albicans was the most frequent species, followed by Nakaseomyces glabratus, C. tropicalis and C. parapsilosis. Resistance varied among species, with elevated rates for fluconazole. ERG2 was notably overexpressed in amphotericin B-resistant isolates, while ERG11 and MDR1 showed species-dependent variation. Conclusions: Resistance mechanisms in Candida are species-specific and drug-dependent. Accurate species identification and understanding their molecular profiles are essential to guide targeted antifungal therapy and improve clinical outcomes. Full article

Background: Vulnerable road users (VRUs), including children and older adults, face a high risk of fatal road traffic accidents (RTAs) due to limited protection and greater injury susceptibility. Romania reports some of the highest child and elderly RTA mortality rates in the European Union. This study analyzed medico-legal autopsies from the Timisoara Institute of Legal Medicine (TILM) between 2017 and 2021 to compare fatalities in these two groups and identify key risk factors. Methods: A retrospective analysis was conducted on autopsy records of children (0–17 years) and older adults (>70 years) who died in RTAs during the study period. Data on demographics, type of road user, traumatic injuries, cause of death, and accident circumstances were extracted and supplemented by police reports. Comparative statistical analyses were performed for categorical and continuous variables. Results: Among 395 RTA autopsies, 23 (5.8%) involved children and 51 (12.9%) older adults. Most child victims were passengers (56.5%), whereas elderly fatalities occurred mainly among pedestrians (33.3%) and cyclists (25.5%), with statistically significant differences between age groups. Polytrauma was the leading cause of death in both categories, though isolated cranio-cerebral trauma was proportionally more frequent in children. Crash circumstances also showed age-related patterns, with children more involved in high-energy collisions and older adults more frequently struck as pedestrians. Survival intervals showed a similar distribution across groups. Conclusions: Child and elderly RTA fatalities in Romania share common determinants, primarily driver-related behaviors and insufficient safety measures, while also exhibiting distinct age-related vulnerabilities. Autopsy-based data highlights these patterns and can guide targeted interventions such as stricter law enforcement, public education, and infrastructure improvements. Full article

Background/Objectives: Myeloid sarcoma (MS) is a rare extramedullary manifestation of myeloid blasts, with limited systematic data, particularly regarding molecular (NGS) concordance between MS tissue and bone marrow. We hypothesized that clonal heterogeneity may exist between these sites due to their distinct biological environments. Methods: We conducted a systematic review and meta-analysis of 85 studies encompassing 7241 MS patients, to evaluate clinical characteristics, mutational profiles, treatment patterns, and outcomes. Mutational concordance or discordance between MS and bone marrow was assessed in a subset of 112 patients. Results: Male predominance (59%) and skin/soft tissue localization (31%) were most common. NPM1 (25%) and FLT3 (20%) were the most frequently reported mutations. Among 112 patients with paired sequencing, 56% showed discordance in mutational profiles. NPM1 was significantly enriched in MS sites compared to bone marrow (35% vs. 21%, p = 0.02) and was associated with skin involvement. Discordance was more frequent in isolated and secondary MS. Venetoclax with hypomethylating agents achieved a 44% response rate, mainly in secondary MS. Post-transplant isolated extramedullary relapse occurred in 46% of relapsed patients and was linked to high rates of graft-versus-host disease. The pooled median overall survival was 12.8 months. Conclusions: MS demonstrates significant molecular heterogeneity. Routine site-specific NGS profiling may guide targeted therapy in this rare disease. Full article

Fritillaria pallidiflora Schrenk ex Fisch. & C.A.Mey. (Yi Beimu) is a culturally significant Beimu drug in Northwest China, officially listed in the Chinese Pharmacopoeia and traditionally used to clear heat, moisten the lung, resolve phlegm, and relieve cough and wheeze. This narrative, critical review synthesizes current evidence on ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics/toxicology, and conservation of F. pallidiflora to support sustainable, evidence-based development. Literature was retrieved from major English and Chinese databases and screened for studies that unambiguously involved Yi Beimu or its key constituents. Ethnomedicinal records consistently support antitussive, expectorant, and anti-asthmatic use in Xinjiang and the Ili River Valley. Chemically, F. pallidiflora is rich in cevanine-type steroidal alkaloids (e.g., imperialine, peimine, yibeinones), steroidal saponins (pallidiflosides), polysaccharides, and minor phenolics. Preclinical data show that alkaloids relax airway smooth muscle, suppress inflammatory mediators, and contribute to antitussive and anti-asthmatic effects, while polysaccharides and total alkaloid extracts exhibit antioxidant and cytoprotective activity in cell and animal models of airway injury. Additional studies report cytotoxic saponins and seed-derived antimicrobial peptides. Pharmacokinetic work highlights low to moderate and variable oral bioavailability, shaped by P-glycoprotein efflux and CYP-mediated metabolism, and reveals potential hERG channel inhibition for peimine as a cardiac safety concern. Overharvesting and habitat loss have reduced wild resources, underscoring the need for conservation, cultivation, and marker-guided quality control. Overall, Yi Beimu shows credible ethnopharmacological rationale and promising multi-target pharmacology for respiratory disorders, but translation will require bioactivity-guided isolation coupled with PK–PD-guided in vivo studies, rigorous safety evaluation, and conservation-aware cultivation to move from traditional remedy toward validated therapeutic resource. Full article

Epstein–Barr virus (EBV) is distributed worldwide and shows a seroprevalence of over 90% in adults, while seroprevalence in children varies depending on geographic and socioeconomic factors. Although primary EBV infection (pEBV) is often asymptomatic in early childhood, infection later in life may present with a variety of symptoms, most commonly as infectious mononucleosis, though many other clinical manifestations may occur. We present four clinical cases to illustrate the diverse and uncommon manifestations of pEBV and to support diagnostic reasoning. The first case demonstrates a diagnostic challenge of pEBV in a patient with severe cholestatic hepatitis in the setting of a recent travel. The second case highlights bilateral eyelid swelling (Hoagland sign) as a potentially isolated early symptom of pEBV, which clinicians should consider within its broad differential diagnosis. In the third case, we emphasize the importance of clinical judgment in contrast to premature closure in the face of repeatedly negative EBV serologies and advocate for further diagnostic evaluation, such as PCR testing, when pEBV is strongly suspected. The fourth case describes a fatal outcome of pEBV late in life, complicated by hemophagocytic lymphohistiocytosis. Unusual presentations of pEBV may complicate the diagnostic process and may lead to unnecessary testing. Our case series underscores the broad clinical spectrum of pEBV and highlights key features that aid in distinguishing it from important differential diagnoses. Awareness of characteristic laboratory findings, including reactive lymphocytosis, elevated large unstained cells, persistent fever, and lymphadenopathy, splenomegaly, as well as mild-to-moderate hepatitis is essential for guiding a targeted diagnostic approach for pEBV. Full article

Cancer remains a major global health burden driven by genetic, metabolic, and microenvironmental alterations. Although reactive oxygen species (ROS) and oxidative stress have long been implicated in cancer biology, current understanding remains fragmented and, in several areas, conceptually disputed considering how ROS and oxidative stress thresholds determine the switch between tumor-promoting signaling and cytotoxic outcomes, and whether redox-based therapies can be safely and selectively applied across different cancer types. Moreover, existing studies often examine isolated pathways or single ROS, leaving unanswered the question of how spatial and temporal ROS dynamics and oxidative stress responses shape carcinogenesis, metastasis, and therapeutic resistance. This review moves beyond descriptive summarization by critically examining unresolved mechanistic gaps, including (i) how ROS and oxidative stress interact with epigenetic and metabolic reprogramming, (ii) the context-dependent role of ROS-driven oxidative stress within the tumor microenvironment and immune evasion, and (iii) why ROS-targeting and oxidative stress-modulating therapies have shown inconsistent clinical translation despite promising preclinical data. We highlight areas of consensus as well as conflicting evidence, synthesizing recent advances across multiple cancer types to clarify where ROS and oxidative stress function as drivers, modulators, or vulnerabilities. Finally, we outline emerging research priorities, such as real-time redox profiling, subtype-specific targeting strategies, and combination approaches, to guide the development of more precise and effective ROS- and oxidative-stress-based interventions. Full article

Alcohol’s chronic neurotoxic and degenerative effects mediate alcohol-related brain damage (ARBD), which is marked by neurobehavioral, cognitive, and motor deficits. Major underlying abnormalities include impairments in signaling through the insulin and insulin-like growth factor (IGF) pathways, which regulate energy metabolism. This study examined the potential role of dysregulated incretin network-related mechanisms as mediators of ARBD and evaluated a non-invasive serum exosome (S-EV)-based approach for detecting brain abnormalities. Frontal lobe tissue and S-EVs isolated from Long–Evans adolescent rats maintained for 2 weeks on control or 24% ethanol (caloric) containing liquid diets (n = 8/group) were analyzed using multiplex magnetic bead-based enzyme-linked immunosorbent assays (ELISAs). ARBD was associated with significantly reduced insulin, C-peptide, glucagon, ghrelin, leptin, GIP, and amylin levels in the frontal lobe and/or S-EV samples. In contrast, chronic ethanol exposure had no significant effects on PP, PYY, or GLP-1, and it did not increase proinflammatory cytokine expression. Chronic ethanol feeding broadly affected (primarily inhibiting) the expression of metabolic hormones linked to insulin/IGF signaling. The reductions in GIP and amylin suggest potential targets for therapeutic intervention to enhance brain energy metabolism via insulin networks. On the other hand, the findings suggest that GLP-1 receptor agonists may have limited efficacy in remediating the effects of ARBD. Finally, the results support the use of non-invasive S-EV assays to detect and guide treatment for metabolic brain dysfunction in ARBD. Full article

Seismic data migration is a critical step for accurate subsurface imaging. While Ocean Bottom Cable (OBC) surveys provide high-quality seismic data, reliance on primary reflections alone leads to significant illumination gaps. Receiver-side ghost waves can mitigate these gaps; however, conventional mirror migration suffers from low resolution and amplitude inaccuracy. To address these limitations, this study introduces a high-resolution mirror migration framework based on Point Spread Function (PSF)-guided inversion imaging. The methodology involves first separating the OBC wavefield to isolate ghost-wave components, followed by applying standard mirror migration to produce an initial, blurred image. Subsequently, the PSFs of down-going ghost waves are estimated to characterize imaging distortions, and image-domain least squares migration (LSM) is implemented via PSF deconvolution to reconstruct high-resolution reflectivity. Numerical experiments on complex models demonstrate that the proposed method preserves the additional illumination provided by this wavefield, substantially improves the spatial resolution of imaging targets, and enhances lateral continuity. Quantitative analysis confirms this enhancement through a significant extension of the effective vertical wavenumber bandwidth and the recovery of higher-frequency content. The framework provides a robust and computationally efficient solution for high-fidelity OBC imaging, enabling more reliable subsurface interpretation. Full article

Background and Clinical Significance: Vestibular disorders include a wide range of conditions with overlapping symptoms such as dizziness, vertigo and imbalance, often offering diagnostic challenges when distinguishing between peripheral and central etiology. Accurate differentiation is essential for establishing effective treatment plans. In rare or atypical cases with subtle findings, comprehensive diagnostic tools—such as extended vestibular tests and structured questionnaires like the Dizziness Handicap Inventory (DHI)—are critical for diagnosis and monitoring patient recovery. Case Presentation: A 35-year-old female presented with chronic imbalance and motion-induced dizziness persisting for four years. The patient had a surgical history of right-sided functional neck dissection for a parotid tumor. A comprehensive audiovestibular evaluation was performed, including pure tone audiometry (PTA), tympanometry, videonystagmography (VNG), cervical vestibular evoked myogenic potentials (cVEMP), ocular vestibular evoked myogenic potentials (oVEMP), video head impulse testing (vHIT), computerized dynamic posturography (CDP), and magnetic resonance imaging (MRI). The Dizziness Handicap Index (DHI) was administered at baseline and post-treatment to monitor subjective symptom changes. Objective testing revealed marked right–left amplitude asymmetry on cVEMP, which were recorded from the trapezius muscle due to prior neck dissection surgery, indicating isolated right-sided saccular hypofunction. Following targeted vestibular rehabilitation and pharmacologic treatment, the 3-month reassessment demonstrated resolution of symptoms and a reduction in DHI scores from 24 to 6. Conclusions: Comprehensive vestibular testing, performed in a single diagnostic session, enabled the accurate identification of isolated right-sided saccular hypofunction in this complex post-surgical case. Combining cVEMP, CDP, and DHI assessment provided a complete functional profile, guided targeted rehabilitation, and allowed objective monitoring of recovery. Full article

African swine fever virus (ASFV) is a highly contagious pathogen causing African swine fever in wild boars, warthogs and domestic pigs. The disease leads tosubstantial economic losses to the global pork industry and poses a grave threat to biodiversity. The early-encoded structural protein p22, owing to its immunodominant characteristics and high conservation across most genotypes, represents a promising diagnostic target and subunit vaccine candidate. In this study, the soluble extracellular domain of p22 protein (aa 30–177) was successfully expressed and purified, yielding 1.220 g/L. Eleven strains of monoclonal antibodies against p22 were generated, with four selected for B-cell epitope screening. Bioinformatic prediction-guided design was employed to generate overlapping truncations and peptides for epitope mapping. Based on those strategies, three novel linear B-cell epitopes were identified to be ³⁰KKQQPPKK³⁷, ¹³⁰WGTDDCTG¹³⁷ and ¹⁵⁰YVYNNPHH¹⁵⁷ by monoclonal antibodies. Sequence alignment across ASFV isolates revealed 100% evolutionary conservation in genotypes I/II, with minor variation in genotypes IV/VIII/XX/XXII. This study provided valuable data for broadening the ASFV antigen spectrum and identifying immunological targets for subunit vaccine formulation strategies. Full article

Among many metal ions in biological systems, iron plays a fundamental role. Transferrins are iron-binding glycoproteins responsible for transporting Fe³⁺ in vertebrate blood. Neisseria meningitidis, a Gram-negative pathogen causing meningitis, relies on iron for survival and acquires it from human transferrin (hTf) using two surface proteins, TbpA and TbpB. These proteins interact with hTf to form a ternary TbpA–TbpB–hTf complex, enabling iron capture from the host. The absence of an experimental crystal structure for this complex has hindered computational studies, a detailed understanding of Fe³⁺ dissociation, and designing efficient therapeutics. This study presents the first computational model of the ternary complex, its validation, and molecular dynamics simulations. Structural analyses revealed key electrostatic interactions regulating Fe³⁺ coordination and essential contact regions between proteins. The role of Lys359 from TbpA was investigated via QM/MM calculations by evaluating Fe³⁺ binding energies of isolated hTf, the ternary complex, and Lys359Ala, Lys359Arg, Lys359Asp mutant models. Results revealed that the proton transfer from Lys359 leads to disruption of Tyr517–Fe³⁺ coordination, facilitating iron transfer to the bacterial system. Natural bond orbital analysis confirmed this mechanism. The findings provide new molecular insight into N. meningitidis iron acquisition and identify Lys359 as a potential target for covalent inhibitor design, guiding the development of novel therapeutics against meningococcal infection. Full article

Aging is a major risk factor for neurodegenerative diseases in which microglia-driven neuroinflammation plays a critical role in neuronal dysfunction and disease progression. In this study, we sought to isolate bioactive metabolites from Quercus acuta Thunb. fruits—which have traditionally been used in oriental medicine but are chemically and pharmacologically underexplored—and evaluate their anti-neuroinflammatory potential. A total of 14 compounds were isolated from an ethanol extract of Q. acuta fruits through bioactivity-guided isolation, and their structures were identified by NMR spectroscopy. Notably, this study is the first to demonstrate that 3,5,7,2′,6′-pentahydroxyflavanone and 2,5-dihydroxybenzaldehyde, among the compounds isolated from Q. acuta fruits, exhibit significant anti-neuroinflammatory activities. Both compounds reduced the production of proinflammatory mediators, including IL-6 and TNF-α, while inhibiting the expression of iNOS and COX-2. Moreover, they significantly inhibited NF-κB activation in lipopolysaccharide-induced BV2 microglia. Collectively, these findings indicate that Q. acuta fruits contain bioactive constituents with previously unreported anti-neuroinflammatory properties, supporting their potential as a natural source for the development of therapeutic agents targeting age-related neuroinflammation. Full article

Koalas (Phascolarctos cinereus) are threatened by habitat loss, fragmentation, and population isolation, increasing the risk of inbreeding and extinction. Genomic tools are valuable for guiding management decisions, and a standardised tool genomic is the most effective approach. In this study, an integrated genomic SNP assay was developed and validated as a comprehensive monitoring tool for koala conservation. The panel unifies SNP markers from previous approaches (DArTseq, exon-capture, whole-genome sequencing) into a standardised platform and incorporates novel fitness-related loci linked to immunity, thermoregulation, diet, and reproduction, alongside pathogen targets such as koala retrovirus (KoRV) and koala papillomavirus (KoAA). The assay was validated across key conservation applications, including population diversity and differentiation, parentage assignment, sex determination, provenance testing, and pathogen screening, using a variety of sample types (blood, tissue, swabs, scat), from previously tested populations across the distribution. A total of 3358 informative SNPs were identified, including 210 high-confidence outliers associated with immune and stress-response functions, indicating strong potential to capture adaptive variation. By integrating existing genomic resources with new adaptive and predominant pathogen loci, this cost-effective, standardised assay provides a unifying genomic framework for koala management, supporting applications from veterinary diagnostics to long-term monitoring under the National Koala Recovery Plan. Full article