Search Results (20,228)

Background and Clinical Significanc: Neuropathic corneal pain is a debilitating condition characterized by ocular pain disproportionate to clinical signs, often resulting from peripheral and central sensitization of the corneal somatosensory pathway. Emerging evidence suggests that chronic involuntary muscle contraction in blepharospasm may lead to irritation of trigeminal afferents and corneal neurogenic inflammation, potentially predisposing patients to neuropathic corneal pain. Given its debilitating nature, early recognition can prevent the progression of neuropathic sequelae. This study examines the potential role of blepharospasm as a predisposing factor contributing to neuropathic corneal pain. Case Presentation: This retrospective case series describes three cases (median age: 50 years) of neuropathic corneal pain in association with blepharospasm and their clinical course following multimodal treatment over a median follow-up period of one year. Ocular surface was evaluated using slit-lamp biomicroscopy, while corneal nerve structure and morphology were assessed with in vivo confocal microscopy. All the three subjects presented with minimal ocular surface staining but disproportionate ocular pain characterized by burning sensation and photophobia. Proparacaine challenge testing was performed to determine the subtype of neuropathic corneal pain. Pain symptoms and quality of life were evaluated using the Ocular Pain Assessment Survey and Ocular Surface Disease Index questionnaires. In vivo confocal microscopy demonstrated characteristic corneal nerve abnormalities including reduced corneal nerve density, increased nerve tortuosity, and the presence of microneuromas. Treatment included oral Pregabalin or Gabapentin, topical lubricants, Cyclosporine 0.05% (1 case), and 20% autologous serum eye drops (1 case). Two of the three cases received four to five injections of botulinum toxin for blepharospasm, whereas one had undergone a single injection prior to review. All patients also received weekly periorbital quantum molecular resonance electrotherapy for two months. Improvements were observed across multiple domains of the Ocular Pain Assessment Survey and Ocular Surface Disease Index evaluation, including ocular pain, photophobia, non-ocular pain, and quality-of-life measures following multimodal treatment. The co-existence of blepharospasm and neuropathic corneal pain observed in our cases supports a possible association between chronic periocular muscle hyperactivity and corneal nociceptor sensitization. Proposed mechanisms include chronic trigeminal nerve irritation, neurogenic inflammation, and sensitization mediated by pro-inflammatory neuropeptides. Multimodal treatment targeting both motor hyperactivity and neuropathic pain pathways appeared to provide symptomatic relief, including the use of quantum molecular resonance electrotherapy, which might modulate pain pathways, block nociceptor neurotransmission, and accelerate corneal nerve regeneration. Given the complexity of the neural pathways responsible for ocular discomfort, further studies are required to elucidate the relationship between neuropathic corneal pain and blepharospasm in larger cohorts, as well as refine existing therapeutic approaches, including evaluating the therapeutic role of electrotherapy. Conclusions: Blepharospasm may represent a potential predisposing factor of neuropathic corneal pain. Early recognition and concurrent treatment of blepharospasm and neuropathic corneal pain can effectively relieve symptoms and improve quality of life. Adopting a multimodal treatment approach is therefore recommended. Full article

Protein–protein interactions are a fundamental component of most biological processes in living organisms. Therefore, enhancing these molecular interactions is of major importance in the life sciences field. In this paper we present the redesign of a protein–protein complex using single-elitist and multi-objective evolutionary algorithms. We focus on a structural complex composed of a bacteriophage protein interacting with a bacterial protein, emphasizing the interaction zone, which is defined by the closest distance between residues from proteins and comprises thirty-eight positions. Our approach fuses physics-based energy calculations with data-driven models to maximize the effectiveness of the search process. By simultaneously minimizing interaction energy and maximizing the log-likelihood ratio, the proposed algorithms show a balance between thermodynamic stability and biological sequence plausibility. This hybrid strategy guides the mutation of specific residues, enabling the identification of optimal solutions that are both physically robust and evolutionarily relevant. Results demonstrate that the evolved Pareto optimal set exhibits a significant improvement in binding affinity, with mean interface energy decreasing from +32 to −60 REU (Rosetta Energy Units). Furthermore, the analysis identifies key conserved residue positions, validating the capability of the framework to produce energetically favorable and biologically consistent protein designs. Full article

Background:Scutellaria baicalensis (Scu) extract has been traditionally used in the treatment of stroke-related syndromes, yet its underlying molecular mechanisms, particularly those involving ferroptosis, remain to be fully elucidated. Purpose: This study aims to validate the hypothesis that Scu extract improves cerebral ischemia-reperfusion injury (CIRI) by inhibiting ferroptosis through the PI3K/AKT signaling pathway. Methods: This study employed middle cerebral artery occlusion (MCAO) in male Sprague-Dawley (SD) rats and oxygen–glucose deprivation/reoxygenation (OGD/R) models to evaluate the protective effects of Scu extract against CIRI. Multiple approaches were integrated to elucidate the underlying mechanisms. Furthermore, a range of experimental techniques, including neurological function assessment, TTC staining, histopathological analysis, biochemical assays, qPCR, transmission electron microscopy (TEM), reactive oxygen species (ROS) detection, Western blotting, and immunofluorescence, were used to comprehensively validate its neuroprotective effects. Results: Scu extract significantly improved neurological outcomes and attenuated brain injury in MCAO rats. Proteomic analysis revealed significant enrichment of ferroptosis-related pathways, which was supported by reduced mitochondrial damage, decreased iron accumulation, and restoration of the SLC7A11/GPX4 axis. Subsequently, UPLC/Q-TOF-MS analysis revealed that four major bioactive components were absorbed in MCAO rats. KEGG pathway analysis based on network pharmacology further indicated that the PI3K/AKT signaling pathway is a key regulatory target. Notably, pharmacological inhibition of PI3K with LY294002 markedly abolished the anti-ferroptotic effects of Scu extract, which was further confirmed in vitro. Conclusions: This study demonstrates that Scu extract confers neuroprotection against CIRI in MCAO rats potentially through inhibiting ferroptosis via activation of the PI3K/AKT pathway. Full article

Osmotic stress severely limits the growth and development of tomato (Solanum lycopersicum L.) by reducing cellular water potential, disrupting redox homeostasis, and impairing physiological functions. Micro–nano bubble (MNB) treatment can increase dissolved oxygen in the root-zone solution and improve the root-zone environment, which may benefit root metabolic activity and stress adaptation. However, the underlying molecular mechanisms are still not elucidated. To explore the underlying molecular mechanisms of how MNB-mediated root oxygenation alleviates osmotic stress in tomato, we have integrated the physiological and biochemical alterations, variable-pressure scanning electron microscopy (VP-SEM), and transcriptomic analysis (RNA-seq) under osmotic stress. The results revealed that MNBs significantly reduced PEG-induced wilting and decreased reactive oxygen species (ROS) accumulation and relative electrical conductivity (REC). Indeed, MNBs also markedly upregulated the expression of root aquaporins PIP2.7 and PIP2.4, suppressed the expression of NCED1 in leaves, and increased levels of endogenous growth-promoting hormones, including IAA and GA₃, under osmotic stress. VP-SEM observations showed that MNB-treated plants exhibited a relatively more open stomatal appearance compared with PEG-treated plants. Together, these findings suggest that MNBs mitigate PEG-induced osmotic stress in tomato, potentially by improving the root-zone aeration environment and coordinating water transport-related gene expression, antioxidant defense, and hormonal balance. These results provide a promising physical approach and theoretical basis for improving tomato stress tolerance under osmotic stress. Full article

Viral hemorrhagic fevers (VHFs) are severe infectious diseases caused by RNA viruses of the families Arenaviridae, Filoviridae, Flaviviridae, and Hantaviridae, characterized by high morbidity, significant case fatality rates, and frequent diagnostic uncertainty in early disease stages. For military medical services, timely clinical recognition and laboratory confirmation are essential to guide patient management, prevent nosocomial transmission, and maintain operational continuity, particularly in endemic or resource-limited deployment settings. This review critically examines current diagnostic approaches to VHF-causative agents, emphasizing their use in clinical and field medical settings. The diagnostic process, from exposure through specimen collection, laboratory testing, and result interpretation is analyzed, including the use of molecular, serological, and antigen-based assays. Particular attention is given to deployable diagnostic platforms and their role in bridging the gap between frontline clinical suspicion and definitive laboratory confirmation. Biosafety requirements and infection prevention measures are discussed as integral components of clinical diagnostic workflows, aligned with guidance from the World Health Organization and the Centers for Disease Control and Prevention. Comparative analyses of virus-specific diagnostic timelines and laboratory requirements are presented to support differential diagnosis and clinical decision-making. Emerging technologies, including rapid molecular assays and genomic methods, are evaluated for their potential to improve early diagnosis and patient outcomes. This review highlights the central role of diagnostic readiness in clinical management of the VHFs and provides evidence-based considerations to support military clinicians facing high-risk febrile illnesses in operational environments. Full article

As global ecosystems and food systems face unprecedented anthropogenic and climatic challenges, there is a demand for an integrated understanding of biological systems. Proteomics has emerged as a definitive approach offering a direct view of the molecular phenotype, yet it is traditionally separated into plant and animal disciplines. With recent advances in mass spectrometry (MS) and bioinformatics tools, this prospective review proposes that combining a One Health proteomics approach with deep-learning data analysis can revolutionize global food security, animal productivity, and ecosystem health by uncovering proteoform signatures that drive resilience across life. The potential of a unified One Health proteomic framework, highlighting major developments, including 4D proteomics, Data-Independent Acquisition (DIA), and single-cell resolution, and emphasizes their capacity to resolve the complex proteoform landscape across kingdoms. Review emphasizes the applications of proteogenomics as a cross-disciplinary tool to improve genome annotations, explain evolutionary differences, discover biomarkers in animals and resolve complex signaling networks in plants under stress. Nevertheless, contemporary proteogenomics methods still show limitations in their ability to comprehensively resolve proteoforms due to the fact that the use of peptide-based approaches makes it difficult to fully appreciate the post-translational modifications specific to each protein isoform. We show that One Health proteomics will provide a transformative roadmap for deciphering the functional proteoform signatures that underpin resilience across the tree of life. Full article

Background and Objectives: Seroma formation is the most common postoperative complication following mastectomy and axillary dissection, negatively affecting wound healing and delaying adjuvant therapy. Despite numerous surgical and pharmacological approaches, no universally effective strategies have been established. This study aimed to comparatively evaluate the effects of porcine dermal collagen (PDC), tranexamic acid (TXA), and thymoquinone (TQ) on seroma formation and tissue repair. Materials and Methods: A randomized controlled experimental study was conducted using 40 female Wistar albino rats that underwent modified radical mastectomy and axillary dissection. All surgical and postoperative procedures were performed in accordance with the institutional animal welfare and ethical guidelines, including postoperative analgesic administration. The animals were divided into four groups: control, PDC, TXA, and TQ (n = 10 each). Seroma volume was measured on postoperative day 14. Histopathological evaluation, immunohistochemical analysis (FGF2, VEGF, TGF-β1, p53), and quantitative real-time PCR were performed to assess tissue remodeling and molecular responses. Results: All treatment groups demonstrated a significant reduction in seroma volume compared to the control group, with the most pronounced decrease observed in the TQ and TXA groups (p < 0.0001), while PDC showed a moderate effect (p < 0.01). Histopathological analysis revealed increased collagen deposition and fibrin formation in the PDC and TQ groups, whereas TXA exhibited a more limited remodeling profile than the others. Immunohistochemical and molecular analyses showed significant upregulation of VEGF across all groups, with broader and more consistent increases in the PDC and TQ groups. TGF-β1 and FGF2 expression demonstrated region-specific increases, particularly in the thoracic tissue. p53 expression remained relatively stable in the TXA group but was elevated in specific regions in the PDC and TQ groups. Importantly, the increased inflammatory infiltration, edema, vascular proliferation, and fibrin deposition observed in the TQ group may reflect not only active tissue remodeling processes but also prolonged inflammatory activation and enhanced fibrotic responses and should therefore be interpreted cautiously. Conclusions: PDC, TXA, and TQ differentially modulate postoperative seroma formation via distinct biological mechanisms. While TXA primarily exerts a targeted anti-seroma effect and PDC enhances extracellular matrix stabilization, TQ is associated with broader angiogenic, inflammatory, and tissue remodeling responses within this preclinical rat model. These findings should be considered exploratory and hypothesis-generating, and additional mechanistic studies and clinical investigations are necessary before definitive therapeutic conclusions can be established regarding the use of TQ in human breast surgery settings. Full article

Surface-enhanced Raman spectroscopy (SERS) has emerged as a transformative tool in biomedical diagnostics, offering a highly sensitive and non-invasive method for detecting molecular biomarkers at exceptionally low concentrations. This approach takes advantage of the plasmonic characteristics of customized metallic nanostructures that produce intense localized electromagnetic fields via localized surface plasmon resonance and facilitate electron transfer reactions that notoriously enhance the intrinsically weak Raman scattering signals of molecular entities which reside on or next to their surfaces. SERS-based assays have shown remarkable potential in detecting cancer biomarkers, circulating tumor DNA (ctDNA), and proteins at early stages, enabling timely and targeted intervention. Additionally, the combination of SERS with AI-driven data analysis has facilitated real-time diagnostics, enhancing the precision and efficiency of point-of-care testing. Despite its promising capabilities, challenges such as substrate fouling, signal degradation, and the need for better biocompatibility remain. Nevertheless, ongoing research in substrate development, coupled with advances in AI, positions SERS as a leading technology for future diagnostic tools. This paper explores the current state of SERS in biomedical applications, highlighting its potential to revolutionize diagnostics and personalized medicine while addressing the existing limitations and future research directions. Full article

Dermatophytosis remains one of the most prevalent superficial fungal infections worldwide and is increasingly encountered as a persistent or difficult-to-treat syndrome. A major clinical problem is that apparent treatment failure is often attributed to antifungal resistance, although many cases are instead driven by diagnostic uncertainty, corticosteroid-modified disease, reinfection, inadequate exposure, poor adherence, and limited drug delivery within keratinized tissues. This narrative review was developed to clarify the distinction between true antifungal resistance and clinical recalcitrance, with particular attention to terbinafine-resistant Trichophyton species, Trichophyton indotineae, tinea incognito, onychomycosis, dermatophytoma, and high-barrier skin and nail infections. We synthesized peer-reviewed literature and guideline-level evidence addressing epidemiology, molecular mechanisms of resistance, clinical phenotypes of recalcitrance, diagnostic escalation, therapeutic decision-making, and antifungal delivery in keratinized tissues. The review contributes a dermatology-centered conceptual framework in which persistent dermatophytosis is interpreted through both microbiological resistance and modifiable recalcitrance drivers. This approach emphasizes confirmation of fungal disease when indicated, phenotypic and anatomic classification, avoidance of inappropriate corticosteroid combinations, optimization of dose, duration, vehicle, and adherence, measures to improve drug access and reduce protected fungal burden in high-barrier disease, and prevention of reinfection from reservoirs. The proposed framework may support more rational antifungal use and reduce unnecessary escalation; however, it is based on narrative synthesis rather than a systematic review or prospective validation. Additional studies are needed to determine how such structured clinical approaches affect clinical outcomes, relapse rates, antifungal exposure, and resistance emergence in real-world dermatology practice. Full article

Inflammatory bowel disease (IBD) poses a significant global health burden with rising incidence, particularly in Asia. This study employed an integrative network pharmacology approach combined with molecular docking to elucidate the therapeutic mechanism of ganoderic acid A (GAA) against IBD. Potential GAA targets were retrieved from pharmacogenomic databases, while IBD-related genes were curated from OMIM and GeneCards databases. Weighted gene co-expression network analysis of IBD transcriptomic datasets (GSE38713, GSE126124) identified disease-associated modules, with the yellow module exhibiting the strongest positive correlation. Functional enrichment analyses demonstrated significant involvement of overlapping targets in lipid metabolism, the inflammatory response, and the mitogen-activated protein kinase (MAPK) signaling cascade pathway. We identified 14 IBD-GAA-ferroptosis-related genes and 54 key module genes. Intersection analysis revealed 5 overlapping targets, including tumor necrosis factor-α(TNF-α), peroxisome proliferators-activated receptor γ (PPARγ), MAPK14, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic α (PIK3CA), and Caspase 3 (CASP3). Molecular docking confirmed high-affinity binding of GAA to these targets, with binding energies ranging from −7.3 to −10 kcal/mol. Crucially, experimental evaluation demonstrated the pivotal role of GAA in alleviating disease pathology. GAA treatment suppressed the significantly elevated levels of TNF-α and p-MAPK14 in the organoids using a cytokine/LPS-induced IBD model. These findings collectively suggest a potential involvement of GAA in pathways associated with ferroptosis regulation, although direct experimental evidence for ferroptosis markers remains to be established. The observed multi-target effects on immune regulation and cellular proliferation/differentiation provide a foundation for further mechanistic investigation. Full article

Euonymus maackii is an important ornamental tree species valued for its autumn foliage in northern China. To precisely elucidate the molecular mechanisms underlying the distinct leaf coloration types in E. maackii during autumn, this study aimed to identify the optimal reference genes for qRT-PCR normalization across different tissues, developmental stages, and autumn leaf coloration types. Using 10 different tissues of E. maackii as experimental materials, 10 candidate reference genes were comprehensively evaluated for expression stability using three software tools, including geNorm, and the RefFinder online platform, with structural genes of the pigment biosynthesis pathway employed for validation. The comprehensive evaluation revealed that TIP41 was the most stable reference gene across different tissues, developmental stages, and the full sample set; EF-1α exhibited the highest stability among samples representing different autumn leaf coloration types; and GAPDH was the least stable in all sample groups. Quantitative validation of target genes demonstrated that when EF-1α and TIP41 were used in combination for normalization, the expression patterns of pigment biosynthesis structural genes were highly consistent with the phenotypic changes observed in autumn leaf coloration. In summary, this study recommends TIP41 as a universal reference gene for expression analysis across different tissues and developmental stages of E. maackii; for studies involving different autumn leaf coloration types, a dual-reference normalization approach combining EF-1α and TIP41 is recommended. Full article

Serratia marcescens has emerged as an important opportunistic pathogen in intensive care units (ICUs), where critically ill patients, invasive devices, antimicrobial exposure, and complex environmental reservoirs create favorable conditions for colonization, infection, and recurrent outbreaks. This narrative review synthesizes evidence from the past decade regarding the clinical and molecular epidemiology, environmental persistence, device-associated transmission, biofilm-mediated resistance, and infection-control strategies of S. marcescens in ICU settings. The literature was reviewed using an integrative approach informed by Ferrari’s narrative review framework, with thematic synthesis across clinical, microbiological, environmental, and genomic domains. Recent evidence indicates that ICU-associated S. marcescens infections frequently involve respiratory tract colonization, ventilator-associated pneumonia, bloodstream infection, urinary tract infection, and device-related transmission. Hospital water systems, sink drains, wet surfaces, ventilator circuits, reusable equipment, and contaminated antiseptic or liquid products may serve as persistent reservoirs, particularly when biofilm formation supports long-term survival and recurrent dissemination. At the molecular level, S. marcescens demonstrates substantial genomic diversity, intrinsic and acquired antimicrobial resistance, inducible AmpC β-lactamase activity, efflux-mediated tolerance, and plasmid-associated resistance gene transfer. This review particularly emphasizes the molecular determinants that enable S. marcescens to persist in ICU ecosystems, including AmpC-mediated β-lactam resistance, efflux-associated tolerance, quorum-sensing-regulated biofilm formation, plasmid-mediated horizontal gene transfer, and WGS-defined clonal transmission. Whole-genome sequencing, rapid molecular diagnostics, active surveillance, environmental sampling, and integrated infection-control bundles have become increasingly important for distinguishing clonal outbreaks from endemic transmission and guiding timely interventions. Emerging perspectives emphasize the need to combine antimicrobial stewardship, environmental engineering, respiratory-care auditing, anti-biofilm strategies, and AI-assisted real-time surveillance into adaptive ICU infection-control frameworks. Overall, S. marcescens should be regarded not merely as an episodic outbreak organism, but as a highly adaptable ICU-associated pathogen requiring multidisciplinary prevention strategies. Full article

Flavonoids are essential secondary metabolites that predominantly affect flower pigmentation in plants. Understanding the molecular mechanisms underlying flower color divergence is crucial for ornamental plant breeding. This study aimed to elucidate the factors responsible for the differences in color between white-petaled Cosmos bipinnatus and orange-petaled Cosmos sulphureus. We employed an integrated approach combining untargeted LC–MS/MS metabolomics and high-throughput transcriptome sequencing of fresh petals to analyze pigment composition and differential gene expression. Petal pigment extraction, total flavonoid quantification, and metabolomic profiling consistently revealed that differences in flavonoid abundance are responsible for flower color divergence between the two species. In contrast, carotenoids, previously considered potential contributors to flower coloration, were neither evident in the oil phase of the pigment extracts nor detected by metabolomic analysis. Flavonoid compounds accumulated at relatively high levels in the orange petals of C. sulphureus, reaching 11.36 times that of C. bipinnatus, contributing to its bright appearance. Transcriptomic analysis revealed differences in gene expression patterns between the two species, highlighting key candidate genes involved in the flavonoid biosynthesis pathway, such as chalcone synthase. These findings indicate that the orange coloration of C. sulphureus may be associated with CHS-regulated accumulation of naringenin chalcone and downstream compounds in the flavonoid metabolic pathway after CHS, providing valuable theoretical support for a deeper understanding of the causes underlying the differences in flower color between C. bipinnatus and the orange-petaled C. sulphureus. Full article

The most persistent biomedical challenges of the 21st century are neurodegenerative disorders (NDs), where molecular alterations lead to devastating clinical consequences and progressive neuronal loss. The prevalence of neurodegeneration is continuously rising and becoming the main contributor to chronic disability and mortality. Despite their clinical differences, many conditions share pathogenic processes, including oxidative stress, protein misfolding and aggregation, mitochondrial dysfunction, and neuroinflammation. Instead of functioning independently, these processes cooperate to form a self-reinforcing network that gradually weakens synapses and ultimately leads to neuronal death. This study redefines neurodegeneration as a disorder of system-level failure by emphasizing poor cellular stress integration. In addition to demonstrating how gut microbiome gene networks impact inflammation and amyloid production, new research highlights the relationships between mitochondrial–lysosomal interactions, endoplasmic reticulum stress responses, and transcriptionally driven synaptic vulnerability. A key molecular topic is the interaction and pathogenic convergence of the JAK/STAT, HIF-1α, and Notch signaling pathways. Under ongoing metabolic stress, prolonged stimulation of this triad increases inflammation, hinders the regenerative processes, and maintains pseudo-hypoxic conditions, explaining why single-target treatments have mostly been unsuccessful. This review also explores progress in fluid, digital, and imaging biomarkers that facilitate early diagnosis and patient stratification, and assesses new disease-modifying approaches such as antisense oligonucleotides, immunomodulators, gene therapies, and small-molecular agents. Artificial intelligence is emphasized as an essential tool for integrating multimodal data, drug discovery and predictive modeling. Full article

Multidrug resistance (MDR) remains a major obstacle in cancer therapy, driving treatment failure and disease progression across diverse malignancies. A key determinant of MDR is the overexpression of ATP-binding cassette (ABC) transporters, particularly P-glycoprotein (P-gp/ABCB1), which actively effluxes structurally diverse chemotherapeutic agents and reduces their intracellular accumulation. Despite extensive investigation, clinically effective strategies to overcome P-gp-mediated resistance remain limited. This review provides a comprehensive analysis of the molecular mechanisms underlying P-gp function, including its structural organization, regulation of expression, and role in cellular drug disposition. We highlight the interplay between P-gp activity, oxidative stress, metabolic reprogramming and the tumor microenvironment, emphasizing the complexity of MDR as a dynamic and adaptive process. Emerging therapeutic approaches targeting P-gp-mediated resistance are also discussed, including natural bioactive compounds, nanotechnology-based drug delivery systems, polymeric carriers and novel anticancer agents designed to evade efflux mechanisms. Integrating mechanistic insights with advanced pharmacological strategies may improve intracellular drug retention and therapeutic efficacy. A deeper understanding of P-gp-driven MDR is essential for the development of effective interventions aimed at overcoming drug resistance and improving clinical outcomes in cancer patients. Full article