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Herpesviruses employ sophisticated immune evasion strategies to establish lifelong infections, subverting type I interferon (IFN-I) responses critical for antiviral defense. However, their adaptive mechanisms across species remain poorly characterized. Using duck plague virus (DPV)-an avian alphaherpesvirus model-we identify a cooperative immune evasion axis wherein ICP27 orchestrates UL55-mediated immunosuppression through dual regulatory mechanisms: its RNA-binding domain (RGG) facilitates UL55 mRNA nuclear export, while its C-terminal domain (CTD) stabilizes UL55 protein via direct interaction. This partnership enables synergistic suppression of IFN-I signaling-co-expression of ICP27 and UL55 inhibits Poly(I:C)-induced immune genes (IFN-β, Mx, OASL, IL-6) more potently than either protein alone. UL55 functions as a precision-targeted IFN-I antagonist, selectively degrading RIG-I and IRF7 through proteasomal pathways-confirmed by proteasome inhibitor rescue (MG132), structural modeling (AlphaFold), and binding assays (Co-IP). Evolutionarily, UL55 homologs (DPV, Herpes simplex virus type 1 [HSV-1], Varicella zoster virus [VZV]) conserve RIG-I targeting but diverge in IRF3/IRF7 regulation-adaptations shaped by UL55 sequence divergence (38.68% identity) and host biology (e.g., waterfowl IRF3 deficiency). This work establishes ICP27-UL55 as a key regulatory axis in herpesviral immune evasion and redefines UL55 as a conserved yet adaptable immunosuppressor in Alphaherpesvirinae.IMPORTANCEThis study fundamentally advances herpesvirology by defining a novel immune evasion paradigm in duck plague virus. We reveal ICP27 as a master regulator that coordinates UL55 immunosuppression through a two-tiered mechanism: RGG domain-mediated mRNA nuclear export and CTD-dependent protein stabilization-an unreported strategy in herpesviruses. UL55 selectively degrades RIG-I and IRF7 via proteasomal pathways, enabling precise IFN-I suppression with minimal immune activation. Crucially, ICP27-UL55 synergy inhibits Poly(I:C)-induced immune genes (IFN-β, Mx, OASL, IL-6) more effectively than individual proteins. Evolutionary analyses demonstrate conserved targeting of RIG-I across alphaherpesvirus UL55 homologs (DPV, HSV-1, VZV) but host-adapted divergence in IRF3/IRF7 regulation, shaped by UL55 sequence variation (38.68% identity) and host biology (e.g., avian IRF3 deficiency). These findings provide the first evidence of effector coordination through integrated transcriptional/post-translational regulation in herpesviruses. Disrupting ICP27-UL55 interaction offers new antiviral targets, while UL55-deficient strains serve as vaccine candidates for poultry disease control.

The modernization of traditional fermented foods is often constrained by a limited understanding of the complex microbial ecosystems underpinning their quality. Guizhou sour soup, a representative Chinese fermented food, exemplifies this challenge. This review systematically reveals that its distinctive characteristics stem from a raw material-driven fermentation ecology. Red sour soup and rice sour soup cultivate specific functional microbial communities centered on lactic acid bacteria and yeasts, exhibiting clear dynamic succession patterns. This gives rise to markedly different flavor profiles-the former dominated by alcohols and terpenes, the latter characterized by esters and organic acids-with microbial metabolism serving as the primary mechanism for flavor formation. Concurrently, sour soup is rich in bioactive compounds, demonstrating health potential including antioxidant effects and regulation of the gut microbiota. However, current research lacks systematic analysis of microbial interaction networks, specific flavor metabolic pathways, and structure-activity relationships of bioactive components, which severely hinders process standardization and industrial upgrading. To address this, this paper establishes an integrated associative framework linking "raw materials-process-microbes-quality." This not only provides a critical theoretical basis for standardized production and targeted flavor regulation of Guizhou sour soup but also offers a scientific framework for modernizing similar traditional fermented foods worldwide.

Disruptions in cellular energy metabolism have emerged as central contributors to a broad spectrum of human diseases. While conventional therapeutic strategies can alleviate symptoms, they typically target downstream disease manifestations and often fail to address the underlying energetic dysregulation fueling disease progression. Bioenergetic organelles-engineered from mitochondria and thylakoids-represent a transformative approach by restoring cellular energy homeostasis. Functioning as autonomous metabolic modules, they generate ATP, reductive equivalents, and oxygen in situ, while concurrently modulating redox balance, oxygen tension, and immune-metabolic signaling to restore cellular homeostasis. Recent preclinical evidence highlights their therapeutic versatility, including alleviating tumor hypoxia, restoring bioenergetic function in myocardial and neuronal tissues, reducing inflammatory damage, and normalizing immune cell metabolism. Unlike nanocarriers that primarily serve as delivery vehicles, these bioenergetic organelles actively remodel pathological microenvironments by integrating metabolic restoration with multi-targeted therapeutic actions. This review outlines the design principles, mechanistic basis, and disease-specific applications of artificial bioenergetic organelles, while also addressing key translational challenges such as targeted delivery, immunocompatibility, functional longevity, critical considerations regarding biological safety, and the long-term metabolic fate of these constructs. Positioned at the convergence of bioenergetics, nanotherapeutics, and synthetic biology, these biomimetic systems offer a flexible platform for redefining disease intervention through precise metabolic regulation.

Alzheimer's disease (AD) is a chronic, progressive, neurodegenerative condition marked by memory loss and cognitive decline. It is characterized by neuropathological features such as amyloid plaque accumulation, neurofibrillary tangles of tau protein, and inflammatory changes in the brain. Recent research emphasizes how gut microbes influence the onset and progression of AD primarily through the gut-brain connection, a bidirectional communication system. The human gastrointestinal tract (GI) contains trillions of bacteria, primarily Bacteroidetes, Firmicutes, and Actinobacteria, which play vital roles in digestion, metabolic regulation, and immune modulation. However, factors such as diet, lifestyle, and environmental exposure can disrupt microbial balance, weaken intestinal barrier function, and initiate systemic inflammation. Such dysbiosis has been linked to defective regulation of the amyloid precursor protein (APP), leading to increased deposition of amyloidogenic peptides (Aβ). Moreover, the enteric nervous system, which expresses APP, may serve as an initial site of amyloid deposition, affecting gastrointestinal motility and inflammatory susceptibility. The gut microbiota also produces key bioactive compounds, including neurotransmitters such as serotonin, dopamine, acetylcholine, histamine, and gamma-aminobutyric acid (GABA), which influence the central nervous system (CNS) through neural, immune, and endocrine pathways. An imbalance in these neuroactive molecules may disrupt synaptic signaling and contribute to Alzheimer's-related cognitive dysfunction. Therefore, improving our understanding of gut-brain communication may advance knowledge of AD development and support the creation of new therapies. This review highlights the strong association between intestinal microbes and Alzheimer's pathogenesis, emphasizing microbiota modulation through probiotics, prebiotics, postbiotics, synbiotics, and antibiotics as potential therapeutic approaches, supported by emerging clinical trial evidence.

To explore the feasibility and mechanism of CPBMP among patients with oral cancer in China. We conducted a mixed methods study that included a single-center, randomized controlled trial to determine the effect of CPBMP on pain in patients with oral cancer and a semistructured interview to explore the mechanism of action of CPBMP and factors influencing its implementation. A total of 76 individuals participated in the RCT. Patients were randomized to receive a standard recovery protocol (control group) or the CPBMP (intervention group). The outcomes included pain, pain catastrophizing, fear of pain, self-efficacy, and quality of life. Saliva samples of cortisol were collected from 12 randomly selected participants in each group. From the intervention arm, 10 participants were randomly selected for interviews in this study. The semistructured questions were analyzed using content analysis. There was a significant difference in pain intensity, fear of pain, pain catastrophizing, pain self-efficacy, and quality of life (all p&#x2009;<&#x2009;0.001) between the intervention and control groups. There was a significant difference over time in pain intensity, fear of pain, pain catastrophizing, pain self-efficacy, and quality of life (all p&#x2009;<&#x2009;0.05). The interaction effects were significant for pain intensity, fear of pain, pain catastrophizing, pain self-efficacy, and quality of life (all p&#x2009;<&#x2009;0.001). There was a significant difference in the morning (p&#x2009;=&#x2009;0.028) and at 17:00 (p&#x2009;=&#x2009;0.036) salivary cortisol level between the experimental group and the control group within 24&#xa0;h before the beginning of radiotherapy. There was no significant difference in salivary cortisol slopes between the intervention and control groups (p&#x2009;>&#x2009;0.05). The interview results included two parts: "psychological mechanism of CPBMP" and "implementation of CPBMP, situational factors, and feedback." The former extracted four themes: "effects of emotion regulation on pain," "changes in pain cognition," "impact of self-efficacy on pain," and "improvement of pain coping skills," and five subthemes. The latter extracted three themes: "implementation of CPBMP (acceptability)," "situational factors," and "feedback and improvement," and eight subthemes. The CPBMP showed a positive effect on promoting patients' pain intensity, fear of pain, pain catastrophizing, pain self-efficacy, and quality of life, which effect is affected by individual characteristics. And CPBMP improves pain-related outcomes through psychological adjustment and regulation of HPA axis activity.

To evaluate the association between apical periodontitis (AP) diagnosis and cytokine expression, exploring the mediating role of global 5-hydroxymethylcytosine (5-hmC) and the enzymes involved in DNA methylation and demethylation. A cross-sectional study included individuals with symptomatic AP (SAP; n&#x2009;=&#x2009;18), asymptomatic AP (AAP; n&#x2009;=&#x2009;19), and healthy periodontal ligament (HPL) (n&#x2009;=&#x2009;11). mRNA levels of DNA methyltransferases (DNMT): DNMT1, DNMT3A; Ten-Eleven Translocation (TET) enzymes: TET2, TET3; and cytokines: IL-1&#x3b2;, and IL-6 were assessed by qRT-PCR in apical lesions and healthy periodontal ligament. Global %5-hmC was quantified by ELISA. Generalized structural equation models (GSEM) were used to evaluate the association between AP diagnosis and cytokine expression, considering %5-hmC and the expression of DNMT and TET genes as potential mediators, adjusted for age. SAP samples showed significantly higher DNMT1, DNMT3A, TET2, TET3, IL-1&#x3b2;, and IL-6 mRNA levels (p&#x2009;&#x2264;&#x2009;0.05) and lower %5-hmC compared to HPL, but not when compared with AAP (p&#x2009;>&#x2009;0.05). In AAP and SAP, DNMT3A, TET2, and TET3 correlated positively with IL-1&#x3b2; and IL-6, while in SAP, DNMT1, DNMT3A, and TET3 were inversely correlated with %5-hmC (p&#x2009;&#x2264;&#x2009;0.05), an association not observed in AAP (p&#x2009;>&#x2009;0.05). Furthermore, higher TET3 expression was associated with increased IL-1&#x3b2; and IL-6 mRNA levels (p&#x2009;&#x2264;&#x2009;0.05) and with decreased global %5-hmC levels (p&#x2009;&#x2264;&#x2009;0.05) in apical tissues. Upregulated TET3 expression is associated with proinflammatory responses and global methylation profiles in apical lesions, suggesting a potential role in the epigenetic regulation of AP. Epigenetic regulation of inflammatory cytokines may contribute to disease activity in periapical periodontitis.

Receptor tyrosine kinases are key regulators of various fundamental cellular processes, and dysregulation of their activities may lead to many human diseases including cancer. EphA2 is a member of the Eph subfamily of receptor tyrosine kinases that play an important role in regulating tissue patterning, homeostasis, and regeneration. Accumulating evidence indicates that EphA2 is a critical regulator of cancer development and progression and can function as both a tumor suppressor and an oncogenic driver. When acting as an oncogenic driver, EphA2 can promote tumor initiation, growth, invasion, metastasis, stemness, and angiogenesis by activating or enhancing the oncogenic signaling pathways. High expression of EphA2 in a wide range of human tumor tissues is closely associated with poor prognosis, thus it is a very promising target for cancer treatment. A number of studies on EphA2-targeted cancer treatment are currently at the clinical trial stage. In this review, we discuss the oncogenic roles and mechanisms of action of EphA2 in cancer development and progression, which could provide novel insights into EphA2-targeted cancer treatment.

Peritoneal metastasis is a major contributor to progression, recurrence, and treatment failure in epithelial ovarian cancer (EOC) and is closely associated with dynamic remodeling of the peritoneal tumor microenvironment (TME). Interactions among tumor cells, ascites, the omental niche, stromal components, and immune cells collectively shape metastatic dissemination and therapeutic response. CC chemokines are important regulators of these processes, linking immune-cell trafficking with tumor-cell plasticity, metabolic adaptation, angiogenesis, and therapy resistance. This review summarizes the roles of CC chemokines in EOC progression within a chemokine-driven peritoneal niche remodeling framework encompassing four key stages: early dissemination, survival in ascites, omental colonization, and therapy resistance. Among the major signaling axes, CCL2-CCR2 is primarily associated with monocyte recruitment and myeloid-dominant immunosuppression, whereas CCL5-CCR5 is linked to stromal immune regulation and cancer stem-like phenotypes. Additional pathways, including CCL18, CCL20-CCR6, CCL22-CCR4, and CCL1-CCR8, contribute to T-regulatory cell recruitment, immune suppression, and hypoxia-associated responses. The review further discusses the limited efficacy of chemokine-targeted monotherapy, highlighting challenges posed by signaling redundancy, compensatory pathways, spatial heterogeneity, and insufficient biomarker-guided patient selection. Recent advances in single-cell and spatial transcriptomic technologies have improved the characterization of compartment-specific chemokine programs within the EOC microenvironment. Finally, emerging combination strategies involving chemokine blockade together with immune checkpoint inhibitors, metabolic interventions, PARP inhibitors, and ferroptosis-related approaches are evaluated. However, successful clinical translation will require precise patient stratification, effective toxicity management, and validation in clinically annotated cohorts.

We present a pump-free, gravity-assisted microfluidic lab-on-a-chip platform for the rapid detection of the rice blast pathogen Magnaporthe oryzae by targeting the AvrPi9 gene. The system integrates precise thermal control, programmable fluidic sequencing, and lateral-flow readout, enabling low-power diagnostics without complex instrumentation. Temperature regulation is achieved using a LinkIt 7697 development board, coupled with a proportional-integral-derivative (PID) controller, to drive a Peltier element. This maintains a stable reaction environment at 39&#x2009;&#xb1;&#x2009;0.5&#xa0;&#xb0;C for recombinase polymerase amplification (RPA). The microfluidic chip (65&#xa0;mm &#xd7; 34&#xa0;mm &#xd7; 5&#xa0;mm) is fabricated via laser cutting and hot pressing, with the reaction chamber validated for spatial temperature uniformity through infrared thermal imaging. To enhance operational reliability in field settings, the platform utilizes a manual pin-actuated puncture mechanism to initiate fluidic transport. After a 5-minute isothermal amplification, the physical piercing of a sealing membrane opens strategic air vents, inducing a capillary-driven flow and pressure imbalance that facilitates the pump-free transport of 30 &#xb5;L of RPA products into the lateral flow strip (LFS). This deterministic mechanical gating replaces complex actuators, ensuring a 100% success rate for vent opening. Visual results appear within 2&#xa0;min, with a total assay time of approximately 15&#xa0;min, achieving a detection limit of 10 pg/&#xb5;L for AvrPi9. The system demonstrates high specificity, with no cross-reactivity to non-target pathogens, including Bipolaris oryzae, Sarocladium oryzae, and Ephelis sp., owing to strategic primer mismatches. This robust, pin-actuated, valve-free system highlights the potential for reliable, low-power, field-deployable nucleic acid diagnostics in point-of-care settings. While this study serves primarily as a hardware engineering proof-of-concept focusing on pump-free fluidic transportation, it establishes a foundational architecture for decentralized molecular diagnostics. Future translational development will focus on integrating raw matrix sample preparation to bypass the current limitation of requiring purified nucleic acid inputs.

Protein-DNA binding-site prediction is essential for understanding gene regulation and protein function, but remains difficult because DNA recognition depends on both sequence context and three-dimensional structure. We developed RGTBind, a graph transformer that combines multi-scale radial basis function distance encoding with a learnable threshold-gating mechanism to model spatially informative residue interactions. On the independent Test_129 and Test_181 benchmarks, RGTBind achieved the best F1, AUC, and MCC among the compared methods, supporting the value of distance-aware attention with structure-guided neighbor selection for residue-level protein-DNA binding-site prediction. Each protein was represented as a residue-level graph derived from AlphaFold2-predicted structures. Residue features included AlphaFold2 single representations, DSSP-derived structural descriptors, PSI-BLAST position-specific scoring matrices (PSSM), and HHblits hidden Markov model (HMM) profiles. Pairwise C &#x3b1; -C &#x3b1; distances were encoded using a multi-scale radial basis function scheme and incorporated into a graph transformer through spatially biased multi-head self-attention and a learnable threshold gate. Sequence redundancy was reduced with CD-HIT. The model was trained with AdamW using five-fold cross-validation on Train_573 and evaluated on the Test_129 and Test_181 benchmark datasets.

BRG1/BRM-associated factor (BAF)-family chromatin remodelers regulate transcription and genome organization by repositioning nucleosomes. The human non-canonical BAF (ncBAF) complex is uniquely defined by the presence of BRD9 and GLTSCR1/GLTSCR1L, as well as the absence of the ARID1/2 scaffold and the canonical nucleosome-binding module found in cBAF and PBAF. How ncBAF assembles and engages nucleosomes remains elusive. Here, we present a cryo-EM structure of ncBAF bound to a nucleosome, integrated with biochemical assays and crosslinking mass spectrometry analyses. The ncBAF complex adopts a three-module architecture comprising an ATPase motor module, a repositioned actin-related protein (ARP) module, and a highly flexible Base module. The ncBAF-specific subunits BRD9 and GLTSCR1L are largely dispensable for complex assembly and nucleosome remodeling. Instead, BCL7A directly engages the H2A-H2B acidic patch and the H2A N-terminal tail, providing a structural substitute for SMARCB1 in stimulating remodeling activity. These findings reveal how ncBAF compensates for the loss of the canonical nucleosome-binding module through modular reorganization, providing a structural framework for understanding ncBAF-mediated chromatin regulation and its roles in development and disease.

Transdermal delivery systems (TDDS) mark a revolutionary concept in contemporary pharmacological treatments, providing an efficient replacement for the classical methods of drug administration through the oral route and other parenteral routes of administration, bypassing the first-pass effect and ensuring better patient compliance. Nevertheless, the topical delivery of drugs often becomes an issue due to the role played by the stratum corneum, which acts as the primary resistance point on the skin. For this purpose, ethosome-based nanoparticles have been recognized as a highly flexible carrier system. In contrast to liposomes, ethosomes exhibit a high content of ethanol (20-45%) that helps fluidize the bilayer structure of lipids present in the skin and facilitate transdermal permeation of drugs. This review offers an in-depth insight into the various designs of ethosome carriers and provides a detailed classification of the systems into Classical, Binary, and Transethosomes. The manuscript makes a thorough comparison among the systems based on their structural differences, their respective modes of penetration, and relative strengths in terms of drug loading and physicochemical stability. Moreover, the complexities involved in their preparation are illustrated, particularly the importance of the stirrer speed, typically between 700 and 1200 RPM, and other parameters, including temperature maintenance and lipid: ethanol ratios, that determine the size and distribution of the vesicles formed. Alongside formulation approaches, the potential of ethosomes as a therapy against various skin diseases like psoriasis, acne, and fungal infections is highlighted, in addition to the application in systemic vaccinations. Importantly, this review addresses the issues associated with the implementation of the technology in clinical settings, especially concerning shelf-life stability of the preparations, cutaneous irritation due to ethanol, and the absence of international regulations for topical nanosystems. Through integration of relevant research conducted up until 2024 and 2025, the review forms the basis for next-generation ethosomes.

Mood disorders are increasingly recognised as disorders of circadian dysregulation, with sleep abnormalities acting as both risk factors and clinical hallmarks. Despite extensive evidence linking circadian disruption to affective pathology, the precise molecular mechanisms remain incompletely defined. The present study aimed to identify shared genetic determinants of the sleep-circadian-mood axis and to discover natural neuromodulators that stabilise melatonergic signalling. Using an integrative network pharmacology and computational modelling approach, 644 overlapping genes across mood disorders, circadian rhythm, and insomnia were identified and mapped into protein-protein interaction networks. Functional enrichment revealed convergence on neuroinflammatory signalling (IL6, TNF, STAT3), circadian machinery (CLOCK, ARNTL, PER, CRY), and melatonergic signalling. Notably, melatonin receptors emerged as mechanistically coherent and clinically actionable GPCR targets, despite lower cluster scores relative to inflammation-dominant modules. Structure-based virtual screening of&#x2009;~&#x2009;1,50,000 natural compounds against Melatonin 1 receptor identified taxifolin (-&#x2009;9.527&#xa0;kcal/mol) and tanshinone IIA (-&#x2009;9.515&#xa0;kcal/mol) as top candidates. Molecular dynamics simulations demonstrated that taxifolin formed highly stable protein-ligand complexes, characterised by sustained hydrogen bonding, reduced RMSD/RMSF fluctuations, and favourable interaction energetics. In contrast, tanshinone showed weaker hydrogen bonding, indicating higher ligand mobility. To provide preliminary biological validation, immunocytochemistry analysis was performed to assess the expression of circadian regulators (CLOCK and BMAL1 (ARNTL)) following treatment. Taxifolin modulated circadian protein expression in a manner comparable to melatonin, indicating an effect on cellular circadian signalling pathways. In conclusion, this study provides a systems-level framework linking circadian disruption, neuroinflammation, and mood pathology, while nominating taxifolin as a natural neuromodulator of melatonergic-associated pathways. These findings highlight taxifolin's translational potential as a safer alternative to synthetic melatonergic agents, representing a new direction in neurotherapy for mood disorders.

The intervention effects and underlying mechanisms of Lactobacillus strains against hypercholesterolemia in mice have been extensively documented. However, fewer studies have focused on the cholesterol-lowering potential and the corresponding metabolic regulatory mechanisms of Pediococcus acidilactici. In the present study, we first characterized the in vitro probiotic properties of a novel lactic acid bacterial strain, Pediococcus acidilactici Z123 (P. acidilactici Z123), which exhibited prominent cholesterol-lowering activity. Subsequently, intragastric administration of P. acidilactici Z123 was carried out in a mouse model of high-fat diet-induced hypercholesterolemia to assess its intervention effect and elucidate the underlying molecular mechanisms. The results revealed that P. acidilactici Z123 possessed desirable probiotic characteristics such as auto-aggregation, adhesion ability, and gastrointestinal fluid tolerance, and showed good biosafety, inculding antibiotic susceptibility and no hemolytic activity. In vivo results demonstrated that supplementation with P. acidilactici Z123 effectively alleviated excessive body weight gain and reduced visceral fat accumulation, improved serum lipid profiles, and ameliorated the histological morphology of the liver and epididymal adipose tissue. Untargeted metabolomics indicated that P. acidilactici Z123 exerted a significant regulatory effect on lipolysis in adipocytes, PPAR and AMPK signaling pathways, primary bile acid metabolism, bile secretion, tryptophan metabolism, etc. Notably, such metabolic regulation was further verified at the transcriptional level. Quantitative reverse transcription PCR (qRT-PCR) analysis revealed that P. acidilactici Z123 intervention could inhibit cholesterol synthesis by downregulating the expression of Hmgcr and Srebf1, and upregulating the expression of Prkaa1. Meanwhile, it also elevated the expression of genes related to fatty acid oxidation (Cpt1a, Ppar&#x3b1;) and bile acid synthesis (Cyp7a1). The present findings will provide valuable theoretical evidence for the development and application of novel functional probiotic products with lipid-regulating properties.

Pseudomonas aeruginosa and Staphylococcus aureus are major opportunistic pathogens capable of developing antibiotic resistance and forming device-associated biofilms, which complicate clinical management. The present study aimed to investigate the antimicrobial and anti-biofilm properties of dermcidin-derived peptides against clinical isolates of these bacteria. Clinical isolates of methicillin-susceptible and methicillin-resistant S. aureus (MSSA and MRSA), as well as carbapenem-susceptible and carbapenem-resistant P. aeruginosa (CSPA and CRPA), were examined for their susceptibility to dermcidin-derived peptides (DCD-1&#xa0;L, SSL-23, and SSL-25). The in vitro inhibitory activity of the peptides on bacterial adhesion and biofilm formation was evaluated at sub-MIC levels, while their biofilm-disrupting potential was assessed on mature biofilms. Furthermore, the expression of key biofilm-associated and quorum-sensing genes was quantified using qRT-PCR following peptide exposure. Dermcidin-derived peptides markedly inhibited bacterial attachment and biofilm formation at sub-inhibitory concentrations (1/2, 1/4, and 1/8 MIC). In addition, they exhibited strong biofilm eradication activity at higher concentrations (8&#xd7;-64&#xd7; MIC). Gene expression analysis revealed significant down-regulation of adhesion- and quorum-sensing-related genes in both S. aureus and P. aeruginosa after treatment. The results suggest that dermcidin-derived peptides, regardless of their net charge, possess potent inhibitory effects on bacterial attachment and biofilm development. These findings highlight their potential as promising therapeutic agents for the prevention and control of biofilm-associated infections.

Skeletal muscle (SkM) atrophy is an associated disorder of cachexia, sarcopenia, immobilization, and denervation and is responsible for increased mortality and morbidity. SkM atrophy is often characterized by increased protein degradation and decreased protein synthesis in skeletal muscle. Increased protein catabolism is firmly associated with protein ubiquitination, an associated post-transcriptional modification of proteins that mediate diverse cellular functions like cell growth, cell death, DNA damage repair, and protein degradation. During the SkM atrophy, the extents of ubiquitination decide the degradative pathway of proteins as well as organelles. The ubiquitination process is regulated by three enzymes, ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and an E3 ubiquitin ligase (E3) to mediate the transfer of ubiquitin to the Lys residue of the targeted protein. More than 600 E3 ligases (Reviewed Uniprot Database) known to date are tissue-specific, organ-specific, and ubiquitous. Hence, E3 ligases may be selective drug targets due to their involvement in the regulation of stabilities and functions of proteins. Muscle atrophy F-box protein (MAFbx)/atrogin-1, and E3 ubiquitin-protein ligase TRIM63 (MuRF-1) are highly explored muscle-specific E3 ligases. However, the inhibition of MAFbx and MuRF-1 cannot stop the muscle atrophy completely. Hence, the involvement of other highly expressed E3 ubiquitin-protein ligases in SkM i.e., TRIM7, UBE2O, MIB2, and CHIP are also important factors in SkM atrophy. Hence, this review aimed to highlight the interplay and importance of E3 ligases in SkM atrophy.