Search Results (1,444)

Candida tropicalis has emerged as one of the most clinically relevant non-albicans Candida species, owing to its increasing global prevalence, high mortality associated with invasive infections, and rising rates of antifungal resistance. Although traditionally considered an opportunistic pathogen, growing evidence indicates that its remarkable adaptive capacity is driven by the coordinated regulation of multiple biological processes that promote host colonization, persistence, and immune evasion. In this review, we summarize current knowledge on the epidemiology, biology, genomic organization, virulence factors, and host–pathogen interactions of C. tropicalis. Particular emphasis is placed on recent advances in comparative genomics and functional studies that have expanded our understanding of the molecular determinants underlying adhesion, biofilm formation, morphogenesis, extracellular hydrolytic enzyme production, thermotolerance, cell wall remodeling, and immune evasion. We also integrate orthology analyses identifying putative C. tropicalis homologs of well-characterized Candida albicans virulence genes, highlighting the evolutionary conservation of key pathogenic mechanisms while emphasizing species-specific adaptations that remain functionally unexplored. Finally, we discuss current knowledge of antifungal resistance and the emerging relationship between genomic plasticity, stress adaptation, and pathogenicity. Together, this review provides an updated and comprehensive overview of the biological mechanisms that contribute to the success of C. tropicalis as an emerging opportunistic pathogen and identifies key areas requiring further investigation to improve diagnosis, treatment, and the development of novel antifungal strategies. Full article

Understanding how dams restructure fish diversity is critical for biodiversity conservation and reservoir management. Here, we integrated species, taxonomic, and functional diversity within a unified framework to assess fish community responses to the Datengxia Water Conservancy Project impoundment on the Hongshui River (Pearl River basin). Based on surveys before (2013) and after (2020–2022) impoundment across upstream, downstream, and tributary reaches, we recorded 162 species, including four nationally protected, four endangered, two critically endangered, and 19 exotic taxa. Our three-dimensional assessment uncovered three key patterns: (1) a marked community shift toward limnophilic and slow-flowing species, with three new dominants (Ptychidio jordani, Culter alburnus, and Oreochromis mossambicus) emerging, while rheophilic and migratory forms contracted; (2) trait-selective diversity losses—locomotion-related functional richness (FRic) declined substantially (up to 42.1% at Wuxuan), whereas feeding-related FRic increased markedly (up to 55.1% at Laibin), and reproduction-related traits exhibited stable compositional profiles (spring-dominated spawning, demersal-adhesive eggs) with heterogeneous index responses across sections; taxonomic diversity revealed closer taxonomic relatedness and structural imbalance; (3) a consistent spatial gradient (tributary > downstream > upstream), with downstream assemblages exhibited lower spatial variation in diversity indices. These community shifts were observed alongside habitat modification (lotic habitat shrinkage and fragmentation) and coincided with exotic invasions and over-dominance of resident species. These patterns should be interpreted as descriptive findings given the observational design. This three-dimensional assessment framework provides complementary insights for evaluating dam-related ecological impacts, generating testable hypotheses for future research and conservation planning. Full article

Obesity is one of the most pressing public health challenges of our time, with a growing impact on metabolic and reproductive dysfunction in women. The expansion of visceral adipose tissue drives a chronic, low-grade systemic inflammatory state that has been associated with functional changes in the ovary, the endometrium, and the placenta across different stages of the reproductive process. This structured narrative review, guided by a PICo-framed research question and literature searches across PubMed/MEDLINE, Scopus, Web of Science, Embase, and ScienceDirect, examined the main immunometabolic mechanisms underlying female obesity and their reported associations with ovarian dysfunction, implantation failure, placental dysfunction, infertility, and preeclampsia. The evidence indicates that chronic low-grade inflammation, insulin resistance (IR), and functional hyperandrogenemia may impair folliculogenesis, oocyte quality, and ovarian reserve, while cytokine and adhesion-molecule dysregulation in the endometrium has been linked to impaired decidualization and a narrower implantation window. At the maternal–fetal interface, this same inflammatory substrate has been associated with deficient trophoblast invasion, inadequate spiral artery remodeling, and angiogenic imbalance, mechanisms widely implicated in the pathophysiology of preeclampsia. Rather than demonstrating a proven longitudinal chain within the same individual, the evidence reviewed here, drawn from heterogeneous populations, study designs, and experimental models, supports a conceptual, hypothesis-generating model in which obesity-related systemic inflammation may contribute to dysfunction across the ovary, endometrium, and placenta. Clinically, these findings support further investigation of reproductive biomarkers and early screening strategies for women with obesity, particularly in the context of assisted reproduction, alongside emerging preconception therapeutic approaches that remain largely investigational. Female obesity should therefore be understood not merely as a metabolic disorder, but as an immunometabolic condition potentially associated with dysfunction across the ovary–endometrium–placenta axis, an integrative framework that may help guide future preventive and therapeutic strategies for reproductive health, pending confirmation in longitudinal studies. Full article

Rapid hemostasis, oxidative stress resistance, and minimally invasive administration are crucial performance requirements for high-performance wound covering. Inspired by the dynamic remodeling properties of the native extracellular matrix, we fabricated a multifunctional injectable hydrogel through dynamic Schiff-base crosslinking between oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CMCS), combined with magnesium ion (Mg²⁺) coordination. The effects of Mg²⁺ content on hydrogel properties were systematically investigated. The hydrogels gelled rapidly under physiological conditions and showed good injectability, self-healing behavior, and favorable adhesion to moist tissues. Notably, Mg²⁺ incorporation significantly enhanced hemostatic performance in a mouse tail amputation model, reducing blood loss from 391.7 mg to approximately 75 mg and shortening hemostasis time from 151.7 s to 50.3 s. The 2, 2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging efficiency reached approximately 80%, and the hydrogel effectively scavenged intracellular reactive oxygen species (ROS) without compromising cytocompatibility or fibroblast activity. This study presents a biomimetic and easily prepared hydrogel platform that integrates pro-coagulant activity, redox regulation, and on-demand injectability, showing translational potential as bioactive wound covering for bleeding control and oxidative microenvironment regulation. Full article

The intestinal immune system is essential for insects to defend against pathogenic infections, while the dual oxidase-reactive oxygen species (DUOX-ROS) pathway is a key component. However, the role of the DUOX-ROS pathway in Bombyx mori against Nosema bombycis, a significant pathogen of this species, remains poorly characterized. In this study, four core components of the DUOX-ROS pathway in B. mori (BmGαq, BmPLCβ1, BmPLCβ4, and BmDUOX) were identified using bioinformatics. Pathogen induction experiments showed significant upregulation of BmDUOX and increased ROS production following N. bombycis infection. Immunofluorescence and antibody-blocking assays demonstrated that BmDUOX localizes to the plasma membrane and is essential for inhibiting spore adhesion and invasion. This study provides the first systematic evidence of DUOX-ROS-mediated anti-microsporidian immunity in B. mori, which may provide a theoretical basis for the future development of ROS-based disease control strategies in sericulture. Full article

CD97 is an adhesion G-protein-coupled receptor encoded by ADGRE5 that integrates extracellular signals (including cell adhesion, ligand binding, and mechanical stimulation) with intracellular signal transduction. Recent structural studies have further elucidated tethered/intramolecular agonist (TIA)/Stachel recognition and engagement of the seven-transmembrane domain (7TMD), activation-associated 7TMD conformational changes, and G-protein coupling, including the structural basis for the preferential coupling of CD97 to G13. Currently, antibody–drug conjugates (ADCs) targeting CD97 are supported by in vitro proof-of-concept evidence, whereas chimeric antigen receptor (CAR) strategies have shown antitumor activity in animal models of glioblastoma (GBM) and acute myeloid leukemia (AML). Existing research indicates that CD97 is involved in maintaining stem-like states, invasion and metastasis, metabolic adaptation, and stress survival in certain tumors, and its function varies depending on tumor type and cellular environment. Because CD97 is also expressed in normal immune cells and various nonhematopoietic tissues, systemic targeted therapy may be limited by on-target/off-tumor toxicity. This article reviews the latest advances in CD97 structure and signal transduction, and explores its tumor-related functions, biomarker value, evidence for ADC and CAR-related therapies, as well as early exploratory directions involving RNA-mediated downregulation and structure-guided interventions. Full article

CA, a major bioactive component of cinnamon essential oil, possesses broad-spectrum antibacterial, anti-inflammatory, and antioxidant activities and is widely recognized as a safe food additive. In the context of exploring natural plant extracts for the prevention and alleviation of bovine mastitis, it is noteworthy that research and clinical reports on the use of cinnamon essential oil for bovine mastitis are relatively limited. In this study, S. aureus isolates recovered from subclinical bovine mastitis were used to establish a mastitis infection model, and the antioxidant and anti-inflammatory effects of CA were preliminarily investigated in both mouse mastitis models and mammary epithelial cells (MAC-T). Studies have demonstrated that in a mouse model of mastitis, CA reduces inflammatory cell infiltration, decreases myeloperoxidase (MPO) activity, and inhibits S. aureus colonization in mammary tissue. CA alleviates oxidative stress by lowering malondialdehyde (MDA) levels, enhancing superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, and activating the Nrf2/HO-1/xCT antioxidant pathway. In addition, CA suppresses the activation of the TLR4/NF-κB signalling pathway and modulates the expression of Bax and Bcl-2, accompanied by reduced levels of pro-inflammatory cytokines, including tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), ultimately ameliorating mastitis in mice. In the MAC-T cell infection model, CA significantly inhibited S. aureus adhesion and invasion and decreased the production of pro-inflammatory cytokines and mediators. CA also activated the Nrf2/HO-1/xCT antioxidant pathway, which led to decreased intracellular reactive oxygen species (ROS), concurrently inhibited the TLR4/NF-κB pathway, and downregulated apoptotic protein expression, ultimately attenuating inflammation in MAC-T cells. Collectively, these findings demonstrate that CA exerts protective effects against inflammation and oxidative damage in both mammary tissues and epithelial cells infected with S. aureus. Thus, this study provides a theoretical and practical basis for further exploring CA as a candidate therapy for bovine mastitis. Full article

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening thrombotic microangiopathy caused by severe ADAMTS13 deficiency due to anti-ADAMTS13 autoantibodies. The resulting persistence of ultra-large von Willebrand factor (VWF) multimers promotes uncontrolled platelet adhesion and aggregation in the microcirculation, leading to thrombocytopenia, microangiopathic hemolytic anemia, and ischemic organ injury. Therapeutic plasma exchange (TPE) has transformed the prognosis of iTTP by removing circulating autoantibodies and replenishing functional ADAMTS13, and it remains a life-saving intervention in acute disease. However, TPE is invasive, resource-intensive, dependent on central venous access and plasma availability, and associated with catheter-related, hemodynamic, metabolic, infectious, and plasma-related adverse events. The therapeutic landscape has changed substantially with the incorporation of immunosuppression and the anti-VWF nanobody caplacizumab. Caplacizumab rapidly blocks VWF–platelet interactions at the effector level, whereas corticosteroids and B-cell-directed therapy target the autoimmune basis of iTTP. Triple therapy with TPE, immunosuppression, and caplacizumab accelerates platelet recovery and reduces unfavorable outcomes. At the same time, accumulating observational evidence and early prospective data suggest that selected patients may achieve remission with caplacizumab plus immunosuppression without routine first-line TPE. This perspective review critically re-evaluates the role of TPE in contemporary iTTP management. We propose that TPE should no longer be viewed exclusively as an obligatory universal first-line intervention, but rather as a contextualized component of individualized, response-adapted care. TPE remains indispensable for severe, unstable, or refractory disease and must be immediately available when TPE-free treatment is attempted. Safe implementation of TPE-free strategies requires experienced centers, rapid ADAMTS13 testing, immediate access to caplacizumab and immunosuppression, careful patient selection, and close clinical and laboratory monitoring. Defining which patients can be treated safely without TPE is a central challenge for future trials and guideline development. Full article

Streptococcus salivarius-derived extracellular vesicles (SsEVs) have emerged as important mediators of host–microbe communication, but their role in oral squamous cell carcinoma (OSCC) remains unclear. In this study, SsEVs were isolated and characterized by transmission electron microscopy and nanoparticle tracking analysis, and their uptake by CAL-27 cells was confirmed by fluorescence imaging. Functional assays demonstrated that SsEVs inhibited the proliferation, migration, and invasion of CAL-27 cells in a concentration-dependent manner. RNA sequencing revealed substantial transcriptional reprogramming following SsEV treatment, with enrichment analyses indicating the suppression of pathways associated with cell adhesion, extracellular matrix remodeling, lipid metabolism, and particularly Notch signaling. Gene set enrichment analysis (GSEA) and gene set nariant analysis (GSVA) consistently identified Notch signaling as significantly downregulated. Further validation showed that SsEVs markedly decreased the expression of JAG1, NOTCH1, and HEYL at both the mRNA and protein levels. In a CAL-27 xenograft model, SsEV treatment significantly inhibited tumor growth and reduced JAGGED1, NOTCH1, and HEYL expression in tumor tissues, as confirmed by immunohistochemistry. Collectively, these findings demonstrate that SsEVs suppress OSCC progression both in vitro and in vivo by inhibiting the JAG1–NOTCH1–HEYL signaling axis, suggesting that microbiota-derived extracellular vesicles may represent a promising therapeutic approach for OSCC. Full article

This study investigates the effect of Arundodonax L.-derived lignin on the rheological behaviour, mechanical performance and oxidative ageing resistance of bitumen. Arundo donax is a fast-growing invasive grass with high lignin content, representing a promising sustainable biomass source for bitumen modification. Lignin was extracted via the Acid Detergent Lignin method, yielding a fine powder (50–300 μm). The incorporation of 6 wt% lignin into a 35/50 paving-grade bitumen induced significant changes in binder behaviour. Infrared spectroscopy (FTIR) confirmed the polyaromatic and oxygenated nature of lignin and indicated that its interaction with bitumen is primarily physical, involving polar intermolecular interactions rather than chemical bonding. Lignin modification significantly increased stiffness, elasticity, and rutting resistance, as evidenced by higher softening point, complex modulus, and recovery after creep loading. Furthermore, FTIR analysis confirmed a reduced susceptibility to oxidative ageing, demonstrated by lower increases in carbonyl and sulfoxide indexes after ageing. This suggests distinct antioxidant activity associated with the phenolic structures of lignin. Despite these benefits, severe long-term ageing led to a marked reduction in fatigue life, ductility, low-temperature cracking resistance, and adhesive properties. Overall, these results demonstrate that Arundo donax-derived lignin is a promising sustainable modifier for bitumen, though optimisation of the dosage and blending conditions is necessary to balance durability against long-term fracture performance. Full article

Pectin, a natural biopolymer, is a cost-effective, biocompatible, non-toxic, abundant, and flexible material, making it suitable for recording high-quality bioelectric signals from the dynamic surface of the human body. In this work, pectin-based flexible bioelectrodes were developed for the non-invasive monitoring of biopotentials. The bioelectrodes are composed of pectin, polyaniline emeraldine salt (PANI-ES), glycerol, and polydimethylsiloxane (PDMS) and therefore abbreviated as PPGP. The PPGP electrodes demonstrated a bulk electrical conductivity of (7.54 ± 0.81) × 10⁻³ S/cm, a very low impedance of 34 Ω, and a high charge storage capacity of 4.63 ± 2.70 mC/cm². The surface morphology of the PPGP electrode plays a crucial role in enhancing biopotential signal detection by improving adhesion to skin contours. PPGP electrodes have been successfully used for high-fidelity electromyographic (EMG) bioelectric signal measurements. The developed PPGP bioelectrodes have the potential to advance next-generation human–machine interface (HMI) technologies and wearable healthcare systems, including prosthetic control, rehabilitation monitoring, and assistive communication devices. Full article

Avian pathogenic Escherichia coli (APEC) induces avian colibacillosis and brings huge economic losses to global poultry production. The small alarmone (p)ppGpp mediates the bacterial stringent response, a vital pathway modulating microbial stress adaptation and pathogenic capacity. The functions of the (p)ppGpp synthase gene relA in APEC pathogenesis remain poorly characterized. In this study, we constructed a relA deletion mutant (ΔrelA) and its complemented strain (CΔrelA). The phenotypic and pathogenic characteristics of these strains were investigated. The results showed that deletion of relA did not significantly affect bacterial growth or motility. However, the ΔrelA strain showed increased susceptibility to aminoglycoside antibiotics. Furthermore, the enhanced interbacterial competition of the mutant was associated with the upregulation of core genes in the type VI secretion system (T6SS). Importantly, relA was essential for APEC adhesion to and invasion of avian DF-1 cells, as well as for colonization and virulence in ducklings, where ΔrelA exhibited significantly attenuated infectivity and reduced bacterial loads in the liver and spleen. Furthermore, transcriptomic analysis revealed that RelA deletion downregulated genes involved in integral components of the membrane, and further assays confirmed compromised membrane integrity in the mutant strain. These findings suggest that RelA maintains membrane integrity, which underpins its contributions to antibiotic resistance and virulence. These findings indicate that relA plays a key role in APEC virulence, antibiotic resistance, and membrane homeostasis, and could provide a theoretical basis for targeting the stringent response as a potential strategy to control avian colibacillosis. Full article

The kallikrein–kinin system (KKS) and the kallikrein-related peptidase (KLK) family are interconnected proteolytic networks that regulate inflammatory signaling, vascular permeability, extracellular matrix remodeling, and tissue barrier dynamics. Beyond their classical vasoactive and inflammatory functions, accumulating evidence indicates that kinin peptides, including bradykinin, Lys-bradykinin, and their des-Arg⁹ metabolites, together with selected KLKs, modulate cell–cell and cell–extracellular matrix adhesion. Through B1 and B2 kinin receptor activation, the KKS influences endothelial adhesion molecule expression, leukocyte integrin activation, neutrophil trafficking, focal adhesion kinase/Src signaling, cytoskeletal remodeling, and matrix metalloproteinase activity. In parallel, KLKs directly reshape the adhesive microenvironment by cleaving junctional proteins, including E-cadherin and desmosomal components, and extracellular matrix substrates such as fibronectin, laminin, vitronectin, fibrinogen, and collagens. These coordinated actions affect epithelial and endothelial barrier integrity, leukocyte transmigration, angiogenesis, fibrosis, epithelial–mesenchymal transition, tumor cell migration, invasion, and metastatic dissemination. This review critically summarizes current evidence linking KKS and KLK activity to adhesion-dependent processes in inflammation and cancer, emphasizing how proteolytic signaling may either preserve tissue homeostasis or promote pathological barrier disruption depending on cellular context, receptor expression, protease activity, and microenvironmental cues. Understanding these mechanisms may refine the identification of adhesion-related biomarkers and support the development of targeted therapeutic strategies for inflammatory disorders, fibrotic remodeling, and cancer progression. Full article

Melanoma dissemination depends on tumor cell plasticity, extracellular matrix remodeling, and adaptive signaling pathways that promote survival, migration, invasion, and therapeutic resistance. In this study, we investigated the antitumor effects of the plant-derived Kunitz-type protease inhibitor EcTI using both in vitro B16F10-Nex2 melanoma cells and an in vivo murine melanoma model, focusing on adhesion-dependent signaling, autophagy, mitochondrial dysfunction, and regulated cell death. EcTI was efficiently internalized by melanoma cells and showed partial colocalization with lysosomal and mitochondrial compartments, suggesting intracellular trafficking toward these organelles. Treatment reduced cell adhesion to extracellular matrix proteins, particularly fibronectin and laminin, and inhibited migration, invasion, and angiogenic signaling. These effects were associated with modulation of the adhesion-dependent FAK/Src/ERK signaling axis and decreased MMP-9 activity. EcTI also disrupted autophagy, as indicated by accumulation of acidic vesicular organelles, increased LC3-II levels, and modulation of ULK1, Ambra1, and Beclin-1 signaling. In parallel, EcTI induced mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential, intracellular Ca²⁺ dysregulation, and increased reactive oxygen species production. These alterations triggered regulated cell death involving apoptotic and necroptosis-like mechanisms. Importantly, EcTI significantly suppressed tumor growth in vivo without detectable systemic toxicity and modulated inflammatory mediators associated with tumor progression. Overall, these findings demonstrate that EcTI exerts broad antitumor activity by modulating multiple signaling pathways associated with melanoma progression and represents a promising therapeutic candidate for melanoma treatment. Full article

Endometriosis is a chronic, oestrogen-responsive inflammatory disease characterised by endometrial-like tissue outside the uterine cavity. Because retrograde menstruation is common, lesion establishment probably requires cellular competence and a permissive ectopic microenvironment. This hypothesis-driven narrative review evaluates fascin (FSCN1) as a candidate cytoskeletal effector and considers antecedent eutopic priming versus induction after ectopic adhesion. Functional evidence was integrated with a targeted public-data screen. Donor-level reanalysis of GSE179640 found no conclusive overall eutopic case–control difference and predominantly non-epithelial expression. Exploratory analysis of GSE203191 suggested higher FSCN1 expression within a HSPA6+ stromal subcluster in diagnosed cases, without a comparable epithelial signal or detectable increase in subcluster abundance. This small post hoc analysis remains hypothesis-generating. FSCN1 was absent from the published HECA stromal/macrophage differential-expression lists and was not prioritised by the 2023 endometriosis GWAS. The current evidence therefore argues against uniform epithelial or whole-eutopic overexpression but permits a lineage-restricted stromal state. Fascin participates in autophagy- and miR-145-sensitive invasion networks, although these pathways are pleiotropic. Validation requires cycle- and lineage-resolved tissue mapping, compositional controls, matched lesions, and direct FSCN1 perturbation. Fascin should currently be regarded as a candidate multi-marker component and preclinical target, not a validated biomarker or systemic therapeutic target. Full article