Search Results (59,174)

Catheter-associated urinary tract infections are often caused by biofilm formation on device surfaces. This paper presents an antimicrobial catheter-coating hydrogel comprising p(HEMA) and carboxyl-functionalized p(HEMA-co-MA), loaded with benzalkonium chloride (BAC) to increase hydrophilicity, pH responsiveness, and antibiofilm activity. Hydrogels were prepared by free-radical polymerization, loaded with BAC via swelling, and their physicochemical properties were characterized. Furthermore, microbiological assessment focused on the detection of MIC/MBC/MFC, disk diffusion, biofilm assays, SEM imaging, and RT-qPCR sequencing were used to determine the impact on biofilm-related gene expression to evaluate antimicrobial activity against major catheter-associated urinary tract infection (CAUTI)-associated pathogens and identify the higher BAC loading p(HEMA) and enhanced hydrophilicity and pH-responsive swelling (p(HEMA-co-MA)). The two hydrogels exhibited a wide range of antimicrobial activity and provided lasting inhibition for up to 8 days. It is worth noting that the MA-functionalized hydrogel exhibited a high intrinsic antifouling property, and biofilm development was reduced by more than 85% in BAC-loaded formulations. SEM and gene-expression studies showed reduced microbial adhesion and substantial repression of virulence and biofilm-associated genes. In summary, BAC-loaded p(HEMA) and p(HEMA-co-MA) coatings exhibit strong antimicrobial and antiadhesive properties, and the incorporation of MA results in more effective biofilm suppression, which supports their future use as advanced catheter coatings to prevent the development of device-related infections. Full article

Background: Plasma fibrinogen (FIB) levels exhibit a significant elevation during the acute phase of ischemic stroke (IS), and their dynamic fluctuations serve as important biomarkers for stroke onset, disease progression, and long-term prognosis. Tong-Qiao-Huo-Xue Decoction (TQHXD) is highly effective in treating blood stasis syndromes affecting the head and face. Nevertheless, the association between TQHXD and FIB in the underlying mechanism of treating IS warrants further investigation. Methods: Proteomics analysis predicted the potential therapeutic targets of TQHXD for IS. An in vivo model of middle cerebral artery occlusion followed by reperfusion (MCAO/R) was created in mice. To explore the interaction between FIB and NLRP3, as well as to verify the particular healing outcomes of TQHXD. Results: An increased blood–brain barrier (BBB) permeability was observed after MCAO/R, accompanied by substantial accumulation of FIB in the brain. In vivo experiments demonstrated that FIB triggered the activation of the NLRP3 inflammasome in microglia. Proteomic analysis revealed a significant increase in FIB levels following model induction, which were markedly reduced after treatment with TQHXD; KEGG pathway enrichment analysis indicated that these changes were primarily associated with the NOD-like receptor signaling pathway. Laser speckle contrast imaging showed that TQHXD treatment significantly improved cerebral blood flow and attenuated brain injury in mice. Fluorescence imaging, ELISA, and Western blotting results collectively demonstrated that TQHXD effectively reduced FIB accumulation and suppressed NLRP3 inflammasome activation. MD and pull-down experiments further demonstrated a strong interaction strength between FIB and NLRP3. Conclusions: FIB accumulates in the ischemic penumbra following CIRI, while TQHXD can effectively down-regulate FIB expression and inhibit NLRP3 inflammasome activation to mitigate CIRI. These findings provide a novel theoretical foundation and treatment direction for stroke management in clinical settings. Full article

Antimicrobial resistance (AMR) was associated with 4.95 million deaths in 2019 and may cause 10 million deaths annually by 2050. We synthesize evidence on how the black soldier fly (Hermetia illucens) has evolved an expanded antimicrobial peptide (AMP) repertoire, which structural features drive family-specific activity, what mechanisms are directly demonstrated in H. illucens, and how AI contributes. PubMed, Web of Science, and Scopus (plus targeted Google Scholar) were searched from inception to 1 February 2026; studies were included when they reported BSF peptide identities, expression/proteomics, evolutionary analyses, quantitative activity, mechanistic assays, or BSF-focused computation, and claims were tiered as predicted, expression-supported, or experimentally supported. The literature supports 50–80 BSF AMP genes, plausibly shaped by gene duplication and balancing/diversifying selection in microbe-rich substrates, with marked induction plasticity across tissues, development, diet, and challenge. SAR is family-dependent: defensin-like peptides rely on disulfide-stabilized CSαβ folds and cationic surface topology; cecropin-like peptides on amphipathic α-helices with selectivity trade-offs; attacin-like peptides on β-architecture where charge-based heuristics are weak; and diptericin/proline-rich peptides remain largely inference-driven in BSF. Mechanistic evidence is strongest for membrane/envelope-centered killing by DLP4 and pore-associated envelope disruption by a recombinant attacin-like peptide, whereas pore geometry, oligomerization, intracellular targets, and broad “resistance-proof” claims remain unresolved. Key gaps include assay heterogeneity, salt/serum stability, selectivity/toxicity, resistance-risk testing, and limited in vivo validation, which must be addressed for credible AMR-relevant translation. Full article

Background: Advanced lung adenocarcinoma (LUAD) is the leading cause of cancer-related deaths, with existing treatments hampered by drug resistance. This underscores the urgent need to identify novel therapeutic targets. The role of neuropeptide Y (NPY) receptors in LUAD remains unclear, and this study aimed to investigate their expression profiles, prognostic significance, and the antitumor potential of Euphorbia Factor L2 (EFL2). Methods: Bioinformatics analyses were performed to evaluate NPY receptors in LUAD. Lentivirus-mediated stable neuropeptide Y receptor 5 (NPY5R) knockdown, functional assays including CCK-8, flow cytometry, and scratch assay, PRESTO-Tango, RNA sequencing (RNA-seq), and qPCR were employed to validate the antitumor effects of EFL2 and the functional role of NPY5R. Results: High expression of NPY5R correlated with poor prognosis and immune cell infiltration in LUAD. EFL2 targeted NPY5R, inhibiting A549 cell proliferation and migration while inducing apoptosis. NPY5R knockdown further enhanced these antitumor effects, and the combination of NPY5R knockdown and EFL2 treatment synergistically enriched extracellular matrix (ECM), phosphatidylinositol 3-kinase (PI3K)-Akt, and mitogen-activated protein kinase (MAPK) pathways. Four potential molecular targets were identified. Conclusions: NPY5R is a promising therapeutic target for LUAD. While no clinical drugs targeting NPY5R are currently available, preclinical evidence supports its potential for anticancer drug development. EFL2 exerts antitumor effects via targeting NPY5R, offering useful guidance for developing novel LUAD therapies. Full article

Background: Prostate cancer is a leading malignancy among males, and conventional chemotherapy is often limited by insufficient tumor selectivity and systemic toxicity. Prostate-specific membrane antigen (PSMA), which is highly expressed on prostate cancer cells, represents a promising target for precision drug delivery. In this study, we developed a folate-modified, PSMA-targeting nanoliposome loaded with docetaxel (DFL) to enhance tumor specificity and therapeutic efficacy. Methods: DFL was prepared using a thin-film hydration–sonication method and characterized through physicochemical analyses. Cellular uptake and cytotoxicity were evaluated in PSMA-high LNCaP cells, with PSMA knockdown used to assess target-dependent internalization. Antitumor efficacy was examined with a microfluidic system and LNCaP xenograft nude mice, and safety was evaluated by measuring hepatic and renal biomarkers and performing histopathological analysis of major organs. Results: DFL demonstrated favorable physicochemical properties and significantly enhanced cellular uptake and cytotoxicity in LNCaP cells relative to control formulations. PSMA knockdown markedly attenuated cellular sensitivity to DFL, confirming PSMA-dependent internalization. A 3D microfluidic perfusion platform further corroborated robust and selective DFL uptake under dynamic flow conditions, thereby strengthening the translational relevance of the targeting effect beyond static cultures. In vivo, DFL substantially inhibited tumor progression in LNCaP xenograft models, reducing both tumor volume and weight by more than 50%. TUNEL assays showed increased apoptosis, and immunohistochemistry revealed reduced Ki-67 expression with concomitant upregulation of Caspase-3. No significant alterations in hepatic or renal biomarkers were observed, and histopathological evaluation demonstrated no treatment-associated lesions in major organs. Conclusions: A folate-modified, PSMA-targeting docetaxel nanoliposome was successfully developed, demonstrating enhanced tumor-specific drug delivery and improved antitumor activity with favorable biocompatibility in preclinical models. DFL represents a promising nanomedicine strategy for the precision chemotherapy of prostate cancer. Full article

Ultra-dense networks (UDNs) enable next-generation wireless systems by providing high capacity through aggressive base-station densification. However, dense deployments increase interference and energy consumption, making Quality-of-Service (QoS) aware performance evaluation and optimization challenging. Stochastic geometry (SG) provides a tractable framework for modeling large-scale UDNs, but its use is often limited by simplifying assumptions and simulation requirements. In parallel, Deep Learning (DL) offers scalable tools for capturing complex network behavior from data. This paper proposes a scalable analytical and data-driven framework for performance evaluation and energy efficiency (EE) optimization in UDNs. SG-based analysis is used to derive expressions for key metrics, including coverage probability and EE, under practical QoS constraints such as base-station density, transmit power, activation probability, and SINR thresholds. These results are used to construct a supervised learning dataset, where network parameters and SG derived metrics serve as inputs, and simulation outcomes act as labels. A DL model is trained to capture the nonlinear mapping between network configurations and performance metrics. Results show that the proposed framework predicts coverage probability and EE accurately for unseen UDN scenarios while substantially reducing computational complexity compared to conventional SG-based methods, without violating QoS constraints. Full article

Metallothioneins (MTs) and heat shock protein 70 (HSP70) are key regulators of cellular stress response and metal homeostasis and play important roles in tumor biology. The aim of this study was to examine their expression patterns and potential prognostic significance in different molecular subtypes of breast cancer (BC), with special emphasis on triple-negative breast cancer (TNBC) and the Luminal A subtype, compared with benign breast lesions (fibroadenomas). A total of 90 tissue samples were included, and the expression of MTs in the cytoplasm and nucleus and HSP70 in the nucleus of tumor cells was analyzed immunohistochemically and correlated with clinicopathological features and treatment outcomes. Distinct expression patterns of HSP70 and MTs were observed between malignant and benign samples, as well as among the analyzed molecular subtypes of BC, suggesting their involvement in cellular adaptive mechanisms associated with malignant transformation. TNBC was characterized by less favorable clinicopathological features compared to the Luminal A subtype, including higher histological grade, increased proliferative activity, and a higher incidence of recurrence and metastatic disease. Survival analyses confirmed a worse outcome for patients with TNBC, while HSP70 and MTs expression did not show independent prognostic value in multivariate models. In conclusion, although HSP70 and MTs play important biological roles in the cellular response to stress and tumor adaptation, their expression in this study does not represent an independent prognostic indicator of clinical outcome. Nevertheless, the observed expression patterns provide insight into the complex mechanisms of tumor adaptation and emphasize the need for integrative approaches in BC biomarker research. Full article

Small heat shock proteins (HSP20s) are known to function as molecular chaperones that bind to denatured proteins under high-temperature stress and assist in their conformational recovery, thereby contributing to plant thermotolerance. In the present study, three HSP20 genes—PcHSP12.8, PcHSP12.9, and PcHSP13.4—were identified in the transcriptome of Polygonatum cyrtonema Hua. Bioinformatics analysis indicated their phylogenetic relationships, conserved domains, and potential tertiary structures. RT-qPCR analysis revealed up-regulation of all three genes in response to heat stress. Subcellular localization studies further suggested that PcHSP12.8, PcHSP12.9, and PcHSP13.4 are predominantly localized in the nucleus. Heterologous expression of these genes in a heat-sensitive yeast mutant appeared to improve cell survival under heat stress relative to the control strain. In Arabidopsis thaliana overexpressing these genes, moderate improvements in germination rate, root elongation, and stress survival were observed compared to wild-type plants under heat stress. Transgenic lines also showed a tendency toward reduced reactive oxygen species accumulation, as reflected by decreased 3,3′-diaminobenzidine (DAB) and nitroblue tetrazolium (NBT) staining, together with increased activities of catalase (CAT) and peroxidase (POD), as well as higher chlorophyll retention under thermal stress. Taken together, these findings imply that the three PcHSP20 genes could be involved in thermotolerance in P. cyrtonema. Full article

Glioblastoma (GBM) is an aggressive tumor with limited therapeutic options. Zika virus (ZIKV) has demonstrated activity against GBM; however, the cellular pathways behind this interaction remain unclear. We systematically reviewed open-access primary studies assessing differentially expressed genes (DEGs) in GBM models infected with wild-type or engineered ZIKV using transcriptomic approaches (inclusion criteria); reviews, restricted-access studies, commentaries, preprints, abstracts, and articles lacking data or not meeting these conditions were excluded (PROSPERO CRD420251077092). We performed a pathway analysis of reported DEGs. PubMed and Google Scholar were searched up to 5 March 2025; 139 records were identified and 5 met the eligibility criteria. Risk of bias was evaluated using an adapted ToxRTool for in vitro experiments and the SYRCLE RoB tool for in vivo models. Altogether, 4360 genes were reported as upregulated and 2072 as downregulated; 12 genes (DNAJB9, SESN2, PMAIP1, PPP1R15A, KLF4, ATF3, IFNB1, IFNL1, ANKRD33B, ZC3HAV1, OASL, and CCL5) were consistently upregulated, none were consistently downregulated. Pathway analysis of the studies providing complete DEG lists identified 23 commonly enriched pathways mostly related to interferon signaling. These findings may help guide future research in this field; nevertheless, methodological heterogeneity limits comparability, reinforcing the need for standardized protocols. Funding: ITpS, CNPq, and FAPEMIG. Full article

Chinese tongue sole (Cynoglossus semilaevis) is an important aquaculture species in China. Under high-temperature conditions, genetically female fish can undergo sex reversal and develop into phenotypic males (pseudomale fish). Previous studies have demonstrated that apoptosis might function in sex differentiation. Based on this, we identified and characterized the functions of six caspase genes (caspase1-like, caspase3a, caspase6, caspase8, caspase8-like, caspase9) in Chinese tongue sole. These six caspase genes were expressed in all analyzed tissues of both males and females. They were detected to be expressed in the gonads at various developmental stages, with expression levels peaking between 7 months and 2 years of age. In situ hybridization (ISH) analysis showed that the caspase genes were mainly localized in spermatocytes and oocytes. Promoter activity analysis indicated that with the exception of caspase3a, the remaining five caspase genes exhibited promoter activity and were regulated by transcription factors, including sp1 and gata4. High-temperature stimulation can significantly affect the expression of caspases in the gonads of both male and female fish, with female fish showing a more pronounced response. An siRNA-mediated knockdown experiment revealed that following caspase knockdown, the expression of sex differentiation-related genes, heat shock transcription factors (hsf), and heat shock proteins (hsp) in Chinese tongue sole was significantly altered. Based on these findings, we speculate that caspases play an important role in the sex differentiation process by responding to temperature stimuli. Full article

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, underscoring the need to elucidate molecular mechanisms that regulate tumor cell state and behavior. Leucine zipper–like post-translational regulator 1 (LZTR1) regulates RAS/mitogen-activated protein kinase (MAPK) signaling, yet LZTR1-dependent transcriptional alterations in HCC cells remain poorly defined. To address this gap and determine how LZTR1 loss reshapes signaling, transcriptional programs, and cellular phenotypes, we established a LZTR1 knockout (KO) Hep3B model and combined pathway profiling with transcriptomic and functional analyses. Immunoblotting revealed increased phosphorylation across the RAF–MEK–ERK–RSK cascade in LZTR1 KO cells. Transcriptome-wide RNA sequencing (RNA-Seq) identified differentially expressed genes, and selected findings were validated by qRT-PCR. Gene set enrichment analysis indicated that the epithelial–mesenchymal transition (EMT) gene set was enriched in control cells. At the protein level, LZTR1 loss remodeled EMT-associated markers in a hybrid epithelial–mesenchymal pattern consistent with epithelial–mesenchymal plasticity (EMP). Vimentin was suppressed at transcript and protein levels. Functionally, LZTR1 KO cells exhibited impaired wound closure and reduced transwell migration and invasion. Collectively, these findings define an EMP-related molecular and phenotypic state associated with LZTR1 deficiency in Hep3B cells, providing insight into how LZTR1 loss reshapes tumor cell behavior in HCC. Full article

Tea is a vital economic crop in China, with many anthocyanin-rich cultivars having been bred. Photoperiod is an important environmental factor that regulates anthocyanin production in plants. Nonetheless, the precise mechanisms by which photoperiod affects anthocyanin biosynthesis in tea plants remain unclear. In this study, the purple-leaf cultivar Camellia sinensis ‘Ziyan’ was exposed to three different photoperiods: 8 h/16 h (light/dark, short-day, SD), 14 h/10 h (light/dark, medium-day, MD), and 20 h/4 h (light/dark, long-day, LD). A comprehensive analytical approach, including transcriptomics, enzymology, and quantitative anthocyanin analysis, was used to uncover the molecular and biochemical processes regulating anthocyanin synthesis in purple-leaf tea plants grown under varying photoperiods. The results showed that the delphinidin, cyanidin, pelargonidin, and total anthocyanin contents in the long-day treatment were 178.10%, 92.37%, 50.40%, and 148.76% higher, respectively, than those in the short-day treatment. Under long-day conditions, all structural genes associated with anthocyanin synthesis were upregulated, and enzymatic activities related to anthocyanin synthesis were significantly increased. Furthermore, the regulatory genes (MYB1, MYB73, MYB111, MYB48, MYB75, MYB113, MYB5, MYB12, MYB5a, MYB5b, and WRKY41) were differentially expressed under short- and long-day treatments. These findings suggest that extended photoperiods activate the expression of structural genes through gene regulation and enhancement of enzymatic activity, thereby facilitating anthocyanin biosynthesis. This study provides novel insights into the photoperiodic regulation of anthocyanin biosynthesis in tea plants. Full article

Background: Cutaneous melanoma is an aggressive malignancy driven by complex interactions between tumor cells and the host immune system. Tumor progression is shaped not only by intrinsic tumor characteristics but also by immune-mediated processes within the tumor microenvironment. Cytokines, particularly interleukins, are key regulators of inflammation, immune cell recruitment, and tumor behavior. Cytokine profiling provides an integrated assessment of soluble immune mediators from tumor and stromal cells, reflecting both local and systemic immune responses. Methods: This narrative review summarizes and synthesizes the current literature addressing the biological and clinical relevance of selected interleukins, including IL-6, IL-8, IL-10, IL-2, IL-17, and IL-18, in cutaneous melanoma. Published data were evaluated with a focus on their immunomodulatory functions and potential implications for prognostic assessment. Results: Interleukins demonstrated distinct and context-dependent prognostic and predictive relevance in cutaneous melanoma. Elevated IL-2 levels correlated with sentinel lymph node positivity, supporting its prognostic value in early disease. Increased circulating IL-6 and IL-8 were consistently associated with tumor burden, advanced disease, and reduced survival. IL-10 expression reflected tumor progression and immune modulation. IL-17 signatures predicted response to combined immune checkpoint inhibition, particularly in BRAFV600-mutant melanoma. IL-18 exhibited dual roles, associating with both immune activation and favorable outcomes depending on tumor context. Conclusions: Interleukin profiling offers a biologically relevant framework for understanding immune regulation in cutaneous melanoma. Integrating interleukin signatures into prognostic models may support more refined risk stratification and advance the implementation of personalized medicine approaches in melanoma management. Full article

Luteolin (Ltn), a natural flavonoid, effectively inhibits microglial activation in Alzheimer’s disease (AD) with promising therapeutic potential, but its efficacy is severely limited by the blood–brain barrier (BBB). To overcome this obstacle, this study prepared poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs)—designated as TGN/RAP12-RBC-NPs@Ltn—which were coated with red blood cell membranes (RBCm) functionalized with two peptides, TGN (TGNYKALHPHN) and RAP12 (EAKIEKHNHYQK). The results demonstrated that TGN significantly enhanced BBB permeability, while RAP12 enabled effective targeting and delivery of TGN/RAP12-RBC-NPs@Ltn to microglial mitochondria in the brain. In addition, the presence of RBCm significantly inhibited the phagocytosis of NPs by macrophages, exerting a notable role in immune evasion. Meanwhile, the study confirmed that encapsulating Ltn within NPs significantly enhanced cognitive function in APP/PS1 mice, modulated the expression of key mitochondrial metabolic enzymes—pyruvate dehydrogenase (PDH) and its phosphorylated forms (pS232PDH, pS293PDH, pS300PDH)—in microglia, thereby ameliorating mitochondrial dysfunction and effectively regulating the neuroinflammatory environment in the mouse brain, and ultimately contributed to therapeutic efficacy. From this, it could be seen that TGN/RAP12-RBC-NPs@Ltn could significantly enhance the therapeutic effect of Ltn on AD, providing an effective treatment strategy for delaying the progression of AD. Full article

Oxidative stress has been reported to be implicated in the pathogenesis of many neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. Enhancing antioxidant response, through the activation of the transcription factor Nrf2, may represent a potential strategy, based on in vitro models. To identify scaffolds potentially able to modulate the Nrf2-Keap1 interaction, docking experiments were carried out using a library of commercially available and in-house synthesized molecules. Compounds 1–4 were selected, and their direct and indirect antioxidant activity was evaluated in an acute oxidative stress model induced by Fenton’s reaction in the human neuroblastoma SH-SY5Y cell line. Results showed that these compounds exerted the most pronounced protective effect under the tested conditions at the following concentrations: 10 μM for 1, 25 μM for 2, 10 μM for 3, and 5 μM for 4. Moreover, these molecules notably decreased intracellular ROS production and lipid peroxidation by-products and increased the GSH/GSSG ratio. Furthermore, these molecules promoted the protein expression of antioxidant enzymes downstream of the Nrf2 transcriptional pathway. Interestingly, compound 3 resulted in being the most active among the four. Full article