Search Results (369)

Bacteriophages are ubiquitous biological entities that profoundly influence microbiology research and biotechnology. Among coliphages, T1-like viruses (family Drexlerviridae) are notoriously known for their environmental stability and propensity to contaminate laboratory cultures and equipment. Despite this, the genomic features that may underlie their persistence and recurrent detection as laboratory contaminants remain insufficiently characterized. Here, we describe a novel T1-like bacteriophage, KanT1, identified as a recurrent contaminant emerging from environmental samples. Comparative genomics and phylogenetic analyses position KanT1 within the Tunavirus lineage, confirming its close relationship to canonical T1-like phages. Structure-informed annotation enabled the functional characterization of previously unannotated proteins, highlighting the importance of integrating structural predictions into phage genome analysis. Notably, we provide novel details regarding the distribution of superinfection exclusion cassette cor and identify an SH3 domain-containing protein associated with the lysis cassette. We show that SH3 is widespread, though non-universal, across Drexlerviridae genomes. Given the established role of SH3 domains as determinants of cell-wall binding specificity for endolysins of phages infecting Gram-positive bacteria, we propose that this protein represents an auxiliary component of the T1-like lysis module. Together, these findings expand the current understanding of T1-like phage genome organization and provide new insights into molecular features that may contribute to their broad host range and persistence in laboratory environments. Full article

LL-37, a 37-amino acid human-derived antimicrobial peptide, was shown in our earlier clinical study to shorten the negative conversion time of the Omicron BA.5.1.3 variant of SARS-CoV-2. In this work, we investigated the broad mechanism of LL-37 by examining its inhibitory effect on non-enveloped virus Enterovirus 71 (EV71). LL-37 treatment dose-dependently reduced EV71 viral RNA abundance, suppressed virus-encoded protein expression, and decreased infectious titers, acting predominantly at a post-entry stage of the viral life cycle. Transcriptomic analysis revealed that the SH3 and cysteine-rich domain protein (Stac) was uniquely upregulated by LL-37 irrespective of EV71 infection. Short hairpin RNA (shRNA)-mediated Stac silencing significantly enhanced EV71 infection, while Stac overexpression markedly reduced it. Furthermore, we found that LL-37 activates the EGFR–ERK signaling pathway, leading to time-dependent upregulation of Stac expression. These findings uncover a novel host-directed mechanism by which LL-37 combats EV71 infection and suggests a potential therapeutic use of LL-37 against non-enveloped viral disease. Full article

Background/Objective: Child health serves as a foundational part of human development. Inequities in access to key health services remain high in Sub-Saharan Africa (SSA), most notably among children from disadvantaged, racially, or ethnically marginalized groups. The objective of this structured narrative review is to evaluate and aggregate the available evidence on racial/ethnic disparities in childhood healthcare access in SSA. Methods: A comprehensive search on African Index Medicus (AIM), Web of Science and PubMed for studies published between 2010 and 2025 was executed using relevant MeSH terms and Boolean operators. Studies on healthcare access inequalities among racial or ethnic groups in SSA were included. This study was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Ten articles were included. Ethnicity was an independent contributor to inequities in childhood healthcare across four domains: vaccination coverage (lower for Hausa/Fulani in Nigeria and Somali/Luhya in Kenya compared to dominant groups), timeliness of vaccination, child mortality (higher in economically and ethnically marginalized groups), and nutritional status (elevated stunting and underweight odds in certain ethnic minorities). Conclusions: Racial and ethnic inequalities in child healthcare access across SSA are driven by multi-factor structural, geographical, and cultural barriers. Although socioeconomic improvement reduces some disparities, it does not eradicate them, highlighting that ethnic identity continues to shape health outcomes independently. Addressing these disparities requires strengthening culturally inclusive healthcare delivery, improving access in underserved regions, and integrating ethnicity-disaggregated monitoring into national health systems. Full article

Long non-coding RNAs (lncRNAs) encoded by viruses play crucial roles in viral infection, pathogenesis processes, the interaction between viruses and hosts, and immune escape. Herein, by employing RNA pull-down, mass spectrometry technology, and RNA immunoprecipitation, we identified a host protein (G3BP2) that specifically interacts with the lncRNA encoded by the infectious bronchitis virus (IBV). Additionally, we identified a novel host miRNA (novel-340) in IBV-infected H1299 cells and further verified that novel-340 can target the 3′-UTR (untranslated region) of G3BP2 and downregulate its expression in a dose-dependent manner. We discovered that IBV-lncRNA may facilitate IBV replication in H1299 cells through direct interaction with G3BP2 and/or the regulation of the IBV-lncRNA/novel-340/G3BP2 interactive regulatory network. This work deepens the understanding of the biological function of IBV-lncRNA. Full article

Accurate identification of Alzheimer’s disease (AD)-related cellular characteristics from microscopy images is essential for understanding neurodegenerative mechanisms at the cellular level. While most computational approaches focus on macroscopic neuroimaging modalities, cell type classification from microscopy remains relatively underexplored. In this study, we propose a hybrid vision transformer–convolutional neural network (ViT–CNN) framework that integrates DeiT-Small and EfficientNet-B7 to classify three AD-related cell types—astrocytes, cortical neurons, and SH-SY5Y neuroblastoma cells—from phase-contrast microscopy images. We perform a comparative evaluation against conventional CNN architectures (DenseNet, ResNet, InceptionNet, and MobileNet) and prompt-based multimodal vision–language models (GPT-5, GPT-4o, and Gemini 2.5-Flash) using zero-shot, few-shot, and chain-of-thought prompting. Experiments conducted with stratified fivefold cross-validation show that the proposed hybrid model achieves a test accuracy of 61.03% and a macro F1 score of 61.85, outperforming standalone CNN baselines and prompt-only LLM approaches under data-limited conditions. These results suggest that combining convolutional inductive biases with transformer-based global context modeling can improve generalization for cellular microscopy classification. While constrained by dataset size and scope, this work serves as a proof of concept and highlights promising directions for future research in domain-specific pretraining, multimodal data integration, and explainable AI for AD-related cellular analysis. Full article

Background: Intrinsic capacity (IC) is key to promoting healthy aging, and managing declines in IC is crucial for delaying functional deterioration in older adults. Digital health interventions (DHIs) hold promising potential for addressing IC decline. This scoping review aims to synthesize existing evidence by mapping the types of DHIs employed and examining their effects across the five domains of IC in older adults. Methods: The review was conducted following the five-stage framework of Arksey and O’Malley and the PRISMA-ScR guideline. The search was performed across PubMed, Embase, CINAHL, Cochrane Library, PsycINFO, SinoMed, and CNKI databases for studies published between 1 January 2015 and 31 July 2025. Relevant studies were identified using MeSH terms and free-text terms related to “older adults”, “digital health”, and “intrinsic capacity”. Results: Based on the eligibility criteria, 81 studies were included. The DHIs identified encompassed virtual reality, exergames, computerized cognitive training, mHealth, internet-based interventions, telehealth, digital hearing aids, assistive robotics, and visual biofeedback. Most studies focused on single-domain interventions (74%), with cognition being the most targeted (40.7%), while sensory (4.9%) and vitality (2.5%) domains received the least attention. No digital interventions targeted all five IC domains. Regarding efficacy, many DHIs reported statistically significant improvements in one or more IC domains; however, the magnitude and consistency of these effects varied considerably across studies. Conclusions: Preliminary evidence suggests that DHIs show potential in managing declines in IC among older adults. However, evidence quality varies significantly, often derived from small-scale studies. Future research should focus on establishing clinical effectiveness through adequately powered trials and on integrating DHIs into comprehensive intervention strategies that target all domains of IC, with robust evaluation of their outcomes. Full article

Mutations in leucine-rich repeat kinase 2 (LRRK2) are among the most common genetic causes of Parkinson’s disease (PD), yet substantial heterogeneity exists among pathogenic variants. How mutations in distinct functional domains of LRRK2 differentially perturb cellular homeostasis remains incompletely understood. Here, we compared two pathogenic LRRK2 mutations—G2019S in the kinase domain and I1371V in the GTPase domain—across multiple cellular models, including SH-SY5Y and U87 cells, and healthy human iPSC-derived floor plate cells. We demonstrate that the I1371V mutation induces markedly more severe cellular dysfunction than G2019S. I1371V-expressing cells exhibited elevated LRRK2 autophosphorylation at S1292 and robust hyperphosphorylation of Rab8A and Rab10, indicating enhanced downstream signaling. These alterations impaired sterol trafficking, leading to selective depletion of membrane cholesterol without changes in total cellular cholesterol. Consequently, I1371V cells displayed increased membrane fluidity, disrupted microdomain organization, altered membrane topology, reduced caveolin-1 expression, and impaired dopamine transporter surface expression and dopamine uptake. Lipidomic profiling further revealed a broad disruption of lipid homeostasis, including reductions in cholesteryl esters, sterols, sphingolipids, and glycerophospholipids, whereas G2019S cells showed comparatively modest changes. Pharmacological intervention revealed mutation-specific responses, with the non-selective LRRK2 modulator GW5074 outperforming the kinase-selective inhibitor MLi-2 in restoring Rab8A phosphorylation, membrane integrity, and dopaminergic function. Collectively, these findings identify membrane lipid dysregulation as a central cell biological mechanism in LRRK2-associated PD and underscore the importance of variant-specific therapeutic strategies. Full article

G3BP2 is an important RNA-binding protein that belongs to the mammalian Ras-GAP SH3 domain-binding protein (G3BP) family. Its structure enables it to bind to RNA or proteins, regulate nuclear–cytoplasmic shuttling, and participate in various functions, including cell growth, differentiation, migration, and RNA and protein metabolism. Studies have found that G3BP2 is involved in the occurrence and development of various human diseases, such as high expression across multiple tumor diseases, including gastric cancer, breast cancer, non-small-cell lung cancer, esophageal squamous cell carcinoma, colorectal cancer, and pancreatic ductal adenocarcinoma, driving the occurrence of human tumors, participating in tumor progression, and playing an essential role in promoting the proliferation, invasion, and migration of tumor cells. Additionally, G3BP2 is closely associated with various non-tumor diseases, including viral infections, as well as cardiovascular and cerebrovascular diseases. This review elucidates the role of G3BP2 in the development and progression of various diseases, identifying biomarkers and therapeutic targets for clinical diagnosis and treatment based on G3BP2. Full article

Background: Non-small cell lung carcinoma (NSCLC) is the most prevalent form of lung cancer, and its progression is closely associated with constitutive activation of signal transducer and activator of transcription 3 (STAT3). This study used surface plasmon resonance (SPR) technology to develop a STAT3-targeting recognition system and identify natural STAT3-targeting compounds from the traditional Chinese medicine Psoralea corylifolia and to evaluate their anti-NSCLC activities, with particular attention to reactive oxygen species (ROS) regulation. Methods: The SPR biosensor immobilized with STAT3 was used to screen and enrich STAT3-binding constituents of Psoralea corylifolia, and to determine ligand-STAT3 affinities. Molecular docking was performed to characterize interactions within the STAT3 SH2 domain. Functional effects were assessed in A549 cells using proliferation and scratch migration assays. Antioxidant capacity was evaluated via hydroxyl radical and superoxide anion scavenging assays, and intracellular ROS levels were measured in hydrogen peroxide (H₂O₂)-induced oxidative stress models in human umbilical vein endothelial cells (HUVECs) and A549 cells. Results: SPR analysis showed that psoralen and isopsoralen bind to STAT3, with equilibrium dissociation constants (KD) of 80.92 µM and 28.11 µM, respectively. Molecular docking further confirmed their interaction with the STAT3 SH2 domain. Both compounds inhibited A549 proliferation and reduced migration. Beyond direct STAT3 inhibition, both compounds demonstrated notable free radical scavenging activity. In a H₂O₂-induced oxidative stress model, pretreatment with psoralen or isopsoralen significantly reduced ROS levels in HUVECs, while increasing ROS accumulation in A549 lung cancer cells. Conclusions: This work identifies psoralen and isopsoralen as novel dual-function STAT3 inhibitors that exert anti-NSCLC effects through combined STAT3 suppression and context-dependent ROS modulation, and demonstrates the utility of SPR for screening bioactive natural products. Full article

Hibernation profoundly alters host–pathogen dynamics by suppressing metabolism and immune function, posing unique challenges for infection control. In this study, we examined how genomic variation modulates infection and physiological traits in temperate bats during hibernation. We combined infection screening, haematology, blood biochemistry, and whole-genome sequencing across five vespertilionid species, identifying over 170,000 single nucleotide variants (SNVs) and assessing their associations with 23 health-related variables. Using the phylogenetically informed treeWAS framework, we detected 515 significant SNVs linked to traits including fungal, protozoan and bacterial infections, acid–base balance, and blood cell indices. These SNVs mapped to 137 unique genes, which were enriched for functional domains related to cytoskeletal dynamics, membrane trafficking, and intracellular signalling (e.g., SH3, C2, BAR, semaphorin). Notably, canonical immune effector genes were underrepresented, and several trait-associated SNVs appeared in blocks across multiple scaffolds, pointing to regulatory loci as key modulators of hibernator health. Our findings support the hypothesis that bats rely on infection tolerance rather than resistance during hibernation, with genomic variation in regulatory and signalling pathways shaping their physiological responses to infection under energy-limited conditions. Full article

Background/Objectives: Parkinson’s disease (PD) is one of the most prevalent neurodegenerative disorders. Despite its multifactorial etiology, PD pathophysiology shared specific features such as cytoplasmic α-synuclein inclusions, oxidative stress, mitochondrial dysfunction, and impaired autophagy. Bromodomain and Extra-Terminal domain (BET) proteins, functioning as epigenetic readers, have recently emerged as promising therapeutic targets due to their regulatory role in redox homeostasis, neuroinflammation, and autophagy. However, their potential involvement in PD pathophysiology remains largely unexplored. Therefore, we aimed at evaluating whether BET modulation could ameliorate the parkinsonian phenotype in two cellular models. Methods: Differentiated SH-SY5Y and N1E-115 neuronal cells were exposed to rotenone toxin to mimic PD phenotype and co-treated with the small BET inhibitor JQ1. Results: BET inhibition significantly counteracted rotenone-induced cell death, neuromorphological alterations, and α-synuclein accumulation. These protective effects were accompanied by restoration of redox balance, as indicated by enhanced activation of the antioxidant system and suppression of the pro-oxidant NADPH oxidase complex. Moreover, JQ1 treatment alleviated mitochondrial dysfunction and corrected autophagy impairments triggered by rotenone. Conclusions: These data highlight a novel role for BET proteins in neurodegeneration, suggesting that their modulation may represent a promising approach to counteract PD neuropathology. Full article

Isothiocyanates (ITCs) are well-known electrophilic agents with antioxidant and anticancer properties, largely attributed to their ability to activate the Nrf2/ARE pathway. Building on previous work with C1-ITC glycosyl derivatives, we designed and synthesized a new series of S-glycosyl isothiocyanates in which the ITC group was repositioned to the C6 carbon of the glucose scaffold. This structural rearrangement yielded stable and synthetically accessible derivatives with markedly enhanced biological profiles. Several compounds showed potent Nrf2 activation at non-cytotoxic concentrations, with CD values comparable to or exceeding those of natural ITCs. In parallel, the new C6-ITC derivatives displayed significant antiproliferative activity against leukemia and solid tumor cell lines. Among them, the phenylsulfone derivative 13 emerged as a particularly promising dual-action molecule, combining strong Nrf2 induction with low-micromolar cytotoxicity. Molecular docking was used as a hypothesis-generating approach and suggested a possible interaction with the STAT3 SH2 domain, although further studies are needed to validate this target. Overall, these results support glucose-based ITCs as a versatile platform for the development of multifunctional antioxidants with complementary anticancer properties. Full article

The presence of aberrant double-stranded DNA (dsDNA) in the cytoplasm of cells is sensed by unique pattern recognition receptors (PRRs) to trigger innate immune response. The cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway is activated by the presence of non-self or mislocalized self-dsDNA from nucleus or mitochondria released in response to DNA damage or cellular stress in the cytoplasm. Activation of cGAS leads to the synthesis of the second messenger cyclic GMP–AMP (cGAMP), which binds and activates STING, triggering downstream signaling cascades that result in the production of type I interferons (IFNs) and proinflammatory cytokines. Here, we show that diverse immunostimulatory dsDNA ligands and chemotherapy agents like Doxorubicin and Taxol trigger the integrated stress response (ISR) by activating endoplasmic reticulum (ER) stress kinase, protein kinase RNA-like ER kinase (PERK), in addition to the canonical IFN pathways. PERK-mediated phosphorylation and inactivation of the alpha subunit of eukaryotic translation initiation factor-2 (eIF2α) result in the formation of stress granules (SGs). SG formation by dsDNA was significantly reduced in PERK knockout cells or by inhibiting PERK activity. Transcriptional induction of IFNβ and cytokines, ISR signaling, and SG formation by dsDNA was dampened in cells lacking PERK activity, STING, or key stress-granule nucleating protein, Ras-GAP SH3 domain-binding protein 1 (G3BP1), demonstrating an important role of the signal transduction pathway mediated by STING and SG assembly. Lastly, STING regulates reactive oxygen species (ROS) production in response to DNA damage, highlighting the crosstalk between DNA sensing and oxidative stress pathways. Together, our data identify STING–PERK–G3BP1 signaling axis that couples cytosolic DNA sensing to stress response pathways in maintaining cellular homeostasis. Full article

S. suis is a prominent zoonotic pathogen responsible for diseases such as arthritis in piglets, swine septicemia, and meningitis. The emergence of multi-drug resistance (MDR) underscores the urgent need for the development of novel antibacterial strategies. In this context, a systematic evaluation of the antibacterial potential of the bacteriophage lytic enzyme Ply900 was conducted in this study, along with an analysis of its domain functions and an in vivo study of its therapeutic dynamics. Ply900 exhibits potent in vitro lytic activity against multiple bacteria, including Streptococcus suis, Streptococcus agalactiae, and Staphylococcus aureus. Notably, it possesses broad biochemical stability, with tolerance to diverse environmental conditions. In a mouse model of S. suis serotype 2 SC19 infection, both the direct Ply900 treatment group and the triple therapy group achieved effective eradication of S. suis, with markedly improved survival rates. The remaining bacteria remained susceptible to Ply900, with no evidence of induced resistance development. Mechanistic analysis revealed that the SH3B domain of Ply900 enhances targeted cleavage efficiency by binding synergistically to peptidoglycan with the CHAP domain, with CYS-34, HIS-59, and ASP-28 serving as key amino acid sites for Ply900’s cleavage activity. Collectively, these findings lay the foundation for the potential dual applications of the lysin Ply900, both in the clinical treatment of S. suis infections and in the prevention and control of these pathogenic bacteria in livestock farming. Full article

Circumferential guided wave detection technology can serve as an alternative method for detecting casing bond defects. Due to the presence of the cement cladding, the circumferential SH guided waves transmit shear waves into the cement cladding as they propagate in the cementing casing, which cause the circumferential SH guided waves to show attenuation characteristics. In this study, the cementing casing structure was considered as a steel substratum semi-infinite domain cemented cladding pipe structure, and the corresponding dispersion and attenuation characteristics of circumferential SH guided waves were numerically solved based on the state matrix and Legendre polynomial hybrid method. In addition, a finite element simulation model of cementing casing was established to explore the interaction between SH guided waves and bonding defects. The relationship between the amplitude of SH guided waves and the size of the bonding defects was established through the attenuation coefficient. Moreover, an experimental platform for cementing casing detection is constructed to detect bonding defects of different sizes and to achieve the acoustic analysis of cementing defects in cementing casing, which provides a research path for the non-destructive testing and evaluation of bonding defects in cementing casing. Full article