Search Results (1,507)

Multimodal luminescent materials integrating spectral and temporal information are highly desirable for dynamic optical information encoding. However, constructing such systems often requires complicated molecular design or multiple synthetic steps. Herein, we report a simple Sb-introduction strategy to regulate excited-state dynamics in the zero-dimensional (0D) organic–inorganic hybrid metal halide (AP)₂ZnCl₄ (AP = 2-aminoacetophenone). The pristine host intrinsically combines prompt AP⁺ fluorescence with long-lived AP⁺-derived room-temperature phosphorescence (RTP). Upon Sb introduction, an additional broad Sb-related localized/self-trapped excitonic emission appears and the excited-state relaxation kinetics are redistributed while the native RTP pathway remains operative. These composition-dependent responses enable a proof-of-concept sequential time-gated optical encoding/decoding scheme with “WWW”, “SUV”, and “RTP” outputs. The results highlight dopant-mediated excited-state regulation in 0D hybrid metal halides for dynamic optical information encoding. Full article

Ruminants harbor a ruminal microbiome that converts their host-indigestible diet into nutrients. This microbiome contains three distinct communities: liquid, solid, and epithelial (or epimural). Currently, there is limited research examining the diet-dependent responses of all three microbiomes within the same animal. Here, we used next-generation 16S rRNA sequencing to characterize the ruminal solid (RS), liquid (RL), and epimural (RE) microbiotas of 13 lactating and cannulated Holstein dairy cows fed either a high- or low-starch diet in a crossover experimental design. Independent of diet, we found that all sample types were dominated by the phyla Firmicutes and Bacteroidetes. Proteobacteria and Epsilonbacteraeota were also highly abundant but only in the RE. Although the total VFA molar abundance did not differ between diets, propionate and valerate were found to increase with the high-starch diet, while acetate was increased with the low-starch diet. Overall, we found that the RE microbiota was more diverse than the RS and RL communities, with diet impacting community diversity in the RS. We found that sample type, diet treatment, and their interaction significantly impacted community structure and composition. Notably, Prevotella was most abundant in the RL and RS, particularly on the low-starch diet. We also found that Lachnospiraceae were significantly enriched in the RS and RL with a high-starch diet, whereas Succiniclasticum was highly abundant in the RE with a low-starch diet. These data suggest that diet influences all three ruminal microbiomes and provides a useful framework for understanding the role of these microbiomes in mediating host production. Full article

Antimicrobial resistance (AMR) is a growing global health threat driven in part by inappropriate and unnecessary antibiotic use resulting from diagnostic uncertainty at the point of care. In outpatient and acute-care settings, clinicians are often unable to rapidly distinguish between viral and bacterial infections, leading to empiric antibiotic prescribing that contributes to the emergence and spread of resistant pathogens. This review examines current and emerging rapid diagnostic technologies for differentiating bacterial and viral infections, including molecular assays, rapid antigen tests, biomarker-based diagnostics, host-response platforms, hematologic methods, and artificial intelligence-based decision-support systems. These technologies are evaluated based on diagnostic accuracy, turnaround time, cost, accessibility, and clinical actionability within real-world healthcare settings. Although several emerging and point-of-care (POC) technologies can provide results within approximately 6–15 min, their ability to consistently align with the timing, workflow, and clinical decision-making requirements of frontline outpatient and emergency-care settings remains variable and incompletely established. Future progress in antimicrobial stewardship will depend on developing rapid, clinically actionable diagnostic systems that integrate seamlessly into patient care and reduce unnecessary antibiotic use. Full article

Background: Influenza remains a significant global public health threat, causing substantial morbidity and mortality worldwide. While vaccination serves as the best preventive strategy, considerable interindividual variability in vaccine-induced immune responses persists. The ZBTB46 rs2281929 polymorphism (c.A31G; p.T11A; ACG>GCG), which corresponds to the evolutionarily conserved mouse mutation Zbtb46^T11A (c.A31G; ACT>GCT), has been associated with enhanced antibody responses to influenza vaccination in humans, though its functional mechanisms remain unknown. This study aimed to investigate how this mutation affects influenza vaccine immunogenicity using a knock-in mouse model. Methods: A Zbtb46^T11A knock-in mouse model was generated using CRISPR/Cas9 technology. Homozygous (HO) and wild-type (WT) mice were immunized with a quadrivalent influenza vaccine in a prime-boost regimen. Humoral immune responses were assessed by Enzyme-linked immunosorbent assay, hemagglutination inhibition (HI), and microneutralization (MN) assays. Antibody-secreting cells (ASCs) were quantified by Enzyme-linked immunospot assays. Germinal center B cells, plasma cells, plasmablast cells, conventional dendritic cell (cDC) subsets, and T helper (Th) cells were analyzed by flow cytometry. Statistical comparisons were performed using a two-sample t-test. Results: The Zbtb46^T11A mutation did not alter Zbtb46 protein expression or its abundance in cDCs. Following vaccination, HO mice exhibited significantly enhanced humoral responses, including higher HA-specific IgG titers, HI and MN antibody levels, and increased numbers of ASCs. Flow cytometry revealed elevated proportions of germinal center B cells and plasma cells in HO mice. Furthermore, HO mice showed a selective expansion of type 1 cDCs (cDC1s) and a concomitant increase in Th1 cell frequencies and IFN-γ-secreting cells, while cDC2 proportions and Th2 responses remained unchanged. Conclusions: The Zbtb46^T11A mutation is associated with enhanced influenza vaccine immunogenicity, concomitant with increased cDC1 proportions, Th1 polarization, and germinal center-dependent humoral immunity. These observed associations suggest a candidate mechanism whereby Zbtb46 modulation may shape adaptive immunity, though further functional studies are required to establish causality. These findings provide insights into host genetic variation in vaccine responsiveness and may inform personalized vaccination strategies. Full article

Background: The emergence of multidrug-resistant (MDR) uropathogenic Escherichia coli (UPEC) poses a significant public health challenge, and alternative treatments are urgently needed. Methods: Here, we identified clinical MDR-UPEC strains AT82 and AT84 collected from hospitalized patients that display extensive antimicrobial resistance at both genetic and phenotypic levels. Due to their high resistance profile, we systematically customized a phage cocktail from our coliphage library using hierarchical clustering based on host specificity and candidate selection through bacterial suppression profiles. Results: This pipeline yielded four lytic coliphages, designated Phi25-4, Phi25-6, Phi50-4, and Killian. Their genomes are relatively large ranging from 112–169 kbp and cluster into two distinct lineages comprising two closely related groups: Phi25-4/Phi50-4 and Phi25-6/Killian. Although each phage exhibited potent antibacterial activity, none alone sustained bacterial suppression during prolonged treatment. To overcome this limitation, we systematically compared the antibacterial activity of all possible phage combinations. Conclusions: The four-phage cocktail outperformed all two- or three-phage formulations, sustaining significant growth inhibition of AT82 and AT84 for up to 16 h and reducing area under the curve by more than 80% relative to controls. Cocktail potency was dose-dependent, with lower phage doses yielding the least viable cells at 48 h. Additionally, this cocktail exerted prophylactic action, significantly reducing UPEC invasion by several orders of magnitude, while the phage cocktail alone induced minimal proinflammatory cytokine responses in human bladder epithelium. Together, these findings provide an effective phage cocktail and a complementary framework for cocktail design against urinary tract infections caused by MDR bacteria. Full article

Deep-sea hydrothermal vents and cold seeps sustain highly productive animal communities through chemosynthetic symbioses, among which bathymodioline mussels are prominent examples. Bathymodioline gill bacteriocytes accommodate intracellular chemosynthetic symbionts, including sulfur- and/or methane-oxidizing bacteria depending on the host species, while remaining sheltered in an epithelium continuously exposed to environmental microorganisms, creating a fundamental immunological problem: how can an innate defense system remain effective without eliminating the microbial partners on which host nutrition depends? This review examines this problem through Bathymodiolus azoricus, integrating two decades of work on its cellular immunity, gill transcriptome, microbial challenge responses and symbiosis biology with recent mechanistic studies from related bathymodiolines. Central to the present synthesis are previously reported B. azoricus observations showing that gill tissue can mount local transcriptional responses to bacterial challenge, while hemolymph serum differentially modulates immune-gene expression following exposure to symbiont preparations or non-symbiotic Vibrio. Immune-gene expression also varies along the anterior–posterior gill axis, with lower expression in the posterior budding zone than in mature anterior filaments. We interpret this zonation primarily as a feature of tissue maturation rather than demonstrated active immune suppression, consistent with evidence that newly formed filaments are initially aposymbiotic and become colonized only after formation. Together, these observations evoke a host–symbiont–pathogen triad in which local gill-tissue responses, systemic humoral modulation and gill development constitute interacting levels of immune organization and compartmentalization. As a working hypothesis, we propose that this triad is reconciled principally through spatial and developmental compartmentalization of immune competence rather than through generalized immune suppression, predicting that immune-gene expression should track gill maturation state rather than symbiont occupancy per se. We consider this tissue-level model alongside comparative evidence for putative symbiont-uptake mechanisms, post-engulfment microbial discrimination, lysosomal regulation, symbiont digestion and bacteriocyte turnover, including the mTORC1-dependent phagosome-digestion checkpoint demonstrated in Bathymodiolus japonicus. Rather than assuming that these mechanisms are conserved across species, we distinguish explicitly between findings established in B. azoricus, evidence from other bathymodiolines and canonical pathways used as mechanistic context. We conclude by identifying unresolved components of B. azoricus immunity, including the prophenoloxidase system, the broader antimicrobial-peptide repertoire and the relationship between cellular checkpoints and tissue-level gill zonation, and consider the prospective biotechnological relevance of mechanisms that tolerate persistent microbial symbiosis without loss of immune vigilance. Full article

Poria cocos (syn. Wolfiporia cocos) is an obligate saprophytic fungus that can produce sclerotia only when cultivated on pine wood. Despite its wide cultivation, the nutritional adaptation of this fungus to pine substrate and the host defensive responses triggered during colonization remain poorly characterized. Elucidating how Poria cocos colonizes pine and triggers host defenses is critical to uncover its nutrient dependence. GO and KEGG analyses revealed that protein degradation, carbon metabolism, protein processing in the endoplasmic reticulum, and proteasome pathways were the major enriched pathways, indicating that a large amount of pine wood protein was degraded after Poria cocos colonization. Consistent with these omics signatures, the fungus acquired its primary nitrogen source via breakdown of pine structural and metabolic proteins, while pine carbohydrates acted as its main carbon source. Nutritional profiling confirmed the depletion of soluble protein and total sugars in pine wood, alongside elevated defensive polyphenols and flavonoids, reflecting an active stress response from viable pine parenchyma cells upon colonization. No significant shifts in mineral element concentrations were detected in colonized pine wood, indicating that Poria cocos selectively absorbs target minerals without altering the overall mineral pool of host wood tissue. Collectively, this work elucidates the core nutritional strategy of Poria cocos during pine colonization and identifies key molecular clues to advance optimized artificial cultivation, laying a solid theoretical foundation for revealing its obligate saprophytic lifestyle. Full article

Silk fibroin (SF)- and silk sericin (SS)-based antibacterial hydrogels are increasingly engineered as local antimicrobial platforms, yet cross-study interpretation is limited by inconsistent material reporting and by conflation of bacterial inhibition with tissue repair. We performed a structured evidence-mapping and critical synthesis of a frozen 2020–July 2026 corpus of 94 references. The original 46-record core map was re-audited at the original-article level: 43 full-text-verified, non-retracted primary studies were retained for detailed evidence grading, 2 records available only at abstract/database level were retained descriptively but not graded, and 1 subsequently retracted study was excluded from quantitative synthesis. Among the 43 graded studies, metal-ion/nanozyme/catalytic systems were most common (12/43, 27.9%), followed by release-mediated (11/43, 25.6%), multimodal (9/43, 20.9%), contact-active/anti-adhesive (6/43, 14.0%), and light-responsive systems (5/43, 11.6%). Sixteen studies (37.2%) used deliberately infected animal models, whereas only 4 (9.3%) reached a biofilm or adherent-bacteria-level endpoint in the graded map. Biological claim ceilings (C0–C5) are assessed independently from translation gates spanning material identity, reproducibility, mechanism, host safety, sterilization/storage, resistance, long-term fate, and deployment. Across mechanisms, SF and SS most often function as structural, interfacial, or transport-regulating matrices; direct silk-dependent bactericidal causality remains uncommon. The central translational deficit is failure to quantitatively link silk molecular identity and network architecture to antimicrobial exposure, bacterial killing, host selectivity, and long-term material fate. Full article

Cat- and dog-derived allergenic proteins are important indoor exposure sources, but allergen exposure, IgE sensitization, and clinically manifest allergy are distinct biological and clinical states. Major molecules include the cat secretoglobin Fel d 1 and several dog lipocalins, including Can f 1, together with serum albumins, kallikreins, and other components that can contribute to species-specific sensitization or cross-reactivity. These proteins are transported in the environment on heterogeneous carriers such as dander fragments, dust, and aerosol particles, allowing both direct and indirect exposure. Clinical relevance depends on the concordance among exposure, molecular sensitization, symptoms, and host factors rather than on environmental detection alone. This narrative review integrates molecular allergen biology with environmental dissemination, IgE-mediated immune mechanisms, clinical phenotypes, diagnostic interpretation, and management. Particular emphasis is placed on the distinction between molecular homology, IgE cross-reactivity, and clinically relevant cross-allergy; on the complementary role and limitations of component-resolved diagnosis; and on the variable evidence supporting environmental control and cat- versus dog-allergen immunotherapy. Standard pharmacotherapy remains central to symptom control, whereas biologics and allergen-neutralizing approaches are restricted to specific indications or remain investigational. A precision-management framework therefore requires molecular results to be interpreted in the context of exposure–response concordance, clinical phenotype, and inflammatory disease characteristics. Full article

Leptoglossus chilensis is a native South American coreid bug of economic and quarantine relevance whose chemical ecology remains undescribed. In this exploratory study, we characterised adult volatile and cuticular chemistry using dynamic headspace sampling (DHS), cuticular wash (CW), solid-phase microextraction (SPME), supercritical fluid extraction (SFE), and quantified electroantennographic (EAG) dose–responses in males and females in relation to a panel of eight literature-informed compounds (hexanal, hexyl acetate, hexyl formate, β-caryophyllene, (E)-β-farnesene, ocimene, benzyl alcohol and 2-phenylethanol). EAG responses were evaluated at six concentrations using a Bayesian hierarchical four-parameter Hill model. Across the four methods, 128 compounds were detected, of which 69 met a ≥20% detection-frequency threshold and were retained as the representative profile. Of these, hexanal, hexyl acetate, hexyl formate, and β-caryophyllene were detected in L. chilensis extracts, the latter only in male DHS collections; this compound is more likely to be a host plant volatile than an insect-produced signal. All eight compounds elicited concentration-dependent antennal responses in both sexes. Among these four compounds, β-caryophyllene yielded the lowest fitted EC₅₀ in both females (9 µg mL⁻¹ [90% CrI: 5–16]) and males (9 µg mL⁻¹ [90% CrI: 5–15]), although curves remained unsaturated; because delivered antennal dose was not measured and volatility differs substantially among the tested compounds, this cannot be interpreted as evidence of greater antennal sensitivity to β-caryophyllene specifically, and cross-compound EC₅₀ comparisons throughout this study are restricted to this caveat. All four Hill parameters were identifiable in both sexes for benzyl alcohol, (E)-β-farnesene, hexyl formate, and 2-phenylethanol. These results provide the first chemical and peripheral olfactory reference for L. chilensis and identify targets for behavioural and field evaluation. Full article

Background & Aims: Signaling within the tumor microenvironment (TME) emerges from dynamic crosstalk among cancer cells, host tissues, and the microbiome. Orthotopic and ectopic xenograft models are widely used in preclinical liver cancer research, yet it remains unclear to what extent tumor location shapes systemic host responses and gut–liver communication. We therefore investigated how anatomical context influences host transcriptomes and spatially resolved intestinal microbial ecosystems in hepatoblastoma (HB). Methods: We integrated bacterial/archaeal ecology with host and xenograft transcriptomes in orthotopic versus ectopic hepatoblastoma xenografts in male athymic CAnN.Cg-Foxn1nu/Crl mice. Single-sample GSEA, sparsity-aware networks, and DIABLO multi-block integration mapped pathway-level coordination across intestinal segments, stool, secondary lymphoid organs, livers, and tumors. Results: Tumor localization was associated with compartment-specific differences in host signaling, with the mesenteric lymph node and liver showing prominent shifts in TNFA/NF-κB, hypoxia, unfolded protein response, xenobiotic metabolism, mTORC1, KRAS, epithelial–mesenchymal transition, and MYC/E2F cell-cycle axes. Archaea exhibited pronounced, niche-specific signatures that showed positive correlations with proliferative and inflammatory Hallmarks and negative correlations with interferon pathways. Multi-omics integration (r ≥ 0.85) indicated coordinated variation linking specific microbial families to host and tumor programs and positioned the xenograft block as a hub connecting EMT, mTORC1, and angiogenesis to defined archaeal and bacterial taxa. Conclusions: Tumor topography remodels TME signaling through compartment-dependent host–microbiome–tumor crosstalk, with archaeal domains emerging as salient correlates of proliferative and stress-response networks. These findings provide a systems framework and testable hypotheses for therapeutic modulation of TME signaling via interkingdom interactions. Full article

Large Language Models (LLMs) are increasingly incorporated into software systems. Their non-deterministic behavior, external hosting, response latency, and operational cost create challenges for established design approaches such as Clean Architecture. This paper examines the integration of an LLM component into a layered software system and compares three possible placements within Clean Architecture: Domain, Application, and Infrastructure. The evaluation considers dependency management, testability, separation of concerns, and implementation complexity. The study proposes an approach in which the LLM is implemented in the Infrastructure layer and accessed through an interface defined in the Application layer. This approach is combined with the Command and Query Responsibility Segregation pattern to isolate LLM interaction within dedicated query handlers. The proposed pattern is demonstrated through the implementation of Budget, a personal finance tracking system that uses GPT-4.1 to convert free-form natural language input into structured transaction records. The results show that placement in the infrastructure layer provides the clearest separation between business logic and external AI services and avoids the introduction of non-deterministic behavior into the core application logic. Full article

The host immune response plays a central role in determining biomaterial performance, particularly through early macrophage activation dynamics at the tissue–biomaterial interface. This study evaluated the response of THP-1-derived human macrophages cultured on a fibrous extracellular matrix-like polydioxanone (PDO) mesh under basal (M0), M1-induced, and M2-induced in vitro conditions. Macrophage responses were assessed by gene expression analysis, immunofluorescence staining of macrophage- and polarization-associated markers, scanning electron microscopy (SEM), and metabolic and viability assays. Distinct stimulus- and time-dependent responses were observed across transcriptional, marker distribution, morphological, and metabolic readouts. Pro-inflammatory gene expression increased under M1-polarizing conditions at 72 h and declined at 96 h, whereas anti-inflammatory and M2-associated markers progressively increased under M2 stimulation, reaching higher levels at 96 h. Immunofluorescence confirmed macrophage differentiation under basal conditions and showed condition-dependent distributions of CD86- and CD206-associated signals, consistent with the transcriptional profiles. SEM revealed stable cell–material interactions and polarization-associated morphological heterogeneity. Metabolic and viability assays confirmed viable cells under all conditions, with activity patterns consistent with induced activation states. Under basal (M0) conditions, macrophages cultured on the PDO mesh maintained a basal phenotype without evidence of marked pro-inflammatory activation. Overall, these findings indicate that fibrous PDO meshes support macrophage viability, differentiation, and stimulus-responsive activation, highlighting their potential as immunologically compatible polymeric platforms for regenerative biomaterial applications. Full article

Chagas disease control relies on chemical interventions, currently compromised by insecticide resistance. Triatoma virus (TrV) emerges as a biological candidate, requiring standardized methodologies to purify, quantify, and relate viral doses to biological effects in triatomines. We established a comprehensive protocol for the quantitative study of TrV using Rhodnius prolixus as a model, combining physical purification via sucrose gradients and absolute quantification by qPCR targeting the TrVgp1 gene to link viral load with host survival. Primers were validated, and a plasmid standard curve was constructed for absolute quantification. Four isolation methods from Triatoma infestans macerates were compared, including an optimized discontinuous gradient protocol (EGM). High (6 × ${10}^6$ viral genome copies/µL) and low (2.47 × ${10}^5$ viral genome copies/µL) doses of EGM-purified TrV were evaluated in oral infections of R. prolixus over 16 days post-inoculation (dpi). The EGM protocol achieved the highest yields, around ${10}^9$ virus genome copies/µL of purified viral stock. Intestinal viral replication was dose-dependent, exhibiting distinct kinetic phases between low (3–7 dpi) and high (9–12 dpi) inoculum cohorts. Only the high dose significantly reduced host survival. In conclusion, this protocol allows high-yield TrV purification and absolute quantification in R. prolixus, establishing a robust dose–response foundation to assess triatomine susceptibility for integrated biological control programs. Full article

The gut microbiota can influence tumor immunity and treatment responses through microbial metabolism, intestinal barrier regulation, and immune–inflammatory signaling, but whether exercise engages these mechanisms through the muscle–gut axis remains uncertain. This review integrates evidence from exercise physiology, microbial metabolism, and tumor immunology to examine how exercise-associated host signals may reshape the intestinal ecological niche and microbial function. Three candidate muscle–gut axes are proposed: the myokine–enteroendocrine–substrate delivery–short-chain fatty acid (SCFA) axis, the exercise-associated lactate–microbial cross-feeding–propionate axis, and the muscle-derived endocrine signaling–intestinal epithelial repair–hypoxic niche axis. Separate studies support exercise-associated IL-6/GLP-1/PYY regulation and gastrointestinal transit, lactate entry into the intestinal lumen and lactate-associated microbial remodeling, Veillonella atypica-mediated propionate production, and irisin/apelin-related epithelial repair. Together, these pathways may influence microbial metabolism, barrier homeostasis, and immune–tumor interactions. However, tumor-related links remain incomplete, and none has been validated as a complete causal chain in a single tumor-bearing exercise model. Relatively complete preclinical evidence comes from mouse melanoma, where endurance exercise enhanced microbial folate-dependent one-carbon metabolism and formate output, with microbiota-derived formate promoting CD8⁺ T-cell antitumor activity and immune checkpoint inhibitor efficacy. Regular exercise with an appropriate load and adequate recovery may support microbial and intestinal barrier homeostasis, whereas excessive or prolonged exercise with inadequate recovery may impair barrier integrity. Human evidence remains limited and largely associative and does not establish microbiota-mediated improvements in tumor immunity or treatment responses. These candidate axes therefore require causal validation in tumor-bearing exercise models and prospective human studies. Full article