Search Results (724)

Organoid and organ-on-chip technologies are rapidly evolving platforms for viral research that integrate stem cell biology, tissue engineering, and microfluidics to recapitulate key structural, mechanical, biochemical, and cellular features of human and animal physiology. By incorporating multicellular organoids into perfused microfluidic systems, these models can provide complex, dynamic, and physiologically relevant micro-environments for investigating virus–host interactions that are difficult to capture in conventional two-dimensional cultures and static organoids. Controlled flow, shear stress, extracellular matrix organization, tissue–tissue interfaces, and multicellular signaling enable mechanistic investigation of viral infectivity, dissemination, tissue injury and immune activation. Integration of real-time imaging and biosensors further permits longitudinal monitoring of viral replication, host responses, and tissue integrity, expanding the potential of these platforms for antiviral drug discovery. Recent organoid-on-chip studies using brain, skin, vaginal, respiratory, and intestinal models have demonstrated how tissue architecture, mechanical forces, glycocalyx dynamics, and immune–stromal interactions influence viral tropism and pathogenesis. In this review, we provide a mechanistic and translational overview of organoid and organ-on-chip technologies for studying viral infections, with particular emphasis on models of herpes simplex virus (HSV)-mediated disease. We further examine advances in immune integration, multi-organ systems, biosensing, and computational approaches that are expanding the complexity and predictive potential of these models. Importantly, patient-derived organoids and organ-on-chip platforms can capture interindividual differences in viral susceptibility, host responses, and therapeutic efficacy, providing pharmaceutical research with more precise, patient-relevant data to support drug prioritization and precision antiviral medicine. Finally, we discuss key barriers to broader adoption, including organoid maturation, biological and technical variability, reproducibility, scalability, biosafety, cost, standardization, and regulatory validation. Collectively, these advances position organoid and organ-on-chip technologies as powerful human-relevant models that bridge reductionist in vitro systems and human disease, while continued optimization, standardization, and validation will be essential to realize their full potential for mechanistically informed antiviral discovery, therapeutic development, and precision medicine. Full article

Many epidemiological models assume either closed populations or continuous demographic turnover. We consider an intermediate setting in which exchange occurs through discrete pulses. In this paper, we introduce a population-conserving compartmental epidemiological model with pulse population exchange at a set of prescribed times. At each pulse, a fraction of the population in each compartment is replaced by a combination of susceptible and immunized individuals. In contrast to typical pulse birth or pulse vaccination models where only a single compartment undergoes a pulse population change, the pulses in this model have competing effects: removing infectious individuals reduces the force of infection, while introducing new susceptibles increases it. In addition, when some part of the incoming population is immunized, the net effect of pulses becomes state-dependent. After presenting the model, we prove both conservation of total population and non-negativity in each compartment. We then show that while the non-pulsed system has only the disease-free equilibrium, the demographic changes introduced by the pulses can produce two new types of solution: a pulse-periodic endemic equilibrium and a second wave of infection. We derive an exact expression for a post-pulse endemic equilibrium in terms of the integrals of the solutions between equispaced pulses using the Poincaré map. Next, we identify the exact threshold at which the pulse-induced reduction in the susceptible population changes sign. Above the threshold, the pulses in all compartments contribute to a net reduction in the force of infection. Below this threshold, competing effects take hold—incoming susceptible individuals replenish the susceptible compartment, while departing exposed and infectious individuals no longer contribute to secondary infections. Finally, using parameters motivated by recent outbreaks of disease on cruise ships, we characterize this threshold mechanism and investigate the effect of pulse start time on the solution trajectories. Full article

Urban transmission of dengue and other Aedes aegypti-borne diseases is shaped by the interaction of vector ecology, human mobility, climate, and spatial heterogeneity. Capturing these interactions in city-specific settings requires models that are detailed enough to represent local transmission processes, while remaining computationally feasible for calibration, validation, and sensitivity analysis. This study presents a hybrid agent-based modeling and simulation (HABMS) approach, supported by high-performance computing (HPC), for simulating urban vector-borne disease transmission. Human residents are represented as mobile agents with stochastic infection dynamics, while mosquito populations are represented at the patch level through discrete-time equations. The model incorporates geospatial structure, temperature, land-use-based human movement, and local contextual information to represent transmission within urban environments. The framework was applied to Santa Marta, Colombia, as a city-specific case study. Transmission parameters were calibrated using surrogate-based Bayesian optimization, and their influence was assessed through sensitivity analysis. High-performance computing made the large number of stochastic simulations required for calibration and sensitivity analysis feasible. The calibrated model reproduced the magnitude and main seasonal shape of the observed dengue epidemic, including the peak and early decline. However, the model did not fully reproduce the late low-incidence tail of the season, indicating the need to incorporate external introductions of infection and rainfall-driven seasonal forcing of vector recruitment in future versions. A control scenario run on the calibrated baseline, a 30% reduction in larval carrying capacity, lowered the simulated seasonal attack rate by about three quarters and moved the system below the threshold at which local transmission is self-sustaining, illustrating the relative comparisons the calibrated model supports. This study contributes an adaptable hybrid model architecture and a high-performance implementation that make city-specific calibration and sensitivity analysis computationally feasible, demonstrated through a case study in Santa Marta. Full article

Implant-associated infections (IAIs) persist as a critical complication in biomaterial transplantation, driven by rapid microbial colonization, biofilm encapsulation, and escalating antibiotic resistance. Conventional antibiotic-based treatments and passive antimicrobial coatings often fail to achieve long-term infection control due to limited biofilm penetration, localized cytotoxicity, and active agent depletion. To overcome these limitations, piezoelectric nanocomposite coatings utilize a dynamic, stimulus-responsive framework that converts physiological mechanical forces or external ultrasound into localized electrical signals. These surface-bound electric fields systematically mitigate bacterial adhesion, eradicate mature biofilms via targeted reactive oxygen species (ROS) generation, disrupt microbial metabolic pathways, and favorably modulate the peri-implant immune microenvironment while supporting host tissue repair. This review evaluates the material design principles and classifications of inorganic, organic, and hybrid piezoelectric nanocoatings. We detail their multifaceted antibacterial mechanisms and trace their therapeutic potential in orthopedic and dental implants, as well as wound management. Lastly, we analyze current engineering bottlenecks to chart a clear trajectory for their clinical translation. Full article

The development of intrusion detection and network security solutions for securing Internet of Things (IoT) networks is constrained by the limited availability of representative network security datasets. Many existing datasets rely on centralised traffic collection and do not capture the non-Independent and Identically Distributed (non-IID) characteristics inherent to edge environments. To address this limitation, this work presents a device-level IoT network dataset generated using the open-source Gotham testbed, a virtualised smart city environment. Network traffic is collected in a distributed manner at the interfaces of 78 heterogeneous IoT devices operating across multiple protocols, including MQTT, CoAP, and RTSP. The dataset comprises over 31.8 million packet-level records, each described by 22 features. It includes both benign traffic and multiple attack classes, namely Network Scanning, Brute Force, Infection, Denial of Service (DoS), and Command and Control (C&C) Communication. Ground-truth labels are assigned using a deterministic process based on orchestration logs. The dataset preserves device-level traffic distributions and captures non-IID characteristics without artificial partitioning. It is publicly available and can be used to support reproducible evaluation of intrusion detection approaches and network analysis tasks in both centralised and distributed learning settings. Full article

Collateral sensitivity, an evolutionary trade-off accompanying antibiotic resistance, offers a potential strategy to counteract multidrug resistance. Here, we characterized collateral sensitivity profiles in plasmid-bearing and plasmid-free Escherichia coli (E. coli) lineages evolved under diverse antibiotic selection pressures. Across six independent meropenem (MEM)-evolved lineages derived from two distinct genetic backgrounds, a conserved collateral sensitivity to amphenicols consistently emerged during adaptive laboratory evolution (ALE). Whole genome sequencing identified recurrent mutations in envZ, mrdA and yghB, with yghB as an important genetic determinant associated with amphenicol sensitivity. Functional characterization of yghB disruption revealed that loss of YghB function affected membrane integrity and proton motive force (PMF) homeostasis, accompanied by altered efflux-associated activity, increased intracellular accumulation of amphenicols and altered Mg²⁺ homeostasis. In the ΔyghB background, these alterations were further associated with disrupted ribosome homeostasis and reduced translational capacity. Restoration of Mg²⁺ partially recovered ribosome-associated processes and amphenicol resistance in the ΔyghB mutant, suggesting that Mg²⁺ limitation contributes to yghB-associated amphenicol sensitivity. Furthermore, amphenicol treatment improved infection outcomes against MEM-resistant mutants in both Galleria mellonella and murine septicemia models. Collectively, MEM resistance evolution in E. coli generates robust collateral sensitivity to amphenicols, in which recurrent yghB mutations represent an important genetic basis. Functional analysis of yghB disruption further suggests that altered membrane energetics, efflux-associated processes and Mg²⁺-dependent ribosome homeostasis may contribute to this collateral sensitivity, revealing a potential therapeutic opportunity based on evolutionary trade-offs. Full article

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are clinically relevant pathogens in lung transplant (LT) recipients, but their impact on lung function and the benefit of ribavirin remains uncertain. We conducted a prospective multicenter observational cohort study of adult LT recipients with RSV or hMPV infection diagnosed between 2021 and 2024 at five centers, with follow-up for up to 12 months. Ribavirin was prescribed at the treating physician’s discretion. Multivariable analysis assessed the association between ribavirin and percentage change in forced expiratory volume in the first second (FEV₁) at 90 days, using FEV₁ three months before infection as baseline and adjusting for baseline FEV₁, pre-existing chronic lung allograft dysfunction, and time since transplantation. Seventy-six patients were included; 60 (78.9%) had RSV and 16 (21.1%) hMPV. Lower respiratory tract infection occurred in 48.7%, and an acute ≥10% FEV₁ decline at 14 days was observed in 29.3%. Among patients with lower respiratory tract infection, 45.9% received corticosteroids alone and 37.8% corticosteroids plus ribavirin. No statistically significant between-group differences in allograft dysfunction or mortality were observed. RSV and hMPV infections after LT were frequently associated with lower respiratory involvement and lung function decline. In this observational cohort, ribavirin use was not independently associated with 90-day FEV₁ change; however, residual confounding and limited statistical power preclude conclusions regarding treatment efficacy. Full article

Mammalian orthoreoviruses (MRVs) are segmented, double-stranded RNA viruses that infect a broad range of mammalian hosts, including humans. Although MRVs have been detected in wastewater in parts of Southeast Asia, they have not previously been reported in U.S. wastewater. Using the VirCapSeq-VERT pan-viral sequencing assay, we identified MRV type 2 (MRV-2) in a wastewater sample collected in March 2024 from the United States Air Force Academy. Complete genome sequences were recovered for all 10 segments. Phylogenetic analyses showed that the virus clustered most closely with an MRV isolate recovered from a big brown bat (Eptesicus fuscus) in Pennsylvania, with additional genomic similarity to a second bat-derived isolate from Nebraska. The MRV sequence signal declined rapidly in subsequent wastewater samples and was nearly undetectable two weeks later. These findings represent the first reported detection of MRV in U.S. wastewater and demonstrate the utility of pan-viral wastewater surveillance for identifying uncommon viruses with potential public health relevance. Continued genomic and epidemiologic surveillance will improve understanding of MRV circulation and zoonotic transmission in North America. Full article

Polymer hydrogels have been widely explored for wound repair, yet conventional designs remain passive barriers with limited mechanical intervention. Contractile hydrogels address this gap by undergoing network densification and macroscopic shrinkage, which can be converted into wound-edge traction through interfacial adhesion. This review classifies contractile hydrogels into temperature-responsive, pH-regulated, intermolecular-interaction-driven, and solvent-mediated systems according to their dominant contraction mechanisms. The transduction of contraction-derived mechanical cues into biochemical signals is discussed across tissue, cellular, and molecular scales, with emphasis on the well-supported integrin/focal adhesion kinase (FAK)-associated focal adhesion pathway and mechanosensitive ion channels. Current applications in acute full-thickness defects, infected and diabetic chronic wounds, surgical incisions, and scar control are critically surveyed. Finally, key challenges pertaining to force transmission efficiency, spatiotemporal controllability, biosafety, and clinical translatability are discussed. This review aims to provide design guidelines for the rational development of contractile hydrogel platforms for advanced wound management. Full article

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma, also known clinically as gastric MALT lymphoma (GML) or MALToma, is an indolent B-cell neoplasm strongly associated with chronic Helicobacter pylori (H. pylori) infection. While early-stage disease is based on persistent antigenic stimulation and chronic inflammation, the metabolic and molecular transitions that drive monoclonal B-cell autonomy remain poorly understood. Importantly, H. pylori maintain this long-term colonization by defusing the host’s innate immunity; specifically, its lipid A portion features unique elongated acyl chains, composed of 16–18 carbon atoms, that fail to bind to and activate host TLR4/MD2 receptors, resulting in exceptionally weak endotoxic potency. Persistent colonization relies on key oncoproteins, particularly cytotoxin-associated gene A (CagA) and vacuolar cytotoxin A (VacA), which orchestrate early inflammatory infiltration (neutrophils, Th1, Th2 and Th17 cells) before shifting the microenvironment toward a suppressive regulatory T cell (Treg) phenotype. In this study, we propose a new critical step in the oncogenesis of gastric metastasis: chronic mitochondrial and immunometabolic adaptation within the gastric microenvironment. We claim that H. pylori act not only as a trigger for infection but also as a chronic driver of mitochondrial adaptation to oxidative stress and hypoxia, which subsequently results in defective mitophagy. CagA- and VacA-mediated mitochondrial damage induces reactive oxygen species (ROS) and functional hypoxia, stabilizing HIF-1α to force a glycolytic metabolic shift, while incomplete mitophagy rescues metabolically altered, apoptosis-resistant clones to drive monoclonal B-cell expansion. Within this ecological-microenvironmental framework, the predominantly cytoplasmic sequestration of BCL10 and the NF-κB subunit p65 observed in GML is reinterpreted not as evidence of signaling inactivity, but as a dynamically regulated adaptive state. This configuration is orchestrated by mitochondrial stress responses that enable adaptation to the chronic microenvironmental pressures imposed by H. pylori, acting in concert with the metabolic programs governed by MYC, NRF2, and BCL2. Overall, this review outlines the multi-step pathogenesis of H. pylori-mediated GML, highlighting how mitochondrial dysfunction and metabolic remodeling drive the transition from chronic infection to malignant transformation. Full article

Climate variability can modulate zoonotic disease risk by altering interactions among wildlife hosts, vectors, and human environments, yet long-term evidence linking large-scale climate oscillations to natural plague systems remains scarce. We investigated the influence of El Niño–Southern Oscillation (ENSO)-related climate variability on rodent host dynamics in a long-established plague focus in Jianchuan County, southwestern China. Using continuous monthly surveillance data from 1978 to 2025, we analyzed population dynamics of two ecologically distinct plague hosts—the wild rodent Apodemus chevrieri and the domestic rodent Rattus tanezumi—together with flea infection rates and local climate variables. Generalized additive models showed that ENSO, quantified by the Southern Oscillation Index (SOI), exerted significant delayed effects on both rodent populations, with El Niño conditions consistently associated with increased host abundance. Wavelet coherence analyses revealed synchronized ENSO–rodent oscillations at dominant 2–3-year periodicities, indicating persistent large-scale climate forcing. In contrast, responses to local environmental factors differed between species: surface temperature strongly constrained the wild rodent A. chevrieri, whereas the domestic R. tanezumi showed weaker thermal sensitivity, consistent with buffering by human-modified indoor habitats. Flea infection rates declined as rodent densities increased, suggesting a dilution effect within the host–vector system. By integrating long-term wildlife surveillance, climate indicators, and vector data, this study provides empirical evidence that ENSO-driven climate variability plays a central role in regulating plague source activity at the human–animal–environment interface. These findings highlight the value of climate-informed, ecology-based surveillance frameworks for anticipating periods of elevated plague risk and strengthening early warning systems in endemic regions. Full article

Infection associated with orthopedic implants remains a major challenge in the development of biomimetic materials for bone tissue engineering. Surface modification strategies are widely employed to transform bioinert metallic substrates into bioactive interfaces that promote tissue integration while preventing bacterial colonization. This study investigated the effect of incorporating silver nanoparticles (nAg) into hydroxyapatite–barium titanate (HA–BT) coatings on their structural, mechanical, piezoelectric, biological, and antibacterial properties. Raw materials were characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM), whereas coatings were evaluated by XRD, scanning electron microscopy (SEM), tensile adhesion testing, electrochemical analysis, piezoresponse force microscopy (PFM), cell viability, and antibacterial assays. The coatings exhibited secondary phases, including β-tricalcium phosphate (β-TCP), tetracalcium phosphate (TTCP), and calcium oxide (CaO), generated during atmospheric plasma spraying (APS), while no silver oxide phases were detected after nAg incorporation. SEM observations revealed homogeneous phase distribution and strong coating–substrate adhesion. The addition of nAg did not significantly affect adhesive strength (44.58 ± 2.2 MPa for HA30BT and 43.28 ± 2.8 MPa for HA30BT–nAg). Protein adsorption studies indicated moderate albumin affinity (K_ads = 0.45) for nAg-containing coatings. Both coatings exhibited piezodynamic activity with d₃₃ values of approximately 13 pm/V. MTT assays confirmed non-cytotoxic behavior, with viability reductions below 2%. Osteocalcin expression demonstrated comparable osteogenic activity in coatings with and without nAg, regardless of low-intensity pulsed ultrasound stimulation. These findings highlight the potential of HA–BT–nAg coatings as multifunctional surfaces for bone regeneration and infection prevention. Full article

Fusarium oxysporum f. sp. radicis-cucumerinum (Forc) V03-2g and Fusarium oxysporum f. sp. radicis-lycopersici (Forl) ZUM2407 both cause foot and root rot in cucumber, but differ in host range. Forc V03-2g possesses Secreted in Xylem (SIX) effector genes, whereas Forl ZUM2407 does not, raising questions about their distinct infection strategies on this host. Using comparative transcriptomic analysis (in cucumber at 7 and 14 days post-inoculation (dpi) and in tomato at 2 dpi) we show that Forl ZUM2407 induces a delayed defense response in cucumber compared to Forc V03-2g. In turn, Forc V03-2g rapidly activates accessory chromosome effectors on cucumber, while Forl ZUM2407 initially deploys core chromosome genes, activating distinct from Forc V03-2g accessory genes only by 14 dpi. Thereby, Forc V03-2g and Forl ZUM2407 use distinct accessory gene repertoires (unique to each strain) and distinct core gene transcription strategies to infect the same host. Full article

The DUF538 gene family, harboring unknown functional proteins, has been reported to take active roles in plant development and response to adversities, while few studies of genome-wide identification and functional verification have been performed in cotton. Hence, two ancestral diploid species, G. arboretum and G. raimondii, and two cultivated tetraploid ones, G. hirsutum and G. barbadense, were chosen in this study to investigate the cotton DUF538 gene family, resulting in 37, 37, 70, and 70 members identified, respectively. A phylogenetic tree was constructed on these cotton DUF538 genes, together with 22 A. thaliana ones, which were divided into seven groups unevenly distributed across nearly all chromosomes. High-degree conservatism, while rich in diversity, was separately observed in gene structure and conserved motif analyses between the same groups and different groups, and a great number of gene-replication events were detected from intraspecific and interspecific collinearity analyses, implying this was the driving force for DUF538 family expansion. Multiple cis-acting elements relevant to adversity-stress responses were found in the promoter region, which were consistent with the transcriptome expression analyses in response to low-temperature and drought stress and Verticillium wilt infection. Coincidentally, GhDUF538-7 showed the core position in the protein–protein interaction network and was identified in the overlapping region of the interval of four reported VW resistance-related QTLs. The gene function of GhDUF538-7 was verified via gene cloning, relative expression-pattern detection, and virus-induced gene silencing (VIGS) experiment. The TRV:DUF538-7 plants showed more serious VW symptoms, significantly severe disease indices, relatively higher fungal biomass, and increased brown vascular bundles compared with TRV:00 plants. Significantly lower expression levels of marker genes PR4 and MYC2 in jasmonate signaling pathways indicated GhDUF538-7 as a potentially positive regulatory factor in plant defense via hormone signal transduction. This study not only broadened the research perspective of evolution and functional differentiation of the cotton DUF538 gene family, but it also revealed the cooperative relationship between DUF538-7 and the JA pathway for further molecular mechanisms of cotton resistance to VW infection. Full article

Staphylococcus aureus is an important zoonotic pathogen. In recent years, it has been isolated from diseased aquatic animals, causing skin ulcers and septicemia, establishing itself as an emerging pathogen in aquaculture. Rampant antibiotic use has accelerated antimicrobial resistance, a trend that has gradually curtailed the potency of conventional antibiotic therapies, underscoring the urgent need for novel therapies. Here, we screened 20 amino acids and found that exogenous proline significantly enhances the bactericidal activity of amikacin against S. aureus. This synergistic effect extends to other aminoglycoside antibiotics, including neomycin sulfate and gentamicin, and is also effective against drug-resistant strains such as MRSA USA300. Furthermore, we evaluated the efficacy of this combination in eradicating persisters and biofilms. Mechanistically, exogenous proline potentiates amikacin-mediated killing by modulating two key bactericidal pathways. On one hand, it enhances antibiotic uptake by augmenting the proton motive force via the electron transport chain. On the other hand, it amplifies oxidative stress through a multi-pronged mechanism involving the suppression of ROS-scavenging enzymes, activation of the Fenton reaction, and reduction in intracellular nitric oxide (NO) levels, ultimately culminating in bacterial cell death. This study proposes a promising strategy for combating S. aureus in aquaculture and healthcare-associated infections. Full article