Search Results (486)

Nipah virus (NiV) is a highly pathogenic bat-borne zoonotic pathogen that poses a significant threat to human and animal health, with fatality rates exceeding 70% in some outbreaks. Despite its significant public health impact, there are currently no licensed vaccines or specific therapeutics available. Various virological tools—such as reverse genetics systems, replicon particles, VSV-based pseudoviruses, and recombinant Cedar virus chimeras—have been widely used to study the molecular mechanisms of NiV and to support vaccine development. Building upon these platforms, we developed a replication-competent recombinant vesicular stomatitis virus (rVSVΔG-eGFP-NiV_BD F/G) expressing NiV attachment (G) and fusion (F) glycoproteins. This recombinant virus serves as a valuable tool for investigating NiV entry mechanisms, cellular tropism, and immunogenicity. The virus was generated by replacing the VSV G protein with NiV F/G through reverse genetics, and protein incorporation was confirmed via immunofluorescence and electron microscopy. In vitro, the virus exhibited robust replication, characteristic cell tropism, and high viral titers in multiple cell lines. Neutralization assays showed that monoclonal antibodies HENV-26 and HENV-32 effectively neutralized the recombinant virus. Furthermore, immunization of golden hamsters with inactivated rVSVΔG-eGFP-NiV_BD F/G induced potent neutralizing antibody responses, demonstrating its robust immunogenicity. These findings highlight rVSVΔG-eGFP-NiV_BD F/G as an effective platform for NiV research and vaccine development. Full article

The human skin microbiota, a complex community of bacterial, fungal, and viral organisms, plays a crucial role in maintaining skin homeostasis and regulating host-pathogen interactions. Dysbiosis within this microbial ecosystem has been implicated in various dermatological conditions, including acne vulgaris, psoriasis, seborrheic dermatitis, and atopic dermatitis. This review, for the first time, provides recent advancements in all four layers of omic technologies—metagenomics, metatranscriptomics, metaproteomics, and metabolomics—offering comprehensive insights into microbial diversity, in the context of functional skin modeling. Thus, this review explores the application of these omic tools to in vitro skin models, providing an integrated framework for understanding the molecular mechanisms underlying skin–microbiota interactions in both healthy and pathological contexts. We highlight the importance of developing advanced in vitro skin models, including the integration of immune components and endothelial cells, to accurately replicate the cutaneous microenvironment. Moreover, we discuss the potential of these models to identify novel therapeutic targets, enabling the design of personalized treatments aimed at restoring microbial balance, reinforcing the skin barrier, and modulating inflammation. As the field progresses, the incorporation of multi-omic approaches into skin-microbiome research will be pivotal in unraveling the complex interactions between host and microbiota, ultimately advancing therapeutic strategies for skin-related diseases. Full article

Vaccine adjuvants are non-immunogenic agents that enhance or modulate immune responses to co-administered antigens and are essential to modern vaccines. Despite their importance, few are approved for human use. The rise of new pathogens and limited efficacy of some existing vaccines underscore the need for more advanced and effective formulations, particularly for vulnerable populations. Aluminum-based adjuvants are commonly used in vaccines and effectively promote humoral immunity. However, they mainly induce a Th2-biased response, making them suboptimal for diseases requiring cell-mediated immunity. In contrast, saponin-based adjuvants from the Quillajaceae family elicit a more balanced Th1/Th2 response and generate antigen-specific cytotoxic T cells (CTL). Due to ecological damage and limited availability caused by overharvesting Quillaja saponaria Molina barks, efforts have intensified to identify alternative plant-derived saponins with enhanced efficacy and lower toxicity. Quillaja brasiliensis (A.St.-Hil. and Tul.) Mart. (syn. Quillaja lancifolia D.Don), a related species native to South America, is considered a promising renewable source of Quillajaceae saponins. In this review, we highlight recent advances in vaccine adjuvant research, with a particular focus on saponins extracted from Q. brasiliensis leaves as a sustainable alternative to Q. saponaria saponins. These saponin fractions are structurally and functionally comparable, exhibiting similar adjuvant activity when they were formulated with different viral antigens. An alternative application involves formulating saponins into nanoparticles known as ISCOMs (immune-stimulating complexes) or ISCOM-matrices. These formulations significantly reduce hemolytic activity while preserving strong immunoadjuvant properties. Therefore, research advances using saponin-based adjuvants (SBA) derived from Q. brasiliensis and their incorporation into new vaccine platforms may represent a viable and sustainable solution for the development of more less reactogenic, safer, and effective vaccines, especially for diseases that require a robust cellular immunity. Full article

Pest management is undergoing a transformative shift with the development of the cutting-edge antisense technologies: RNA interference (RNAi), contact unmodified antisense DNA biotechnology (CUADb), and the CRISPR-associated proteins (CRISPR/Cas). These approaches function by facilitating sequence-specific pairing of nucleic acids followed by nuclease-mediated cleavage, offering exceptional precision for targeted pest control. While RNA-guided mechanisms such as RNAi and CRISPR/Cas were initially characterized in non-insect systems, primarily as innate defenses against viral infections, the DNA-guided CUADb pathway was first identified in insect pests as a functional pest control strategy. Its broader role in ribosomal RNA (rRNA) biogenesis was recognized later. Together, these discoveries have revealed an entirely new dimension of gene regulation, with profound implications for sustainable pest management. Despite sharing a common principle of sequence-specific targeting RNAi, CUADb, and CRISPR/Cas differ in several key aspects, including their mechanisms of action, target specificity, and applicability. Rather than serving as universal solutions, each technology is likely to be optimally effective against specific pest groups. Moreover, these technologies allow for rapid adaptation of control strategies to overcome target-site resistance, ensuring long-term efficacy. This review summarizes the core functional characteristics, potential applications, and current limitations of each antisense technology, emphasizing their complementary roles in advancing environmentally sustainable pest control. By integrating foundational biological discoveries with applied innovations, this work provides a new perspectives on incorporating antisense-based strategies into next-generation integrated pest management systems. Full article

Background/Objective: Oral lichen planus (OLP) is a chronic inflammatory disorder of the oral mucosa with unclear etiology. Increasing evidence implicates oral microbial dysbiosis in its pathogenesis, but little is known about supragingival plaque communities in relation to clinical subtypes. This cross-sectional case–control study aimed to characterize the supragingival plaque microbiota and microbial interaction networks in erosive OLP (E-OLP), non-erosive OLP (NE-OLP), and healthy controls (HCs), to elucidate microbial patterns associated with disease severity. Methods: Supragingival plaque samples were collected from 90 participants (30 per group) and analyzed using 16S rRNA gene sequencing. Alpha and beta diversity metrics, differential abundance, and co-occurrence network analyses were performed. Results: E-OLP exhibited pronounced dysbiosis, including the enrichment of pro-inflammatory taxa (e.g., Prevotella, Parvimonas) and depletion of health-associated commensals (e.g., Rothia, Capnocytophaga). Network analysis revealed the stepwise disintegration of microbial community structure from HC to NE-OLP to E-OLP, with reduced connectivity and increased dominance of pathogenic clusters in E-OLP. These microbial alterations aligned with clinical findings, as E-OLP patients showed significantly higher Reticulation/keratosis, Erythema, and Ulceration (REU) scores for erythema and ulceration compared to NE-OLP. Conclusions: Supragingival plaque dysbiosis and ecological disruption are strongly associated with OLP severity and subtype. This study highlights the utility of plaque-based microbial profiling in capturing lesion-proximal dysbiotic signals, which may complement mucosal and salivary analyses in future diagnostic frameworks. Multi-omics approaches incorporating fungal, viral, and metabolic profiling are warranted to fully elucidate host–microbe interactions in OLP. Full article

Head and neck squamous cell carcinomas (HNSCCs) that develop from the mucosal epithelium in the oral cavity, pharynx, and larynx are a heterogeneous group of malignant tumors. A lack of appropriate screening and diagnostic methods leads to late diagnoses, with the majority of patients having locally advanced disease, which is associated with a high risk of local recurrence and a poor prognosis and is usually treated with combination therapies. Biomarkers for predicting the therapy response and risk of recurrence in HNSCC patients are urgently needed. Liquid biopsy, e.g., the profiling of circulating biomarkers in bodily fluids, is a promising approach with increasing utility in the early detection and diagnosis of cancer, monitoring cancer progression, patient stratification and treatment selection, detecting minimal residual disease (MRD), and predicting recurrence across different cancer types, including HNSCC. Among liquid biomarkers, circulating tumor DNA (ctDNA), which is based on detecting tumor-specific mutations, insertions/deletions, copy number alterations, and methylation, is the most promising transformative tool in cancer management and personalized cancer treatment. In this review, we provide an update of recent data on the role of non-viral ctDNA in the management of HNSCC patients. Accumulating data suggests the enormous potential of ctDNA profiling by serial sampling during and after definitive therapy in detecting MRD and predicting recurrence in HNSSC patients treated with a single treatment modality (surgery or radiotherapy) or with combination therapies, including immune-checkpoint-inhibitor-based immunotherapy. By incorporating the latest immunotherapy trials and organizing the data by the treatment modality, this review offers a novel perspective not found in previous surveys. Full article

The virus-first theory presents a model in which viral lineages emerged before cells. This proposal aims to give the theory greater relevance by offering a plausible evolutionary framework that explains both (i) the origin of viruses from prebiotic chemistry and (ii) how viruses contributed to the emergence of cells. Here, we propose that viruses should be understood as a distinct class of ribonucleoprotein (RNP) systems, some of which evolved directly from the RNP-world. In our model, simple progenotes produced capsid-like particles through the evolution of a single gene encoding a self-assembling peptide. This allowed the formation of icosahedral shells around RNA genomes, as observed today in certain viral families whose capsids consist of ~60 identical subunits derived from a single gene product. These early capsids enabled mobility and protection, representing key intermediates toward biological complexity. Over time, some of those populations acquired additional peptides and evolved more elaborate architectures. Finally, the incorporation of lipid-binding domains in those capsid-like peptides allowed the formation of proteolipidic membranes akin to those found in modern cells. This model provides a gradualistic and logically coherent evolutionary path from the RNP-world to the emergence of cellular life, emphasizing the foundational role of viruses in early evolution. Full article

Hepatocellular carcinoma (HCC) is the sixth most common malignancy globally and remains one of the leading causes of cancer-related mortality. Its incidence continues to rise worldwide, and it is currently the fastest-growing cancer by incidence in the United States. HCC most often arises in the context of chronic liver disease, particularly cirrhosis. While chronic viral hepatitis (hepatitis B and C) has traditionally been the primary etiologic factor, recent advances in antiviral therapies and prevention strategies have shifted the epidemiological landscape. Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease are increasingly prominent risk factors, especially in Western populations. This shift underscores the need for targeted risk factor modification, improved early detection, and enhanced surveillance protocols. The management of HCC necessitates a multidisciplinary approach, incorporating locoregional therapies, surgical resection, liver transplantation, and systemic therapies for advanced-stage disease. Recent advances in systemic treatments, including immune checkpoint inhibitors and combination therapies, have transformed the therapeutic landscape. Despite these developments, significant challenges persist in optimizing treatment, identifying predictive biomarkers, and personalizing therapy. Ongoing research is focused on refining molecular classifications and advancing precision medicine strategies to improve outcomes. This review provides a comprehensive overview of the etiology, surveillance strategies, diagnostic approaches, molecular features, and current treatment modalities for HCC. Full article

Herpes simplex virus type 1 (HSV-1) is a widespread pathogen responsible for recurrent infections, primarily affecting the skin and mucous membranes. With the aim of targeting both the viral infection and the associated inflammatory response, biotechnologically produced Lavandula angustifolia Miller (L. angustifolia) extract, rich in rosmarinic acid, was incorporated into liposomal formulations intended for topical application. Lavender is known for its strong anti-inflammatory, antioxidant, wound-healing, and antiviral properties. However, its low stability under certain conditions limits its therapeutic potential. Four different formulations were developed: conventional liposomes, glycerosomes, hyalurosomes, and glycerohyalurosomes. The vesicles were characterized for size, stability, and entrapment efficiency. Glycerosomes were the smallest (~58 nm), while the other formulations ranged around 77 nm, all maintaining a highly negative surface charge, ensuring stability and reduced aggregation. Glycerol-containing formulations demonstrated superior stability over 12 months, while liposomes and hyalurosomes increased their size after only two months. Entrapment efficiency reached up to 100% for most vesicles, except for glycerohyalurosomes (~54%). In vitro studies on Normal Human Dermal Fibroblasts (NHDFs) demonstrated that all formulations were biocompatible and enhanced cell viability under oxidative stress. Glycerosomes, hyalurosomes, and glycerohyalurosomes exhibited significant anti-inflammatory activity by reducing MMP-1 and IL-6 levels in LPS-stimulated fibroblasts. Furthermore, these preliminary results highlighted promising antiviral activity against HSV-1 of the obtained formulations, particularly when applied during or post-infection. Overall, these phospholipid vesicles offer a dual therapeutic approach, combining antioxidant, anti-inflammatory, and antiviral effects, positioning them as promising candidates for the treatment of HSV-induced skin lesions and related inflammatory conditions. Full article

Background/Objectives: Baculoviruses represent promising gene delivery vectors for mammalian systems, combining high safety profiles with substantial cargo capacity. While pseudotyping with vesicular stomatitis virus G-protein (VSV-G) enhances transduction efficiency, optimal expression strategies during the Autographa californica multiple nucleopolyhedrovirus (AcMNPV) infection cycle remain unexplored. This study investigates how VSV-G expression timing affects pseudotype incorporation into budded virions (BVs) and subsequent transduction efficacy. Methods: Three recombinant AcMNPV constructs were generated, each expressing VSV-G under distinct baculoviral promoters (ie1, gp64, and p10) and GFP via a CMV promoter. VSV-G incorporation was verified by Western blot, while transduction efficiency was quantified in mammalian cell lines (fluorescence microscopy/flow cytometry) and rat hind limbs. Viral productivity was assessed through production kinetics and plaque assays. Results: All the pseudotyped viruses showed significantly enhanced transduction capacity versus controls, strongly correlating with VSV-G incorporation levels. The p10 promoter drove the highest VSV-G expression and transduction efficiency. Crucially, BV production yields and infectivity remained unaffected by VSV-G expression timing. The in vivo results mirrored the cell culture findings, with p10-driven constructs showing greater GFP expression at low doses (10⁴ virions). Conclusions: Strategic VSV-G expression via very late promoters (particularly p10) maximizes baculoviral transduction without compromising production yields. This study establishes a framework for optimizing pseudotyped BV systems, demonstrating that late-phase glycoprotein expression balances high mammalian transduction with preserved insect-cell productivity—a critical advancement for vaccine vector development. Full article

Bovine alphaherpesvirus 1 (BoAHV-1) is a promising oncolytic virus that can infect the human lung carcinoma cell line A549. In an effort to adapt the virus to grow more rapidly in these cells through the serial passaging of viral progeny, we were unsuccessful. Here, we found that extracellular vesicles (EVs) secreted by BoAHV-1-infected A549 cells (referred to as EDVs) contain 59 viral proteins, including both viral structure proteins (such as gC and gD) and viral regulatory proteins (such as bICP4 and bICP22), as identified via a proteomic analysis. These EDVs can bind to and enter target cells, inhibit viral particles binding to cells, and stimulate the production of IFN-α and IFN-β in A549 cells. When EDVs are inoculated into rabbits via either the conjunctival sacs or intravenously, they can be readily detected in neurons within the trigeminal ganglia (TG), where they reduce viral replication and promote the transcription of IFN-γ. Furthermore, incorporation of the known anti-herpesvirus drug Acyclovir (ACY) into the EDVs leads to synergistically enhanced antiviral efficacy. Collectively, the EDVs exhibit antiviral effects by blocking viral binding to target cells and stimulating the innate immune response, thereby leading to the failure of the serial passaging of viral progeny in these cells, and these EDVs may serve as a promising vector for delivering drugs targeting TG tissues for antiviral purposes. Full article

Background: African Swine Fever (ASF) is a viral hemorrhagic disease characterized by diverse clinical and pathological manifestations depending on the virulence of isolates/strains and the immunological status of pigs. The use of modified live viruses (MLVs) is currently the most common approach in developing vaccines against ASF. However, despite the availability of dozens of MLV candidates that meet basic safety and efficacy criteria—such as the absence of severe clinical signs and survival after challenge with a virulent strain—no broadly accepted vaccine has yet been developed. Here, we propose viremia testing as an essential criterion for evaluating candidate ASF vaccines, with levels exceeding 10⁴ HAD₅₀/TCID₅₀ and lasting longer than 21–28 days post vaccination considered unfavorable indicators. Methods: We analyzed ASF MLV vaccines obtained through the deletion of one, two, or more genes, focusing on viremia kinetics after vaccination and challenge with virulent ASFV strains. Post mortem data were used to assess viral persistence in organs. Results: Most MLV candidates, especially those with single-gene deletions, demonstrated relatively high viremia levels after vaccination and challenge. Viral persistence was frequently detected in organs upon necropsy. MLVs with an additional EP402R gene deletion showed low viremia after vaccination but high levels after challenge. Nevertheless, several candidates with favorable viremia profiles were identified, including those obtained via targeted deletions or serial passaging in cell cultures. Conclusions: Incorporating viremia assessment as a primary screening criterion can significantly narrow down the selection of promising MLV candidates and help accelerate the development of effective emergency vaccines for use in ASF-affected regions. Full article

This study explores the viral dynamics of SARS-CoV-2 infection within host cells by incorporating the pharmacological effects of andrographolide—a bioactive compound extracted from Andrographis paniculata, renowned for its antiviral, anti-inflammatory, and immunomodulatory properties. Through the application of mathematical modeling, the interactions among the virus, host cells, and immune responses are simulated to provide a comprehensive analysis of viral behavior over time. Two distinct models were employed to assess the impact of varying andrographolide dosages on viral load, target cell populations, and immune responses. One model revealed a clear dose–response relationship, whereas the other indicated that additional biological or pharmacological factors may modulate drug efficacy. Both models demonstrated stability, with basic reproductive numbers (R₀) suggesting the potential for viral propagation in the absence of effective therapeutic interventions. This study emphasizes the significance of understanding the pharmacokinetics (PK) and pharmacodynamics (PD) of andrographolide to optimize its therapeutic potential. The findings also underscore the necessity for further investigation into the compound’s absorption, distribution, metabolism, and excretion (ADME) characteristics, as well as its prospective applications in the treatment of not only COVID-19 but also other viral infections. Overall, the results lay a foundational framework for future experimental research and clinical trials aimed at refining andrographolide dosing regimens and improving patient outcomes. Full article

Self-assembling protein nanocages (SAPNs) are distinct natural structures formed by the self-assembly of identical subunits, providing a highly efficient platform and a novel strategy for vaccine development and RNAi therapy. Their internal cavity allows for precise cargo encapsulation, while the externally modifiable surface supports multivalent antigen presentation, thereby enhancing stability, targeted delivery, and immune activation. In addition to serving as stable subunit vaccines with multivalent antigen display, SAPNs can be incorporated into mRNA vaccines (SAPN-RNA vaccines) by pre-fusing with the antigen. This strategy stabilizes secreted antigenic proteins with prolonged presentation to the immune system, and improves vaccine efficacy while reducing off-target effects and minimizing required doses. Additionally, SAPNs can overcome cellular uptake barriers, enhance DNA vaccine efficacy, and enable the co-delivery of antigens and adjuvants. Functionalization with adjuvants or targeting ligands further improves their immunostimulatory properties and specificity. The SAPN-RNAi strategy optimizes siRNA delivery by promoting lysosomal escape, enhancing targeted uptake, and protecting siRNA from degradation through SAPN encapsulation. This review examines the structural and functional properties of protein nanocages and their applications in vaccine design and RNAi delivery, emphasizing their synergistic effects, and exploring current progress, challenges, and future directions. In conclusion, SAPNs represent a versatile multifunctional platform with broad applicability across subunit, mRNA and DNA vaccines, adjuvant co-delivery, and RNAi therapeutics, with significant potential against viral infections. Full article

Bitter melon, an important medicinal and edible economic crop, is often threatened by diseases such as downy mildew, powdery mildew, viral diseases, anthracnose, and blight during its growth. Efficient and accurate disease detection is of significant importance for achieving sustainable disease management in bitter melon cultivation. To address the issues of weak generalization ability and high computational demands in existing deep learning models in complex field environments, this study proposes an improved lightweight YOLOv8-LSW model. The model incorporates the inverted bottleneck structure of LeYOLO-small to design the backbone network, utilizing depthwise separable convolutions and cross-stage feature reuse modules to achieve lightweight design, reducing the number of parameters while enhancing multi-scale feature extraction capabilities. It also integrates the ShuffleAttention mechanism, strengthening the feature response in lesion areas through channel shuffling and spatial attention dual pathways. Finally, WIoUv3 replaces the original loss function, optimizing lesion boundary regression based on a dynamic focusing mechanism. The results show that YOLOv8-LSW achieves a precision of 95.3%, recall of 94.3%, mAP50 of 98.1%, mAP50-95h of 95.6%, and F1-score of 94.80%, which represent improvements of 2.2%, 2.7%, 1.2%, 2.2%, and 2.46%, respectively, compared to the original YOLOv8n. The effectiveness of the improvements was verified through heatmap analysis and ablation experiments. The number of parameters and GFLOPS were reduced by 20.58% and 20.29%, respectively, with an FPS of 341.58. Comparison tests with various mainstream deep learning models also demonstrated that YOLO-LSW performs well in the bitter melon disease detection task. This research provides a technical solution with both lightweight design and strong generalization ability for real-time detection of bitter melon diseases in complex environments, which holds significant application value in promoting precision disease control in smart agriculture. Full article