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In China, H9N2 subtype avian influenza outbreak is firstly reported in Guangdong province in 1992. Subsequently, the disease spreads into vast majority regions nationwide and has currently become endemic there. Over vicennial genetic evolution, the viral pathogenicity and transmissibility have showed an increasing trend as year goes by, posing serious threat to poultry industry. In addition, H9N2 has demonstrated significance to public health as it could not only directly infect mankind, but also donate partial or even whole cassette of internal genes to generate novel human-lethal reassortants like H5N1, H7N9, H10N8 and H5N6 viruses. In this review, we mainly focused on the epidemiological dynamics, biological characteristics, molecular phylogeny and vaccine strategy of H9N2 subtype avian influenza virus in China to present an overview of the situation of H9N2 in China.

Influenza A virus is a negative-sense single-stranded RNA virus that belongs to Orthomyxoviridae family. Based on the antigenic characteristics of hemagglutinin (HA) and neuraminidase (NA) influenza viruses are classified into multiple subtypes. H9N2 belongs to the low pathogenic Avian Influenza Viruses (AIVs) and is one of the widely spread viruses in poultry, which can pose a threat to humans by directly infecting or providing internal genes for various zoonotic avian influenza strains. It has the potential to directly or indirectly participate in becoming an AIV that causes a human pandemic. When the virus enters a host, the innate immune system is activated first by pattern recognition receptors. The cytokines produced at the site of infection recruit innate immune cells and antigen-presenting cells and those cells subsequently transmit antigenic signals to adaptive immune cells (i.e. B cells and T cells), to trigger specific humoral and cellular immune responses. As a result, humoral and cellular immunity can clear virus and infected cells via antibody-mediated neutralization and cytotoxicity, respectively. Understanding how chicken immune systems respond to H9N2 is a top priority for effectively controlling the virus's spread and designing vaccines. In this review, we comprehensively discuss the role of the chicken immune system in defending against H9N2, and clarify the current limitations in understanding chicken immune responses to H9N2 virus, thereby providing potential directions for future research as research on the chicken respiratory mucosal immune system has been stagnant for more than 20 years especially on how the mucosal immune system in chicken responds to avian influenza.

Cyclic GMP-AMP synthase (cGAS) is an essential sensor of aberrant cytosolic DNA for initiating innate immunity upon invading pathogens and cellular stress, which is considered as a potential drug target for autoimmune and autoinflammatory diseases. Here, we report the discovery of a class of cyclopeptide inhibitors of cGAS identified by an in vitro screening assay from a focused library of cyclic peptides. These cyclopeptides specifically bind to the DNA binding site of cGAS and block the binding of dsDNA with cGAS, subsequently inhibit dsDNA-induced liquid phase condensation and activation of cGAS. The specificity and potency of one optimal lead XQ2B were characterized in cellular assays. Concordantly, XQ2B inhibited herpes simplex virus-1 (HSV-1)-induced antiviral immune responses and enhanced HSV-1 infection in vitro and in vivo. Furthermore, XQ2B significantly suppressed the elevated levels of type I interferon and proinflammatory cytokines in primary macrophages from Trex1 -/- mice and systemic inflammation in Trex1 -/- mice. XQ2B represents the specific cGAS inhibitor targeting protein-DNA interaction and phase separation and serves as a scaffold for the development of therapies in the treatment of cGAS-dependent inflammatory diseases. Cyclic GMP-AMP synthase (cGAS) is critical in modulating cellular inflammation. Here, the authors report a class of cyclopeptide inhibitors of cGAS targeting protein DNA interaction and phase separation.

Lysosomes are acidic organelles that mediate the degradation and recycling of cellular waste materials. Damage to lysosomes can cause lysosomal membrane permeabilization (LMP) and trigger different types of cell death, including apoptosis. Newcastle disease virus (NDV) can naturally infect most birds. Additionally, it serves as a promising oncolytic virus known for its effective infection of tumor cells and induction of intensive apoptotic responses. However, the involvement of lysosomes in NDV-induced apoptosis remains poorly understood. Here, we demonstrate that NDV infection profoundly triggers LMP, leading to the translocation of cathepsin B and D and subsequent mitochondria-dependent apoptosis in various tumor and avian cells. Notably, the released cathepsin B and D exacerbate NDV-induced LMP by inducing the generation of reactive oxygen species. Additionally, we uncover that the viral Hemagglutinin neuraminidase (HN) protein induces the deglycosylation and degradation of lysosome-associated membrane protein 1 (LAMP1) and LAMP2 dependent on its sialidase activity, which finally contributes to NDV-induced LMP and cellular apoptosis. Overall, our findings elucidate the role of LMP in NDV-induced cell apoptosis and provide novel insights into the function of HN during NDV-induced LMP, which provide innovative approaches for the development of NDV-based oncolytic agents.

The eukaryotic translation elongation factor 1 (eEF1) family exhibits critical roles in RNA viral infection beyond its canonical function in protein synthesis. This review analyzes the structural characteristics of eEF1A and the eEF1B complex, and their regulatory mechanisms during viral infection. eEF1A impacts viral replication by stabilizing viral RNA-dependent RNA polymerase (RdRp) complexes, modulating genomic RNA synthesis, and facilitating viral assembly through cytoskeletal regulation. eEF1B subunits contribute through enhancing viral mRNA translation, regulating nuclear transport of viral components, and mediating post-translational modifications. The high conservation of eEF1 proteins across species and their involvement in multiple stages of viral replication establish them as promising broad-spectrum antiviral targets. Current eEF1-targeting compounds like plitidepsin demonstrate efficacy against diverse viral families, though therapeutic development faces challenges in balancing antiviral activity with host toxicity. This review provides a theoretical foundation for developing novel antiviral strategies targeting host–virus interaction interfaces and offers insights into addressing emerging infectious diseases.

The gymnosperm Welwitschia mirabilis belongs to the ancient, enigmatic gnetophyte lineage. It is a unique desert plant with extreme longevity and two ever-elongating leaves. We present a chromosome-level assembly of its genome (6.8 Gb/1 C) together with methylome and transcriptome data to explore its astonishing biology. We also present a refined, high-quality assembly of Gnetum montanum to enhance our understanding of gnetophyte genome evolution. The Welwitschia genome has been shaped by a lineage-specific ancient, whole genome duplication (~86 million years ago) and more recently (1-2 million years) by bursts of retrotransposon activity. High levels of cytosine methylation (particularly at CHH motifs) are associated with retrotransposons, whilst long-term deamination has resulted in an exceptionally GC-poor genome. Changes in copy number and/or expression of gene families and transcription factors (e.g. R2R3MYB, SAUR) controlling cell growth, differentiation and metabolism underpin the plant’s longevity and tolerance to temperature, nutrient and water stress.

Pseudorabies virus (PRV) has evolved multiple strategies to evade host antiviral responses to benefit virus replication and establish persistent infection. Recently, tripartite motif 26 (TRIM26), a TRIM family protein, has been shown to be involved in a broad range of biological processes involved in innate immunity, especially in regulating viral infection. Herein, we found that the expression of TRIM26 was significantly induced after PRV infection. Surprisingly, the overexpression of TRIM26 promoted PRV production, while the depletion of this protein inhibited virus replication, suggesting that TRIM26 could positively regulate PRV infection. Further analysis revealed that TRIM26 negatively regulates the innate immune response by targeting the RIG-I-triggered type I interferon signalling pathway. TRIM26 was physically associated with MAVS independent of viral infection and reduced MAVS expression. Mechanistically, we found that NDP52 interacted with both TRIM26 and MAVS and that TRIM26-induced MAVS degradation was almost entirely blocked in NDP52-knockdown cells, demonstrating that TRIM26 degrades MAVS through NDP52-mediated selective autophagy. Our results reveal a novel mechanism by which PRV escapes host antiviral innate immunity and provide insights into the crosstalk among virus infection, autophagy, and the innate immune response.

In recent years, minimally invasive techniques have made significant advancements in the management of upper urinary tract stones and have become the mainstream treatment modality. The core procedures currently routinely performed include extracorporeal shock wave lithotripsy (SWL), percutaneous nephrolithotomy (PCNL), and flexible ureteroscopy with lithotripsy (FURL). SWL is widely adopted due to its non-invasive advantage; however, its stone-free rate (SFR) can be affected by factors such as stone hardness, anatomical location, and patient body type. FURL (or RIRS) is performed through natural body cavities, resulting in minimal trauma; meanwhile, PCNL demonstrates significant efficiency advantages in managing large stone burdens. Currently, PCNL technology continues to evolve toward minimally invasive (miniaturization) and precision-oriented approaches. Concurrently, FURL technology has achieved significant breakthroughs through the integration of key innovations such as intelligent pressure control systems and flexible negative pressure suction sheaths. Therefore, systematically reviewing the latest advancements in minimally invasive surgical treatments for upper urinary tract stones and objectively evaluating their efficacy based on evidence-based medicine (such as comparing the clinical efficacy of PCNL versus FURL combined with novel negative pressure devices) will provide valuable practical guidance for clinicians in developing individualized and optimized treatment plans.

Many DNA viruses develop various strategies to inhibit cell death to facilitate their replication. However, whether influenza A virus (IAV), a fast-replicating RNA virus, attenuates cell death remains unknown. Here, we report that IAV infection induces TAK1 phosphorylation in a murine alveolar epithelial cell line (LET1) and a murine fibroblastoma cell line (L929). The TAK1-specific inhibitor 5Z-7-Oxzeneonal (5Z) and TAK1 knockout significantly enhance IAV-induced apoptosis, as evidenced by increased PARP, caspase-8, and caspase-3 cleavage. TAK1 inhibition also increases necroptosis as evidenced by increased RIPK1 S166 , RIPK3 T231/S232 , and MLKL S345 phosphorylation. Mechanistically, TAK1 activates IKK, which phosphorylates RIPK1 S25 and inhibits its activation. TAK1 also activates p38 and its downstream kinase MK2, which phosphorylates RIPK1 S321 but does not affect RIPK1 activation. Further investigation revealed that the RIPK1 inhibitor Nec-1 and RIPK1 knockout abrogate IAV-induced apoptosis and necroptosis; re-expression of wild-type but not kinase-dead (KD)-RIPK1 restores IAV-induced cell death. ZBP1 knockout abrogates IAV-induced cell death, whereas RIPK3 knockout inhibits IAV-induced necroptosis but not apoptosis. 5Z treatment enhances IAV-induced cell death and slightly reduces the inflammatory response in the lungs of H1N1 virus-infected mice and prolongs the survival of IAV-infected mice. Our study provides evidence that IAV activates TAK1 to suppress RIPK1-dependent apoptosis and necroptosis, and that RIPK3 is required for IAV-induced necroptosis but not apoptosis in epithelial cells.

Background Four species within Anaplasma genus are emerging zoonotic pathogens, which are transmitted by ticks and generate veterinary and public health concerns. Here, we performed a molecular survey of Anaplasma in Ankang, Northwest China. Methods Hard ticks were collected and identified using morphological and molecular methods. Human-pathogenic Anaplasma species were tested using nested polymerase chain reaction. The nearly complete rrs , gltA , and groEL genes sequences from revealed Anaplasma species were amplified and sequenced to determine their molecular characteristics and their phylogeny. Results All ticks collected in Ankang belonged to the Rhipicephalus microplus . Novel unclassified Anaplasma strains genetically related to A. platys and A. capra were detected in these ticks. Co-infection of these two organisms was also found. The novel unclassified Anaplasma strains identified in this study formed a distinct phylogenetic lineage based on the groEL gene and two lineages based on the gltA gene within A. platys and related strains group. The revealed A. capra strains identified in this study were most closely related to those detected in humans and other vertebrate animals. Conclusion We revealed the presence of A. capra , a novel human pathogens in R. microplus ticks in previously unrecognized endemic regions. We also detected a novel unclassified Anaplasma species genetically related to A. platys . The epidemiology of anaplasmosis caused by these two Anaplasma species in humans should be assessed in future studies.