Biology subjects

Huang, X.-Y.

Publications and source records attributed to Huang, X.-Y..

6 recordsLinked to original sources

bioRxiv2026

Multi-kingdom microbial diversity and interaction landscapes in mosquitoes revealed by 5,163 individual meta-transcriptomes

Mosquitoes are pathogen vectors embedded within diverse microbial ecosystems. However, the nature and interactions among their multi-kingdom microbiome remain poorly understood. We conducted a nationwide single-mosquito meta-transcriptomic survey of 5,163 mosquitoes representing 100 species across China, integrating viral discovery with marker-gene profiling of bacteria, archaea, fungi, and other eukaryotic microbes. From this, we identified 1,606 microbial species-level taxa, including extensive novel diversity, and revealed pronounced host species-specific organization of mosquito-associated communities. We detected 34 pathogens or potential pathogens of human or animal relevance, whose prevalence, abundance, host range, and geographic distribution defined distinct epidemiological patterns. Network analysis uncovered pervasive cross-kingdom microbial associations, including candidate antiviral relationships involving Wolbachia and other microbial taxa. Our study establishes a detailed view of the full-spectrum microbiome and provides a resource and conceptual framework for studying vector competence, pathogen emergence, and microbiome-informed mosquito-borne disease control.

microbiology↗

bioRxiv2026

Transition metal-triggered immunity via an Arabidopsis NLR pair

Plants are challenged by multiple biotic (e.g. pathogens) and abiotic (e.g. heavy metals) stressors. Some transition metals can enhance plants defense against pathogens, but the mechanism remains unclear. Here, we demonstrate that an Arabidopsis head-to-head gene pair of intracellular nucleotide-binding leucine-rich repeat (NLR) receptors, both expressed in the endodermis of roots, antagonistically control transition metal-triggered immunity. One NLR, STM2 binds transition metal ions, such as Cd2+, Cu2+ and Zn2+, with its LRR domain to enhance its NAD+ hydrolytic activity and immune responses via the EDS1/PAD4/ADR1 module, triggering enhanced resistance to bacterial wilt Ralstonia solanacearum. The other NLR, STM1 suppresses STM2 to protect plants from transition metal-triggered immunity and growth inhibition in the presence of excess metals. STM1 also dampens resistance to the pathogen. Our study defines an NLR activated by transition metals and reveals a trade-off between susceptibility to pathogens and sensitivity to transition metals that are pervasive in soil.

plant biology↗

bioRxiv2025

Viral protease-Initiated Pyroptosis Activator mRNA therapy as a Universal Antiviral Strategy

Although therapeutic drugs targeting gasdermin (GSDM)-mediated pyroptosis have made remarkable progress in treating various diseases, their potential for antiviral therapy remains largely unexplored. Inspired by the autoinhibitory mechanism of GSDM proteins and the clinical success of mRNA vaccines, herein we propose a concept of viral protease-initiated pyroptosis (VIP) mRNA therapy as a universal antiviral strategy. Using Hepatitis A virus (HAV) as a model, we rationally engineered an HAV-specific VIP activator (VIPA) by replacing the native gasdermin D (GSDMD) cleavage motif with that of HAV 3C protease. Expression of this VIPA selectively triggered pyroptosis in HAV-infected cells, thereby terminating viral replication. Remarkably, in vivo delivery of VIPA mRNA via lipid nanoparticles (LNPs) significantly suppressed viral replication and shedding, alleviated liver injury, and elicited a pyroptosis-driven antiviral immune response in uninfected cells. Similarly, VIPA against Zika virus (ZIKV) also exhibited potent antiviral efficacy in both cell culture and mouse models. Furthermore, a generative artificial intelligence (AI) platform was deployed to design de novo cleavage motifs for the SARS-CoV-2 main protease NSP5, together with experimental screening, yielding optimized VIPAs with enhanced antiviral potency. Our work establishes the concept of VIPA mRNA therapy as a versatile platform for the treatment of diverse viral infections via "kill-and-alert" mechanism.

microbiology↗

bioRxiv2023

Competitive fitness and homologous recombination of SARS-CoV-2 variants of concern

SARS-CoV-2 variants continue to emerge and cocirculate in humans and wild animals. The factors driving the emergence and replacement of novel variants and recombinants remain incompletely understood. Herein, we comprehensively characterized the competitive fitness of SARS-CoV-2 wild type (WT) and three variants of concern (VOCs), Alpha, Beta and Delta, by coinfection and serial passaging assays in different susceptible cells. Deep sequencing analyses revealed cell-specific competitive fitness: the Beta variant showed enhanced replication fitness during serial passage in Caco-2 cells, whereas the WT and Alpha variant showed elevated fitness in Vero E6 cells. Interestingly, a high level of neutralizing antibody sped up competition and completely reshaped the fitness advantages of different variants. More importantly, single clone purification identified a significant proportion of homologous recombinants that emerged during the passage history, and immune pressure reduced the frequency of recombination. Interestingly, a recombination hot region located between nucleotide sites 22995 and 28866 of the viral genomes could be identified in most of the detected recombinants. Our study not only profiled the variable competitive fitness of SARS-CoV-2 under different conditions, but also provided direct experimental evidence of homologous recombination between SARS-CoV-2 viruses, as well as a model for investigating SARS-CoV-2 recombination. ImportanceSARS-CoV-2 variants or subvariants keep emerging and the epidemic strains keeps changing in humans and animals. The continued replacement of the epidemic strains was attributed to higher competitive fitness evolved by the newly appeared ones than the older ones, but which factors affect the final outcomes are still not entirely clear. In this study, we performed in vitro coinfection and serial passage with three VOCs and WT under different conditions. Our results showed that the competition outcomes of these viral strains varied in different cell lines or under different immune pressure, confirming the probable effects of these two factors for the competitive fitness of different SARS-CoV-2 viral strains. Meanwhile, strikingly, we found that coinfection and serial passage with different SARS-CoV-2 viral strains can mimic the recombination process of SARS-CoV-2 occurred in coinfection individual, indicating it is a novel model to investigate the SARS-CoV-2 recombination mechanism.

microbiology↗

bioRxiv2020

Unacylated ghrelin and AZP531 suppress the 3D growth of breast cancers

Breast cancer is the most common type of cancer in women and notwithstanding important therapeutic advances, it remains the second leading cause of cancer-related death in the US. Despite extensive research relating to the hormone ghrelin, responsible for the stimulation of growth hormone release and appetite, little is known of the effects of its unacylated form, especially in cancer. One major area of research relates to its reported effects to increase insulin sensitivity in diabetics, this being the basis for the development of unacylated ghrelin analog, AZP531 or livoletide, now in clinical trials for the treatment of Prader-Willi Syndrome. The mechanism of action of unacylated ghrelin is largely uncharacterized, in any system, because it does not bind to or activate the cognate ghrelin receptor, GHSR1a. The present study aimed to characterize effects of unacylated ghrelin on breast cancer cells, define its mechanism of action, and explore the therapeutic potential of unacylated ghrelin or analog AZP531. We report potent effects of unacylated ghrelin, at picomolar doses, on the growth of breast cancer cells, dependent on 3D culture and activation of Gi. Suppression of MAPK signaling by unacylated ghrelin leads to cell cycle arrest and apoptosis. AZP531 also suppresses the growth of breast cancer cells in vitro and in xenografts, and may be a novel approach for the safe and effective treatment of breast cancer.

cancer biology↗

bioRxiv2018

Human sperm chromatin forms spatially restricted nucleosome domains consistent with programmed nucleosome positioning

In human sperm, a fraction of its chromatin retains nucleosomes that are positioned on specific sequences containing genes and regulatory units essential for embryonic development. This nucleosome positioning (NP) feature provides an inherited epigenetic mark for sperm. However, it is not known whether there is a structural constraint for these nucleosomes and, if so, how they are localized in a three-dimensional (3D) context of the sperm nucleus. In this study, we examine the 3D organization of sperm chromatin and specifically determine its 3D localization of nucleosomes using structured illumination microscopy. A fraction of the sperm chromatin form nucleosome domains (NDs), visible as microscopic puncta ranging from 40 m to 700 m in diameter, and these NDs are precisely localized in the postacrosome region (PAR), outside the sperms core chromatin. Importantly, these types of NDs exist only in sperm from fertile men but not in sperm from sterile men. This study uncovers a new spatially restricted sub-nuclear structure containing NDs that are consistent with NPs of the sperm. This represents a novel form of epigenetic mark for healthy sperms and can provide a potential new therapeutic and diagnostic target for treating male infertility.

cell biology↗