Biology subjects

Xiang, F.

Publications and source records attributed to Xiang, F..

4 recordsLinked to original sources

bioRxiv2026

Engineering Upd-like to broadly restrict arbovirus infection and vector competence in mosquitoes

The global expansion of mosquito-borne viruses poses a growing threat to public health, yet the endogenous signals that activate antiviral immunity in mosquito vectors remain incompletely understood. Here, we identify Aedes aegypti Upd as an activator of JAK/STAT signaling that restricts arbovirus infection. Loss of Upd increased infection and dissemination of the flaviviruses ZIKV and DENV, as well as the alphavirus SINV, whereas blood meal inducible midgut overexpression reduced ZIKV and SINV infection. Mechanistically, Upd associated with the extracellular region of the Domeless (Dome) receptor, and Upd deficiency markedly reduced STAT phosphorylation and nuclear accumulation in the midgut. Upd expression was transiently induced in the midgut by an uninfected blood meal but remained elevated following ZIKV challenge, linking physiological responses to blood feeding with antiviral defense. In mammal mosquito transmission models, Upd overexpression reduced viral acquisition from infected hosts, whereas Upd deficiency enhanced viral dissemination and increased transmission following systemic infection. Together, these findings identify Upd as an endogenous regulator of mosquito JAK/STAT signaling and provide proof of principle that temporally targeted Upd expression can reduce arbovirus susceptibility and vector competence.

microbiology↗

bioRxiv2025

A Syngeneic Immunocompetent Mouse Model of Gallbladder Cancer Reveals Tumorigenesis and Therapeutic Response

PurposeGallbladder cancer (GBC) is a rare but highly lethal malignancy with one of the poorest prognoses among cancers of the digestive system cancers. However, current experimental models of GBC face critical limitations, particularly their dependence on immunodeficient hosts, which precludes the investigation of the tumor microenvironment. We aimed to establish a novel syngeneic immunocompetent mouse model that recapitulates human GBC and enables the investigation of tumor-immune interactions. Experimental DesignWe engineered a murine cell line (mGBC1-ZH) from normal mouse gallbladder organoids expressing Kras and Trp53 (encoding mouse p53) mutations. Tumorigenic potential of mGBC1-ZH was evaluated by subcutaneous and orthotopic implantation. RNA-Seq and WES was used to demonstrate its characterization and similarity with human GBC. Immunohistochemistry, CCK8, and transwell assays wereused to investigate the role of CXCL5 in GBC. Therapeutic responses to standard first-line chemotherapeutic agents was evaluated in the syngeneic GBC model. ResultsThis model supports both subcutaneous and orthotopic tumor growth in immunocompetent C57BL/6J hosts while preserving hallmark features of human GBC, including biliary epithelial differentiation (CK7+/CK19+), aggressive histopathology, and an immunosuppressive "cold" tumor microenvironment. Genomic characterization revealed recurrent chromosomal instability and copy number alterations mirroring human GBC. Comprehensive transcriptomic profiling revealed profound gene expression changes during the model development, and resembled transcriptional features between mGBC1-ZH and human GBC cell lines and samples. CXCL5 was found to be upregulated in human GBC, and promote proliferation, metastasis, and neutrophils infiltration of GBC in the syngeneic mouse model. Functional validation of the syngeneic GBC model demonstrated therapeutic responsiveness to frontline chemotherapeutics gemcitabine and cisplatin with significant in vivo tumor regression. ConclusionsIn summary, we establised a novel syngeneic GBC mouse model, overcoming the limitations of traditional models by enabling studies in immunocompetent hosts. This model provides valuable insights into the molecular evolution from normal gallbladder cells to transformed cancer cells and establishes a robust platform for both mechanistic studies and therapeutic development.

cancer biology↗

bioRxiv2021

Inhibition of Kallikrein-related peptidases 7 restrains pancreatic tumor growth through induction of ferroptosis

Pancreatic cancer is one of the most aggressive and lethal malignancies with extremely poor prognosis, and KLK7 was considered as a potential therapeutic target. In this study, we analyzed the expression of KLK7 in TCGA and GTEx databases and found that KLK7 had a negative correlation to long-term survival rate (>1.5 years) of pancreatic cancer patients. Compound 42 is a coumarinic derivative, a suicide substrate inhibitor of KLK7, which has been proved to inhibit the proliferation of PANC-1 cells in vitro effectively in our previous study. In this study, we further investigated the inhibition ability of Compound 42 in tumor formation and development in CDX and PDX tumor models of pancreatic cancer subsequently. Besides, we studied the inhibitory mechanism of Compound 42 and the result showed that Compound 42 arrested the pancreatic cancer cell cycle in G0/G1 phase and induced ferroptosis through down-regulation of GPX4 protein level and accumulation of iron ion. Thus, these experiments demonstrate that Compound 42, suppressing pancreatic cancer in vivo, is expected to become a novel drug for pancreatic cancer treatment.

molecular biology↗

bioRxiv2016

Biased phylodynamic inferences from analysing clusters of viral sequences

Phylogenetic methods are being increasingly used to help understand the transmission dynamics of measurably evolving viruses, including HIV. Clusters of highly similar sequences are often observed, which appear to follow a power law behaviour, with a small number of very large clusters. These clusters may help to identify subpopulations in an epidemic, and inform where intervention strategies should be implemented. However, clustering of samples does not necessarily imply the presence of a subpopulation with high transmission rates, as groups of closely related viruses can also occur due to non-epidemiological effects such as over-sampling. It is important to ensure that observed phylogenetic clustering reflects true heterogeneity in the transmitting population, and is not being driven by non-epidemiological effects.\n\nWe quantify the effect of using a falsely identified transmission cluster of sequences to estimate phylodynamic parameters including the effective population size and exponential growth rate. Our simulation studies show that taking the maximum size cluster to re-estimate parameters from trees simulated under a randomly mixing, constant population size coalescent process systematically underestimates the overall effective population size. In addition, the transmission cluster wrongly resembles an exponential or logistic growth model 95% of the time. We also illustrate the consequences of false clusters in exponentially growing coalescent and birth-death trees, where again, the growth rate is skewed upwards. This has clear implications for identifying clusters in large viral databases, where a false cluster could result in wasted intervention resources.

genetics↗