Biology subjects

WU, J.

Publications and source records attributed to WU, J..

4 recordsLinked to original sources

bioRxiv2023

Zbtb46 coordinates angiogenesis and immunity to control tumor outcome

Tumor-angiogenesis and -immunity play critical roles in cancer progression and outcome. An inverse correlation of these two1 hints at common regulatory mechanism(s). Here, we report that Zbtb46, a repressive transcription factor and a widely accepted marker for classical dendritic cells (DCs)2, 3, constitutes one such regulatory mechanism. Zbtb46 was downregulated in both DCs and endothelial cells (ECs) by tumor-derived factors to facilitate robust tumor growth. Zbtb46 downregulation led to a hallmark pro-tumor microenvironment (TME), including dysfunctional vasculature and immunosuppressive cell accumulation. Analysis of cancer patient data revealed a similar association of low ZBTB46 expression with an immunosuppressive TME and a worse prognosis. In contrast, enforced Zbtb46 expression mitigated the pro-tumor TME features and restricted tumor growth. Mechanistically, Zbtb46-deficient ECs were highly angiogenic, and Zbtb46-deficient bone-marrow progenitors upregulated Cebpb and diverted the DC program to myeloid lineage output, potentially explaining the myeloid lineage skewing phenomenon in cancer4-7. Conversely, enforced Zbtb46 expression normalized tumor vessels and, by suppressing Cebpb, skewed bone-marrow precursors towards more DC generation over macrophages, leading to an immune-hot TME. Remarkably, Zbtb46 mRNA treatment synergized with anti-PD1 immunotherapy to improve tumor management in pre-clinical models. These findings identify Zbtb46 as a common regulatory mechanism for angiogenesis and for myeloid lineage skewing in cancer and suggest that maintaining its expression could have therapeutic benefits.

cancer biology↗

bioRxiv2023

Study on the expression of RAD51 in non-small cell lung cancer based on bioinformatics

ObjectiveRAD51 is a DNA repair protein, which participates in the resistance of tumor cells to radiotherapy/chemotherapy and reduces the therapeutic effect. Based on the research status of RAD51 at home and abroad and the analysis of online databases, the purpose of this study was to explore the relationship between RAD51 expression and clinical patient survival and prognosis. It is expected to provide a new theoretical basis for the clinical treatment of lung cancer patients, help identify new molecular markers, and provide new targets for the biological therapy of lung cancer patients. Methodsthe RNA Seq data of NSCLC in TCGA database were downloaded, and the expression of RAD51 gene in NSCLC and normal tissues were analyzed by R studio software. Clinical correlation analysis revealed its correlation with the clinicopathological characteristics of non-small cell lung cancer. Survival analysis was used to evaluate the relationship between the expression level and the prognosis of patients. CIBERSORT and TIMER were used to evaluate the correlation between the expression level of CIBERSORT and immune cells in the tumor microenvironment. The protein expression level of RAD51 in non-small cell lung cancer was evaluated by HPA. ResultsRAD51 was highly expressed in lung cancer (p<0.05), which was significantly associated with poor prognosis of lung adenocarcinoma patients (p=0.0026), but not with lung squamous cell carcinoma (p=0.76). The expression level of RAD51 mRNA was associated with different pathological stages of lung adenocarcinoma (p=0.000528), but not with different pathological stages of lung squamous cell carcinoma (p=0.326). RAD51 was positively correlated with the expression of TP53, BRAF, EGFR, MYC, PD-L1, and KRAS (p<0.001). In lung adenocarcinoma, lung cancer cells were positively correlated with CD4+memory T cells, CD8+T cells, and M1 macrophages (p<0.001). In lung squamous cell carcinoma, tumor cells were positively correlated with M1 macrophages (p<0.05), but not with CD4+T memory cells, CD8+T cells, M2 macrophages, and Tregs cells (p>0.05). The HPA database indicated that RAD51 protein was positive in non-small cell lung cancer. ConclusionRAD51 is highly expressed in non-small cell lung cancer and is associated with poor prognosis. RAD51 can be used as a biomarker related to the prognosis of non-small cell lung cancer and is expected to become a target for the diagnosis and treatment of non-small cell lung cancer.

bioinformatics↗

bioRxiv2020

Simultaneously monitoring aquatic and terrestrial biodiversity using riverine water eDNA: seasonal variation of monitoring effectiveness

Environmental DNA (eDNA) metabarcoding for biodiversity monitoring is a critical technical advance. Both aquatic and terrestrial biodiversity information can be detected in riverine water eDNA. However, it remains unverified whether riverine water eDNA can be used to simultaneously monitor aquatic and terrestrial biodiversity. Our specific objective was to assess the effectiveness of monitoring aquatic and riparian biodiversity using riverine water eDNA. We proposed that the monitoring effectiveness (the proportion of aquatic and terrestrial biodiversity information detected by riverine water eDNA samples) could be approximated by the transportation effectiveness of land-to-river and upstream-to-downstream biodiversity information flow. We conducted a case study in a watershed on the Qinghai-Tibet Plateau and estimated the effectiveness of using riverine water eDNA to monitor aquatic and riparian biodiversity based on comparing the operational taxonomic units (OTUs) and species assemblages of three taxonomic communities detected in riverine water eDNA samples and riparian soil eDNA samples in spring, summer, and autumn. The aquatic and riparian biodiversity of a watershed on the Qinghai-Tibet Plateau could be simultaneously effectively monitored using riverine water eDNA on summer or autumn rainy days. Monitoring bacterial communities was more efficient than monitoring eukaryotic communities. On summer rainy days, 43%-76% of riparian species could be detected in water eDNA samples, 92%-99% of upstream species could be detected in a 1-km downstream eDNA sample, and more than 50% of dead bioinformation (i.e., the bioinformation labeling the biological material without life activity and fertility) could be monitored 4-6 km downstream for eukaryotes and 13-19 km for bacteria. We encourage more studies on the monitoring effectiveness for each taxonomic community in other watersheds with different environmental conditions. We believe that in future ecological research, conservation and management, we could efficiently monitor and assess the aquatic and terrestrial biodiversity by simply using riverine water eDNA samples.

ecology↗

bioRxiv2020

Augmenting Vascular Disease Diagnosis by Vasculature-awareUnsupervised Learning

Vascular diseases are among the leading causes of death and threaten human health worldwide. Imaging examination of vascular pathology with reduced invasiveness is challenging due to the intrinsic vasculature complexity and the non-uniform scattering from bio-tissues. Here, we report VasNet, a vasculature-aware unsupervised learning algorithm that augments pathovascular recognition from small sets of unlabeled fluorescence and digital subtraction angiography (DSA) images. The VasNet adopts the multi-scale fusion strategy with a domain adversarial neural network (DANN) loss function that induces biased pattern reconstruction, by strengthening the features relevant to the retinal vasculature reference while weakening the irrelevant features. VasNet delivers outputs of "Structure + X", where X refers to multi-dimensional features such as blood flows, the distinguishment of blood dilation and its suspicious counterparts, and the dependence of new pattern emergence on a disease progression, which may assist the discovery of novel diagnostics. Therefore, explainable imaging output from VasNet and other algorithm extensions hold the promise to revolutionize the practice of medical diagnosis, as it improves performance while reduces the cost on human expertise, equipment exquisite and time consumption.

bioengineering↗