Si Wang

The National Genomics Data Center (NGDC), part of the China National Center for Bioinformation (CNCB), provides a family of database resources to support global research in both academia and industry. With the explosively accumulated multi-omics data at ever-faster rates, CNCB-NGDC is constantly scaling up and updating its core database resources through big data archive, curation, integration and analysis. In the past year, efforts have been made to synthesize the growing data and knowledge, particularly in single-cell omics and precision medicine research, and a series of resources have been newly developed, updated and enhanced. Moreover, CNCB-NGDC has continued to daily update SARS-CoV-2 genome sequences, variants, haplotypes and literature. Particularly, OpenLB, an open library of bioscience, has been established by providing easy and open access to a substantial number of abstract texts from PubMed, bioRxiv and medRxiv. In addition, Database Commons is significantly updated by cataloguing a full list of global databases, and BLAST tools are newly deployed to provide online sequence search services. All these resources along with their services are publicly accessible at https://ngdc.cncb.ac.cn.

Introduction: Glioblastoma multiforme (GBM) pathobiology is characterized by its significant induction of immunosuppression within the tumor microenvironment, predominantly mediated by immunosuppressive tumor-associated myeloid cells (TAMCs). Myeloid cells play a pivotal role in shaping the GBM microenvironment and influencing immune responses, with direct interactions with effector immune cells critically impacting these processes. Methods: Our study investigates the role of the CXCR6/CXCL16 axis in T-cell myeloid interactions within GBM tissues. We examined the surface expression of CXCL16, revealing its limitation to TAMCs, while microglia release CXCL16 as a cytokine. The study explores how these distinct expression patterns affect T-cell engagement, focusing on the consequences for T-cell function within the tumor environment. Additionally, we assessed the significance of CXCR6 expression in T-cell activation and the initial migration to tumor tissues. Results: Our data demonstrates that CXCL16 surface expression on TAMCs results in predominant T-cell engagement with these cells, leading to impaired T-cell function within the tumor environment. Conversely, our findings highlight the essential role of CXCR6 expression in facilitating T-cell activation and initial migration to tumor tissues. The CXCL16-CXCR6 axis exhibits dualistic characteristics, facilitating the early stages of the T-cell immune response and promoting T-cell infiltration into tumors. However, once inside the tumor, this axis contributes to immunosuppression. Discussion: The dual nature of the CXCL16-CXCR6 axis underscores its potential as a therapeutic target in GBM. However, our results emphasize the importance of carefully considering the timing and context of intervention. While targeting this axis holds promise in combating GBM, the complex interplay between TAMCs, microglia, and T cells suggests that intervention strategies need to be tailored to optimize the balance between promoting antitumor immunity and preventing immunosuppression within the dynamic tumor microenvironment.

Understanding the spatial relationship and functional interaction of immune cells in glioblastoma (GBM) is critical for developing new therapeutics that overcome the highly immunosuppressive tumor microenvironment. Our study showed that B and T cells form clusters within the GBM microenvironment within a 15-μm radius, suggesting that B and T cells could form immune synapses within the GBM. However, GBM-infiltrating B cells suppress the activation of CD8 + T cells. To overcome this immunosuppression, we leveraged B-cell functions by activating them with CD40 agonism, IFNγ, and BAFF to generate a potent antigen-presenting B cells named B Vax . B Vax had improved antigen cross-presentation potential compared to naïve B cells and were primed to use the IL15-IL15Ra mechanism to enhance T cell activation. Compared to naïve B cells, B Vax could improve CD8 T cell activation and proliferation. Compared to dendritic cells (DCs), which are the current gold standard professional antigen-presenting cell, B Vax promoted highly proliferative T cells in-vitro that had a stem-like memory T cell phenotype characterized by CD62L + CD44 - expression, high TCF-1 expression, and low PD-1 and granzyme B expression. Adoptive transfer of B Vax -activated CD8 + T cells into tumor-bearing brains led to T cell reactivation with higher TCF-1 expression and elevated granzyme B production compared to DC-activated CD8 + T cells. Adoptive transfer of B Vax into an irradiated immunocompetent tumor-bearing host promoted more CD8 + T cell proliferation than adoptive transfer of DCs. Moreover, highly proliferative CD8 + T cells in the B Vax group had less PD-1 expression than those highly proliferative CD8 + T cells in the DC group. The findings of this study suggest that B Vax and DC could generate distinctive CD8 + T cells, which potentially serve multiple purposes in cellular vaccine development.

Glioblastoma is a Grade 4 primary brain tumor defined by therapy resistance, diffuse infiltration, and near-uniform lethality. The underlying mechanisms are unknown, and no treatment has been curative. Using a recently developed creatine kinase inhibitor (CKi), we explored the role of this inhibitor on GBM biology in vitro. While CKi minimally impacted GBM cell proliferation and viability, it significantly affected migration. In established GBM cell lines and patient-derived xenografts, CKi ablated both the migration and invasion of GBM cells. CKi also hindered radiation-induced migration. RNA-seq revealed a decrease in invasion-related genes, with an unexpected increase in glutathione metabolism and ferroptosis protection genes post-CKi treatment. The effects of CKi could be reversed by the addition of cell-permeable glutathione. Carbon-13 metabolite tracing indicated heightened glutathione biosynthesis post-CKi treatment. Combinatorial CKi blockade and glutathione inhibition or ferroptosis activation abrogated cell survival. Our data demonstrated that CKi perturbs promigratory and anti-ferroptotic roles in GBM, identifying the creatine kinase axis as a druggable target for GBM treatment.

Leishmaniasis is a neglected tropical disease with significant global public health implications, leading to diverse clinical manifestations. It disproportionately affects impoverished populations in over 90 countries, making it a major health concern worldwide. This study provides a comprehensive analysis of the global burden of leishmaniasis from 1990 to 2021 across 204 countries and territories, using data from the Global Burden of Disease Study 2021. It estimates the disability-adjusted life years (DALYs) associated with leishmaniasis, assessing its impact across different age groups, sexes, and sociodemographic index (SDI) categories. The findings show a decline in the global age-standardized DALY rate for visceral leishmaniasis, from 75.73 to 5.39 per 100,000 population (a reduction of 92.9%). However, the DALY rate for cutaneous and mucocutaneous leishmaniasis has increased from 3.86 to 4.88 per 100,000 (a 26.4% rise), particularly in low- and middle-SDI countries. The study also reveals significant sex disparities in occupational risk factors, with men being more vulnerable to environmental and industrial exposures. Additionally, nutritional deficiencies, particularly calcium and zinc deficiencies, are identified as significant global risk factors. The results underscore the need for targeted public health interventions, particularly those addressing nutritional deficiencies and occupational exposures. Region-specific health strategies should be developed to account for local risk factors, sex differences, and the varying impacts of environmental and industrial exposures, especially in less developed regions.