Yujia Jiang

EBV activation specifically occurs in a subset of patients following CD7 CAR-T therapy, subsequently leading to EBV-positive lymphoproliferative disorder (EBV+ LPD), descriptively referred to as post-CD7 CAR-T lymphoproliferative disorder (PCLD) in this study. To comprehensively characterize PCLD, we employed single-nucleus RNA sequencing, ATAC sequencing, and Stereo-seq to perform multi-omic spatial profiling of PCLD, and compared it with classical post-transplant lymphoproliferative disorder (PTLD), EBV-negative diffuse large B-cell lymphoma (EBV- DLBCL) and normal lymph nodes. Infiltrating T cells in PCLD are uniquely characterized by CD7 negativity, exhibiting limited proliferation upon infection stimulation and impaired antiviral activity against EBV. Macrophages are recruited in an attempt to sustain viral clearance; however, the Macro_IDO1 subset emerges as the dominant macrophage population, exhibiting an immunosuppressive phenotype marked by elevated IDO1 expression. Spatially, macrophages, predominantly Macro_IDO1, aggregate to form an immunosuppressive niche that restricts T-cell infiltration and is enriched for inhibitory ligand-receptor interactions, including the PD-1/PD-L1 axis. T-cell function is further compromised, enabling sustained EBV infection of B cells and driving malignant transformation. EBV-driven B cells undergo plasmacytic differentiation and sustained proliferation, actively remodeling the microenvironment. This study provides a comprehensive molecular characterization of lymphoproliferative disorder following CD7 CAR-T therapy, elucidates spatial tumor-immune interactions, mechanisms of EBV-driven B-cell transformation and potential intervention strategies.

The early organogenesis stage is a critical phase of embryogenesis that lays the foundation for organ development, and is characterized by dynamic and spatially organized transcriptional programs. However, limited spatial transcriptomic information has constrained our understanding of early primate organogenesis. Here we present a comprehensive three-dimensional (3D) spatial transcriptomic atlas of cynomolgus monkey embryos at Carnegie stages (CS) 9 and 10, capturing key morphogenetic events including cardiogenesis, gut tube regionalization, neurulation, axial mesendoderm patterning and early somitogenesis. Using high-resolution spatial transcriptomics and 3D reconstruction, we identify spatially defined lineage domains across germ layers and resolve regionally restricted gene expression, transcription factor activity, and signalling landscapes along major embryonic axes, exemplified by the emergence of dorsoventrally patterned spinal cord subpopulations during neurulation. Cross-species comparisons with human and mouse datasets reveal conserved and species-biased transcriptional programs. Together, this atlas provides a foundational reference for studying early primate development.

Simazine is a widely used herbicide and known as an environmental estrogen. Multiple studies have proved simazine can induced the degeneration of dopaminergic neuron resulting in a degenerative disease‐like syndrome. Herein, we explored the neurotoxicity of simazine on the dopaminergic nervous system of embryos and weaned offspring during the maternal gestation period or the maternal gestation and lactation periods. We found that simazine disturbed the crucial components expression involved in Lmx1a/Wnt1 pathway of dopaminergic neuron in embryonic and weaned offspring. Furthermore, morphological and behavioral tests performed on weaned male offspring treated by simazine suggested that the grip strength, autonomic exploring, and the space sense ability were weakened, as well as the pathological damage of dopaminergic neuron was clearly observed. But, the same neurotoxicity of simazine is less significantly observed in female offspring. Our findings will provide reliable reference for the determination of environmental limits and new insight into the pathogenesis of nonfamilial neurodegenerative diseases related to environmental risk factors.

Background: Despite the advances in early detection and treatment methods, breast cancer still has a high mortality rate, even in those patients predicted to have a good prognosis. The purpose of this study is to identify a microRNA signature that could better predict prognosis in breast cancer and add new insights to the current classification criteria. Materials and methods: We downloaded microRNA sequencing data along with corresponding clinicopathological data from The Cancer Genome Atlas (TCGA). Of 1,098 breast cancer patients identified, 253 patients with fully characterized microRNA profiles were selected for analysis. A three-microRNA signature was generated in the training set. Subsequently, the performance of the signature was confirmed in a validation set. After construction of the signature, we conducted additional experiments, including flow cytometry and the Cell Counting Kit-8 assay, to illustrate the correlation of this microRNA signature with breast cancer cell cycle, apoptosis, and proliferation. Results: Three microRNAs (hsa-mir-31, hsa-mir-16-2, and hsa-mir-484) were identified to be significantly and independently correlated with patient prognosis, and performed with good stability. Our results suggest that higher expression of hsa-mir-484 indicated worse prognosis, while higher expression of hsa-mir-31 and hsa-mir-16-2 indicated better prognosis. Moreover, additional experiments confirmed that this microRNA signature was related to breast cancer cell cycle and proliferation. Conclusion: Our results indicate a three-microRNA signature that can accurately predict the prognosis of breast cancer, especially in basal-like and hormone receptor-positive breast cancer subtypes. We recommend more aggressive therapy and more frequent follow-up for high-risk groups.