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Integrative multi-omics analysis identifies stromal-immune crosstalk as a determinant of immunotherapy efficacy and establishes a prognostic signature in gastric cancer

Comput Biol Chem. 2026 Apr 23;124(Pt 1):109095. doi: 10.1016/j.compbiolchem.2026.109095. Online ahead of print.

ABSTRACT

Immune checkpoint inhibitors like pembrolizumab exhibit variable efficacy in metastatic gastric cancer (GC). This study aimed to identify molecular drivers of pembrolizumab response, explore mechanisms of immune checkpoint inhibitors (ICIs) efficacy, and develop a prognostic signature. Transcriptomic analysis of pembrolizumab-treated GC (TIGER database) identified 165 response-associated differentially expressed genes (DEGs). Functional annotation and single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) revealed that responder-upregulated genes (R-DEGs) were enriched in immune activation pathways and mainly localized to CD8 + T/NK cells. In contrast, non-responder-upregulated genes (D-DEGs) were linked to extracellular matrix (ECM) remodeling and mainly expressed in fibroblasts/endothelial cells. CellChat analysis demonstrated that key DEGs mediate immune-stromal crosstalk via MHC-I and collagen/laminin signaling. A prognostic signature (Lasso-StepCox[forward] Riskscore; LSR: APOD, APOH, BATF2, GJA1, MAGED1, SLC5A1, SLCO2A1, VWF, VCAN) was derived and validated in four independent GC cohorts from the GEO and Cancer Genome Atlas (TCGA) database. Multi-omics analyses showed that LSR-high tumors exhibited aggressive clinicopathological features, increased stromal components, reduced cytotoxic immune infiltration, diminished tumor mutational burden (TMB), and poorer prognosis. Immunohistochemistry (IHC) and spatial transcriptomics in GC showed that stromal VWF/VCAN expression correlates with reduced CD8⁺ T cell granzyme B expression, suggesting T cell dysfunction. High VWF expression in GC predicted poor survival, and a combined VWF/VCAN score showed enhanced prognostic stratification. This study highlights stromal-immune crosstalk as a driver of pembrolizumab resistance and provides a signature as a clinical tool for prognosis and personalized therapy in metastatic GC.

PMID:42068630 | DOI:10.1016/j.compbiolchem.2026.109095

Mummified early Permian reptile reveals ancient amniote breathing apparatus

Nature, Published online: 08 April 2026; doi:10.1038/s41586-026-10307-y

A mummified fossil of the early Permian reptile Captorhinus reveals the potential ancestral amniote breathing mechanism and its impact on terrestrial vertebrate evolution.

xLLM Technical Report

arXiv:2510.14686v2 Announce Type: replace-cross Abstract: We introduce xLLM, an intelligent and efficient Large Language Model (LLM) inference framework designed for high-performance, large-scale enterprise-grade serving, with deep optimizations for diverse AI accelerators. To address these challenges, xLLM builds a novel decoupled service-engine architecture. At the service layer, xLLM-Service features an intelligent scheduling module that efficiently processes multimodal requests and co-locates online and offline tasks through unified elastic scheduling to maximize cluster utilization. This module also relies on a workload-adaptive dynamic Prefill-Decode (PD) disaggregation policy and a novel Encode-Prefill-Decode (EPD) disaggregation policy designed for multimodal inputs. Furthermore, it incorporates a distributed architecture to provide global KV Cache management and robust fault-tolerant capabilities for high availability. At the engine layer, xLLM-Engine co-optimizes system and algorithm designs to fully saturate computing resources. This is achieved through comprehensive multi-layer execution pipeline optimizations, an adaptive graph mode and an xTensor memory management. xLLM-Engine also further integrates algorithmic enhancements such as optimized speculative decoding and dynamic EPLB, collectively serving to substantially boost throughput and inference efficiency. Extensive evaluations demonstrate that xLLM delivers significantly superior performance and resource efficiency. Under identical TPOT constraints, xLLM achieves throughput up to 1.7x that of MindIE and 2.2x that of vLLM-Ascend with Qwen-series models, while maintaining an average throughput of 1.7x that of MindIE with Deepseek-series models. xLLM framework is publicly available at https://github.com/jd-opensource/xllm and https://github.com/jd-opensource/xllm-service.
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