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Biology subjects

wei, y.

Publications and source records attributed to wei, y..

2 recordsLinked to original sources

From local motifs to global dynamical stability in the mouse brain connectome

Brain connectomics provides insights into the architectural organization of neural circuits across the brain. But it remains unclear how neurons and their connections give rise to brain-wide activity. Here, using a sparse detailed mouse brain connection map called "bouton-net," we studied how specific neuron patterns (motifs) and groups (modules) affect information processing. We discovered that complex, "two-way" connections are much more common than expected. These patterns appear across all brain regions, suggesting they are a universal rule for brain wiring. We also found that different brain modules do not communicate randomly; instead, they talk through a small group of highly connected neurons. By testing these organization patterns with computer models, we found that the brain may not be wired for the best memory capacity or nonlinear processing capability, but to ensure that capability remains stable. This structure provides the foundation for a reliable, "crash-proof" biological network.

neuroscience↗

Ligand-independent c-Met activation by HHLA2 drives hepatocellular carcinoma and predicts c-MET inhibitor efficacy

The HGF/c-Met signaling pathway facilitates the initiation, progression, and metastasis of hepatocellular carcinoma (HCC). c-Met activation, however, is complex and not solely dependent on HGF, hindering targeted therapy development. This study identifies a critical oncogenic role for HHLA2, a B7 family member, in HCC and highlights its potential as a therapeutic target. We demonstrate that HHLA2 directly interacts with and activates c-Met through N-glycosylation, triggering sustained signaling and promoting aggressive HCC features. Mechanistically, we identified the pro-tumorigenic role of HHLA2 required downstream upregulation of MMP9 and VEGFA, both implicated in tumor progression. In multiple mouse models, HHLA2 overexpression accelerated tumor progression, metastasis, and reduced liver NK cell infiltration, all of which were reversed by c-Met inhibition. In a cohort of 176 HCC patients, HHLA2 expression strongly correlated with c-Met phosphorylation, advanced tumor stage, and poor prognosis. Importantly, HHLA2 expression predicted sensitivity to c-Met inhibitors in cell lines and patient-derived organoids and could be detected in patient serum, suggesting its potential as a prognostic biomarker. Collectively, our findings reveal an HHLA2-mediated mechanism of c-Met activation and provide a strong rationale for targeting the HHLA2-c-Met axis as a novel therapeutic strategy, with HHLA2 serving as a potential prognostic biomarker. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=173 SRC="FIGDIR/small/622557v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@8b10dforg.highwire.dtl.DTLVardef@b43dorg.highwire.dtl.DTLVardef@394c4aorg.highwire.dtl.DTLVardef@1bfbc8c_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗