Biology subjects

Lu, Y. D.

Publications and source records attributed to Lu, Y. D..

4 recordsLinked to original sources

bioRxiv2026

Genomic classification and immune profiling define mucosal melanoma

Mucosal melanoma is a rare, lethal melanoma subtype with distinct genetics and limited benefit from immunotherapy. To define features associated with mucosal melanoma clinical outcomes, we assembled a large, multimodally profiled cohort spanning primary and metastatic disease. Compared with cutaneous melanoma, primary mucosal melanoma showed greater genomic heterogeneity, ploidy and aneuploidy, and a more dedifferentiated, proliferative transcriptional state. Analysis of genomic sequencing of 339 patients with mucosal melanoma identified four mutually exclusive genomic subtypes: CDK4/MDM2/CCND1, SF3B1-mutated, TP53/ATRX, and mucosal melanoma Triple WT, associated with distinct anatomic sites but similar outcomes. In the tumor microenvironment, we observed reduced T cell infiltration and increased CD163+ tumor-associated macrophages in mucosal melanoma relative to cutaneous melanoma. In matched longitudinal samples, CD163+ tumor-associated macrophages increased with disease progression and immunotherapy resistance. CD163+ tumor-associated macrophages engaged non-regulatory T cells through GAL9-TIM-3 interactions, nominating TIM-3 blockade as a therapeutic strategy for mucosal melanoma. These findings define the distinct aggressive biology of mucosal melanoma and highlight potential therapeutic targets and mechanisms of immune resistance.

cancer biology↗

bioRxiv2026

Modeling development of tertiary lymphoid structures in pulmonary tuberculosis by 3D profiling and trajectory analysis

Tertiary lymphoid structures (TLSs) are sites of immune organization in peripheral tissues that arise from chronic inflammation. They play important roles in infection control and cancer but the mechanisms controlling their formation remain only partly understood. Here, we combine high-plex imaging, serial-section 3D reconstruction, and optimal transport trajectory modeling to reconstruct TLSs in human lungs infected with Mycobacterium tuberculosis. We find that the extended and irregular shape of TLSs is poorly captured by 2D histopathology or spatial profiling, making assessment of developmental stage (early, primary, or secondary) error prone. In contrast, modeling TLS development in 3D using optimal transport reveals two trajectories that differ in the timing and coordination of follicular dendritic cell association, germinal center consolidation, and position within the tissue. These findings highlight the value of volumetric analysis in understanding immune organization and provide new insights into TLS biology. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=98 SRC="FIGDIR/small/725201v2_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@11b4daorg.highwire.dtl.DTLVardef@7871feorg.highwire.dtl.DTLVardef@1840c2dorg.highwire.dtl.DTLVardef@3b6028_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LI3D reconstruction of TB-infected lung reveals TLSs to be extended, heterogeneous structures that are frequently misclassified in 2D C_LIO_LITLS maturation follows continuous trajectories rather than discrete histological stages C_LIO_LIOptimal transport modeling identifies distinct maturation paths with divergent follicular dynamics C_LIO_LIGerminal center organization and Tfh-FDC interactions emerge along maturation trajectories C_LIO_LITLS maturation states are shaped by spatially localized microenvironmental niches. C_LI

immunology↗

bioRxiv2026

Volumetric Cyclic Immunofluorescence for 3D Spatial Profiling of Immune Structures in Human FFPE Tissue

Mapping how parenchymal, immune, and stromal cells interact with extended structures such as blood vessels and nerves is challenging using conventional thin-section tissue imaging. Volumetric methods such as light-sheet fluorescence microscopy (LSFM) are ideal in these cases and LSFM is widely used in animal models such as fish and mice. This is enabled by well-established clearing methods, genetically encoded reporters, and vascular dyes. However, LSFM is rarely utilized for human tissue, which is primarily available as formaldehyde-fixed paraffin embedded (FFPE) specimens. Here, we present an approach to volumetric cyclic immunofluorescence (v-CyCIF) that enables 40-plex or greater imaging of immune and other cell types in human specimens up to 1 mm thick. We demonstrate the use of v-CyCIF to study neuroimmune interactions and lymphoid structures in normal and cancer tissues. Following LSFM imaging, specimens can be re-embedded and sectioned to ~50 {micro}m thick for high-resolution confocal imaging of punctate structures and cell-cell junctions. v-CyCIF therefore provides a flexible framework for multi-scale 3D profiling of clinical specimens across imaging formats and resolutions.

cancer biology↗

bioRxiv2020

Gut Microbiota Mediates the Protective Effects of Andrographolide Inhibits Inflammation and Nonalcoholic Fatty Liver Disease(NAFLD) in High-Fat Diet induced ApoE(-/-) Mice

Mechanisms relating the gut bacteria to Nonalcoholic Fatty Liver Disease (NAFLD) have been proposed containing the dysbiosis-induced dysregulation of hepatic lipid metabolism that allows for the translocation of microbial components and leads to hepatic inflammation and steatosis. Andrographolide (AG) regulates inflammation mediated by NF-{kappa}B pathway which also play a key role in reduction of inflammation and fibrosis in experimental nonalcoholic steatohepatitis (NASH), yet the mechanisms linking this effect to gut microbiota remain obscure. Here we show that ApoE knockout (Apoe -/-) mice fed a high-fat diet (HFD) supplemented with AG regulates levels of biochemical index and inflammatory cytokines associated with gut microbe. Moreover, HEPG2 cells induced by ox-LDL were used as validation in vitro. H&E staining and Oil-Red staining were respectively used for tissue and cells morphology. Gut microbiota were examined by 16S rRNA sequencing. Expression of NF-{kappa}B, C/EBP{beta} and PPAR-{gamma} in liver and HEPG2 cells were detected by western blot and qRT-PCR. The results showed, among others, that AG alleviate hepatic steatosis and fat content in HEPG2 cells, while it induced decreased levels of Bacteroides, and increased levels of Faecalibaculum, Akkermansia. We further identified that inhibition of NF-{kappa}B/C/EBP{beta}/PPAR-{gamma} pathway of hepatic steatosis model in vivo and vitro by AG also contributes to prevention of HFD-induced inflammation and dislipidemia. Importantly, as result of pearson correlation, Bacteroides may be the most relevant one fundamentally involved in the mechanism of AG attenuates NAFLD. Together, our findings uncover an interaction between AG and gut microbiota as a novel mechanism for the anti-NAFLD effect of AG acting through prevention of microbial dysbiosis, dislipidemia and inflammation. ImportanceHFD due to gut microbial dysbiosis is a major contributor to the pathogenesis of dislipidemia and inflammation, which primarily mediates the development of NAFLD. A treatment strategy to reduce both dislipidemia and inflammation appears to be an effective approach for addressing the issue of NAFLD. Andrographolide (AG) is the major effect component in traditional Chinese medicine Chuan-xin-lian (Andrographis). Little is known about the role of gut microbiota in the anti-NAFLD effect of AG. 16S rRNA gene sequencing revealed that AG significantly decreased Bacteroides and increased Faecalibaculum, Akkermansia. By using vivo and vitro experiment, we prove that gut microbiota plays a key role in AG-induced protective against high-fat-diet-induced dislipidemia and inflammation. Moreover, NF-{kappa}B/C/EBP{beta}/PPAR-{gamma} pathway inhibition was partially involved in the beneficial effect of AG. Together, these data suggest that the gut microbiome is a critical factor for the anti-NAFLD effects of AG.

pharmacology and toxicology↗