Spatial Heterogeneity of PD-1/PD-L1 Defined Osteosarcoma Microenvironments at Single-Cell Spatial Resolution.

Osteosarcoma, predominantly affecting children and adolescents, is a highly aggressive bone cancer with a 5-year survival rate of 65% to 70%. The spatial dynamics between tumor-associated macrophage (TAM) and other cellular subtypes, including T cells, osteoblasts, and osteoclasts, are critical for understanding the complexities of the osteosarcoma tumor microenvironment (TME) and can provide insights into potential immunotherapeutic strategies. Our study employs a pioneering approach that combines deep learning-based digital image analysis with multiplex fluorescence immunohistochemistry to accurately implement cell detection, segmentation, and fluorescence intensity measurements for the in-depth study of the TME.

CD206 M2-like macrophages protect against intervertebral disc degeneration partially by targeting R-spondin-2.

Objective: This study aimed to explore the specific function of M2 macrophages in intervertebral disc degeneration (IDD).

Methods: Intervertebral disc (IVD) samples from normal (n = 4) and IDD (n = 6) patients were collected, and the expression of M2-polarized macrophage marker, CD206, was investigated using immunohistochemical staining. Nucleus pulposus cells (NPCs) in a TNF-α environment were obtained, and a mouse caudal IVD puncture model was established.

Effect of hepatic NPC1L1 on cholesterol gallstone disease and its mechanism.

Cholesterol gallstone disease (CGD) is associated with bile cholesterol supersaturation. The Niemann-Pick C1-like 1 (NPC1L1), the inhibitory target of ezetimibe (EZE), is a critical sterol transporter of cholesterol absorption. Intestinal NPC1L1 facilitates the absorption of cholesterol, whereas hepatic NPC1L1 promotes cholesterol uptake by hepatocytes and reduces bile cholesterol supersaturation.

FGF15 promotes hepatic NPC1L1 degradation in lithogenic diet-fed mice.

Background: Cholesterol gallstone disease (CGD) is accompanied by biliary cholesterol supersaturation. Hepatic Niemann-Pick C1-like 1 (NPC1L1), which is present in humans but not in wild-type (WT) mice, promotes hepatocyte cholesterol uptake and decreases biliary cholesterol supersaturation. In contrast, intestinal NPC1L1 promotes intestinal cholesterol absorption, increasing biliary cholesterol supersaturation.

Tumor-Infiltrating Lymphocyte-Based Risk Score for Predicting Prognosis in Gastric Cancer.

Tumor-infiltrating lymphocytes (TILs) in gastric cancer are closely related to clinical prognosis; however, little is known regarding the immune microenvironment in this disease. Thus, RNA-sequencing data from gastric cancer patients were downloaded from the Gene Expression Omnibus (GEO). The proportion of immune cells was determined based on a deconvolution algorithm (CIBERSORT), and gene expression profiles were analyzed in the context of clinical outcomes to construct an immune risk score.

-methyladenosine (mA) RNA methylation signature as a predictor of stomach adenocarcinoma outcomes and its association with immune checkpoint molecules.

Objective: Although -methyladenosine (mA) RNA methylation is the most common mRNA modification process, few studies have examined the role of mA in stomach adenocarcinomas (STADs).

Methods: In this retrospective study, we analyzed 293 STAD samples from The Cancer Genome Atlas with complete clinicopathological feature profiles. The mA methylation risk signature was derived from LASSO-Cox regression analyses with 15 mA regulators.