GPR176 Is a Biomarker for Predicting Prognosis and Immune Infiltration in Stomach Adenocarcinoma.

Immunotherapy based on immune checkpoint inhibitors (ICIs) is considered to be a promising treatment for stomach adenocarcinoma (STAD), but only a minority of patients benefit from it. It is believed that the poor therapeutic efficacy is attributed to the complex tumor immune microenvironment (TIM) of STAD. Therefore, elucidating the specific regulatory mechanism of TIM in STAD is critical. Previous study suggests that GRP176 may be involved in regulating the pace of circadian behavior, and its role in tumors has not been reported. In this study, we first found that GPR176 was highly expressed in STAD and negatively correlated with patient prognosis. Next, we investigated the relationship between GPR176 and clinical characteristics, and the results showed that the stage is closely related to the level of GPR176. In addition, our further analysis found that GRP176 expression level was significantly correlated with chemotherapeutic drug sensitivity and ICI response. KEGG and GO analyses showed that GPR176 might be involved in stromal remodeling of STAD. Furthermore, we analyzed the association between GPR176 expression and immune implication, and the results revealed that GPR176 was negatively related to the infiltration of various immune cells. Interestingly, GPR176 induced the conversion of TIM while reducing the tumor immune burden (TMB). The expression of GRP176 is closely related to the level of various immunomodulators. Moreover, we performed univariate and multivariate regression analyses on the immunomodulators and finally obtained 4 genes (CRCR4, TNSF18, PDCD1, and TGFB1). Then, we constructed a GRP176-related immunomodulator prognostic model (GRIM) based on the above 4 genes, which was validated to have good predictive power. Finally, we developed a nomogram based on the risk score of GRIM and verified its accuracy. These results suggested that GPR176 is closely related to the prognosis and TIM of STAD. GPR176 may be a new potential target for immunotherapy in STAD.

Syntheses of functionalized benzocoumarins by photoredox catalysis.

Direct functionalization of inert C(sp3)-H bonds is an attractive synthetic technology for the preparation of pharmaceutically significant compounds in modern synthetic organic chemistry. In this work, we report a new method for the synthesis of functionalized benzocoumarins through the strategy of activation of multiple C-H bonds on 2-aryl toluenes under visible-light-enabled photoredox conditions. This method has the advantages of high functional group compatibility, mild reaction conditions, and effectively avoiding the use of strong oxidants and precious metal catalysts. Detailed mechanistic investigations, including spectroscopic and electrochemical studies, support the reaction's mechanistic course.

Di-µ-methacrylato-bis-[diaquabis(meth-acryl-ato)europium(III)] methacrylic acid disolvate.

In the title centrosymmetric complex, [Eu(2)(C(4)H(5)O(2))(6)(H(2)O)(4)]·2C(4)H(6)O(2), the unique Eu(III) cation is coordinated by seven carb-oxylate O atoms from four methacrylate ligands and two water mol-ecules in a slightly disorted tricapped trigonal-prismatic environment. Two Eu(III) ions are bridged by carboxyl-ate groups, forming a dinuclear complex. The formula unit also contains two mol-ecules of methacrylic acid. In the crystal structure, mol-ecules are linked via inter-molecular O-H⋯O hydrogen bonds, forming one-dimensional chains propagating along the b-axis direction.