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Abstract Immunotherapy has dramatically changed the landscape of treatment for colorectal cancer (CRC), but currently lack of effective predictive biomarker, especially for tumors with mismatch repair (MMR) proficiency. The response of immunotherapy is associated with the cell–cell interactions in tumor microenvironment, encompassing processes such as cell–cell recognition, binding, and adhesion. However, the function of immunoglobulin superfamily (IGSF) genes in tumor immune microenvironment remains uncharacterized. This study quantified the immune landscape by leveraging a gene expression matrix from publicly accessible databases. The associations between IGSF6 gene expression and immune cell infiltration were assessed. The expression levels of IGSF6, CD8+ T cells, CD4+ T cells and CD68+ macrophage cells in cancer tissues from CRC patients and CRC cell lines were evaluated. IGSF6 was more highly expressed in CRC tumor tissues than adjacent normal tissues. And IGSF6 was significantly correlated with immune cell infiltration in MMR-proficient patients. Remarkably, MMR-proficient patients with high IGSF6 expression showed more sensitive to immunotherapy and chemotherapy than those with low IGSF6 expression. In summary, IGSF6 could be a novel biomarker to evaluate immune infiltration and predict therapeutic effect for MMR-proficient CRC.

Background: In the Montreal classification, L4 Crohn’s disease (CD) is defined as an ileal disease, including L4-esophagogastric duodenum (EGD), L4-jejunum, and L4-proximal ileal involvement. According to the previous studies, the prognosis of L4 disease was worse than that of non-L4 disease. Among L4 diseases, the phenotypes of L4-jejunum and L4-proximal ileum indicated that the risk of abdominal surgery was higher. However, the prognosis of L4-esophagogastroduodenal remains largely elusive. Therefore, we aim to investigate whether the prognosis differs between CD patients with and without esophagogastroduodenal involvement.Methods: In this study, patients with L4-EGD phenotype (n = 74) who underwent gastroscopy, ileocolonoscopy, biopsies, and CTE from 2018 to 2020 were compared with L4 non-EGD controls (n = 148) who were randomly selected at a ratio of 1:2 in the same period. Demographic information inclusive of disease conduct and location, important points of the surgery, and hospitalization have been collected. The distinction between L4-EGD patients and non-L4-EGD patients was identified by way of multivariable logistic regression analysis. The Kaplan–Meier technique was used to consider the possibility of abdominal surgical operation and complications, observed by means of Cox percentage hazard fashions to decide if L4 EGD independently estimated the endpoints inclusive of the abdominal surgery and the occurrences of complications.Results: L4-EGD group (n = 74) had a lower proportion of intestinal fistula than the control group (n = 148) (17.6% versus 34.5%; p = 0.009), and the probabilities of requiring abdominal surgery and multiple abdominal surgeries were also lower (21.6% versus 36.5%; p = 0.025), (6.8% versus 18.9%; p = 0.016), respectively. The frequency of hospitalization was lower in the L4-EGD group than in the control group (3-7 versus 4–9; p = 0.013). L4-EGD phenotype was found to be an independent protective factor for abdominal surgery and intestinal fistula in the Cox regression model, with HRs of 0.536 (95%CI: 0.305–0.940; p = 0.030) and 0.478 (95%CI: 0.259–0.881; p = 0.018), respectively.Conclusion: Our data suggest that the L4-EGD phenotype may have a better prognosis compared to the Non-L4-EGD phenotype. Our data may advocate a revision of the Montreal classification including separate designations for L4-EGD disease.

Objective: To identify the active ingredients, potential targets, and mechanism of Rhizoma coptidis by bioinformatics method, and to explore the hypoglycemic effect of Rhizoma coptidis by in vitro experiments. Methods: The chemical components of Rhizoma coptidis were collected through database search, and oral bioavailability and drug-likeness were used for preliminary screening. The targets of Rhizoma coptidis and diabetes-related targets were collected by database retrieval and reverse docking techniques, and the biological process of cross-set proteins was analyzed. The inhibitory effects of Rhizoma coptidis on α-glucosidase, α-amylase activity, and advanced glycation end products (AGEs) were determined via in vitro experiments. In addition, the effects of Rhizoma coptidis on pre-adipocyte differentiation, absorption of glucose by adipocytes, and the level of intracellular triglyceride were investigated using the adipocyte differentiation model. Results: There were 11 potentially active ingredients in Rhizoma coptidis. IL-6, caspase-3, epidermal growth factor receptor (EGFR), MYC, and estrogen receptor 1 were considered as the key genes. The bioinformatics analysis showed that Rhizoma coptidis played an anti-diabetic role mainly via biological processes and signaling pathways including hormone receptor activity, glutathione binding, steroid binding, etc. In vitro experiments showed that the extract of Rhizoma coptidis inhibited the activities of α-glucosidase and α-amylase, and the generation of AGEs; meanwhile, the extract promoted the absorption of glucose by adipocytes. In addition, the extract of Rhizoma coptidis decreased triglyceride level. Conclusions: Our network pharmacology and in vitro experiments demonstrate the anti-diabetic effects and possible underlying mechanisms of Rhizoma coptidis extract.

Purpose: A certain number of early-stage colorectal cancer (CRC) patients suffer tumor recurrence after initial curative resection. In this context, an effective prognostic biomarker model is constantly in need. Autophagy exhibits a dual role in tumorigenesis. Our study aims to develop an autophagy-related gene (ATG) signature-based on high-throughput data analysis for disease-free survival (DFS) prognosis of patients with stage I/II CRC.Methods: Gene expression profiles and clinical information of CRC patients extracted from four public datasets were distributed to discovery and training cohort (GSE39582), validation cohort (TCGA CRC, n = 624), and meta-validation cohort (GSE37892 and GSE14333, n = 420). Autophagy genes significantly associated with prognosis were identified.Results: Among 655 autophagy-related genes, a 10-gene ATG signature, which was significantly associated with DFS in the training cohort (HR, 2.76[1.56–4.82]; p = 2.06 × 10–4), was constructed. The ATG signature, stratifying patients into high and low autophagy risk groups, was validated in the validation (HR, 2.29[1.15–4.55]; p = 1.5 × 10–2) and meta-validation cohorts (HR, 2.5[1.03–6.06]; p = 3.63 × 10–2) and proved to be prognostic in a multivariate analysis. Functional analysis revealed enrichment of several immune/inflammatory pathways in the high autophagy risk group, where increased infiltration of T regulatory cells (Tregs) and decreased infiltration of M1 macrophages were observed.Conclusion: Our study established a prognostic ATG signature that effectively predicted DFS for early-stage CRC patients. Meanwhile, the study also revealed the possible relationship among autophagy process, immune/inflammatory response, and tumorigenesis.

The mixed-valent PbRhOundergoes a Verwey-type transition atK, below which the development of Rh/Rhcharge order induces an abrupt conductor-to-insulator transition in resistivity. Here we investigate the effect of pressure on the Verwey-type transition of PbRhOby measuring its electrical resistivity under hydrostatic pressures up to 8 GPa with a cubic anvil cell apparatus. We find that the application of high pressure can suppress the Verwey-type transition around 3 GPa, above which a metallic state is realized at temperatures below ∼70 K, suggesting the melting of charge order by pressure. Interestingly, the low-temperature metallic region shrinks gradually upon further increasing pressure and disappears completely at P > 7 GPa, which indicates that the charge carriers in PbRhOundergo a reentrant localization under higher pressures. We have constructed a temperature-pressure phase diagram for PbRhOand compared to that of FeO , showing an archetype Verwey transition. [ABSTRACT FROM AUTHOR]