Search

An immune-related gene signature (IRGS) was established to better understand the molecular and immunologic characteristics of microsatellite instable (MSI) and microsatellite stable (MSS) endometrial carcinoma (EC), and provide potential immunotherapy directions for MSS patients. Top 20 immune-related hub genes were screened by weight gene coexpression network analysis (WGCNA), and an IRGS was further established through Cox regression analysis. The molecular and immune characteristics were clarified in IRGS high and low risk groups. Expression and MS status validation of the IRGS were conducted through quantitative real-time Polymerase Chain Reaction (rt-qPCR) and immunohistochemistry (IHC) analysis. The IRGS includes 2 oncogenes (AGTR1 and HTR3C) and 2 tumor suppressor genes (CD3E and SERPIND1). Patients in IRGS high-risk group were more with MSS status, higher tumor grade, later FIGO stage, serous histology and elder ages compared with IRGS low-risk group (P < 0.05). Besides, patients in MSS group were more FIGO stages II–IV (42.7% vs. 26%), serous histology (35.7% vs. 5.3%) and with higher IRGS risk score (1.51 ± 3.11 vs. 1.02 ± 0.67) (P < 0.05) than patients in MSI group. Furthermore, patients in IRGS high-risk group had higher tumor purity, more Macrophages M1 and Macrophages M2 infiltrating, higher proportion of Macrophages M2 and Dendritic cells activated, lower proportion of T cells regulatory (Tregs), lower tumor mutation burden (TMB). Correspondingly, subjects in IRGS low-risk group had higher immunphenoscores than IRGS high-risk group. The relative mRNA level of AGTR1 and HTR3C were gradually increase, while CD3E and SERPIND1 were reversed in rt-qPCR. Through IHC experiments, AGTR1(69.2% vs 30%, P = 0.074) and HTR3C (76.9% vs 30%, P = 0.024) had higher positive staining rates in ECs than non-ECs. While SERPIND1 (84.6% vs 20%, P = 0.003) and CD3E (61.5% vs 40%, P = 0.000) had higher positive staining rates in non-ECs. IRGS is a potential diagnostic and prognostic biomarker for EC. IRGS low risk group might benefit from immune checkpoint inhibitors, while IRGS high risk group deserve other potential immunotherapy. [ABSTRACT FROM AUTHOR]

Lightweight and high-strength aerogels are specially required in thermal insulation and thermal protection. However, maintaining light weight and high-strength still represents a formidable challenge. Herein we explore a strategy to introduce polyvinylmethyldimethoxysilane (PVMDMS) into polybenzoxazine (PBO) for enhancing the skeleton, and PVMDMS-PBO aerogels were prepared by sol-gel method and ambient pressure drying. The resulting PVMDMS-PBO aerogels possess a 3D nano-porous network structure, and the density can be as low as 0.11 g/cm3. The compressive strength of PVMDMS-PBO aerogels at 10 % strain (10% ε) is 0.55 MPa, much higher than the 0.12 MPa at 10% ε of the pure PBO aerogels with a similar density of 0.13 g/cm3. With increasing PVMDMS content, the thermal conductivity of PBO aerogel decreased from 0.0489 W/(m·K) to 0.0432 W/(m·K). The peak heat release rate decreased from 125.0 W/g to 91.7 W/g. The lightweight, high strength, excellent flame retardancy and thermal insulation of PVMDMS-PBO aerogels make them conducive to thermal insulation application. Highlights: The PVMDMS-PBO aerogels possess a low density of 0.11g/cm3 by ambient pressure drying. The PVMDMS-PBO aerogels exhibit high compressive strength of 0.55 MPa at 10 % stain. The PVMDMS-PBO aerogels have superior thermal insulation and flame retardancy. [ABSTRACT FROM AUTHOR]

Nicotine addiction and the occurrence of lymph node spread are two major significant factors associated with esophageal cancer's poor prognosis; however, nicotine's role in inducing lymphatic metastasis of esophageal cancer remains unclear. Here we show that OTU domain-containing protein 3 (OTUD3) is downregulated by nicotine and correlates with poor prognosis in heavy-smoking esophageal cancer patients. OTUD3 directly interacts with ZFP36 ring finger protein (ZFP36) and stabilizes it by inhibiting FBXW7-mediated K48-linked polyubiquitination. ZFP36 binds with the VEGF-C 3-'UTR and recruits the RNA degrading complex to induce its rapid mRNA decay. Downregulation of OTUD3 and ZFP36 is essential for nicotine-induced VEGF-C production and lymphatic metastasis in esophageal cancer. This study establishes that the OTUD3/ZFP36/VEGF-C axis plays a vital role in nicotine addiction-induced lymphatic metastasis, suggesting that OTUD3 may serve as a prognostic marker, and induction of the VEGF-C mRNA decay might be a potential therapeutic strategy against human esophageal cancer. The mechanism of how VEGF-C is regulated to promote lymphatic metastasis of oesophageal cancer is unclear. Here the authors show that nicotine prevents the mRNA decay of VEGF-C mRNA and promotes lymphatic metastasis by downregulating deubiquitinase OTUD3 and RNA binding protein ZFP36. [ABSTRACT FROM AUTHOR]

Polybenzoxazine (PBO) aerogels were prepared from 4,4′-diamino-diphenylmethane (MDA) benzoxazine monomer by HCl-catalyzed ring-opening polymerization at room temperature after CO2 supercritical drying. This study systematically analyzes the microstructures, thermal insulation properties, compressive properties, and thermal stabilities of the PBO aerogels. The aerogel structure was a cross-linked three-dimensional network with a pore size of 10–140 nm. The conductivity of the aerogels was 0.035–0.057 W/m K under ambient conditions, reducing to 0.009 W/m K at 3 Pa. The compressive strength reached 14.42 MPa under 10% strains, much greater than in SiO2 aerogels of similar density (0.40 g/cm3) reinforced by high-silica glass fiber, which is only 1.30 MPa. Hydrogen bonding interaction was found to be critical for constructing the three-dimensional network structure of the aerogels. This work provides a valuable reference for exploring new structures and expanding the thermal insulation applications of PBO aerogels. [ABSTRACT FROM AUTHOR]