The cyclooxygenase-expressing mesenchyme resists intestinal epithelial injury by paracrine signaling.

Paracrine signals play pivotal roles in organ homeostasis. Mesenchymal stromal cells (MSCs) play a key role in regulating epithelium homeostasis in the intestine while their paracrine effects are poorly characterized. Here, we identified prostaglandin E2 (PGE2) secreted by cyclooxygenase (COX)-expressing MSCs as a vital factor to maintain the intestinal mucosal barrier. We found that MSCs-induced organoid swelling through paracrine effect in vitro, a process due to enhanced water adsorption and is mediated by the COX-PGE2-EP4 axis. To further explore the regulatory effect of this axis on the intestinal epithelial barrier in vivo, we established the conditional knockout mouse model to specifically delete COX in MSCs and found that PGE2 reduction downregulated the gene Muc2 and induced a gastric metaplasia-like phenotype. Moreover, PGE2 defects increased the susceptibility of intestinal epithelium to colitis. Our study uncovers the paracrine signaling of COX-expressing MSCs in intestinal mucosal barrier maintenance, providing a basis for understanding the role of mesenchymal cells in the pathophysiological function of the intestine.

Pan-cancer analysis and experimental validation of DTL as a potential diagnosis, prognosis and immunotherapy biomarker.

BACKGROUND: DTL has been found to be related with multiple cancers. However, comprehensive analyses, which identify the prediction value of DTL in diagnosis, prognosis, immune infiltration and treatment, have rarely been reported so far. METHODS: Combined with the data online databases, the gene expression, gene mutation, function enrichment and the correlations with the immunity status and clinical indexes of DTL were analyzed. Expression of DTL and the degree of immune cell infiltration were examined by immunofluorescence (IF) and immunohistochemistry (IHC) and analyzed by statistical analysis. Furthermore, the influences of DTL on the cell cycle, cell proliferation and apoptosis were detected by live cell imaging, IF and flow cytometric (FC) analysis. Genomic stability assays were conducted by chromosome slide preparation. RESULTS: DTL was widely expressed in various cells and tissues, while it was overexpressed in tumor tissues except acute myeloid leukemia (LAML). Pan-cancer bioinformatics analysis showed that the expression of DTL was correlated with the prognosis, immunotherapy, and clinical indexes in various cancers. In addition, gene set enrichment analysis (GSEA) uncovered that DTL was enriched in oocyte meiosis, pyrimidine metabolism, the cell cycle, the G2M checkpoint, mTORC1 signaling and E2F targets. Furthermore, the overexpression of DTL, and its association with immune cell infiltration and clinical indexes in liver hepatocellular carcinoma (LIHC), bladder urothelial carcinoma (BLCA) and stomach adenocarcinoma (STAD) were verified in our study. It was also verified that overexpression of DTL could regulate the cell cycle, promote cell proliferation and cause genomic instability in cultured cells, which may be the reason why DTL plays a role in the occurrence, progression and treatment of cancer. CONCLUSIONS: Collectively, this study suggested that DTL is of clinical value in the diagnosis, prognosis and treatment of various cancers, and may be a potential biomarker in certain cancers.

Directed molecular structure design of coordination polymers with different ligands for regulating output performance of triboelectric nanogenerators.

A triboelectric nanogenerator (TENG) provides an effective method to harvest mechanical energy from the environment. The morphology and structure of frictional electrode materials of this type of device affect the output performance significantly. Metal-organic coordination polymers (CPs) with special structure advantages offer a vast pool of materials enabling high performances. Two Co-CPs based on terephthalic acid and 2,5-dihydroxyterephthalic acid ligands, respectively, were used to fabricate TENGs. Detailed electrical characterizations of the TENG devices revealed that the introduction of the substituent groups in the organic ligands leads to the structural changes of CPs, which ultimately leads to significant differences in the output performance.

Construction of a ferroptosis-related eight gene signature for predicting the prognosis and immune infiltration of thyroid cancer.

Background: Thyroid cancer is the most common malignant tumor of the endocrine system. Most patients with thyroid cancer have a good prognosis, although a small proportion experience recurrence and metastasis and have a poor prognosis. Ferroptosis is a novel form of regulated cell death (RCD); previous studies have confirmed that ferroptosis was associated with thyroid cancer. The purpose of this study was to investigate the key ferroptosis-related genes in thyroid cancer and their relationship with prognosis and immune cell infiltration. Methods: In this study, 497 thyroid cancer RNA expression datasets were downloaded from the cancer genome atlas (TCGA) cohort and a prognostic risk model for eight ferroptosis-related genes (FRGs) was constructed by Lasso-Cox regression. The prognostic value of the risk model and the correlation of prognostic features with immune scores and tumor immune cell infiltration were systematically analyzed. Results: The prognostic risk model for eight FRGs (DPP4, TYRO3, TIMP1, CDKN2A, SNCA, NR4A1, IL-6 and FABP4) were constructed and validated in training and testing cohorts. Kaplan-Meier curve and receiver operating characteristic (ROC) curve analysis confirmed that that the ferroptosis-related eight gene signature had good predictive value for the prognosis of thyroid cancer (THCA) patients. Multivariate regression analysis further showed that the risk score of the prognostic model could be used as an independent prognostic factor for THCA patients. Functional enrichment analysis showed that DEGs in high risk and low risk groups were involved in immune-related biological processes and that there were significant differences in immune cell infiltration between the two risk groups. Conclusion: We identified eight key genes related to ferroptosis in THCA patients. Further studies are now needed to investigate the mechanisms involved; these genes may represent clinical diagnostic and prognostic biomarkers.

A prognostic model for cervical cancer based on ferroptosis-related genes.

Background: Ferroptosis is widely involved in the occurrence and development of various cancers, but a specific mechanism involving ferroptosis in cervical cancer is still unclear. Methods: Based on the expressions of ferroptosis-related genes, a prognostic model was constructed using lasso regression, and the overall predictive performance of this model was verified. An in-depth analysis of the prognostic model was then conducted. Results: The prognostic model showed good predictive performance in both the validation and test sets. Mechanism analysis indicated that differences in the tumor microenvironment were the basis of the predictive ability of the model. Notably, CA9 mRNA was significantly overexpressed in cervical carcinoma, tissues but not in normal cervix tissues. A pair of ceRNAs (CA9/ULBP2) could be involved in the carcinogenesis and development of cervical cancer, and the potential target might be hsa-miR-34a. In addition, predicted miRNAs and drugs for these DEGs were identified. Conclusions: We constructed a prognostic model with good predictive performance, based on the expression of ferroptosis-related genes. Further research found that the ceRNA pairs of ULBP2/CA9 could regulate cervical cancer through hsa-miR-34a. These results identified the mechanism of ferroptosis in cervical cancer, and might provide novel therapeutics for cervical cancer patients.

Fluorescent porous organic polymers for detection and adsorption of nitroaromatic compounds.

A fluorescent porous organic polymer (FPOP) with strong fluorescence and tunable emission colors, was synthesized through a simple cost-effective method via Scholl coupling reaction. Experiments proved the stability and excellent detection and adsorption ability, and microporous nature of the material. Luminescence of FPOP was quenched when addition of nitroaromatic compounds. The properties along with large-scale and low-cost preparation make these FPOP potential candidates for fluorescence detection of nitroaromatic compounds. Additionally, FPOP shows higher adsorption capacity and rate than other reported adsorbents, and has the possibility of being an effective adsorbent for industrial usage. Moreover, a fluorescent test paper was further developed and is found to be sensitive to 10-8 M level, complete with a rapid response time and visual detection. This newly developed strategy may open up an avenue for exploring porous polymers, particularly those with a strong fluorescence, for the large-scale fabrication of FPOP for various advanced applications.

Research Progress of Ferroptosis in Adiposity-Based Chronic Disease (ABCD).

Ferroptosis is a multistep regulated cell death process induced by iron accumulation and lipid peroxidation. Classical GPX4-dependent pathway and GPX4-independent pathways can independently and synergistically inhibit ferroptosis and jointly maintain the oxidative balance of the body. WHO defines obesity as "a condition of abnormal or excessive fat accumulation in adipose tissue, to the extent that health may be impaired," and obesity is also defined as an adiposity-based chronic disease (ABCD). Obesity is a systemic disease that leads to metabolic abnormalities in various systems, resulting in a series of complications including obesity cardiomyopathy, atherosclerosis, nonalcoholic fatty liver disease, and diabetes mellitus. Emerging evidence shows that ferroptosis is closely associated with the occurrence and progression of various diseases. In recent years, ferroptosis has been found to play critical roles in obesity and its complications. This review discusses the mechanisms of how ferroptosis is initiated and controlled and discusses the research progress of ferroptosis in obesity and its complications.

Inhibition of porcine epidemic diarrhea virus by Alpiniae oxyphyllae fructus polysaccharide 3.

Porcine epidemic diarrhea virus (PEDV) is a deadly pathogen that still plagues suckling piglets. However, there is still no anti-PEDV drug available in clinics. To develop potential anti-PEDV drugs, the antiviral activity of Alpiniae oxyphyllae fructus polysaccharide 3 (AOFP3) against PEDV infection in IPEC-J2 cells were assessed in our present study. The structural characterization of AOFP3 was studied by using HPAEC, GC-MS, FT-IR and NMR techniques. At the same time, the anti-PEDV activity of AOFP3 was investigated by performing RT-qPCR, Western blot and immunofluorescence assays. The results showed that AOFP3 (44.4 kDa) was composed of glucose and galacturonic acid at a molar ratio of 77.54:22.46 and consisted of →4)-α-D-Glcp-(1→, →4,6)-α-D-Glcp-(1→, T-α-D-Glcp-(1→ and →4)-α-D-GalAp-(1→. AOFP3 significantly decreased PEDV titer in IPEC-J2 cells and prevented cellular damage of IPEC-J2 cells caused by PEDV infection. Furthermore, AOFP3 showed an antioxidative activity in inhibiting PEDV reproduction. Therefore, AOFP3 was expected to be a material of anti-PEDV drug.

Hydrogen Attenuates Myocardial Injury in Rats by Regulating Oxidative Stress and NLRP3 Inflammasome Mediated Pyroptosis.

Purpose: Hydrogen (H2) is an antioxidant with anti-inflammatory and apoptosis functions.This study aimed to estimate the effects of H2 on acute myocardial infarction (AMI) in rats and its association with the inhibition of oxidative stress and cardiomyocyte pyroptosis. Methods: Sixty-four rats were randomly divided into three groups (Sham, AMI, and H2). The left anterior descending coronary artery (LAD) of rats in the AMI and H2 groups was ligated, while rats in the Sham group were threaded without ligation. In addition, 2% H2 was administered by inhalation for 24 h after ligation in the H2 group. Transthoracic echocardiography was performed after H2 inhalation, followed by collection of the serum and cardiac tissue of all rats. Results: H2 inhalation ameliorated the cardiac dysfunction, infarct size and inflammatory cell infiltration caused by AMI. Meanwhile, H2 inhalation reduced the concentration of serum Troponin I (TnI), brain natriuretic peptide (BNP), reactive oxygen species (ROS), cardiac malondialdehyde (MDA), and 8-OHdG. In addition, H2 inhalation inhibited cardiac inflammation and pyroptosis relative proteins expression. Conclusion: H2 effectively promoted heart functions in AMI rats by regulating oxidative stress and pyroptosis.