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Objective: The intestine is responsible for approximately one‐third of uric acid (UA) excretion. The effect of commensal Enterococcus faecalis (E. faecalis), one of the most colonized bacteria in the gut, on UA excretion in the intestine remains to be investigated. The aim of this study was to evaluate the effect of commensal E. faecalis on UA metabolism and gut microbiota. Methods: The 16S rRNA gene sequencing was used to examine the species of Enterococcus in mouse fecal content. E. faecalis strain was isolated from mouse feces and identified to be E. faecalis W5. The hyperuricemia (HUA) animal model was established with yeast‐rich forage and 250 mg·kg−1·day−1 potassium oxonate. Oral administration of E. faecalis W5 was given for 20 days, serving as the Efa group. Results: Disrupted intestinal barrier, activated proinflammatory response and low UA excretion in the intestine were found in HUA mice. After E. faecalis W5 treatment, the gut barrier was restored and serum UA level was decreased. Additionally, fecal and intestinal UA levels were elevated, intestinal urate transporter ABCG2 and purine metabolism were upregulated. Moreover, short‐chain fatty acid levels were increased, and intestinal inflammation was ameliorated. Conclusions: Commensal E. faecalis W5 ameliorated HUA through reversing the impaired gut barrier, promoting intestinal UA secretion by regulating ABCG2 expression, and decreasing intestinal UA synthesis by regulating purine metabolism. The results may provide the potential for developing treatments for HUA through the intestine. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is identified as a primary cause of death around the world. The current chemotherapies are not cost‐effective. Therefore, finding novel potential therapeutic target is urgent. Titin (TTN) is a muscle protein that is critical in hypertrophic cardiomyopathy. However, its role in CRC is not well understood. The study focused on exploring the possible role of TTN in CRC carcinogenesis. TTN mRNA and protein expression levels presented an obvious downregulation in CRC tissue samples, relative to normal control (p < 0.05). TTN expression significantly correlated with the clinical stage (normal vs. Stage 1, p < 0.05; normal vs. Stage 4, p < 0.05), node metastasis (normal vs. N1, p < 0.05; N1 vs. N2, p < 0.05), histological type (normal vs. adenocarcinoma, p < 0.05), race (Caucasian vs. Asian, p < 0.05; African‐American vs. Asian, p < 0.05) and TP53 mutation (normal vs. TP53 mutation, p < 0.05), considering The Cancer Genome Atlas database. However, for patients who had higher TTN expression, the overall survival was remarkably shorter than patients who had low TTN expression. Furthermore, TTN was lowly expressed in four CRC cell lines. TTN overexpression facilitated CRC cells in terms of the proliferation, metastasis and invasion. Based on gene set enrichment analysis, the ERB pathway might be responsible for TTN‐related CRC. Besides, TTN was involved in the response to azacitidine. Overall, TTN might serve as a potential novel therapeutic target for treating and overcoming chemotherapy resistance in CRC. [ABSTRACT FROM AUTHOR]

Objective: To assess the clinical efficacy of fucoidan‐assisted standard quadruple therapy (SQT) in Helicobacter pylori (H. pylori) eradication and the improvement of gut microbiota. Methods: An open‐label randomized controlled trial was conducted at the Affiliated Hospital of Qingdao University in Shandong Province, China. Ninety patients who tested positive for H. pylori were randomized to the standard quadruple therapy (SQT) group (SQ), SQT + fucoidan combination group (SF), and fucoidan + sequential SQT group (FS), respectively. Stool samples were collected for gut microbiota composition at baseline and after treatment. Results: After H. pylori eradication, the relative abundances of most conditional pathogens in the SQ decreased, while those of several beneficial bacteria increased or decreased (P < 0.05). In FS, the abundances of most beneficial bacteria increased gradually from baseline to week 12, while those of the conditional pathogens decreased (P < 0.05). The abundance of Bifidobacterium had a decreasing trend in SQ, but remained unchanged in SF and increased in FS (P < 0.05). The abundances of most beneficial bacteria were significantly higher in FS than in SQ and SF (P < 0.05). Addition of fucoidan enhanced symptom improvement during H. pylori eradication compared with SQT alone. Conclusions: Fucoidan considerably improved gut dysbiosis during SQT for H. pylori eradication. Gut microbiota can be maintained by the addition of fucoidan before eradication therapy with SQT rather than by concomitant addition with therapy. Fucoidan‐assisted SQT could relieve gastrointestinal symptoms during H. pylori eradication. [ABSTRACT FROM AUTHOR]

According to the Japanese Gastric Cancer Treatment Guidelines 2018 (5th edition) for GCP, if the depth of invasion of the lesion is diagnosed as T1a and the diameter of the lesion is <=2 cm or <=3 cm, EMR or ESD is sufficient for complete resection.25 When it is accompanied by malignant lesions, surgical resection should be performed. All the 13 lesions were diagnosed as GCP based on pathologic evidence, seven lesions were simple GCP (Figure 3A), one coexisted with lipoma, and one coexisted with hyperplastic polyps. Gastritis cystica profunda (GCP) is a rare gastric lesion with atypical clinical symptoms and signs. [Extracted from the article]

Liquid‐like thermoelectric (TE) materials have the advantages of ultrahigh performance, low cost, and environment friendly, but their stability is greatly limited by the possible Cu/Ag deposition under a large current and/or temperature gradient. The pratical application based on liquid‐like TE materials requires both a high TE figure of merit (zT) for high energy conversion efficiency and large critical voltage for good stability, but they are very difficult to be simultaneously achieved in one material. In this work, both the zT and critical voltage are simultaneously optimized in Cu2Se via tailoring chemical compositions at multiple atomic positions, i.e., introducing Cu deficiency at the Cu‐sites to lower Cu ion chemical potential and alloying sulfur at the Se‐sites to reduce carrier concentrations. A maximum zT of 2.0 at 1000 K has been successfully achieved for Cu1.96Se0.8S0.2, about a 30% improvement over that for Cu2Se. More importantly, Cu1.96Se0.8S0.2 demonstrates a much higher critical voltage than Cu2Se, yielding a greatly enhanced service stability under the conditions with/without a temperature gradient. An Ni/Mo/Cu1.96Se0.8S0.2 TE unileg is successfully fabricated with a stable power output even after 400 thermal cycles between 473 and 873 K. This study greatly accelerates the real application of Cu2Se‐based liquid‐like materials. [ABSTRACT FROM AUTHOR]

Celastrol could inhibit cancer cell growth in vitro. However, effect(s) of celastrol on gastric cancer is not well studied. Therefore, we investigated the effects of celastrol on human gastric cancer cell line MKN45 and the underlying mechanisms. We found that celastrol inhibited cell proliferation, migration, and invasion and induced cell apoptosis and G2/M cell cycle arrest (p < .05, p < .01, or p < .001). Under celastrol treatment, overexpression of microRNA-21 (miR-21) increased cell viability, migration, and invasion and inhibited cell apoptosis compared with negative control (p < .05, p < .01, or p < .001). In addition, the phosphorylation of PTEN was significantly up-regulated, whereas PI3K, AKT, p65, and IκBα phosphorylation was statistically decreased by celastrol (p < .05 or p < .01) and then further reversed by miR-21 overexpression (p < .05 or p < .01). On the other side, miR-21 silence showed contrary results (p < .05) as relative to miR-21 overexpression. In conclusion, celastrol inhibits proliferation, migration, and invasion and inactivates PTEN/PI3K/AKT and nuclear factor κB signaling pathways in MKN45 cells by down-regulating miR-21. [ABSTRACT FROM AUTHOR]

Liquid‐like materials are one family of promising thermoelectric materials discovered in the past years due to their advantanges of ultrahigh thermoelectric figure of merit (zT), low cost, and environmental friendliness. However, their practial applications are greatly limited by the low service stability from the Cu/Ag metal deposition under large current and/or temperature gradient. Both high zT for high efficiency and large critical voltage for good stability are required for liquid‐like materials, but they are usually strongly correlated and hard to be tuned individually. Herein, based on the thermodynamic analysis, it is shown that such a correlation can be decoupled through doping immobile ions into the liquid‐like sublattice. Taking Cu2−δS as an example, doping immobile Fe ions in Cu1.90S scarcely degrades the initial large critical voltage, but significantly enhances the zT to 1.5 at 1000 K by tuning the carrier concentration to the optimal range. Combining the low‐cost and environmentally friendly features, these Fe‐doped Cu2−δS‐based compounds show great potential in civil applications. This study sheds light on the realization of both good stability and high performance for many other liquid‐like thermoelectric materials that have not been considered for real applications before. [ABSTRACT FROM AUTHOR]

Prognostic indicators in lung adenocarcinoma (LUAD) have been seeking under database analysis, and remarkable advance is on the way.This study calculated the scores of stromal and immune components of the tumor microenvironment (TME) in 551 LUAD samples using the ESTIMATE algorithm on The Cancer Genome Atlas (TCGA) database. R package ''limma'' was used to selected differentially expressed genes (DEG). We have analyzed the DEGs by means of Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichments. The protein‐protein network, univariate Cox analysis, and Lasso regression analysis were performed to selected survival‐related genes. Gene Set Enrichment Analysis (GSEA) represented the enriched pathway of CC chemokine receptor 2 (CCR2). The ratios of immune cells in the TME of each LUAD sample were obtained using the R package "limma" and CIBERSORT algorithm in R 4.0.2.The ImmuneScore was positively correlated with prognosis regarding survival rate, T classification of TNM stages, and clinicopathological staging characteristics. GO and KEGG enrichments showed DEGs were associated with immune‐related activities. Three genes of LUAD were selected from the PPI network and Cox proportional hazards regression analysis. CCR2 was the most survival correlated gene by Lasso regression analysis. GSEA results showed that C2 kegg gene sets in the CCR2 high‐expression group were mainly enriched in the B cell or T cell receptor signaling pathway and natural killer cell‐mediated cytotoxicity. Correlation of CCR2 expression with prognosis was conducted, implicating a positive correlation with the prognosis of survival rate and M classification, negative correlation with the prognosis of T and N classifications. The correlation between CCR2 and tumor‐infiltrating immune cells (TICs) was analyzed, and 14 kinds of TICs were found closely correlated with CCR2 expression through difference analysis.Therefore, CCR2 has prognostic value as an immune indicator in LUAD. [ABSTRACT FROM AUTHOR]