Multi-cohort validation: A comprehensive exploration of prognostic marker in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common form of RCC. It is characterized by resistance to traditional radiotherapy and chemotherapy, as well as an unfavorable clinical prognosis. Although TYMP is implicated in the advancement of tumor progression, the role of TYMP in ccRCC is still not understood. Heightened TYMP expression was identified in ccRCC through database mining and confirmed in RCC cell lines. Indeed, TYMP knockdown impacted RCC cell proliferation, migration, and invasion in vitro. TYMP showed a positive correlation with clinicopathological parameters (histological grade, pathological stage). Moreover, patients with high TYMP expression were indicative of poor prognosis in TCGA-ccRCC and external cohorts. The results of single-cell analysis showed that the distribution of TYMP was predominantly observed in monocytes and macrophages. Furthermore, there is a significant association between TYMP and immune status. Methylation analysis further elucidated the relationship between TYMP expression and multiple methylation sites. Drug sensitivity analysis unveiled potential pharmaceutical options. Additionally, mutation analyses identified an association between TYMP and the ccRCC driver genes like BAP1 and ROS1. In summary, TYMP may serve as a reliable prognostic indicator for ccRCC.

A novel 10-gene ferroptosis-related prognostic signature in acute myeloid leukemia.

Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies and exhibits a high rate of relapse and unfavorable outcomes. Ferroptosis, a relatively recently described type of cell death, has been reported to be involved in cancer development. However, the prognostic value of ferroptosis-related genes (FRGs) in AML remains unclear. In this study, we found 54 differentially expressed ferroptosis-related genes (DEFRGs) between AML and normal marrow tissues. 18 of 54 DEFRGs were correlated with overall survival (OS) (P<0.05). Using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis, we selected 10 DEFRGs that were associated with OS to build a prognostic signature. Data from AML patients from the International Cancer Genome Consortium (ICGC) cohort as well as the First Affiliated Hospital of Wenzhou Medical University (FAHWMU) cohort were used for validation. Notably, the prognostic survival analyses of this signature passed with a significant margin, and the riskscore was identified as an independent prognostic marker using Cox regression analyses. Then we used a machine learning method (SHAP) to judge the importance of each feature in this 10-gene signature. Riskscore was shown to have the highest correlation with this 10-gene signature compared with each gene in this signature. Further studies showed that AML was significantly associated with immune cell infiltration. In addition, drug-sensitive analysis showed that 8 drugs may be beneficial for treatment of AML. Finally, the expressions of 10 genes in this signature were verified by real-time quantitative polymerase chain reaction. In conclusion, our study establishes a novel 10-gene prognostic risk signature based on ferroptosis-related genes for AML patients and FRGs may be novel therapeutic targets for AML.

Machine learning identifies exosome features related to hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most malignant tumors with a poor prognosis. There is still a lack of effective biomarkers to predict its prognosis. Exosomes participate in intercellular communication and play an important role in the development and progression of cancers. Methods: In this study, two machine learning methods (univariate feature selection and random forest (RF) algorithm) were used to select 13 exosome-related genes (ERGs) and construct an ERG signature. Based on the ERG signature score and ERG signature-related pathway score, a novel RF signature was generated. The expression of BSG and SFN, members of 13 ERGs, was examined using real-time quantitative polymerase chain reaction and immunohistochemistry. Finally, the effects of the inhibition of BSG and SFN on cell proliferation were examined using the cell counting kit-8 (CCK-8) assays. Results: The ERG signature had a good predictive performance, and the ERG score was determined as an independent predictor of HCC overall survival. Our RF signature showed an excellent prognostic ability with the area under the curve (AUC) of 0.845 at 1 year, 0.811 at 2 years, and 0.801 at 3 years in TCGA, which was better than the ERG signature. Notably, the RF signature had a good performance in the prediction of HCC prognosis in patients with the high exosome score and high NK score. Enhanced BSG and SFN levels were found in HCC tissues compared with adjacent normal tissues. The inhibition of BSG and SFN suppressed cell proliferation in Huh7 cells. Conclusion: The RF signature can accurately predict prognosis of HCC patients and has potential clinical value.

Retracted: Resistin-Like Molecule Beta (RELM-ß) Regulates Proliferation of Human Diabetic Nephropathy Mesangial Cells via Mitogen-Activated Protein Kinases (MAPK) Signaling Pathway.

This publication has been retracted by the Editor due to the identification of non-original figure images and manuscript content that raise concerns regarding the credibility and originality of the study and the manuscript. Reference: Yun-Qian Wang, Cong-Cong Fan, Bao-Ping Chen, Jun Shi. Resistin-Like Molecule Beta (RELM-ß) Regulates Proliferation of Human Diabetic Nephropathy Mesangial Cells via Mitogen-Activated Protein Kinases (MAPK) Signaling Pathway. Med Sci Monit 2017; 23:3897-3903. DOI: 10.12659/MSM.905381.

Evaluation of the Cholesterol-Lowering Mechanism of Enterococcus faecium Strain 132 and Lactobacillus paracasei Strain 201 in Hypercholesterolemia Rats.

Hypercholesterolemia can cause many diseases, but it can effectively regulated by Lactobacillus. This study aimed to evaluate the cholesterol-lowering mechanism of Enterococcus faecium strain 132 and Lactobacillusparacasei strain 201. These results showed that both the strains decreased serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), liver TC and TG and increased fecal TC, TG and total bile acid (TBA) levels. Additionally, both strains also reduced glutamic-pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST) and levels of tissue inflammation levels to improve the lipid profile, and they reduced fat accumulation partially by alleviating inflammatory responses. Furthermore, both strains regulated the expression of the CYP8B1, CYP7A1, SREBP-1, SCD1 and LDL-R gene to promote cholesterol metabolism and reduce TG accumulation. Interventions with both strains also altered the gut microbiota, and decreasing the abundance of Veillonellaceae, Erysipelotrichaceae and Prevotella. Furthermore, fecal acetic acid and propionic acid were increased by this intervention. Overall, the results suggested that E. faecium strain 132 and L. paracasei strain 201 can alleviate hypercholesterolemia in rats and might be applied as a new type of hypercholesterolemia agent in functional foods.

Probiotics supplementation improves hyperglycemia, hypercholesterolemia, and hypertension in type 2 diabetes mellitus: An update of meta-analysis.

Background: Although many studies have shown that consumption of probiotics is relevant to diabetes, the effects of probiotics improves clinical outcomes in type 2 diabetes have yielded conflicting results. The aim of this meta-analysis was conducted to assess the effects of probiotics supplementation on glycemic, blood lipids, pressure and inflammatory control in type 2 diabetes.Methods: PubMed, Web of science, Embase and the Cochrane Library databases were searched for relevant studies from February 2015 up to Janurary 2020, with no language restrictions. The pooled results were calculated with the use of a random-effects model to assess the impact of supplemental probiotics on glycemic, blood lipids, pressure and inflammatory control in type 2 diabetes. Additionally, subgroup analysis was conducted based on patients age, body mass index (BMI), country and duration of the probiotics supplement, respectively.Results: 13 studies were included in this meta-analysis, involving a total of 818 participants in 8 countries. Overall, compared with control groups, the subjects who received multiple species of probiotics had a statistically significant reduction in fasting blood sugar (FBS), homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), triglycerides (TG), systolic blood pressure (SBP), diastolic blood pressure (DBP) and tumor necrosis factor (TNF) -α [standardized mean difference (SMD): -0.89 mg/Dl, 95% CI: -1.66, -0.12 mg/dL; SMD: -0.43, 95% CI: -0.63, -0.23; SMD: -0.19 mg/dL, 95% CI: -0.36, -0.01 mg/dL; SMD: -0.23 mg/dL, 95% CI: -0.40, -0.05 mg/dL; SMD: -5.61 mmHg, 95% CI: -9.78, -1.45 mmHg; SMD: -3.41 mmHg, 95% CI: -6.12, -0.69 mmHg; and SMD: 6.92 pg/ml, 95% CI: 5.95, 7.89 pg/ml, respectively]. However, the subjects who received single-species of probiotic or probiotic with co-supplements in food only changed FBS, HOMA-IR, DBP and TG levels. Moreover, subgroup analyses revealed that the effects of probiotics supplementation on FBS, HMOA-IR, SBP and DBP are significantly influenced by patients age, body mass index (BMI), country and duration of the probiotics supplement.Conclusion: Our analysis revealed that glycemic, lipids, blood pressure and inflammation indicators are significantly improved by probiotic supplementation, particularly the subjects who ages ≤ 55, baseline BMI< 30 kg/m2, duration of intervention more than 8 weeks, and received multiple species probiotic.

Characterization and Genomic Analysis of Escherichia coli O157:H7 Bacteriophage FEC14, a New Member of Genus Kuttervirus.

Escherichia coli O157:H7 is an important foodborne pathogen that has become a major worldwide factor affecting the public safety of food. Bacteriophage has gradually attracted attention because of its ability to kill specific pathogens. In this study, a lytic phage of E. coli O157:H7, named FEC14, was isolated from hospital sewage. Transmission electron microscopy analysis showed that phage FEC14 had an isometric head 80 ± 5 nm in diameter and a contractile tail whose terminal spikes present an umbrella-like structure. Phage FEC14 revealed 158,639 bp double-stranded DNA, with the G+C content of 44.6%, 209 ORFs and four tRNAs. Genome DNA of FEC14 could not be digested by some endonucleases. Many of the features of phage FEC14 are very similar to those of the newly classified genus "Kuttervirus", including morphology, genome size and organization, etc. Phage FEC14 is proposed to be a new isolate of genus "Kuttervirus" within the family Ackermannviridae, moreover, the endonuclease resistance of phage FEC14, has priority over other genera of bacteriophages for its use in biocontrol of foodborne pathogens.

CD74 knockout protects against LPS-induced myocardial contractile dysfunction through AMPK-Skp2-SUV39H1-mediated demethylation of BCLB.

BACKGROUND AND PURPOSE: Lipopolysaccharides (LPS), an outer membrane component of Gram-negative bacteria, triggers myocardial anomalies in sepsis. Recent findings indicated a role for inflammatory cytokine MIF and its receptor, CD74, in septic organ injury, although little is known of the role of MIF-CD74 in septic cardiomyopathy. EXPERIMENTAL APPROACH: This study evaluated the impact of CD74 ablation on endotoxaemia-induced cardiac anomalies. Echocardiographic, cardiomyocyte contractile and intracellular Ca2+ properties were examined. KEY RESULTS: Our data revealed compromised cardiac function (lower fractional shortening, enlarged LV end systolic diameter, decreased peak shortening, maximal velocity of shortening/relengthening, prolonged duration of relengthening and intracellular Ca2+ mishandling) and ultrastructural derangement associated with inflammation, O2 - production, apoptosis, excess autophagy, phosphorylation of AMPK and JNK and dampened mTOR phosphorylation. These effects were attenuated or mitigated by CD74 knockout. LPS challenge also down-regulated Skp2, an F-box component of Skp1/Cullin/F-box protein-type ubiquitin ligase, while up-regulating that of SUV39H1 and H3K9 methylation of the Bcl2 protein BCLB. These effects were reversed by CD74 ablation. In vitro study revealed that LPS facilitated GFP-LC3B formation and cardiomyocyte defects. These effects were prevented by CD74 ablation. Interestingly, the AMPK activator AICAR, the autophagy inducer rapamycin and the demethylation inhibitor difenoconazole inhibited the effects of CD74 ablation against LPS-induced cardiac dysfunction, while the SUV39H1 inhibitor chaetocin or methylation inhibitor 5-AzaC ameliorated LPS-induced GFP-LC3B formation and cardiomyocyte contractile dysfunction. CONCLUSION AND IMPLICATIONS: Our data suggested that CD74 ablation protected against LPS-induced cardiac anomalies, O2 - production, inflammation and apoptosis through suppression of autophagy in a Skp2-SUV39H1-mediated mechanism.

Defects controlled hole doping and multivalley transport in SnSe single crystals.

SnSe is a promising thermoelectric material with record-breaking figure of merit. However, to date a comprehensive understanding of the electronic structure and most critically, the self-hole-doping mechanism in SnSe is still absent. Here we report the highly anisotropic electronic structure of SnSe investigated by angle-resolved photoemission spectroscopy, in which a unique pudding-mould-shaped valence band with quasi-linear energy dispersion is revealed. We prove that p-type doping in SnSe is extrinsically controlled by local phase segregation of SnSe2 microdomains via interfacial charge transferring. The multivalley nature of the pudding-mould band is manifested in quantum transport by crystallographic axis-dependent weak localisation and exotic non-saturating negative magnetoresistance. Strikingly, quantum oscillations also reveal 3D Fermi surface with unusual interlayer coupling strength in p-SnSe, in which individual monolayers are interwoven by peculiar point dislocation defects. Our results suggest that defect engineering may provide versatile routes in improving the thermoelectric performance of the SnSe family.

Resistin-Like Molecule Beta (RELM-ß) Regulates Proliferation of Human Diabetic Nephropathy Mesangial Cells via Mitogen-Activated Protein Kinases (MAPK) Signaling Pathway.

BACKGROUND Resistin-like molecule beta (RELM-ß) has been reported to be associated with diabetic nephropathy (DN). However, the role of RELM-ß in DN is poorly understood. This study was conducted to delineate the underlying mechanisms of action and to investigate the role of RELM-ß in the primitive development of DN via MAPK signaling pathways. MATERIAL AND METHODS Lentivirus-mediated vectors and RNAi technology were used to establish the model of RELM-ß up-regulated and down-regulated expression in human mesangial cells (HMCs). The proliferation of HMCs was detected through CCK-8 method. The cell cycle and cell proliferation of HMCs was detected through flow cytometry. The MAPKs pathway protein activity was detected through Western blotting. RESULTS The HMCs with up-regulated and down-regulated expression of RELM-ß increased or decreased significantly at 2-3 days. The HMCs with high glucose intervention reversed the proliferation inhibition. The HMCs with exogenous glucose or RELM-ß protein intervention partially reversed the cell cycle inhibition. Among the MAPKs pathway, the phosphorylation activity of p38MAPK and JNK increased or decreased and ERK1/2 did not change in the overexpression or inhibition of RELM-ß. The p38 MAPK pathway inhibitor SB202190 significantly inhibited the proliferation of HMCs caused by overexpression of RELM-ß. Up-regulated expression of RELM-b induced the phosphorylation of p38 MAPK, JNK in HMCs and promoted HMCs proliferation and participated in early DN through the MAPKs pathway. CONCLUSIONS The results provide evidence that RELM-b is a potential molecular target for the treatment of DN.

An anionic zeolite-like metal-organic framework (AZMOF) with a Moravia network for organic dye absorption through cation-exchange.

An anionic zeolite-like metal-organic framework (AZMOF) with a twisted partially augmented the net, known as the "Moravia" net, [(CH3)2NH2]6[Sr13(O)3()8(OH)2(H2O)16]·xS (, where S represents non-coordinated solvent molecules, and is the abbreviation of benzo-(1,2;3,4;5,6)-tris-(thiophene-2'-carboxylic acid)), has been solvothermally synthesized and characterized, which possesses an anionic framework and nano-sized sodalite cage. Through cation-exchange, is capable of uptaking large organic cationic dyes including Rhodamine B (RB), Basic Red 2 (BR2), Crystal Violet (CV) and Methylene Blue (MB), amongst which the adsorption capability for RB (up to 545 mg g(-1)), and BR2 (up to 675 mg g(-1)) is the highest for reported absorbants to date.