MFN2 suppresses the accumulation of lipid droplets and the progression of clear cell renal cell carcinoma.

Dissolving the lipid droplets in tissue section with alcohol during a hematoxylin and eosin (H&E) stain causes the tumor cells to appear like clear soap bubbles under a microscope, which is a key pathological feature of clear cell renal cell carcinoma (ccRCC). Mitochondrial dynamics have been reported to be closely associated with lipid metabolism and tumor development. However, the relationship between mitochondrial dynamics and lipid metabolism reprogramming in ccRCC remains to be further explored. We conducted bioinformatics analysis to identify key genes regulating mitochondrial dynamics differentially expressed between tumor and normal tissues and immunohistochemistry and Western blot to confirm. After the target was identified, we created stable ccRCC cell lines to test the impact of the target gene on mitochondrial morphology, tumorigenesis in culture cells and xenograft models, and profiles of lipid metabolism. It was found that mitofusin 2 (MFN2) was downregulated in ccRCC tissues and associated with poor prognosis in patients with ccRCC. MFN2 suppressed mitochondrial fragmentation, proliferation, migration, and invasion of ccRCC cells and growth of xenograft tumors. Furthermore, MFN2 impacted lipid metabolism and reduced the accumulation of lipid droplets in ccRCC cells. MFN2 suppressed disease progression and improved prognosis for patients with ccRCC possibly by interrupting cellular lipid metabolism and reducing accumulation of lipid droplets.

Elucidating carbon conversion and bacterial succession by amending Fenon-like systems during co-composting of pig manure and branch.

The essential point of current study was to investigate the effect of a Fenton-like system established by oxalic acid and Fe(II) on gas emission, organic matter decomposition and humification during composting. Branches were pretreated with Fenton reagents (0.02 M FeCl2·4H2O + 1.5 M H2O2) and then adding 10 % oxalic acid (OA). The treatments were marked as B1 (control), B2 (Fenton reagent), B3 (10% OA) and B4 (Fenton-like reagent). The results collected from 80 d of composting showed that adding Fenton-like reagent benefited the degradation of organic substances, as reflected by the total organic carbon and dissolved organic carbon, and the maximum decomposition rate was observed in B4. In addition, the Fenton-like reagent could improve the synthesis of humus characterized by complex and stable compounds, which was consistent with the spectral parameters (SUVA254, SUVA280, E253/E203 and Fourier transform-infrared indicators) of DOC. Furthermore, the functional microbial succession performance and linear discriminant effect size analyses provided microbial evidence of humification improvement. Notably, compared with the control, the minimum value of CH4 cumulation was reported in B4, which decreased by 30.44 %. Concluded together, the addition of a Fenton-like reagent composed by OA and Fe(II) is a practical way to improve the humification. Furthermore, the mechanisms related to the promotion of humification should be investigated from free radicals, functional genes, and metabolic pathways.

DMSO/SOCl2-Enabled Synthesis of 3-Chloroindoles via Desulfonylative Chlorocyclization of N,N-Disubstituted 2-Alkynylanilines.

The application of the DMSO/SOCl2 system enabled the intramolecular cyclization/chlorination of N,N-disubstituted 2-alkynylanilines, leading to the synthesis of a series of 3-chloroindoles with moderate to good yields. Differing from the previously reported interrupted Pummerer reaction featuring the introduction of SMe moiety, the current approach adopted an alternative pathway that realized the incorporation of chlorine atom to the indole skeleton via a desulfonylative chlorocyclization process.

Humification and fungal community succession during pig manure composting: Membrane covering and mature compost addition.

The objective of this study was to elucidate the combined effect of a semi-permeable membrane (M) and mature compost (MC) on humification and fungal community succession in pig manure composting. Compared with the control, the concentrations of humic substances (HSs) increased by 44.54 % (M + 15 % MC) and 43.90 % (M). During the thermophilic phase, Aspergillus (67.26 %) was the dominant genus in the M + 15 % MC treatment. Membrane covering increased the relative abundance (RA) of other phyla (except for Ascomycetes and Basidiomycetes) on the 14th day and Basidiomycetes on the 80th day in M treatment. Humic acid, HSs were positively correlated with the RA of genera Myceliophthora, Kernia, and Mycothermus. Myceliophthora was the key genus in the M + 15 % MC treatment on the 80th day. The results showed that 15 % MC addition under membrane covering optimizes the quality of composting products.

Exploring gaseous emissions and pivotal enzymatic activity during co-composting of branch and pig manure: The effect of particle size of bulking agents.

The purpose of current study was to probe the effect of various length of branch on gaseous emissions and vital enzymatic activity. Four lengths (< 2 cm, 2 cm, 5 cm, and > 5 cm) of clipped branch were mingled with collected pig manure for 100 days aerobic fermentation. The consequence demonstrated that the amendment of 2 cm of branch showed conducive to decline the greenhouse gas emissions, which the CH4 emissions decreased by 1.62-40.10%, and the N2O emissions decreased by 21.91-34.04% contrasted with other treatments. Furthermore, the peak degree of enzymatic activities was also observed in 2 cm of branch treatment by the optimizing living condition for microbes. In view of microbiological indicators, the most abundant and complex bacterial community could be monitor in 2 cm of branch composting pile, which verified the microbial facilitation. Summing up, the strategy of 2 cm branch amendment would be recommended.

Combination of ultrafast dynamic contrast-enhanced MRI-based radiomics and artificial neural network in assessing BI-RADS 4 breast lesions: Potential to avoid unnecessary biopsies.

Objectives: To investigate whether combining radiomics extracted from ultrafast dynamic contrast-enhanced MRI (DCE-MRI) with an artificial neural network enables differentiation of MR BI-RADS 4 breast lesions and thereby avoids false-positive biopsies. Methods: This retrospective study consecutively included patients with MR BI-RADS 4 lesions. The ultrafast imaging was performed using Differential sub-sampling with cartesian ordering (DISCO) technique and the tenth and fifteenth postcontrast DISCO images (DISCO-10 and DISCO-15) were selected for further analysis. An experienced radiologist used freely available software (FAE) to perform radiomics extraction. After principal component analysis (PCA), a multilayer perceptron artificial neural network (ANN) to distinguish between malignant and benign lesions was developed and tested using a random allocation approach. ROC analysis was performed to evaluate the diagnostic performance. Results: 173 patients (mean age 43.1 years, range 18-69 years) with 182 lesions (95 benign, 87 malignant) were included. Three types of independent principal components were obtained from the radiomics based on DISCO-10, DISCO-15, and their combination, respectively. In the testing dataset, ANN models showed excellent diagnostic performance with AUC values of 0.915-0.956. Applying the high-sensitivity cutoffs identified in the training dataset demonstrated the potential to reduce the number of unnecessary biopsies by 63.33%-83.33% at the price of one false-negative diagnosis within the testing dataset. Conclusions: The ultrafast DCE-MRI radiomics-based machine learning model could classify MR BI-RADS category 4 lesions into benign or malignant, highlighting its potential for future application as a new tool for clinical diagnosis.

Effect of prior cancer history on survival of patients with esophageal carcinoma: a propensity score matching, population-based study.

Background: When conducting esophageal cancer clinical trials, prior cancer history is frequently considered an exclusion criterion due to the assumption that prior malignancy may exert significant interference with the prognosis in patients with esophageal carcinoma. This study aimed to evaluate the impact of prior cancer on survival of patients with esophageal cancer and provide valuable assistance for trial design. Methods: Data regarding patients diagnosed with esophageal cancer between 2011 and 2016 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and divided into two groups depending on the presence or absence of prior cancer history. Propensity score matching (PSM) was performed to minimize the confounding bias caused by covariates. Subsequently, Kaplan-Meier analysis and multivariate Cox proportional hazards models were used to compare all-cause and esophageal cancer-specific survival between patients with and without prior cancer. Results: Among 17,123 patients with esophageal carcinoma included in this study, 2,224 (13%) patients had prior cancer history. Before PSM, Kaplan-Meier curves between the two groups classified by prior cancer history showed no significant differences in all-cause (HR =1.047, 95% CI: 0.995-1.102, P=0.077) and esophageal cancer-specific survival (HR =0.986, 95% CI: 0.928-1.048, P=0.65). Similar results were obtained after PSM. In multivariate Cox analysis, prior malignancy was not significantly associated with all-cause (HR =1.002, 95% CI: 0.936-1.072, P=0.965) and esophageal cancer-specific survival (HR =0.964, 95% CI: 0.890-1.045, P=0.374). Subgroup analysis stratified by timing of prior cancer demonstrated that prior cancer had no significant effect on prognosis in the recent latency period subgroups (P>0.05). Furthermore, patients with a prior cancer of lung and bronchus (P=0.013) or head and neck (P=0.012) displayed significantly worse survival than patients without prior cancer, while other types of prior cancer showed no significant effect. Conclusions: The findings suggest that prior cancer is likely not a definite factor that has an impact on all-cause and esophageal cancer-specific survival. Therefore, exclusion criteria of prior cancer history in esophageal cancer clinical trials should be seriously reconsidered.

Inhibitory effect of tumor necrosis factor-α on the basolateral Kir4.1/Kir5.1 channels in the thick ascending limb during diabetes.

Diabetic nephropathy is a major contributor to the morbidity and mortality of patients with diabetes. TNF-α expression is elevated during diabetes and is implicated in the pathogenesis of diabetic nephropathy; however, its underlying molecular mechanisms remain unclear. The present study aimed to investigate the effect and molecular mechanism of TNF-α on the basolateral inwardly rectifying potassium (Kir)4.1/Kir5.1 channels in the thick ascending limb (TAL) of rat kidneys using western blotting and the patch clamp technique to provide a theoretical basis for the cause of the decrease in kidney concentrating capacity during diabetes. The results demonstrated that urinary TNF-α excretion and protein TNF-α expression in the TAL increased and basolateral Kir4.1/Kir5.1 channel activity decreased during diabetes; however, diabetic rats exhibited amelioration of Kir4.1/Kir5.1 activity with a soluble TNF-α antagonist, TNF receptor fusion protein (TNFR:Fc). These results suggested that TNF-α inhibited the activity of the basolateral Kir4.1/Kir5.1 channel in the TAL of rat kidneys during diabetes. In addition, the protein expression levels of phospholipase A2 (PLA2) and cyclooxygenase-2 (COX2) increased in diabetic rats, the effects of which deceased following treatment with TNFR:Fc compared with the diabetic group. Furthermore, an agonist of PLA2 (melittin) and COX2 production [prostaglandin E2 (PGE2)] inhibited the basolateral Kir4.1/Kir5.1 channels. Taken together, the results of the present study suggested that the inhibitory effect of TNF-α on the basolateral Kir4.1/Kir5.1 channels in the TAL during diabetes is mediated by the PLA2/COX2/PGE2 signaling pathway.

B7 score and T cell infiltration stratify immune status in prostate cancer.

BACKGROUND: Although immune checkpoint inhibitors (ICIs), especially programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) axis blockers, exhibit prominent antitumor effects against numerous malignancies, their benefit for patients with prostate cancer (PCa) has been somewhat marginal. This study aimed to assess the feasibility of B7-H3 or HHLA2 as alternative immunotherapeutic targets in PCa. METHODS: Immunohistochemistry was performed to evaluate the expression pattern of PD-L1, B7-H3 and HHLA2 and the infiltration of CD8+ and Foxp3+ lymphocytes in 239 PCa tissues from two independent cohorts. The correlations between B7-H3 and HHLA2 and clinicopathological features, including the presence of CD8+ and Foxp3+ tumor-infiltrating lymphocytes (TILs), were explored. RESULTS: HHLA2 expression was much higher than PD-L1 expression but lower than B7-H3 expression in PCa tissues. High expression of both B7-H3 and HHLA2 was significantly associated with higher Gleason score and tumor stage, lymph node metastasis and dismal overall survival (OS) and cancer-specific survival (CSS). Moreover, a high B7 score, defined as high B7-H3 expression and/or high HHLA2 expression, was an independent prognostic predictor for PCa. Of note, a high B7 score was negatively correlated with CD8+ TILs. Importantly, a new immune classification, based on the B7 score and CD8+ TILs, successfully stratified OS and CSS in PCa. CONCLUSIONS: Both B7-H3 and HHLA2 have a critical impact on the immunosuppressive microenvironment, and the B7 score could be used as an independent prognostic factor for PCa. The B7 score combined with CD8+ TILs could be used as a new immune classification to stratify the risk of death, especially cancer-related death, for patients with PCa. These findings may provide insights that could improve response to immune-related comprehensive therapy for PCa in the future.