MAP4K family kinases act in parallel to MST1/2 to activate LATS1/2 in the Hippo pathway.

The Hippo pathway plays a central role in tissue homoeostasis, and its dysregulation contributes to tumorigenesis. Core components of the Hippo pathway include a kinase cascade of MST1/2 and LATS1/2 and the transcription co-activators YAP/TAZ. In response to stimulation, LATS1/2 phosphorylate and inhibit YAP/TAZ, the main effectors of the Hippo pathway. Accumulating evidence suggests that MST1/2 are not required for the regulation of YAP/TAZ. Here we show that deletion of LATS1/2 but not MST1/2 abolishes YAP/TAZ phosphorylation. We have identified MAP4K family members--Drosophila Happyhour homologues MAP4K1/2/3 and Misshapen homologues MAP4K4/6/7-as direct LATS1/2-activating kinases. Combined deletion of MAP4Ks and MST1/2, but neither alone, suppresses phosphorylation of LATS1/2 and YAP/TAZ in response to a wide range of signals. Our results demonstrate that MAP4Ks act in parallel to and are partially redundant with MST1/2 in the regulation of LATS1/2 and YAP/TAZ, and establish MAP4Ks as components of the expanded Hippo pathway

Retroperitoneoscopic laparo-endoscopic single-site radical nephrectomy (RLESS-RN): initial experience with a homemade port

We successfully performed 6 LESS radical nephrectomy via the retroperitoneal approach (RLESS) using the Alexis wound retractor as a single access with conventional laparoscopic instruments. The results demonstrated that our RLESS technique of radical nephrectomy is a safe and feasible procedure for management of localized renal cancer

REG3A overexpression functions as a negative predictive and prognostic biomarker in rectal cancer patients receiving CCRT

Background. Concurrent chemoradiotherapy (CCRT) is suggested before resection surgery in the control of rectal cancer. Unfortunately, treatment outcomes are widely variable and highly patientspecific. Notably, rectal cancer patients with distant metastasis generally have a much lower survival rate. Accordingly, a better understanding of the genetic background of patient cohorts can aid in predicting CCRT efficacy and clinical outcomes for rectal cancer before distant metastasis. Methods. A published transcriptome dataset (GSE35452) (n=46) was utilized to distinguish prospective genes concerning the response to CCRT. We recruited 172 rectal cancer patients, and the samples were collected during surgical resection after CCRT. Immunohistochemical (IHC) staining was performed to evaluate the expression level of regenerating family member 3 alpha (REG3A). Pearson's chi-squared test appraised the relevance of REG3A protein expression to clinicopathological parameters. The Kaplan-Meier method was utilized to generate survival curves, and the log-rank test was performed to compare the survival distributions between two given groups. Results. Employing a transcriptome dataset (GSE35452) and focusing on the inflammatory response (GO: 0006954), we recognized that REG3A is the most significantly upregulated gene among CCRT nonresponders (log2 ratio=1.2472, p=0.0079). Following IHC validation, high immunoexpression of REG3A was considerably linked to advanced post-CCRT tumor status (p<0.001), post-CCRT lymph node metastasis (p=0.042), vascular invasion (p=0.028), and low-grade tumor regression (p=0.009). In the multivariate analysis, high immunoexpression of REG3A was independently correlated with poor disease-specific survival (DSS) (p=0.004) and metastasis-free survival (MeFS) (p=0.045). The results of the bioinformatic analysis also supported the idea that REG3A overexpression is implicated in rectal carcinogenesis. Conclusion. In the current study, we demonstrated that REG3A overexpression is correlated with poor CCRT effectiveness and inferior patient survival in rectal cancer. The predictive and prognostic utility of REG3A expression may direct patient stratification and decisionmaking more accurately for those patients

Research on the Separation and Reorganization of Wheat Protein and the Quality of Wheat Noodles

This study uses Polyacrylamide gel electrophoresis (SDS-PAGE) and acid polyacrylamide gel electrophoresis (A-PAGE) to identify the composition of high molecular weight glutenin subunits (HMW-GS)and the translocation of gliadin 1BL/1RS in two high quality wheat flour. The gliadin and glutenin are separated and extracted from wheat flour by separating and recombining, then re-proportionated with proportions. The cooking quality and texture of reconstituted noodles are analyzed to identify the relationship between gliadin, glutenin and noodle’s quality. The results show that when the protein content is constant, the water absorption of recombinant noodles is negatively correlated with (gluten: alcohol) (P＜0.05), while the dry matter loss rate is not highly relevant to gluten: alcohol. The hardness, firmness and tensile strength of recombinant noodles are positively correlated with gluten: alcohol (P＜0.05). The viscosity is negatively correlated with gluten: alcohol (P＜0.05). Meanwhile, it is found that when the properties of high molecular weight glutenin and gliadin are the same, only the composition of low molecular weight glutenin is different from the precipitation value, but the properties of reconstituted noodles are similar. Therefore, we conclude that high molecular weight glutenin has a greater impact on the quality of noodles

The evaluation of JAK inhibitors on effect and safety in alopecia areata: a systematic review and meta-analysis of 2018 patients

BackgroundJAK inhibitors treat various autoimmune diseases, but an updated systematic review in treating alopecia areata is currently lacking.ObjectiveEvaluate the specific efficacy and safety of JAK inhibitors in alopecia areata by systematic review and meta-analysis.MethodsEligible studies in PubMed, Embase, Web of Science, and Clinical Trials up to May 30, 2022, were searched. We enrolled in randomized controlled trials and observational studies of applying JAK inhibitors in alopecia areata.Results6 randomized controlled trials with 1455 patients exhibited SALT50 (odd ratio [OR], 5.08; 95% confidence interval [CI], 3.49-7.38), SALT90 (OR, 7.40; 95% CI, 4.34-12.67) and change in SALT score (weighted mean difference [WSD], 5.55; 95% CI, 2.60-8.50) compared to the placebo. The proportion of 26 observational studies with 563 patients of SALT5 was 0.71(95% CI, 0.65-0.78), SALT50 was 0.54(95% CI 0.46-0.63), SALT90 was 0.33(95% CI, 0.24-0.42), and SALT score (WSD, -2.18; 95% CI, -3.12 to -1.23) compared with baseline. Any adverse effects occurred in 921 of 1508 patients; a total of 30 patients discontinued the trial owing to adverse reactions.LimitationsFew randomized controlled trials met the inclusion criteria and insufficiency of eligible data.ConclusionJAK inhibitors are effective in alopecia areata, although associated with an increased risk