Nutritional Risk Index as a Prognostic Factor Predicts the Clinical Outcomes in Patients With Stage III Gastric Cancer.

Objective: This study is aimed to determine the potential prognostic significance of nutritional risk index (NRI) in patients with stage III gastric cancer. Methods: A total of 202 patients with stage III gastric cancer were enrolled in this study. NRI was an index based on ideal body weight, present body weight, and serum albumin levels. All patients were divided into two groups by receiver operating characteristic curve: low NRI group (NRI<99) and high NRI group (NRI≥99). The relationship between NRI and clinicopathologic characteristics was evaluated by Chi-square test. The clinical survival outcome was analyzed by Kaplan-Meier method and compared using log-rank test. The univariate and multivariate analyses were used to detect the potential prognostic factors. A nomogram for individualized assessment of disease-free survival (DFS) and overall survival (OS). The calibration curve was used to evaluate the performance of the nomogram for predicted and the actual probability of survival time. The decision curve analysis was performed to assess the clinical utility of the nomogram by quantifying the net benefits at different threshold probabilities. Results: The results indicated that NRI had prognostic significance by optimal cutoff value of 99. With regard to clinicopathologic characteristics, NRI showed significant relationship with age, weight, body mass index, total protein, albumin, albumin/globulin, prealbumin, glucose, white blood cell, neutrophils, lymphocyte, hemoglobin, red blood cell, hematocrit, total lymph nodes, and human epidermal growth factor receptor 2 (P<0.05). Through the univariate and multivariate analyses, NRI, total lymph nodes, and tumor size were identified as the independent factor to predict the DFS and OS. The nomogram was used to predict the 1-, 3-, and 5-year survival probabilities, and the calibration curve showed that the prediction line matched the reference line well for 1-, 3-, and 5-year DFS and OS. Furthermore, the decision curve analysis also showed that the nomogram model yielded the best net benefit across the range of threshold probability for 1-, 3-, 5-year DFS and OS. Conclusions: NRI is described as the potential prognostic factor for patients with stage III gastric cancer and is used to predict the survival and prognosis.

Correction: Mori et al. Involvement of DPY19L3 in Myogenic Differentiation of C2C12 Myoblasts. Molecules 2021, 26, 5685.

In the original article [...].

Involvement of DPY19L3 in Myogenic Differentiation of C2C12 Myoblasts.

DPY19L3 has been identified as a C-mannosyltransferase for thrombospondin type-1 repeat domain-containing proteins. In this study, we focused on the role of DPY19L3 in the myogenic differentiation of C2C12 mouse myoblast cells. We carried out DPY19L3 gene depletion using the CRISPR/Cas9 system. The result showed that these DPY19L3-knockout cells could not be induced for differentiation. Moreover, the phosphorylation levels of MEK/ERK and p70S6K were suppressed in the DPY19L3-knockout cells compared with that of parent cells, suggesting that the protein(s) that is(are) DPY19L3-mediated C-mannosylated and regulate(s) MEK/ERK or p70S6K signaling is(are) required for the differentiation.

Requirement for C-mannosylation to be secreted and activated a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4).

BACKGROUND: C-mannosylation is a unique type of glycosylation. A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) is a multidomain extracellular metalloproteinase that contains several potential C-mannosylation sites. Although some ADAMTS family proteins have been reported to be C-mannosylated proteins, whether C-mannosylation affects the activation and protease activity of these proteins is unclear. METHODS: We established wild-type and mutant ADAMTS4-overexpressing HT1080 cell lines. Recombinant ADAMTS4 was purified from the conditioned medium of the wild-type ADAMTS4-overexpressing cells, and the C-mannosylation sites of ADAMTS4 were identified by LC-MS/MS. The processing, secretion, and intracellular localization of ADAMTS4 were examined by immunoblot and immunofluorescence analyses. ADAMTS4 enzymatic activity was evaluated by assessing the cleavage of recombinant aggrecan. RESULTS: We identified that ADAMTS4 is C-mannosylated at Trp404 in the metalloprotease domain and at Trp523, Trp526, and Trp529 in the thrombospondin type 1 repeat (TSR). The replacement of Trp404 with Phe affected ADAMTS4 processing, without affecting secretion and intracellular localization. In contrast, the substitution of Trp523, Trp526, and Trp529 with Phe residues suppressed ADAMTS4 secretion, processing, intracellular trafficking, and enzymatic activity. CONCLUSIONS: Our results demonstrated that the C-mannosylation of ADAMTS4 plays important roles in protein processing, intracellular trafficking, secretion, and enzymatic activity. GENERAL SIGNIFICANCE: Because C-mannosylation appears to regulate many ADAMTS4 functions, C-mannosylation may also affect other members of the ADAMTS superfamily.

High Trap Formation and Low Metabolite Production by Disruption of the Polyketide Synthase Gene Involved in the Biosynthesis of Arthrosporols from Nematode-Trapping Fungus Arthrobotrys oligospora.

A group of morphology regulatory arthrosporol metabolites have been recently characterized from carnivorous fungus Arthrobotrys oligospora that can develop trapping networks to capture their prey. A combination of genetic manipulation and chemical analyses was applied to characterize the function of one polyketide synthase (PKS) gene AOL_s00215g283 in A. oligospora, which was putatively involved in the production of 6-methylsalicylic acid. High-performance liquid chromatography analysis showed that the disruption of the PKS gene not only led to the total loss of the arthrosporol A but also resulted in significant reduction in the production of secondary metabolites in the cultural broth of the mutant ΔAOL_s00215g283 strain. Interestingly, the mutant strain displayed significant increases in the trap formation and the nematicidal activity by 10 and 2 times, respectively, higher than the wild-type strain. These findings revealed a pathogenicity-related biosynthetic gene of this agriculturally important biological agent and have implications for establishment of efficient fungal biocontrol agents.