Total Synthesis of the Proposed Structure of Neaumycin B.

The total synthesis of the proposed structure of anti-glioblastoma natural product neaumycin B was achieved in 22 steps (longest linear sequence). The synthesis features HCl-mediated [6,6]-spiroketalization, a combination of Krische iridium-catalyzed crotylation, Marshall palladium-catalyzed propargylation, Fürstner nickel-catalyzed regio- and enantioselective vicinal monoprotected diol formation, Brown crotylation and asymmetric halide-aldehyde cycloaddition, so as to establish the challenging contiguous stereocenters.

Effect of Chaihu plus Longgu Muli decoction plus five-element music therapy in the treatment of cancer-related depression.

BACKGROUND: Ninety percent of tumour patients have negative emotions during or after anti-tumour treatment, resulting in depression. Western medicine antidepressants have many adverse reactions. Patients often discontinue antidepressants due to intolerance. AIM: This study aims to observe the clinical effect of Chaihu plus Longgu Muli decoction with five-element music therapy in treating cancer-related mild and moderate depression. METHODS: A total of 120 patients with depression in the Oncology Department of Tangshan Hospital of Traditional Chinese Medicine, Hebei Province, from July 2017 to March 2019, were selected and randomly divided into the control and study groups (60 cases each) by the random number table method. The study group was treated with Chaihu plus Longgu Muli decoction with five-element music therapy for depression. The control group was treated with escitalopram tablets. After three courses of treatment, the degree of depression, clinical efficacy, quality of life, serum norepinephrine (NE) and 5-hydroxytryptamine (5-HT) levels were observed. RESULTS: After treatment, the HAMD-24 (Hamilton Depression 24) scale scores of the study group (13.93 ± 6.32) were lower than the control group (19.04 ± 7.46), and the difference was statistically significant (x2 = 4.048, p = 0.008). The total effective rate of the study group (93.33%) was higher than the control group (73.33%), and the difference was statistically significant (x2 = 7.260, p = 0.000). After treatment, according to the QLQ-C30 (quality of life questionnaire) scale, the functional score of the study group was higher than the control group (p < 0.05), and the symptom score of the study group was lower than the control group (p < 0.05). After treatment, the serum NE and 5-HT levels in the study group were higher than the control group, and the difference was statistically significant (p < 0.05) (NE: 221.81 ± 31.14 vs 198.91 ± 29.97, t = 4.078, p = 0.000; 5-HT: 141.41 ± 20.35 vs 125.32 ± 14.58, t = 5.781, p = 0.000). CONCLUSION: Chaihu plus Longgu Muli decoction with five-element music therapy can effectively alleviate patients' cancer-related depression and improve their quality of life, which is worthy of promotion.

Long non-coding RNA NRAV enhances proliferation and invasion of hepatocellular carcinoma cells by modulating the Wnt/ß-catenin signaling pathway.

Many dysregulated lncRNAs have been reported to perform an integral function in hepatocellular carcinoma (HCC). However, the role of long non-coding RNA (lncRNA) NRAV in HCC has not been elucidated. To address this issue, we investigated the function of NRAV in HCC in this research. Through bioinformatics prediction and real-time quantitative polymerase chain reaction validation, we found that NRAV plays an upmodulating role in HCC cells and tissues, and patients with high NRAV expression showed a poor prognosis. Cell viability was examined by conducting a Cell Counting Kit-8 analysis. Subsequently, the proliferation capacity of the cells was analyzed utilizing cell colony formation assay, and transwell invasion experiments were conducted to identify the cell invasion ability. To determine the association between NRAV and miR-199a-3p, and CDGSH iron-sulfur domain-containing protein 2 (CISD2), we conducted a dual luciferase assay. The protein and gene expressions were estimated utilizing Western blot. Findings illustrated that the overexpression of NRAV enhanced the HCC cell viability, proliferation and invasion, whereas they were inhibited significantly by down expression of NRAV. The dual-luciferase assay showed that miR-199a-3p is not only a target for NRAV but also interacts with the 3' UTR of CISD2 in HCC cells. MiR-199a-3p/CISD2 axis performs a function in NRAV-mediated cell behavior regulation. NRAV may trigger the Wnt/ß-catenin signaling via the modulation of the miR-199a-3p/CISD2 axis in HCC. The findings of this work can provide novel insights into clinical diagnosis and the treatment of HCC in the future.Abbreviations: HCC, hepatocellular carcinoma; LncRNA, long non-coding RNA; CISD2, CDGSH iron-sulfur domain-containing protein 2; CCK-8, Cell Counting Kit-8; cDNA, single-stranded complementary DNA; RT-qPCR, real-time quantitative polymerase chain reaction; BCA, bicinchoninic acid; ceRNA, competing endogenous RNAs.

Elastase Inhibitor Cyclotheonellazole A: Total Synthesis and In Vivo Biological Evaluation for Acute Lung Injury.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the most common complications in COVID-19. Elastase has been recognized as an important target to prevent ALI/ARDS in the patient of COVID-19. Cyclotheonellazole A (CTL-A) is a natural macrocyclic peptide reported to be a potent elastase inhibitor. Herein, we completed the first total synthesis of CTL-A in 24 linear steps. The key reactions include three-component MAC reactions and two late-stage oxidations. We also provided seven CTL-A analogues and elucidated preliminary structure-activity relationships. The in vivo ALI mouse model further suggested that CTL-A alleviated acute lung injury with reductions in lung edema and pathological deterioration, which is better than sivelestat, one approved elastase inhibitor. The activity of CTL-A against elastase, along with its cellular safety and well-established synthetic route, warrants further investigation of CTL-A as a candidate against COVID-19 pathogeneses.

Complex Network Clustering by a Multi-objective Evolutionary Algorithm Based on Decomposition and Membrane Structure.

The field of complex network clustering is gaining considerable attention in recent years. In this study, a multi-objective evolutionary algorithm based on membranes is proposed to solve the network clustering problem. Population are divided into different membrane structures on average. The evolutionary algorithm is carried out in the membrane structures. The population are eliminated by the vector of membranes. In the proposed method, two evaluation objectives termed as Kernel J-means and Ratio Cut are to be minimized. Extensive experimental studies comparison with state-of-the-art algorithms proves that the proposed algorithm is effective and promising.