Tetrandrine Inhibits Skeletal Muscle Differentiation by Blocking Autophagic Flux

Tetrandrine is well known to act as a calcium channel blocker. It is a potential candidate for a tumor chemotherapy drug without toxicity. Tetrandrine inhibits cancer cell proliferation and induces cell death through apoptosis and autophagy. As cancer patients usually experience complications with sarcopenia or muscle injury, we thus assessed the effects of tetrandrine on skeletal muscle cells. We report in this study that a low dose of tetrandrine (less than 5 μM) does not affect the proliferation of C2C12 myoblasts, but significantly inhibits myogenic differentiation. Consistently, tetrandrine inhibited muscle regeneration after BaCl₂-induced injury. Mechanistic experiments showed that tetrandrine decreased the p-mTOR level and increased the levels of LC3 and SQSTM1/p62 during differentiation. Ad-mRFP-GFP-LC3B transfection experiments revealed that the lysosomal quenching of GFP signals was suppressed by tetrandrine. Furthermore, the levels of DNM1L/Drp1, PPARGA1 and cytochrome C (Cyto C), as well as caspase 3 activation and ROS production, were decreased following tetrandrine administration, indicating that the mitochondrial network signaling was inhibited. Our results indicate that tetrandrine has dual effects on autophagic flux in myoblasts during differentiation, activation in the early stage and blockade in the late stage. The ultimate blocking of autophagic flux by tetrandrine led to the disruption of mitochondria remodeling and inhibition of myogenic differentiation. The inhibitory effects of tetrandrine on skeletal muscle differentiation may limit its application in advanced cancer patients. Thus, great attention should be paid to the clinical use of tetrandrine for cancer therapy.     

Development and Use of a Kinetical and Real-Time Monitoring System to Analyze the Replication of Hepatitis C Virus

In microbiological research, it is important to understand the time course of each step in a pathogen’s lifecycle and changes in the host cell environment induced by infection. This study is the first to develop a real-time monitoring system that kinetically detects luminescence reporter activity over time without sampling cells or culture supernatants for analyzing the virus replication. Subgenomic replicon experiments with hepatitis C virus (HCV) showed that transient translation and genome replication can be detected separately, with the first peak of translation observed at 3–4 h and replication beginning around 20 h after viral RNA introduction into cells. From the bioluminescence data set measured every 30 min (48 measurements per day), the initial rates of translation and replication were calculated, and their capacity levels were expressed as the sums of the measured signals in each process, which correspond to the areas on the kinetics graphs. The comparison of various HuH-7-derived cell lines showed that the bioluminescence profile differs among cell lines, suggesting that both translation and replication capacities potentially influence differences in HCV susceptibility. The effects of RNA mutations within the 5′ UTR of the replicon on viral translation and replication were further analyzed in the system developed, confirming that mutations to the miR-122 binding sites primarily reduce replication activity rather than translation. The newly developed real-time monitoring system should be applied to the studies of various viruses and contribute to the analysis of transitions and progression of each process of their life cycle.     

miR-199a: A Tumor Suppressor with Noncoding RNA Network and Therapeutic Candidate in Lung Cancer

Lung cancer is the leading cause of cancer death worldwide. miR-199a, which has two mature molecules: miR-199a-3p and miR-199a-5p, plays an important biological role in the genesis and development of tumors. We collected recent research results on lung cancer and miR-199a from Google Scholar and PubMed databases. The biological functions of miR-199a in lung cancer are reviewed in detail, and its potential roles in lung cancer diagnosis and treatment are discussed. With miR-199a as the core point and a divergence outward, the interplay between miR-199a and other ncRNAs is reviewed, and a regulatory network covering various cancers is depicted, which can help us to better understand the mechanism of cancer occurrence and provide a means for developing novel therapeutic strategies. In addition, the current methods of diagnosis and treatment of lung cancer are reviewed. Finally, a conclusion was drawn: miR-199a inhibits the development of lung cancer, especially by inhibiting the proliferation, infiltration, and migration of lung cancer cells, inhibiting tumor angiogenesis, increasing the apoptosis of lung cancer cells, and affecting the drug resistance of lung cancer cells. This review aims to provide new insights into lung cancer therapy and prevention.     

Regulation of Autophagy Machinery in Magnaporthe oryzae

Plant diseases cause substantial loss to crops all over the world, reducing the quality and quantity of agricultural goods significantly. One of the world’s most damaging plant diseases, rice blast poses a substantial threat to global food security. Magnaporthe oryzae causes rice blast disease, which challenges world food security by causing substantial damage in rice production annually. Autophagy is an evolutionarily conserved breakdown and recycling system in eukaryotes that regulate homeostasis, stress adaption, and programmed cell death. Recently, new studies found that the autophagy process plays a vital role in the pathogenicity of M. oryzae and the regulation mechanisms are gradually clarified. Here we present a brief summary of the recent advances, concentrating on the new findings of autophagy regulation mechanisms and summarize some autophagy-related techniques in rice blast fungus. This review will help readers to better understand the relationship between autophagy and the virulence of plant pathogenic fungi.     

Crosstalk between Growth and Osmoregulation of GHRH-SST-GH-IGF Axis in Triploid Rainbow Trout (Oncorhynchus mykiss)

Smolting is an important development stage of salmonid, and an energy trade-off occurs between osmotic regulation and growth during smolting in rainbow trout (Oncorhynchus mykiss). Growth hormone releasing hormone, somatostatin, growth hormone and insulin-like growth factor (GHRH-SST-GH-IGF) axis exhibit pleiotropic effects in regulating growth and osmotic adaptation. Due to salmonid specific genome duplication, increased paralogs are identified in the ghrh-sst-gh-igf axis, however, their physiology in modulating osmoregulation has yet to be investigated. In this study, seven sst genes (sst1a, sst1b, sst2, sst3a, sst3b, sst5, sst6) were identified in trout. We further investigated the ghrh-sst-gh-igf axis of diploid and triploid trout in response to seawater challenge. Kidney sst (sst1b, sst2, sst5) and sstr (sstr1b1, sstr5a, sstr5b) expressions were changed (more than 2-fold increase (except for sstr5a with 1.99-fold increase) or less than 0.5-fold decrease) due to osmoregulation, suggesting a pleiotropic physiology of SSTs in modulating growth and smoltification. Triploid trout showed significantly down-regulated brain sstr1b1 and igfbp2a1 (p < 0.05), while diploid trout showed up-regulated brain igfbp1a1 (~2.61-fold, p = 0.057) and igfbp2a subtypes (~1.38-fold, p < 0.05), suggesting triploid trout exhibited a better acclimation to the seawater environment. The triploid trout showed up-regulated kidney igfbp5a subtypes (~6.62 and 7.25-fold, p = 0.099 and 0.078) and significantly down-regulated igfbp5b2 (~0.37-fold, p < 0.05), showing a conserved physiology of teleost IGFBP5a in regulating osmoregulation. The IGFBP6 subtypes are involved in energy and nutritional regulation. Distinctive igfbp6 subtypes patterns (p < 0.05) potentially indicated trout triggered energy redistribution in brain and kidney during osmoregulatory regulation. In conclusion, we showed that the GHRH-SST-GH-IGF axis exhibited pleiotropic effects in regulating growth and osmoregulatory regulation during trout smolting, which might provide new insights into seawater aquaculture of salmonid species.     

用不对称醚作调节剂合成苯乙烯-异戊二烯-丁二烯橡胶的反应动力学

以苯乙烯(St)、异戊二烯(Ip)和丁二烯(Bd)为单体,正丁基锂(n-BuLi)为引发荆,乙基乙二醇叔丁基醚(BET)为结构调节剂,合成了线型无规结构的苯乙烯-异戊二烯-丁二烯橡胶(SIBR),进行了聚合反应动力学研究,并与以四氢呋喃(THF)为结构调节剂的体系进行了比较.结果表明,BET的加入提高了聚合反应速率;随反应温度的升高和BET/n-BuLi(摩尔比)的增大,聚合反应速率加快,尤其是St的反应速率提高显著;BET调节聚合速率的能力明显高于THF.     

轮毂轴承橡胶密封圈硫化模具的设计

针对轮毂轴承橡胶密封圈加工过程中出现的工艺问题,从模具结构上进行改进性的尝试,保证了产品的质量要求。     

东西方文学审美的契合——从"冰山理论"与"言意观"谈起

海明威独创的冰山理论,是现代西方最具影响的文学理论之一,它开创了一种语言简洁而内蕴丰富的全新创作观,对同时代以及现今的文学创作产生了深远的影响.与此对应的是,中国古代"言意观"正视"言不尽意"的事实,追求"意在言外"的创作目的,主张以有限的言说传递无限生动、丰富的审美空间."冰山理论"与中国的"言意观"作为中西方诗学的代表性理论,在语言观、审美追求等方面的融通之处使得对两者的比较研究具有深远而广泛的实践意义.