Self-Amplifying RNA Approach for Protein Replacement Therapy

Messenger RNA (mRNA) technology has already been successfully tested preclinically and there are ongoing clinical trials for protein replacement purposes; however, more effort has been put into the development of prevention strategies against infectious diseases. Apparently, mRNA vaccine approval against coronavirus disease 2019 (COVID-19) is a landmark for opening new opportunities for managing diverse health disorders based on this approach. Indeed, apart from infectious diseases, it has also been widely tested in numerous directions including cancer prevention and the treatment of inherited disorders. Interestingly, self-amplifying RNA (saRNA)-based technology is believed to display more developed RNA therapy compared with conventional mRNA technique in terms of its lower dosage requirements, relatively fewer side effects, and possessing long-lasting effects. Nevertheless, some challenges still exist that need to be overcome in order to achieve saRNA-based drug approval in clinics. Hence, the current review discusses the feasibility of saRNA utility for protein replacement therapy on various health disorders including rare hereditary diseases and also provides a detailed overview of saRNA advantages, its molecular structure, mechanism of action, and relevant delivery platforms.     

Cryogenic 3D Printing of w/o Pickering Emulsions Containing Bifunctional Drugs for Producing Hierarchically Porous Bone Tissue Engineering Scaffolds with Antibacterial Capability

How to fabricate bone tissue engineering scaffolds with excellent antibacterial and bone regeneration ability has attracted increasing attention. Herein, we produced a hierarchical porous β-tricalcium phosphate (β-TCP)/poly(lactic-co-glycolic acid)-polycaprolactone composite bone tissue engineering scaffold containing tetracycline hydrochloride (TCH) through a micro-extrusion-based cryogenic 3D printing of Pickering emulsion inks, in which the hydrophobic silica (h-SiO₂) nanoparticles were used as emulsifiers to stabilize composite Pickering emulsion inks. Hierarchically porous scaffolds with desirable antibacterial properties and bone-forming ability were obtained. Grid scaffolds with a macroscopic pore size of 250.03 ± 75.88 μm and a large number of secondary micropores with a diameter of 24.70 ± 15.56 μm can be fabricated through cryogenic 3D printing, followed by freeze-drying treatment, whereas the grid structure of scaffolds printed or dried at room temperature was discontinuous, and fewer micropores could be observed on the strut surface. Moreover, the impartment of β-TCP in scaffolds changed the shape and density of the micropores but endowed the scaffold with better osteoconductivity. Scaffolds loaded with TCH had excellent antibacterial properties and could effectively promote the adhesion, expansion, proliferation, and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells afterward. The scaffolds loaded with TCH could realize the strategy to “kill bacteria first, then induce osteogenesis”. Such hierarchically porous scaffolds with abundant micropores, excellent antibacterial property, and improved bone-forming ability display great prospects in treating bone defects with infection.     

Agrobacterium sp. ZX09 β-Glucan Attenuates Enterotoxigenic Escherichia coli-Induced Disruption of Intestinal Epithelium in Weaned Pigs

To explore the protective effect of dietary β-glucan (BGL) supplementation on intestinal epithelium exposure to enterotoxigenic Escherichia coli (ETEC), thirty-two weaned pigs were assigned to four groups. Pigs were fed with a basal diet or basal diet containing 500 mg/kg BGL, and were orally infused with ETEC or culture medium. Results showed BGL supplementation had no influence on growth performance in weaned pigs. However, BGL supplementation increased the absorption of D-xylose, and significantly decreased the serum concentrations of D-lactate and diamine oxidase (DAO) in the ETEC-challenged pigs (p < 0.05). Interestingly, BGL significantly increased the abundance of the zonula occludens-1-(ZO-1) in the jejunal epithelium upon ETEC challenge (p < 0.05). BGL supplementation also increased the number of S-phase cells and the number of sIgA-positive cells, but significantly decreased the number of total apoptotic cells in the jejunal epithelium upon ETEC challenge (p < 0.05). Moreover, BGL significantly increased the duodenal catalase (CAT) activity and the ileal total superoxide dismutase (T-SOD) activity in the ETEC-challenged pigs (p < 0.05). Importantly, BGL significantly decreased the expression levels of critical inflammation related proteins such as the tumor necrosis factor-α (TNF-α), interlukin-6 (IL-6), myeloid differentiation factor 88 (MyD88), and nuclear factor-κB (NF-κB) in the jejunal and ileal mucosa upon ETEC challenge (p < 0.05). BGL also elevated the propanoic acid content and the abundance of Lactobacillus and Bacillus in the colon upon ETEC challenge (p < 0.05). These results suggested BGL could alleviate the ETEC-induced intestinal epithelium injury, which may be associated with suppressed inflammation and improved intestinal immunity and antioxidant capacity, as well as the improved intestinal macrobiotic.     

Cyt-C Mediated Mitochondrial Pathway Plays an Important Role in Oocyte Apoptosis in Ricefield Eel (Monopterus albus)

Apoptosis plays a key role in the effective removal of excessive and defective germ cells, which is essential for sequential hermaphroditism and sex change in vertebrates. The ricefield eel, Monopterus albus is a protogynous hermaphroditic fish that undergoes a sequential sex change from female to male. Previous studies have demonstrated that apoptosis is involved in sex change in M. albus. However, the apoptotic signaling pathway is unclear. In the current study, we explored the underlying mechanism of apoptosis during gonadal development and focused on the role of the mitochondrial apoptosis signaling pathway in sex change in M. albus. Flow cytometry was performed to detect apoptosis in gonads at five sexual stages and ovary tissues exposed to hydrogen peroxide (H₂O₂) in vitro. Then the expression patterns of key genes and proteins in the mitochondrial pathway, death receptor pathway and endoplasmic reticulum (ER) pathway were examined. The results showed that the apoptosis rate was significantly increased in the early intersexual stage and then decreased with the natural sex change from female to male. Quantitative real-time PCR revealed that bax, tnfr1, and calpain were mainly expressed in the five stages. ELISA demonstrated that the relative content of cytochrome-c (cyt-c) in the mitochondrial pathway was significantly higher than that of caspase8 and caspase12, with a peak in the early intersexual stage, while the levels of caspase8 and caspase12 peaked in the late intersexual stage. Interestingly, the Pearson’s coefficient between cyt-c and the apoptosis rate was 0.705, which suggests that these factors are closely related during the gonadal development of M. albus. Furthermore, the cyt-c signal was found to be increased in the intersexual stage by immunohistochemistry. After incubation with H₂O₂, the mRNA expression of mitochondrial pathway molecules such as bax, apaf-1, and caspase3 increased in ovary tissues. In conclusion, the present results suggest that the mitochondrial apoptotic pathway may play a more important role than the other apoptotic pathways in sex change in M. albus.     

Array-level boosting method with spatial extended allocation to improve the accuracy of memristor based computing-in-memory chips

Memristor based computing-in-memory chips have shown the potentials to accelerate deep neural networks with high energy efficiency.Due to the inherent filament-...     

软煤钻杆研究进展及发展趋势

系统总结了软煤钻孔失稳机理及规律,提出钻孔失稳主要受煤体基本力学性质、孔周应力环境、孔隙压力及钻进方式等因素的影响,指出增大围岩力学强度,减小塑性区范围与钻孔径向位移是提高钻孔稳定性及成孔率的关键。分析了现有钻孔失稳控制技术的适用条件及优缺点,认为研发随钻护孔防喷与可视化修复一体化技术是瓦斯抽采钻孔失稳防治的发展方向。系统梳理了传统注浆加固材料的研究现状,认为研制并使用兼具固孔抑喷与释放瓦斯潜能的纳米浆泡材料,能延长钻孔服务周期,提高瓦斯抽采效率,应用前景可观。

     

涡流管热冷出口压力比对其性能的影响研究

采用Fluent数值模拟的方法,以R41、R23、R32、R290、R1234yf、R134a为工质对涡流管进行三维数值模拟,得出不同工质涡流管制冷效应、制热效应以及分离效应随热冷出口压力比的变化规律,并以R41为工质分析不同流道数目涡流管性能随热冷出口压力比的变化规律。模拟结果表明:R41的制冷、制热以及分离效应最好,最大分离效应可达5 K左右;不同工质涡流管制热效应以及分离效应随热冷出口压力比的增大而增大,制冷效应随热冷出口压力比的增大而减小;不同热冷出口压力比条件下,随着喷嘴流道数的增加涡流管制冷效应逐渐降低而制热效应逐渐升高。