Recent advances in the application of multiplex genome editing in Saccharomyces cerevisiae.

Saccharomyces cerevisiae is a widely used microorganism and a greatly popular cell factory for the production of various chemicals. In order to improve the yield of target chemicals, it is often necessary to increase the copy numbers of key genes or engineer the related metabolic pathways, which traditionally required time-consuming repetitive rounds of gene editing. With the development of gene-editing technologies such as meganucleases, TALENs, and the CRISPR/Cas system, multiplex genome editing has entered a period of rapid development to speed up cell factory optimization. Multi-copy insertion and removing bottlenecks in biosynthetic pathways can be achieved through gene integration and knockout, for which multiplexing can be accomplished by targeting repetitive sequences and multiple sites, respectively. Importantly, the development of the CRISPR/Cas system has greatly increased the speed and efficiency of multiplex editing. In this review, the various multiplex genome editing technologies in S. cerevisiae were summarized, and the principles, advantages, and the disadvantages were analyzed and discussed. Finally, the practical applications and future prospects of multiplex genome editing were discussed. KEY POINTS: • The development of multiplex genome editing in S. cerevisiae was summarized. • The pros and cons of various multiplex genome editing technologies are discussed. • Further prospects on the improvement of multiplex genome editing are proposed.

Systematic review and meta-analysis of the effects of exercise on depression in adolescents.

BACKGROUND: Depression is widespread among adolescents and seriously endangers their quality of life and academic performance. Developing strategies for adolescent depression has important public health implications. No systematic review on the effectiveness of physical exercise for adolescents aged 12-18 years with depression or depressive symptoms has previously been conducted. This study aims to systematically evaluate the effect of physical exercise on adolescent depression in the hope of developing optimum physical exercise programs. METHODS: Nine major databases at home and abroad were searched to retrieve randomized controlled trials (RCTs) on exercise interventions among adolescents with depression or depressive symptoms. The retrieval period started from the founding date of each database to May 1, 2021. The methodological quality of the included articles was evaluated using the modified PEDro scale. A meta-analysis, subgroup analysis, sensitivity analysis, and publication bias tests were then conducted. RESULTS: Fifteen articles, involving 19 comparisons, with a sample size of 1331, were included. Physical exercise significantly reduced adolescent depression (standardized mean difference [SMD] = - 0.64, 95% CI - 0.89, - 0.39, p < 0.01), with a moderate effect size, in both adolescents with depression (SMD = -0.57, 95% CI - 0.90, - 0.23, p < 0.01) and adolescents with depressive symptoms (SMD = - 0.67, 95% CI - 1.00, - 0.33, p < 0.01). In subgroups of different depression categories (depression or depressive symptoms), aerobic exercise was the main form of exercise for the treatment of adolescents with depression. For adolescents with depression, interventions lasting 6 weeks, 30 min/time, and 4 times/week had optimum results. The effects of aerobic exercise and resistance + aerobic exercise in the subgroup of adolescents with depressive symptoms were significant, while the effect of physical and mental exercise (yoga) was not significant. For adolescents with depressive symptoms, aerobic exercise lasting 8 weeks, 75-120 min/time, and 3 times/week had optimum results. Physical exercise with moderate intensity is a better choice for adolescents with depression and depressive symptoms. CONCLUSIONS: Physical exercise has a positive effect on the improvement of depression in adolescents. The protocol for this study was registered with INPLASY (202170013). DOI number is 10.37766/inplasy2021.7.0013. Registration Date:2021.7.06.

Exercise protects against spinal cord injury through miR-21-mediated suppression of PDCD4.

Spinal cord injury (SCI) can lead to different levels of paraplegia. Studies have shown that exercise exerts wide protective effects against various diseases, and microRNAs (miRNAs) are involved in its beneficial effects. However, the specific role of miRNAs in the protective effects of exercise against SCI remains unclear. Here, we showed that exercise exerted protective effects against SCI as evidenced by increased locomotor activity and spinal cord cell survival in rats with SCI. Exercise upregulated circulating miR-21, detected by miRNA microarray, in rats with SCI. Treating SCI rats with agomiR-21 upregulated circulating miR-21 and exerted protective effects against SCI. Additionally, downregulating miR-21 using antagomir-21 abolished the protective effects of exercise on SCI. Programmed cell death protein 4 (PDCD4) was found to be the target of miR-21. These results suggested that exercise protects against SCI, at least partly, through miR-21-mediated suppression of PDCD4.

Protective effect of brain-derived neurotrophic factor and neurotrophin-3 overexpression by adipose-derived stem cells combined with silk fibroin/chitosan scaffold in spinal cord injury.

Objectives: Spinal cord injury (SCI) is a most debilitating traumatic injury, and cytotherapy is a promising alternative treatment strategy. Here we investigated the effect and mechanism of adipose-derived stem/stromal cells (ASCs) with overexpressing brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) (BDNF-NT3) in combination with silk fibroin/chitosan scaffold (SFCS) in SCI.Methods: Female Sprague-Dawley rats were used as an SCI model. SFCS,SFCS and ASCs, or ASCs overexpressing NT3, BDNF, and BDNF-NT3 were implanted into SCI rats. Basso, Beattie, and Bresnahan score, pathological changes, and spinal cord tissue and nerve fiber morphology were observed and assayed. GAP-43, GFAP, and caspase-3 expression was determined using immunohistochemistry and western blotting.Results: Smoother spinal cords, less scar tissue, and lower inflammatory activity were found in the SFCS, SFCS and ASCs, ASCs with NT3, BDNF, and BDNF-NT3 overexpression treatment than in the untreated SCI rat groups. Increasing formation of nerve fibers was observed in the above groups in order. GAP-43 expression significantly increased, while GFAP and caspase-3 expression significantly decreased. These results indicated obvious alleviation in pathological changes and BDNF-NT3 overexpression in ASCs combined with SFCS treatment in SCI rats.Conclusion: Thus, BDNF-NT3 overexpression from ASCs with SFCS had synergistic neuroprotective effects on SCI and may be a treatment option for SCI.

Exercise, brain plasticity, and depression.

Depression is a common mental disorder characterized by high incidence, high disability, and high fatality, causing great burden to the society, families, and individuals. The changes in brain plasticity may be a main reason for depression. Recent studies have shown that exercise plays a positive role in depression, but systematic and comprehensive studies are lacking on brain plasticity changes in depression. To further understand the antidepressive effect of exercise and the changes in brain plasticity, we retrieved related literatures using key words "depression," "depressive disorder," "exercise," "brain plasticity," "brain structure," and "brain function" from the database of Web of Science, PubMed, EBSCO host, and CNKI, hoping to provide evidence for exercise in preventing and treating depression. Increase in exercise has been found negatively correlated with the risk of depression. Randomized controlled experiments have shown that aerobic exercise, resistance exercise, and mind-body exercise can improve depressive symptoms and levels. The intensity and long-term effect of exercise are now topical research issues. Exercise has been proven to reshape the brain structure of depression patients, activate the function of related brain areas, promote behavioral adaptation changes, and maintain the integrity of hippocampal and white matter volume, thus improving the brain neuroprocessing and delaying cognitive degradation in depression patients. Future studies are urgently needed to establish accurate exercise prescriptions for improving depressive symptoms, and studies on different depressive populations and studies using multimodal brain imaging combined with multiple analytical methods are also needed.

CuInS2 nanotube array on indium tin oxide: synthesis and photoelectrochemical properties.

CuInS(2) nanotube (NT) arrays were synthesized on indium tin oxide (ITO) substrates for the first time using a successive ionic layer absorption and reaction (SILAR) process with self-dissolved ZnO nanowire (NW) templates. The p-type CuInS(2) NT array shows promising conversion efficiency in a photoelectrochemical cell with polysulfide electrolyte.