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991.
Jorge D García-García Kristen Van Gelder Jaya Joshi Ulschan Bathe Bryan J Leong Steven D Bruner Chang C Liu Andrew D Hanson 《Plant physiology》2022,188(2):971
Continuous directed evolution of enzymes and other proteins in microbial hosts is capable of outperforming classical directed evolution by executing hypermutation and selection concurrently in vivo, at scale, with minimal manual input. Provided that a target enzyme’s activity can be coupled to growth of the host cells, the activity can be improved simply by selecting for growth. Like all directed evolution, the continuous version requires no prior mechanistic knowledge of the target. Continuous directed evolution is thus a powerful way to modify plant or non-plant enzymes for use in plant metabolic research and engineering. Here, we first describe the basic features of the yeast (Saccharomyces cerevisiae) OrthoRep system for continuous directed evolution and compare it briefly with other systems. We then give a step-by-step account of three ways in which OrthoRep can be deployed to evolve primary metabolic enzymes, using a THI4 thiazole synthase as an example and illustrating the mutational outcomes obtained. We close by outlining applications of OrthoRep that serve growing demands (i) to change the characteristics of plant enzymes destined for return to plants, and (ii) to adapt (“plantize”) enzymes from prokaryotes—especially exotic prokaryotes—to function well in mild, plant-like conditions.Continuous directed evolution using the yeast OrthoRep system is a powerful way to improve enzymes for use in plant engineering as illustrated by “plantizing” a bacterial thiamin synthesis enzyme. 相似文献
992.
Yu-An Hsu Chih-Sheng Chen Yao-Chien Wang En-Shyh Lin Ching-Yao Chang Jamie Jiin-Yi Chen Ming-Yen Wu Hui-Ju Lin Lei Wan 《Current issues in molecular biology》2021,43(2):716
Resveratrol is a key component of red wine and other grape products. Recent studies have characterized resveratrol as a polyphenol, and shown its beneficial effects on cancer, metabolism, and infection. This study aimed to obtain insights into the biological effects of resveratrol on myopia. To this end, we examined its anti-inflammatory influence on human retinal pigment epithelium cells and in a monocular form deprivation (MFD)-induced animal model of myopia. In MFD-induced myopia, resveratrol increased collagen I level and reduced the expression levels of matrix metalloproteinase (MMP)2, transforming growth factor (TGF)-β, and nuclear factor (NF)-κB expression levels. It also suppressed the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β. Resveratrol exhibited no significant cytotoxicity in ARPE-19 cells. Downregulation of inflammatory cytokine production, and inhibition of AKT, c-Raf, Stat3, and NFκB phosphorylation were observed in ARPE-19 cells that were treated with resveratrol. In conclusion, the findings suggest that resveratrol inhibits inflammatory effects by blocking the relevant signaling pathways, to ameliorate myopia development. This may make it a natural candidate for drug development for myopia. 相似文献
993.
Hsuan-Miao Liu Cheng-Hui Wang Zi-Yu Chang Tse-Hung Huang Tzung-Yan Lee 《Current issues in molecular biology》2021,43(3):1828
Insulin resistance (IR) is a villain role to the pathology of fatty liver diseases implicated in adipose tissue dysfunction, which is characterized by lipid droplets (LDs) accumulation and hypoxia-inducible factor 1α (HIF1α) related macrophage infiltration. HIF1α is required for its lipogenic actions in adipocytes, while and it regulates M1 and M2 polarization features of macrophages. Losartan has been shown to be an insulin sensitizer in obese states, actions involving in HIF1α signaling. However, the exact mechanisms accounting for these effects have not been fully elucidated. Therefore, GTT, ITT, and HOMA-IR were identified losartan alleviated IR signaling in obese mice. This alleviation may through inhibits HIF1α by suppressing STAT3-NF-κB signaling, which, in turn, revealed HIF1α-dependent decreases the angiogenesis pathway in adipose tissue, including regulation of VEGF and TGFβR2 levels. In white adipose tissue, a set of lipogenesis-related genes, Srebp1, Fas, and Scd-1 were markedly downregulated after losartan intervention, as well as reduced LDs size and LD-associated proteins, perilipin family proteins (PLINs) compared with obese mice. Losartan abolished macrophage infiltration with upregulation of M2 and inhibition of M1 macrophage markers in obese mice. Our data suggest that losartan attenuated obese-induced fatty liver, linked to alleviating inflammation in adipose tissues and a shift in M1/M2 macrophage balance. Furthermore, losartan might improve mitochondria biogenesis by upregulating SIRT1, PGC1α, UCP1, and mRNA of Tfam, Cd137, Tmem26, Ucp1 expression in white adipose tissue compared with the obese group. Taken together, losartan may improve IR and adipose dysfunction by inhibiting lipotoxicity and HIF1α pathways. 相似文献
994.
995.
Kai-Che Wei Cheng-Len Sy Wen-Hwa Wang Chia-Ling Wu Shang-Hung Chang Yu-Tung Huang 《PLoS neglected tropical diseases》2022,16(2)
BackgroundDengue virus (DENV) infection may be associated with increased risks of major adverse cardiovascular effect (MACE), but a large-scale study evaluating the association between DENV infection and MACEs is still lacking.Methods and findingsAll laboratory confirmed dengue cases in Taiwan during 2009 and 2015 were included by CDC notifiable database. The self-controlled case-series design was used to evaluate the association between DENV infection and MACE (including acute myocardial infarction [AMI], heart failure and stroke). The "risk interval" was defined as the first 7 days after the diagnosis of DENV infection and the "control interval" as 1 year before and 1 year after the risk interval. The incidence rate ratio (IRR) and 95% confidence interval (CI) for MACE were estimated by conditional Poisson regression. Finally, the primary outcome of the incidence of MACEs within one year of dengue was observed in 1,247 patients. The IRR of MACEs was 17.9 (95% CI 15.80–20.37) during the first week after the onset of DENV infection observed from 1,244 eligible patients. IRR were significantly higher for hemorrhagic stroke (10.9, 95% CI 6.80–17.49), ischemic stroke (15.56, 95% CI 12.44–19.47), AMI (13.53, 95% CI 10.13–18.06), and heart failure (27.24, 95% CI 22.67–32.73). No increased IRR was observed after day 14.ConclusionsThe risks for MACEs are significantly higher in the immediate time period after dengue infection. Since dengue infection is potentially preventable by early recognition and vaccination, the dengue-associated MACE should be taken into consideration when making public health management policies. 相似文献
996.
Xiaoman Li Liang Wang Jialin Hao Qingfeng Zhu Min Guo Changjing Wu Sihui Li Qiqiang Guo Qiuhong Ren Ning Bai Fei Yi Bo Jiang Wenyu Zhang Yanling Feng Hongde Xu Han Jiang Xiaoyue Zhai Guohua Zhang Hong-long Ji Xuesong Yang Dan Zhang Jianhua Fu Jianjun Chang Xiaoyu Song Liu Cao 《International journal of biological sciences》2022,18(3):1107
The lamellar body (LB), a concentric structure loaded with surfactant proteins and phospholipids, is an organelle specific to type 2 alveolar epithelial cells (AT2). However, the origin of LBs has not been fully elucidated. We have previously reported that autophagy regulates Weibel-Palade bodies (WPBs) formation, and here we demonstrated that autophagy is involved in LB maturation, another lysosome-related organelle. We found that during development, LBs were transformed from autophagic vacuoles containing cytoplasmic contents such as glycogen. Fusion between LBs and autophagosomes was observed in wild-type neonate mice. Moreover, the markers of autophagic activity, microtubule-associated protein 1 light chain 3B (LC3B), largely co-localized on the limiting membrane of the LB. Both autophagy-related gene 7 (Atg7) global knockout and conditional Atg7 knockdown in AT2 cells in mice led to defects in LB maturation and surfactant protein B production. Additionally, changes in autophagic activity altered LB formation and surfactant protein B production. Taken together, these results suggest that autophagy plays a critical role in the regulation of LB formation during development and the maintenance of LB homeostasis during adulthood. 相似文献
997.
998.
In order to meet the requirements for miniaturization detection of oil shale pyrolysis process and solve the problem of low sensitivity of oil and gas detection... 相似文献
999.
探讨阿魏酸钠(SF)对增生性瘢痕成纤维细胞(HSFb)增殖及胶原合成的影响.体外培养HSFb,MTT法计算SF的LC50及最佳药物时间后,分为空白对照组、SF干预组(高、中、低浓度分别为0.3、0.03、0.003 mg/mL),培养72 h后,在倒置显微镜和透射电镜下观察HSFb微观形态学变化;MTT法、Wester... 相似文献
1000.
Yue Ren Yang Li Yaojie Wang Tianlei Wen Xuhang Lu Shenghai Chang Xing Zhang Yuequan Shen Xue Yang 《The Journal of biological chemistry》2022,298(5)
Calcium homeostasis modulator 1 (CALHM1) is a voltage- and Ca2+-gated ATP channel that plays an important role in neuronal signaling. However, as the previously reported CALHM structures are all in the ATP-conducting state, the gating mechanism of ATP permeation is still elusive. Here, we report cryo-EM reconstructions of two Danio rerio CALHM1 heptamers with ordered or flexible long C-terminal helices at resolutions of 3.2 Å and 2.9 Å, respectively, and one D. rerio CALHM1 octamer with flexible long C-terminal helices at a resolution of 3.5 Å. Structural analysis shows that the heptameric CALHM1s are in an ATP-nonconducting state with a central pore diameter of approximately 6.6 Å. Compared with those inside the octameric CALHM1, the N-helix inside the heptameric CALHM1 is in the “down” position to avoid steric clashing with the adjacent TM1 helix. Molecular dynamics simulations show that as the N-helix moves from the “down” position to the “up” position, the pore size of ATP molecule permeation increases significantly. Our results provide important information for elucidating the mechanism of ATP molecule permeation in the CALHM1 channel. 相似文献