普通烟草NtODB基因的电子克隆、表达及生物信息学分析

ODB基因在植物同源重组依赖性的DNA双键断裂修复过程中起重要作用,对植物诱变育种具有潜在的应用价值.克隆烟草NtODB基因并分析其表达特征为丰富ODB基因在同源重组DNA修复过程中的作用提供证据.为得到烟草NtODB基因序列,采用电子克隆技术获得该基因cDNA序列并克隆验证.进一步使用生物信息学方法分析该基因表达特征...     

Joint Microbial and Metabolomic Network Estimation with the Censored Gaussian Graphical Model

Joint analysis of microbiome and metabolomic data represents an imperative objective as the field moves beyond basic microbiome association studies and turns towards mechanistic and translational investigations. We present a censored Gaussian graphical model framework, where the metabolomic data are treated as continuous and the microbiome data as censored at zero, to identify direct interactions (defined as conditional dependence relationships) between microbial species and metabolites. Simulated examples show that our method metaMint performs favorably compared to the existing ones. metaMint also provides interpretable microbe-metabolite interactions when applied to a bacterial vaginosis data set. R implementation of metaMint is available on GitHub.

     

The progress and perspectives of CAR-T cell therapy

CAR-T cell therapy has already achieved world-renowned clinical effects in the treatment of hematological malignancies. Due to the tumor heterogeneity, immunosuppressive microenvironment, and other factors, CAR-T cell therapy has still not shown obvious clinical efficacy in clinical treatment of solid tumors. However, great progress has been made in the preparation of CAR-T cells in recent years, including T cells redirected for universal cytokine mediated killing, universal CAR -T cells, non-viral vector CAR-T cells, SynNotch technology, SUPRA CAR technology, regulated CAR-T cells, and bi-specific CAR-T cells, etc. Future research and development of CAR-T cell therapy will be focused on these following aspects: the combined application of CAR-T cells with different targets, known as "Cocktail CAR-T cells", is expected to increase efficiency toward solid tumors; based on systemic biology/synthetic biology theories, CAR-T cells are likely to be transformed to robot or intelligent system by introducing sensors, logic gates, and logic circuits. This article mainly comments on research progress and perspectives on CAR-T cell therapy in solid tumor treatment.     

水稻恢复系M630稻瘟病抗性改良及其代谢组研究

稻瘟病是水稻的主要病害之一,改良水稻稻瘟病抗性对水稻生产、推广具有重要意义.本研究以携带广谱抗稻瘟病基因Pi9材料9311-Pi9为供体,水稻优良恢复系M630为受体,将杂交、回交与分子标记辅助选择和背景筛选相结合,获得改良恢复系M630-Pi9.主要农艺性状和稻米品质分析显示改良后的M630-Pi9及其杂交组合徽两优...     

Four New Nanaomycins Produced by Streptomyces hebeiensis Derived from Lichen

Four new nanaomycins ( 1  –  4 ), together with two known compounds, nanaomycin αA ( 5 ) and nanaomycin βA ( 6 ) were isolated from a fermentation broth of Streptomyces hebeiensis derived from lichen. The structures of the new nanaomycins 1  –  4 were established using comprehensive NMR spectroscopic data analysis as well as UV, IR, and MS data. The antimicrobial activities of 1  –  6 were evaluated against Gram‐positive bacteria and fungus. Compounds 5 and 6 showed antimicrobial activities against the test microorganisms, while 1  –  4 were inactive at 100 μg/ml.     

Modeling the impact of reproductive mode on masting

Masting is defined as the intermittent highly variable production of seed in a plant population. According to reproductive modes, that is, sexual and asexual reproduction, masting species can be separated into three groups, that is, (1) species, for example, bamboo, flower only once before they die; (2) species, for example, Fagus, reproduce sexually; and (3) species, for example, Stipa tenacissima, reproduce both sexually and asexually. Several theories have been proposed to explore the underlying mechanisms of masting. However, to our knowledge, no theory has been found to explain the mechanism of masting species that reproduce both sexually and asexually. Here we refine the Resource Budget Model by considering a trade‐off between sexual and asexual reproduction. Besides the depletion efficient (i.e., the ratio of the cost of seed setting and the cost of flowering), other factors, such as the annual remaining resource (i.e., the rest of the resource from the photosynthetic activity after allocating to growth and maintenance), the trade‐off between sexual and asexual reproduction, and the reproductive thresholds, also affect masting. Moreover, two potential reproductive strategies are found to explain the mechanisms: (1) When the annual remaining resource is relatively low, plants reproduce asexually and a part of the resource is accumulated as the cost of asexual reproduction is less than the annual remaining resource. Plants flower and set fruits once the accumulated resource exceeds the threshold of sexual reproduction; (2) when the annual remaining resource is relatively high, and the accumulated resource surpasses the threshold of sexual reproduction, masting occurs. Remarkably, under certain depletion efficient, more investigation in sexual reproduction will lead plants to reproduce periodically. Additionally, plants investigate less resource to reproduce periodically when depletion efficient keeps increasing as plants can reproduce efficiently. Overall, our study provides new insights into the interpretation of masting, especially for species that reproduce both sexually and asexually.     

Piperine protects against pyroptosis in myocardial ischaemia/reperfusion injury by regulating the miR-383/RP105/AKT signalling pathway

miRNA-mediated pyroptosis play crucial effects in the development of myocardial ischaemia/reperfusion (I/R) injury (MIRI). Piperine (PIP) possesses multiple pharmacological effects especially in I/R condition. This study focuses on whether PIP protects MIRI from pyroptosis via miR-383-dependent pathway. Rat MIRI model was established by 30 minutes of LAD ligation and 4 hours of reperfusion. Myocardial enzymes, histomorphology, structure and function were detected to evaluate MIRI. Recombinant adenoviral vectors for miR-383 overexpression or miR-383 silencing or RP105 knockdown were constructed, respectively. Luciferase reporter analysis was used to confirm RP105 as a target of miR-383. Pyroptosis-related markers were measured by Western blotting assay. The results showed that I/R provoked myocardial injury, as shown by the increases of LDH/CK releases, infarcted areas and apoptosis as well as worsened function and structure. Pyroptosis-related mediators including NLRP3, cleaved caspase-1, cleaved IL-1β and IL-18 were also reinforced after MIRI. However, PIP treatment greatly ameliorated MIRI in parallel with pyroptotic repression. In mechanistic studies, MIRI-caused elevation of miR-383 and decrease of RP105/PI3K/AKT pathway were reverted by PIP treatment. Luciferase reporter assay confirmed RP105 as a miR-383 target. miR-383 knockdown ameliorated but miR-383 overexpression facilitated pyroptosis and MIRI. Moreover, the anti-pyroptotic effect from miR-383 silencing was verified to be relied on the RP105/PI3K/AKT signalling pathway. Additionally, our present study further indicated the miR-383/RP105/AKT-dependent approach resulting from PIP administration against pyroptosis in MIRI. Therefore, PIP treatment attenuates MIRI and pyroptosis by regulating miR-383/RP105/AKT pathway, and it may provide a therapeutic manner for the treatment of MIRI.     

TGF-β isoforms inhibit hepatitis C virus propagation in transforming growth factor beta/SMAD protein signalling pathway dependent and independent manners

Transforming growth factor beta (TGF-β) plays an important role in the viral liver disease progression via controlling viral propagation and mediating inflammation-associated responses. However, the antiviral activities and mechanisms of TGF-β isoforms, including TGF-β1, TGF-β2 and TGF-β3, remain unclear. Here, we demonstrated that all of the three TGF-β isoforms were increased in Huh7.5 cells infected by hepatitis C virus (HCV), but in turn, the elevated TGF-β isoforms could inhibit HCV propagation with different potency in infectious HCV cell culture system. TGF-β isoforms suppressed HCV propagation through interrupting several different stages in the whole HCV life cycle, including virus entry and intracellular replication, in TGF-β/SMAD signalling pathway–dependent and TGF-β/SMAD signalling pathway–independent manners. TGF-β isoforms showed additional anti-HCV activities when combined with each other. However, the elevated TGF-β1 and TGF-β2, not TGF-β3, could also induce liver fibrosis with a high expression of type I collagen alpha-1 and α-smooth muscle actin in LX-2 cells. Our results showed a new insight into TGF-β isoforms in the HCV-related liver disease progression.     

Down-regulated LINC00115 inhibits prostate cancer cell proliferation and invasion via targeting miR-212-5p/FZD5/Wnt/β-catenin axis

Prostate cancer is the second most frequent malignancy in men worldwide, and its incidence is increasing. Therefore, it is urgently required to clarify the underlying mechanisms of prostate cancer. Although the long non-coding RNA LINC00115 was identified as an oncogene in several cancers, the expression and function of LINC00115 in prostate cancer have not been explored. Our results showed that LINC00115 was significantly up-regulated in prostate cancer tissues, which was significantly associated with a poor prognosis for prostate cancer patients. Functional studies showed that knockdown LINC00115 inhibited cell proliferation and invasion. In addition, LINC00115 served as a competing endogenous RNA (ceRNA) through sponging miR-212-5p to release Frizzled Family Receptor 5 (FZD5) expression. The expression of miR-212-5p was noticeably low in tumour tissues, and FZD5 expression level was down-regulated with the knockdown of LINC00115. Knockdown LINC00115 inhibited the Wnt/β‑catenin signalling pathway by inhibiting the expression of FZD5. Rescue experiments further showed that LINC00115 inhibits prostate cancer cell proliferation and invasion via targeting miR-212-5p/ FZD5/ Wnt/β-catenin axis. The present study provided clues that LINC00115 may be a promising novel therapeutic target for prostate cancer patients.     

Reengineering substrate specificity of <Emphasis Type="Italic">E. coli</Emphasis> glutamate dehydrogenase using a position-based prediction method

Objective

To re-engineer the active site of proteins for non-natural substrates using a position-based prediction method (PBPM).

Results

The approach has been applied to re-engineer the E. coli glutamate dehydrogenase to alter its substrate from glutamate to homoserine for a de novo 1,3-propanediol biosynthetic pathway. After identification of key residues that determine the substrate specificity, residue K92 was selected as a candidate site for mutation. Among the three mutations (K92V, K92C, and K92M) suggested by PBPM, the specific activity of the best mutant (K92 V) was increased from 171 ± 35 to 1328 ± 71 μU mg^?1.

Conclusion

The PBPM approach has a high efficiency for re-engineering the substrate specificity of natural enzymes for new substrates.