Quorum Sensing System Used as a Tool in Metabolic Engineering

Quorum sensing (QS) is a ubiquitous cell–cell communication mechanism in microbes that coordinates population‐level cell behaviors, such as biofilm production, virulence, swarming motility, and bacterial persistence. Efforts to engineer QS systems to take part in metabolic network regulation represent a promising strategy for synthetic biology and pathway engineering. Recently, design, construction, and implementation of QS circuits for programmed control of bacterial phenotypes and metabolic pathways have gained much attention, but have not been reviewed recently. In this article, the architectural organizations and genetic contributions of the naturally occurring QS components to understand the mechanisms are summarized. Then, the most recent progress in application of QS toolkits to develop synthetic networks for novel cell behaviors creation and metabolic pathway engineering is highlighted. The current challenges in large‐scale application of these QS circuits in synthetic biology and metabolic engineering fields are discussed and future perspectives for further engineering efforts are provided.     

Rapid anti‐depressant‐like effects of ketamine and other candidates: Molecular and cellular mechanisms

Major depressive disorder takes at least 3 weeks for clinical anti‐depressants, such as serotonin selective reuptake inhibitors, to take effect, and only one‐third of patients remit. Ketamine, a kind of anaesthetic, can alleviate symptoms of major depressive disorder patients in a short time and is reported to be effective to treatment‐resistant depression patients. The rapid and strong anti‐depressant‐like effects of ketamine cause wide concern. In addition to ketamine, caloric restriction and sleep deprivation also elicit similar rapid anti‐depressant‐like effects. However, mechanisms about the rapid anti‐depressant‐like effects remain unclear. Elucidating the mechanisms of rapid anti‐depressant effects is the key to finding new therapeutic targets and developing therapeutic patterns. Therefore, in this review we summarize potential molecular and cellular mechanisms of rapid anti‐depressant‐like effects based on the pre‐clinical and clinical evidence, trying to provide new insight into future therapy.     

不同水肥一体化方式对苹果氮素吸收利用特性及产量和品质的影响

以‘嘎啦/八棱海棠’为试材,借助¹⁵N同位素示踪技术,研究了撒施(T₁)、滴灌施氮(T₂)和渗灌施氮(T₃)对嘎啦苹果氮素吸收利用、分配特性和产量品质的影响,以期进一步完善苹果园水肥一体化技术,挖掘提高氮素利用率的途径。结果表明: T₃处理苹果叶片的叶面积、叶绿素和氮含量显著高于T₁和T₂处理。各时期土壤矿化氮(N_min)含量在20~40 cm土层表现为T₃＞T₂＞T₁处理,在0~20 cm土层表现为T₂＞T₃＞T₁处理。同一器官的Ndff值(树体各器官从肥料中吸收到的¹⁵N占该器官全氮量的比例)在各时期均以T₃处理最高,T₂其次,T₁处理最低。果实成熟期的树体¹⁵N利用率表现为T₃＞T₂＞T₁处理,其中T₃处理的树体¹⁵N利用率为24.2%,分别是T₂和T₁处理的1.19和1.65倍。果实成熟期T₁处理的¹⁵N分配率在营养器官最高,T₂处理在贮藏器官最高,T₃处理在生殖器官最高。各处理的单果重、产量、可溶性固形物、硬度、可溶性糖及糖酸比均以T₃处理最高,T₂其次,T₁处理最低。渗灌施氮处理显著促进了嘎啦苹果树体叶片生长和氮素利用,并提高了果实产量和品质。     

The Salicylic Acid Signaling Pathway Plays an Important Role in the Resistant Process of Brassica rapa L. ssp. pekinensis to Plasmodiophora brassicae Woronin

Journal of Plant Growth Regulation - Clubroot disease, caused by Plasmodiophora brassicae Woronin infection, leads to significant yield and economic losses in cruciferous vegetables. However, the...     

Feedback regulation of coronary artery disease susceptibility gene ADTRP and LDL receptors LDLR/CD36/LOX-1 in endothelia cell functions involved in atherosclerosis

A high level of low-density lipoprotein cholesterol (LDL) is one of the most important risk factors for coronary artery disease (CAD), the leading cause of death worldwide. However, a low concentration of LDL may be protective. Genome-wide association studies revealed that variation in ADTRP gene increased the risk of CAD. In this study, we found that a low concentration of oxidized-LDL induced the expression of ADTRP. Further analyses showed that knockdown of the expression of LDL receptor genes LDLR, CD36, or LOX-1 significantly downregulated ADTRP expression, whereas overexpression of LDLR/CD36/LOX-1 markedly increased ADTRP expression through the NF-κB pathway. Like ADTRP, LDLR, CD36 and LOX-1 were all involved in endothelial cell (EC) functions relevant to the initiation of atherosclerosis. Downregulation of LDLR/CD36/LOX-1 promoted monocyte adhesion to ECs and transendothelial migration of monocytes by increasing expression of ICAM-1, VCAM-1, E-selectin and P-selectin, decreased EC proliferation and migration, and increased EC apoptosis, thereby promoting the initiation of atherosclerosis. Opposite effects were observed with the overexpression of ADTRP and LDLR/CD36/LOX-1 in ECs. Interestingly, through the NF-κB and AKT pathways, overexpression of ADTRP significantly upregulated the expression of LDLR, CD36, and LOX-1, and knockdown of ADTRP expression significantly downregulated the expression of LDLR, CD36, and LOX-1. These data suggest that ADTRP and LDL receptors LDLR/CD36/LOX-1 positively regulate each other, and form a positive regulatory loop that regulates endothelial cell functions, thereby providing a potential protective mechanism against atherosclerosis. Our findings provide a new molecular mechanism by which deregulation of ADTRP and LDLR/CD36/LOX-1 promote the development of atherosclerosis and CAD.     

Divergent DNA methylation contributes to duplicated gene evolution and chilling response in tea plants

The tea plant (Camellia sinensis) is a thermophilic cash crop and contains a highly duplicated and repeat-rich genome. It is still unclear how DNA methylation regulates the evolution of duplicated genes and chilling stress in tea plants. We therefore generated a single-base-resolution DNA methylation map of tea plants under chilling stress. We found that, compared with other plants, the tea plant genome is highly methylated in all three sequence contexts, including CG, CHG and CHH (where H = A, T, or C), which is further proven to be correlated with its repeat content and genome size. We show that DNA methylation in the gene body negatively regulates the gene expression of tea plants, whereas non-CG methylation in the flanking region enables a positive regulation of gene expression. We demonstrate that transposable element-mediated methylation dynamics significantly drives the expression divergence of duplicated genes in tea plants. The DNA methylation and expression divergence of duplicated genes in the tea plant increases with evolutionary age and selective pressure. Moreover, we detect thousands of differentially methylated genes, some of which are functionally associated with chilling stress. We also experimentally reveal that DNA methyltransferase genes of tea plants are significantly downregulated, whereas demethylase genes are upregulated at the initial stage of chilling stress, which is in line with the significant loss of DNA methylation of three well-known cold-responsive genes at their promoter and gene body regions. Overall, our findings underscore the importance of DNA methylation regulation and offer new insights into duplicated gene evolution and chilling tolerance in tea plants.     

Stromal cell‐derived factor‐1/Exendin‐4 cotherapy facilitates the proliferation,migration and osteogenic differentiation of human periodontal ligament stem cells in vitro and promotes periodontal bone regeneration in vivo

ObjectivesStromal cell‐derived factor‐1 (SDF‐1) actively directs endogenous cell homing. Exendin‐4 (EX‐4) promotes stem cell osteogenic differentiation. Studies revealed that EX‐4 strengthened SDF‐1‐mediated stem cell migration. However, the effects of SDF‐1 and EX‐4 on periodontal ligament stem cells (PDLSCs) and bone regeneration have not been investigated. In this study, we aimed to evaluate the effects of SDF‐1/EX‐4 cotherapy on PDLSCs in vitro and periodontal bone regeneration in vivo.MethodsCell‐counting kit‐8 (CCK8), transwell assay, qRT‐PCR and western blot were used to determine the effects and mechanism of SDF‐1/EX‐4 cotherapy on PDLSCs in vitro. A rat periodontal bone defect model was developed to evaluate the effects of topical application of SDF‐1 and systemic injection of EX‐4 on endogenous cell recruitment, osteoclastogenesis and bone regeneration in vivo.ResultsSDF‐1/EX‐4 cotherapy had additive effects on PDLSC proliferation, migration, alkaline phosphatase (ALP) activity, mineral deposition and osteogenesis‐related gene expression compared to SDF‐1 or EX‐4 in vitro. Pretreatment with ERK inhibitor U0126 blocked SDF‐1/EX‐4 cotherapy induced ERK signal activation and PDLSC proliferation. SDF‐1/EX‐4 cotherapy significantly promoted new bone formation, recruited more CXCR4⁺ cells and CD90⁺/CD34^‐ stromal cells to the defects, enhanced early‐stage osteoclastogenesis and osteogenesis‐related markers expression in regenerated bone compared to control, SDF‐1 or EX‐4 in vivo.ConclusionsSDF‐1/EX‐4 cotherapy synergistically regulated PDLSC activities, promoted periodontal bone formation, thereby providing a new strategy for periodontal bone regeneration.