Intracoronary application of nicorandil regulates the inflammatory response induced by percutaneous coronary intervention

Intracoronary application of nicorandil can effectively reduce the myocardial no‐reflow (MNR) after percutaneous coronary intervention (PCI). We sought to investigate the mechanisms of nicorandil in preventing MNR, besides that of dilating the coronary microvasculature. A total of 60 patients undergoing PCI were enrolled and randomly divided into a nicorandil group and a control group. Before PCI, 2 mg of nicorandil or an equal volume of normal saline was injected into the coronary artery. Blood samples were collected before, 24 hours and 1 week after PCI and inflammatory cytokines were tested. In the control group, the expression of pro‐inflammatory cytokines was significantly increased, while the anti‐inflammatory cytokines were decreased 24 hours after PCI. In contrast, these changes were reversed in the nicorandil group, indicating that nicorandil regulated the inflammatory response induced by PCI. Then, proteomic analysis was performed to further elucidate the potential mechanisms. A total of 53 differentially expressed proteins (DEPs) were found 24 hours after PCI in the control group, and the changes of these relevant genes were reversed in the nicorandil group. These DEPs were significantly enriched in the inflammatory pathways. In conclusion, the intracoronary application of nicorandil before PCI can regulate the inflammatory responses induced by PCI, which might be an important mechanism of nicorandil in preventing MNR.     

Biogenic production of DMSP and its degradation to DMS—their roles in the global sulfur cycle

Dimethyl sulfide(DMS) is the most abundant form of volatile sulfur in Earth's oceans, and is mainly produced by the enzymatic clevage of dimethylsulfoniopropionate(DMSP). DMS and DMSP play important roles in driving the global sulfur cycle and may affect climate. DMSP is proposed to serve as an osmolyte, a grazing deterrent, a signaling molecule, an antioxidant, a cryoprotectant and/or as a sink for excess sulfur. It was long believed that only marine eukaryotes such as phytoplankton produce DMSP. However, we recently discovered that marine heterotrophic bacteria can also produce DMSP, making them a potentially important source of DMSP. At present, one prokaryotic and two eukaryotic DMSP synthesis enzymes have been identified.Marine heterotrophic bacteria are likely the major degraders of DMSP, using two known pathways: demethylation and cleavage.Many phytoplankton and some fungi can also cleave DMSP. So far seven different prokaryotic and one eukaryotic DMSP lyases have been identified. This review describes the global distribution pattern of DMSP and DMS, the known genes for biosynthesis and cleavage of DMSP, and the physiological and ecological functions of these important organosulfur molecules, which will improve understanding of the mechanisms of DMSP and DMS production and their roles in the environment.     

异养微生物固定CO2的合成生物学研究进展

人类活动造成大气二氧化碳（CO₂）浓度不断升高,使当今世界面临着气候变化的重大危机。微生物CO₂固定为实现地球“碳中和”提供了一条有前景的绿色发展路线。与自养微生物相比,异养微生物具有更快的生长速度和更先进的遗传工具,但是其固定CO₂的能力还很有限。近年来,基于合成生物学技术强化异养微生物CO₂固定受到诸多关注,主要包括优化能量供给、改造羧化途径以及基于异养微生物间接固定CO₂。本综述将围绕上述3个方面重点讨论异养微生物CO₂固定的研究进展,为将来更好地利用微生物CO₂固定技术实现“碳达峰、碳中和”提供参考。     

Production of phenylpyruvic acid by engineered l-amino acid deaminase from Proteus mirabilis

Biotechnology Letters - This study aimed to develop an efficient enzymatic strategy for the industrial production of phenylpyruvate (PPA) from l-phenylpyruvic acid (l-Phe). l-amino acid deaminase...     

CIGAR‐seq,a CRISPR/Cas‐based method for unbiased screening of novel mRNA modification regulators

Cellular RNA is decorated with over 170 types of chemical modifications. Many modifications in mRNA, including m⁶A and m⁵C, have been associated with critical cellular functions under physiological and/or pathological conditions. To understand the biological functions of these modifications, it is vital to identify the regulators that modulate the modification rate. However, a high‐throughput method for unbiased screening of these regulators is so far lacking. Here, we report such a method combining pooled CRISPR screen and reporters with RNA modification readout, termed CRISPR integrated gRNA and reporter sequencing (CIGAR‐seq). Using CIGAR‐seq, we discovered NSUN6 as a novel mRNA m⁵C methyltransferase. Subsequent mRNA bisulfite sequencing in HAP1 cells without or with NSUN6 and/or NSUN2 knockout showed that NSUN6 and NSUN2 worked on non‐overlapping subsets of mRNA m⁵C sites and together contributed to almost all the m⁵C modification in mRNA. Finally, using m¹A as an example, we demonstrated that CIGAR‐seq can be easily adapted for identifying regulators of other mRNA modification.     

Advances in computational ChIA-PET data analysis

Genome-wide chromatin interaction analysis has become important for understanding 3D topological structure of a genome as well as for linking distal cis-regulatory elements to their target genes. Compared to the Hi-C method, chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) is unique, in that one can interrogate thousands of chromatin interactions (in a genome) mediated by a specific protein of interest at high resolution and reasonable cost. However, because of the noisy nature of the data, efficient analytical tools have become necessary. Here, we review some new computational methods recently developed by us and compare them with other existing methods. Our intention is to help readers to better understand ChIA-PET results and to guide the users on selection of the most appropriate tools for their own projects.     

The expression level of surface marker Trop2 in gastric cancer stem-like cells

This study aims to prepare gastric cancer stem-like cells(GCSCs) using a serum-free suspension culture, then identify it preliminarily, and observe the expression level of Trop2. Serum-free DMEM/F12 medium and low-adhesion dish were used for suspended culture of gastric cancer (GC) cell lines MGC803. The morphological characteristics of cell spheres were observed by optical microscope; the positive rates of the CD44, CD54, EpCAM and Trop2 in MGC803 and MGC803-spheres were detected by FACS; the changes of the cell cycle in the MGC803-spheres were explored by FACS and compared with that in MGC803; the mRNA level of cancer stem cells(CSCs) regulatory genes and Trop2 in MGC803-spheres and MGC803 were detected by qRT-PCR. MGC803-spheres formed after MGC803 was cultured in serum-free medium for about 14 days; the levels of CD44, CD54, EpCAM and Trop2 in MGC803-spheres group were higher than those in MGC803 group (P<0.05). The G1 phase of cell cycle in the MGC803-spheres group was obviously lower than that in MGC803 group, and the S phase of the cell cycle in MGC803-spheres group was obviously higher than that in the MGC803 group (P<0.05). The mRNA level in the CSCs regulatory genes (Oct4, Snail, Nanog) and Trop2 in MGC803-spheres group were much higher than those in MGC803 group (P<0.05). MGC803-spheres could form in serum-free and suspension culture condition. The type of cells has the characteristic of CSCs, which appears in a higher proliferation state and over expression CSCs regulating genes and Trop2.     

环太湖复合型生态网络构建

生态网络构建的定量化研究已在生态规划中发挥了重要作用,但复合型生态网络构建却仍旧停留在理论探索与创新阶段。以环太湖地区为例,基于RS和GIS软件平台,采用最短路径分析方法模拟研究区潜在的生态廊道;然后叠加景观、游憩图谱网络,进行无标度网络的构建和检测,构建空间效能好的环太湖复合型生态网络图谱,并据此有针对性地提出复合型生态网络结构和框架优化的建议。研究结果表明,环太湖区域的生态网络和景观、游憩网络可以通过图谱分析和无标度网络检测进行整合,构建出空间效能好的复合型生态网络模型,从而指导环湖生态、景观、游憩资源的耦合发展与廊道建设;通过对不同分区的图谱形态和指标分析,具有小世界网络特征的太湖北部的苏州段和无锡段应以保护和连接为重点,南部的湖州段无标度网络特征明显,成长潜力较好,需要进行高质量的规划保护和开发。     

PTX3, a key component of innate immunity, is induced by SAA via FPRL1-mediated signaling in HAECs

Serum amyloid A (SAA) is regarded as an important acute phase protein in coronary artery diseases. However, its involvement in the immune response of atherosclerosis is poorly understood. The present study was designed to investigate the influence of SAA on the secretion of long pentraxin 3 (PTX3), a key component of innate immunity, in human aortic endothelial cells (HAECs). Our study revealed that recombinant SAA up-regulated PTX3 production in a remarkable dose- and time-dependent manner and the activation of formyl peptide receptor-like 1 (FPRL1) was crucial for SAA-induced expression of PTX3 in HAECs. Meanwhile, SAA-induced PTX3 production could be significantly down-regulated by using the specific siRNA sequences for Jun N-terminal kinases (JNK). Furthermore, the activation of activator protein-1 (AP-1) was necessary for the up-regulation of PTX3 expression. We also found that the activation of nuclear factor-kappa B (NF-κB) played an important role in this process. Our findings demonstrate that SAA up-regulates PTX3 production via FPRL1 significantly, and thus, contributes to the inflammatory pathogenesis of atherosclerosis.