从蚕的生命到艺术：中国古代生命观的哲学表达

中国考古出土的蚕业实物及蚕的艺术形象比较丰富,蚕的艺术形象如蚕纹、陶蚕蛹、牙雕蚕、玉石蚕、铜蚕、金蚕等,可统称为"蚕的模拟形态"。对蚕的模拟形态的功用,已有的诸多解释都有待完善。研究表明,蚕的模拟形态或艺术形象表达的功用或为饰品,或为装饰图案,或有待进一步考究。但无论哪种功用,用"蚕"这一形象都蕴含了特有的用意。通过对中国古代生命观的考察,文章认为蚕的艺术形象折射出相应的中国古代哲学生命观,即中国古人追求的死而复生、生生不息、羽化成仙、长乐无极等观念。     

Differential gene expression of the healthy conjunctiva during the day

PurposeTo determine if there is diurnal variation in gene expression in normal healthy conjunctival cells.MethodsBulbar conjunctival swab samples were collected from four healthy subjects in the morning and evening of the same day. The two swab samples were taken from one eye of each participant, with a minimum of five hours gap between the two samples. RNA was extracted and analysed using RNA sequencing (RNA-Seq).ResultsA total of 121 genes were differentially expressed between the morning and the evening conjunctival samples, of which 94 genes were upregulated in the morning, and 27 genes were upregulated in the evening. Many of the genes that were upregulated in the morning were involved in defence, cell turnover and regulation of gene expression, while the genes upregulated in the evening were involved in signalling and mucin production.ConclusionsThis study has identified several genes whose expression changes over the course of the day. Knowledge of diurnal variations of conjunctival gene expression provides an insight into the regulatory status of the healthy eye and provides a baseline for examining changes during ocular surface disease.     

Optimal design and operation of integrated microgrids under intermittent renewable energy sources coupled with green hydrogen and demand scenarios

Renewable energy integration into existing or new energy hubs together with Green technologies such as Power to Gas and Green Hydrogen has become essential because of the aim of keeping the average global temperature rise within 2 ^°C with regard to the Paris Agreement. Hence, all energy markets are expected to face substantial transitions worldwide. On the other hand, investigation of renewable energy systems integrated with green chemical conversion, and in particular combination of green hydrogen and synthetic methanation, is still a scarce subject in the literature in terms of optimal and simultaneous design and operation for integrated energy grids under weather intermittency and demand uncertainty. In fact, the integration of such promising new technologies has been studied mainly in the operational phase, without considering design and management simultaneously. Thus, in this work, a multi-period mixed-integer linear programming (MILP) model is formulated to deal with the aforementioned challenges. Under current carbon dioxide limitations dictated by the Paris Agreement, this model computes the best configuration of the renewable and non-renewable-based generators, their optimal rated powers, capacities and scheduling sequences from a large candidate pool containing thirty-nine different equipment simultaneously. Moreover, the effect of the intermittent nature of renewable resources is analyzed comprehensively under three different scenarios for a specific location. Accordingly, a practical scenario generation method is proposed in this work. It is observed that photovoltaic, oil co-generator, reciprocating ICE, micro turbine, and bio-gasifier are the equipment that is commonly chosen under the three different scenarios. Results also show that concepts such as green hydrogen and power-to-gas are currently not preferable for the investigated location. On the other hand, analysis shows that if the emission limits are getting tightened, it is expected that constructing renewable resource-based grids will be economically more feasible.     

安徽地区汉族心血管疾病患者SLCO1B1与ApoE基因多态性分布及其在他汀类药物临床个体化应用中的意义

目的：探讨脂质及药物代谢相关基因SLCO1B1和ApoE的基因多态性在安徽地区汉族心血管疾病患者中的分布，以评估他汀类药物个体化用药的效益/风险比。方法：利用PCR-荧光探针法技术检测2019年1月至2020年8月合肥市第二人民医院736例心血管疾病患者外周血基因组中SLCO1B1基因的rs2306283（388A>G）和rs4149056（521T>C）位点和ApoE基因的rs429358（388T>C）和rs7412（526C>T）位点的基因多态性分布特点，并与已报道的中国其他地区汉族心血管疾病患者的数据进行比较，分析不同地区间的基因型分布差异。结果：检测到安徽地区汉族心血管疾病患者中SLCO1B1基因型有6种，分别为*1a/*1a型（6.11%）、*1a/*1b型（29.08%）、*1b/*1b型（44.57%）、*1a/*15型（4.08%）、*1b/*15型（15.49%）、*15/*15型（0.68%），未检测到*1a/*5型、*5/*5型和*5/*15型；ApoE基因有6种表型，分别为E2/E2型（0.41%）、E2/E3型（11.96%）、E2/E4型（1.09%）、E3/E3型（67.66%）、E3/E4型（17.93%）、E4/E4型（0.95%）。两种基因的基因多态性频率分布满足Hardy-Weinberg遗传平衡，具有群体代表性。本研究人群中携带SLCO1B1正常肌病风险型的比例最高，约占79.76%；SLCO1B1中度肌病风险型和高度肌病风险型的人群比例较低，分别为19.57%和0.68%。ApoE大众类基因型比例最高，约占68.75%；ApoE保护类基因型及风险类基因型的人群比例分别为12.37%和18.88%。不同性别间SLCO1B1和ApoE基因表型患者差异无统计学意义。与华南地区心血管疾病患者相比，安徽地区ApoE基因多态性分布差异有统计学意义（P<0.05）。结论：安徽地区736例心血管疾病患者SLCO1B1和ApoE基因型分别以他汀药物剂量耐受性较高的正常肌病风险型和对他汀药物敏感的大众类基因型为主，服用他汀类药物诱发肌病的风险较低，降脂疗效较好；且两种基因的多态性分布均不受性别的影响，但ApoE基因多态性分布特征可能在地域上存在差异。因此，检测SLCO1B1和APOE基因多态性对于临床评估效益/风险比有重要的指导意义。     

In Vivo Simultaneous Analysis of Gene Expression by Dual-Color Luciferases in Caenorhabditis elegans

Both fluorescent and luminescent observation are widely used to examine real-time gene expression patterns in living organisms. Several fluuorescent and luminescent proteins with specific optical properties have been developed and applied for simultaneous, multi-color observation of more than two gene expression profiles. Compared to fluorescent proteins, however, the application of multi-color luminescent imaging in living organisms is still limited. In this study, we introduced two-color luciferases into the soil nematode C. elegans and performed simultaneous analysis of two gene expression profiles. Using a green-emitting luciferase Eluc (emerald luciferase) and red-emitting luciferase SLR (stable luciferase red), the expression patterns of two genes were simultaneously observed in single animals from embryonic to adult stages over its whole life span. In addition, dual gene activities were observed at the single embryo level, with the simultaneous observation of morphological changes. These are the first application of a two-color luciferase system into a whole animal and suggest that precise relationship of expression patterns of multiple genes of interest can be analyzed over the whole life of the animal, dependent on the changes in genetic and/or environmental conditions.     

Evaluation of a Novel Plasmid for Simultaneous Gene Electrotransfer-Mediated Silencing of CD105 and CD146 in Combination with Irradiation

Targeting tumor vasculature through specific endothelial cell markers represents a promising approach for cancer treatment. Here our aim was to construct an antibiotic resistance gene-free plasmid encoding shRNAs to simultaneously target two endothelial cell markers, CD105 and CD146, and to test its functionality and therapeutic potential in vitro when delivered by gene electrotransfer (GET) and combined with irradiation (IR). Functionality of the plasmid was evaluated by determining the silencing of the targeted genes using qRT-PCR. Antiproliferative and antiangiogenic effects were determined by the cytotoxicity assay tube formation assay and wound healing assay in murine endothelial cells 2H-11. The functionality of the plasmid construct was also evaluated in malignant melanoma tumor cell line B16F10. Additionally, potential activation of immune response was measured by induction of DNA sensor STING and proinflammatory cytokines by qRT-PCR in endothelial cells 2H-11. We demonstrated that the plasmid construction was successful and can efficiently silence the expression of the two targeted genes. As a consequence of silencing, reduced migration rate and angiogenic potential was confirmed in 2H-11 endothelial cells. Furthermore, induction of DNA sensor STING and proinflammatory cytokines were determined, which could add to the therapeutic effectiveness when used in vivo. To conclude, we successfully constructed a novel plasmid DNA with two shRNAs, which holds a great promise for further in vivo testing.     

Role of the HSP70 Co-Chaperone SIL1 in Health and Disease

Cell surface and secreted proteins provide essential functions for multicellular life. They enter the endoplasmic reticulum (ER) lumen co-translationally, where they mature and fold into their complex three-dimensional structures. The ER is populated with a host of molecular chaperones, associated co-factors, and enzymes that assist and stabilize folded states. Together, they ensure that nascent proteins mature properly or, if this process fails, target them for degradation. BiP, the ER HSP70 chaperone, interacts with unfolded client proteins in a nucleotide-dependent manner, which is tightly regulated by eight DnaJ-type proteins and two nucleotide exchange factors (NEFs), SIL1 and GRP170. Loss of SIL1′s function is the leading cause of Marinesco-Sjögren syndrome (MSS), an autosomal recessive, multisystem disorder. The development of animal models has provided insights into SIL1′s functions and MSS-associated pathologies. This review provides an in-depth update on the current understanding of the molecular mechanisms underlying SIL1′s NEF activity and its role in maintaining ER homeostasis and normal physiology. A precise understanding of the underlying molecular mechanisms associated with the loss of SIL1 may allow for the development of new pharmacological approaches to treat MSS.     

Mechanisms of Reciprocal Regulation of Gonadotropin-Releasing Hormone (GnRH)-Producing and Immune Systems: The Role of GnRH,Cytokines and Their Receptors in Early Ontogenesis in Normal and Pathological Conditions

Different aspects of the reciprocal regulatory influence on the development of gonadotropin-releasing hormone (GnRH)-producing- and immune systems in the perinatal ontogenesis and their functioning in adults in normal and pathological conditions are discussed. The influence of GnRH on the development of the immune system, on the one hand, and the influence of proinflammatory cytokines on the development of the hypothalamic-pituitary-gonadal system, on the other hand, and their functioning in adult offspring are analyzed. We have focused on the effects of GnRH on the formation and functional activity of the thymus, as the central organ of the immune system, in the perinatal period. The main mechanisms of reciprocal regulation of these systems are discussed. The reproductive health of an individual is programmed by the establishment and development of physiological systems during critical periods. Regulatory epigenetic mechanisms of development are not strictly genetically controlled. These processes are characterized by a high sensitivity to various regulatory factors, which provides possible corrections for disorders.