Deepm5C: A deep-learning-based hybrid framework for identifying human RNA N5-methylcytosine sites using a stacking strategy

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基于网络药理学和分子对接技术探讨生脉注射液抗新型冠状病毒肺炎的作用机制

目的采用网络药理学与分子对接技术探讨生脉注射液的活性成分和治疗新型冠状病毒肺炎(COVID-19)的潜在作用机制。方法利用TCMSP及BATMAN-TCM数据库筛选生脉注射液的活性化合物,通过TCMSP及Targetnet在线数据库预测作用靶点,通过Cytoscape3.7.1构建活性成分-作用靶点网络图;在GeneCards及OMIM数据库中以"coronavirus pneumonia"为关键词搜索冠状病毒肺炎相关疾病靶点,与生脉注射液化合物靶点进行交集筛选出共同靶点作为研究靶点,将共同靶点导入STRING数据库获取数据后在Cytoscape 3.7.1软件中构建蛋白质-蛋白质相互作用网络图;利用R语言进行GO(gene ontology)功能、KEGG(Kyoto encyclopedia of genes and genomes)通路富集分析,预测其作用机制,并构建"成分-靶点-通路"网络图;通过DiscoveryStudio 2.5软件对关键靶点进行分子对接分析。结果生脉注射液筛选得到22个活性化合物,分别为邻苯二甲酸二辛酯、β-谷甾醇、当归酰基戈米辛O、戈米辛A、戈米辛R、五味子丙素、内南五味子酯乙、长南酸、南五味子内酯、香蒲木脂素B、新杜松烷酸A、新杜松烷酸B、新杜松烷酸C、新南五味子木脂宁、五味子内酯A、五味子内酯E、五味子酸、尿苷、薯蓣皂苷元、鸟嘌呤核苷、N-反式阿魏酰酪胺、豆甾醇。相应作用靶点224个,与COVID-19的共同靶点16个,分别为CASP3、CASP8、PTGS2、BCL2、BAX、PRKCA、PTGS1、PIK3CG、F10、NOS3、DPP4、NOS2、TLR9、ACE、ICAM1、PRKCE,关键靶点涉及CASP3、PTGS2、NOS2、NOS3、ICAM1。GO功能富集分析得到生物过程(BP)条目771个,细胞组成(CC)条目11个,分子功能(MF)条目79个。KEGG通路富集分析筛选得到67条(P0.05)信号通路,主要涉及糖尿病并发症AGE-RAGE信号通路、凋亡通路、P53信号通路、小细胞肺癌通路等。分子对接结果显示与关键靶点对接较好的成分有五味子内酯E、豆甾醇、N-反式阿魏酰酪胺。结论生脉注射液中的活性化合物五味子内酯E、豆甾醇、N-反式阿魏酰酪胺等能作用于CASP3、PTGS2、NOS2、NOS3等靶点调节多条信号通路发挥抗炎、免疫调节、抗休克、增加血氧饱和度等作用,从而可能发挥对COVID-19的治疗作用。     

四象体质类型与糖调节受损糖尿病转化率的临床研究＊

目的 探讨糖调节受损（IGR）四象体质类型与客观指标相关性。方法 临床收集的122名成年人分为太阳人、太阴人、少阳人和少阴人（因太阳人人数较少，忽略不计）等四种体质，测量空腹血糖（FBG）、餐后2小时血糖（2hBG）、血脂四项等指标，半年后未经治疗，再次测量这些指标，计算糖尿病转化率。结果 IGR者中太阴人所占比例为55.8%，少阳人为21.7%，少阴人为22.5%。其中，朝鲜族的IGR占比明显高于满族和汉族。太阴人与少阳人、少阴人比较，FBG及2hBG、血脂四项、收缩压、舒张压、体重方面有显著性差异（P < 0.05），超重及肥胖人数太阴人中占61.2%、少阳人中占53.8%、少阴人中占29.6%。半年后复查，太阴人与少阳人、少阴人比较，FBG及2hBG、血脂四项、收缩压、舒张压方面有显著性差异（P < 0.05），糖尿病的转化率为太阴人32.8%，少阳人23.1%，少阴人3.7%。结论 IGR者中太阴人所占比例最高。IGR太阴人的FBG及2hBG、血脂四项、收缩压、舒张压、体重偏高，半年后复查，太阴人的DM转化率最高。     

Ethics as ritual: smoothing over moments of dislocation in biomedicine

Applications of biomedical R&D currently imply substantial societal concerns. This paper explores, based on semi‐structured interviews with scientists in Norway, how biomedical researchers experience and tackle such concerns in their daily work. It shows how ritualised routine responses to dislocatory moments help maintain order in the daily work of the interviewed scientists; they do not address directly but instead smooth over concerns by a ritualised way of using ethics. This may foreclose substantive reflection and function as a stabiliser for ‘business as usual’. Overall, the current way of responding to concerns as described by the interviewees may contribute to a depoliticisation of important issues. The paper contributes to sociological work on ethics by linking it to recent discussions on Responsible Research and Innovation (RRI) and by the empirical research presented. The insights can also help improve science policies such as RRI.     

欧盟和美国对药品说明书【适应症】项目的撰写要求及启示

介绍欧盟和美国有关药品说明书[适应症]项目撰写的法规和指导原则，特别是最近欧洲药品管理局（EMA）发布的"治疗适应症的用语"。从这些管理文件得到的启示是相关法规规定不宜太粗糙，应具体、精准，应包括内容和格式的规定；而且要有指导原则伴随，以保证法规落到实处。熟悉掌握药品说明书[适应症]项目的撰写要求对规范撰写其他项目有普遍指导意义，对于药品说明书的监管也有裨益。     

Positive and detached reappraisal in older adulthood: A temporal examination of gaze patterns

Abstract

Objectives: Cognitive reappraisal is an emotion regulation strategy that involves the adaptive restructuring of one’s thoughts surrounding an emotionally evocative stimulus. Previous studies have produced mixed results on how distinct reappraisal and attentional processes are, but few studies have teased apart specific reappraisal methods. This is of particular interest in aging as older adults’ regulation success may vary by reappraisal type. The current study examined whether detached and positive reappraisal are associated with distinct temporal patterns of attention in a sample of older adults.

Method: 29 older adult participants viewed negative IAPS images and were instructed to implement both positive and detached reappraisal while eye movements were monitored. Participants also reported on their mood before and after viewing the images.

Results: Participants fixated on negative areas early on and looked at them less over time, however their attention was oriented specifically towards the most negative region during reappraisal. They also re-fixated on the negative areas of the images during the last second of viewing during detached reappraisal, and reported feeling best while using this strategy.

Conclusion: These findings provide information about the temporal nature of visual attention while utilizing distinct cognitive reappraisal strategies. Results highlight the importance of further teasing apart differences between detached and positive reappraisal as regulatory success and attentional shifts differ between these reappraisal types in older adulthood.     

Pre-implantation Genetic Diagnosis: The Road Forward in Canada

The use of pre-implantation genetic diagnosis (PGD) is increasing as the list of indications it can test for constantly expands. This raises new challenges for clinicians and prospective parents regarding possible uses and calls for guidance. Policy approaches towards PGD vary greatly worldwide. The 2004 Canadian Assisted Human Reproduction Act does not provide guidance, except for prohibiting non-medical sex selection. Criminal legislation is an unsuitable policy instrument to regulate human genetics and reproductive medicine. We call for professional societies to issue guidelines regarding the uses of PGD that would establish the standard of care and legal norms. Such guidelines should be based on a patient-centered approach and respect individual autonomy in reproductive decision-making. Canadian approaches to PGD should also consider issues related to equity of access. Moreover, since PGD often raises concerns about eugenic uses, guidelines should also consider its societal impact and its implementation should be accompanied by policies that maintain or increase social support for people with disabilities. Finally, public engagement could provide an evidence-base regarding Canadian societal values and concerns that should guide regulatory reform, for example, the regulation of non-medical sex selection through PGD.     

Neurogenesis in the adult hippocampus: history,regulation, and prospective roles

Background: The hippocampus is one of the sites in the mammalian brain that is capable of continuously generating controversy. Adult neurogenesis is a remarkable process, and yet an intensely debatable topic in contemporary neuroscience due to its distinctiveness and conceivable impact on neural activity. The belief that neurogenesis continues through adulthood has provoked remarkable efforts to describe how newborn neurons differentiate and incorporate into the adult brain. It has also encouraged studies that investigate the consequences of inadequate neurogenesis in neuropsychiatric and neurodegenerative diseases and explore the potential role of neural progenitor cells in brain repair. The adult nervous system is not static; it is subjected to morphological and physiological alterations at various levels. This plastic mechanism guarantees that the behavioral regulation of the adult nervous system is adaptable in response to varying environmental stimuli. Three regions of the adult brain, the olfactory bulb, the hypothalamus, and the hippocampal dentate gyrus, contain new-born neurons that exhibit an essential role in the natural functional circuitry of the adult brain. Purpose/Aim: This article explores current advancements in adult hippocampal neurogenesis by presenting its history and evolution and studying its association with neural plasticity. The article also discusses the prospective roles of adult hippocampal neurogenesis and describes the intracellular, extracellular, pathological, and environmental factors involved in its regulation. Abbreviations AHN Adult hippocampal neurogenesis

AKT Protein kinase B

BMP Bone Morphogenic Protein

BrdU Bromodeoxyuridine

CNS Central nervous system

DG Dentate gyrus

DISC1 Disrupted-in-schizophrenia 1

FGF-2 Fibroblast Growth Factor 2

GABA Gamma-aminobutyric acid

Mbd1 Methyl-CpG-binding domain protein 1

Mecp2 Methyl-CpG-binding protein 2

mTOR Mammalian target of rapamycin

NSCs Neural stem cells

OB Olfactory bulb; P21: cyclin-dependent kinase inhibitor 1

RBPj Recombination Signal Binding protein for Immunoglobulin Kappa J Region

RMS Rostral migratory Stream

SGZ Subgranular zone

Shh Sonic hedgehog

SOX2 SRY (sex determining region Y)-box 2

SVZ Subventricular zone

Wnt3 Wingless-type mouse mammary tumor virus