Addressing high excitation conditions in time-resolved X-ray diffraction experiments and issues of biological relevance

One of the most important fundamental questions connecting chemistry to biology is how chemistry scales in complexity up to biological systems where there are innumerable possible pathways and competing processes. With the development of ultrabright electron and x-ray sources, it has been possible to literally light up atomic motions to directly observe the reduction in dimensionality in the barrier crossing region to a few key reaction modes. How do these chemical processes further couple to the surrounding protein or macromolecular assembly to drive biological functions? Optical methods to trigger photoactive biological processes are needed to probe this issue on the relevant timescales. However, the excitation conditions have been in the highly nonlinear regime, which questions the biological relevance of the observed structural dynamics.     

A mechanistic spatio-temporal modeling of COVID-19 data

Understanding the evolution of an epidemic is essential to implement timely and efficient preventive measures. The availability of epidemiological data at a fine spatio-temporal scale is both novel and highly useful in this regard. Indeed, having geocoded data at the case level opens the door to analyze the spread of the disease on an individual basis, allowing the detection of specific outbreaks or, in general, of some interactions between cases that are not observable if aggregated data are used. Point processes are the natural tool to perform such analyses. We analyze a spatio-temporal point pattern of Coronavirus disease 2019 (COVID-19) cases detected in Valencia (Spain) during the first 11 months (February 2020 to January 2021) of the pandemic. In particular, we propose a mechanistic spatio-temporal model for the first-order intensity function of the point process. This model includes separate estimates of the overall temporal and spatial intensities of the model and a spatio-temporal interaction term. For the latter, while similar studies have considered different forms of this term solely based on the physical distances between the events, we have also incorporated mobility data to better capture the characteristics of human populations. The results suggest that there has only been a mild level of spatio-temporal interaction between cases in the study area, which to a large extent corresponds to people living in the same residential location. Extending our proposed model to larger areas could help us gain knowledge on the propagation of COVID-19 across cities with high mobility levels.     

Some new results on Cox–Czanner divergence and their applications in survival studies

In the present communication, we propose a quantile-based measure for the divergence between two survival functions. This can also be used in a dynamic way where the divergence between survival functions varies with time. Several new properties of the proposed measure are investigated with suitable examples. The behavior of the measure for various reliability models is also investigated. A real data analysis is employed to compare the relative efficacy of two treatment groups using the proposed divergence measure.     

定量分析调控人类免疫缺陷病毒潜伏与激活的动力学机制

目的 治疗艾滋病最大的障碍在于无法根除人类免疫缺陷病毒（HIV）潜伏于人体细胞所形成的病毒存储库。构建描述病毒存储库建立分子机制的动力学模型需考虑生物体内的噪声环境和多重影响因素,本文通过一种全新的动力学结构分解方法将随机微分方程的确定性部分与随机性噪声分开,从而在仅需分析常微分方程不动点的情况下即可判断不同药物靶点的作用效果。方法 使用连续的随机微分方程构建了HIV转录过程的动力学模型,简化了描述系统所需方程的维度,增大了模型的可探索空间,在此基础上,通过计算得到的势能函数和概率分布函数直观表示病毒潜伏与激活的不同表达状态以及它们之间的关系。结果 定量分析了不同动力学参数对系统稳态和势函数的影响程度,分别得到了系统处于双稳态和单稳态时的参数范围,并将不同因素对动力系统分岔的影响程度与生物学实验结果对比,验证了本工作的理论基础。结论 本文突破了以往离散、随机的方法,可以通过常微分方程定量分析HIV转录调控的动力学机制,有利于推广到处理高维情况,进一步研究艾滋病在生物体内的发生发展,从而指导设计实验寻找临床上的治疗方案。     

生长抑素在糖尿病大鼠胰腺外分泌功能降低中的作用

本实验观察到,用链佐霉素造成大鼠糖尿病模型,其胰腺组织中生长抑素含量明显升高。大鼠皮下注射生长抑素(100μg·kg~(-1)·d~(-1))5d,其胰腺组织中淀粉酶的含量明显降低。体外胰腺灌流也表明,生长抑素能抑制CCK—8刺激引起的胰腺淀粉酶释放。以上结果提示,糖尿病时胰腺组织中生长抑素含量的增加可能在胰腺外分泌功能降低中有一定的作用。     

Insights into circular RNAs: Biogenesis,function and their regulatory roles in cardiovascular disease

As a distinctive member of the noncoding RNA family, circular RNAs (circRNAs) are generated from single-stranded, covalently closed structures and are ubiquitous in mammalian cells and tissues. Due to its atypical circular architecture, it was conventionally deemed insignificant dark matter for a prolonged duration. Nevertheless, studies conducted over the last decade have demonstrated that this abundant, structurally stable and tissue-specific RNA has been increasingly relevant in diverse diseases, including cancer, neurological disorders, diabetes mellitus and cardiovascular diseases (CVDs). Therefore, regulatory pathways controlled by circRNAs are widely involved in the occurrence and pathological processes of CVDs through their function as miRNA sponges, protein sponges and protein scaffolds. To better understand the role of circRNAs and their complex regulatory networks in CVDs, we summarize current knowledge of their biogenesis and function and the latest research on circRNAs in CVDs, with the hope of paving the way for the identification of promising biomarkers and therapeutic strategies for CVDs.     

Neuronal specificity and its development in the Drosophila wing disc and its derivatives

The imaginal wing disc of flies gives rise to the adult wing blade and dorsal thorax (notum). A great deal has been learned in recent years about the process of neurogenesis in this disc; a number of genes that play crucial roles in the formation of sensory mother cells and in the differentiation of the sensory organs have been identified and their roles defined. Given this extensive background of developmental genetics, it has seemed profitable to summarize what is known about the end-products of neural development, the adult sensory organs. Discussed are their physiological function and role in behavior, the pathways followed by their axons in the CNS, and both genes and epigenetic processes that might play some role in the later stages of neural development and in adult function. The highly individual characteristics of certain of the sensory organs is emphasized, both in the context of their adult roles and as a challenge for future studies in developmental genetics. © 1993 John Wiley & Sons, Inc.     

水罐疗法联合白头翁汤灌肠对溃疡性结肠炎患者Th1/Th2免疫平衡及肠黏膜屏障功能的影响

摘要 目的：探讨水罐疗法联合白头翁汤灌肠对溃疡性结肠炎（UC）患者Th1/Th2免疫平衡及肠黏膜屏障功能的影响。方法：选取2020年2月~2022年5月期间湖南中医药大学第一附属医院收治的UC患者100例。根据随机数字表法分为对照组（n=50）和研究组（n=50）。对照组患者接受白头翁汤灌肠,研究组在此基础上接受水罐疗法。对比两组疗效、中医证候评分、Th1/Th2免疫平衡及肠黏膜屏障功能变化情况。结果：研究组的总有效率明显高于对照组（P<0.05）。治疗后,两组里急后重、身热不扬、腹泻黏液脓血便、小便短赤、肛门灼热、腹痛、口干口苦等症状评分均降低,且研究组低于对照组同期（P<0.05）。治疗后,两组Th1/Th2相关指标白介素（IL）-2、γ-干扰素（IFN-γ）均降低,且研究组较对照组低;IL-4、IL-10均升高,且研究组较对照组高（P<0.05）。治疗后,两组肠黏膜屏障功能指标二胺氧化酶（DAO）、D-乳酸（D-LA）均降低,且研究组低于对照组同期（P<0.05）。结论：水罐疗法联合白头翁汤灌肠治疗UC患者,总有效率高,可缓解中医证候,疗效显著,对调节患者的Th1/Th2免疫平衡及肠黏膜屏障功能具有重要作用。     

尿铜蓝蛋白、肾损伤因子1与糖尿病肾病患者肾功能的关系及对预后不良的预测价值研究

摘要 目的：探讨尿铜蓝蛋白（CP）、肾损伤因子1（KIM-1）与糖尿病肾病（DKD）患者肾功能的关系及对预后不良的预测价值。方法：回顾性分析2017年1月～2019年1月陆军第八十二集团军医院肾内科收治的160例DKD患者（DKD组）的临床资料,随访3年,根据是否发展为终末期肾脏疾病（ESRD）分为预后不良组42例和预后良好组118例,另选取同期56例单纯2型糖尿病（T2DM）患者作为T2DM组和47例体检健康者作为对照组。采用微量法和酶联免疫吸附试验法检测尿CP、KIM-1水平,并计算尿白蛋白/肌酐比值（UACR）和估算肾小球滤过率（eGFR）。通过Spearman相关性分析DKD患者尿CP、KIM-1与UACR、eGFR的相关性,单因素和多因素Logistic回归分析DKD患者预后不良的影响因素,受试者工作特征（ROC）曲线分析尿CP、KIM-1对DKD患者预后不良的预测价值。结果：随访3年,160例DKD患者有42例发展为ESRD,预后不良发生率为26.25％（42/160）。DKD组尿CP、KIM-1、UACR高于T2DM组、对照组,eGFR低于T2DM组、对照组（P＜0.05）;T2DM组尿CP、KIM-1、UACR高于对照组,eGFR低于对照组（P＜0.05）。Spearman相关性分析显示,DKD患者尿CP、KIM-1与UACR呈正相关（P均＜0.001）,与eGFR呈负相关（P均＜0.001）。多因素Logistic回归分析显示,高血压、DKD分期4期和糖化血红蛋白（HbA1c）（较高）、低密度脂蛋白胆固醇（LDL-C）（较高）、UACR（较高）、尿CP（较高）、尿KIM-1（较高）为DKD患者预后不良的独立危险因素（P＜0.05）,eGFR（较高）为独立保护因素（P＜0.05）。ROC曲线分析显示,尿CP、KIM-1联合预测DKD患者预后不良的曲线下面积大于各指标单独预测。结论：DKD患者尿CP、KIM-1升高与肾功能降低和预后不良密切相关,尿CP、KIM-1联合预测DKD患者预后不良的价值较高。