Time serial transcriptome reveals Cyp2c29 as a key gene in hepatocellular carcinoma development

Objective:Hepatocellular carcinoma(HCC)is a severely lethal cancer that usually originates from chronic liver injury and inflammation.Although progress on diagnosis and treatment is obvious,the cause of HCC remains unclear.In this study,we sought to determine key genes in HCC development.Methods:To identify key regulators during HCC progression,we performed transcriptome sequencing to obtain time series gene expression data from a mouse model with diethylnitrosamine-induced liver tumors and further verified gene expression and function in vitro and in vivo.Results:Among the differentially expressed genes,Cyp2c29 was continuously downregulated during HCC progression.Overexpression of Cyp2c29 suppressed N F-kB activation and proinflammatory cytokine production by increasing the production o f 14,15-epoxyeicosatrienoic acid in vitro.Furthermore,overexpression of Cyp2c29 in vivo protected against liver inflammation in mouse models of liver injury induced by both acetaminophen and CC14.Two human homologs of mouse Cyp2c29,CYP2C8 and CYP2C9,were found to be downregulated in human HCC progression,and their expression was positively correlated with overall survival in patients with HCC(significance:P=0.046 and 0.0097,respectively).Conclusions:Collectively,through systematic analysis and verification,we determined that C yp2c29 is a novel gene involved in liver injury and inflammation,which may be a potential biomarker for HCC prevention and prognosis determination.

Strong ozone production at a rural site in the North China Plain: Mixed effects of urban plumes and biogenic emissions

Regional ozone （O3） pollution has drawn increasing attention in China over the recent decade, but the contributions from urban pollution and biogenic emissions have not been clearly elucidated. To better understand the formation of the regional O3 problem in the North China Plain （NCP）, intensive field measurements of O3 and related parameters were conducted at a rural site downwind of Ji＇nan, the capital city of Shandong province, in the summer of 2013. Markedly severe 03 pollution was recorded, with the 03 mixing ratios exceeding the Chinese national ambient air quality standard on 28 days （a frequency of 78%） and with a maximum hourly value of 198 ppbv. Extensive regional transport of well-processed urban plumes to the site was identified. An observation-constrained chemical box model was deployed to evaluate in situ photochemical O3 production on two episodes. The results show that the in situ formation accounted for approximately 46% of the observed O3 accumulation, while the remainder （54%） was contributed by regional transport of the O3-laden urban plumes. The in situ ozone production was in a mixed controlled regime that reducing either NOx or VOCs would lead to a reduction of ozone formation. Biogenic VOCs played an important role in the local ozone formation. This study demonstrates the significant mixed effects of both anthropogenic pollution from urban zones and biogenic emission in rural areas on the regional 03 pollution in the NCP region, and may have general applicability in facilitating the understanding of the formation of secondary pollution over China.

Long-term exposure to titanium dioxide nanoparticles promotes diet-induced obesity through exacerbating intestinal mucus layer damage and microbiota dysbiosis

Titanium dioxide nanoparticles (TiO2-NPs) are commonly used as food additives, including some high-fat foods that are risk factors for obesity. However, little is known about the effects of chronic TiO2-NPs digestion in the population on high fat diet (HFD). Herein, we reported that TiO2-NPs exacerbated HFD-induced obesity by disruption of mucus layer and alterations of gut microbiota. Oral intake of TiO2-NPs significantly increased body weight, liver weight, and amount of adipose tissues, especially in HFD-fed mice. Mechanistic studies revealed TiO2-NPs induced colonic mucus layer disruption and obesity-related microbiota dysbiosis. The damage on mucus was demonstrated through down-regulation of Muc2 gene and the absorption of mucin protein by TiO2-NPs. Consequently, mucus layer damage combined microbiota dysbiosis escalated the low-grade systemic inflammation, which exacerbated HFD-induced obesity. In contrast, gut microbiota depletion eliminated these effects, indicating gut microbiota were necessary for TiO2-NPs-induced inflammation and obesity. All the results stated the alarming role of TiO2-NPs in the HFD-driven obesity and emphasized the reevaluating the health impacts of nanoparticles commonly used in daily life, particularly, in susceptible population.

STUDY ON THE CENTRALIZATION STRATEGY OF THE BLOOD ALLOCATION AMONG DIFFERENT DEPARTMENTS WITHIN A HOSPITAL

By far, the researches on how to distribute blood products among different departments in hospital have not been further studied, though the problem of blood shortage and wastage that caused by improper blood allocation is severe, which may endanger patient＇s lives and impose considerable costs on hospitals. In order to solve this problem, this paper mainly studies on how to distribute the blood items among different departments within a hospital and investigates the allocation approach with the novel management method by centralizing the inventory of several different departments. By integrating the blood inventory requirements of some departments, the hospital could reduce the rate of blood shortage and wastage effectively, release the pressure of the occupancy of resources and reduce the bullwhip effect of blood products. This paper illustrates the centralization principle in hospital and formulates the mixed integer programming model to work out the optimal allocation network scheme and the optimal inventory setting for every department. And the results of the numerical example demonstrate that this centralization method could considerably reduce blood shortage and wastage in hospital by about 72% and 90% respectively. Furthermore, it could decrease the total cost by about 108,540 RMB a month on blood supply chain management in the hospital and improve the effect of some certain surgeries by transfusing the fresh blood to patients.

Simulation modeling and optimization for ambulance allocation considering spatiotemporal stochastic demand

To ensure a timely response to emergencies,governments are obliged to implement effective ambulance allocation plans.In practice,an emergency medical service(EMS)system works in an uncertain environment,with stochastic demand,response-times,and travel-times.This uncertainty significantly affects ambulance allocation planning.How-ever,few studies in this field adequately consider the effect of spatiotemporal uncertainty in demand,because it is difficult to measure it quantitatively.As a result,few analytic models capture the dynamic nature of an EMS system and,thus,the allocation plans they generate are not efficient in practice.Therefore,this study proposes a simulation-based optimization method for ambulance allocation.A simulation model is constructed to mimic the operational processes of an EMS system,and to evaluate the performance of an ambulance allocation plan in an uncertain environment.Gaussian mixture model clus-tering is used to derive the uncertain spatial demand.Then,the simulation generates emergency demand based on the obtained spatial distribution.A Gaussian-process-based search algorithm is used together with the simulation model to identify optimal solutions.To validate the proposed method,a case study is conducted using data on emergency patients in the Shanghai Songjiang District.Compared with the current plan adopted in Songjiang,the experimental results demonstrate that the delay time and frequency of the EMS system can be reduced significantly by employing the proposed methods.Further-more,nearly 41%of the allocation cost can be saved.

基于核苷酸配合物的多级手性的研究进展

手性是自然界中普遍存在的一种特殊对称性.生物体展示了跨多尺度的手性信息与传递的功能.研究多级手性的传递、诱导与放大是涉及化学、生物、物理、材料等多个学科的基本科学问题.从分子手性到宏观手性可在不同的长度与尺度下分为四个层级:构型(分子)手性(一级)、构象手性(二级)、相手性(三级)、宏观手性(四级).基于核苷酸配位超分子组装体的X射线单晶结构研究并结合固(晶)态圆二色谱分析方法是研究多级手性问题的有效途径.深刻认识与理解多尺度的手性组装、手性诱导与手性传递不仅有助于我们认识生物体的结构与功能的关系,而且还为合理设计与合成手性功能材料与人工分子机器提供理论基础.本文基于本课题组在核苷酸手性配位超分子组装体方面的研究成果,阐述了一种有效研究构象手性与相手性的方法,即X射线单晶衍射技术与固态圆二色光谱相关联的手性研究方法.首次将有机化学中的轴手性拓展至一维配位聚合物中而创新地提出“拓展轴手性”的概念.在精确晶体结构数据分析的基础上,揭示了金属配位键、氢键、π-π堆积作用等在手性诱导、手性组装和手性传递等方面的作用.同时,对未来手性研究提出了展望.