Serotonin receptor 2B induces visceral hyperalgesia in rat model and patients with diarrhea-predominant irritable bowel syndrome

BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea(IBS-D)was investigated in the present study.AIM To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D.METHODS Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls.The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores.The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint.Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1(TRPV1)expression were examined following 5-HT2B receptor antagonist adminis-tration.Changes in visceral sensitivity after administration of the TRPV1 antago-INTRODUCTION Irritable bowel syndrome(IBS)is a chronic functional bowel disorder characterized by recurrent abdominal pain with altered bowel habits that affects approximately 15%of the population worldwide[1].IBS significantly impacts the quality of life of patients.Although the pathogenesis of IBS is not completely understood,the role of abnormal visceral sensitivity in IBS has recently emerged[2,3].5-Hydroxytryptamine(5-HT)is known to play a key role in the physiological states of the gastrointestinal tract.Plasma 5-HT levels in IBS with diarrhea(IBS-D)patients were greater than those in healthy controls[4],suggesting a possible role of 5-HT in the pathogenesis of IBS-D.The serotonin receptor 2(5-HT2 receptor)family comprises three subtypes:5-HT2A,5-HT2B,and 5-HT2c.All 5-HT2 receptors exhibit 46%-50%overall sequence identity,and all of these receptors preferentially bind to Gq/11 to increase inositol phosphates and intracellular calcium mobilization[5].5-HT2B receptors are widely expressed throughout the gut,and experimental evidence suggests that the primary function of 5-HT2B receptors is to mediate contractile responses to 5-HT through its action on smooth muscle[6].The 5-HT2B receptor is localized to both neurons of the myenteric nerve plexus and smooth muscle in the human colon.The 5-HT2B receptor mediates 5-HT-evoked contraction of longitudinal smooth muscle[6].These findings suggest that the 5-HT2B receptor could play an important role in modulating colonic motility,which could affect sensory signaling in the gut.Other laboratories have shown that the 5-HT2B receptor participates in the development of mechanical and formalin-induced hyperalgesia[7,8].A 5-HT2B receptor antagonist reduced 2,4,6-trinitrobenzene sulfonic acid(TNBS)and stress-induced visceral hyperalgesia in rats[9,10].However,the role of the 5-HT2B receptor in IBS-D patients and in acetic acid-and wrap restraint-induced IBS-D rat models was not investigated.

β-Arrestin-2 enhances endoplasmic reticulum stress-induced glomerular endothelial cell injury by activating transcription factor 6 in diabetic nephropathy

BACKGROUND Glomerular endothelial cell(GENC)injury is a characteristic of early-stage diabetic nephropathy(DN),and the investigation of potential therapeutic targets for preventing GENC injury is of clinical importance.AIM To investigate the role ofβ-arrestin-2 in GENCs under DN conditions.METHODS Eight-week-old C57BL/6J mice were intraperitoneally injected with streptozotocin to induce DN.GENCs were transfected with plasmids containing siRNA-β-arrestin-2,shRNA-activating transcription factor 6(ATF6),pCDNA-β-arrestin-2,or pCDNA-ATF6.Additionally,adeno-associated virus(AAV)containing shRNA-β-arrestin-2 was administered via a tail vein injection in DN mice.RESULTS The upregulation ofβ-arrestin-2 was observed in patients with DN as well as in GENCs from DN mice.Knockdown ofβ-arrestin-2 reduced apoptosis in high glucose-treated GENCs,which was reversed by the overexpression of ATF6.Moreover,overexpression ofβ-arrestin-2 Led to the activation of endoplasmic reticulum(ER)stress and the apoptosis of GENCs which could be mitigated by silencing of ATF6.Furthermore,knockdown ofβ-arrestin-2 by the administration of AAV-shRNA-β-arrestin-2 alleviated renal injury in DN mice.CONCLUSION Knockdown ofβ-arrestin-2 prevents GENC apoptosis by inhibiting ATF6-mediated ER stress in vivo and in vitro.Consequently,β-arrestin-2 may represent a promising therapeutic target for the clinical management of patients with DN.

绵竹蚕女墓与古蜀蚕丛国

绵竹蚕女墓及绵竹、广汉一带流传的“女化蚕”的故事,与《蜀王本纪》《华阳国志》等典籍以及近现代相关方志的佐证,再加上三星堆出土文物、甲骨文“蜀”字造形的印证,说明从岷山来到三星堆地区的古蜀人,是将植桑养蚕、缫丝制衣作为谋生立足的支柱产业的。所以人们将带领蜀人走出大山的部落首领称为蚕丛王。绵竹、绵远河也因着这些故事和兴盛的丝绸产业而得名。

流延茂金属线性低密度聚乙烯加工性能研究

利用ME30/9100V3流延膜机加工茂金属聚乙烯HPR3518CB,研究了加工温度、冷却温度、主机转速对茂金属线性低密度聚乙烯(mLLDPE)制品力学性能、光学性能的影响规律,结合实际加工表现确定了HPR3518CB的流延膜合适的加工窗口:机筒温度230~240℃,冷辊温度为20~25℃,挤出速率为20~30r/min。

基于BERT的中文新闻标题分类

为解决海量新闻标题分类任务准确率低的问题,提出了一种基于BERT的中文新闻标题分类算法。使用BERT预训练的词向量作为嵌入层,根据输入文本进一步优化词向量,使用单向GRU网络提取主要的文本特征,连接注意力机制,对特征加权求和来调整权重比例,连接单向LSTM网络提取上下文特征,进行分类。实验结果表明,BGAL模型在进行中文新闻标题分类任务时,可以有效兼顾分类精度和运算效率,在处理THUCNews数据集时,达到了94.78%的准确度,比BERT_RNN高出1.07%。

长链非编码RNA在非小细胞肺癌中的研究进展

非小细胞肺癌(non-small cell lung cancer,NSCLC)是肺癌的主要亚型之一,发病率和死亡率高,严重威胁人类健康。目前NSCLC的诊疗仍然面临诸多挑战,亟需探寻有效的治疗靶点和诊断、预后的生物标志物。长链非编码RNA(long noncoding RNA,lncRNA)是一种长度超过200个核苷酸的非编码RNA,对癌症的发生发展和诊疗具有重要意义。大量研究表明lncRNA在NSCLC中的异常调控,对肿瘤细胞的增殖、生长、发展起着重要的调节作用,对于NSCLC的诊断、治疗和预后具有潜在的临床应用价值。本文对lncRNA在NSCLC的发生发展、临床诊疗及预后中的研究进展作一综述。

基于地域特征的物流仓储中心逆向选址算法

物流仓储中心地址的选取,从根本上决定了物品出发地和运达地之间的距离,直接关系到物品能否被及时高效地运输,以及配送成本和仓储成本能否最小化。针对传统物流仓储中心选址求解算法脱离实际应用、且容易出现局部最优、求解速度较慢和注意力单一等问题。为减少物流配送时间,降低物流成本,切实提出选址解决方案,通过对K均值聚类算法和帝王蝶优化算法(Monarch butterfly optimization, MBO)进行改进,研究了京津冀地区物流仓储中心的选址问题。实验仿真结果表明:所提出的改进帝王蝶优化算法较其他优化算法在求解精度、收敛速度和迭代次数上均有优势,能够有效完成物流仓储中心选址问题,切实可以缩短物流配送距离,提高物流配送效率。

桂枝-白芍药对研究进展

桂枝-白芍为典型的相制配伍,源于《伤寒论》之桂枝汤,为临床常用的调和营卫、温通止痛药对,其研究主要包括:桂枝-白芍的配伍理论规律、临床应用及药效学效应、功效物质基础、桂枝-白芍药对的配伍作用机制等方面。目前,主要存在以下问题:(1)配伍效应的量化指标方面,应采用多学科交叉、基于多指标综合指数法的药对配伍效应整合法,系统科学评价桂枝-白芍药对配伍效应及量效关系。(2)机制研究方面,应基于体内吸收、分布、代谢及排泄过程,与网络药理学、代谢组学及生物分子技术结合,建立成分-效应关联,明确药对效应成分及靶器官、靶蛋白等,全面揭示桂枝-白芍不同用量比例配伍效应及机制。(3)药效物质基础研究方面,应用现代中药药效物质辨识技术和验证手段,如:选择性成分敲除、质量标志物分层三维整合、基于比较代谢组的药对配伍优效研究法等,揭示桂枝-白芍药对功效物质及作用机制。

Arsenic trioxide induces apoptosis of human gastrointestinal cancer cells

AIM: To investigate the changes in apoptosis in gastrointestinal cancer cells from patients with gastrointestinal cancers treated with arsenic trioxide (As2O3); and to study the possible molecular mechanisms of such changes by detecting the expression levels of p53 and Bcl-2.

Highly active and stable porous polymer heterogenous catalysts for decomposition of formic acid to produce H_2

Formic acid(FA)has attracted extensive attention as a hydrogen storage material.Here,we develop two heterogeneous catalysts based on porous organic polymers(POPs).After loading the Ru species,the catalyst bearing the triphenylphosphine ligand showed excellent performance in terms of activity and stability for the decomposition of FA to produce hydrogen.

Creation mechanism of electron-positron pair on equally spaced multiple localized fields

We investigate the electron-positron creation process from multiple equally spaced distributed oscillating electric fields.The computational quantum field theory(CQFT)is applied to analyze the effect of the number of local fields,the distance between them,and their potential height on the created particle number.It is found that whether adjacent electric fields overlap plays an important role.The creation rate exhibits a direct linear relationship with the number of fields when they do not overlap,but exceeds the sum of the rate when the fields alone.They exhibit a distinctly nonlinear relationship when they overlap,and in particular exhibit a quadratic relationship when the fields completely overlap.These phenomena corroborate that the particle pair creation in the interaction region is non-uniform and influenced by the strength of the central strongest electric field.

In situ doping brushite on zinc manganese oxide toward enhanced water oxidation performance: Mimicry of an oxygen‐evolving complex

We report in situ doping of brushite on zinc manganese oxide（ZMO）, fabricated by calcining a Mn（II） oxalate‐impregnated metal‐organic framework. The doping process was conducted in com‐bination with the photocatalytic water oxidation reaction which was catalyzed by ZMO in neutral phosphate‐buffered aqueous solution containing [Ru（bpy）3]^2＋‐Na2S2O8 and calcium（II） triflate salt, exhibiting greatly enhanced water oxidation performance with optimized turnover frequency of 0.18 mmol（O2） mol（Mn）^（–1） s^（–1）. Different analytical techniques indicated that photodeposited calci‐um‐phosphate（CaP） acted as a co‐catalyst to promote the O2 evolution activity of ZMO. This system involved the use of manganese oxide and calcium ion, and the operation was conducted under am‐bient temperature and neutral conditions, thus, it efficiently mimicked the oxygen‐evolving complex in photosystem II.

The structural, electronic, and optical properties of organic–inorganic mixed halide perovskites CH_3NH_3Pb(I_(1-y)X_y)_3(X = Cl, Br)

Methylammmonium lead iodide perovskites（CH3NH3PbI3） have received wide attention due to their superior optoelectronic properties. We performed first-principles calculations to investigate the structural, electronic, and optical properties of mixed halide perovskites CH3NH3Pb（I（1-y）Xy）3（X = Cl, Br; y = 0, 0.33, 0.67）. Our results reveal the reduction of the lattice constants and dielectric constants and enhancement of band gaps with increasing doping concentration of Cl-/Br-at I-. Electronic structure calculations indicate that the valance band maximum（VBM） is mainly governed by the halide p orbitals and Pb 6 s orbitals, Pb 6 p orbitals contribute the conduction band minimum（CBM） and doping does not change the direct semiconductor material. The organic cation [CH3NH3]~＋does not take part in the formation of the band and only one electron donates to the considered materials. The increasing trends of the band gap with Cl content from y = 0（0.793 eV） to y = 0.33（0.953 eV） then to y = 0.67（1.126 eV）. The optical absorption of the considered structures in the visible spectrum range is decreased but after doping the stability of the material is improving.

Aging Characteristics and Influencing Factors of the Sheds of Composite Insulators in Karst Regions of China

In recent years,more and more high-voltage overhead transmission lines were built passing through the karst regions in southwestern China.This type of special landform seems to have an adverse effect on the aging of the sheds of the line suspension composite insulators,which may lead to unexpected flashover and line tripping.In order to find out the particularity of the aging characteristics of insulators operating in the karst regions,samples in operation were selected from both the karst regions and the flatlands.Hydrophobicity,amount of surface contamination,and contaminant composition of the sheds were studied,then a comparison of performance between the two was made,and the possible influencing factors that cause such differences were discussed.The results show that the overall aging of the sheds of the composite insulators operating at the karst regions is more aggravated,which is caused by the combined influence of factors including the special topography,climate,and pollution in the area.The strong wind crossing the col will bring about the mutual scraping on the edges and stress concentration at the root of the sheds,leaving scratches and root cracks;the infiltration from these rupture of acid liquid,if any,will accelerate the aging and corroding of the internal silicone rubber material;moreover,the carbonates enriched on the surface of the sheds will gradually transform into more corrosive sulfates in an acidic environment,leading to further deterioration and chalking of the sheds of the insulators.The research work in this paper can provide guidance for the current operation and maintenance of composite insulators in the karst areas,as well as having important reference values for the layout design and insulation configuration of transmission lines to be built across karst landforms in the future.

Treatment Principles of Obesity with Chinese Herbal Medicine: Literature Analysis by Text Mining

Obesity represents a social health problem worldwide, associated with serious health risks and increased mortality. The prevalence of obesity is reported to be increasing in both developed and developing countries. Obesity is associated with a significant range of comorbidities and is linked with increases in mortality, thus the treatment of obesity is very important. Chinese herbal medicine (CHM) has been used for weight management both in China and in western countries for many years, the effectiveness and safety of CHMs in obesity have been proved. Yet the principles of treating obesity with CHMs are hard to manage due to the complexity of TCM theory. In this study, a novel text mining method was developed based on a comprehensive collection of literatures in order to explore the treatment principles more intuitively. Networks of TCM patterns and CHMs which are most frequently used in obesity treatment are built-up and analyzed, two major principles are explored in treating obesity: one is resolving phlegm and dampness, the other is clearing heat and reinforcing deficiency. These findings might guide the clinicians in treatment of obesity.

Design of Ca-type todorokite catalysts with highly active for the selective reduction of NO_(x) by NH_(3) at low temperatures

Ca-type todorokite catalysts were designed and prepared by a simple redox method and applied to the selective reduction of NO_(x) by NH_(3)(NH_(3)-SCR)for the first time.Compared with the Na-type manjiroite prepared by the same method,the todorokite catalysts with different Mn/Ca ratios showed greatly improved catalytic activity for NO_(x) reduction.Among them,Mn8Ca4 catalyst exhibited the best NH_(3)-SCR performance,achieving 90%NO_(x) conversion within temperature range of 70-275℃ and having a high sulphur resistance.Compared to the Na-type manjiroite sample,Ca-type todorokite catalysts possessed an increased size of tunnel,resulting in a larger specific surface area.As increased the amounts of Ca doping,the Na content in Ca-type todorokite catalysts significantly decreased,providing larger amounts of Bronsted acid sites for NH_(3) adsorption to produce NH_(4)^(+).The NH_(4)^(+)species were highly active for reaction with NO+O_(2),playing a determining role in NH_(3)-SCR process at low temperatures.Meanwhile,larger amounts of surface adsorbed oxygen contained over the Ca-doping samples than that over Na-type manjiroite,promoting the oxidation of NO and fast SCR processes.Over the Ca-type todorokite catalysts,furthermore,nitrates produced during the flow of NO+O_(2),were more active for reaction with NH_(3) than that over Na-type manjiroite,benefiting the occurrence of NH_(3)-SCR process.This study provides novel insights into the design of NH_(3)-SCR catalysts with high performance.

社区老年脑健康体检与痴呆风险筛查体系构建与实践——北京方案

2019年5月6日,"北京老年脑健康体检(痴呆风险筛查)项目启动及培训会"在北京师范大学举行,标志着北京市老年脑健康体检(痴呆风险筛查)项目正式启动.北京市东城区、西城区、朝阳区、海淀区、丰台区、石景山区共6个辖区内的9.6万名65岁以上常住老年人将免费接受脑健康体检服务.该项目由北京市卫生健康委员会立项,旨在通过结合老年痴呆早期发现、及时防治的主动健康管理理念,建立社区痴呆及轻度认知障碍(mild cognitive impairment,MCI)综合防控系统,提升北京市老年群体脑健康水平,同时也为政府在全国老年痴呆疾病领域的科学决策提供数据及技术支持.

基于氮,膦配体多孔有机聚合物材料的设计合成及其催化应用

多孔有机聚合物(porous organic polymers,POPs)是近年来涌现出的由纯粹的有机分子砌块,通过共价键连接而成的一类具有高比表面积、丰富的孔结构、低骨架密度和良好热稳定性的新型材料。而N,P配体在均相过渡金属络合物催化的氢甲酰化反应、偶联反应、加氢反应、硅氢加成反应,CO2环加成等反应中具有重要的应用,通过合理的设计和修饰N,P配体的电子效应和立体结构,可有效地调控目标产物的收率和选择性。得益于有机合成策略的多样性,POPs材料也具有合成路径及构建方式多样,可较为方便地在聚合物骨架中定点引入特定功能位点的特点,这为基于N,P配体均相过渡金属催化剂的多相化提供了全新的思路与契机。本文将对国内国外相关课题组及本课题组在基于N,P配体POPs材料的设计合成及其催化应用方面所做的工作进行简要的总结归纳,并对该方向进行相应的工业应用前景展望。

Research progress on synergistic anti-tumor mechanisms of compounds inTraditional Chinese Medicine

The curative effects of Chinese herbal compounds result from the coordination of numerous natural compounds.We aimed to review the mechanism of action of Traditional Chinese Medicine(TCM)compounds(TCMC),explore the rationality of formulation theory and synergistic effects in TCM compounds,and analyze the effectiveness of drug compatibility of TCMC in molecular biology.This literature review covers the mechanisms of the anti-tumor effects of compounds,and their synergistic antitumor mechanisms.We aim to provide reference for the effective development and use of natural resources and the organic combination of TCM and modern medicine using molecular biology.

Correlation between cold and hot pattern in traditional Chinese medicine and gene expression profiles in rheumatoid arthritis

Clinical manifestations of rheumatoid arthritis(RA)are diversified,and based on the manifestations,the patients with RA could be classified into different patterns under traditional Chinese medicine.These patterns decide the selection of herbal prescription,and thus they can help find a subset of rheumatoid arthritis patients for a type of therapy.In the present study,we combine genome-wide expression analysis with methods of systems biology to identify the functional gene networks for the sets of clinical symptoms that comprise the major information for pattern classification.Clinical manifestations in rheumatoid arthritis were clustered with factor analysis,and two factors(similar to cold and hot patterns in traditional Chinese medicine)were found.Microarray technology was used to reveal gene expression profiles in CD4^(+)T cells from 21 rheumatoid arthritis patients.Protein-protein interaction information for these genes from databases and literature data was searched.The highly-connected regions were detected to infer significant complexes or pathways in this protein-protein interaction network.The significant pathways and function were extracted from these subnetworks using the Biological Network Gene Ontology tool.The genes significantly related to hot and cold patterns were identified by correlations analysis.MAPK signalling pathway,Wnt signaling pathway,and insulin signaling pathway were found to be related to hot pattern.Purine metabolism was related to both hot and cold patterns.Alanine,aspartate,and tyrosine metabolism were related to cold pattern,and histindine metabolism and lysine degradation were related to hot pattern.The results suggest that cold and hot patterns in traditional Chinese medicine were related to different pathways,and the network analysis might be used for identifying the pattern classification in other diseases.