The Multifaceted Mas-Related G Protein-Coupled Receptor Member X2 in Allergic Diseases and Beyond

Recent research on mast cell biology has turned its focus on MRGPRX2, a new member of the Mas-related G protein-coupled subfamily of receptors (Mrgprs), originally described in nociceptive neurons of the dorsal root ganglia. MRGPRX2, a member of this group, is present not only in neurons but also in mast cells (MCs), specifically, and potentially in other cells of the immune system, such as basophils and eosinophils. As emerging new functions for this receptor are studied, a variety of both natural and pharmacologic ligands are being uncovered, linked to the ability to induce receptor-mediated MC activation and degranulation. The diversity of these ligands, characterized in their human, mice, or rat homologues, seems to match that of the receptor’s interactions. Natural ligands include host defense peptides, basic molecules, and key neuropeptides such as substance P and vasointestinal peptide (known for their role in the transmission of pain and itch) as well as eosinophil granule-derived proteins. Exogenous ligands include MC secretagogues such as compound 48/80 and mastoparan, a component of bee wasp venom, and several peptidergic drugs, among which are members of the quinolone family, neuromuscular blocking agents, morphine, and vancomycin. These discoveries shed light on its capacity as a multifaceted participant in naturally occurring responses within immunity and neural stimulus perception, as in responses at the center of immune pathology. In host defense, the mice Mrgprb2 has been proven to aid mast cells in the detection of peptidic molecules from bacteria and in the release of peptides with antimicrobial activities and other immune mediators. There are several potential actions described for it in tissue homeostasis and repair. In the realm of pathologic response, there is evidence to suggest that this receptor is also involved in chronic inflammation. Furthermore, MRGPRX2 has been linked to the pathophysiology of non-IgE-mediated immediate hypersensitivity drug reactions. Different studies have shown its possible role in other allergic diseases as well, such as asthma, atopic dermatitis, contact dermatitis, and chronic spontaneous urticaria. In this review, we sought to cover its function in physiologic processes and responses, as well as in allergic and nonallergic immune disease.     

Graphite Oxide and Aromatic Amines: Size Matters

Experimental and theoretical studies are performed in order to illuminate, for first time, the intercalation mechanism of polycyclic aromatic molecules into graphite oxide. Two representative molecules of this family, aniline and naphthalene amine are investigated. After intercalation, aniline molecules prefer to covalently connect to the graphene oxide matrix via chemical grafting, while napthalene amine molecules bind with the graphene oxide surface through π–π interactions. The presence of intercalated aromatic molecules between the graphene oxide layers is demonstrated by X‐ray diffraction, while the type of interaction between graphene oxide and polycyclic organic molecules is elucidated by X‐ray photoelectron spectroscopy. Combined quantum mechanical and molecular mechanical calculations describe the intercalation mechanism and the aniline grafting, rationalizing the experimental data. The present work opens new perspectives for the interaction of various aromatic molecules with graphite oxide and the so‐called “intercalation chemistry”.     

X射线干涉光刻光束线关键光学元件热-结构耦合分析

为了保证上海光源X射线干涉光刻光束线的稳定性,减小热变形对实验结果的影响,对X射线干涉光刻光束线的3个关键光学元件——偏转镜、聚焦镜和精密四刀狭缝进行热-结构耦合分析。首先,计算偏转镜、聚焦镜和精密四刀狭缝所承载的功率密度;然后,建立其有限元模型;最后,获得光学元件的温度场和热变形的结果。结果表明,偏转镜和聚焦镜采用间接水冷方式可有效抑制热变形,冷却后的最大面形误差分别为7.2μrad和9.2μrad。精密四刀狭缝未冷却时,刀片组件温度介于271.56~273.27℃,刀口热变形为0.19 mm,直线导轨热变形为0.08 mm;经过铜辫子冷却后,刀片组件温度降至22.24~23.94℃,刀口热变形降至0.2μm,直线导轨热变形降至0.1μm;采用影像法和接触探头法测试后,刀口直线度、平行度和重复精度均满足技术要求。偏转镜、聚焦镜和精密四刀狭缝的热变形通过间接水冷和铜辫子的冷却方式可以得到很大程度的抑制,进而保证光斑质量。     

Dihydrotanshinone,a Natural Diterpenoid,Preserves Blood-Retinal Barrier Integrity via P2X7 Receptor

Activation of P2X7 signaling, due to high glucose levels, leads to blood retinal barrier (BRB) breakdown, which is a hallmark of diabetic retinopathy (DR). Furthermore, several studies report that high glucose (HG) conditions and the related activation of the P2X7 receptor (P2X7R) lead to the over-expression of pro-inflammatory markers. In order to identify novel P2X7R antagonists, we carried out virtual screening on a focused compound dataset, including indole derivatives and natural compounds such as caffeic acid phenethyl ester derivatives, flavonoids, and diterpenoids. Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) rescoring and structural fingerprint clustering of docking poses from virtual screening highlighted that the diterpenoid dihydrotanshinone (DHTS) clustered with the well-known P2X7R antagonist JNJ47965567. A human-based in vitro BRB model made of retinal pericytes, astrocytes, and endothelial cells was used to assess the potential protective effect of DHTS against HG and 2′(3′)-O-(4-Benzoylbenzoyl)adenosine-5′-triphosphate (BzATP), a P2X7R agonist, insult. We found that HG/BzATP exposure generated BRB breakdown by enhancing barrier permeability (trans-endothelial electrical resistance (TEER)) and reducing the levels of ZO-1 and VE-cadherin junction proteins as well as of the Cx-43 mRNA expression levels. Furthermore, HG levels and P2X7R agonist treatment led to increased expression of pro-inflammatory mediators (TLR-4, IL-1β, IL-6, TNF-α, and IL-8) and other molecular markers (P2X7R, VEGF-A, and ICAM-1), along with enhanced production of reactive oxygen species. Treatment with DHTS preserved the BRB integrity from HG/BzATP damage. The protective effects of DHTS were also compared to the validated P2X7R antagonist, JNJ47965567. In conclusion, we provided new findings pointing out the therapeutic potential of DHTS, which is an inhibitor of P2X7R, in terms of preventing and/or counteracting the BRB dysfunctions elicited by HG conditions.     

Eu@C86 isomers: Calculated relative populations

Abstract

Relative populations of four energy-lowest IPR (isolated-pentagon-rule) isomers of Eu@C₈₆ are computed using the Gibbs energy based on characteristics from density functional theory calculations (M06-2X/3-21G?～?SDD entropy term, M06-2X/6-31G*～SDD or B2PLYP(D)/6-31G*～SDD energetics). The calculations confirm that the recently isolated Eu@C₁(7)-C₈₆ species is a major isomer in a relevant temperature region. Relationship to the empty C₈₆ cages is discussed, too.     

Matrix influence on the piezoelectric properties of piezoelectric ceramic/polymer composite exhibiting particle alignment

This study was addressed to the influence of an electric field strength applied at fabrication process and matrix properties, such as the dielectric constant and the Young's modulus, on “pseudo‐1‐3 piezoelectric ceramic/polymer composite” in order to further enhance the piezoelectricity of that. The pseudo‐1‐3 piezoelectric ceramic/polymer composite consists of linearly ordered piezoelectric ceramic particles in polymer material. Silicone gel, silicone rubber, urethane rubber, and poly‐methyl‐methacrylate, which exhibit different dielectric constants and Young's modulus, were used as matrices to evaluate the matrix influence. The piezoelectricity of the pseudo‐1‐3 piezoelectric ceramic/polymer composite was evaluated using the piezoelectric strain constant d₃₃. The d₃₃ is one of the indices of the piezoelectric properties for piezoelectric materials. As a result, it was confirmed that d₃₃ of the pseudo‐1‐3 piezoelectric ceramic/polymer composite increased with the increase of the electric filed strength applied at fabrication process, though, it reached a constant value at a certain strength value. Further it was confirmed that dielectric constant of the matrix had a small influence on d₃₃ of the pseudo‐1‐3 piezoelectric ceramic/polymer composite, however, in case of matrix of lower Young's modulus, d₃₃ was increase. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41817.     

X80焊管H_2S环境应力腐蚀开裂行为研究

采用三点弯曲加载法和微电极扫描测试技术,研究了X80高强度级管线钢及其焊缝区的抗H2S环境应力腐蚀开裂(SSCC)行为。测定了焊接接头的显微硬度分布,分析了显微组织结构、力学性能及抗腐蚀性能之间的相关性。研究表明,热影响区(HAZ)对应力腐蚀开裂最为敏感,母材的纵向和横向取样对应力腐蚀敏感性影响不显著,薄壁管材比厚壁管材有较好的抗H2S环境应力腐蚀性能。HAZ晶粒粗大、硬度高,局部腐蚀倾向大,由此导致该区SSCC敏感性高。     

校园网宿舍网络管理模式的探讨

讨论了高校学生宿舍区网络的特点，结合天津商学院校园网的实践，讨论了校园网宿舍网络管理的模式。     

磷钨酸乙醇染色法在嗜铬颗粒电镜X射线显微分析中的应用

通过比较常规透射电镜制样法、快速冷冻固定－冷冻超薄切片法及磷钨酸乙醇（EPTA）染色法在嗜铬颗粒透射电镜X射线显微分析中的应用，发现磷钨酸乙醇染色法能使嗜铬颗粒电子着色，从而较好地显示嗜铬颗粒的超微结构。同时磷钨酸乙醇染色法也以在一定程度上原位保留生物样品中元素，可以应用于检测样品元素含量的变化或比较样品元素含量的组间差别，提示磷钨酸乙醇染色法是一种可应用于透射电镜X射线显微分析的经济简便的生物样品制备方法。     

Si1-xGex/Si应变材料的生长及热稳定性研究

利用分子束外延（MBE）技术生长了Ge组份为0.1-0.46的Si1-xGex外延层。X射线衍射线测试表明，SiGe/Si异质结材料具有良好的结晶质量和陡峭界面，其它参数与可准确控制。通过X射线双晶衍射摆曲线方法，研究了经700℃、800℃和900℃退火后应变SiGe/Si异质结材料的热稳定性。结果表明，随着退火温度的提高，应变层垂直应变逐渐减小，并发生了应变弛豫，导致晶体质量退化；且Ge组分越小，Si1-xGex应变结构的热稳定性越好；室温下长时间存放的应变材料性能稳定。