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.     

一种X煤在首钢的应用实践

针对当前优质炼焦煤资源越来越少，而高炉生产对焦炭质量指标要求越来越高的情况下，对具有低灰、高硫特点的X煤进行了系统的炼焦试验研究。结果发现，在炼焦生产中合理配加5%～8%的X煤不会造成焦炭硫分升高的不利影响，焦炭灰分下降明显，强度保持稳定。该研究成果成功应用于首钢炼焦生产，焦炭各项指标均达标，这不仅扩大了炼焦煤的使用范围，而且在资源使用方面为公司焦炭灰分的降低提供了支持。     

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”.     

30Cr13不锈钢冶炼过程夹杂物控制技术

  针对30Cr13生产过程中存在的轧材非金属夹杂物合格率偏低仅85%左右的问题，通过对30Cr13不锈钢精炼过程钢中非金属夹杂物存在形态进行分析，并结合现有精炼工艺制度，在实验室研究的基础上制定了不锈钢精炼过程非金属夹杂物控制方案。工业应用后，精炼结束钢中大于5 μm的非金属夹杂物总数、形状以及尺寸等参数均得到了有效改善，钢水洁净度大大提高。     

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.     

Hit to Leads with Cytotoxic Effect in Leukemic Cells: Total Synthesis Intermediates as a Molecule Treasure Chest

A previously designed and developed 12-step total synthesis that includes [1,1′-biphenyl]-2-amine and carbazole intermediates and that ultimately produces the carbazole alkaloid carbazomycin G was exploited as a screening compound library with the goal of identifying potential lead compound(s) with cytotoxic effect. These compounds were investigated by using in-vitro tests involving the two human cell lines HL-60 and MOLM-13, which both model acute myeloid leukaemia (AML). The in-vitro biological test results were used together with the molecular structures of the various intermediates in a concise SAR analysis. Several of the intermediates revealed cytotoxicity (IC₅₀<10⁻⁴ M), although the final natural product carbazomycin G did not reveal cytotoxicity versus the two said human cell lines.     

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.     

基于Parlay X的电信业务网关的研究

下一代网络对运营商而言更关键的地方在于它使高效、灵活的开发和部署各种丰富多彩的电信业务成为可能。本文介绍了开放业务接口ParlayX,对基于ParlayX的电信业务网关实现业务功能所采取的两种业务实现方式进行举例,并比较分析,说明了ParlayX电信业务网关在电信业务实现框架中所起到的作用。