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”.     

Assessing students' conceptual understanding using an online three‐tier diagnostic test

When solving a mathematical problem, students who do not have sufficient conceptual understanding may perform poorly and exhibit misconceptions. This study was aimed to examine students' conceptual understanding and significant misconceptions when solving number sense‐related problems. An online three‐tier diagnostic test was administered to 125 fifth‐grade students with varied socio‐economic backgrounds in Hong Kong. Only 14.40% of the students exhibited high performance with high confidence, indicating that these students had a profound conceptual understanding of number sense. In addition, the majority of the students (66.40%) did not demonstrate number sense; these students exhibited several significant misconceptions and could solve the questions only by using a rule‐based method or guessing. Accordingly, most students performed unsatisfactorily on number sense‐related problems. This study is imperative in identifying early predictors and provides information for further compatible interventions in the teaching and learning of number sense in Hong Kong in particular and worldwide in general.     

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.     

Low cycle fatigue behavior of a eutectic 80Au/20Sn solder alloy

The eutectic 80Au/20Sn solder alloy is widely used in high power electronics and optoelectronics packaging. In this study, low cycle fatigue behavior of a eutectic 80Au/20Sn solder alloy is reported. The 80Au/20Sn solder shows a quasi-static fracture characteristic at high strain rates, and then gradually transforms from a transgranular fracture (dominated by fatigue damage) to intergranular fracture (dominated by creep damage) at low strain rates with increasing temperature. Coffin-Manson and Morrow models are proposed to evaluate the low cycle fatigue behavior of the 80Au/20Sn solder. Besides, the 80Au/20Sn solder has enhanced fatigue resistance compared to the 63Sn/37Pb solder.     

燃气热水器在无回水管水路中实现零冷水的方案研究

本文分析了燃气热水器行业针对无回水管水路系统实现零冷水功能的现有技术方案,指出现有技术方案存在的一些缺陷,并结合试验研究,对无回水管水路系统提出了一套全新的实现零冷水功能的技术解决方案。     

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.     

浅析火力发电厂汽水系统中内径管与外径管的设计选择

按照管道加工工艺的不同,管道可分为内径控制管和外径控制管。通过热轧工艺生产的外径控制无缝钢管,可满足火力发电厂汽水系统中绝大部分管道的使用要求。对于超(超)临界机组的主蒸汽和高温再热蒸汽管道采用的P91/P92材质的大口径厚壁无缝钢管,由于对材料性能和加工工艺有特殊要求,因此宜采用内径控制管。     

Unsteady free convection of second‐grade nanofluid with a new time‐space fractional heat conduction

The Caputo and Caputo–Fabrizio derivative are applied to study a second‐grade nanofluid over a vertical plate. A comparative analysis is presented to study the unsteady free convection of a second‐grade nanofluid with a new time–space fractional heat conduction. The governing equations with mixed time–space fractional derivatives are non‐dimensionalized and solved numerically, and a comparison between the Caputo and the Caputo–Fabrizio models is made. It is found that the temperature is higher for the Caputo–Fabrizio fractional model than the Caputo model, but the higher velocity only exists near the vertical plate for the Caputo–Fabrizio model than the Caputo model. Moreover, the velocity for the Caputo model will exceed the Caputo–Fabrizio model as y evolves.