In Vivo Electrophysiology of Peptidergic Neurons in Deep Layers of the Lumbar Spinal Cord after Optogenetic Stimulation of Hypothalamic Paraventricular Oxytocin Neurons in Rats

The spinal ejaculation generator (SEG) is located in the central gray (lamina X) of the rat lumbar spinal cord and plays a pivotal role in the ejaculatory reflex. We recently reported that SEG neurons express the oxytocin receptor and are activated by oxytocin projections from the paraventricular nucleus of hypothalamus (PVH). However, it is unknown whether the SEG responds to oxytocin in vivo. In this study, we analyzed the characteristics of the brain–spinal cord neural circuit that controls male sexual function using a newly developed in vivo electrophysiological technique. Optogenetic stimulation of the PVH of rats expressing channel rhodopsin under the oxytocin receptor promoter increased the spontaneous firing of most lamina X SEG neurons. This is the first demonstration of the in vivo electrical response from the deeper (lamina X) neurons in the spinal cord. Furthermore, we succeeded in the in vivo whole-cell recordings of lamina X neurons. In vivo whole-cell recordings may reveal the features of lamina X SEG neurons, including differences in neurotransmitters and response to stimulation. Taken together, these results suggest that in vivo electrophysiological stimulation can elucidate the neurophysiological response of a variety of spinal neurons during male sexual behavior.     

Functional Coupling of Slack Channels and P2X3 Receptors Contributes to Neuropathic Pain Processing

The sodium-activated potassium channel Slack (K_Na1.1, Slo2.2, or Kcnt1) is highly expressed in populations of sensory neurons, where it mediates the sodium-activated potassium current (I_KNa) and modulates neuronal activity. Previous studies suggest that Slack is involved in the processing of neuropathic pain. However, mechanisms underlying the regulation of Slack activity in this context are poorly understood. Using whole-cell patch-clamp recordings we found that Slack-mediated I_KNa in sensory neurons of mice is reduced after peripheral nerve injury, thereby contributing to neuropathic pain hypersensitivity. Interestingly, Slack is closely associated with ATP-sensitive P2X3 receptors in a population of sensory neurons. In vitro experiments revealed that Slack-mediated I_KNa may be bidirectionally modulated in response to P2X3 activation. Moreover, mice lacking Slack show altered nocifensive responses to P2X3 stimulation. Our study identifies P2X3/Slack signaling as a mechanism contributing to hypersensitivity after peripheral nerve injury and proposes a potential novel strategy for treatment of neuropathic pain.     

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.     

Effects of sintering temperature and Bi2O3, Y2O3 and MgO co-doping on the dielectric properties of X8R BaTiO3-based ceramics

Bi₂O₃, Y₂O₃ and MgO co-doped BaTiO₃ (BT)-based X8R ceramics were synthesized successfully for the first time. The effects of the sintering temperature and Bi₂O₃, Y₂O₃ and MgO dopants on the dielectric properties were investigated systematically. Bi₂O₃ doping can increase the Curie temperature (T_c), but reduces the overall dielectric permittivity. On the other hand, Y₂O₃ doping is beneficial to the formation of core-shell microstructure and the increase of T_c, whereas MgO can prevent excessive Y₂O₃ from diffusing into grain core, and thereby further contributes to the generation of the core–shell microstructure. The generation of the typical core-shell microstructure was confirmed and investigated in detail by using transmission electron microscopy (TEM). It is argued that the synergistic effects of Bi₂O₃, Y₂O₃ and MgO co-doping in terms of the formation of the core-shell structure and the increase of T_c, can help improve the temperature stability of the dielectric permittivity effectively. Increasing the sintering temperature leads to an increase in the grain size, which in turn leads to an increase in the overall dielectric permittivity due to the grain size effect.     

The corrosion behavior and mechanism of X65 steel induced by iron‐oxidizing bacteria in the seawater environment

The corrosion behavior and mechanism of iron‐oxidizing bacteria (IOB) on X65 steel in seawater are studied. This study uses the methods of weight loss, electrochemical measurements, and surface analysis. The results show that the IOB increases the corrosion damage degree of steel. Pittings are observed in the medium with IOB. The potentiodynamic polarization curves show that the anodic reaction rate is accelerated in the corrosion process of IOB. The synergies in corrosion between the metal surface, abiotic corrosion products, and bacterial cells, and the pitting corrosion mechanism of X65 steel are discussed.     

双相区加速冷却处理对X80管线钢组织与性能的影响

采用双相区加速冷却法(加速冷却始冷温度为700 ℃)对X80管线钢进行热处理,获得了贝氏体和铁素体(B+F)双相组织。然后通过组织表征、力学性能测试以及在3.5wt%NaCl溶液中的耐蚀性进行研究。结果表明:热处理后获得的管线钢组织由板条状贝氏体、多边形铁素体及少量马氏体/奥氏体岛组成。与热处理前相比,(B+F)双相管线钢屈强比较低,为0.65,初始加工硬化指数为0.31,均匀伸长率达8.3%,塑性显著提升;双相组织中含有52.4%的铁素体,因而耐腐蚀性明显提高。通过双相区加速冷却法获得的(B+F)两相组织在塑变过程中发生协调变形,可以适应大变形的需求,同时耐蚀性优异,为大变形管线钢实际生产提供一定的借鉴。     

厚壁X80管线钢管不同壁厚处的低温拉伸性能研究

为了研究厚壁X80管线钢管不同壁厚处的显微组织与低温环境下拉伸性能的关系，利用光学显微镜、电伺服拉伸试验机和低温试验箱等分析手段对壁厚为32.1 mm的X80管线钢管的显微组织和拉伸性能进行了分析。试验结果表明:由于X80管线钢管壁厚较厚，显微组织在厚度方向上的整体均匀性较差，中心层的组织晶粒度与外层相比较为粗大。温度由20 ℃下降至－60 ℃时，3组试样的抗拉强度、屈服强度均有上升趋势；在同一温度下，3组试样强度由大到小的顺序为:外层＞内层＞中心。     

Design,Synthesis, and in vitro Evaluation of P2X7 Antagonists

The P2X7 receptor is a promising target for the treatment of various diseases due to its significant role in inflammation and immune cell signaling. This work describes the design, synthesis, and in vitro evaluation of a series of novel derivatives bearing diverse scaffolds as potent P2X7 antagonists. Our approach was based on structural modifications of reported (adamantan-1-yl)methylbenzamides able to inhibit the receptor activation. The adamantane moieties and the amide bond were replaced, and the replacements were evaluated by a ligand-based pharmacophore model. The antagonistic potency of the synthesized analogues was assessed by two-electrode voltage clamp experiments, using Xenopus laevis oocytes that express the human P2X7 receptor. SAR studies suggested that the replacement of the adamantane ring by an aryl-cyclohexyl moiety afforded the most potent antagonists against the activation of the P2X7 cation channel, with analogue 2-chloro-N-[1-(3-(nitrooxymethyl)phenyl)cyclohexyl)methyl]benzamide ( 56 ) exhibiting the best potency with an IC₅₀ value of 0.39 μM.     

X80钢JCOE制管过程应变强化规律及其影响因素研究

为了探究X80钢制管过程中应变强化规律及其影响因素，采用厚度22 mm不同厂家生产的6种X80热轧钢板，以相同的JCOE制管工艺生产出 Φ1 219 mm×22 mm规格钢管，并对6种钢板的拉伸性能以及钢板、钢管拉伸性能差异进行了检测。根据检测结果，从化学成分、显微组织等方面分析了制管前后拉伸性能变化的影响因素。分析结果显示，X80钢制管后屈服强度、屈强比有较大幅度的升高，不同材料的升高幅度不同。研究表明，拉伸性能的变化与合金成分无明显的规律，主要与显微组织有关。