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Major depressive disorder is the most common mental disorder with significant economic burden and limited treatments. Acupuncture has emerged as a promising non-pharmacological treatment for reducing depressive symptoms. However, the potential mechanisms and clinical effectiveness of acupuncture are not fully understood. This review aimed to: (1) summarize the available evidence on the mechanisms and clinical effectiveness of acupuncture for depression, and then (2) compare with pharmacological interventions, guiding future studies. Studies with animal models of depression and patients have shown that acupuncture could increase hippocampal and network neuroplasticity and decrease brain inflammation, potentially to alleviating depressive disorders. Overall clinical studies indicated that acupuncture could relieve primary depression, particularly milder cases, and was helpful in the management of post-stroke depression, pain-related depression, and postpartum depression both as an isolated and adjunct treatment. It was emphasized that acupuncture combined with antidepressant pharmacological treatment not only enhanced the improvement of primary and secondary depressive symptoms but also reduced the side effects of the medical treatment, which is the main cause for high dropout rates with drug treatment. In summary, substantial evidence from animal and human researches supported the beneficial effect of acupuncture in depression. However, most clinical trials of acupuncture were small, and it is unclear whether their findings can be generalized, so more studies are needed.

The effects of TiB2 and Zr on the microstructure, aging response and mechanical properties of hot-extruded Al–Zn–Mg–Cu based materials were investigated and compared by multi-scale microstructure characterization techniques. The results showed that proper addition of TiB2 particles could refine grain size during solidification, promote dynamic recrystallization during extrusion, and inhibit grain growth during solution treatment. Meanwhile, Zr addition had minor influence on the grain refinement during solidification, but could effectively suppress recrystallization and grain growth compared with the Zr-free alloy. Furthermore, the TiB2 addition could simultaneously enhance the aging kinetics and peak-aged hardness of the materials. Comparatively, Zr addition could also improve the peak-aged hardness with minor effect on the aging kinetics of the materials. Finally, the quench sensitivity, elastic modulus and tensile properties of the materials were compared and studied. Specifically, the relationship between the microstructure and mechanical properties, and the strengthening mechanisms were discussed in detail.

Inflammatory cytokines produced by muscularis macrophages largely contribute to the pathological signs of postoperative ileus (POI). Electroacupuncture (EA) can suppress inflammation, mainly or partly via activation of vagal efferent. The goal of this study was to investigate the mechanisms by which EA stimulation at an hindlimb region ameliorates inflammation in POI. Methods: Intestinal motility and inflammation were examined after 24 h after intestinal manipulation (IM)-induced POI in mice. Local immune response in the intestinal muscularis, expression of macrophages, α7 nicotinic acetylcholine receptor (α7nAChR), Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) were determined by flow cytometry, Western Blot, qPCR and immunofluorescence. The effects of α7nAChR antagonists (methyllycaconitine and α-bungarotoxin) and JAK2/STAT3 inhibitors (AG490 and WP1066) were also administered in a subset of mice prior to EA. In the parasympathetic pathways, intestinal motility and inflammation were determined after cervical vagotomy and sub-diaphragmatic vagotomy. The expression of gamma absorptiometry aminobutyric acid (GABAA) receptor in dorsal motor nucleus of vagal (DMV) cholinergic neurons was assessed by immunofluorescence and the response to DMV microinjection of bicuculine (antagonist of GABAA receptor) or muscimol (agonist of GABAA receptor) were assessed. Results: EA suppressed intestinal inflammation and promoted gastrointestinal motility. Mechanistically, EA activated the α7nAChR-mediated JAK2/STAT3 signaling pathway in macrophages which reduced the production of inflammatory cytokines. Furthermore, we also demonstrated that hindlimb region stimulation drove vagal efferent output by inhibiting the expression of GABAA receptor in DMV to ameliorate inflammation. Conclusions: The present study revealed that EA of hindlimb regions inhibited the expression of GABAA receptor in DMV neurons, whose excited vagal nerve, in turn suppressed IM-induced inflammation via activation of α7nAChR-mediated JAK2/STAT3 signaling pathway.

The current clinical evidence and underlying mechanisms of acupuncture and moxibustion in the treatment of irritable bowel syndrome (IBS) were summarized, so as to better optimize clinical treatment. The relevant articles of acupuncture and moxibustion in the treatment of IBS in recent years were retrieved and summarized. We found that the clinical efficacy of acupuncture and moxibustion in the treatment of IBS was relatively reliable. However, the mutual relationships among various mechanisms of action such as abnormal gastrointestinal motility, high visceral sensitivity, intestinal microenvironment disorders, and abnormal intestinal-brain interactions need to be further explored. The authors believe that in-depth explorations of the bidirectional regulation of "gut-brain axis", the law of changes in the abundance and diversity of intestinal flora, and the establishment of a more ideal animal model of TCM syndrome differentiation are useful ideas for subsequent research.对当前针灸治疗肠易激综合征（IBS）的临床证据及内在机制进行总结，进而更好地优化临床治疗。检索并梳理近年来针灸治疗IBS的相关文献，发现针灸疗法的临床疗效较为明确，但其胃肠道动力异常、内脏高敏感性、肠道微环境失调和肠脑互动异常等多种作用机制间的相互关系还需进一步探讨。笔者认为深度挖掘 “肠-脑轴”的双向调节作用、肠道菌群丰富度及多样性的变化规律、建立更理想的中医辨证动物模型等是后续研究深入探讨的思路。.

To investigate the involvement of peripheral adenosine receptors in the effect of electroacupuncture (EA) on visceral pain in mice with inflammatory bowel disease (IBD). 2,4,6-Trinitrobenzene sulfonic acid (TNBS) was used to induce the visceral pain model. EA (1 mA, 2 Hz, 30 min) treatment was applied to bilateral acupoints “Dachangshu” (BL25) 1 day after TNBS injection once daily for 7 consecutive days. Von Frey filaments were used to measure the mechanical pain threshold. Western blot was used to detect the protein expression levels of adenosine 1 receptor (A1R), adenosine 2a receptor (A2aR), adenosine 2b receptor (A2bR), adenosine 3 receptor (A3R), substance P (SP), and interleukin 1 beta (IL-1β) in colon tissue. EA significantly ameliorated the disease-related indices and reduced the expression of SP and IL-1β in the colon tissues of mice with IBD. EA increased the expression of A1R, A2aR, and A3R and decreased the expression of A2bR in the colon tissue. Furthermore, the administration of adenosine receptor antagonists influenced the effect of EA. EA can inhibit the expression of the inflammatory factors SP and IL-1β by regulating peripheral A1, A2a, A2b, and A3 receptors, thus inhibiting visceral pain in IBD mice. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11302-019-09655-4) contains supplementary material, which is available to authorized users.

D-ring modified glucocorticoids are attractive synthetic targets owing to their broad application in medicinal chemistry. Herein, we reported a practical synthesis of 16α-bromo-17α-hydroxysteroids from easily available 16β-bromo isomers via a Raney Ni-catalyzed bromide exchange reaction. The catalytic Finkelstein-type reaction features high yield, mild reaction condition, short reaction time and simple operation. The method provided an efficient approach to prepare 17α-hydroxy-15-pregnen-20-ones.

Purpose: We determined whether electroacupuncture (EA) reduces Netrin-1-induced myelinated primary afferent nerve fiber sprouting in the spinal cord and pain hypersensitivity associated with postherpetic neuralgia (PHN) through activation of μ-opioid receptors. Methods: PHN was induced by systemic injection of resiniferatoxin (RTX) in rats. Thirty-six days after RTX injection, a μ-opioid receptor antagonist, beta-funaltrexamine (β-FNA) or a κ-opioid receptor antagonist, nor Binaltorphimine (nor-BNI), was injected intrathecally 30 mins before EA, once every other day for 4 times. Mechanical allodynia was tested with von Frey filaments. The protein expression level of Netrin-1 and its receptors (DCC and UNC5H2) were quantified by using western blotting. The myelinated primary afferent nerve fiber sprouting was mapped with the transganglionic tracer cholera toxin B-subunit (CTB). Results: Treatment with 2 Hz EA at “Huantiao” (GB30) and “Yanglingquan” (GB34) decreased the mechanical allodynia at 22 days and the myelinated primary afferent nerve fiber preternatural sprouting into the lamina II of the spinal dorsal horn at 42 days after RTX injection. Also, treatment with 2 Hz EA reduced the protein levels of DCC and Netrin-1 and promoted the expression of UNC5H2 in the spinal dorsal horn 42 days after RTX injection. Furthermore, the μ-opioid receptor antagonist β-FNA, but not the κ-opioid receptor antagonist nor-BNI, reversed the effect of EA on neuropathic pain caused by RTX. In addition, morphine inhibited the Netrin-1 protein level induced by RTX in SH-SY5Y cells. Conclusions: Through activation of μ-opioid receptors, treatment with EA reduces the expression level of DCC and Netrin-1 and changes a growth-permissive environment in spinal dorsal horn into an inhibitory environment by increasing UNC5H2, thus decreasing RTX-caused primary afferent nerve sprouting in the spinal dorsal horn and neuropathic pain.

In this study, pharmaceutically relevant quinazoline-2,4(1H,3H)-diones were synthesized eco-efficiently by cycloaddition of CO2 and 2-aminobenzonitrile in water, catalyzed by melamine as a thermoregulated catalyst. Quinazoline-2,4(1H,3H)-dione was produced selectively with 92% yield at 120 °C, 4.2 MPa, and automatically separated from the hot catalytic aqueous solution, which was reused directly for several runs until its activity decreased in an obvious manner. Then, the catalyst melamine was recrystallized from the spent aqueous solution via simple cooling and reused for another several catalytic runs. The efficient valorization of CO2 and the straightforward stepwise recovery of the products and catalyst were important to save energy and minimize process waste for the practical industrial production.

Xiao-Cui Yuan,1 Qiang Wang,2 Wen Su,3 Hong-Ping Li,1 Cai-Hua Wu,3 Fang Gao,1 Hong-Chun Xiang,1 He Zhu,1 Li-Xue Lin,1 Xue-Fei Hu,1 Jie Cao,4 Jing-Jing Li,1 Man Li1 1Department of Neurobiology and Key Laboratory of Neurological Diseases of Ministry of Education, The Institute of Brain Research, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; 2Department of Anesthesiology, First Affiliated Hospital of Xi’an JiaoTong University, Xi’an, People’s Republic of China; 3Department of Acupuncture, Wuhan First Hospital, Wuhan 430030, People’s Republic of China; 4Department of Neurology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China Purpose: Knee osteoarthritis (KOA) is a highly prevalent, chronic joint disorder, with chronic pain as its typical symptom. Although studies have shown that an activated peripheral CB2 receptor can reduce acute pain, whether the CB2 receptor is involved in electroacupuncture (EA) inhibiting chronic pain and the involved mechanism remains unclear. The aim of this study was to investigate whether EA may strengthen peripheral CB2 receptor-inhibited chronic pain in a mouse model of KOA. Materials and methods: KOA was induced by intra-articular injection of monosodium iodoacetate (MIA) into the left knee joint of mice. Thermal hyperalgesia was tested with the hot plate test, and mechanical allodynia was quantified using von Frey filaments. The expression of CB2 receptor and IL-1β were quantified by using immunofluorescence labeling. Results: EA treatment at 2Hz+1mA significantly increased the expression of CB2 receptor in fibroblasts and decreased the expression of IL-1β in the menisci compared with that in the KOA group. However, EA had no effect on the expression of IL-1β in CB2−/− mice. At 2Hz+1mA, EA significantly increased mechanical threshold, thermal latency, and weight borne after KOA modeling. However, knockout of the CB2 receptor blocked these effects of EA. After 2Hz+1mA treatment, EA significantly reduced the Osteoarthritis Research Society International (OARSI) score after KOA modeling. However, EA had no significant effect on the OARSI score in CB2−/− mice. Conclusion: EA reduced the expression of IL-1β by activating the CB2 receptor, thus inhibiting the chronic pain in the mouse model of KOA. Keywords: cannabinoid, acupuncture, inflammatory pain, IL-1&beta

A broad-range, sensitive and reliable multiresidue analytical method is presented for identifying and inspecting 176 pesticide residues, including organophosphate, organochlorine, synthetic pyrethroid, organonitrogen and carbamate, in pre-harvested fruits and vegetables. Pesticide residues were extracted from samples with acetone, followed by liquid-liquid partition and solid-phase extraction. Seventy one and 83 pesticides were determined, respectively, by gas chromatography with a flame photometric detector and an electron capture detector. Nineteen carbamate pesticides and several metabolites were measured by high-performance liquid chromatography (HPLC) with a post-column derivation system and a fluorescence detector; and three additional pesticides, i.e., carbendazim, thiabendazole, and imidacloprid, were detected by HPLC using an ultraviolet detector at 280 nm. The proposed method was validated for 14 fruits and 8 vegetables using samples spiked with pesticide standards (0.1- 5.0 μg/g) in triplicate. Good sensitivity and repeatability were obtained with detection limits of 0.001- 0.03 μg/g, and all limits of detection were lower than one-fifth of their specific maximum residue levels. The recovery rates for most pesticides in various fruits and vegetables were 60-120% with relative standard deviations ＜ 20%. With more than 4,300 samples collected from the field examined to assess the performance, it is proposed that this method be applied for routine monitoring, legislation implementation and farmer education programs.

Tourette syndrome (TS), a developmental neurobehavioral disorder, is characterized by involuntary behavioral stereotypies. Clinical studies have confirmed the positive effect of acupuncture on treating TS, but the underlying mechanisms are not fully understood. In the present study, we used behavioral tests, Western blotting, double-immunofluorescence labeling, and fluorescence spectrophotometry to investigate whether acupuncture performed at acupoints “Baihui” (GV20) and “Yintang” (GV29) affected behavioral stereotypies and regulated the dopamine (DA) system in three different brain regions in Balb/c mice injected with 3,3′-iminodipropionitrile (IDPN) as a model for TS. We found that acupuncture alleviated behavioral stereotypies, down-regulated the expression of D1R and D2R in the striatum (STR) and substantia nigra pars compacta (SNpc), and decreased the concentration of DA in the STR, SNpc, and prefrontal cortex (PFC) as well. Moreover, acupuncture reduced the expression of tyrosine hydroxylase (TH) in the SNpc. Conclusively, acupuncture ameliorated behavioral stereotypies by regulating the DA system in the STR, SNpc, and PFC. Our findings provide novel evidence for the therapeutic effect of acupuncture on TS.

The resolution of a conventional optical imaging radar system is constrained by the diffraction limit of the telescope's aperture. The combination of lidar and synthetic aperture processing techniques can overcome the diffraction limit and provide a higher resolution air borne remote sensor. Atmospheric turbulence is an important factor affecting lidar imaging, and the phase screen simulation method is an effective method to simulate the degradation of laser signal propagating through turbulent atmosphere. By using Monte-Carlo random factor, the randomness of phase screens can be improved. The lidar imaging with different turbulence intensity is also calculated in this paper, then the improved rank one phase estimation autofocus method is used to compensate the imaging phase errors. The results show that the method of generating phase screen is consistent with the statistics of atmospheric turbulence, which can well simulate the effect of atmospheric turbulence on synthetic aperture lidar, and the influence on synthetic aperture lidar azimuth resolution is greater when atmospheric turbulence is stronger. Improved rank one phase estimation algorithm has good autofocus effect, which can effectively compensate the phase errors and enhance the image quality degraded by turbulence.

Equilenin 2 and its derivatives are important intermediates in the synthesis of steroidal drugs. Until now, these estrogens were produced by extraction from pregnant mare’s urine due to the lack of efficient synthetic methods. Most reported semisyntheses of equilenin involve expensive raw materials or toxic reagents to suppress undesired epimerization at C/D ring juncture. Herein, we reported a practical synthesis of highly pure equilenin and its derivatives from an easily available raw material 6 with conventional reagents.

Background Chronic pain is a major clinical problem with limited treatment options. Previous studies have demonstrated that activation of adenosine monophosphate-activated protein kinase (AMPK) can attenuate neuropathic pain. Inflammation/immune response at the site of complete Freund’s adjuvant (CFA) injection is known to be a critical trigger of the pathological changes that produce inflammatory pain. However, whether activation of AMPK produces an analgesic effect through inhibiting the proinflammatory cytokines, including interleukin-1β (IL-1β), in inflammatory pain remains unknown. Methods Inflammatory pain was induced in mice injected with CFA. The effects of AICAR (5-aminoimidazole-4-carboxyamide ribonucleoside, an AMPK activator), Compound C (an AMPK inhibitor), and IL-1ra (an IL-1 receptor antagonist) were tested at day 4 after CFA injection. Inflammatory pain was assessed with von Frey filaments and hot plate. Immunoblotting, hematoxylin and eosin (H&E) staining, and immunofluorescence were used to assess inflammation-induced biochemical changes. Results The AMPK activator AICAR produced an analgesic effect and inhibited the level of proinflammatory cytokine IL-1β in the inflamed skin in mice. Moreover, activation of AMPK suppressed CFA-induced NF-κB p65 translocation from the cytosol to the nucleus in activated macrophages (CD68+ and CX3CR1+) of inflamed skin tissues. Subcutaneous injection of IL-1ra attenuated CFA-induced inflammatory pain. The AMPK inhibitor Compound C and AMPKα shRNA reversed the analgesic effect of AICAR and the effects of AICAR on IL-1β and NF-κB activation in inflamed skin tissues. Conclusions Our study provides new information that AMPK activation produces the analgesic effect by inhibiting NF-κB activation and reducing the expression of IL-1β in inflammatory pain. Electronic supplementary material The online version of this article (10.1186/s12974-019-1411-x) contains supplementary material, which is available to authorized users.

Purpose: We determined whether electroacupuncture (EA) reduces Netrin-1-induced myelinated primary afferent nerve fiber sprouting in the spinal cord and pain hypersensitivity associated with postherpetic neuralgia (PHN) through activation of μ-opioid receptors. Methods: PHN was induced by systemic injection of resiniferatoxin (RTX) in rats. Thirty-six days after RTX injection, a μ-opioid receptor antagonist, beta-funaltrexamine (β-FNA) or a κ-opioid receptor antagonist, nor Binaltorphimine (nor-BNI), was injected intrathecally 30 mins before EA, once every other day for 4 times. Mechanical allodynia was tested with von Frey filaments. The protein expression level of Netrin-1 and its receptors (DCC and UNC5H2) were quantified by using western blotting. The myelinated primary afferent nerve fiber sprouting was mapped with the transganglionic tracer cholera toxin B-subunit (CTB). Results: Treatment with 2 Hz EA at “Huantiao” (GB30) and “Yanglingquan” (GB34) decreased the mechanical allodynia at 22 days and the myelinated primary afferent nerve fiber preternatural sprouting into the lamina II of the spinal dorsal horn at 42 days after RTX injection. Also, treatment with 2 Hz EA reduced the protein levels of DCC and Netrin-1 and promoted the expression of UNC5H2 in the spinal dorsal horn 42 days after RTX injection. Furthermore, the μ-opioid receptor antagonist β-FNA, but not the κ-opioid receptor antagonist nor-BNI, reversed the effect of EA on neuropathic pain caused by RTX. In addition, morphine inhibited the Netrin-1 protein level induced by RTX in SH-SY5Y cells. Conclusions: Through activation of μ-opioid receptors, treatment with EA reduces the expression level of DCC and Netrin-1 and changes a growth-permissive environment in spinal dorsal horn into an inhibitory environment by increasing UNC5H2, thus decreasing RTX-caused primary afferent nerve sprouting in the spinal dorsal horn and neuropathic pain.

As a promising electrochemical storage material, graphene has drawn tremendous attention due to its fascinating features, such as excellent mechanical flexibility, high specific surface area and superior conductivity. Nevertheless, the severe restacking of graphene sheets decreases the active surface area and decelerates the ion transport kinetics, hindering the practical application. Literatures reveals that constructing an exfoliated holey sheet structure helps solve this problem. In this work, the novel porous reduced graphene oxide with exfoliated sheets is fabricated via a hydrothermal assembly-calcination method by using Ni(NO3)2•6H2O as the activator. The dosage of Ni(NO3)2•6H2O is optimized according to the electrochemical properties of the corresponding electrode materials for the three-electrode supercapacitors. The results show that the optimal p-RGO-5 displays a high specific capacitance of 253.8 F g−1 at 1.0 A g−1. Moreover, the p-RGO-5-based symmetric supercapacitor delivers a specific energy of 24.67 W h kg−1 at the specific power of 400.00 W kg−1, in addition to superior cycling stability and high rate capability. Our work offers an effective approach for fabricating porous graphene, which is promising in the fields of energy conversion and storage devices.

Compared with bulk materials, porous electrodes possess superior supercapacitive performance due to the effective enlarged specific surface areas, which have aroused tremendous attention in recent years. In this work, porous carbon materials derived from glucose were facilely fabricated via a hydrothermal pre-carbonisation-calcination strategy using sodium dodecyl sulfate (SDS) as the dispersant and ZnCl2 as the activation agent. Benefitting from the uniform dispersion of SDS and the activation effect of ZnCl2, the optimised sample, SAGC-1-4, possesses a hierarchical porous structure with large specific surface area (2360 m2 g−1) and huge total pore volume (1.241 cm3 g−1), leading to an enhanced supercapacitive performance. As a result, SAGC-1-4 presented a specific capacitance of 303.02 F g−1 at 1.0 A g−1 in the three-electrode configuration. Meanwhile, the SAGC-1-4-based symmetric supercapacitor displayed an excellent rate performance with a high energy density of 31.59 Wh kg−1 at a power density of 400.00 W kg−1 in comparison with many carbon materials previously reported. Thus, our work offers an effective strategy for the fabrication of porous carbon for high-performance energy conversion and storage devices.

Netrin-1 is a neuronal guidance molecule implicated in the development of spinal cord neurons and cortical neurons. In the adult spinal cord, UNC5H (repulsive receptor of netrin-1), but not deleted in colorectal cancer (DCC) (attractive receptor of netrin-1), constitutes a major mode of netrin-1 signal transduction, which may be involved in axon repulsion and inhibits neurite outgrowth. Abnormal sprouting of myelinated afferent fibers in the spinal dorsal horn can cause mechanical allodynia associated with postherpetic neuralgia (PHN, Shingles) and other neuropathic pains. However, whether netrin-1 participates in sprouting of myelinated afferent fibers and mechanical allodynia remains unknown. In an ultropotent TRPV1 agonist resiniferatoxin (RTX)-induced PHN-like model, RTX treatment for 6 weeks increased netrin-1 expression in dorsal horn neurons, including NK-1-positive projection neurons. In human neuroblastoma SH-SY5Y cells, we found that TRPV1 antagonist capsazepine antagonized RTX-induced upregulation of netrin-1. After RTX treatment, UNC5H2 expression was gradually decreased, whereas DCC expression was significantly increased. Silencing netrin-1 in the spinal dorsal horn significantly attenuated RTX-induced mechanical allodynia and sprouting of myelinated fibers into the spinal lamina II. Our results suggest that RTX treatment upregulates netrin-1 expression through activation of TRPV1 receptors and change UNC5H2-rich spinal dorsal horn into a growth-permissive environment by increasing DCC expression, thus enhancing the sprouting of myelinated afferent nerves. Netrin-1 may be targeted for reducing primary afferent sprouting and mechanical allodynia in PHN and other neuropathic pain conditions.

Knee osteoarthritis (KOA) is a highly prevalent, chronic joint disorder, which can lead to chronic pain. Although electroacupuncture (EA) is effective in relieving chronic pain in the clinic, the involved mechanisms remain unclear. Reduced diffuse noxius inhibitory controls (DNIC) function is associated with chronic pain and may be related to the action of endocannabinoids. In the present study, we determined whether EA may potentiate cannabinoid receptor-mediated descending inhibitory control and inhibit chronic pain in a mouse model of KOA. We found that the optimized parameters of EA inhibiting chronic pain were the low frequency and high intensity (2 Hz + 1 mA). EA reversed the reduced expression of CB1 receptors and the 2-arachidonoylglycerol (2-AG) level in the midbrain in chronic pain. Microinjection of the CB1 receptor antagonist AM251 into the ventrolateral periaqueductal gray (vlPAG) can reversed the EA effect on pain hypersensitivity and DNIC function. In addition, CB1 receptors on GABAergic but not glutamatergic neurons are involved in the EA effect on DNIC function and descending inhibitory control of 5-HT in the medulla, thus inhibiting chronic pain. Our data suggest that endocannabinoid (2-AG)-CB1R-GABA-5-HT may be a novel signaling pathway involved in the effect of EA improving DNIC function and inhibiting chronic pain.

Background Paclitaxel is commonly used as a cancer chemotherapy drug that frequently causes peripheral neuropathic pain. Inflammasome is a multiprotein complex consisting of Nod-like receptor proteins (NLRPs), apoptosis-associated speck-like protein, and caspase-1, which functions to switch on the inflammatory process and the release of interleukin-1β. Growing evidences have supported that peripheral interleukin-1β is critical in enhancing paclitaxel-induced neuropathic pain. However, whether activation of NLRP3 inflammasome in peripheral nerve contributes to paclitaxel-induced neuropathic pain is still unclear. Results Paclitaxel induced mechanical allodynia of rats from day 3 and worsened gradually till 3 weeks after injection. Paclitaxel resulted in expression of NLRP3 and activated fragments of caspase-1 and interleukin-1β in L4-6 dorsal root ganglia and sciatic nerve three weeks after injection, indicating activation of NLRP3 inflammasome. The expression of NLRP3 was located in CD68-labeled macrophages infiltrating in L4-6 dorsal root ganglia and sciatic nerve, and paclitaxel increased the expression of NLRP3 in macrophage. Moreover, the paclitaxel elicited mitochondria damage, which became swollen and enlarged in macrophages and axons of sciatic nerve three weeks after injection. In vitro, paclitaxel increased the number of damaged mitochondria and mitochondrial reactive oxygen species production in the rat alveolar macrophage cell line NR8383. The administration of a non-specific reactive oxygen species scavenger, phenyl-N-tert-butylnitrone, markedly alleviated mechanical allodynia and inhibited the activation of NLRP3 inflammasome in L4-6 dorsal root ganglia and sciatic nerve of the paclitaxel-induced neuropathic pain model. Conclusions Paclitaxel induced mechanical allodynia and activation of NLRP3 inflammasome in infiltrated macrophages of L4-6 dorsal root ganglia and sciatic nerve. Paclitaxel elicited mitochondria damage and reactive oxygen species production may result in activation of NLRP3 inflammasome in peripheral nerve, which contributes to paclitaxel-induced neuropathic pain.

The therapeutic effect of electroacupuncture (EA) on inflammatory pain has been well recognized clinically. The inflammasome promotes the maturation of the inflammatory cytokines, and EA can stimulate cannabinoid CB2 receptors in inflamed tissues. In this study we investigated whether EA inhibits NLRP3 inflammasome activation through CB2 receptors and thus relieving inflammatory pain. Assay of Caspase-1 activity and western blotting revealed that complete Freund's adjuvant (CFA) injection activated the NLRP3 inflammasome in the skin tissue in rats, which was attenuated by EA treatment. Immunofluorescence labeling showed that NLRP3 inflammasome elicited by CFA in the skin macrophages were decreased by EA. Nociceptive behavioral tests demonstrated that in CB2 receptor knockout mice, the EA effects on NLRP3 inflammasomes were largely attenuated. In addition, in vitro studies in a macrophage cell line showed that CB2 receptor stimulation inhibited the NLRP3 inflammasome activation. Thus, our results suggest a novel signaling pathway through which CB2 receptors are involved in the analgesic effect of EA on inflammatory pain. Stimulation of CB2 receptors inhibits NLRP3 inflammasome activation in inflamed skin tissues. These results suggest that EA reduces the inflammatory pain by inhibiting the activation of NLRP3 inflammasome through CB2 receptors. Our findings provide novel information about the mechanisms through which EA and CB2 receptor activation reduce inflammatory pain.

A novel thermomechanical processing was developed for producing fine grained Al-Mg-Li alloy sheets. The influences of static recrystallization annealing on the grain structure and superplastic behavior were investigated. The results show that the refined microstructure has a variation in the distribution of grain size, shape and texture across the normal direction of the sheet. The surface layer (SL) has fine, nearly equiaxed grains with a rotated cube ND {001}«310» orientation, whereas the center layer (CL) has coarse, elongated grains with a portion of α fiber orientation. Increasing static recrystallized temperature results in grain growth in the full thickness, decreasing of grain aspect ratio in the center layer, texture sharpening in the surface layer, but weakening in the center layer as well as decreasing of superplastic elongation. Increasing the annealing temperature also produces an sharpening of the rotated cube {001}«310» component and a decreasing of the α fiber texture in the full thickness of the sheet. The formation mechanisms of recrystallization texture at various temperatures and layers were discussed.

Precipitation response of a recently developed β-type Ti–25Nb–2Mo–4Sn alloy (wt%) during aging was investigated in detail. Experimental results indicate that the metastable ω or equilibrium α phase can form alternatively even under the same aging condition, depending on the condition prior to the aging, i.e., solution treatment or severe cold rolling. This provides, for the first time, the direct evidence for the competition between ω and α in aged β-type Ti alloys. This peculiar aging response is found to be closely related to high-density dislocations and grain boundaries which suppress the formation of ω but favor the precipitation of fine α phase.

Mobile geosocial networking services could be the killer app for next-generation mobile computing. However, the privacy issue--in particular, location privacy--has both users and government authors concerned. The authors address this issue for the "nearby friend alert" service, common in mobile geosocial networks. They review representative works on privacy-preserving proximity detection and present a new quantitative solution. They adopt the grid-and-hashing paradigm and develop optimal grid overlay and multilevel grids to increase the detection accuracy while saving the wireless bandwidth. Based on these techniques, they devise the client-side location update scheme and the server-side update handling procedure for continuous proximity detection. Simulation results show that their approach is efficient and scalable under various system parameters and user moving speeds.

A fast and efficient method has been demonstrated for the trace determination of six important metabolites of synthetic pyrethroids including cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (cis- and trans-Cl2CA), cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (cis-Br2CA), 4-fluoro-3-phenoxybenzoic acid (4-F-3-PBA), 3-phenoxybenzoic acid (3-PBA), and 2-phenoxybenzoic acid (2-PBA) in environmental water samples using hollow fiber (HF)-mediated liquid-phase microextraction (LPME) coupled with in-syringe derivatization (ISD) followed by gas chromatography (GC) with electron capture detector (ECD) analysis. This method utilizes a HF membrane segment impregnated with extraction solvent as the LPME sampling probe, which was connected to a microsyringe pre-filled with derivatizing agents, and it was immersed into sample solution for extraction. After extraction, the extracting solution was subjected to derivatization reaction that was performed inside the syringe barrel followed by GC-ECD analysis. Under optimal conditions, the best extraction efficiency was obtained using sampling probe (2.0 cm hollow fiber) impregnated with 1-octanol immersed into water sample (5.0 mL, adjusted pH below 1.0) and stirring (1,250 rpm) for 10 min at 70 °C and diisopropylcarbodiimide (2 μL) and 1,1,1,3,3,3-hexafluoro-2-propanol (1 μL) were the derivatizing agents used. The detection limits of 3 ng mL−1 for cis- and trans-Cl2CA, 2 ng mL−1 for cis-Br2CA, 6 ng mL−1 for 4-F-3-PBA, and 0.6 ng mL−1 for 3-PBA and 2-PBA. The method showed good linearity (R 2 = 0.973−0.998), repeatability from 4.0 to 13 % (n = 5), recovery from 79.2 to 95.7 %, and enrichment factors ranged between 109 and 159 for target analytes spiked in water samples. The proposed method and conventional methods were compared. Results suggested that the proposed HF-LPME-ISD/GC-ECD method was a rapid, simple, inexpensive, and eco-friendly technique for the analysis of metabolites of pyrethroids.

Based on the crack propagation mechanism of elastic-plastic fracture, a finite element analysis was performed upon the effect of compressive loading on fatigue crack tip stress field in LY12M aluminum alloy. By the validation of test data, two actual engineering models and a published double-parameter crack growth model, called Zhang-model, are all suitable in the case of negative stress ratio, and are used to describe the test data in the corresponding coordinate system. By comparing the degrees of linear correlation, R2, of each fitting line, it shows that Zhang-model is a better engineering method for life prediction of fatigue crack growth under negative stress ratio of aluminum alloy, some factors can be obtained from elastic-plastic finite element computation, and it will save a lot of funds in the new materials research.

The effects of quenching and aging (T6, T7 and RRA) on the microstructural evolution of an Al-Zn-Mg-Cu alloy were investigated by hardness test, optical microscopy (OM), transmission electron microscopy (TEM) and differential scanning calorimetry (DSC) measurements. It is found that the hardness of T6 aged sample after water-quenching is the highest. The quench sensitivities of T7 and RRA are almost the same, which are 1.2% higher than that of T6. TEM observation shows that the quench sensitivity for the studied alloy is mainly caused by heterogeneous precipitation during slow quenching. Many n phases precipitate on Al 3 Zr dispersoids inside recrystallized grains and at (sub) grain boundaries, while T and S phases form in the substructure with high density of dislocations and defects. After aging, the n ' precipitates are coarser in the vicinity of equilibrium n phase. However, the size and morphology of the precipitates show different characteristics among T6, T7 and RRA treatments. The DSC results are highly consistent with the TEM observation. The DSC curves of T6 aged samples are different from those of T7 and RRA aged samples, which also reflects the differences on the microstructure.

Due to the invariance to scale and rotation, image matching method based on Log-Polar transformation has been extensively applied in target detection and location. This paper analyses the effect on image matching accuracy from variation of scale and rotation, and proposes a modified image matching method based on analysis of data reliability for matching, this method can eliminate the interference from invalid data and improve the image matching performance. Experiments show that this method has better performance in accuracy.