Activating active motifs in Ni-Fe oxide by introducing dual-defect for oxygen evolution reaction in alkaline seawater.

Developing simple and energy-saving pathways to prepare high-efficient and robust non-noble metal based electrocatalysts remains a huge challenge to hydrogen production from seawater electrolysis. Here we demonstrate a facile hydrothermal-calcination-etching approach that simultaneously achieves the required surface N doping and Fe vacancies generation to activate the Ni-O-Fe active motifs in N-vFe-NiFe2O4/NF. The unique localized environments (Ni-N-Fe structures and unsaturated O- and N-coordination) due to dual-defect strategy can effectively regulate the electronic structure of the Ni-O-Fe motif to make the motif more reactive. As a result, the N-vFe-NiFe2O4/NF catalyst exhibits overpotentials of 210, 213 and 222 mV to deliver 100 mA cm-2 in 1.0 M KOH, simulated seawater and alkaline seawater environments, respectively. Theoretical calculations prove that the Ni-O-Fe structure is the active motif and that the presence of special localized environments can optimize the adsorption of key intermediates on the activated active motifs.

Acoustic emission features of granite from different rockburst areas in Sangzhuling Railway Tunnel.

In order to investigate the acoustic emission (AE) features of rocks in different (medium and strong) rockburst areas, the Sangzhuling Railway Tunnel granite in China was taken as an example, the mineral composition of rocks in different rockburst areas was analyzed by using XRD (X-ray diffraction) method. The Original rock cores of different rockburst areas were processed into standard rock specimens (diameter 50 mm, height 100 mm) in different directions (transverse, oblique and longitudinal). AE feature parameters (event number, ringing count and energy) of standard rock specimens during indoor uniaxial compression test were obtained by using AE technique. The variation law of AE feature parameters of rocks in different rockburst grade areas was then analyzed. The AE features of failure precursor of rocks in different rockburst areas were therefore discussed. It shows that compared with rocks in medium rockburst area, the content of quartz and feldspar of rocks in strong rockburst area is high, while the content of biotite is low; the rock in the strong rock burst area released more energy during the failure process with about 2-3 times that of the rock in the medium rock burst area; the cumulative ringing curve of rock in medium burst area is a stepped type, while the cumulative ringing curve of rock in strong burst area is the smoothed type; the end of the second and first AE quiet period may be regarded as the failure precursor of rocks in medium and strong rockburst area, respectively. The results presented herein are important for understanding the mechanisms of rockburst.

Co─Mn Bimetallic Nanowires by Interfacial Modulation with/without Vacancy Filling as Active and Durable Electrocatalysts for Water Splitting.

Active and stable nonnoble electrocatalysts for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) are required for water splitting by sustainable electricity. Here, Mn bonded with O and P is incorporated to modulate Co3S4 and Co2P respectively to enhance the catalytic activity and extend the catalyst lifetime. Mn3O4 adjusts the electronic structure of Co3S4 and Co atom fills the oxygen vacancy in Mn3O4. The interfacial interaction endows Co3S4/Mn3O4 to a lower reaction barrier due to ideal binding energies for OER intermediates. Structure stability of active sites and enhanced Co─S bonds by Operando Raman spectroscopy and theoretical calculations reduce the dissolution of Co3S4/Mn3O4, resulting in a lifetime of 500 h at 50 mA cm-2 for OER. The modulation of Co2P by MnP weakens the interaction between Co sites and adsorbed H*, achieving a high activity under a large current for HER. The assembled electrolyzer affords 50 mA cm-2 at 1.58 V and exhibits a lifetime of 350 h at 50 mA cm-2. The calculations disclose the electron interaction for the activity and stability, as well as the enhanced conductivity. The findings develop new avenues toward promoting catalytic activity and stability, making Co─Mn bimetallic nanowires efficient electrocatalysts for nonnoble water electrolyzers.

Catalyst Selection over an Electrochemical Reductive Coupling Reaction toward Direct Electrosynthesis of Oxime from NOx and Aldehyde.

Aqueous electrochemical coupling reactions, which enable the green synthesis of complex organic compounds, will be a crucial tool in synthetic chemistry. However, a lack of informed approaches for screening suitable catalysts is a major obstacle to its development. Here, we propose a pioneering electrochemical reductive coupling reaction toward direct electrosynthesis of oxime from NOx and aldehyde. Through integrating experimental and theoretical methods, we screen out the optimal catalyst, i.e., metal Fe catalyst, that facilitates the enrichment and C-N coupling of key reaction intermediates, all leading to high yields (e.g., ∼99% yield of benzaldoxime) for the direct electrosynthesis of oxime over Fe. With a divided flow reactor, we achieve a high benzaldoxime production of 22.8 g h-1 gcat-1 in ∼94% isolated yield. This work not only paves the way to the industrial mass production of oxime via electrosynthesis but also offers references for the catalyst selection of other electrochemical coupling reactions.

Strong Interface Coupling Enables Stability of Amorphous Meta-Stable State in CoS/Ni3S2 for Efficient Oxygen Evolution.

Rational design of heterostructure catalysts through phase engineering strategy plays a critical role in heightening the electrocatalytic performance of catalysts. Herein, a novel amorphous/crystalline (a/c) heterostructure (a-CoS/Ni3S2) is manufactured by a facile hydrothermal sulfurization method. Strikingly, the interface coupling between amorphous phase (a-CoS) and crystalline phase (Ni3S2) in a-CoS/Ni3S2 is much stronger than that between crystalline phase (c-CoS) and crystalline phase (Ni3S2) in crystalline/crystalline (c/c) heterostructure (c-CoS/Ni3S2) as control sample, which makes the meta-stable amorphous structure more stable. Meanwhile, a-CoS/Ni3S2 has more S vacancies (Sv) than c-CoS/Ni3S2 because of the presence of an amorphous phase. Eventually, for the oxygen evolution reaction (OER), the a-CoS/Ni3S2 exhibits a significantly lower overpotential of 192 mV at 10 mA cm-2 compared to the c-CoS/Ni3S2 (242 mV). An exceptionally low cell voltage of 1.51 V is required to achieve a current density of 50 mA cm-2 for overall water splitting in the assembled cell (a-CoS/Ni3S2 || Pt/C). Theoretical calculations reveal that more charges transfer from a-CoS to Ni3S2 in a-CoS/Ni3S2 than in c-CoS/Ni3S2, which promotes the enhancement of OER activity. This work will bring into play a fabrication strategy of a/c catalysts and the understanding of the catalytic mechanism of a/c heterostructures.

Tip-like Fe-N4 Sites Induced Surface Microenvironments Regulation Boosts the Oxygen Reduction Reaction.

Single atom catalysts with defined local structures and favorable surface microenvironments are significant for overcoming slow kinetics and accelerating O2 electroreduction. Here, enriched tip-like FeN4 sites (T-Fe SAC) on spherical carbon surfaces were developed to investigate the change in surface microenvironments and catalysis behavior. Finite element method (FEM) simulations, together with experiments, indicate the strong local electric field of the tip-like FeN4 and the more denser interfacial water layer, thereby enhancing the kinetics of the proton-coupled electron transfer process. In situ spectroelectrochemical studies and the density functional theory (DFT) calculation results indicate the pathway transition on the tip-like FeN4 sites, promoting the dissociation of O-O bond via side-on adsorption model. The adsorbed OH* can be facilely released on the curved surface and accelerate the oxygen reduction reaction (ORR) kinetics. The obtained T-Fe SAC nanoreactor exhibits excellent ORR activities (E1/2 =0.91 V vs. RHE) and remarkable stability, exceeding those of flat FeN4 and Pt/C. This work clarified the in-depth insights into the origin of catalytic activity of tip-like FeN4 sites and held great promise in industrial catalysis, electrochemical energy storage, and many other fields.

Vacancy-induced catalytic mechanism for alcohol electrooxidation on nickel-based electrocatalyst.

Owing to outstanding performances, nickel-based electrocatalysts are commonly used in electrochemical alcohol oxidation reactions (AORs), and the active phase is usually vacancy-rich nickel oxide/hydroxide (NiOx Hy ) species. However, researchers are not aware of the catalytic role of atom vacancy in AORs. Here, we study vacancy-induced catalytic mechanisms for AORs on NiOx Hy species. As to AORs on oxygen-vacancy-poor ß-Ni(OH)2 , the only redox mediator is electrooxidation-induced electrophilic lattice oxygen species, which can only catalyze the dehydrogenation process (e.g., the electrooxidation of primary alcohol to carboxylic acid) instead of the C-C bond cleavage. Hence, vicinal diol electrooxidation reaction involving the C-C bond cleavage is not feasible with oxygen-vacancy-poor ß-Ni(OH)2 . Only through oxygen vacancy-induced adsorbed oxygen-mediated mechanism, can oxygen-vacancy-rich NiOx Hy species catalyze the electrooxidation of vicinal diol to carboxylic acid and formic acid accompanied with the C-C bond cleavage. Crucially, we examine how vacancies and vacancy-induced catalytic mechanisms work during AORs on NiOx Hy species.

Selective Electroreduction of 5-Hydroxymethylfurfural to Dimethylfuran in Neutral Electrolytes via Hydrogen Spillover and Adsorption Configuration Adjustment.

5-Hydroxymethylfurfural (HMF), one of the essential C6 biomass derivatives, has been deeply investigated in electrocatalytic reduction upgrading. Nevertheless, the high product selectivity and rational design strategy of electrocatalysts for electrocatalytic HMF reduction is still a challenge. Here, a high selective electro-reduction of HMF to dimethylfuran (DMF) on palladium (Pd) single atom loaded on titanium dioxide (Pd SA/TiO2 ) via hydrogen spillover and adsorption configuration adjustment in neutral electrolytes is achieved. Combining density functional theory calculations and in situ characterization, it is revealed that Pd single atom could weaken the interaction between Pd atoms and adsorbed hydrogen (*H) to promote the *H spillover for increasing *H coverage on the surface and maintain the tilted adsorption configuration to activate C═O bond; thus the selectivity of DMF on Pd SA/TiO2 increases to 90.33%. Besides, it is elaborated that low *H coverage on TiO2 favors the formation of bis(hydroxymethyl)hydro-furoin (BHH), and the flat adsorption configuration of HMF on Pd nanoparticles benefits to form 2,5-dihydroxymethylfuran (DHMF). This work provides a promising approach for modifying electrocatalysts to realize the selective electroreduction of HMF to value-added products.

Strong electron coupling of FeP4/Ni2P to boost highly-efficient electrochemical nitrate reduction to ammonia.

Electrochemical reduction of contaminated nitrate to ammonia (NRA) opens a new window for mass production of ammonia and the alleviation of energy crises and environmental pollution. However, fabricating effective catalysts for the NRA still faces significant challenges. Herein, a highly-efficient NRA catalyst, FeP4/Ni2P, was successfully constructed. The strong electron coupling at heterointerfaces of FeP4/Ni2P promoted the generation of abundant active hydrogen *H, inhibited the competition of the HER, accelerated the hydrogenation of the NRA. Benefiting from these, the catalyst displays good NRA catalytic activity in the neutral electrolyte, with the NH3 FE of 97.83 ± 0.091 %, NH3 selectivity of 98.67 ± 0.50 %, NH3 yield rate of 0.262 ± 0.01 mmol·h-1·cm-2, and NO3- conversion rate of 93.02 ± 0.14 %. The DFT theoretical calculations demonstrated that the FeP4/Ni2P heterointerfaces played a critical role in shearing the H-OH bonds of water, resulting in generating more active hydrogen as a key NRA hydrogenation source, and hindering the *H dimerization to form H2, enhancing the NH3 selectivity. This work has a certain reference value for designing excellent catalysts for the NRA.

Selective Anchoring by Surface Sulfur Species Coupled with Rapid Interface Electron Transfer for Ultrahigh Capacity Extraction of Uranium from Seawater.

Improving the adsorption selectivity, enhancing the extraction capacity, and ensuring the structural stability of the adsorbent are the key to realize the high efficiency recovery of uranium. In this work, we utilized the strong Lewis acid-base interaction between S2- and U(VI)O22+ coupling rapid electron transfer at the MnS/U(VI)O22+ solid-liquid interface to achieve excellent selectivity, high adsorption capacity, and rapid extraction of uranium. The as-synthesized MnS adsorbent exhibited an ultrahigh uranium extraction capacity (2457.05 mg g-1) and a rapid rate constant (K = 9.11 × 10-4 g h-1 mg-1) in seawater with 100.7 ppm of UO2(NO3)2 electrolyte. The kinetic simulation reveals that this adsorption process is a chemical adsorption process and conforms to a pseudo-second-order kinetic model, indicating electron transfer at the MnS/U(VI)O22+ solid-liquid interface. The relevant (quasi) in situ spectroscopic characterization and theoretical calculation results further revealed that the outstanding uranium extraction property of MnS could be attributed to the highly selective UO22+ adsorption of MnS with lower adsorption energy as a result of the strong interaction between S2- and UO22+ and the rapid mass transfer and interface electron transfer from S2- and low-valent Mn(II) to U(VI)O22+.

Preliminary study on the anti-CO2 stress and growth ability of hypsizygus marmoreus mutant strain HY68.

BACKGROUND: A high concentration of CO2 will stagnate the development of the newly formed primordia of Hypsizygus marmoreus, hinder the development of the mushroom cap, thereby inhibiting the normal differentiation of the fruiting body. Moreover, in the previous experiment, our research group obtained the mutant strain HY68 of H. marmoreus, which can maintain normal fruiting under the condition of high concentration of CO2. Our study aimed to evaluate the CO2 tolerance ability of the mutant strain HY68, in comparison with the starting strain HY61 and the control strain HY62. We analyzed the mycelial growth of these strains under various conditions, including different temperatures, pH levels, carbon sources, and nitrogen sources, and measured the activity of the cellulose enzyme. Additionally, we identified and predicted ß-glucosidase-related genes in HY68 and analyzed their gene and protein structures. RESULTS: Our results indicate that HY68 showed superior CO2 tolerance compared to the other strains tested, with an optimal growth temperature of 25 °C and pH of 7, and maltose and beef paste as the ideal carbon and nitrogen sources, respectively. Enzyme activity assays revealed a positive correlation between ß-glucosidase activity and CO2 tolerance, with Gene14147 identified as the most closely related gene to this activity. Inbred strains of HY68 showed trait segregation for CO2 tolerance. CONCLUSIONS: Both HY68 and its self-bred offspring could tolerate CO2 stress. The fruiting period of the strains resistant to CO2 stress was shorter than that of the strains not tolerant to CO2 stress. The activity of ß-GC and the ability to tolerate CO2 were more closely related to the growth efficiency of fruiting bodies. This study lays the foundation for understanding how CO2 regulates the growth of edible fungi, which is conducive to the innovation of edible fungus breeding methods. The application of the new strain HY68 is beneficial to the research of energy-saving production in factory cultivation.

Appendicular Skeletal Muscle Mass Index Level (ASMI) and Its Influencing Factors in Healthy Adult Males.

Background: We aimed to retrospectively analyze the level of appendicular skeletal muscle mass index (ASMI) in adult males and its influencing factors for early screening and intervention of sarcopenia. Methods: From January 2020 to December 2021, adult male medical examiners from the Health Management Center of the Affiliated Hospital of North Sichuan Medical College, Chengdu City, China were selected as the research subjects. The ASMI level was measured by bioelectrical impedance (BIA) method. The subjects were divided into four groups according to the quartiles of ASMI level, the levels of related indicators between the groups were compared, and the related factors affecting the ASMI level were analyzed. Results: The detection rate of sarcopenia was about 1.09% (78/7187). One-way ANOVA or nonparametric test results showed that age, BMI, WHR, SBP, DBP, FPG, HbA1c, AST, ALT, GGT, Cr, UA, TG, TC, HDLC, LDL-C and FT3 levels were significantly different among the four ASMI groups (P<0.05). ASMI was positively correlated with BMI, WHR, SBP, DBP, FPG, HbA1c, AST, ALT, GGT, Cr, UA, TG, TC, LDL-C, FT3, and TSH (all P<0.05); negatively correlated with age and HDL-C (all P<0.05). Age, WHR and TG were independent risk factors for ASMI level, and BMI was an independent protective factor for ASMI level. Conclusion: The ASMI level in healthy adult males is related to age, obesity, blood pressure, glucose and lipid metabolism disorder, inflammation and thyroid hormone, among which age, BMI, WHR and TG are independent influencing factors of ASMI level.

Anion-induced electronic localization and polarized cobalt clusters for highly efficient water splitting.

It is a promising pathway to use anions to regulate electronic structures, reasonably design and construct highly efficient catalysts for water splitting. Herein, a N-regulated Co cluster catalyst confined in carbon nanotubes, N-Co NCNTs, was constructed successfully. Nitrogen anions played a crucial role in optimizing the electronic structures of Co clusters and enhancing localization of electrons, resulting in polarized cobalt clusters. The N-induced electronic localization and the resulting polarized Co clusters are responsible for the improvement of catalytic activity. N-Co NCNTs exhibited ultra-low overpotentials of 178 mV and 92 mV for the OER and HER to achieve 10 mA cm-2 in an alkaline electrolyte, respectively. Its long-term catalytic durability is mainly attributed to the obstacle to the surface oxidation of Co clusters caused by N-regulation. N-Co NCNTs maintained a stable current density for 160 h at 10 mA cm-2. DFT computations confirmed the decisive role played by nitrogen anions in regulating the electronic structure. This work provides a pathway for understanding and designing highly efficient anion-regulated catalysts.

Efficacy of low-intensity pulsed ultrasound in the treatment of COVID-19 pneumonia.

PURPOSE: As a public health emergency of international concern, coronavirus disease 2019 (COVID-19) still lacks specific antiviral drugs, and symptomatic treatment is currently the mainstay. The overactivated inflammatory response in COVID-19 patients is associated with a high risk of critical illness or even death. Low-intensity pulsed ultrasound (LIPUS) can mitigate inflammation and inhibit edema formation. We aimed to investigate the efficacy of LIPUS therapy for COVID-19 pneumonia. MATERIALS AND METHODS: 62 patients were randomly assigned to a treatment group (LIPUS treatment area - Group 1; self-control area - Group 2) and an external control group (Group 3). The primary outcomes were the volume absorption rate (VAR) and the area absorption rate (AAR) of lung inflammation in CT images. RESULTS: After an average duration of treatment 7.2 days, there were significant differences in AAR and VAR between Group 1 and Group 2 (AAR 0.25 vs 0.12, p=0.013; VAR 0.35 vs 0.11, p=0.005), and between Group 1 and Group 3 (AAR 0.25 vs 0.11, p=0.047; VAR 0.35 vs 0.19, p=0.042). Neither AAR nor VAR was statistically different between Group 2 and Group 3. After treatment, C-reactive protein, interleukin-6, leukocyte, and fingertip arterial oxygen saturation (SaO2) improved in Group 1, while in Group 3 only fingertip SaO2 increased. CONCLUSION: LIPUS therapy reduced lung inflammation and serum inflammatory factor levels in hospitalized COVID-19 patients, which might be a major advancement in COVID-19 pneumonia therapy.

Electrocatalytic Synthesis of Nylon-6 Precursor at Almost 100 % Yield.

Synthesis of cyclohexanone oxime via the cyclohexanone-hydroxylamine process is widespread in the caprolactam industry, which is an upstream industry for nylon-6 production. However, there are two shortcomings in this process, harsh reaction conditions and the potential danger posed by explosive hydroxylamine. In this study, we presented a direct electrosynthesis of cyclohexanone oxime using nitrogen oxides and cyclohexanone, which eliminated the usage of hydroxylamine and demonstrated a green production of caprolactam. With the Fe electrocatalysts, a production rate of 55.9 g h-1 gcat -1 can be achieved in a flow cell with almost 100 % yield of cyclohexanone oxime. The high efficiency was attributed to their ability of accumulating adsorbed hydroxylamine and cyclohexanone. This study provides a theoretical basis for electrocatalyst design for C-N coupling reactions and illuminates the tantalizing possibility to upgrade the caprolactam industry towards safety and sustainability.

Kinetic Understanding of Catalytic Selectivity and Product Distribution of Electrochemical Carbon Dioxide Reduction Reaction.

CO2 can be electrochemically reduced to different products depending on the nature of catalysts. In this work, we report comprehensive kinetic studies on catalytic selectivity and product distribution of the CO2 reduction reaction on various metal surfaces. The influences on reaction kinetics can be clearly analyzed from the variation of reaction driving force (binding energy difference) and reaction resistance (reorganization energy). Moreover, the CO2RR product distributions are further affected by external factors such as electrode potential and solution pH. A potential-mediated mechanism is found to determine the competing two-electron reduction products of CO2 that shifts from thermodynamics-controlled product formic acid at less negative electrode potentials to kinetic-controlled product CO at more negative electrode potentials. Based on detailed kinetic simulations, a three-parameter descriptor is applied to identify the catalytic selectivity of CO, formate, hydrocarbons/alcohols, as well as side product H2. The present kinetic study not only well explains the catalytic selectivity and product distribution of experimental results but also provides a fast way for catalyst screening.

Dopant-Induced Surface Self-Etching of Cobalt Carbonate Hydroxide Boosts Efficient Water Splitting.

Herein, vanadium-doped cobalt carbonate hydroxide, V-CoCH, was synthesized as efficient catalyst for water splitting. Vanadium species were partially dissolved in the early stages of the oxygen-evolution reaction (OER), inducing self-etching of the catalyst surface, which is helpful for catalyst surface reconstruction and resulted in a higher number of active sites and oxygen vacancies. The synergy between V-doping and oxygen vacancies improved the catalytic activity: V-CoCH showed an exceptional OER catalytic performance with an overpotential of 183 mV at 10 mA cm-2 . The water-splitting cell consisting of V-CoCH only required 1.52 V to reach 10 mA cm-2 . Theoretical calculations revealed that vanadium in V-CoCH played an important role in electron regulation of active sites. The oxygen vacancies had an important effect on improvement of the OER performance through not only the exposure of more active sites but also through modulation of the electronic structure. This work provides an effective strategy for constructing high-performance electrocatalysts.

The role of various components in Ru-NiCo alloys in boosting the performance of overall water splitting.

Understanding the synergistic mechanism of multi-component alloys is crucial and challenging for overall water splitting. Herein, Ru-NiCo0.5-600 °C and Ru-Ni0.75Co with excellent electrocatalytic activity are designed and synthesized. The Ru-NiCo0.5-600 °C alloy exhibits remarkable HER activity with an overpotential of 42, 77 and 93 mV at 10 mA cm-2 in alkaline, acidic and neutral conditions, and the Ru-Ni0.75Co electrocatalyst presents outstanding OER activity with an overpotential of 176 mV at 10 mA cm-2 in 1.0 M KOH. The Ru-NiCo0.5-600 °C ||Ru-Ni0.75Co cell requires only 1.48 and 1.69 V to reach 10 and 100 mA cm-2 towards overall water splitting. A series of experiments reveal that the strong electronic coupling among Ru, Ni and Co regulates the electronic structure and enhances the intrinsic catalytic activity and stability of the as-synthesized Ru-NiCo electrocatalysts. Systematic experimental and theoretical results prove that Ni atoms act as the active sites of dissociating water, while Ru and Co are respectively the active centers of proton and hydroxyl adsorption for HER and OER. Our work provides a new perspective for profoundly understanding the synergistic effect of multi-component alloys towards water splitting.

Effect and underlying mechanisms of spirocyclopiperazinium salt compound DXL-A-24 in rats following spinal nerve ligation.

PURPOSE: Neuropathic pain represents a significant public health problem and its effective management remains a challenge. The present study is designed to evaluate the analgesic effect of the spirocyclopiperazinium salt compound DXL-A-24 in spinal nerve ligation (SNL) model, and further to explore the possible molecular mechanisms. METHODS: SNL model was established on rats, and mechanical allodynia and thermal hyperalgesia were estimated with the von Frey and hot plate tests; the expression of CaMKIIα, CREB, JAK2, STAT3 and c-fos was determined by western blotting; the protein level of TNF-α was analysed by ELISA; the mRNA expression of TNF-α and c-fos was detected using qRT-PCR analysis and the receptor blocking test was used for target searching. RESULTS: Administration of DXL-A-24 (1, 0.5, 0.25 mg/kg, i.g.) obviously relieved SNL-induced mechanical allodynia and thermal hyperalgesia in rats (P < 0.01), with the percentage of pain threshold elevation (PTE%) was 103 %, 68 % and 47 %, respectively, in mechanical allodynia; the percentage of maximal possible effect (MPE%) was 56 %, 34 % and 21 %, respectively, in thermal hyperalgesia on day 7 after SNL. Pretreatment with peripheral α7 nicotinic or M4 muscarinic receptor antagonist, the effect of DXL-A-24 was completely blocked (P > 0.05). DXL-A-24 significantly reduced the upregulated pCaMKIIα, pCREB, pJAK2, pSTAT3 and TNF-α protein (P < 0.01), which could be blocked by α7 nicotinic receptor or M4 muscarinic receptor antagonist. In addition, administration of DXL-A-24 attenuated the mRNA and protein expression of c-fos and TNF-α mRNA in DRG of SNL rat. We did not observe significant acute toxicity and chronic hepatorenal impairment at effective dose and high dose. CONCLUSIONS: We report firstly that administration of DXL-A-24 displays obvious antineuropathic pain effects in SNL rats. The underlying mechanism may involve the reduction of the CaMKIIα/CREB and JAK2/STAT3 signalling pathways, and the suppression of TNF-α and c-fos expression, which may be mediated by activating peripheral α7 nicotinic and M4 muscarinic receptors. This study may provide a new perspective for developing new antineuralgic drug.

Electroacupuncture ameliorates cerebrovascular impairment in Alzheimer's disease mice via melatonin signaling.

AIMS: Cerebrovascular impairment contributes to the pathogenesis of Alzheimer's disease (AD). However, it still lacks effective intervention in clinical practice. Here, we investigated the efficacy of electroacupuncture (EA) in cerebrovascular repair in 3xTg-AD mice and its mechanism. METHODS: 3xTg-AD mice were employed to evaluate the protective effect of EA at ST36 acupoint (EAST36). Behavioral tests were performed to assess neurological disorders. Laser speckle contrast imaging, immunostaining, and Western blot were applied to determine EAST36-boosted cerebrovascular repair. The mechanism was explored in 3xTg mice and endothelial cell cultures by melatonin signaling modulation. RESULTS: EAST36 at 20/100 Hz effectively alleviated the olfactory impairment and anxiety behavior and boosted cerebrovascular repair in AD mice. EAST36 attenuated cerebral microvascular degeneration in AD mice by modulating endothelial cell viability and injury. Consequently, the Aß deposits and neural damage in AD mice were reversed after EAST36. Mechanistically, we revealed that EAST36 restored melatonin levels in AD mice. Melatonin supplement mimicked the EAST36 effect on cerebrovascular protection in AD mice and endothelial cell cultures. Importantly, blockage of melatonin signaling by antagonist blunted EAST36-induced cerebrovascular recovery and subsequent neurological improvement. CONCLUSIONS: These findings provided strong evidence to support EAST36 as a potential nonpharmacological therapy against cerebrovascular impairment in AD. Further study is necessary to better understand how EAST36 treatment drives melatonin signaling.