Unconventional Synthesis of Hierarchically Twinned Copper as Efficient Electrocatalyst for Nitrate-Ammonia Conversion.

Twin boundary (TB) engineering provides exciting opportunities to tune the performance levels of metal-based electrocatalysts. However, the controllable construction of TB greatly relies on surfactants, blocking active sites, and electron transfer by surfactants. Here, a surfactant-free and facile strategy is proposed for synthesizing copper (Cu) nanocatalysts with dense hierarchical TB networks (HTBs) by the rapid thermal reductions in metastable CuO nanosheets in H2 . As revealed by in situ transmission electron microscopy, the formation of HTBs is associated with the fragmentation of nanosheets in different directions to generate abundant crystal nuclei and subsequently unconventional crystal growth through the collision and coalescence of nuclei. Impressively, the HTBs endow Cu with excellent electrocatalytic performance for direct nitrate-ammonia conversion, superior to that of Cu with a single-oriented TB and without TB. It is discovered that the HTBs induce the formation of compressive strains, thereby creating a synergistic effect of TBs and strains to efficiently tune the binding energies of Cu with nitrogen intermediates (i.e., NO2 *) and thus promote the tandem reaction process of NO3 - -to-NO2 - and subsequent NO2 - -to-NH3 electrocatalysis. This work demonstrates the crucial role of HTBs for boosting electrocatalysis via the synergistic effect of TBs and strains.

Electroacupuncture alleviates neuropathic pain caused by SNL by promoting M2 microglia polarization through PD-L1.

As a common clinical disease, neuropathic pain is difficult to be cured with drugs. The occurrence and progression of pain is closely related to the response of spinal microglia. Aspartof the regulation of microglialactivity,PD-L1 playsacriticalrole. Loss of PD-L1 promoted the polarization of M1-like microglia. Increased expression of PD-L1 promoted M2-like polarization. Electroacupuncture has a significant analgesic effect in clinical practice, but its specific mechanism remains to be further explored. In this study, we verified the role of PD-L1 in EA analgesia and the underlying molecular mechanism through spinal nerve ligation (SNL) in rats and lipopolysaccharide (LPS)-treated BV2 microglial cells. Forbehavioralstudiesofrats,mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured, and spinal cord neuros were examined under transmission electron microscopyto determine changes to their myelin structure. The expression levels of PD-L1 and M1/M2-specific markers in rat spinal cord and BV2 microglial cells were measured by enzyme-linked immunosorbent assay, flow cytometry, immunofluorescence staining and Western blot analysis. Our study showed that EA increased the pain threshold, reduced the destruction of myelin structure, promoted the expression of PD-L1 and PD-1, inhibited the MAPK signaling pathway, and promoted the conversion of microglial polarization from the M1 phenotype to the M2 phenotype in SNL rats. PD-L1 knockdown reversed these effects of EA. In addition, PD-L1 knockdown activated the MAPK signaling pathway, promoted microglial polarization to the M1 phenotype, decreased the expression of anti-inflammatory mediators and increased the expression of proinflammatory factors in LPS-stimulated BV2 microglial cells. Our results showed that EA may regulate the excitability of primary afferent neurons through PD-L1 and then inhibit the MAPK signaling pathway to promote the transformation of activated M1 microglia into M2 microglia, reduce inflammatory reactions, and finally achieve analgesic effects. A therapy targeting PD-L1 may be an effective strategy for treating neuropathic pain.

Electroacupuncture inhibits dendritic spine remodeling through the srGAP3-Rac1 signaling pathway in rats with SNL.

Previous studies have shown that peripheral nerve injury can lead to abnormal dendritic spine remodeling in spinal dorsal horn neurons. Inhibition of abnormal dendritic spine remodeling can relieve neuropathic pain. Electroacupuncture (EA) has a beneficial effect on the treatment of neuropathic pain, but the specific mechanism remains unclear. Evidence has shown that slit-robo GTPase activating protein 3 (srGAP3) and Rho GTPase (Rac1) play very important roles in dendritic spine remodeling. Here, we used srGAP3 siRNA and Rac1 activator CN04 to confirm the relationship between SrGAP3 and Rac1 and their roles in improving neuropathic pain with EA. Spinal nerve ligation (SNL) was used as the experimental model, and thermal withdrawal latency (TWL), mechanical withdrawal threshold (MWT), Western blotting, immunohistochemistry and Golgi-Cox staining were used to examine changes in behavioral performance, protein expression and dendritic spines. More dendritic spines and higher expression levels of srGAP3 were found in the initial phase of neuropathic pain. During the maintenance phase, dendritic spines were more mature, which was consistent with lower expression levels of srGAP3 and higher expression levels of Rac1-GTP. EA during the maintenance phase reduced the density and maturity of dendritic spines of rats with SNL, increased the levels of srGAP3 and reduced the levels of Rac1-GTP, while srGAP3 siRNA and CN04 reversed the therapeutic effects of EA. These results suggest that dendritic spines have different manifestations in different stages of neuropathic pain and that EA may inhibit the abnormal dendritic spine remodeling by regulating the srGAP3/Rac1 signaling pathway to alleviate neuropathic pain.

Tumor-Targeting Near-Infrared Dimeric Heptamethine Cyanine Photosensitizers with an Aromatic Diphenol Linker for Imaging-Guided Cancer Phototherapy.

Phototherapy is considered a promising alternative to conventional tumor treatments due to its noninvasive modality and effective therapeutic effect. However, designing a photosensitizer with satisfactory therapeutic effect and high security remains a considerable challenge. Herein, a series of dimeric heptamethine cyanine photosensitizers with an aromatic diphenol linker at the meso position is developed to improve the photothermal conversion efficiency (PCE). Thanks to the extended conjugate system and high steric hindrance, the screened 26NA-NIR and 44BP-NIR exhibit high PCE (≈35%), bright near-infrared (NIR) fluorescence, excellent reactive oxygen species (ROS) generation capability, and improved photostability. Furthermore, their outstanding performance on imaging-guided PDT-PTT synergistic therapy is demonstrated by in vivo and in vitro experiments. In conclusion, this study designs a series of dimeric heptamethine cyanine photosensitizers and presents two compounds for potential clinical applications. The strategy provides a new method to design NIR photosensitizers for imaging-guided cancer treatment.

Changyanning regulates gut microbiota and metabolism to ameliorate intestinal injury induced by ETEC K88.

Enterotoxigenic Escherichia coli (ETEC) is a common pathogen of swine colibacillosis, which can causing a variety of diseases initiate serious economic losses to the animal husbandry industry. The traditional Chinese medicine Changyanning (CYN) often used for diarrhea caused by the accumulation of damp heat in the gastrointestinal tract, has anti-bacterial, anti-inflammatory and anti-oxidation effects. This study investigated the effect of CYN on gut microbiota and metabolism in mice infected with ETEC K88. A total of 60 Kunming mices were divided into Control group, ETEC K88 group, CYN.L group (2.5 g/kg), CYN.M group (5 g/kg), CYN.H group (10 g/kg) and BTW group (10 g/kg), determined clinical symptoms, intestinal morphology, inflammatory responses, gut microbiota as well as serum metabolites. CYN administration elevated ETEC K88-induced body weight loss, ameliorated duodenum, ilem, colon pathological injury, and reduced the increase of spleen index caused by ETEC. CYN also reduced the levels of pro-inflammatory cytokines (IL-6, TNE-α) in the serum. 16s rRNA gene sequencing results showed that CYN increased the abundance of beneficial bacteria Lactobacillus but decreased the abundance of pathogenic bacteria Escherichia in the feces of mice. Moreover, CYN participates in amino acid biosynthesis and metabolism in the process of serum metabolism to regulates ameliorate intestinal injury induced by ETEC K88. In conclusion, CYN regulates gut microbiota and metabolism to ameliorate intestinal injury induced by ETEC K88.

Electroacupuncture inhibits dendritic spine remodeling through the srGAP3-Rac1 signaling pathway in rats with SNL

Previous studies have shown that peripheral nerve injury can lead to abnormal dendritic spine remodeling in spinal dorsal horn neurons. Inhibition of abnormal dendritic spine remodeling can relieve neuropathic pain. Electroacupuncture (EA) has a beneficial effect on the treatment of neuropathic pain, but the specific mechanism remains unclear. Evidence has shown that slit-robo GTPase activating protein 3 (srGAP3) and Rho GTPase (Rac1) play very important roles in dendritic spine remodeling. Here, we used srGAP3 siRNA and Rac1 activator CN04 to confirm the relationship between SrGAP3 and Rac1 and their roles in improving neuropathic pain with EA. Spinal nerve ligation (SNL) was used as the experimental model, and thermal withdrawal latency (TWL), mechanical withdrawal threshold (MWT), Western blotting, immunohistochemistry and Golgi-Cox staining were used to examine changes in behavioral performance, protein expression and dendritic spines. More dendritic spines and higher expression levels of srGAP3 were found in the initial phase of neuropathic pain. During the maintenance phase, dendritic spines were more mature, which was consistent with lower expression levels of srGAP3 and higher expression levels of Rac1-GTP. EA during the maintenance phase reduced the density and maturity of dendritic spines of rats with SNL, increased the levels of srGAP3 and reduced the levels of Rac1-GTP, while srGAP3 siRNA and CN04 reversed the therapeutic effects of EA. These results suggest that dendritic spines have different manifestations in different stages of neuropathic pain and that EA may inhibit the abnormal dendritic spine remodeling by regulating the srGAP3/Rac1 signaling pathway to alleviate neuropathic pain.

Tanshinone IIA protected against lipopolysaccharide-induced brain injury through the protective effect of the blood-brain barrier and the suppression of oxidant stress and inflammatory response.

Brain microvascular endothelial cells are essential components of the blood-brain barrier (BBB) that acts as a selective physical barrier and plays protective roles in maintaining brain homeostasis. Tanshinone IIA (Tan IIA), isolated from Salvia miltiorrhiza Bunge, exhibited healthy effects such as antioxidant effects, anti-inflammatory effects, and cardiovascular protective effects. Here, we tried to investigate the positive effect and the potential mechanism of Tan IIA on the lipopolysaccharide (LPS)-induced brain injury in mice and brain microvascular endothelial cells in vitro. In vivo, Tan IIA inhibited the brain injury, and the enhancement of blood-brain barrier permeability in the LPS-induced brain injury in mice. Moreover, Tan IIA suppressed inflammatory response and oxidant response in LPS-treated mice evidenced by low levels of serum TNF-α and IL-1ß, high superoxide dismutase (SOD) activity and low malondialdehyde (MDA) in the brain. In vitro, Tan IIA suppressed the generation of reactive oxygen species (ROS) and MDA, and promoted SOD activity in LPS-stimulated brain microvascular endothelial cells. Moreover, Tan IIA promoted the expression of Claudin5, ZO-1, Nrf2, HO-1 and NQO1 in LPS-stimulated brain microvascular endothelial cells. In conclusion, Tan IIA protected against the LPS-induced brain injury via the suppression of oxidant stress and inflammatory response and protective effect of the BBB through activating Nrf2 signaling pathways and rescue of the tight junction proteins in microvascular endothelial cells, supporting the application of Tan IIA and Salvia miltiorrhiza Bunge as food supplements for the treatment of brain disease.

GC-MS analysis of organic acids in rat urine: A protocol of direct ultrasound-assisted derivatization.

The aim of the present study was to develop a novel ultrasound-assisted derivatization method for analysis of urine that can be used for preliminary screening and monitoring of metabolic disorders. Here we describe an ultrasound-assisted derivatization method followed by GC-MS analysis to quantify 26 organic acids in urine. The optimum levels of the variables affecting the yield of derivatization were investigated, including urease doses, derivatization reagents and derivatization conditions (duration time, reaction temperature and sonic power). The method exhibited the best results with 80 µl urease. The optimal reaction conditions were 100 µl BSTFA, 80% ultrasound power, 70°C and 40 min. This method showed satisfactory linearity, good reproducibility and an acceptable limit of detection and accuracy. Therefore, it could potentially be used to as a standard method to enable comparisons between laboratories. Finally, we applied our method to urine samples from pregnant rats administered 2 or 10 mg/kg folic acid supplementation.

Targeted metabolomics analysis reveals the association between maternal folic acid supplementation and fatty acids and amino acids profiles in rat pups.

Maternal diet during pregnancy can influence offspring's health by affecting development and metabolism. This study aimed to analyze the influence of maternal folic acid (FA) supplementation on the metabolism of rat pups using targeted metabolomics. Twenty female rats were randomly assigned to a FA supplementation (FAS group, n = 10) or control group (n = 10), which were fed AIN93G diet with 2 or 10 mg/kg FA, respectively. We then measured amino acids and their derivatives, biogenic amines, and fatty acids in the female rats and their pups by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC/MS-MS) and gas chromatography-mass spectrometry (GC/MS-MS). In maternal rats, the significant changes of three metabolites (proline, γ-aminobutyric acid and esterified octadecatetraenoic acid, P < 0.05) were observed in FAS group. For the rat pups, FAS pups had significantly lower homocysteine and higher FA levels than control pups. The lower levels of amino acids (leucine, isoleucine, serine, proline) were obtained in FAS pups. Furthermore, there were the decreased esterified fatty acids (arachidonic acid, eicosapentaenoic acid, and docosatetraenoic acid) and free fatty acids (oleic acid, linoleic acid, γ-linolenic acid, octadecatetraenoic acid, arachidonic acid, eicosapentaenoic acid and selacholeic acid) in FAS pups. Metabolic changes in the FAS pups were characterized by changes in fatty acids and amino acids. These results suggested that FA supplementation during pregnancy influenced amino acids and fatty acids metabolism in rat pups. This study provides new insights into the regulation of amino acids and fatty acids metabolism during early life.