[Effect of Xiaoxuming Decoction on activation of astrocytes in acute cerebral ischemia/reperfusion injury].

This study investigated the effect of Xiaoxuming Decoction(XXMD) on the activation of astrocytes after cerebral ischemia/reperfusion(I/R) injury. The model of cerebral IR injury was established using the middle cerebral artery occlusion method. Fluorocitrate(FC), an inhibitor of astrocyte activation, was applied to inhibit astrocyte activation. Rats were randomly divided into a sham group, a model group, a XXMD group, a XXMD+FC group, and a XXMD+Vehicle group. Neurobehavioral changes at 24 hours after cerebral IR injury, cerebral infarction, histopathological changes observed through HE staining, submicroscopic structure of astrocytes observed through transmission electron microscopy, fluorescence intensity of glial fibrillary acidic protein(GFAP) and thrombospondin 1(TSP1) measured through immunofluorescence, and expression of GFAP and TSP1 in brain tissue measured through Western blot were evaluated in rats from each group. The experimental results showed that neurobehavioral scores and cerebral infarct area significantly increased in the model group. The XXMD group, the XXMD+FC group, and the XXMD+Vehicle group all alleviated neurobehavioral changes in rats. The pathological changes in the brain were evident in the model group, while the XXMD group, the XXMD+FC group, and the XXMD+Vehicle group exhibited milder cerebral IR injury in rats. The submicroscopic structure of astrocytes in the model group showed significant swelling, whereas the XXMD group, the XXMD+FC group, and XXMD+Vehicle group protected the submicroscopic structure of astrocytes. The fluorescence intensity and protein expression of GFAP and TSP1 increased in the model group compared with those in the sham group. However, the XXMD group, the XXMD+FC group, and XXMD+Vehicle group all down-regulated the expression of GFAP and TSP1. The combination of XXMD and FC showed a more pronounced effect. These results indicate that XXMD can improve cerebral IR injury, possibly by inhibiting astrocyte activation and down-regulating the expression of GFAP and TSP1.

[Effect of Xiaoxuming Decoction on synaptic plasticity following acute cerebral ischemia-reperfusion in rats].

This study aims to explore the effect of Xiaoxuming Decoction on synaptic plasticity in rats with acute cerebral ischemia-reperfusion. A rat model of cerebral ischemia-reperfusion injury was established by middle cerebral artery occlusion(MCAO). Rats were randomly assigned into a sham group, a MCAO group, and a Xiaoxuming Decoction(60 g·kg~(-1)·d~(-1)) group. The Longa score was rated to assess the neurological function of rats with cerebral ischemia for 1.5 h and reperfusion for 24 h. The 2,3,5-triphenyltetrazolium chloride(TTC) staining and hematoxylin-eosin(HE) staining were employed to observe the cerebral infarction and the pathological changes of brain tissue after cerebral ischemia, respectively. Transmission electron microscopy was employed to detect the structural changes of neurons and synapses in the ischemic penumbra, and immunofluorescence, Western blot to determine the expression of synaptophysin(SYN), neuronal nuclei(NEUN), and postsynaptic density 95(PSD95) in the ischemic penumbra. The experimental results showed that the modeling increased the Longa score and led to cerebral infarction after 24 h of ischemia-reperfusion. Compared with the model group, Xiaoxuming Decoction intervention significantly decreased the Longa score and reduced the formation of cerebral infarction area. The modeling led to the shrinking and vacuolar changes of nuclei in the brain tissue, disordered cell arrangement, and severe cortical ischemia-reperfusion injury, while the pathological damage in the Xiaoxuming Decoction group was mild. The modeling blurred the synaptic boundaries and broadened the synaptic gap, while such changes were recovered in the Xiaoxuming Decoction group. The modeling decreased the fluorescence intensity of NEUN and SYN, while the intensity in Xiaoxuming Decoction group was significantly higher than that in the model group. The expression of SYN and PSD95 in the ischemic penumbra was down-regulated in the model group, while such down-regulation can be alleviated by Xiaoxuming Decoction. In summary, Xiaoxuming Decoction may improve the synaptic plasticity of ischemic penumbra during acute cerebral ischemia-reperfusion by up-regulating the expression of SYN and PSD95.

Chronic ß-adrenergic stress contributes to cardiomyopathy in rodents with collagen-induced arthritis.

Patients with rheumatoid arthritis (RA) have a much higher incidence of cardiac dysfunction, which contributes to the high mortality rate of RA despite anti-arthritic drug therapy. In this study, we investigated dynamic changes in cardiac function in classic animal models of RA and examined the potential effectors of RA-induced heart failure (HF). Collagen-induced arthritis (CIA) models were established in rats and mice. The cardiac function of CIA animals was dynamically monitored using echocardiography and haemodynamics. We showed that cardiac diastolic and systolic dysfunction occurred in CIA animals and persisted after joint inflammation and that serum proinflammatory cytokine (IL-1ß, TNF-α) levels were decreased. We did not find evidence of atherosclerosis (AS) in arthritic animals even though cardiomyopathy was significant. We observed that an impaired cardiac ß1AR-excitation contraction coupling signal was accompanied by sustained increases in blood epinephrine levels in CIA rats. Furthermore, serum epinephrine concentrations were positively correlated with the heart failure biomarker NT-proBNP in RA patients (r2 = +0.53, P < 0.0001). In CIA mice, treatment with the nonselective ßAR blocker carvedilol (2.5 mg·kg-1·d-1, for 4 weeks) or the specific GRK2 inhibitor paroxetine (2.5 mg·kg-1·d-1, for 4 weeks) effectively rescued heart function. We conclude that chronic and persistent ß-adrenergic stress in CIA animals is a significant contributor to cardiomyopathy, which may be a potential target for protecting RA patients against HF.

Flower-like molybdenum disulfide/cobalt ferrite composite for the extraction of benzotriazole UV stabilizers in environmental samples.

Benzotriazole UV stabilizers (BUVSs) are a class of emerging contaminants of concern; the development of rapid and convenient monitoring method for these trace-level pollutants in waters is of crucial significance in environmental science. Here, a novel magnetic flower-like molybdenum disulfide/cobalt ferrite nanocomposite (MoS2/CoFe2O4) was synthesized by hydrothermal reaction. Compared with the conventional Fe3O4-based magnetic composites, the proposed material just required a minimum consumption of Co/Fe towards the equivalent of MoS2 while providing superior magnetization performance. Taking advantages of high adsorption capacity, extraordinary stability, and repeatability in construction, MoS2/CoFe2O4 was applied to the extraction to BUVSs. The enrichment factors of three BUVSs were in the range 164-193 when 20 mL of environmental water sample was loaded on 40 mg of the adsorbent. MoS2/CoFe2O4 could be regenerated and recycled at least 10 cycles of adsorption/desorption with recoveries of 80.1-111%. The method of MoS2/CoFe2O4-based extraction coupled with high-performance liquid chromatography-variable wavelength detector was applied to the monitoring of BUVSs in seawater, lake water, and wastewater, which gave detection limits (S/N = 3) of 0.023-0.030 ng·mL-1 and recoveries of 80.1-110%. The intra-day and inter-day precisions (relative standard deviation, RSDs, n = 3) were in the range 1.6-7.5% and 3.2-11.5%, respectively. The approach is an alternative for efficient and sensitive extraction and determination of trace-level environmental pollutants in waters.

Monodispersed CaCO3@hydroxyapatite/magnetite microspheres for efficient and selective extraction of benzoylurea insecticides in tea beverages samples.

A novel monodispersed CaCO3@hydroxyapatite/magnetite microsphere (CaCO3 @HAP/Fe3O4) was prepared via an in-situ growth strategy, and applied as an adsorbent for efficient and selective adsorption of benzoylurea insecticides (BUs) in various tea beverages samples. The sorbent exhibited uniformity in particle size, good mono-dispersibility and excellent solvent stability. The adsorption equilibrium of BUs (100 ng/mL) in 10 mL of tea beverages samples was achieved on 20 mg of CaCO3 @HAP/Fe3O4 within 10 min. The adsorption followed pseudo-second-order kinetics and Langmuir models and the maximum adsorption capacities of 131.9-161.3 mg/g were accomplished via hydrophobic interactions, hydrogen bonding, and the affinity of F atom and Ca2+. Coupled with high performance liquid chromatography, the method offered wide linear ranges of 0.8-1000 ng/mL with correlation coefficients (r) ≥ 0.9995, low limits of detection of 0.2-0.3 ng/mL and large enrichment factors of 75.7-102. The recoveries ranged from 75.7%- 102% with intra- and inter-day precisions of 1.9%- 9.3% and 1.6%- 11.8%, respectively. In addition, CaCO3 @HAP/Fe3O4 could be easily regenerated and reused at least 10 times with no significant loss of recovery. These results revealed an alternative strategy for fast and convenient determination of BUs in tea beverages samples and proved the great feasibility of CaCO3 @HAP/Fe3O4 in the application for the selective adsorption of BUs.

TNF-α impairs EP4 signaling through the association of TRAF2-GRK2 in primary fibroblast-like synoviocytes.

Our previous study showed that chronic treatment with tumor necrosis factor-α (TNF-α) decreased cAMP concentration in fibroblast-like synoviocytes (FLSs) of collagen-induced arthritis (CIA) rats. In this study we investigated how TNF-α impairs cAMP homeostasis, particularly clarifying the potential downstream molecules of TNF-α and prostaglandin receptor 4 (EP4) signaling that would interact with each other. Using a cAMP FRET biosensor PM-ICUE3, we demonstrated that TNF-α (20 ng/mL) blocked ONO-4819-triggered EP4 signaling, but not Butaprost-triggered EP2 signaling in normal rat FLSs. We showed that TNF-α (0.02-20 ng/mL) dose-dependently reduced EP4 membrane distribution in normal rat FLS. TNF-α significantly increased TNF receptor 2 (TNFR2) expression and stimulated proliferation in human FLS (hFLS) via ecruiting TNF receptor-associated factor 2 (TRAF2) to cell membrane. More interestingly, we revealed that TRAF2 interacted with G protein-coupled receptor kinase (GRK2) in the cytoplasm of primary hFLS and helped to bring GRK2 to cell membrane in response of TNF-α stimulation, the complex of TRAF2 and GRK2 then separated on the membrane, and translocated GRK2 induced the desensitization and internalization of EP4, leading to reduced production of intracellular cAMP. Silencing of TRAF2 by siRNA substantially diminished TRAF2-GRK2 interaction, blocked the translocation of GRK2, and resulted in upregulated expression of membrane EP4 and intracellular cAMP. In CIA rats, administration of paroxetine to inhibit GRK2 effectively improved the symptoms and clinic parameters with significantly reduced joint synovium inflammation and bone destruction. These results elucidate a novel form of cross-talk between TNFR (a cytokine receptor) and EP4 (a typical G protein-coupled receptor) signaling pathways. The interaction between TRAF2 and GRK2 may become a potential new drug target for the treatment of inflammatory diseases.

Chemo- and regioselective ring-opening of donor-acceptor oxiranes with N-heteroaromatics.

The first ring-opening of D-A oxiranes with N-heteroaromatics in a chemoselective C-C bond cleavage manner was achieved. In the presence of 5 mol% of Y(OTf)3 as the catalyst, diverse N-heteroaromatics, including benzotriazoles, purines, substituted benzimidazole, imidazole and pyrazole, reacted well with various D-A oxiranes, providing acyclic nucleoside analogues containing a N-glycosidic bond in up to 97% yield and up to >95 : 5 regioselectivity. Through simple transformation, the Ganciclovir analogue could also be obtained.

Intraspecific nucleotide divergence in Saccharomycodes ludwigii, and proposal of Saccharomycodes pseudoludwigii sp. nov, a new apiculate yeast isolated from China.

The six synonyms currently accepted under Saccharomycodes ludwigii were investigated for by phenotypic properties, however, the sequence diversity of the rRNA and protein coding genes have not yet been determined. Nine strains including the type strains of synonyms of S. ludwigii deposited in the CBS yeast collection, Westerdijk Fungal Biodiversity Institute, Utrecht, The Netherlands, were analyzed using a multi-locus sequence analysis (MLSA) approach that included sequences of 18S ribosomal RNA (rRNA), the D1/D2 domains of the 26S rRNA, the ITS region (including the 5.8S rRNA) and fragments of genes encoding the largest subunit of the RNA polymerase II (RPB1 and RPB2) and translation elongation factor 1-α (TEF1). Our results showed that the nine strains have identical D1/D2, 18S and RPB2 sequences and similar ITS, RPB1 and TEF1 sequences, which indicated that they are conspecific. In addition, a novel species of Saccharomycodes, S. pseudoludwigii sp. nov. (type CGMCC 2.4526 T) that was isolated from fruit and tree bark in China, is proposed. The MycoBank number of this new species is MB 811,650.

Electrooxidative Iridium-Catalyzed Regioselective Annulation of Benzoic Acids with Internal Alkynes.

Electrochemically driven, Cp*Ir(III)-catalyzed regioselective annulative couplings of benzoic acids with alkynes have been established herein. The combination of iridium catalyst and electricity not only circumvents the need for stoichiometric amount of chemical oxidant, but also ensures broad reaction compatibility with a wide array of sterically and electronically diverse substrates. This electrochemical approach represents a sustainable strategy as an ideal alternative and supplement to the oxidative annulations methodology to be engaged in the synthesis of isocoumarin derivatives.

The Anti-apoptosis Effect of Single Electroacupuncture Treatment via Suppressing Neuronal Autophagy in the Acute Stage of Ischemic Stroke Without Infarct Alleviation.

The main purpose of the study was to investigate the antiapoptotic effect of electroacupuncture (EA) in the acute stage of ischaemic stroke in rats. The cerebral ischemia model was established by middle cerebral artery occlusion (MCAO)/reperfusion in rats. A single EA treatment was performed at the acute stage of ischaemic stroke. The neurological function, brain water content, apoptotic cell number, and cerebral infarct volume were assessed in stroke rats. The expression of autophagy-related proteins (LC3II/I, Beclin1, P62, and LAMP1), Sirtuin 1 (SIRT1), p-JNK, p-ERK1/2, and cleaved caspase-3 (CCAS3) were measured by Western blot, immunofluorescence, and immunohistochemistry. Rapamycin (RAP, an activator of autophagy) was used to confirm the antiapoptotic effect of EA via regulating autophagy. The brain edema infarct size and apoptotic cell number were increasing within 3 days following stroke, and brain edema reached its peak at 24 h after stroke. EA treatment at 24 h after ischaemic stroke obviously suppressed the number of apoptotic cells and brain edema. However, there were no significant differences in infarct volumes among EA-12 h, EA-24 h, and MCAO/R group. Moreover, EA treatment at 24 h after ischaemic stroke obviously suppressed the expression of CCAS3, LC3II/I, Beclin1 while increasing the level of P62 and LAMP1 and hence mediating autophagy, which was reversed by RAP. Meanwhile, the expression of SIRT1, p-ERK1/2, p-JNK were promoted by EA at 24 h after ischaemic stroke. In conclusion, EA treatment may suppress apoptosis possibly via regulating autophagy in the acute period after ischaemic stroke, hence reducing brain injury.

Proposal of Two New Combinations, Twenty New Species, Four New Genera, One New Family, and One New Order for the Anamorphic Basidiomycetous Yeast Species in Ustilaginomycotina.

Two hundred and forty-four ustilaginomycetous yeast or yeast-like strains were isolated from the soil, skin of animals or humans and plant materials during the past 20 years. Among them, 203 strains represent 39 known species, whereas 41 strains represent several novel species based on the sequence analyses of the rDNA genes [18S rDNA, Internal Transcribed Spacer (ITS) regions, 26S rDNA D1/D2 domain] and three protein genes (RPB1, RPB2, and TEF1). In this study, one new order, one new family, four new genera, twenty new species, and two new combinations were proposed. They are Franziozymales ord. nov., Franziozymaceae fam. nov., Baueromyces gen. nov., Franziozyma gen. nov., Guomyces gen. nov., Yunzhangomyces gen. nov., Baueromyces planticola sp. nov., Franziozyma bambusicola sp. nov., Gjaerumia cyclobalanopsidis sp. nov., Gjaerumia pseudominor sp. nov., Jamesdicksonia aceris sp. nov., Jaminaea lantanae sp. nov., Kalmanozyma hebeiensis sp. nov., Langdonia ligulariae sp. nov., Meira hainanensis sp. nov., Meira pileae sp. nov., Meira plantarum sp. nov., Phragmotaenium parafulvescens sp. nov., Sporisorium cylindricum sp. nov., Sympodiomycopsis europaea sp. nov., Tilletiopsis lunata sp. nov., Tilletiopsis pinicola sp. nov., Yunzhangomyces clavatus sp. nov., Yunzhangomyces cylindricus sp. nov., Yunzhangomyces qinlingensis sp. nov., Yunzhangomyces orchidis sp. nov., Guomyces nicotianae comb. nov., and Yunzhangomces scirpi comb. nov.

Discovery of novel benzofuran scaffold as 4-hydroxyphenylpyruvate dioxygenase inhibitors.

BACKGROUND: 4-Hydroxyphenylpyruvate dioxygenase (HPPD) plays an important role in addressing the issue of plant protection research. This study sheds new light on the differences in molecular scaffold from commercialized HPPD inhibitors. RESULTS: The compounds A1-A18 and B1-B27 were synthesized for in vitro and greenhouse experiments. The greenhouse experiment data indicated that compounds B14 and B18 displayed excellent herbicidal activity, which was higher compared to that of mesotrione. In vitro testing indicated that the compounds were HPPD inhibitors. Moreover, molecular simulation results show that the compounds B14, B18, and mesotrione shared similar interplay with surrounding residues, which led to a perfect interaction with the active site of Arabidopsis thaliana HPPD. Based on crop selectivity results, compounds B14 and B18 were selected for maize studies (injury≤10%), indicating its potential for weed control in maize fields. CONCLUSION: These results showed that the pyrazole-benzofuran structure could be used as possible lead compounds for the development of HPPD inhibitors. © 2020 Society of Chemical Industry.

Comparison of two regimens for patients with thyroid-associated ophthalmopathy receiving intravenous methyl prednisolone: A single center prospective randomized trial.

Intravenous (i.v.) glucocorticoid is recommended for active moderate-to-severe thyroid-associated ophthalmopathy (TAO). However, the details of the treatment schedule are still debatable. The present prospective randomized trial was performed to compare clinical outcomes and serum cytokines between the two regimens. A cohort of 90 patients with active moderate-to-severe TAO was randomized to receive i.v. methyl prednisolone on a weekly protocol or daily scheme. The response rate was evaluated at the 12-week follow-up visit. Serum interleukin (IL)-2, IL-6 and IL-17 levels were measured in 160 patients with TAO, 60 patients with isolated Graves' disease (GD) and 60 normal control (NC) at baseline, as well as patients with active moderate-to-severe TAO at the 12th week after treatment. The daily scheme had a higher response rate than the weekly protocol without a significant difference (77.8 vs. 63.6%, P>0.05). No major adverse events were recorded under either regimen. Overall, minor events were more common on the daily scheme (11.36 vs. 4.35%, P<0.05)than on the weekly protocol, whereas the deterioration of eye symptoms (two patients) was only reported on the weekly protocol. At baseline, the IL-17 level in the TAO group was higher than that in the isolated GD and NC groups (P<0.05). In addition, the IL-17 level in the active TAO group was higher than that in the inactive TAO group (P<0.05). Furthermore, the IL-17 level had significantly decreased under the two regimens at the 12-week visit (P<0.05). In conclusion, for patients with active moderate-to-severe TAO, daily i.v. glucocorticoid therapy has a relative higher response rate than the weekly protocol with a few more minor adverse events. These two regimens have their own merits with regard to adverse effects. IL-17 has the potential to be a biomarker for evaluating TAO activity and treatment effects.

In-situ fabrication of zeolite imidazole framework@hydroxyapatite composite for dispersive solid-phase extraction of benzodiazepines and their determination with high-performance liquid chromatography-VWD detection.

A novel zeolite imidazole framework@hydroxyapatite composite (ZIF-8@HAP) was constructed via in-situ growth and developed for efficient dispersive solid-phase extraction (DSPE) of three benzodiazepines from urine samples. The prepared composite was characterized by scanning electron microscopy, energy-dispersive spectrometer, Fourier-transform infrared spectrometry, X-ray diffractometry, zeta potential analyzer, and nitrogen adsorption-desorption experiment. Characterization results showed typical dodecahedron ZIF-8 crystals that were uniformly located on the surface of rod-like HAP. The combination of ZIF-8 and HAP made the surface area significantly enhanced from 4.68 to 205.44 m2 g-1. Compared with a commercial C18 adsorbent, ZIF-8@HAP exhibited superior removal performance for interfering components from urine and offered better extraction properties for the analytes. The prepared ZIF-8@HAP was applied as an adsorbent in DSPE, and the main experimental parameters, including pH and ionic strength of solution, adsorbent amount, adsorption time, elution solvent, and volume, were investigated. Under optimal conditions, the adsorption for 250 ng mL-1 of each analyte in 4 mL of urine was accomplished within 2 min using 60 mg of adsorbent. The method of ZIF-8@HAP-based DSPE followed by high-performance liquid chromatography gave enhancement factors of 13.3-15.3, linear ranges of 2.5-500 ng mL-1, and limits of detection (S/N = 3) of 0.7-1.4 ng mL-1. The relative recoveries at three spiked levels ranged from 88.7 - 102% with intra-day and inter-day precisions from 3.0 - 10.3% and 2.3 - 12.3%, respectively. These results indicated that the proposed strategy had promising applicability for convenient, rapid, and efficient determination of benzodiazepines in urine samples.Graphical abstract In-situ fabrication of ZIF-8@HAP composite for dispersive solid-phase extraction of benzodiazepines in urine samples.

Inhibition of NLRP3 Inflammasome: A Prospective Target for the Treatment of Ischemic Stroke.

Stroke is one of the major devastating diseases with no effective medical therapeutics. Because of the high rate of disability and mortality among stroke patients, new treatments are urgently required to decrease brain damage following a stroke. In recent years, the inflammasome is a novel breakthrough point that plays an important role in the stroke, and the inhibition of inflammasome may be an effective method for stroke treatment. Briefly, inflammasome is a multi-protein complex that causes activation of caspase-1 and subsequent production of pro-inflammatory factors including interleukin (IL)-18 and IL-1ß. Among them, the NLRP3 inflammasome is the most typical inflammasome, which can detect cell damage and mediate inflammatory response to tissue damage in ischemic stroke. The NLRP3 inflammasome has become a key mediator of post-ischemic inflammation, leading to a cascade of inflammatory reactions and cell death eventually. Thus, NLRP3 inflammasome is an ideal therapeutic target due to its important role in the inflammatory response after ischemic stroke. In this mini review article, we will summarize the structure, assembly, and regulation of NLRP3 inflammasome, the role of NLRP3 inflammasome in ischemic stroke, and several treatments targeting NLRP3 inflammasome in ischemic stroke. The further understanding of the mechanism of NLRP3 inflammasome in patients with ischemic stroke will provide novel targets for the treatment of cerebral ischemic stroke patients.

Discovery of novel arylthioacetic acid derivatives as 4-hydroxyphenylpyruvate dioxygenase inhibitors.

BACKGROUND: 4-Hydroxyphenylpyruvate dioxygenase (HPPD) plays an important role in addressing the issue of plant protection research. In a continuing effort to discover novel HPPD inhibitors, we adopted a bioisosterism strategy to design a series of novel arylthioacetic acid scaffold based on the previously discovered aryloxyacetic acid scaffold. This study sheds new light on the discovery of novel HPPD inhibitors. RESULTS: The compounds A1-A30 and B1-B39 were prepared through an efficient synthetic route for in vitro and glasshouse experiments (herbicidal activities, herbicidal activity spectrum, and crop selectivity). Preliminary bioassay results reveal that these derivatives are promising Arabidopsis thaliana HPPD inhibitors, compounds A11 (Ki = 0.021 µmol L-1 ) and B20 (Ki = 0.022 µmol L-1 ), which exhibit similar activities to that of mesotrione (Ki = 0.020 µmol L-1 ). The glasshouse experiments data indicated that compounds B34 displayed excellent herbicidal activity, which was higher compared to that of mesotrione. Moreover, molecular simulation results show that the compounds B20, B34, and mesotrione shared similar interplay with surrounding residues, which led to a perfect interaction with the active site of Arabidopsis thaliana HPPD. Based on herbicidal results, compound B34 was selected for crop selectivity studies (corn injury ≤ 10%), indicating its potential for weed control in corn fields. CONCLUSION: These bioassay results showed that the compound B34 could be used as a possible lead compound for the development of HPPD inhibitors. © 2020 Society of Chemical Industry.

The role of exosomes in stroke.

Stroke is induced by a partial disruption of cerebral blood flow to the brain and is related to high morbidity and mortality. In the central nervous system, exosomes have been proven to exert neuroprotective effects, reducing brain damage following a stroke. This review was performed by searching the relevant articles in the SCIENCEDIRECT, PUBMED, and Web of Science databases from respective inception to November 2018. We review the relationship between exosomes and angiogenesis, neurogenesis, antiapoptosis, autophagy, and the blood-brain barrier in stroke. Moreover, exosomes are found to be a promising tool for the diagnosis and treatment of stroke. In summary, exosomes provide a novel way to alleviate brain damage following a stroke.

Electroacupuncture Inhibits Neuronal Autophagy and Apoptosis via the PI3K/AKT Pathway Following Ischemic Stroke.

Electroacupuncture (EA) is a safe and effective therapy for ischemic stroke in both clinical and laboratory settings. However, the underlying mechanism behind EA treatment for stroke remains unclear. Here, we aimed to evaluate whether EA treatment at the acupoints of Zusanli (ST36) and Quchi (LI11) exerted a neuroprotective effect on ischemic stroke rats by modulating autophagy and apoptosis via the PI3K/AKT/mTOR signaling pathway. EA was performed at 24 h following brain ischemia/reperfusion (I/R) for 30 min per day for 3 days. Our results indicated that EA treatment significantly decreased neurological deficits and cerebral infarct volume in ischemic stroke rats. Also, EA intervention markedly reduced neuronal apoptosis by suppressing the activation of cleaved caspase-3 (CCAS3) at 72 h following I/R, as shown by a Western blot analysis. Furthermore, EA treatment after ischemic stroke suppressed the ischemia activated expression level of LC3II/I and Atg7 and increased the ischemia inhibited expression level of PI3K, phosphorylation of mTOR, phosphorylation of AKT, P62 and LAMP1, hence mediating the autophagy level of the neurocyte, which was reversed by the PI3K inhibitor Dactolisib. In summary, our results indicate that the protective effects of EA treatment at points of Quchi (LI11) and Zusanli (ST36) in rats following cerebral I/R injury was associated with the inhibition of neuronal apoptosis and autophagy via activating the PI3K/AKT/mTOR signaling pathway.

The Beneficial Role of Exercise Training for Myocardial Infarction Treatment in Elderly.

Worldwide, elderly people have a higher prevalence of myocardial infarction (MI), which is associated with body function aging and a sedentary lifestyle. In addition to medication, exercise training is a well-established supplementary method to prevent and treat cardiovascular diseases (CVDs). Substantial evidence has shown the value of different intensity exercise programs in the prevention and treatment of MI, and exercise rehabilitation programs are also applicable to elderly patients with MI. Although exercise rehabilitation programs could significantly improve function, quality of life (QoL), and lower mortality and morbidity for people with MI, such programs are underused because their mechanisms are not accurately elucidated. To promote the application of exercise therapy for MI, this review summarizes the benefits and mechanisms of exercise rehabilitation for post-MI patients and provides rationalized proposals for outpatient cardiac rehabilitation.

Synthesis and herbicidal activities of aryloxyacetic acid derivatives as HPPD inhibitors.

A series of aryloxyacetic acid derivatives were designed and synthesized as 4-hydoxyphenylpyruvate dioxygenase (HPPD) inhibitors. Preliminary bioassay results reveal that these derivatives are promising Arabidopsis thaliana HPPD (AtHPPD) inhibitors, in particular compounds I12 (K i = 0.011 µM) and I23 (K i = 0.012 µM), which exhibit similar activities to that of mesotrione, a commercial HPPD herbicide (K i = 0.013 µM). Furthermore, the newly synthesized compounds show significant greenhouse herbicidal activities against tested weeds at dosages of 150 g ai/ha. In particular, II4 exhibited high herbicidal activity for pre-emergence treatment that was slightly better than that of mesotrione. In addition, compound II4 was safe for weed control in maize fields at a rate of 150 g ai/ha, and was identified as the most potent candidate for a novel HPPD inhibitor herbicide. The compounds described herein may provide useful guidance for the design of new HPPD inhibiting herbicides and their modification.