Advances in the Modification of Silane-Based Sol-Gel Coating to Improve the Corrosion Resistance of Magnesium Alloys.

As the lightest structural materials, magnesium (Mg) alloys play a significant role in vehicle weight reduction, aerospace, military equipment, energy saving, and emission reduction. However, the poor corrosion resistance of Mg alloys has become a bottleneck restricting its wide application. Developing a good surface protective coating can effectively improve the corrosion resistance of Mg alloys. The silane-based sol-gel coating technology has been widely used in the corrosion protection of Mg alloys in recent years due to its advantages of simple process, accessible tailoring of film composition and structure, and excellent corrosion resistance. Whereas the synthesis of sol-gel coatings includes the hydrolysis and dehydration process, which may inherently contain micron or nano defects in the coatings, thereby making it detrimental to the anti-corrosion effect. Therefore, in order to enhance their protection against corrosion, the appropriate modification of sol-gel coatings has become a current research hotspot. This review is based on the modification methods of silane-based sol-gels on the surface of Mg alloys, which are divided into four categories: bare sol-gel, nanoparticles, corrosion inhibitors, and sol-gel-based composite coatings. The modification methods and corrosion protection mechanism are discussed respectively, and the application, development, and research strategies of silane-based sol-gel coatings are included.

Traditional Chinese Medicine as a Promising Strategy for the Treatment of Alzheimer's Disease Complicated With Osteoporosis.

Alzheimer's disease (AD) and osteoporosis (OP) are progressive degenerative diseases caused by multiple factors, placing a huge burden on the world. Much evidence indicates that OP is a common complication in AD patients. In addition, there is also evidence to show that patients with OP have a higher risk of AD than those without OP. This suggests that the association between the two diseases may be due to a pathophysiological link rather than one disease causing the other. Several in vitro and in vivo studies have also proved their common pathogenesis. Based on the theory of traditional Chinese medicine, some classic and specific natural Chinese medicines are widely used to effectively treat AD and OP. Current evidence also shows that these treatments can ameliorate both brain damage and bone metabolism disorder and further alleviate AD complicated with OP. These valuable therapies might provide effective and safe alternatives to major pharmacological strategies.

A Decreased Absolute Number of Treg Cells in Patients with Active Rheumatoid Arthritis is Associated with Elevated Serum Osteopontin Levels with Disease Progression.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic and refractory autoimmune disease characterized by synovial inflammation with unknown aetiology. Immune system dysfunction mediated by CD4+ T lymphocytes, which is regulated by the cytokine osteopontin (OPN), plays an important role in the pathogenesis of RA. METHODS: In this study, the levels of peripheral CD4+ T subsets and serum OPN in patients with active RA were measured and analysed to determine the possible pathogenesis of RA and to provide potential therapeutic targets. RESULTS: Serum OPN levels in both patients with active RA and patients with refractory RA were higher than those in healthy controls (HCs). Compared with HCs, the absolute numbers of Th2 cells increased in patients with active RA, while the absolute counts of Th1 and Treg cells decreased. There was no significant difference in CD4+ T subset levels between new-onset and refractory patients. As the condition persisted or deteriorated, a gradual increase in the levels of OPN and gradual declines in the absolute counts of Th1 and Treg cells were observed in patients with active RA. The fewest Th1 and Treg cells and the highest OPN levels were observed in patients with high disease activity. The serum OPN level was only significantly negatively correlated with the absolute counts of Treg cells in the CD4+ T lymphocyte subsets. CONCLUSIONS: Fewer Treg cells with the increase in disease activity may be related to the increased OPN concentration, which may provide new ideas and directions for the targeted immunoregulatory treatment of RA.

PI3K/AKT/Nrf2 signalling pathway is involved in the ameliorative effects of xanthohumol on amyloid ß-induced oxidative damage and bone loss.

OBJECTIVE: Xanthohumol (XAN), a natural isoflavone from Humulus lupulus L., possesses biological activities on relieving oxidative stress and osteoporosis (OP). This study aimed to evaluate the antioxidative and osteoprotective effect of XAN on Aß-injured osteoblasts, and explore its underlying mechanism. METHODS: Osteoblasts were pretreated with XAN followed by stimulation with Aß1-42. Cell proliferation, ALP activity, bone mineralization and bone formation index were measured. Apoptosis and reactive oxygen species (ROS) were analysed with flow cytometer. PI3K inhibitor LY294002 or siRNA-Nrf2 was added and transfected in osteoblasts, to further confirm whether the pathway participated in the regulation of XAN-induced cytoprotection. KEY FINDINGS: XAN markedly improved the proliferation, differentiation and mineralization of Aß-injured osteoblasts. Additionally, XAN reduced cell apoptosis rate and ROS level, and increased the expression of p-AKT, Nrf2, NQO1, HO-1 and SOD-2. More importantly, LY294002 or siNrf2 abolished the beneficial effect of XAN on osteoblasts activity and decreased the PI3K expression and inhibited its downstream proteins, indicating XAN activated PI3K/AKT/Nrf2 pathway in Aß-injured osteoblasts. CONCLUSION: It was the first time to reveal the antioxidative and osteoprotective effect of XAN through regulating PI3K/AKT/Nrf2 pathway in Aß-injured osteoblasts, which provides reference for the clinical application of XAN in the prevention and treatment of OP.

Absorption, metabolism, and pharmacokinetic profile of xanthohumol in rats as determined via UPLC-MS/MS.

Xanthohumol, a natural isoflavone from Humulus lupulus L., possesses biological activities. However, the biological fate of xanthohumol in vivo remains unclear. The aim of this study was to investigate the absorption and metabolism of xanthohumol in rats through UPLC-MS/MS. The plasma, urine and fecal samples were collected after oral administration of xanthohumol (25, 50, 100 mg/kg) in SD rats. The contents of xanthohumol and its metabolites were determined by UPLC-MS/MS. A total of 6 metabolites of xanthohumol were identified in rats, including methylated, glucuronidated, acid-catalyzed cyclization and oxidation, indicating xanthohumol underwent phase I and II metabolism. Besides, isoxanthohumol was the major metabolites of xanthohumol. Xanthohumol was rapidly absorbed, metabolized, and eliminated in rats. The pharmacokinetics results showed the Tmax of xanthohumol and isoxanthohumol were 3 and 2.33 h, respectively. The AUC0-t of xanthohumol and isoxanthohumol were 138.83 ± 6.03 and 38.77 ± 4.46 ng/ml·h, respectively. Furthermore, xanthohumol was mainly excreted in the form of prototype through feces and a small amount of xanthohumol was excreted through urine. These results illustrated the absorption, metabolism, and pharmacokinetics process of xanthohumol in rats, and provided a reference for the further rational applications.

Fuzheng Yiliu Formula Regulates Tumor Invasion and Metastasis through Inhibition of WAVE3 Expression.

OBJECTIVE: To explore the mechanism of action of Fuzheng Yiliu formula (FZYLF) in regulation of the invasion and metastasis of MDA-MB-231/Adr human breast cancer cells through WAVE3. METHODS: The MDA-MB-231/Adr cells with high invasive ability were screened by Transwell, and the plasmid with high WAVE3 expression was made for transfection. Plasmid transfection efficiency and protein expression level were verified by polymerase chain reaction (PCR) and western blotting (WB). The effect of FZYLF on cell proliferation and invasion was investigated before and after WAVE3 silencing by flow cytometry. A nude mouse model of tumor metastasis was established to study the antitumor activity of FZYLF. RESULTS: The expression levels of mRNA and proteins of intracellular WAVE3 increased significantly after plasmid transfection, mRNA from 1.37± 0.41 to 9.88 ± 1.31 and protein from 1 ± 0.08 to 5.09 ± 0.03 (P < 0.01). Intervention with FZYLF could significantly affect the activity of MDA-MB-231/Adr cells and inhibit invasion and metastasis, IC50 from 71.04 to 46.41 mg/mL and from 162 ± 14.82 to 81.4 ± 12.05 (P < 0.05 or P < 0.01), and significantly reduce the expression levels of WAVE3 (from 1 ± 0.02 to 0.63 ± 0.04), MMP-9 (from 1 ± 0.05 to 0.63 ± 0.03), NF-κB (p65) (from 1 ± 0.02 to 0.62 ± 0.02), and p-IκBα (from 1 ± 0.03 to 0.68 ± 0.02) (P < 0.05 or P < 0.01). The T/C (%) of FZYLF (13 g crude drug/kg) was 62.06% for MDA-MB-231/Adr tumor xenografted in nude mice, with a tumor inhibition rate of 39.64%. CONCLUSION: FZYLF can inhibit the invasion and proliferation of the MDA-MB-231/Adr human breast cancer cells, and the mechanism of action may be related to the regulation of WAVE3 expression.

Asiatic Acid Interferes with Invasion and Proliferation of Breast Cancer Cells by Inhibiting WAVE3 Activation through PI3K/AKT Signaling Pathway.

OBJECTIVE: To explore the ability of asiatic acid to interfere with the invasion and proliferation of breast cancer cells by inhibiting WAVE3 expression and activation through the PI3K/AKT signaling pathway. METHODS: The MDA-MB-231 cells with strong invasiveness were screened by transwell assay, and plasmids with high expression of WAVE3 were constructed for transfection. The transfection effect and protein expression level of plasmids were verified by PCR and WB. The effects of asiatic acid on cell proliferation and invasion were investigated by flow cytometry. The xenografted tumor models in nude mice were established to study the antitumor activity of asiatic acid. RESULTS: Asiatic acid significantly inhibited the activity of MDA-MB-231 cells, and the expression level of WAVE3 increased significantly in the tissue of ductal carcinoma in situ and was lower than that in the metastasis group. After plasmid transfection, the mRNA and protein expression of WAVE3 increased significantly in the cells. Asiatic acid at different concentrations had an impact on cell apoptosis and invasion and could significantly inhibit the expression of WAVE3, P53, p-PI3K, p-AKT, and other proteins. The T/C(%) of asiatic acid (50 mg/kg) for MDA-MB-231(F10) xenografted tumor in nude mice was 46.33%, with a tumor inhibition rate of 59.55%. Asiatic acid could significantly inhibit the growth of MDA-MB-231 (F10) xenografted tumors in nude mice (p < 0.05). CONCLUSIONS: Asiatic acid interferes with the ability of breast cancer cells to invade and proliferate by inhibiting WAVE3 expression and activation and the mechanism of action may be related to the PI3K/AKT signaling pathway.

Patent foramen ovale closure versus medical therapy for cryptogenic stroke: An updated meta-analysis.

BACKGROUND: The efficacy of patent foramen ovale (PFO) closure for secondary stroke prevention in cryptogenic stroke (CS) patients with PFO is uncertain. This meta-analysis aims to assess whether PFO closure is superior to medical therapy. METHODS: Pooled estimates were calculated using Revman 5.3. The two primary endpoints were stroke and transient ischemic attack (TIA). Secondary outcomes included all-cause mortality, new-onset atrial fibrillation or flutter, major bleeding and any adverse event. RESULTS: Five randomized controlled trials were included. A total of 3440 patients were randomized to either PFO closure (n = 1829) or medical therapy group (n = 1611) and followed for average 2.0-5.9 years. PFO closure reduced the incidence of recurrent stroke in CS patients with PFO compared to medical therapy (Risk ratio (RR) 0.42, 95% confidence intervals (CI) 0.20-0.91, P = 0.03; hazard ratio (HR) 0.34, 95% CI 0.15-0.78, p = 0.01). There were no significant differences between the two groups in TIA (RR 0.78, 95% CI 0.53-1.15, P = 0.21; HR 0.73, 95% CI 0.49-1.09, p = 0.12), all-cause mortality (RR 0.76, 95% CI 0.35-1.63, P = 0.48), major bleeding (RR 0.96, 95% CI 0.42-2.20, P = 0.93) and any adverse event (RR 1.06, 95% CI 0.95-1.18, P = 0.29). Higher risk of new-onset atrial fibrillation or flutter was found in closure group (RR 4.69, 95% CI 2.17-10.12, P < 0.0001). CONCLUSIONS: PFO closure combined with medical therapy showed superiority over medical therapy alone for stroke prevention in carefully selected CS patients with PFO, but increased the risk of atrial fibrillation or flutter.

Hydroxycinnamoylmalated flavone C-glycosides from Lemna japonica.

Three previously undescribed flavone C-glycosides (1-3), along with seven known ones (4-10), were isolated and characterized from the smallest flowering aquatic plant, Lemna japonica. On the basis of spectroscopic analysis and alkaline hydrolysis, compounds 1-3 were identified to be luteolin 6-C-(2″-O-trans-caffeoyl-d-malate)-ß-glucoside (1), apigenin 6-C-(2″-O-trans-caffeoyl-d-malate)-ß-glucoside (2), and luteolin 6-C-(2″-O-trans-coumaroyl-d-malate)-ß-glucoside (3). Compounds 1-3 are characteristic of a trans-coumaroyl-d-malate or trans-caffeoyl-d-malate linked to C-2″ of the glucose, which was reported for the first time. Compounds 1-3 exhibited weak cytotoxicity against HepG-2, SW-620, and A-549 cell lines, with IC50 values between 42.5 and 19.2µg/ml, and moderate antioxidant activity. Meanwhile compound 3 displayed moderate nematocidal activity with an EC50 value of 1.56mg/ml.

[Expression and activity identification of APOBEC3A-HBc fusion protein].

Objective To construct the expression vector of the fusion protein of apolipoprotain B mRNA editing enzyme catalytic polypeptide-like 3A (APOBEC3A) and hepatitis B virus core proteins (HBc) with different sequences, and identify its expression, intracellular localization and cytosine deamination activity. Methods The APOBEC3A gene and the coding sequence of HBc and four kinds of truncated HBc containing C-termimal domain were amplified by PCR. The APOBEC3A with full-length HBc antigen or four kinds of truncated HBc were cloned into a eukaryotic expression vector pcDNA3.0 by In-Fusion method, and confirmed by DNA sequencing. The recombinants were then transfected into HEK293T cells. The expression and localization of the fusion proteins were detected by Western blotting and immunofluorescence cytochemistry. The cytosine deamination activity was analyzed by electrophoresis on a urea denaturing polyacrylamide gel. Results Five kinds of fusion protein were expressed in HEK293T cells successfully, and the expression of the vectors containing the truncated HBc were higher than that of the APOBEC3A-HBc vector containing the full-length HBc. The fusion protein of APOBEC3A-HBc was mainly expressed in the cytoplasm of HEK293T cells, and the fusion proteins of APOBEC3A-HBc144S, APOBEC3A-HBc144E, APOBEC3A-HBc144AAA, APOBEC3A-HBc144A were expressed mainly in the nuclei of HEK293T cells. The cytosine deamination activity of the fusion proteins containing the truncated HBc was higher than that of the fusion protein APOBEC3A-HBc. Conclusion The fusion protein expression vectors of APOBEC3A and HBc with different lengths and sequences have been constructed successfully. The expressing ability, intracellular localization and cytosine deamination activity are obviously different between the fusion protein APOBEC3A-HBc and the fusion proteins containing the truncated HBc.

Indole Alkaloids from Chaetomium globosum.

Two new indole alkaloids chaetocochin J (1) and chaetoglobinol A (8), along with chetomin (2), chetoseminudin A (3), cochliodinol (9), and semicochliodinol (10), were isolated from the rice culture of the fungus Chaetomium globosum. Their structures were elucidated by spectral analysis. Three new epipolythiodioxopiperazines, chaetocochins G-I (5-7), were identified by the combination of UPLC and mass spectrometric analysis. Chaetocochin I contained two sulfur bridges, one formed by three sulfur atoms between C-3 and C-11a, and the other formed by four sulfur atoms between C-3' and C-6'. Chaetocochin I was readily transformed into chetomin (2), chetoseminudin A (3), chaetocochin D (4), chaetocochin G (5), and chaetocochin H (6) by losing sulfur atoms. Compounds 1-3, and 8 exhibited antibacterial activities against Bacillus subtilis with MICs of 25, 0.78, 0.78, and 50 µg/mL, respectively, but not against Gram-negative bacterium (Escherichia coli). Compounds 2 and 8 were inactive against Candida albicans, Fusarium graminearum, Fusarium vasinfectum, Saccharomyces cerevisiae, and Aspergillus niger even at the high concentrations of 200 and 100 µg/mL, respectively. Compound 8 showed free radical scavenging capacity against the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical (ABTS(+•)), with IC50 values of 143.6 and 45.2 µM, respectively. The free radical scavenging capacity rates of compounds 1-3 on the DPPH and ABTS(+•) were less than 20% at the test concentrations (89.9-108.3 µM). The superoxide anion radical scavenging assay indicated that compounds 1-3, and 8 showed 14.8% (90.9 µM), 18.1% (90.9 µM), 51.5% (88.3 µM), and 30.4% (61.3 µM) superoxide anion radical scavenging capacity, respectively.

Concentration depth distribution of grain boundary segregation measured by wavelength dispersive X-ray spectroscopy.

A method using wavelength dispersive X-ray spectroscopy (WDS) is applied to the measurement of grain boundary segregation of Sn in silicon steel. The quantification of monolayer concentration of Sn is acquired, which demonstrates an obvious segregation of Sn at grain boundaries. In consideration of the fact that segregated impurities (Sn or other species) distribute in multilayer and not just monolayer segregation can be characterized by WDS, the Gaussian distribution is applied to formulate the multilayer concentration depth distribution according to the measured total concentration. A correction factor is then put forward to improve the quantification. Based on the measured segregation of Sn and the derived formula of multilayer concentration depth distribution, the grain boundary concentrations of Sn are calculated for different thicknesses of segregated layer. From the experimental measurement, theoretical analyses and calculated results, an effective approach for the research of grain boundary segregation is provided.

A new alternariol glucoside from fungus Alternaria alternate cib-137.

A new secondary metabolite, 2-O-methylalternariol 4-O-ß-[4-methoxyl-glucopyranoside] (1), together with four known compounds alternariol methyl ether (2), altenuene (3), isoaltenuene (4) and 2-(2'S-hydroxypropyl)-5-methyl-7-hydroxychromone (5), was isolated from the fungus Alternaria alternate cib-137. Its structure was elucidated on the basis of spectroscopic data. Compounds 3 and 4 demonstrated moderate activity against Staphylococcus aureus.