Lactobacillus plantarum-derived extracellular vesicles protect against ischemic brain injury via the microRNA-101a-3p/c-Fos/TGF-ß axis.

Currently, the reported source of extracellular vesicles (EVs) for the treatment of ischemic stroke（IS）is limited to mammals. Moreover, these EVs are restricted to clinical translation by the high cost of cell culture. In this respect, Lactobacillus plantarum culture is advantaged by low cost and high yield. However, it is poorly understood whether Lactobacillus plantarum-derived EVs (LEVs) are applicable for the treatment of IS. Here, our results demonstrated that LEVs reduced apoptosis in ischemic neuron both in vivo and in vitro. As revealed by high-throughput sequencing, miR-101a-3p expression was significantly elevated by LEV treatment in OGD/R-induced neurons, as confirmed in the tMCAO mice treated with LEVs. Mechanistically, c-Fos was directly targeted by miR-101a-3p. In addition, c-Fos determined ischemia-induced neuron apoptosis in vivo and in vitro through the TGF-ß1 pathway, miR-101a-3p inhibition aggravated ischemia-induced neuron apoptosis in vitro and in vivo, and miR-101a-3p overexpression produced the opposite results. Hsa-miR-101-3p was downregulated in the plasma of patients with IS but upregulated in the patients with neurological recovery after rt-PA intravenous thrombolysis. In conclusion, Our results demonstrated for the first time that LEVs might inhibit neuron apoptosis via the miR-101a-3p/c-Fos/TGF-ß axis, and has-miR-101-3p is a potential marker of neurological recovery in IS patients.

Annexin A1-derived peptide Ac2-26 facilitates wound healing in diabetic mice.

Impaired wound healing is a common complication of diabetes. In diabetic wounds, macrophages present dysfunctional efferocytosis and abnormal phenotypes, which could result in excessive neutrophil accumulation and prolonged inflammation, thereby eventually hindering wound repair. ANXA1 N-terminal peptide Ac2-26 exhibits a high potential in mitigating inflammation and improving repair; however, its efficacy in diabetic wound repair remains unclear. In this study, a cutaneous excisional wound model was built in genetically diabetic mice. Ac2-26 or a vehicle solution was employed locally in wound sites. Subsequently, wound zones were measured and sampled at different time intervals post-wounding. Using hematoxylin-eosin and Masson's trichrome staining, we observed the histopathological variations and collagen deposition in wound samples. Based on immunohistochemistry and immunofluorescence, the numbers of neutrophils, macrophages, and CD206-positive macrophages in the wound samples were determined. Cytokine expression in wound samples was studied by immunoblot assay. Results showed that Ac2-26 treatment could facilitate diabetic wound closure, down-regulate the number of neutrophils, and improve angiogenesis and collagen deposition. In addition, Ac2-26 application expedited macrophage recruitment and up-regulated the percentage of macrophages expressing CD206, which is a marker for M2 macrophages. Moreover, Ac2-26 inhibited the expressions of TNF-α and IL-6 and up-regulated the expressions of IL-10, TGF-ß, and VEGFA during diabetic wound healing. Hence, based on the aforementioned findings, Ac2-26 application in diabetic wounds could exert anti-inflammatory and pro-repair effects by reducing neutrophil accumulation and facilitating M2 macrophage development.

Efficient cross-coupling of aryl Grignard reagents with alkyl halides by recyclable ionic iron(III) complexes bearing a bis(phenol)-functionalized benzimidazolium cation.

A novel bis(phenol)-functionalized benzimidazolium salt, 1,3-bis(3,5-di-tert-butyl-2-hydroxybenzyl)benzimidazolium chloride (H3LCl, 1), was designed and used to prepare ionic iron(III) complexes of the type [H3L][FeX4] (X = Cl, 2; X = Br, 3). Both 2 and 3 were characterized by elemental analysis, Raman spectroscopy, electrospray ionization mass spectrometry and X-ray crystallography. The catalytic performances of 2 and 3 in cross-coupling reactions using aryl Grignard reagents with primary and secondary alkyl halides bearing ß-hydrogens were studied. This analysis shows that complex 2 has good potential for alkyl chloride-mediated coupling. In comparison, complex 3 showed slightly lower catalytic activity. After decanting the product contained in the ethereal layer, complex 2 could be recycled at least eight times without significant loss of catalytic activity.

Decreased synovial fluid omentin-1 concentrations reflect symptomatic severity in patients with knee osteoarthritis.

The aim of this study was to measure omentin-1 concentrations in serum and synovial fluid (SF) of knee osteoarthritis (OA) patients and to investigate their correlation with patient-reported symptomatic severity. We enrolled 263 knee OA patients and 62 healthy controls. We collected Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores from OA patients and measured omentin-1 concentrations in serum and SF by enzyme-linked immunosorbent assay (ELISA). Our results demonstrated that omentin-1 concentrations in SF but not serum were independently and negatively correlated with self-reported greater pain and physical disability in OA patients. Omentin-1 in SF might serve as a potential biomarker for reflecting the symptomatic severity of OA.

Combustion and emission characteristics for a marine low-speed diesel engine with high-pressure SCR system.

In order to avoid the production of sulfates and nitrates in marine diesel engines that burn sulfur-containing fuels, the operating temperature of their high-pressure selective catalytic reduction (HP-SCR) systems should be higher than 320 °C. For marine low-speed diesel engines, only the pre-turbine exhaust gas temperature can meet this requirement under specific conditions, with the main engine modulation method helping to increase the exhaust gas temperature. However, the main engine modulation method brings down the power output and fuel economy of the main engine and causes the matching problem of the turbine and the other devices with the main engine. The original engine model of the marine low-speed diesel engine and the high-pressure SCR system configuration model have been constructed using one-dimensional simulation software. In addition, the performance of the high-pressure SCR system under the conditions of low-sulfur and high-sulfur exhaust gas was thoroughly analyzed. Moreover, the two main engine modulation schemes of the scavenging bypass and the turbine exhaust bypass of the original engine matching with the high-pressure SCR system were studied. The study found that the weighted average value of the NOx under the condition of low-sulfur exhaust gas met with the requirement of the IMO Tier III regulations when the low-speed diesel engine was matched with the high-pressure SCR system. However, the weighted average value of the NOx under the condition of high-sulfur exhaust gas was slightly higher than that required by the IMO Tier III regulation. In addition, the optimal main engine modulation scheme for this low-speed diesel engine was clarified by comparing the effects of the scavenging bypass and the turbine exhaust bypass modulation on the exhaust performance, and the working performance of the original engine. With an opening of 0.4 of the CBV valve under 25% engine load, the weighted average NOx of the original exhaust gas was 3.38 g/(kW·h), the power had decreased by 0.7%, and the fuel consumption had increased by 1.0%. Furthermore, when the EGB valve opening was 0.3, the weighted average value of NOx was 3.31 g/(kW·h), the power had reduced by 2.4% and the fuel consumption had increased by 2.5%. Both modulation scheme methods made the exhaust performance of the original engine meet the requirements of the IMO Tier III emission regulations, but the scavenging bypass modulation scheme had less impact on the original engine's performance.

Novel Insights on Notch signaling pathways in liver fibrosis.

Liver fibrosis is characterized by an increased and altered deposition of extracellular matrix (ECM) proteins that make up excessive tissue scarring and promote chronic liver injury. Activation of hepatic stellate cells (HSCs) is a pivotal cellular event in the progression of liver fibrosis. However, the mechanisms involved in the development of liver fibrosis are only now beginning to be unveiled. The Notch pathway is a fundamental and highly conserved pathway able to control cell-fate, including cell proliferation, differentiation, apoptosis, regeneration and other cellular activities. Recently, the deregulation of Notch cascade has been found involved in many pathological processes, including liver fibrosis. These data give evidence for a role for Notch signaling in liver fibrosis. In addition，more and more date are available on the role of Notch pathways in the process. Therefore, this review focuses on the current knowledge about the Notch signaling pathway, which dramatically takes part in HSC activation and liver fibrosis, and look ahead on new perspectives of Notch signaling pathway research. Furthermore, we will summarize this new evidence on the different interactions in Notch signaling pathway-regulated liver fibrosis, and support the potentiality of putative biomarkers and unique therapeutic targets.

The association between VEGF -634C/G polymorphisms and osteonecrosis of femoral head: a meta-analysis.

The polymorphism of the vascular endothelial growth factor (VEGF) -634C/G has been correlated with susceptibility to osteonecrosis of the femoral head (ONFH). The aim of this study was to derive a more precise estimation of the relationship between the VEGF -634C/G polymorphism and ONFH by performing a meta-analysis. We searched articles indexed in Pubmed, OVID and Web of Science published up to January 2015 that met our predefined criteria. The strength of the association between VEGF -634C/G polymorphism and ONFH risk was assessed by an odds ratio (OR) with the corresponding 95% CI. Three eligible studies involving 692 cases and 875 controls were identified. Overall, pooled analysis indicated a significant association between VEGF -634C/G polymorphism and ONFH risk (for C vs. G: OR=1.141, 95% CI 1.055-1.235, P=0.001; for CC vs. GG: OR=1.345, 95% CI 1.124-1.610, P=0.001; for CG vs. GG: OR=1.106, 95% CI 1.018-1.202, P=0.017; for CG+CC vs. GG: OR=1.104, 95% CI 1.035-1.177, P=0.003; for CC vs. GG+ CG: OR=1.294, 95% CI 1.051-1.593, P=0.015). No evidence of publication bias was observed. In conclusion, this meta-analysis suggested that polymorphism of VEGF -634C/G was a risk factor for ONFH. This finding needs further confirmation by trans-regional multicenter study with large sample in different ethnic populations, such as Caucasian and Austroloid.

[Isolation and identification of steroidal saponins in total saponin from Dioscorea nipponica Makino].

AIM: To investigate the water-soluble steroidal saponins in total saponin from Dioscorea nipponica Makino and look for new active compounds. METHODS: The compounds were isolated with silica gel, PTLC and HPLC, and their structures were elucidated by acid hydrolysis, physical and chemical data and spectral analysis (IR, NMR, MS, HMQC, HMBC) as well as chemical correlations. RESULTS: The two steroidal saponins (water-insoluble saponin and water-soluble saponin) were isolated from the total saponin of Dioscorea nipponica Makino. The structures were elucidated as diosgenin 3-O-[alpha-L-rhamnopy ranosyl (1-->2)-[beta-D-glucopyranosyl(1-->3)]]-beta-D-glucopyranoside (I), diosgenin 3-O-[alpha-L-rhamnopyranosyl (1-->3)-alpha-L-rhamnopyranosyl (1-->4)-alpha-L-rhamnopyranosyl (1-->4)]-beta-D-glucopyranoside (II). CONCLUSION: Compound II is a new steroidal saponin and firstly isolated from Dioscorea nipponica Makino. It was named as dioscin Dc.

Clinical study of laser photocoagulation combined with VEGF antagonists for DME / 国际眼科杂志(Guoji Yanke Zazhi)

· AIM:To investigate the influence of laser photocoagulation and vascular endothelial growth factor (VEGF) antagonists used alone or as combination therapy on clinical efficacy and safety of patients with diabetic macular edema (DME).· METHODS:Totally 150 patients (156 eyes) with DME were chosen in the period from October 2014 to October 2016 in our hospital and randomly divided into both group including Group A (50 patients 52 eyes) with laser photocoagulation used alone,Group B (50 patients 51 eyes) with VEGF antagonists used alone and Group C (50 patients 53 eyes) with combination therapy;and the best corrected visual acuity,macular fovea thickness and retinal neovascularization leakage area before and after treatment and the complications incidence of both groups were compared.· RESULTS:The best corrected visual acuity of Group B and Group C in 3,6 and 12mo after treatment were significant better than that of Group A (P＜ 0.05).The macular fovea thickness of Group B and Group C in 3,6 and 12mo after treatment were significant lower than that of Group A (P＜0.05).The retinal neovascularization leakage area of Group B and Group C in 3mo after treatment were significant smaller than that of Group A (P＜0.05).The retinal neovascularization leakage area of Group C in 6 and 12mo after treatment were significant smaller than that of Group A and Group B (P＜0.05).There was no significant difference in the complications incidence among 3 groups (P＞0.05).· CONCLUSION:Laser photocoagulation combined with VEGF antagonists in the treatment of patients with DME can efficiently improve visual acuity,reduce macular foveal thickness,control retinal neovascularization leakage and not increase adverse reactions.