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Developing biocatalytic cascades in abiological conditions is of utmost significance, but such processes often suffer from low reaction efficiency because of incompatible reaction environments and suppressed intermediate transportation. Herein we report a new type of biocatalytic cascade by localizing two different enzymes separately in the outer and inner interfacial layers of Pickering emulsion droplets. This versatile approach enables the localization of two enzymes in their preferred reaction microenvironments and simultaneously in nanoscale proximity of each other. The thus-designed interfacial biocatalytic cascades show outstanding catalytic efficiency in alkene epoxidation and thioether oxidation with in situ generation of hydrogen peroxide under mild conditions, 6.9-13.6 times higher than the catalytic efficiency of the free enzymes in solution and their multi-enzymatic counterparts. The remarkable interfacial effect of Pickering droplets was found to be responsible for the significantly enhanced cascading efficiency., (© 2023 Wiley-VCH GmbH.)

Isofurans (IsoFs) are a series of novel discovered lipid peroxidation products. This study focused on the investigation of the angiogenic property of IsoF. MTT stain assay indicated that 1 µm IsoF had the most bioactivity in rat brain endothelial cells (RBECs). IsoF significantly promoted cellular proliferation and migration and remarkably decreased staurosporine-induced apoptosis by TUNEL assay in the RBECs. It successfully up-regulated rat aortic vascularization and choroid explant sprouting, extracellular regulated protein kinases (ERK)1/2, and triggered calcium release. RT-PCR examination indicated that IsoF up-regulated tumor necrosis factor (TNF)α, angiopoietin-1 receptor (Tie2), and vascular endothelial growth factor (VEGF)-A, but did not interfere with caspase 2 and VEGF-C in the RBECs. IsoF has pro-angiogenic activity. Calcium release and ERK1/2 phosphorylation may be involved in the signaling of the IsoF-induced up-regulation of TNFα, Tie2, and VEGF-A, which could be the molecular mechanism of the pro-angiogenic activity of the IsoF., (© The Author(s) 2022. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Background: Doxorubicin, an anthracycline chemotherapeutic agent, is widely used in the treatment of many cancers. However, doxorubicin posts a great risk of adverse cardiovascular events, which are thought to be caused by oxidative stress. We recently reported that the ubiquitin E3 ligase TRIM21 interacts and ubiquitylates p62 and negatively regulates the p62-Keap1-Nrf2 antioxidant pathway. Therefore, we sought to determine the role TRIM21 in cardiotoxicity induced by oxidative damage., Methods: Using TRIM21 knockout mice, we examined the effects of TRIM21 on cardiotoxicity induced by two oxidative damage models: the doxorubicin treatment model and the Left Anterior Descending (LAD) model. We also explored the underlying mechanism by RNA-sequencing of the heart tissues, and by treating the mouse embryonic fibroblasts (MEFs), immortalized rat cardiomyocyte line H9c2, and immortalized human cardiomyocyte line AC16 with doxorubicin., Findings: TRIM21 knockout mice are protected from heart failure and fatality in both the doxorubicin and LAD models. Hearts of doxorubicin-treated wild-type mice exhibit deformed mitochondria and elevated level of lipid peroxidation reminiscent of ferroptosis, which is alleviated in TRIM21 knockout hearts. Mechanistically, TRIM21-deficient heart tissues and cultured MEFs and H9c2 cells display enhanced p62 sequestration of Keap1 and are protected from doxorubicin-induced ferroptosis. Reconstitution of wild-type but not the E3 ligase-dead and the p62 binding-deficient TRIM21 mutants impedes the protection from doxorubicin-induced cell death., Interpretation: Our study demonstrates that TRIM21 ablation protects doxorubicin-induced cardiotoxicity and illustrates a new function of TRIM21 in ferroptosis, and suggests TRIM21 as a therapeutic target for reducing chemotherapy-related cardiotoxicity., Funding: NIH (CA129536; DK108989): data collection, analysis. Shanghai Pujiang Program (19PJ1401900): data collection. National Natural Science Foundation (31971161): data collection. Department of Veteran Affairs (BX004083): data collection. Tianjin Science and Technology Plan Project (17ZXMFSY00020): data collection., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Halophytes can remove large quantities of salts from saline soils, so their importance in ecology has received increasing attention. Preliminary studies have shown that arbuscular mycorrhizal (AM) fungi can improve the salt tolerance of halophytes. However, few studies have focused on the molecular mechanisms and effects of AM fungi in halophytes under different salt conditions. A pot experiment was carried out to investigate the effects of Funneliformis mosseae inoculation on growth, nutrient uptake, ion homeostasis and the expression of salt tolerance-related genes in Suaeda salsa under 0, 100, 200 and 400 mM NaCl. The results showed that F. mosseae promoted the growth of S. salsa and increased the shoot Ca 2+ and Mg 2+ concentrations under no-salt condition and high-salt condition. In addition, AM fungi increased the K + concentration and maintained a high K + /Na + ratio at 400 mM NaCl, while AM fungi decreased the K + concentration and reduced the K + /Na + ratio at 0 mM NaCl. AM fungi downregulated the expression of SsNHX1 in shoots and the expression of SsSOS1 in roots at 400 mM NaCl. These effects may decrease the compartmentation of Na + into leaf vacuoles and restrict Na + transport from roots to shoots, leading to an increase in root Na + concentration. AM symbiosis upregulated the expression of SsSOS1 in shoots and downregulated the expression of SsSOS1 and SsNHX1 in roots at 100 mM NaCl. However, regulation of the genes (SsNHX1, SsSOS, SsVHA-B and SsPIP) was not significantly different with AM symbiosis at 0 mM or 200 mM NaCl. The results revealed that AM symbiosis might induce diverse modulation strategies in S. salsa, depending on external Na + concentrations. These findings suggest that AM fungi may play significant ecological roles in the phytoremediation of salinized ecosystems., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Rhizosphere microbes are essential partners for plant stress tolerance. Recent studies indicate that arbuscular mycorrhizal fungi (AMF) can facilitate the revegetation of soils contaminated by heavy metals though interacting with rhizosphere microbiome. However, it is unclear how AMF affect rhizosphere microbiome to improve the growth of plant under rare earth elements (REEs) stress. AMF (Claroideoglomus etunicatum) was inoculated to maize grown in soils spiked with Lanthanum (0 mg kg -1 , La0; 10 mg kg -1 , La10; 100 mg kg -1 , La100; 500 mg kg -1 , La500). Plant biomass, nutrient uptake, REE uptake and rhizosphere bacterial and fungal community were evaluated. The results indicated that La100 and La500 decreased significantly root colonization rates and nutrition uptake (K, P, Ca and Mg content). La500 decreased significantly α-diversity indexes of bacterial and fungal community. AMF enhanced significantly the shoot and root fresh and dry weight of maize in all La treatments (except for the root fresh and dry weight of La0 and La10 treatment). For La100 and La500 treatments, AMF increased significantly nutrition uptake (K, P, Ca and Mg content) in shoot of maize by 27.40-441.77%. For La500 treatment, AMF decreased significantly shoot La concentration by 51.53% in maize, but increased significantly root La concentration by 30.45%. In addition, AMF decreased bacterial and fungal Shannon index in La0 treatment, but increased bacterial Shannon index in La500 treatment. Both AMF and La500 affected significantly the bacterial and fungal community composition, and AMF led to more influence than La. AMF promoted the enrichment of bacteria, including Planomicrobium, Lysobacter, Saccharothrix, Agrococcus, Microbacterium, Streptomyces, Penicillium and other unclassified genus, and fungi (Penicillium) in La500, which showed the function for promoting plant growth and tolerance of heavy metal. The study revealed that AMF can regulate the rhizosphere bacterial and fungal composition and foster certain beneficial microbes to enhance the tolerance of maize under La stress. Phytoremediation assisted by AMF is an attractive approach to ameliorate REEs-contaminated soils., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) is a new acute espiratory infectious disease that has been in a public health emergency of international concern. In China, the combination of Xuanfei Baidu Formula (XBF) and conventional drug is used in the clinical treatment of patients with new coronary pneumonia, However, there is no comprehensive and systematic evidence on the effectiveness and safety of XBF., Materials and Methods: We search for research in PubMed, China National Knowledge Infrastructure, Wan-fang Database, China Biomedical Database, and Chinese Science Citation Database. For "Xuanfei Baidu Formula" and "COVID-19," we screened suitable articles without language restrictions on keywords, Review Manager 5.3 and STATA 14.2 software was used for the data analysis., Results: The systematic review and meta-analysis will evaluate the efficacy and safety of XBF combined with conventional drug in the treatment of COVID-19., Conclusion: We will provide evidence of XBF for the treatment on COVID-19 patients., Inplasy Registration Number: INPLASY2020120011., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Since its first report in December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly emerged as a pandemic affecting nearly all countries worldwide. So far, there is no specific anti-coronavirus therapy approved for the treatment of COVID-19. In China, some traditional Chinese medicines (TCM) have been successfully applied to the treatment of SARS-CoV-2 and have achieved good clinical results, including the Reyanning mixture, but there is no systematic review about it. This study will systematically evaluate its efficacy and safety in the treatment of COVID-19., Methods: The following electronic bibliographic databases will be searched to identify relevant studies: PubMed, MEDLINE, EMBASE, CNKI, CBM, and Wanfang databases. We will use the Cochrane Handbook for Systematic Reviews of Interventions to assess the risk of bias. The protocol will be conducted according to the approach and Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Manager 5.3 software and STATA 16.0 software were used to perform the meta-analysis., Results: The systematic review and meta-analysis aims to review and pool current clinical outcomes of Reyanning mixture for the treatment of COVID-19., Conclusion: The conclusion of this review will provide evidence to judge whether Reyanning mixture combined with Conventional Western Medicine is an effective and safe intervention for COVID-19., Inplasy Registration Number: INPLASY2020120044., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Since the outbreak of coronavirus disease 2019 (COVID-19) in 2019, it has swept the world with rapid development and is one of the infectious diseases that seriously threatened global public health. Because of the complex pathogenesis, high infectivity, and high fatality rate of COVID-19, there are no effective treatments for this epidemic at present. Traditional Chinese Medicine (TCM) has a long clinical history in the prevention and treatment of such acute infectious diseases. The therapeutic effect of Lianhua Qingwen (LHQW) on this new coronary pneumonia has attracted the attention of all walks of life, and relevant research reports continue to appear. Here, we intend to conduct a systematic review and meta-analysis of randomized controlled trials (RCT) to evaluate the efficacy of LHQW in COVID-19 patients., Methods: We will search each database from the built-in until Dec 2020. The English literature mainly search the Cochrane Library, EMBASE, PubMed, and Web of Science, while the Chinese literature come from CNKI, VIP, Chinese Biomedical Database (CBM), Chinese Science Citation Database (CSCD), and Wan Fang database. Simultaneously, we will retrieve clinical registration tests. This study only screens the RCT of LHQW against COVID-19 and evaluates its efficacy and safety. We will use the Cochrane Handbook to systematically review interventions to assess the risk of bias. The protocol will be reported according to the approach and preferred report items for systematic review and meta-analysis protocols (PRISMA - P). Finally, RevMan software version 5.3 will be used for meta-analysis., Results: The systematic review and meta-analysis aim to review and pool current clinical outcomes of LHQW for treating COVID-19., Conclusion: This study will provide further evidence for the efficacy and safety of LHQW in the treatment of COVID-19., Inplasy Registration Number: INPLASY2020120043., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Coronavirus disease 2019 (COVID-19) is a potentially fatal disease. clinical practice shows that Chinese Patent Medicine (CPM) has played an important role in the outbreak, Among them, Jinhua Qinggan granules, Lianhua Qingwen capsule, and Xuebiqing injection have an effect in treating COVID-19 patients, but it has not been systematically evaluated for efficacy and safety. We provide a protocol for systematic review and meta-analysis., Materials and Methods: Retrieved the database, including the China National Knowledge Infrastructure, Chinese Biomedical Database, Wan Fang database, and PubMed. The quality of each study is assessed according to the criteria of the Cochrane Handbook for Systematic Reviews of Interventions. Using Manager 5.3 software and STATA 16.0 software were used to perform the meta-analysis., Results: The systematic review and meta-analysis aims to review and pool current clinical outcomes of CPM combined with routine western medicine (RWM) for the treatment of COVID-19., Conclusion: This study will provide evidence of CPM (including Jinhua Qinggan granule, Lianhua Qingwen capsule, and Xuebiqing injection) for the treatment on COVID-19 patients.INPLASY Registration number: INPLASY202050050.

A series of 1,2,4-triazole derivatives 1-14 was synthesized to investigate their neuroprotective effects and mechanisms of action. Compounds 5-11 noticeably protected PC12 cells from the cytotoxicity of H 2 O 2 or sodium nitroprusside (SNP). Compound 11 was the most effective derivative. Compound 11 chelated Fe (II) iron, scavenged reactive oxygen species (ROS), and restored the mitochondrial membrane potential (MMP). Moreover, it enhanced the activity of the antioxidant defense system by increasing the serum level of superoxide dismutase (SOD) and promoting the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). Compound 11 caused certain improvements in behavior, the cerebral infarction area, and serum levels of biochemical indicators (TNF-α, IL-1β, SOD and MDA) in a rat MCAO model. The lethal dose (LD 50 ) of compound 11 in mice receiving intraperitoneal injections was greater than 400 mg/kg. Meanwhile, pharmacokinetic experiments revealed high bioavailability of this compound after both oral and intravenous administration (F = 60.76%, CL = 0.014 mg/kg/h) and a longer half-life (4.26 and 5.11 h after oral and intravenous administration, respectively). Based on these findings, compound 11 may be a promising neuroprotectant for the treatment of ischemic stroke., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: The optimal revascularization technique in diabetic patients with complex coronary artery disease (CAD), including left main CAD and multivessel coronary disease (MVD), remains controversial. The current study aimed to compare adverse clinical endpoints of coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) in patients with diabetes mellitus (DM)., Methods: Relevant studies were found from MEDLINE, OVID, Science Direct, Embase and the Cochrane Central database from January 2010 to April 2019. Risk ratio (RR) with 95% confidence interval (CI) was used to express the pooled effect on discontinuous variables. Outcomes evaluated were all-cause mortality, major adverse cardiac/cerebrovascular events (MACCE), cardiac death, myocardial infarction, stroke, and repeat revascularization., Results: Sixteen studies were included (18,224 patients). PCI was associated with the increase risk for MACCE (RR 1.59, 95% CI 1.38-1.85), cardiac death (RR 1.76, 95% CI 1.11-2.80), MI (RR 1.98, 95% CI 1.53-2.57), repeat revascularization (RR 2.61, 95% CI 2.08-3.29). The risks for all-cause mortality (RR 1.23, 95% CI 1.00-1.52) and stroke (RR 0.71, 95% CI 0.48-1.03) were similar between two strategies. Stratified analysis based on studies design and duration of follow-up showed largely similar findings with the overall analyses, except for a significant increased risk of all-cause mortality (RR 1.32, 95% CI 1.04-1.67) in long-term group, and CABG was associated with a higher stroke rate compared to PCI, which are results that were found in RCTs (RR 0.47, 95% CI 0.28-0.79) and mid-term groups (RR 0.39, 95% CI 0.23-0.66)., Conclusions: CABG was superior to PCI for diabetic patients with complex CAD (including left main CAD and/or MVD), but might be associated with a higher risk of stroke mid-term follow-up. Number of Protocol registration PROSPERO CRD 42019138505., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2019.)

Liver X Receptor (LXR) is a potential drug target for atherosclerosis. One of the major challenges in taking LXR modulators to the clinic is steatosis. It was reported that sterol LXR agonists selectively activate LXR in the intestine and macrophage cells rather than in the liver. We hypothesize that sterol LXR agonists may selectively inhibit atherosclerosis without causing hepatic lipogenesis. Thus, based on LXR structure, 12 sterol compounds were designed and tested in a dual-luciferase reporter gene experiment. It was confirmed that compounds 4 and 6 were LXR agonists. Further experiments demonstrated that compounds 4 and 6 inhibit the formation of macrophage foam cells without inducing triglyceride accumulation in either hepatocytes or adipocytes. In vivo studies demonstrated that compound 4 promotes reverse cholesterol transport without inducing hepatic lipogenesis. Thus, we report that these compounds with sterol scaffolds can be promising leads for the treatment of atherosclerosis without inducing steatosis., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Objective: To investigate the expressions of CD4 + CD45RA + T cells and CD4 + CD45RO + T cells in peripheral blood of patients with acute coronary syndrome (ACS) and their significance., Methods: A case-control study was conducted. Ninety-four patients receiving coronary angiography (CAG) admitted to Tianjin Chest Hospital from March 5th to April 27th in 2018 were enrolled. They were divided into non-coronary heart disease (CHD) group (n = 12), unstable angina pectoris (UAP) group (n = 27), acute non-ST elevation myocardial infarction (NSTEMI) group (n = 27) and acute ST elevation myocardial infarction (STEMI) group (n = 28) according to the patients' symptoms, electrocardiogram, troponin test and angiographic results. General data, blood routine parameters, and biochemical indicators were collected. The ratios of CD4 + CD45RA + T cells and CD4 + CD45RO + T cells were determined by flow cytometry. Multivariate Logistic regression was used to evaluate whether CD4 + CD45RA + T cells and CD4 + CD45RO + T cells were associated with STEMI., Results: Ninety-four patients were included initially. After excluding the patients who died during the intervention, 93 patients were enrolled in the data analysis finally, with 12 patients in the non-CHD group, 27 patients in the UAP group, and the same as the NSTEMI group and the STEMI group. Compared with the non-CHD group, white blood cell count (WBC) was decreased (×10 9 /L: 6.03±1.30 vs. 6.60±1.30, P < 0.05), and lymphocyte ratio was increased (0.273±0.059 vs. 0.269±0.070, P > 0.05) in patients of the UAP group; however, in the NSTEMI group and STEMI group, WBC was increased (×10 9 /L: 8.29±2.28, 9.86±2.76 vs. 6.60±1.30, both P < 0.05), and lymphocyte ratio was decreased (0.236±0.076, 0.173±0.094 vs. 0.269±0.070, P > 0.05 and P < 0.05), especially in the STEMI group [WBC (×10 9 /L): 9.86±2.76 vs. 6.60±1.30, lymphocyte ratio: 0.173±0.094 vs. 0.269±0.070, both P < 0.05]. There was no significant difference in biochemical indicators among all of the groups. Flow cytometry results showed that the ratios of CD4 + CD45RO + T cells in the UAP group and NSTEMI group were higher than those in the non-CHD group (0.323±0.074, 0.319±0.078 vs. 0.314±0.058, both P > 0.05); however, the ratio of CD4 + CD45RO + T cells in the STEMI group showed a decreased tendency (0.270±0.057 vs. 0.314±0.058, P > 0.05), and it was significantly lower than that in the UAP group and the NSTEMI group (0.270±0.057 vs. 0.323±0.074, 0.319±0.078, both P < 0.05). There was no significant difference in the ratio of CD4 + CD45RA + T cells among all of the groups. Multivariate Logistic regression analysis showed that CD4 + CD45RA + T cells ratio was not significantly correlated with the occurrence of STEMI [odds ratio (OR) = 0.976, 95% confidence interval (95%CI) was 0.907-1.050, P = 0.518], but CD4 + CD45RO + T cells ratio was significantly correlated with the occurrence of STEMI (OR = 0.888, 95%CI was 0.821-0.961, P = 0.003)., Conclusions: There was no significant difference in the ratio of CD4 + CD45RA + T cells among UAP, NSTEMI and STEMI patients, and CD4 + CD45RO + T cells ratio in the STEMI group was significantly lower than that in the UAP group and NSTEMI group. CD4 + CD45RO + T cells ratio may be risk factor of STEMI.

Oxidative stress is an important cause of neurodegenerative diseases. Antioxidant is an potential important method to treat such diseases. The aim of this study is to discover new and effective antioxidants and their mechanism. The neuroprotective effect of six curcumin pyrozole compounds were first evaluated on sodium nitroprusside (SNP) - induced PC12 cell injury by testing cell viability and LDH release. The results showed that four compounds (C1-C4) have more significant protective effects compared to curcumin and edaravone. Furthermore, compounds C1-C4 can attenuate the intracellular ROS, and compound C3 is the most effective one which can preservate the mitochondria function by inhibiting the mitochondrial membrane potential loss and enhance nuclear translocation of Nrf2 in PC12 cell. These results indicated that C3 may be a potential candidate drug for treating neurodegenerative diseases., (Copyright © 2019. Published by Elsevier Ltd.)

Key Message: A VIGS method by agroinoculation of cotton seeds was developed for gene silencing in young seedlings and roots, and applied in functional analysis of GhBI-1 in response to salt stress. Virus-induced gene silencing (VIGS) has been widely used to investigate the functions of genes expressed in mature leaves, but not yet in young seedlings or roots of cotton (Gossypium hirsutum L.). Here, we developed a simple and effective VIGS method for silencing genes in young cotton seedlings and roots by soaking naked seeds in Agrobacterium cultures carrying tobacco rattle virus (TRV)-VIGS vectors. When the naked seeds were soaked in Agrobacterium cultures with an OD600 of 1.5 for 90 min, it was optimal for silencing genes effectively in young seedlings as clear photo-bleaching phenotype in the newly emerging leaves of pTRV:GhCLA1 seedlings were observed at 12-14 days post inoculation. Silencing of GhPGF (cotton pigment gland formation) by this method resulted in a 90% decrease in transcript abundances of the gene in roots at the early development stage. We further used the tool to investigate function of GhBI-1 (cotton Bax inhibitor-1) gene in response to salt stress and demonstrated that GhBI-1 might play a protective role under salt stress by suppressing stress-induced cell death in cotton. Our results showed that the newly established VIGS method is a powerful tool for elucidating functions of genes in cotton, especially the genes expressed in young seedlings and roots.

AKR1B10 is a member of the human aldo-keto reductase superfamily which is highly expressed in several types of cancers, and has been regarded as a promising cancer therapeutic target. In this paper, a series of polyhydroxy steroids were designed and synthesized to selectively inhibit AKR1B10 activity. The most selective compound, novel compound 6, has an IC50 of 0.83±0.07μM and a selectivity of more than 120-fold for AKR1B10/AKR1B1. Structure-activity relation analyses indicate that hydroxyl at C-19 can significantly improve the selective inhibition of AKR1B10. The binding mode of AKR1B10 and its inhibitors were studied., (Copyright © 2016. Published by Elsevier Inc.)

Steroids have been shown to have multiple effects on the nervous system including neuroprotective activities, and they have the potential to be used for the treatment of neurodegenerative diseases. In this current study, we tested the hypothesis that the marine steroid 24-methylenecholestane-3β,5α,6β,19-tetraol (Tetrol) has a neuroprotective effect. (1) We synthesized Tetrol through a multiple step reaction starting from hyodeoxycholic acid (HDCA). (2) We then evaluated the neuroprotective effect of Tetrol with a glutamate-induced neuronal injury model in vitro. Tetrol concentration dependently increased the survival rate of cerebellar granule neurons challenged with toxic concentration of glutamate. Consistently, Tetrol significantly decreased glutamate-induced lactate dehydrogenase (LDH) release with a threshold concentration of 2.5 μM. (3) We further evaluated the neuroprotective effect of Tetrol in a middle cerebral artery occlusion (MCAO)-induced cerebral ischemia model in rat. Tetrol, at a dose of 12 mg/kg, significantly decreased MCAO-induced infarction volume by ∼50%. (4) Finally, we probed the mechanism and found that Tetrol concentration dependently attenuated N-methyl-d-aspartate (NMDA)-induced intracellular calcium ([Ca(2+)]i) increase with an IC50 of 7.8±0.62 μM, and inhibited NMDA currents in cortical neurons with an IC50 of 10.28±0.71 μM. Taken together, we have synthesized and characterized Tetrol as a novel neuroprotectant through negative modulation of NMDA receptors., (Copyright © 2015. Published by Elsevier Inc.)

Overstimulation of NMDA-type glutamate receptors is believed to be responsible for neuronal death of the CNS in various disorders, including cerebral and spinal cord ischemia. However, the intrinsic and physiological mechanisms of modulation of these receptors are essentially unknown. Here we report that cholestane-3β,5α,6β-triol (triol), a major metabolite of cholesterol, is an endogenous neuroprotectant and protects against neuronal injury both in vitro and in vivo via negative modulation of NMDA receptors. Treatment of cultured neurons with triol protects against glutamate-induced neurotoxicity, and administration of triol significantly decreases neuronal injury after spinal cord ischemia in rabbits and transient focal cerebral ischemia in rats. An inducible elevation of triol is associated with ischemic preconditioning and subsequent neuroprotection in the spinal cord of rabbits. This neuroprotection is effectively abolished by preadministration of a specific inhibitor of triol synthesis. Physiological concentrations of triol attenuate [Ca(2+)]i induced by glutamate and decrease inward NMDA-mediated currents in cultured cortical neurons and HEK-293 cells transiently transfected with NR1/NR2B NMDA receptors. Saturable binding of [(3)H]triol to cerebellar granule neurons and displacement of [(3)H]MK-801 binding to NMDA receptors by triol suggest that direct blockade of NMDA receptors may underlie the neuroprotective properties. Our findings suggest that the naturally occurring oxysterol, the major cholesterol metabolite triol, functions as an endogenous neuroprotectant in vivo, which may provide novel insights into understanding and developing potential therapeutics for disorders in the CNS., (Copyright © 2014 the authors 0270-6474/14/3411426-13$15.00/0.)

Objective: To explore the secondary correction demand rule for unilateral cleft lip patients., Methods: The population in parts of Henan province were investigated by census method. The unilateral cleft lip patients underwent the primary correction were selected and be photographed, and 100 patients were selected randomly into study. The subjective satisfaction for the patients' facial appearance was evaluated by three groups: Professional group(cleft lip and palate specialist), non-professional group (the hospital administrative staff), and family members of patients group. The facial symmetry rate was measured for the patients with consistent subjective evaluation., Results: The rate of facial symmetry and subjective evaluation was not convergence. The subjective evaluation disaffect rates of profes-sional and non-professional groups were higher than that in family members of patients group (P<0.05)., Conclusion: The rate of facial symmetry is not the most suitable method to evaluate the demand of the secondary correction for unilateral cleft lip patients.

We immobilized carbonic anhydrase (CA) onto the surface of membrane oxygenator of polymethyl pentene (PMP) to enhance the removal of carbon dioxide in blood by two steps. We first introduced hydroxyl groups onto PMP surface by water plasma treatment, and then coupled CA onto PMP surface by using cyanate bromide (CNBr) as a crosslinker. After plasma treatment, the contact angle with water and chemical composition of PMP surface were characterized by analysis system of surface contact angle and XPS. Using p-nitrophenyl acetate (p-NPA) as a substrate, the activity, concentration, storage stability and re-usability of immobilized CA on PMP hollow fibers were studied by ultraviolet spectrophotometer. The preliminary data showed that hydroxyl groups could be introduced on the surface of PMP by water plasma treatment, and CA with catalysis activity could be successfully introduced onto PMP surface in high immobilization efficiency. The activity of covalently immobilized CA increased with the increase of concentration of CNBr, and the maximum was 73% of the theoretical activity of CA spread on PMP surface in monolayer in studied range. Covalently immobilized CA showed higher reusability compared to physically adsorbed CA, and higher storage stability compared to free CA in solution at 37 degrees C. The method would be used potentially in the membrane oxygenator to improve the capacity of removal of carbon dioxide in blood in the future.

The blood compatibility of block copolymer membranes of poly(benzyl L-glutamate)/poly(ethylene glycol) and the effect of on the blood compatibility of copolymer were evaluated by the clotting time test, the platelet adhesion and deformation test, and the protein adsorption test. The results showed that in terms of blood compatibility, homopolymer was better than glass and silicone, copolymer was better than homopolymer, and the more the PEG in the copolymer, the better the blood compatibility.