Chiral Brønsted Acid-Catalyzed Asymmetric Reaction via Vinylidene Ortho-Quinone Methides.

Vinylidene ortho-quinone methides (VQMs) have been proven to be versatile and crucial intermediates in the catalytic asymmetric reaction in last decade, and thus have drawn considerable concentrations on account of the practical application in the construction of enantiomerically pure functional organic molecules. However, in comparison to the well established chiral Brønsted base-catalyzed asymmetric reaction via VQMs, chiral Brønsted acid-catalyzed reaction is rarely studied and there is no systematic summary to date. In this review, we summarize the recent advances in the chiral Brønsted acid-catalyzed asymmetric reaction via VQMs according to three types of reactions: a) intermolecular asymmetric nucleophilic addition to VQMs; b) intermolecular asymmetric cycloaddition of VQMs; c) intramolecular asymmetric cyclization of VQMs. Finally, we put forward the remained challenges and opportunities for potential breakthroughs in this area.

Bone marrow mesenchymal stem cells-derived exosomal miR-145-5p reduced non-small cell lung cancer cell progression by targeting SOX9.

BACKGROUND: The role of miR-145-5p in non-small cell lung cancer (NSCLC) has been studied, however, the regulation of hBMSCs-derived exosomes (Exo) transmitted miR-145-5p in NSCLC was still unknown. This study aimed to investigate the role of hBMSCs-derived exosomes (Exo) in the progression of NSCLC. METHODS: The Exo was extracted from hBMSCs and added to A549 and H1299 cell culture, followed by the detection of cell proliferation, migration, and invasion. The correlation between the expression of miR-145-5p and SOX9, as well as their binding relationship was determined by correlation analysis, luciferase gene reporter assay and RNA pull-down assays. The in vivo animal model was established to further verify the impact of hBMSCs-Exo. RESULTS: It showed that miR-145-5p was downregulated and SOX9 was upregulated in NSCLC tissues. HBMSCs-derived Exo, and hBMSCs-Exo with overexpression of miR-145-5p could inhibit cell proliferation, migration, and invasion of both A549 and H1299 cells, and prevent against tumor progression in vivo. MiR-145-5p and SOX9 were found to be able to bind to each other, and a negative correlation were observed between the expression of them in NSCLC tissues. Furthermore, inhibition of SOX9 could reversed the suppressed role of miR-145-5p in vitro and in vivo. CONCLUSION: Therefore, HBMSCs-Exo effectively transmitted miR-145-5p, leading to the suppression of malignant development in NSCLC through the regulation of SOX9.

Ligand-Modulated Catalytic Selectivity of Ag Clusterzyme for Relieving Multiorgan Injury via Inhabiting Acute Oxidative Stress.

The artificial enzymes at the atomic level have shown great potential in chemical biology and nanomedicine, and modulation of catalytic selectivity is also critical to the application of nanozymes. In this work, atomic precision Ag25 clusterzymes protected by single- and dual-ligand were developed. Further, the catalytic activity and selectivity of Ag25 clusterzymes were modulated by adjusting doping elements and ligand. The Ag24Pt1 shows more prominent antioxidant activity characteristics in the dual-ligand system, while the Ag24Cu1 possesses the superoxide dismutase-like (SOD-like) activity regardless of the single- or dual-ligand system, indicating modulated catalytic selectivity. In vitro experiments showed the Ag24Pt1-D can recover radiation induced DNA damages and eliminate the excessive reactive oxygen species (ROS) generated from radiation. Subsequent in vivo radiation protection experiments reveal that Ag24Cu1-S and Ag24Pt1-D can improve the survival rate of irradiated mice from 0 to 40% and 30%, respectively. The detailed biological experiments confirm that the Ag24Cu1-S and Ag24Pt1-D can recover the SOD and 3,4-methylenedioxyamphetamine (MDA) levels via suppressing the chronic inflammation reaction. Nearly 60% of Ag24Cu1-S and Ag24Pt1-D can be excreted after a 1 day injection, and no obvious toxicological reactions were observed 30 days after injection.

Atomically precise silver clusterzymes protect mice from radiation damages.

BACKGROUND: As we know, radiotherapy plays an irreplaceable role in the clinical management on solid tumors. However, due to the non-specific killing effects of ionizing radiation, normal tissues damages would be almost simultaneous inevitably. Therefore, ideal radioprotective agents with high efficiency and low toxicity are always desirable. In this work, atomically precise Ag14 clusterzymes were developed, and their applications in radioprotection were studied in vitro and in vivo for the first time. METHODS: The ultra-small glutathione supported Ag14 clusterzymes were synthesized by convenient sodium borohydride (NaBH4) reduction of thiolate-Ag (I) complexes and then they were purified by desalting columns. The enzyme-like activity and antioxidant capacity of Ag14 clusterzymes have been tested by various commercial kits, salicylic acid method and electron spin resonance (ESR). Next, they were incubated with L929 cells to evaluate whether they could increase cell viability after γ-ray irradiation. And then Ag14 clusterzymes were intravenously injected into C57 mice before 7 Gy whole-body γ-ray irradiation to evaluate the radioprotection effects in vivo. At last, the in vivo toxicities of Ag14 clusterzymes were evaluated through biodistribution test, hematological details, serum biochemical indexes and histological test in female Balb/c mice with intravenous injection of Ag14 clusterzymes. RESULTS: Our studies suggested atomically precise Ag14 clusterzymes were potential radioprotectants. Ag14 clusterzymes exhibited unique superoxide dismutase (SOD)-like activity, strong anti-oxidative abilities, especially on •OH scavenging. The Ag14 clusterzymes could effectively improve cell viability through eliminating ROS and prevent DNA damages in cells dealt with γ-ray irradiation. In vivo experiments showed that Ag14 clusterzymes could improve the irradiated mice survival rate by protecting hematological systems and repairing tissue oxidative stress damage generated by γ-ray irradiation. In addition, bio-distribution and toxicological experiments demonstrated that the ultrasmall Ag14 clusterzymes could be excreted quickly from the body by renal clearance and negligible toxicological responses were observed in mice up to 30 days. CONCLUSION: In summary, atomically precise, ultrasmall and water soluble Ag14 clusterzymes with SOD-like activity were successfully developed and proved to be effective both in vitro and in vivo for radioprotection. Furthermore, with atomically precise molecular structure, Ag14 clusterzymes, on aspect of the catalytic and optical properties, may be improved by structure optimization on atom-scale level for other applications in disease diagnosis and treatment.

Epidemiological and genetic analysis of hand-foot-mouth disease by enterovirus A71 in Taizhou, P. R. China, between 2010 and 2013.

Out of a population of 1,098 enteroviruses (EVs)-positive hand, foot, and mouth disease (HFMD) specimens, 352 were screened positive for EV-A71-accounting for 32.1% of all EV-positive specimens. This percentage denotes EV-A71 as the second major serotype of enteroviruse among HFMD suffers in Taizhou. An epidemic outbreak of EV-A71 among HFMD children was found in Taizhou in the second quarter of 2012. Phylogeny analysis based on the VP1 complete sequences leads us to find a sub-clade (designated TZ1-1) of EV-A71 circulating in Taizhou, whose emergence might be correlated with the epidemic outbreak. This correlation was further supported by the followed two analyses (namely skyline plot of population history and birth-death SIR simulation of epidemic history). And more importantly, at a positively selected site of VP1 caspid, a mutation of N31D was found to be a synapomorphy of TZ1-1 and its occurrence might be correlated with the epidemic outbreak. J. Med. Virol. 89:782-790, 2017. © 2016 Wiley Periodicals, Inc.

Hydrogen sulfide inhibits opioid withdrawal-induced pain sensitization in rats by down-regulation of spinal calcitonin gene-related peptide expression in the spine.

Hyperalgesia often occurs in opioid-induced withdrawal syndrome. In the present study, we found that three hourly injections of DAMGO (a µ-opioid receptor agonist) followed by naloxone administration at the fourth hour significantly decreased rat paw nociceptive threshold, indicating the induction of withdrawal hyperalgesia. Application of NaHS (a hydrogen sulfide donor) together with each injection of DAMGO attenuated naloxone-precipitated withdrawal hyperalgesia. RT-PCR and Western blot analysis showed that NaHS significantly reversed the gene and protein expression of up-regulated spinal calcitonin gene-related peptide (CGRP) in naloxone-treated animals. NaHS also inhibited naloxone-induced cAMP rebound and cAMP response element-binding protein (CREB) phosphorylation in rat spinal cord. In SH-SY5Y neuronal cells, NaHS inhibited forskolin-stimulated cAMP production and adenylate cyclase (AC) activity. Moreover, NaHS pre-treatment suppressed naloxone-stimulated activation of protein kinase C (PKC) α, Raf-1, and extracellular signal-regulated kinase (ERK) 1/2 in rat spinal cord. Our data suggest that H2S prevents the development of opioid withdrawal-induced hyperalgesia via suppression of synthesis of CGRP in spine through inhibition of AC/cAMP and PKC/Raf-1/ERK pathways.

The prognosis of MGMT promoter methylation in glioblastoma patients of different race: a meta-analysis.

O(6)-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair gene. Epigenetic silencing of the MGMT promoter methylation compromises DNA repair and has been associated with longer survival in patients with glioblastoma (GBM) who receive alkylating agents. But the prognostic of MGMT promoter methylation in GBM patients of different race is still ambiguous. Based on an univariate or multivariate analysis between different race (Caucasian and Asian), a meta-analysis of the effects of MGMT promoter methylation on both progression-free survival (PFS) and overall survival (OS) among GBM patients was conducted. A total of 6,309 patients from 50 studies were involved in the analysis. Random effect models were applied to estimate the pooled hazard ratio (HR) with 95 % confidence intervals (CIs) for GBM patients of different race prognosis, the Chi square-based Q test was used to test heterogeneity. Begg's (funnel plot method) and Egger's linear regression tests were adopted to check publication bias (a bias with regard to what is likely to be published, among what is available to be published). The HR value estimated for OS was 0.524 (95 % CI 0.428-0.640) by univariate analysis and 0.427 (95 % CI 0.355-0.513) by multivariate analysis in Caucasian. The HR value estimated for OS was 0.892 (95 % CI 0.469-1.698) by univariate analysis and 0.562 (95 % CI 0.394-0.804) by multivariate analysis in Asian. The HR value estimated for PFS was 0.526 (95 % CI 0.372-0.743) by univariate analysis and 0.437 (95 % CI 0.356-0.537) by multivariate analysis in Caucasian. The HR value estimated for PFS was 0.132 (95 % CI 0.006-3.027) by multivariate analysis in Asian. This data revealed that GBM patients with MGMT promoter methylation had longer OS and PFS by univariate or multivariate analysis in Caucasian regardless of therapeutic intervention. However, GBM patients with MGMT promoter methylation only had longer OS by multivariate analysis in Asian.

Effects of multifaceted optimization management for chronic heart failure: a multicentre, randomized controlled study.

AIMS: In recent years, we have developed the concept of 'clinical pathway based on integrated traditional Chinese and western medicine for the management of Chronic heart failure (CHF)'. The purpose of this study was to assess the implementation effects of multifaceted optimization management of chronic heart failure. METHODS: A total of nine physicians in optimization group from nine research sites received multifaceted intervention (a 1-day training session on how to implement the optimization programme, a written optimization programme for CHF management, supervision from daily quality coordinator, and 1-monthly monitoring and feedback of performance measure) with respect to the management of CHF, comparing to nine physicians in control group who did not receive the aforementioned multifaceted intervention and diagnosed and treated CHF patients with conventional programme (usual care). After that, a total of 256 patients with CHF were enrolled and randomly assigned to receive optimization programme [integration of usual care and traditional Chinese medicine (TCM) treatment] or conventional programme (usual care) for the treatment of CHF. The primary outcome was the change in New York Heart Association (NYHA) functional classification during 24 weeks of treatment. RESULTS: When compared with usual care, multifaceted optimization management resulted in superior improvements in NYHA functional classification at the 12-week visit (P = 0.023), the 16-week, 20-week, and 24-week visits (P < 0.001). It also demonstrated superior performance in comparison with the conventional programme with respect to readmission rate for major adverse cardiovascular events (MACEs), readmission rate for worsening heart failure, plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, left ventricular ejection fraction (LVEF), patient TCM syndrome scores, quality of life, and patients with heart failure with reduced ejection fraction (HFrEF) in optimization group more likely received beta-blockers and ACE inhibitors or ARBs than those in control group (P = 0.038 and P = 0.013, respectively). CONCLUSIONS: It is likely that the multifaceted optimization programme used in this study is feasible would benefit patients with CHF in NYHA functional classification, readmission for worsening heart failure, plasma NT-proBNP level, LVEF, patient TCM syndrome scores, and quality of life. Additionally, it would improve hospital personnel adherence to evidence-based performance measures for HFrEF.

Clinical pathways based on integrative medicine in chinese hospitals improve treatment outcomes for patients with acute myocardial infarction: a multicentre, nonrandomized historically controlled trial.

Objective. To determine the impact of an integrative medicine clinical pathways (CPs) on the length of in-hospital stay and on outcomes for patients with acute myocardial infarction (AMI). Methods. A multicenter nonrandomized controlled trial enrolling 197 consecutive patients with AMI at eight urban TCM hospitals was conducted between 1 January 2010 and 31 October 2010. These patients were enrolled in the interventional group after the CPs had been implemented. The control group included 405 patients with AMI from eight hospitals; these patients were treated between 1 January 2008 and 31 December 2009, before the CPs were implemented. Outcome measures were the length of hospital stay costs of medical care, and major cardiovascular events (MACEs) during hospitalization. Results. Compared with the control group, the patients in intervention group had a shorter length of hospital stay (9.2 ± 4.2 days versus 12.7 ± 8.6 days, P < 0.05), and reduced healthcare costs in hospital (46365.7 ± 18266.9 versus 52866.0 ± 35404.4, P < 0.05). There were statistically significant differences in MACE between the two groups during the hospitalization period (2.5% versus 6.9%, P = 0.03). Conclusion. These data suggest that the development and implementation of the clinical pathways based in Integrative Medicine could further improve quality of care and outcome for patients with AMI.

Design of Monovalent Cerium-Based Metal Organic Frameworks as Bioinspired Superoxide Dismutase Mimics for Ionizing Radiation Protection.

Superoxide dismutase (SOD) is one of the major antioxidants in vivo and is expected to play critical roles on the defense against reactive oxygen species (ROS)-mediated damages, such as ionizing radiation damages. Herein, inspired by the function and structure of natural SODs and cerium oxide nanozymes, two monovalent cerium-based metal organic frameworks (Ce-MOFs), CeIIIBTC and CeIVBTC, were designed for superoxide radical (O2•-) elimination and ionizing radiation protection. These two Ce-MOFs selectively scavenge O2•- and are excellent SOD mimics. Like natural SODs and cerium oxide nanozymes, the SOD-like catalytic mechanism of Ce-MOFs involves a cycle between Ce(IV) and Ce(III). Furthermore, by constructing monovalent Ce-MOFs, we found that high-valent CeIVBTC are more effective SOD-like nanozymes compared to CeIIIBTC. With smaller size, better monodispersity, and more effective SOD-like activity, CeIVBTC nanozymes were further applied for ionizing radiation protection. Both in vitro and in vivo results demonstrated that CeIVBTC nanozymes could efficiently scavenge ROS, prevent cells from γ-ray radiation-induced cell viability decrease and DNA damages, and improve the survival rate of irradiated mice by recovering the bone marrow DNA damage and alleviating oxidative stress of tissues. The protective effect and good biocompatibility of CeIVBTC nanozymes will enable the development of Ce-MOFs-based radioprotectants and facilitate treatment of other ROS-related diseases.

Evaluation of the Ecological Effects of Ecological Restoration Programs: A Case Study of the Sloping Land Conversion Program on the Loess Plateau, China.

The Sloping Land Conversion Program (SLCP) is the largest ecological restoration program in the world. Evaluating the ecological effects of the SLCP not only provides a scientific basis for China to improve the SLCP but also provides a reference for other countries in the world to evaluate the ecological effects of ecological restoration programs being implemented or to be implemented. To this end, we took the Loess Plateau, the core area for the implementation of the SLCP, as an example and, based on multi-source remote sensing data and GIS technology, we conducted a comprehensive evaluation of the ecological effects of the implementation of the SLCP on the Loess Plateau. The results showed that, first, from 2000 to 2018, a total of 12,372.05 km2 of cultivated land was converted into forest land and grassland on the Loess Plateau, and this contributed to an increase in vegetation cover from 45.09% in 2000 to 64.15% in 2018, and a decrease in the soil erosion modulus from 26.41 t·hm-2·yr-1 in 2000 to 17.92 t·hm-2·yr-1 in 2018. Second, the 6-25° slope range is the core area of the Loess Plateau for implementation of the SLCP. In this range, the area of cultivated land converted into forest land and grassland accounts for 60.16% of the total area of transferred cultivated land. As a result, the 6-25° slope range has become the most significant area for improving vegetation cover and reducing the soil erosion intensity, and it is mainly concentrated in the southwestern, central and central-eastern hilly and gully areas of the Loess Plateau. Third, from 2000 to 2018, the climate of the Loess Plateau tended to be warm and humid and was conducive to the implementation of the SLCP. Among these factors, precipitation is the dominant factor in determining the spatial distribution of vegetation on the Loess Plateau, and the increase in precipitation is also the main reason for the promotion of vegetation growth. Fourthly, from 2000 to 2018, the ecological environment of the Loess Plateau was significantly improved as a result of the combined effects of the implementation of the SLCP and climate warming and humidification, but the primary reason is still the implementation of the SLCP.

[Expression of Peroxiredoxin-6 Gene in Patients with Acute Myeloid Leukemia and Its Clinical Significance].

OBJECTIVE: To study the expression of Peroxiredoxin-6 (Prdx6) gene in elderly patients with acute myeloid leukemia (AML) and its clinical significance. METHODS: The expression level of Prdx6 in bone marrow cells of 33 cases of AML, 8 cases of CML and 11 cases of other blood diseases was detected by PCR. The correlation of the abnormal expression of Prdx6 with patient age and blood routine parameters was further analyzed. RESULTS: the expression level of Prdx6 in elderly patients with AML (≥60 years) was significantly lower than that in younger patients (＜60 years) (P＜0.05); the expression level of Prdx6 in low WBC (≤1×109/L) group was lower than that in medium WBC (1-10×109/L) group or high WBC (＞10×109/L) group (P＜0.05); the proportion of WBC count (≤1×109/L) in elderly patients with AML reached 38.5%, which was significantly higher than that in younger patients (5%) (P＜0.05); the overall survival (OS) rate of elderly patients was lower than that of younger patients (P＜0.05). CONCLUSION: The expression of Prdx6 in elderly patients with AML is low, moreover, it relates with low value of WBC in peripheral blood, suggesting that it may be one of poor prognostic factors for the elderly patients with AML.

1-Hydroxymethyl-1-methylethan-aminium chloride.

The asymmetric unit of the title compound, C(4)H(12)NO(+)·Cl(-), contains two independent ion pairs. Weak intra-molecular C-H⋯O and N-H⋯O hydrogen bonds result in the formation of three five-membered rings, which have envelope conformations. The crystal structure contains intermolecular O-H⋯Cl, N-H⋯O, N-H⋯Cl and O-H⋯O hydrogen bonds.

2-Methyl-7-nitro-2,3-dihydro-1-benzofuran.

The dihydro-furan ring of the title compound, C(9)H(9)NO(3), adopts an envelope conformation. The nitro group is twisted slightly away from the attached benzene ring [dihedral angle = 21.9 (1)°].

On the Ecology and Conservation of Sericinus montelus (Lepidoptera: Papilionidae) - Its Threats in Xiaolongshan Forests Area (China).

CONTENTS AND METHODS: Here we present a detailed analysis of the life history, mobility and habitat requirements of the butterfly Sericinus montelus on the basis of extensive field observations, experimental breeding, capture-mark- recapture (CMR) and transect surveys. LIFE HISTORY: We found that S. montelus has three generations per year and overwinters as pupae on shrub branches in Xiaolongshan. The adults of first generation have a peak of emergence in late April. The second generation emerges at the end of June and the third in early to middle August. Within the study region, larvae of S. montelus are monophagous on Aristolochia contorta. Adults fly slowly and lay eggs in clusters. KEY FACTORS: Life tables show that natural enemies and human activities such as mowing, weeding and trampling during the egg and larval stages are key factors causing high mortality, killing up to 43% of eggs and 72% of larvae thereby limiting population growth and recovery. POPULATION ECOLOGY: The populations of S. montelus in Xiaolongshan have a rather patchy distribution. According to CMR data, adults fly a maximum distance of 700m within a lifespan of 6 days. The host plant A. contorta, grows along the low banks of fields, irrigation ditches and paths, and can be highly affected by agricultural activities, like mowing, weeding and herding, which impact larval survival. POPULATION MAINTENANCE: For S. montelus should mainly focus on reducing agricultural threats to the host plant A. contorta and on increasing habitat connectivity.

Efficacy of Danlou Tablet in Patients with Non-ST Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Results from a Multicentre, Placebo-Controlled, Randomized Trial.

This study seeks to investigate potential cardioprotection of Danlou Tablets in patients undergoing PCI with non-ST elevation acute coronary syndrome (NSTE-ACS). 219 patients with NSTE-ACS were randomised to Danlou Tablet pretreatment (n = 109) or placebo (n = 110). No patients received statins prior to PCI and all patients were given atorvastatin (10 mg/day) after procedure. The main endpoint was the composite incidence of major adverse cardiac events (MACEs) within 30 days after PCI. The proportion of patients with elevated levels of cTn I>5 × 99% of upper reference limit was significantly lower in the Danlou Tablet group at 8 h (22.0% versus 34.5%, p = 0.04) and 24 h (23.9% versus 38.2%, p = 0.02) after PCI. The 30-day MACEs occurred in 22.0% of the Danlou Tablet group and 33.6% in the placebo group (p = 0.06). The incidence of MACE at 90-day follow-up was significantly decreased in the Danlou Tablet group compared to the placebo group (23.9% versus 37.3%, p = 0.03). The difference between the groups at 90 days was the incidence of nonfatal myocardial infarction (22% versus 34.5%, p = 0.04). These findings might support that treatment with Danlou Tablet could reduce the incidence of periprocedural myocardial infarction in patients with ACS undergoing PCI.