Publications by authors named "Weijian Ye"

40 Publications

bFGF alleviates diabetes-associated endothelial impairment by downregulating inflammation via S-nitrosylation pathway.

Redox Biol 2021 Feb 20;41:101904. Epub 2021 Feb 20.

School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, 325000, PR China. Electronic address:

Protein S-nitrosylation is a reversible protein modification implicated in both physiological and pathophysiological regulation of protein function. However, the relationship between dysregulated S-nitrosylation homeostasis and diabetic vascular complications remains incompletely understood. Here, we demonstrate that basic fibroblast growth factor (bFGF) is a key regulatory link between S-nitrosylation homeostasis and inflammation, and alleviated endothelial dysfunction and angiogenic defects in diabetes. Subjecting human umbilical vein endothelial cells (HUVECs) to hyperglycemia and hyperlipidemia significantly decreased endogenous S-nitrosylated proteins, including S-nitrosylation of inhibitor kappa B kinase β (IKKβ) and transcription factor p65 (p65), which was alleviated by bFGF co-treatment. Pretreatment with carboxy-PTIO (c-PTIO), a nitric oxide scavenger, abolished bFGF-mediated S-nitrosylation increase and endothelial protection. Meanwhile, nitrosylation-resistant IKKβ and p65 mutants exacerbated endothelial dysfunction in db/db mice, and in cultured HUVECs subjected to hyperglycemia and hyperlipidemia. Mechanistically, bFGF-mediated increase of S-nitrosylated IKKβ and p65 was attributed to synergistic effects of increased endothelial nitric oxide synthase (eNOS) and thioredoxin (Trx) activity. Taken together, the endothelial protective effect of bFGF under hyperglycemia and hyperlipidemia can be partially attributed to its role in suppressing inflammation via the S-nitrosylation pathway.
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http://dx.doi.org/10.1016/j.redox.2021.101904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972985PMC
February 2021

Recent developments on PET radiotracers for TSPO and their applications in neuroimaging.

Acta Pharm Sin B 2021 Feb 25;11(2):373-393. Epub 2020 Aug 25.

Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA 02114, USA.

The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is predominately localized to the outer mitochondrial membrane in steroidogenic cells. Brain TSPO expression is relatively low under physiological conditions, but is upregulated in response to glial cell activation. As the primary index of neuroinflammation, TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), major depressive disorder (MDD) and obsessive compulsive disorder (OCD). In this context, numerous TSPO-targeted positron emission tomography (PET) tracers have been developed. Among them, several radioligands have advanced to clinical research studies. In this review, we will overview the recent development of TSPO PET tracers, focusing on the radioligand design, radioisotope labeling, pharmacokinetics, and PET imaging evaluation. Additionally, we will consider current limitations, as well as translational potential for future application of TSPO radiopharmaceuticals. This review aims to not only present the challenges in current TSPO PET imaging, but to also provide a new perspective on TSPO targeted PET tracer discovery efforts. Addressing these challenges will facilitate the translation of TSPO in clinical studies of neuroinflammation associated with central nervous system diseases.
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http://dx.doi.org/10.1016/j.apsb.2020.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893127PMC
February 2021

The Development of Three-DNA Methylation Signature as a Novel Prognostic Biomarker in Patients with Colorectal Cancer.

Biomed Res Int 2020 25;2020:3497810. Epub 2020 Nov 25.

Department of Biological Sciences, Life Sciences College, Zhaoqing University, Zhaoqing 526061, China.

Aims: The prognosis of colorectal cancer (CRC) remains poor. This study aimed to develop and validate DNA methylation-based signature model to predict overall survival of CRC patients.

Methods: The methylation array data of CRC patients were retrieved from The Cancer Genome Atlas (TCGA) database. These patients were divided into training and validation datasets. A risk score model was established based on Kaplan-Meier and multivariate Cox regression analysis of training cohort and tested in validation cohort.

Results: Among total 14,626 DNA methylation candidate markers, we found that a three-DNA methylation signature (NR1H2, SCRIB, and UACA) was significantly associated with overall survival of CRC patients. Subgroup analysis indicated that this signature could predict overall survival of CRC patients regardless of age and gender.

Conclusions: We established a prognostic model consisted of 3-DNA methylation sites, which could be used as potential biomarker to evaluate the prognosis of CRC patients.
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http://dx.doi.org/10.1155/2020/3497810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714567PMC
November 2020

Successive Immunization With Epitope-Decreasing Dengue Antigens Induced Conservative Anti-Dengue Immune Responses.

Front Immunol 2020 25;11:585133. Epub 2020 Sep 25.

Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research and Technology (SMART), Singapore, Singapore.

Repeated homologous antigen immunization has been hypothesized to hinder antibody diversification, whereas sequential immunization with heterologous immunogens can educate B cell differentiations towards conserved residues thereby facilitating the generation of cross-reactive immunity. In this study, we developed a sequential vaccination strategy that utilized epitope-decreasing antigens to reinforce the cross-reactivity of T and B cell immune responses against all four serotypes dengue virus. The epitope-decreasing immunization was implemented by sequentially inoculating mice with antigens of decreasing domain complexity that first immunized with DENV1 live-attenuated virus, following by the Envelope protein (Env), and then Env domain III (EDIII) subunit protein. When compared to mice immunized with DENV1 live-attenuated virus three times, epitope-decreasing immunization induced higher TNF-α CD8 T cell immune response against consensus epitopes. Epitope-decreasing immunization also significantly improved neutralizing antibody response to heterologous serotypes. Moreover, this sequential approach promoted somatic hypermutations in the immunoglobulin gene of antigen-specific memory B cells in comparison to repeated immunization. This proof-of-concept work on epitope-decreasing sequential vaccination sheds light on how successively exposing the immune system to decreasing-epitope antigens can better induce cross-reactive antibodies.
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http://dx.doi.org/10.3389/fimmu.2020.585133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545740PMC
September 2020

FGF13 Is a Novel Regulator of NF-κB and Potentiates Pathological Cardiac Hypertrophy.

iScience 2020 Oct 30;23(10):101627. Epub 2020 Sep 30.

School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou 325000, China.

FGF13 is an intracellular FGF factor. Its role in cardiomyopathies has been rarely investigated. We revealed that endogenous FGF13 is up-regulated in cardiac hypertrophy accompanied by increased nuclear localization. The upregulation of FGF13 plays a deteriorating role both in hypertrophic cardiomyocytes and mouse hearts. Mechanistically, FGF13 directly interacts with p65 by its nuclear localization sequence and co-localizes with p65 in the nucleus in cardiac hypertrophy. FGF13 deficiency inhibits NF-κB activation in ISO-treated NRCMs and TAC-surgery mouse hearts, whereas FGF13 overexpression shows the opposite trend. Moreover, FGF13 overexpression alone is sufficient to activate NF-κB in cardiomyocytes. The interaction between FGF13 and p65 or the effects of FGF13 on NF-κB have nothing to do with IκB. Together, an IκB-independent mechanism for NF-κB regulation has been revealed in cardiomyocytes both under basal and stressful conditions, suggesting the promising application of FGF13 as a therapeutic target for pathological cardiac hypertrophy and heart failure.
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http://dx.doi.org/10.1016/j.isci.2020.101627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567043PMC
October 2020

Synthesis and preliminary studies of C-labeled tetrahydro-1,7-naphthyridine-2-carboxamides for PET imaging of metabotropic glutamate receptor 2.

Theranostics 2020 14;10(24):11178-11196. Epub 2020 Sep 14.

Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA, 02114, USA.

Selective modulation of metabotropic glutamate receptor 2 (mGlu) represents a novel therapeutic approach for treating brain disorders, including schizophrenia, depression, Parkinson's disease (PD), Alzheimer's disease (AD), drug abuse and addiction. Imaging mGlu using positron emission tomography (PET) would allow for quantification under physiological and pathological conditions and facilitate drug discovery by enabling target engagement studies. In this paper, we aimed to develop a novel specific radioligand derived from negative allosteric modulators (NAMs) for PET imaging of mGlu. A focused small molecule library of mGlu NAMs with tetrahydro naphthyridine scaffold was synthesized for pharmacology and physicochemical evaluation. GIRK dose-response assays and CNS panel binding selectivity assays were performed to study the affinity and selectivity of mGlu NAMs, among which compounds and were selected as PET ligand candidates. Autoradiography in SD rat brain sections was used to confirm the binding specificity and selectivity of [C] and [C] towards mGlu. binding specificity was then studied by PET imaging. Whole body biodistribution study and radiometabolite analysis were conducted to demonstrate the pharmacokinetic properties of [C] as most promising PET mGlu PET ligand. mGlu NAMs were synthesized in 14%-20% yields in five steps. NAMs and were selected to be the most promising ligands due to their high affinity in GIRK dose-response assays. [C] and [C] displayed similar heterogeneous distribution by autoradiography, consistent with mGlu expression in the brain. While PET imaging study showed good brain permeability for both tracers, compound [C] demonstrated superior binding specificity compared to [C]. Further radiometabolite analysis of [C] showed excellent stability in the brain. Compound exhibited high affinity and excellent subtype selectivity, which was then evaluated by autoradiography and PET imaging study after labeling with carbon-11. Ligand [C], which we named [C]MG2-1904, demonstrated high brain uptake and excellent / specific binding towards mGlu with high metabolic stability in the brain. As proof-of-concept, our preliminary work demonstrated a successful example of visualizing mGlu derived from NAMs, which represents a promising chemotype for further development and optimization aimed for clinical translation.
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http://dx.doi.org/10.7150/thno.42587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532674PMC
September 2020

Synthesis and preliminary evaluation of a novel positron emission tomography (PET) ligand for imaging fatty acid amide hydrolase (FAAH).

Bioorg Med Chem Lett 2020 11 27;30(21):127513. Epub 2020 Aug 27.

Center of Cyclotron and PET Radiopharmaceuticals, Department of Nuclear Medicine and PET/CT-MRI Center, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China. Electronic address:

Fatty acid amide hydrolase (FAAH) exerts its main function in the catabolism of the endogenous chemical messenger anandamide (AEA), thus modulating the endocannabinoid (eCB) pathway. Inhibition of FAAH may serve as an effective strategy to relieve anxiety and possibly other central nervous system (CNS)-related disorders. Positron emission tomography (PET) would facilitate us to better understand the relationship between FAAH in certain disease conditions, and accelerate clinical translation of FAAH inhibitors by providing in vivo quantitative information. So far, most PET tracers show irreversible binding patterns with FAAH, which would result in complicated quantitative processes. Herein, we have identified a new FAAH inhibitor (1-((1-methyl-1H-indol-2-yl)methyl)piperidin-4-yl)(oxazol-2-yl)methanone (8) which inhibits the hydrolysis of AEA in the brain with high potency (IC value 11 nM at a substrate concentration of 0.5 µM), and without showing time-dependency. The PET tracer [C]8 (also called [C]FAAH-1906) was successfully radiolabeled with [C]MeI in 17 ± 6% decay-corrected radiochemical yield (n = 7) with >74.0 GBq/μmol (2 Ci/μmol) molar activity and >99% radiochemical purity. Ex vivo biodistribution and blocking studies of [C]8 in normal mice were also conducted, indicating good brain penetration, high brain target selectivity, and modest to excellent target selectivity in peripheral tissues. Thus, [C]8 is a potentially useful PET ligand with enzyme inhibitory and target binding properties consistent with a reversible mode of action.
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http://dx.doi.org/10.1016/j.bmcl.2020.127513DOI Listing
November 2020

Carbidopa suppresses prostate cancer via aryl hydrocarbon receptor-mediated ubiquitination and degradation of androgen receptor.

Oncogenesis 2020 May 13;9(5):49. Epub 2020 May 13.

Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.

Carbidopa, a peripheral decarboxylase inhibitor used with L-DOPA to treat Parkinson's disease, has attracted significant interest in recent years for its anticancer effect. Increasing evidence reveals that Carbidopa can inhibit cancer cell growth and induce apoptosis through aryl hydrocarbon receptor (AHR) in some cancers. However, the antitumor effect of Carbidopa in prostate cancer (PCa) is not fully understood. Androgen receptor (AR) plays a central role in PCa, even in advanced "castrate-resistant" disease. In the present study, we report that Carbidopa suppresses the growth of PCa by downregulating the protein expression of AR. Carbidopa inhibits proliferation and migration of LNCaP cells and promotes apoptosis, but has no effect on the AR-independent prostate cell line DU145. Carbidopa increases ubiquitination of AR in LNCaP cells. Several studies have shown that AHR can act as an E3 ubiquitin ligase and promote the proteasomal degradation of AR. Quantitative RT-PCR, immunofluorescence staining and immunoblotting assay demonstrate that AHR is induced and activated by Carbidopa, and the co-immunoprecipitation assay shows that AR interacts with AHR, firmly confirming that Carbidopa decreases AR protein level though AHR-induced proteasomal degradation. In addition, Carbidopa suppresses PCa growth in vivo when xenografted into immunocompromised mice. Carbidopa treatment increases AHR protein level and decreases AR protein level in tumor tissues. Taken together, our study implicates Carbidopa for the first time in effective suppression of prostate cancer via a mechanism, involving AHR-mediated proteasomal degradation of AR.
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http://dx.doi.org/10.1038/s41389-020-0236-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220950PMC
May 2020

Determination of isosinensetin in rat plasma by UHPLC-MS/MS: Application to oral and intravenous pharmacokinetic study in healthy rats.

J Pharm Biomed Anal 2020 May 26;184:113210. Epub 2020 Feb 26.

The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China. Electronic address:

Isosinensetin is a polymethoxyflavone existing in various kinds of citrus. It has exhibited significant anti-proliferative activity and herb-drug interaction. To date, a specific determination method to quantify isosinensetin concentration in biological matrix has not been developed. In the present study, a highly specific, simple and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) approach was developed and validated for quantification of isosinensetin in rat plasma with subsequent application to a pharmacokinetic study. Isosinensetin and lysionotin (internal standard, IS) were extracted from rat plasma by a single step protein precipitation using acetonitrile as precipitation agent. The chromatographic separation was conducted using an Agilent C18 column with a gradient elution system (0.1 % formic acid aqueous solution and acetonitrile) within 3.5 min. An electrospray ionization (ESI) source operating in positive mode and multiple reaction monitoring (MRM) were used to monitor the transitions of m/z 373.1 → 343.1 for isosinensetin and m/z 345.1 → 315.1 for IS. The developed method was linear within the range of 1-1000 ng/mL and fully validated according to FDA guidelines. The accuracy values reported as relative errors were between 2.0 and 10.0 % for three quality control levels (2, 400 and 800 ng/mL) and lower limit of quantification (LLOQ). The precisions were ≤11.1 % for quality controls and ≤18.1 % for LLOQ. The recoveries and matrix effects of isosinensetin were in the range of 83.4-87.7 % and 105.6-108.8 %, respectively. Other parameters such as selectivity, carryover effect, dilution integrity and stability were also validated and met the acceptance criteria. The method was applied to a pharmacokinetic study in rats following oral and intravenous administration of isosinensetin. Isosinensetin was rapidly absorbed with a poor bioavailability of 2.19 % and quickly eliminated with mean half-life of 1.40 h and 1.76 h for oral and intravenous route, respectively.
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http://dx.doi.org/10.1016/j.jpba.2020.113210DOI Listing
May 2020

CCAT2 contributes to hepatocellular carcinoma progression via inhibiting miR-145 maturation to induce MDM2 expression.

J Cell Physiol 2020 09 9;235(9):6307-6320. Epub 2020 Feb 9.

Pediatric Research Institute, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Long noncoding RNA colon cancer-associated transcript 2 (CCAT2) has been recently found to function as an oncogene in hepatocellular carcinoma (HCC). However, the mechanisms of CCAT2 in HCC development remain to be further explored. In the present study, we found that CCAT2 was abnormally upregulated in HCC cells and tissue specimens, exhibiting an inverse correlation with microRNA (miR)-145 expression. Mechanistic investigation showed that CCAT2 selectively blocked miR-145 processing, leading to decreased mature miR-145 presence. Both the in vitro and in vivo effects of CCAT2 knockdown on the proliferation and metastasis of HCC cells were reversed by miR-145 inhibitor, indicating that miR-145 modulation accounts for CCAT2-meditated HCC progression. Furthermore, miR-145 mimic dramatically suppressed HCC cells' proliferation and metastasis, revealing a tumor suppressor role of miR-145 in HCC. Mechanistically, MDM2 was predicted to be a potential target of miR-145. The luciferase and western blot assay demonstrated that miR-145 mimic largely inhibited MDM2 3'-untranslated region luciferase activity and MDM2 expression, followed by the upregulation of p53/p21 expression. Finally, the coexpression of MDM2 in miR-145 mimic-transfected HCC cells was able to largely compromise the inhibitory effects of miR-145 mimic on HCC cells' proliferation and metastasis in vitro and tumor formation in a xenograft model, confirming MDM2 is the critical mediator of miR-145 in HCC. In summary, our findings indicated that CCAT2 selectively blocks the miR-145 maturation process and plays an oncogene in HCC. Furthermore, a novel CCAT2/miR-145/MDM2 axis was revealed in HCC development and might provide a new target in the molecular treatment of HCC.
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http://dx.doi.org/10.1002/jcp.29630DOI Listing
September 2020

UHPLC-MS/MS method for the quantification of aloin-A in rat plasma and its application to a pharmacokinetic study.

J Pharm Biomed Anal 2020 Jan 25;178:112928. Epub 2019 Oct 25.

The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, China. Electronic address:

Aloin-A (also known as barbaloin), the main bioactive anthraquinone-C-glycoside of Aloe species, exhibits various beneficial pharmacological effects. However, the determination and pharmacokinetic study of aloin-A in rat plasma need to be improved and systematically demonstrated. In the present study, a simple, robust and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for rapid quantification of aloin-A in rat plasma was developed. Plasma preparation was conducted by a single step protein precipitation with obtusin serving as an internal standards (IS) followed by separation of the analytes using an Agilent C18 column with a gradient mobile phase comprised of acetonitrile and formic acid aqueous solution. Negative ion electrospray was used and multiple reaction monitoring transitions were m/z 417.1 → 297.0 for aloin-A and m/z 343.1 → 328.1 for IS, respectively. The developed method was validated with linear range of 1-1000 ng/mL. All validation parameters were well within the acceptance criteria based on the guidance of FDA. The validated approach was successfully applied to analyze samples from a pharmacokinetic study in healthy rats following intravenous and oral administration. Aloin-A was found to be quickly absorbed, extensively distributed and rapidly eliminated. The absolute bioavailability of aloin-A was 5.79%.
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http://dx.doi.org/10.1016/j.jpba.2019.112928DOI Listing
January 2020

A Study of the Synergistic Interaction of Konjac Glucomannan/Curdlan Blend Systems under Alkaline Conditions.

Materials (Basel) 2019 Oct 29;12(21). Epub 2019 Oct 29.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

To improve the gelation performance of konjac glucomannan (KGM) thermo-irreversible gel in the condition of alkaline, this study investigated the interactions between KGM and curdlan (CUD) in terms of the sol state and gelation process. The apparent viscosity, rheological properties during heating and cooling, thermodynamic properties, gelation properties and water holding capacity of KGM/CUD blend systems in an alkaline environment were studied using physical property testing instruments and methods. The results showed that the viscosity of the KGM/CUD blended solution was greater than the value calculated from the ideal mixing rules in the condition of alkaline (pH = 10.58). As the proportion of CUD in the system increased, the intersection of storage modulus (G') and loss modulus (G") shifted to low frequencies, the relaxation time gradually increased, and the degree of entanglement of molecular chains between these two components gradually increased. The addition of CUD helped decrease the gelation temperature of KGM, increased the gelation rate and inhibited the thinning phenomenon of KGM gels at low temperatures (2-20 °C). The addition of CUD increased the hardness and gel strength of KGM but did not significantly improve the water holding capacity of the KGM/CUD blend gel. The process of mixing KGM and CUD improved the thermal stability of the gel. In summary, KGM/CUD exhibited excellent compatibility under alkaline conditions, and the blend systems produced a "viscosifying effect". KC8 and KC5 show better thermal stability, low temperature resistance and gel strength compared to KGM. This blended gel can be used as a structural support material to provide reference for the development of konjac bionic vegetarian products.
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http://dx.doi.org/10.3390/ma12213543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862313PMC
October 2019

Inferring the history of surname Ye based on Y chromosome high-resolution genotyping and sequencing data.

J Hum Genet 2019 Aug 15;64(8):703-709. Epub 2019 May 15.

State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.

Paternal inheritance of both Y chromosome and surnames makes it possible to trace the origin and migration histories of surnames based on high-resolution Y chromosome phylogeny. In this study, 292 male samples with surname Ye () in China were collected to unravel the history of this surname. Among these samples, O-F492 showed the highest frequency (26.71%). Analysis based on Y chromosome genotyping data of 52,798 males from virtually the whole China revealed a close correlation between O-F492 and surname Ye. High-throughput sequencing of 131 unrelated male individuals covering all sub-haplogroups in O-F492 was conducted to update the phylogeny of O-F492. Most of the Ye individuals (43/64, 67.19%) are embedded in three major branches, i.e., O-MF1461, O-MF15219, and O-FGC66159, deriving from the same node (O-FGC66168). These three clades restrictively distributed in different regions, likely attributed to independent differentiations. Coalescent ages of the three subclades are estimated ranging from 1,925 to 1,775 years ago, probably driven by the massive migration from north to south China after Yongjia riot in Jin Dynasty, consistent with the migration history of surname Ye. Our study thus shed important light on the history of the surname Ye from genetic perspective.
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http://dx.doi.org/10.1038/s10038-019-0616-2DOI Listing
August 2019

Total Synthesis-Enabled Systematic Structure-Activity Relationship Study for Development of a Bioactive Alkyne-Tagged Derivative of Neolaxiflorin L.

J Org Chem 2019 06 24;84(11):7007-7016. Epub 2019 May 24.

Laboratory of Chemical Genomics , Peking University Shenzhen Graduate School , Xili, Shenzhen 518055 , China.

Neolaxiflorin L (NL) is a low-abundant Isodon 7,20-epoxy- ent-kuarenoid and was found to be a promising anticancer drug candidate in our previous study. In order to study its structure-activity relationship (SAR), a diversity-oriented synthetic route toward two libraries of (±)-NL analogs, including analogs containing different functionalities in the same 7,20-epoxy- ent-kuarene skeleton and analogs with skeletal changes, has been developed. The results of this total synthesis-enabled SAR successfully led to a bioactive alkyne-tagged NL derivative, which could be a useful probe for proteomics studies.
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http://dx.doi.org/10.1021/acs.joc.9b00748DOI Listing
June 2019

Metallothionein Protects the Heart Against Myocardial Infarction the mTORC2/FoxO3a/Bim Pathway.

Antioxid Redox Signal 2019 08 11;31(5):403-419. Epub 2019 Apr 11.

2 School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, People's Republic of China.

Cardiac-specific overexpression of metallothionein (MT) has been shown to be beneficial in ischemic heart disease, but the detailed mechanisms through which MT protects against myocardial infarction (MI) remain unknown. This study assessed the involvement of the mTORC2/FoxO3a/Bim pathway in the cardioprotective effects of MT. MI was induced in wild-type (FVB) mice and in cardiac-specific MT-overexpressing transgenic (MT-TG) mice by ligation of the left anterior descending (LAD) coronary artery. Cardiac function was better; infarct size and cardiomyocyte apoptosis were lower in MT-TG mice than in FVB mice after MI. Moreover, MT-TG mice exhibited better phenotypes after LAD ligation than FVB mice treated with Mn(III)tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP; a reactive oxygen species [ROS] scavenger) and cardiac-specific catalase-overexpressing transgenic (CAT-TG) mice, which showed the same ROS levels as MT-TG mice after MI. Activation of mechanistic target of rapamycin complex 2 (mTORC2) was essential for the cardioprotective effects of MT against MI. In addition, MT attenuated the downregulation of phospho-FoxO3a after MI, inhibiting the expression of the apoptosis-associated gene , located downstream of FoxO3a, and reducing the level of apoptosis after MI. To mimic ischemic-injured FVB and MT-TG mice , H9c2 and MT-overexpressing H9c2 (H9c2MT7) cardiomyocytes were subjected to oxygen and glucose deprivation, with the results being consistent with those obtained . The cardioprotective effects of MT against MI are not entirely dependent upon its ability to eliminate ROS. Rather, MT overexpression mostly protects against MI through the mTORC2-FoxO3a-Bim pathway.
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http://dx.doi.org/10.1089/ars.2018.7597DOI Listing
August 2019

Determination and pharmacokinetic study of echinatin by UPLC-MS/MS in rat plasma.

J Pharm Biomed Anal 2019 May 19;168:133-137. Epub 2019 Feb 19.

Analytical and Testing Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China. Electronic address:

Echinatin, one of the bioactive components of licorice, has exhibited diverse therapeutic effects, including anti-inflammatory and anti-oxidant effects. However, determination and pharmacokinetic study of echinatin in biomatrices have not been conducted. In this study, a simple and fast ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the quantification of echinatin in rat plasma was developed, fully validated and subsequently well used in a pharmacokinetic research of echinatin after oral and intravenous administration. Rat plasma samples were operated with a simple one-step acetonitrile precipitation, and licochalcone A was used as the internal standard. Chromatographic separation of echinatin was conducted using an UPLC BEN C18 column and a gradient water (containing 0.1% formic acid)-acetonitrile mobile phase. A Waters XEVO TQS-micro Triple-Quadrupole Tandem Mass Spectrometer operating in positive electrospray ionization mode was used for detection. The approach was proved to be linear in the range of 1-1000 ng/mL and well satisfy the requirements from the guidelines of FDA. A pharmacokinetic study of echinatin was carried out by the new developed method following intravenous and oral administration to adult male Sprague-Dawley rats. Echinatin was demonstrated to be quickly absorbed and eliminated and extensively distributed with an absolute bioavailability of approximately 6.81%.
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http://dx.doi.org/10.1016/j.jpba.2019.02.023DOI Listing
May 2019

Catalytic effect of transglutaminase mediated by myofibrillar protein crosslinking under microwave irradiation.

Food Chem 2019 Jun 22;284:45-52. Epub 2019 Jan 22.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

Microwave (MW) heating improved the activity of transglutaminase (TGase) by inducing conformational changes due to structural modification. However, when TGase and myofibrillar protein were heated, the solubility and degree of crosslinking were similar. Further, the gel properties of the mixed solution pre-gelled by MW heating were lower than that obtained with water bath (WB) pre-gelling. We compared the effects on myofibrillar proteins at the same heating rate, our results showed that MW promoted aggregation, as the particle distribution tended toward larger molecular size. The increase of random coil as investigated by circular dichroism (CD) indicated that WB induced the unfolding of myofibrillar protein. MW enhanced intermolecular forces by engendering more disulfide bonds, which hindered the catalysis by TGase. Finally, SDS-PAGE indicated that the myosin molecules had more head crosslinking during MW treatment. MW and WB cause different response behaviors of myofibrillar protein, thereby affecting the catalytic effect of TGase.
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http://dx.doi.org/10.1016/j.foodchem.2019.01.097DOI Listing
June 2019

In(OTf)-Catalyzed Cascade Cyclization for Construction of Oxatricyclic Compounds.

Org Lett 2018 12 13;20(24):7912-7915. Epub 2018 Dec 13.

Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology , Peking University Shenzhen Graduate School , Shenzhen University Town, Xili, Shenzhen 518055 , China.

A highly diastereoselective cascade cyclization reaction has been developed for establishing a series of oxatricyclic compounds using Chan's diene and simple keto alkynal substrates with only 1 mol % of In(OTf) as the catalyst in 82-92% yields. The potential utility of this synthetic strategy has been demonstrated in model studies for the construction the core structures of 1α,8α:4α,5α-diepoxy-4,5-dihydroosmitopsin and cortistatin A.
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http://dx.doi.org/10.1021/acs.orglett.8b03461DOI Listing
December 2018

Baicalin alleviates hyperglycemia-induced endothelial impairment 1 via Nrf2.

J Endocrinol 2018 Oct 1. Epub 2018 Oct 1.

L Jin, School of Pharmacy, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, 325000, P.R. China, Wenzhou, China.

Baicalin is the major component found in Scutellaria baicalensis root, a widely used herb in traditional Chinese medicine, which exhibits strong anti-inflammatory, anti-viral and anti-tumor activities. The present work was devoted to elucidate the molecular and cellular mechanisms underlying the protective effects of Baicalin against diabetes-induced oxidative damage, inflammation and endothelial dysfunction. Diabetic mice, induced by streptozotocin (STZ), were treated with intraperitoneal Baicalin injections. Human umbilical vein endothelial cells (HUVECs) were cultured either in normal glucose (NG, 5.5 mM) or high glucose (HG, 33 mM) medium in the presence or absence of Baicalin for 72 h. We observed an obvious inhibition of hyperglycemia-triggered oxidative damage and inflammation in HUVECs and diabetic aortal vasculature by Baicalin, along with restoration of hyperglycemia-impaired nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway activity. However, the protective effects of Baicalin almost completely abolished in HUVECs transduced with shRNA against Nrf2, but not with nonsense shRNA. Mechanistic studies demonstrated that HG decreased Akt and GSK3B phosphorylation, restrained nuclear export of Fyn and nuclear localization of Nrf2, blunted Nrf2 downstream target genes, and subsequently induced oxidative stress in HUVECs. However, those destructive cascade, were well prevented by Baicalin in HUVECs. Furthermore, LY294002 and ML385 (inhibitor of PI3K and Nrf2) attenuated Baicalin mediated Nrf2 activation and the ability of facilitates angiogenesis in vivo and ex vivo. Taken together, the endothelial protective effect of Baicalin under hyperglycemia condition could be partly attributed to its role in downregulating reactive oxygen species (ROS) and inflammation via the Akt/GSK3B/Fyn-mediated Nrf2 activation.
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http://dx.doi.org/10.1530/JOE-18-0457DOI Listing
October 2018

Microvesicles from malaria-infected red blood cells activate natural killer cells via MDA5 pathway.

PLoS Pathog 2018 10 4;14(10):e1007298. Epub 2018 Oct 4.

Singapore-MIT Alliance for Research and Technology, Infectious Disease Interdisciplinary Research Group, Singapore.

Natural killer (NK) cells provide the first line of defense against malaria parasite infection. However, the molecular mechanisms through which NK cells are activated by parasites are largely unknown, so is the molecular basis underlying the variation in NK cell responses to malaria infection in the human population. Here, we compared transcriptional profiles of responding and non-responding NK cells following exposure to Plasmodium-infected red blood cells (iRBCs) and identified MDA5, a RIG-I-like receptor involved in sensing cytosolic RNAs, to be differentially expressed. Knockout of MDA5 in responding human NK cells by CRISPR/cas9 abolished NK cell activation, IFN-γ secretion, lysis of iRBCs. Similarly, inhibition of TBK1/IKKε, an effector molecule downstream of MDA5, also inhibited activation of responding NK cells. Conversely, activation of MDA5 by liposome-packaged poly I:C restored non-responding NK cells to lyse iRBCs. We further show that microvesicles containing large parasite RNAs from iRBCs activated NK cells by fusing with NK cells. These findings suggest that NK cells are activated through the MDA5 pathway by parasite RNAs that are delivered to the cytoplasm of NK cells by microvesicles from iRBCs. The difference in MDA5 expression between responding and non-responding NK cells following exposure to iRBCs likely contributes to the variation in NK cell responses to malaria infection in the human population.
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http://dx.doi.org/10.1371/journal.ppat.1007298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171940PMC
October 2018

Intervention of transglutaminase in surimi gel under microwave irradiation.

Food Chem 2018 Dec 15;268:378-385. Epub 2018 Jun 15.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China; School of Food Science and Technology, Jiangnan University, Wuxi 214122, China; Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, Wuxi 214122, China.

Transglutaminase (TGase) was selected as model enzyme to investigate the effects of microwave (MW) heating on its activity and structure compared to water bath (WB) heating. MW heating can enhance the activity of TGase and reach the maximum at 20 min, whereas conduction heating has little effect on the activity of TGase. The difference of dielectric properties between MW heating and WB heating were not obvious, but MW heating had higher conductivity than WB heating. The results of ultraviolet and fluorescence spectra show that MW heating can change the enzyme activity by changing the conformation of TGase. The decrease of α-helix and an increase of β-sheet and β-turn investigated by circular dichroism (CD) indicated the secondary structures of TGase were changed when treated by MW heating. Further gel properties test confirmed that TGase treated by MW could improve the functional and mechanical properties of surimi gel.
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http://dx.doi.org/10.1016/j.foodchem.2018.06.067DOI Listing
December 2018

Pro-apoptotic effects of Kangfuxin on human stomach cancer cells and its underlying mechanism.

Oncol Lett 2018 Jul 16;16(1):931-939. Epub 2018 May 16.

Sichuan Key Laboratory of Medical American Cockroach, Chengdu, Sichuan 610000, P.R. China.

Kangfuxin (KFX) is an oral liquid derived from , with complex components. KFX has been demonstrated to exhibit anticancer activity in a variety of different types of tumor, including gastric cancer; however, its underlying molecular mechanism remains unclear. The present study was designed to investigate the pro-apoptotic effects of KFX on SGC-7901 cells, in order to provide a theoretical basis for clinical application. In order to clarify the pro-apoptotic effects of KFX on SGC-7901 cells, MTT analysis was conducted. To evaluate the anticancer effect of KFX, peroxisome proliferator-activated receptor (PPAR)-γ was analyzed by reverse transcription-polymerase chain reaction. Western blot analysis was used to determine the effects of KFX on the expression of cleaved caspase-3, phosphorylated extracellular signal-regulated kinase (p-ERK), ERK, tumor protein p53 (p53), B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X, interleukin (IL)-6 and IL-1β. In addition, terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling (TUNEL) analysis was used to detect apoptosis in SGC-7901 cells. It was revealed that PPAR-γ was increased in SGC-7901 cells following treatment with KFX, shown by an increase in mRNA expression. Furthermore, western blot analysis identified that KFX treatment groups exhibited markedly inhibited levels of Bcl-2, IL-6, IL-1β and p-ERK, and induced p53 protein expression. Additionally, TUNEL and MTT assays demonstrated that treatment with KFX may induce SGC-7901 cell apoptosis and inhibit proliferation. In conclusion, to the best of our knowledge, the results of the present study demonstrated for the first time that KFX may induce SGC-7901 cell apoptosis and inhibit its proliferation, and this may be primarily attributed to its role in mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase/ERK signaling pathway inhibition.
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http://dx.doi.org/10.3892/ol.2018.8713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019916PMC
July 2018

Protein structural development of threadfin bream ( Nemipterus spp.) surimi gels induced by glucose oxidase.

Food Sci Technol Int 2018 Oct 17;24(7):598-606. Epub 2018 Jun 17.

2 State Key Laboratory of Food Science and Technology, Jiangnan University, China.

This study investigated the effect of glucose oxidase on the gel properties of threadfin bream surimi. The gel strength of surimi increased with the addition of 0.5‰ glucose oxidase after two-step heating. Based on the results of the chemical interactions, the hydrophobic interaction and disulfide bond of glucose oxidase-treated surimi samples increased compared with the control samples at the gelation temperature and gel modori temperature. The surface hydrophobicity of samples with glucose oxidase and glucose increased significantly ( p < 0.05) and total sulfhydryl groups decreased significantly ( p < 0.05). The analysis of Raman spectroscopy shows that the addition of glucose oxidase induced more α-helixes to turn into a more elongated random and flocculent structure. Glucose oxidase changes the secondary structure of the surimi protein, making more proteins depolarize and stretch and causing actomyosin to accumulate to each other, resulting in the formation of surimi gel.
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http://dx.doi.org/10.1177/1082013218779239DOI Listing
October 2018

Quantification and pharmacokinetics of alpinetin in rat plasma by UHPLC-MS/MS using protein precipitation coupled with dilution approach to eliminate matrix effects.

J Pharm Biomed Anal 2018 Apr 27;152:242-247. Epub 2017 Dec 27.

The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China. Electronic address:

Alpinetin, a bioactive flavonoid, has attracted great attention due to its diverse therapeutic effects, namely anti-oxidant, anti-tumor and anti-inflammatory effects with low systemic toxicity. Various determination methods have been developed in quality control and plant chemistry areas. However, quantification and pharmacokinetics of alpinetin in biological matrix have not been studied. In the present research, a sensitive, efficient and reliable ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the determination of alpinetin in rat plasma was developed and validated. Plasma samples were processed with protein precipitation (PP) followed by a 5-fold acetonitrile/water (50:50, v/v) dilution to significantly decrease matrix effect which exited in one step PP method. Determination of alpinetin was conducted using positive electrospray ionization tandem mass spectrometry in multiple reaction monitoring mode. Results demonstrated that the method was precise (3.3%-12.3%), accurate (-5.8% to 10.8%) and linear in the range of 1-1000 ng/mL. The new developed method was subsequently applied to a pharmacokinetic research of alpinetin following oral and intravenous dosing to healthy Sprague-Dawley rats. Alpinetin was demonstrated rapid absorption after oral administration with an absolute bioavailability of ∼15.1% and extensive distribution after dosing.
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http://dx.doi.org/10.1016/j.jpba.2017.12.046DOI Listing
April 2018

Dengue Virus-Infected Dendritic Cells, but Not Monocytes, Activate Natural Killer Cells through a Contact-Dependent Mechanism Involving Adhesion Molecules.

mBio 2017 08 1;8(4). Epub 2017 Aug 1.

Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research and Technology, Singapore, Republic of Singapore

Natural killer (NK) cells play a protective role against dengue virus (DENV) infection, but the cellular and molecular mechanisms are not fully understood. Using an optimized humanized mouse model, we show that human NK cells, through the secretion of gamma interferon (IFN-γ), are critical in the early defense against DENV infection. Depletion of NK cells or neutralization of IFN-γ leads to increased viremia and more severe thrombocytopenia and liver damage in humanized mice. studies using autologous human NK cells show that DENV-infected monocyte-derived dendritic cells (MDDCs), but not monocytes, activate NK cells in a contact-dependent manner, resulting in upregulation of CD69 and CD25 and secretion of IFN-γ. Blocking adhesion molecules (LFA-1, DNAM-1, CD2, and 2β4) on NK cells abolishes NK cell activation, IFN-γ secretion, and the control of DENV replication. NK cells activated by infected MDDCs also inhibit DENV infection in monocytes. These findings show the essential role of human NK cells in protection against acute DENV infection , identify adhesion molecules and dendritic cells required for NK cell activation, and delineate the sequence of events for NK cell activation and protection against DENV infection. Dengue is a mosquito-transmitted viral disease with a range of symptoms, from mild fever to life-threatening dengue hemorrhagic fever. The diverse disease manifestation is thought to result from a complex interplay between viral and host factors. Using mice engrafted with a human immune system, we show that human NK cells inhibit virus infection through secretion of the cytokine gamma interferon and reduce disease pathogenesis, including depletion of platelets and liver damage. During a natural infection, DENV initially infects dendritic cells in the skin. We find that NK cells interact with infected dendritic cells through physical contact mediated by adhesion molecules and become activated before they can control virus infection. These results show a critical role of human NK cells in controlling DENV infection and reveal the sequence of molecular and cellular events that activate NK cells to control dengue virus infection.
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http://dx.doi.org/10.1128/mBio.00741-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5539423PMC
August 2017

Sequencing and de novo assembly of 150 genomes from Denmark as a population reference.

Nature 2017 08 26;548(7665):87-91. Epub 2017 Jul 26.

Bioinformatics Research Centre, Aarhus University, 8000 Aarhus, Denmark.

Hundreds of thousands of human genomes are now being sequenced to characterize genetic variation and use this information to augment association mapping studies of complex disorders and other phenotypic traits. Genetic variation is identified mainly by mapping short reads to the reference genome or by performing local assembly. However, these approaches are biased against discovery of structural variants and variation in the more complex parts of the genome. Hence, large-scale de novo assembly is needed. Here we show that it is possible to construct excellent de novo assemblies from high-coverage sequencing with mate-pair libraries extending up to 20 kilobases. We report de novo assemblies of 150 individuals (50 trios) from the GenomeDenmark project. The quality of these assemblies is similar to those obtained using the more expensive long-read technology. We use the assemblies to identify a rich set of structural variants including many novel insertions and demonstrate how this variant catalogue enables further deciphering of known association mapping signals. We leverage the assemblies to provide 100 completely resolved major histocompatibility complex haplotypes and to resolve major parts of the Y chromosome. Our study provides a regional reference genome that we expect will improve the power of future association mapping studies and hence pave the way for precision medicine initiatives, which now are being launched in many countries including Denmark.
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http://dx.doi.org/10.1038/nature23264DOI Listing
August 2017

Determination and pharmacokinetics of engeletin in rat plasma by ultra-high performance liquid chromatography with tandem mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci 2017 Aug 10;1060:144-149. Epub 2017 Jun 10.

Analytical and Testing Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China. Electronic address:

Engeletin, a bioactive flavonoid, has attracted much attention recently by virtue of its multiple biological (anti-diabetic and anti-inflammatory) activities. Despite signifying many therapeutic applications researches indicating quantification or pharmacokinetics of engeletin in biological matrix are still lacking. Here, a simple, sensitive, accurate and reliable ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) approach for the quantification of engeletin in rat plasma was developed and fully validated for the first time. Plasma samples were processed with acetonitrile by a single step protein precipitation and the separation was achieved on a ZORBAX Eclipse Plus C18 Rapid Resolution High Definition column with a gradient acetonitrile-water mobile phase. Quantification of engeletin was carried out by electrospray ionization tandem mass spectrometry in multiple reaction monitoring (MRM) mode with negative ionization. Results revealed that the approach was linearity from 5 to 5000ng/mL (r=0.9937) and proved to be precise (better than 12.3%) and accurate (-3.3%-5.2%). The developed approach was successfully employed to pharmacokinetic study of engeletin following peroral and intravenous administration to rats. The results of pharmacokinetics demonstrated rapid engeletin absorption (T of 15min) after oral administration, extensive distribution after three different dosages and an absolute bioavailability of ∼1.53%. The developed method and pharmacokinetic data can provide a meaningful basis for further studies on engeletin.
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http://dx.doi.org/10.1016/j.jchromb.2017.06.018DOI Listing
August 2017

Diastereoselective Total Synthesis of (±)-Basiliolide B and (±)-epi-8-Basiliolide B.

J Org Chem 2017 04 15;82(7):3463-3481. Epub 2017 Mar 15.

Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School , Shenzhen University Town, Xili, Shenzhen 518055, China.

The C8 and C9 stereogenic centers of the basiliolide/transtaganolide family have been established stereoselectively using a cyclopropane ring-opening strategy, which has been studied by DFT calculations of a variety of lithium-chelating models. The highly functionalized intermediates obtained in this strategy were successfully employed for the diastereoselective total synthesis of (±)-basiliolide B and (±)-epi-8-basiliolide B. The decalin core with a lactone bridge was constructed via a 2-pyrone Diels-Alder (DA) cycloaddition, and the unprecedented seven-membered acyl ketene acetal was established by a biomimetic intramolecular O-acylation cyclization.
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http://dx.doi.org/10.1021/acs.joc.6b02921DOI Listing
April 2017

Solvent-Free DABCO-Mediated [3 + 2] Cycloadditions of Donor-Acceptor Cyclopropanes with Aldehydes: Strategy for Synthesis of Fully Substituted Furans.

J Org Chem 2016 09 4;81(17):7970-6. Epub 2016 Aug 4.

School of Chemistry and Chemical Engineering, Yangzhou University , 180 Siwangting Street, Yangzhou 225002, P. R. China.

DABCO-mediated [3 + 2] cycloadditions of donor-acceptor cyclopropanes with aldehydes under solvent-free conditions have been developed for the preparation of fully substituted furans which are a wide range of structurally interesting and pharmacologically significant compounds. The reaction appears to be general for a variety of 1-cyanocyclopropane-1-carboxylates and aldehydes and tolerates the presence of aromatic moieties with electron-withdrawing and electron-donating substituents.
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http://dx.doi.org/10.1021/acs.joc.6b01259DOI Listing
September 2016

Discovery, genotyping and characterization of structural variation and novel sequence at single nucleotide resolution from de novo genome assemblies on a population scale.

Gigascience 2015 24;4:64. Epub 2015 Dec 24.

BGI-Europe, Ole Maaløes Vej 3, DK-2200 Copenhagen N, Denmark ; Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark.

Background: Comprehensive recognition of genomic variation in one individual is important for understanding disease and developing personalized medication and treatment. Many tools based on DNA re-sequencing exist for identification of single nucleotide polymorphisms, small insertions and deletions (indels) as well as large deletions. However, these approaches consistently display a substantial bias against the recovery of complex structural variants and novel sequence in individual genomes and do not provide interpretation information such as the annotation of ancestral state and formation mechanism.

Findings: We present a novel approach implemented in a single software package, AsmVar, to discover, genotype and characterize different forms of structural variation and novel sequence from population-scale de novo genome assemblies up to nucleotide resolution. Application of AsmVar to several human de novo genome assemblies captures a wide spectrum of structural variants and novel sequences present in the human population in high sensitivity and specificity.

Conclusions: Our method provides a direct solution for investigating structural variants and novel sequences from de novo genome assemblies, facilitating the construction of population-scale pan-genomes. Our study also highlights the usefulness of the de novo assembly strategy for definition of genome structure.
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http://dx.doi.org/10.1186/s13742-015-0103-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690232PMC
July 2016