Publications by authors named "Yumei Yang"

49 Publications

BNT162b2 Vaccine Encoding the SARS-CoV-2 P2 S Protects Transgenic hACE2 Mice against COVID-19.

Vaccines (Basel) 2021 Apr 1;9(4). Epub 2021 Apr 1.

Shanghai Fosun Pharmaceutical Industrial Development, Co. Ltd., 1289 Yishan Road, Shanghai 200233, China.

BNT162b2 is a highly efficacious mRNA vaccine approved to prevent COVID-19. This brief report describes the immunogenicity and anti-viral protective effect of BNT162b2 in hACE2 transgenic mice. Prime-boost immunization with BNT162b2 elicited high titers in neutralizing antibodies against SARS-CoV-2, which correlated with viral clearance and alleviated lung lesions in these mice after viral challenge.
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http://dx.doi.org/10.3390/vaccines9040324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066210PMC
April 2021

Safety and immunogenicity of the SARS-CoV-2 BNT162b1 mRNA vaccine in younger and older Chinese adults: a randomized, placebo-controlled, double-blind phase 1 study.

Nat Med 2021 Apr 22. Epub 2021 Apr 22.

NHC Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China.

An effective vaccine is needed to end the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Here, we assess the preliminary safety, tolerability and immunogenicity data from an ongoing single-center (in Jiangsu province, China), parallel-group, double-blind phase 1 trial of the vaccine candidate BNT162b1 in 144 healthy SARS-CoV-2-naive Chinese participants. These participants are randomized 1:1:1 to receive prime and boost vaccinations of 10 µg or 30 µg BNT162b1 or placebo, given 21 d apart, with equal allocation of younger (aged 18-55 years) and older adults (aged 65-85 years) to each treatment group (ChiCTR2000034825). BNT162b1 encodes the SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) and is one of several messenger RNA-based vaccine candidates under clinical investigation. Local reactions and systemic events were generally dose dependent, transient and mild to moderate. Fever was the only grade 3 adverse event. BNT162b1 induced robust interferon-γ T cell responses to a peptide pool including the RBD in both younger and older Chinese adults, and geometric mean neutralizing titers reached 2.1-fold (for younger participants) and 1.3-fold (for the older participants) that of a panel of COVID-19 convalescent human sera obtained at least 14 d after positive SARS-CoV-2 polymerase chain reaction test. In summary, BNT162b1 has an acceptable safety profile and produces high levels of humoral and T cell responses in an Asian population.
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http://dx.doi.org/10.1038/s41591-021-01330-9DOI Listing
April 2021

Energy dependence on discharge mode of Izhikevich neuron driven by external stimulus under electromagnetic induction.

Cogn Neurodyn 2021 Apr 11;15(2):265-277. Epub 2020 May 11.

Department of Physics, Central China Normal University, Wuhan, 430079 China.

Energy supply plays a key role in metabolism and signal transmission of biological individuals, neurons in a complex electromagnetic environment must be accompanied by the absorption and release of energy. In this paper, the discharge mode and the Hamiltonian energy are investigated within the Izhikevich neuronal model driven by external signals in the presence of electromagnetic induction. It is found that multiple electrical activity modes can be observed by changing external stimulus, and the Hamiltonian energy is more dependent on the discharge mode. In particular, there is a distinct shift and transition in the Hamiltonian energy when the discharge mode is switched quickly. Furthermore, the amplitude of periodic stimulus signal has a greater effect on the neuronal energy compared to the angular frequency, and the average Hamiltonian energy decreases when the discharge rhythm becomes higher. Based on the principle of energy minimization, the system should choose the minimum Hamiltonian energy when maintaining various trigger states to reduce the metabolic energy of signal processing in biological systems. Therefore, our results give the possible clues for predicting and selecting appropriate parameters, and help to understand the sudden and paroxysmal mechanisms of epilepsy symptoms.
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http://dx.doi.org/10.1007/s11571-020-09596-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969689PMC
April 2021

SS-31 protect retinal pigment epithelial cells from H O -induced cell injury by reducing apoptosis.

Clin Exp Pharmacol Physiol 2021 Mar 28. Epub 2021 Mar 28.

The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China.

Evidence has shown that effects from oxidative stress induced damage of retinal or human retinal pigment epithelial (RPE) cells. Antioxidant supplementation is a plausible strategy to avoid oxidative stress and maintain the function of retina. d-Arg-2,6-dimethyltyrosine-Lys-Phe-NH2 (SS-31) has been used in the treatment of many diseases. In this study, we found that SS-31 attenuated hydrogen peroxide (H O )-induced loss of cell viability, reduced oxidative damage and cell apoptosis in RPE cells. HO-1, Trx-1 and Nrf-2 expression levels significantly increased on pre-treatment with SS-31 compared with the H O group. SS-31 inhibited apoptosis through the downregulation of Bax and the upregulation of Bcl-2. Our results suggest that SS-31 had a protective effect against H O treatment in ARPE-19 cells by enhancing the antioxidative enzymes expression and decreasing apoptosis, which could be considered a promising therapeutic intervention for retinal degeneration.
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http://dx.doi.org/10.1111/1440-1681.13484DOI Listing
March 2021

Thyroid function and non-alcoholic fatty liver disease in hyperthyroidism patients.

BMC Endocr Disord 2021 Feb 18;21(1):27. Epub 2021 Feb 18.

Present address: The Department of Endocrinology, Zhongshan hospital, Fudan University, NO. 180 Fenglin Road, Shanghai, 200032, China.

Background: Although thyroid function has been demonstrated to be associated with non-alcoholic fatty liver disease (NAFLD) in different population, the prevalence and features of NAFLD in hyperthyroidism have not been reported. The present study aims to investigate the prevalence of NAFLD and association of thyroid function and NAFLD in hyperthyroidism patients.

Methods: This cross-sectional study was performed in Zhongshan Hospital, Fudan University, China. A total 117 patients with hyperthyroidism were consecutively recruited from 2014 to 2015. Thyroid function and other clinical features were measured, liver fat content was measured by color Doppler ultrasonically, NAFLD was defined in patients with liver fat content more than 9.15%. Statistical analyses were performed with SPSS software package version 13.0.

Results: The prevalence of NAFLD was 11.97% in hyperthyroidism. Patient with NAFLD had lower free triiodothyronine (FT3) and free thyroxine (FT4) levels than patients without NAFLD (P < 0.05). After adjusting for age, gender, metabolic parameters and inflammation factors, higher FT3 were associated with lower liver fat content (β = - 0.072, P = 0.009) and decreased odds ratio of NAFLD (OR = 0.267, 95%CI 0.087-0.817, P = 0.021).

Conclusions: FT3 level was negatively associated with the liver fat content in this population. These results may provide new evidence in the role of thyroid hormone on the regulation of liver fat content and NAFLD.
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http://dx.doi.org/10.1186/s12902-021-00694-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890885PMC
February 2021

Patient Preferences For Specialty Pharmacy Services: A Stated Preference Discrete-Choice Experiment in China.

Front Public Health 2020 9;8:597389. Epub 2020 Dec 9.

West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China.

To survey, analyze, and ascertain the preferences for specialty pharmacy services among patients requiring complex care and to provide evidence to support specialty pharmacy service decision-making in China. To identify essential service attributes and levels, a review of the literature, discussions with specialty pharmacy managers and a pilot questionnaire were conducted. A D-efficient fractional factorial design was used to generate the discrete-choice experiment (DCE) questionnaire. A face-to-face survey of patients with chronic illness and their families or friends was conducted at three specialty pharmacies in Chengdu and Qingdao, China. A mixed logit model was used for estimation. Six relevant attributes were identified and incorporated into the DCE questionnaire. A total of 417 participants completed the survey (mean age 43 years, 45.1% males), and 32.1% had lung cancer. The conditional relative importance showed that the most critical attribute was "frequency of telephone follow-up to monitor adverse drug reactions (ADRs), "followed by "mode of drug delivery," "provider of medication guidance services," and "availability of medical insurance consultation"; the least important attribute was "business hours." A 1 min increase in time spent led to a 0.73% decrease in the probability that a service profile would be chosen. Negative preferences were noted for ADR monitoring by telephone follow-up once a year (β = -0.23, < 0.001) and business hours [8:30-20:00 (Monday to Friday), 8:30-17:30 (weekend)] (β = -0.12, < 0.001). Compared with women, men had a higher preference for service monitoring ADRs once every 3 months. Preference measurements showed that "frequency of telephone follow-up to monitor ADRs" had the most critical impact on decisions, followed by "mode of drug delivery." Specialty pharmacies in China need to take these findings into account to improve their design to increase uptake and patient loyalty.
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http://dx.doi.org/10.3389/fpubh.2020.597389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755860PMC
December 2020

Coexistence of Sarcoidosis and Sjögren's syndrome with hypercalcemia and renal involvement: A case report and literature review.

Endocr Metab Immune Disord Drug Targets 2020 Jun 19. Epub 2020 Jun 19.

Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai. China.

Background: Sarcoidosis and Sjögren's syndrome (SS) are chronic multi-system inflammatory diseases of unknown origin that most commonly attack the salivary glands. Both of the diseases have vague and nonspecific symptoms, causing difficulties for the clinicians to distinguish between the two diseases. Most diagnostic criteria of SS exclude sarcoidosis. However, a coexistence of both diseases should be noted. Here, we reported a case of coexisting sarcoidosis and Sjögren's syndrome, complicated with severe hypercalcemia and renal failure, in addition to a literature review.

Case Report: A 71-year-old man visited our hospital complaining of daily progressive oral dryness, thirst and blurred vision with a feeling of dry eyes for one-year duration. His physical examination showed enlargement of both sides of cervical and supraclavicular lymph nodes. Lung auscultation showed decreased breath sounds with bibasilar inspiratory crackles. However, initial laboratory results revealed severe hypercalcemia with moderate hypercalciuria and renal failure. The final diagnosis was coexisting SS and sarcoidosis according to clinical, radiological and laboratory data. The patient received oral prednisone therapy for 18 months. After a follow-up of years, the serum calcium concentration, renal function, and chest CT scan remained normal after prednisone treatment stopped for more than 18 months.

Conclusion: In the literature, calcium metabolic disorder and renal involvement have not been reported among patients with Sarcoidosis and Sjögren's syndrome, suggesting that calcium metabolic disorder may be underestimated. Serum and urine calcium concentration should be measured in addition to routine laboratory test.
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http://dx.doi.org/10.2174/1871530320666200619133654DOI Listing
June 2020

The Association between eGFR and the Aldosterone-to-Renin Ratio and Its Effect on Screening for Primary Aldosteronism.

Int J Endocrinol 2020 7;2020:2639813. Epub 2020 Feb 7.

Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

Objectives: Long-term exposure to excessive aldosterone secretion from the adrenal gland may cause renal damage in patients with primary aldosteronism (PA). The aldosterone-to-renin ratio (ARR) may be significantly affected by renal function, especially in patients with renal damage related to long-term PA. The objective of this study was to investigate the association between the estimated glomerular filtration rate (eGFR) and ARR as well as its effect on screening for PA.

Methods: This study was performed in Zhongshan Hospital, Fudan University, China. 803 patients with hypertension were consecutively recruited from 2012 to 2015. All participants underwent routine biochemical measurements, including plasma renin activity (PRA) and plasma aldosterone concentration (PAC). In all patients with a PAC higher than 10 ng/dl, a saline perfusion test was conducted, and a CT scan or adrenal venous sampling was also performed if needed. Receiver operating characteristic (ROC) analysis was conducted in all eGFR < 90 and eGFR ≥ 90 groups separately to determine the optimal cut-off values of ARR.

Results: The optimal cut-off point for PA was an ARR of 40 ng/dl per ng/ml.h in the whole population, 52 ng/dl per ng/ml.h in subjects with an eGFR higher than 90 ml/min/1.73 m, and 18 ng/dl per ng/ml.h in subjects with an eGFR lower than 90 ml/min/1.73 m. Patients with an eGFR higher than 90 ml/min/1.73 m had significantly lower PRA and higher ARR levels than patients with an eGFR lower than 90 ml/min/1.73 m ( < 0.05).

Conclusions: Unsuppressed renin and lower ARR levels were associated with decreased eGFR in patients with primary aldosteronism. Diagnostic criteria of ARR by stratified eGFR may be an optimal strategy for the screening of primary aldosteronism.
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http://dx.doi.org/10.1155/2020/2639813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029269PMC
February 2020

Efficacy and Safety of Percutaneous Argon-Helium Cryoablation for Hepatocellular Carcinoma Abutting the Diaphragm.

J Vasc Interv Radiol 2020 Mar 24;31(3):393-400.e1. Epub 2020 Jan 24.

Department of Interventional Therapy, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, Shenzhen 518035, China. Electronic address:

Purpose: To evaluate the efficacy and safety of percutaneous argon-helium cryoablation (CA) for hepatocellular carcinoma (HCC) abutting the diaphragm (<5 mm).

Materials And Methods: A total of 61 consecutive patients (50 men, 11 women; mean age, 56.3 ± 12.1 years old; range, 32-83 years) with 74 HCC tumors (mean size, 3.3 ± 1.7 cm; range, 0.8-7 cm) who were treated with percutaneous argon-helium CA were enrolled in this retrospective study. Adverse events were evaluated according to Common Terminology Criteria for Adverse Events, version 5.0. Local tumor progression (LTP) and overall survival (OS) were analyzed using the Kaplan-Meier method and the log-rank test. The risk factors associated with OS and LTP were evaluated using univariate and multivariate Cox regression analysis.

Results: No periprocedural (30-day) deaths occurred. A total of 29 intrathoracic adverse events occurred in 24 of the 61 patients. Major adverse events were reported in 5 patients (pleural effusion requiring catheter drainage in 4 patients and pneumothorax requiring catheter placement in 1 patient). Median follow-up was 18.7 months (range, 2.3-60.0 months). Median time to LTP after CA was 20.9 months (interquartile range [IQR], 14.1-30.6 months). Median times of OS after CA and diagnosis were 27.3 months (IQR, 15.1-45.1 months) and 40.9 months (interquartile range, 24.8-68.6 months), respectively. Independent prognostic factors for OS included tumor location (left lobe vs right lobe; hazard ratio [HR], 2.031; 95% confidence interval [CI], 1.062-3.885; P = .032) and number of intrahepatic tumors (solitary vs multifocal; HR, 2.684; 95% CI, 1.322-5.447; P = .006). Independent prognostic factors for LTP included age (HR, 0.931; 95% CI, 0.900-0.963; P  < .001), guidance modality (ultrasound vs computed tomography and US; HR, 6.156 95% CI, 1.862-20.348; P  =   .003) and origin of liver disease.

Conclusions: Percutaneous argon-helium CA is safe for the treatment of HCC abutting the diaphragm, with acceptable LTP and OS.
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http://dx.doi.org/10.1016/j.jvir.2019.11.003DOI Listing
March 2020

Retrospective analysis of CT-guided percutaneous cryoablation for treatment of painful osteolytic bone metastasis.

Cryobiology 2020 02 17;92:203-207. Epub 2020 Jan 17.

Department of Interventional Therapy, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen Second People's Hospital, Shenzhen, 518035, China. Electronic address:

This study aimed to evaluate the safety and effectiveness of CT-guided percutaneous cryoablation for treatment of painful osteolytic bone metastases. A total of 26 patients (36 bone metastases) treated with CT-guided percutaneous cryoablation between May 2012 and June 2016 were enrolled in this retrospective study. All procedures were performed under local anesthesia. A visual analog scale (VAS) was used to evaluate pain before the procedure and at 1 day, 1 month, 3 months, and 6 months after the procedure. Complications during and after the procedure were recorded and graded by the Clavien-Dindo classification. The mean VAS pain score was 7.1 ± 1.1 (range, 4-10) before cryoablation. It was significantly lower at all timepoints after treatment: 2.1 ± 1.7 (P < 0.0001) at 1 day after treatment, 1.3 ± 1.8 (P < 0.0001) at 1 month, 1.6 ± 1.7 (P < 0.0001) at 3 months, and 1.8 ± 1.3 (P < 0.0001) at 6 months. The response rates were 91.7%, 94.4%, 91.7%, and 94.4%, respectively, at 1 day, 1 month, 3 months, and 6 months after cryoablation; the complete response rates were 22.2%, 41.7%, 36.1%, and 22.2%, respectively. Adverse events (skin frostbite, nerve injury, pathologic fracture) occurred in 3 patients. CT-guided percutaneous cryoablation under local anesthesia appears to be a safe and effective treatment for painful osteolytic bone metastases. Prospective clinical trials on large samples needed to confirm this conclusion.
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http://dx.doi.org/10.1016/j.cryobiol.2020.01.012DOI Listing
February 2020

Distribution of runs of homozygosity in Chinese and Western pig breeds evaluated by reduced-representation sequencing data.

Anim Genet 2018 Dec 16;49(6):579-591. Epub 2018 Oct 16.

Department of Animal Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China.

Inbreeding, which has several causes including genetic drift, population bottlenecks, mating of close relatives and selection, can leave tracts of runs of homozygosity (ROH) along genomes. Recently, decreasing performance on reproductive traits, which might have resulted from inbreeding, has been observed in Chinese pigs. In this study, 830 individuals from Western and Chinese pig breeds were genotyped using the reduced-representation sequencing method. After imputation and quality control, 60 850 high-confidence SNPs were retained for ROH detection. A simulation was performed to explore the reliability of ROH detection with imputed data. Different ROH-related variables were compared between imputed and non-missing genotypes used in ROH detection. Furthermore, ROH islands were evaluated and annotated to find genes influenced by inbreeding in these pigs. The simulation results showed that imputed data with 0.7 as the average missing genotype rate and three heterozygotes allowed in a sliding window have comparable ROH detected compared with data with no missing genotypes. Compared with Western pig breeds, Chinese pigs had more autosomes covered by ROH longer than 5 Mb, indicating higher inbreeding in Chinese pigs in recent times. Genes related to reproduction, immunity, meat quality and adaptability in Chinese pigs and several genes related to growth speed and immunity in Western pigs were observed in short ROH islands. The reproduction-related gene PRM1 was found to be located in the most frequent long ROH island in Chinese pigs, which might explain the decreasing fertility in Chinese pig breeds.
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http://dx.doi.org/10.1111/age.12730DOI Listing
December 2018

Safety and Short-Term Efficacy of Irreversible Electroporation and Allogenic Natural Killer Cell Immunotherapy Combination in the Treatment of Patients with Unresectable Primary Liver Cancer.

Cardiovasc Intervent Radiol 2019 Jan 27;42(1):48-59. Epub 2018 Aug 27.

Biotherapy Center, Fuda Cancer Hospital of Jinan University, Guangzhou, 510665, China.

Purpose: This study aimed to investigate the safety and short-term efficacy of irreversible electroporation (IRE) combined with allogenic natural killer (NK) cell immunotherapy in the treatment of patients with unresectable primary liver cancer.

Materials And Methods: Between October 2015 and December 2016, 40 patients were enrolled and randomly allocated to either the IRE group (n = 22) or the IRE-NK group (n = 18). All adverse events experienced by the patients were recorded; the changes in tumor biomarkers [AFP, CA 19-9, circulating tumor cells (CTCs)], lymphocyte number and function, quality of life, clinical response, progression-free survival (PFS) and overall survival (OS) were assessed.

Results: Patients who received combination therapy exhibited significantly longer median PFS and OS than who just received IRE (PFS 15.1 vs. 10.6 months, P < 0.05, OS 17.9 vs. 23.2 months, P < 0.05). The combination therapy of IRE and NK cell immunotherapy significantly reduced CTCs and increased immune function and Karnofsky performance status.

Conclusion: Our data suggest a novel, promising combination therapy using IRE and allogenic NK cell immunotherapy. Larger clinical trials are required to confirm these conclusions.
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http://dx.doi.org/10.1007/s00270-018-2069-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267679PMC
January 2019

Mechanistic insights into the photogeneration and quenching of guanine radical cation via one-electron oxidation of G-quadruplex DNA.

Phys Chem Chem Phys 2018 May;20(19):13598-13606

Key Laboratory of Theoretical and Computational Photochemistry of Ministry of Education, Department of Chemistry, Beijing Normal University, Xin-wai-da-jie 19, Beijing 100875, P. R. China.

Herein, mechanistic aspects of the photogeneration and quenching of guanine radical cation through one-electron oxidation of the G-quadruplex of G2T2G2TGTG2T2G2 (TBA) sequence were investigated by a combined quantum mechanical/molecular mechanical (QM/MM) approach at the CASPT2//CASSCF/AMBER level of theory. Herein, one electron promotion of the oxygen lone pair of the photo-excited photosensitizer peroxydisulfate to its O-O σ* orbital was first demonstrated to become tunable through the varied reduction ability of the G base in the presence or absence of interbase hydrogen bonding, thereby dynamically controlling the deprotonation site in G-quadruplex TBA. The quenching of G radical cation mediated by the formation of SO42-via photoinduced electron transfer can be triggered effectively by the deprotonation reaction of free proton rather than that of the hydrogen-bonded proton in G-G (G-quartet) and G-T (loop) aqueous surrounding. By calculating the deprotonation paths for the G radical cation, the deprotonation reactions in G-quadruplex TBA were verified to proceed predominantly along the site of imino proton (N1-H) in the loop moiety; this showed the coexisting occurrence of amino (N2-H) deprotonation in the G-quartet part. The mechanistic features discussed in this study represent significant advances in the understanding of DNA radical chemistry.
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http://dx.doi.org/10.1039/c8cp01718bDOI Listing
May 2018

Mechanistic insights into the formation of oxenium ions and radical intermediates through the photolysis of phenylhydroxylamine and its derivatives.

Phys Chem Chem Phys 2018 Jan;20(4):2220-2229

Key Laboratory of Theoretical and Computational Photochemistry of Ministry of Education, Department of Chemistry, Beijing Normal University, Xin-wai-da-jie 19, Beijing 100875, P. R. China.

The photolysis of photoprecursors to produce oxenium ions has been the subject of extensive experimental studies from femtosecond to microsecond time scales. However, mechanistic insights into the generation of activated intermediate species remain elusive. Herein, we present a theoretical investigation to comprehensively elucidate the possible reaction channels for the formation of oxenium ions and radical intermediates at the multi-configuration perturbation level of theory. Computational results show that photo-initiated electron donation from the phenyl moiety to the repulsive N-O σ* orbital leads to the formation of a diradical intermediate in ground state, and further triggers intramolecular electron transfer from the phenyl moiety to the ammonia radical cation (˙NH). This affords closed-shell singlet oxenium ions and neutral :NH as the major products. However, the generation of open-shell triplet outcomes is shown to rely on the energetically accessible single-triplet crossings and spin-orbital interaction among the involved electronic states. Taken together, these data can be used to determine the electronic structures and related properties, as well as reactivities, of oxenium ions and radicals generated by the photolysis of phenylhydroxylamine and its derivatives.
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http://dx.doi.org/10.1039/c7cp07071cDOI Listing
January 2018

Integrated analysis of tobacco miRNA and mRNA expression profiles under PVY infection provids insight into tobacco-PVY interactions.

Sci Rep 2017 07 7;7(1):4895. Epub 2017 Jul 7.

Department of Agronomy, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, Zhejiang, 310058, P. R. China.

Potato virus Y (PVY) is a globally and economically important pathogen of potato, tobacco, tomato and other staple crops and caused significant yield losses and reductions in quality.To explore the molecular PVY-host interactions, we analysed changes in the miRNA and mRNA profiles of tobacco in response to PVY infection. A total of 81 differentially expressed miRNAs belonging to 29 families and 8133 mRNAs were identified. The Gene Ontology (GO) enrichment analyses showed that genes encoding the DNA/RNA binding, catalytic activity and signalling molecules were all significantly enriched. Moreover, 88 miRNA-mRNA interaction pairs were identified through a combined analysis of the two datasets. We also found evidence showing that the virus-derived siRNAs (vsiRNAs) from the PVY genome target tobacco translationally controlled tumor protein (NtTCTP) mRNA and mediate plant resistance to PVY. Together, our findings revealed that both miRNA and mRNA expression patterns can be changed in response to PVY infection and novel vsiRNA-plant interactions that may regulate plant resistance to PVY. Both provide fresh insights into the virus-plant interactions.
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http://dx.doi.org/10.1038/s41598-017-05155-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501784PMC
July 2017

Liver-Specific Overexpression of Gamma-Glutamyltransferase Ameliorates Insulin Sensitivity of Male C57BL/6 Mice.

J Diabetes Res 2017 4;2017:2654520. Epub 2017 Jun 4.

Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu 610041, China.

In the current study, we developed a liver-specific GGT-overexpressing mice model by rapid injection pLIVE-GGT vector through tail vein and investigated the effects of GGT elevation on glucose metabolism and insulin sensitivity. The serum GGT activity was significantly increased after 7 days of pLIVE-GGT1 vector delivery and lasted for about 3 weeks. GGT overexpression reduced the levels of GSSG and GSH in the liver and serum and had no effects on total antioxidative capacity in the liver, kidney, and skeletal muscle except for the pancreas. Increased GGT activity had no effect on the glucose tolerance but could facilitate blood glucose lowering after intraperitoneal insulin administration. The results of Western blotting showed that increased GGT activity enhanced insulin-induced AKT phosphorylation at Ser473. Furthermore, GGT inhibitor could attenuate the changes of insulin-induced blood glucose uptake and AKT phosphorylation in the liver. In summary, the present study developed a liver-specific GGT-overexpressing mice model and found that GGT elevation in short term had no effects on glucose metabolism but could increase insulin sensitivity through enhancing the activity of insulin signaling pathway.
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http://dx.doi.org/10.1155/2017/2654520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474247PMC
April 2018

Palmitoleate inhibits insulin transcription by activating the ERK1/2 pathway in rat pancreatic β-cells.

Exp Ther Med 2017 Jun 18;13(6):2805-2811. Epub 2017 Apr 18.

Department of Rheumatology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang 322000, P.R. China.

The aim of the present study was to evaluate the effects of palmitoleate on insulin secretion and insulin mRNA levels, and to investigate the transcriptional regulation of insulin. INS-1 rat insulinoma cells were treated with palmitoleate in the presence of high glucose, and the amount of secreted insulin was measured via radioimmunoassay. Reverse transcription-quantitative polymerase chain reaction was performed to evaluate the mRNA levels of insulin and pancreatic and duodenal homeobox 1 (PDX1) under palmitoleate treatment. The levels of PDX1, peroxisome proliferator-activated receptor gamma (PPARG), extracellular signal-regulated kinase (ERK)1/2 and phosphorylated ERK1/2 were measured using western blot analysis. Low concentrations of palmitoleate significantly induced insulin secretion (P=0.024), whereas the mRNA levels of insulin and PDX1 were markedly reduced. However, the inhibitory effects were reversed with the addition of U0126, suggesting that the ERK1/2-mediated pathway may be the underlying mechanism responsible for palmitoleate-induced downregulation of insulin mRNA. Exposure of INS-1 cells to high glucose significantly increased the phosphorylation of ERK1/2 (P=0.039), which was further enhanced by palmitoleate (P=0.025). Exposure of INS-1 cells to high glucose significantly decreased PPARG (P=0.001), which was further decreased by the addition of palmitoleate. U0126 was able to reverse the palmitoleate-induced effects. In conclusion, the present study suggested that palmitoleate may induce insulin secretion and inhibit insulin mRNA expression in pancreatic β-cells.
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http://dx.doi.org/10.3892/etm.2017.4344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450653PMC
June 2017

Ovarian metastasis from non-small cell lung cancer with ALK and EGFR mutations: A report of two cases.

Oncol Lett 2016 Dec 19;12(6):4361-4366. Epub 2016 Oct 19.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China.

Ovarian metastasis from non-small cell lung cancer (NSCLC) is a rare condition. The current study presents the cases of 2 female patients aged 38 and 47 years old, respectively, who were initially diagnosed with NSCLC adenocarcinoma on histology. Both patients initially presented with chest pain and a cough, and subsequently developed ovarian metastases following multiple treatments. The 38-year old patient exhibited an epidermal growth factor receptor mutation, confirmed by scorpion/amplified refractory mutation system analysis from a lung biopsy. The 47-year old exhibited an anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangement, revealed by fluorescence hybridization analysis of the breast tissue biopsy, confirming a diagnosis of ALK rearrangement-positive NSCLC. These patients developed ovarian metastasis in the course of the disease. The current study reports the diagnostic challenges and clinical management of the disease, and provides a review of the literature.
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http://dx.doi.org/10.3892/ol.2016.5292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5228381PMC
December 2016

Autophagy and autophagy dysfunction contribute to apoptosis in HepG2 cells exposed to nanosilica.

Toxicol Res (Camb) 2016 May 8;5(3):871-882. Epub 2016 Mar 8.

School of Public Health , Capital Medical University , Beijing , 100069 , P.R. China . Email: ; ; Tel: +86 010 83911507.

Great concerns have led to the evaluation of the potential hazards of nanosilica to human health and the environment. However, there still exists persistent debates on the biological effects and toxic consequences induced by nanosilica. The present study investigated both autophagy and apoptosis in ICR mice and Human hepatocellular carcinoma cells (HepG2), and then explored the interactive mechanism between these two distinct cell death modalities in HepG2 cells. Mice liver injuries seen by hematoxylin and eosin (HE) staining indicated the hepatotoxic effects of nanosilica. The TUNEL assay and immunohistochemistry results confirmed that nanosilica could induce both apoptosis and autophagy . Flow cytometry analysis demonstrated apoptosis induction , while autophagic ultrastructures, LC3-II expression and immunofluorescence clarified autophagy activation by nanosilica. Apoptosis suppression by the autophagy inhibitor of 3-methyladenine (3-MA) implied that autophagy was involved in apoptotic cell death. A mechanistic study verified that nanosilica induced autophagy negative regulation of mammalian target of rapamycin (mTOR) signaling but not the Beclin-1 associated pathway. The enhancement of p62 accumulation and mTOR down-regulation might account for the molecular mechanism in contribution of autophagy to apoptosis. As an emerging new mechanism of nanomaterial toxicity, autophagy might be a more susceptive indicator for toxicological consequence evaluation in nanoparticle toxicity. The present study provides novel evidence to elucidate the toxicity mechanisms and may be beneficial to more rational applications of nanosilica in the future.
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http://dx.doi.org/10.1039/c5tx00465aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062368PMC
May 2016

Membrane-bound pyrophosphatase of human gut microbe Clostridium methylpentosum confers improved salt tolerance in Escherichia coli, Saccharomyces cerevisiae and tobacco.

Mol Membr Biol 2016 May - Aug;33(3-5):39-50

a School of Life Sciences, Engineering Research Center of Sustainable Development and Utilization of Biomass Energy , Ministry of Education, Key Laboratory of Biomass Energy and Environmental Biotechnology of Yunnan Province, Yunnan Normal University , Kunming , Yunnan , China.

Membrane-bound pyrophosphatases (PPases) are involved in the adaption of organisms to stress conditions, which was substantiated by numerous plant transgenic studies with H-PPase yet devoid of any correlated evidences for other two subfamilies, Na-PPase and Na,H-PPase. Herein, we demonstrate the gene cloning and functional evaluation of the membrane-bound PPase (CmPP) of the human gut microbe Clostridium methylpentosum. The CmPP gene encodes a single polypeptide of 699 amino acids that was predicted as a multi-spanning membrane and K-dependent Na,H-PPase. Heterologous expression of CmPP could significantly enhance the salt tolerance of both Escherichia coli and Saccharomyces cerevisiae, and this effect in yeast could be fortified by N-terminal addition of a vacuole-targeting signal peptide from the H-PPase of Trypanosoma cruzi. Furthermore, introduction of CmPP could remarkably improve the salt tolerance of tobacco, implying its potential use in constructing salt-resistant transgenic crops. Consequently, the possible mechanisms of CmPP to underlie salt tolerance are discussed.
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http://dx.doi.org/10.1080/09687688.2017.1370145DOI Listing
October 2017

Molecular Cloning, Expression Analysis, and Functional Characterization of the H(+)-Pyrophosphatase from Jatropha curcas.

Appl Biochem Biotechnol 2016 Apr 7;178(7):1273-85. Epub 2015 Dec 7.

School of Life Sciences, Engineering Research Center of Sustainable Development and Utilization of Biomass Energy, Ministry of Education, Key Laboratory of Biomass Energy and Environmental Biotechnology of Yunnan Province, Yunnan Normal University, Kunming, 650500, Yunnan, China.

H(+)-pyrophosphatase (H(+)-PPase) is a primary pyrophosphate (PPi)-energized proton pump to generate electrochemical H(+) gradient for ATP production and substance translocations across membranes. It plays an important role in stress adaptation that was intensively substantiated by numerous transgenic plants overexpressing H(+)-PPases yet devoid of any correlated studies pointing to the elite energy plant, Jatropha curcas. Herein, we cloned the full length of J. curcas H(+)-PPase (JcVP1) complementary DNA (cDNA) by reverse transcription PCR, based on the assembled sequence of its ESTs highly matched to Hevea brasiliensis H(+)-PPase. This gene encodes a polypeptide of 765 amino acids that was predicted as a K(+)-dependent H(+)-PPase evolutionarily closest to those of other Euphorbiaceae plants. Many cis-regulatory elements relevant to environmental stresses, molecular signals, or tissue-specificity were identified by promoter prediction within the 1.5-kb region upstream of JcVP1 coding sequence. Meanwhile, the responses of JcVP1 expression to several common abiotic stresses (salt, drought, heat, cold) were characterized with a considerable accordance with the inherent stress tolerance of J. curcas. Moreover, we found that the heterologous expression of JcVP1 could significantly improve the salt tolerance in both recombinant Escherichia coli and Saccharomyces cerevisiae, and this effect could be further fortified in yeast by N-terminal addition of a vacuole-targeting signal peptide from the H(+)-PPase of Trypanosoma cruzi.
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http://dx.doi.org/10.1007/s12010-015-1944-0DOI Listing
April 2016

An acidified thermostabilizing mini-peptide derived from the carboxyl extension of the larger isoform of the plant Rubisco activase.

J Biotechnol 2015 Oct 29;212:116-24. Epub 2015 Aug 29.

School of Life Sciences, Engineering Research Center of Sustainable Development and Utilization of Biomass Energy, Ministry of Education, Key Laboratory of Biomass Energy and Environmental Biotechnology of Yunnan Province, Yunnan Normal University, Kunming 650500, Yunnan, China. Electronic address:

Thermostable fusion peptide partners are valuable in engineering thermostability in proteins. We evaluated the Arabidopsis counterpart (AtRAce) and an acidified derivative (mRAce) of the conserved carboxyl extension (RAce) of plant Rubisco activase (RCA) for their thermostabilizing properties in Escherichia coli and Saccharomyces cerevisiae using a protein fusion strategy. We used AtRAce and mRAce as fusion tails for the thermolabile protein RCA2 from Arabidopsis thaliana and Nicotiana tabacum. The homologous fusion of AtRAce with Arabidopsis RCA2 and the heterologous fusion of AtRAce with tobacco RCA2 increased the thermostability of both proteins. The acidified derivative mRAce conferred greater thermostability upon both proteins as compared with AtRAce. Moreover, mRAce enhanced the thermostability of other two thermolabile proteins from Jatropha curcas: the cytosolic ascorbate peroxidase 1 (JcAPX1) and the TATA-box binding protein isoform 1 (JcTBP1). We further report - for the first time - that JcTBP1 mediates heat tolerance in vivo in yeast. Thus, our study identifies a C-terminal acidic mini-peptide - the acidified derivative mRAce - with potential uses in improving the thermostability of heat-labile proteins and their associated heat tolerance in host organisms.
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http://dx.doi.org/10.1016/j.jbiotec.2015.08.021DOI Listing
October 2015

Endosulfan activates the extrinsic coagulation pathway by inducing endothelial cell injury in rats.

Environ Sci Pollut Res Int 2015 Oct 2;22(20):15722-30. Epub 2015 Jun 2.

Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, Beijing, 100069, China.

Endosulfan, a persistent organic pollutant, is widely used in agriculture as a pesticide. The aim of the present study was to evaluate the blood toxicity of different doses of endosulfan in Wistar rats. The experimental sample was composed of four groups, a control group that did not receive endosulfan and three endosulfan-exposed groups that respectively received 1, 5, or 10 mg/kg/day (doses below LD50), of endosulfan for 21 days. The results showed that endosulfan significantly decreased the prothrombin time (PT) and upregulated the activated coagulation factors VIIa, Xa, and XIIIa; thrombin-antithrombin complex (TAT); and P-selectin. Plasma levels of tissue factor (TF) and malondialdehyde (MDA) were increased in the endosulfan groups. The activated partial thromboplastin time (APTT) and the level of activated coagulation factor IXa showed no obvious changes. Immunohistochemical results showed increased expression of von Willebrand factor (vWF) and the inflammatory cytokine interleukin (IL)-1β in the groups exposed to endosulfan. The pathology and electron microscopy results showed impaired vascular tissue accompanied by the exfoliation of endothelial cells and mitochondrial damage in the endosulfan-exposed groups. In summary, our results suggest that endosulfan damages endothelial cells via oxidative stress and the inflammatory response, leading to the release of TF and vWF into the blood. The TF and vWF in the blood may activate extrinsic coagulation factors and platelets, thus triggering the extrinsic coagulation pathway. There were no obvious effects on the intrinsic coagulation pathway.
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http://dx.doi.org/10.1007/s11356-015-4710-5DOI Listing
October 2015

Heterogeneous expression and biological function of ubiquitin carboxy-terminal hydrolase-L1 in osteosarcoma.

Cancer Lett 2015 Apr 8;359(1):36-46. Epub 2015 Jan 8.

Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address:

Ubiquitin carboxyl terminal hydrolase 1 (UCHL1), a member of the UCH class of DUBs, has been reported as either an oncogene or a tumor suppressor. However, the molecular mechanism underlying the biological function of UCHL1 in osteosarcoma is still unclear. This study was aimed at elucidating the roles of UCHL1 in regulating the biological behavior of osteosarcoma cells. In this study, we found that UCHL1 was elevated in osteosarcoma compared with normal bone tissue. Moreover, UCHL1 expression level was correlated with tumor maximum diameter, high rate of lung metastases and short survival time. Then, we found that knockdown of UCHL1 in osteosarcoma cell MG63 inhibited cell proliferation and significantly increased cell population in the G1 phase. Several cyclins promoting G1/S phase transition were reduced after UCHL1 knockdown, including cell cycle regulator cyclin D1, cyclin E1 and CDK6. Moreover, inhibition of UCHL1 in MG63 cells dramatically induced cell apoptosis. We also found that down-regulation of UCHL1 in MG63 significantly inhibited cell invasion. Then, we found that there was a positive correlation between UCHL1 expression level and the Akt and ERK phosphorylation status. Finally, in vivo data showed that knockdown of UCHL1 inhibited osteosarcoma growth in nude mice. These results indicate that UCHL1 could work as an oncogene and may serve as a promising therapeutic strategy for osteosarcoma.
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http://dx.doi.org/10.1016/j.canlet.2014.12.001DOI Listing
April 2015

Improvement on the thermal stability and activity of plant cytosolic ascorbate peroxidase 1 by tailing hyper-acidic fusion partners.

Biotechnol Lett 2015 Apr 17;37(4):891-8. Epub 2014 Dec 17.

Key Laboratory of Biomass Energy and Environmental Biotechnology of Yunnan Province, Engineering Research Center of Sustainable Development and Utilization of Biomass Energy, Ministry of Education, School of Life Sciences, Yunnan Normal University, Kunming, 650500, Yunnan, China,

Cytosolic ascorbate peroxidase 1 (APX1) plays a crucial role in regulating the level of plant cellular reactive oxygen species and its thermolability is proposed to cause plant heat-susceptibility. Herein, several hyper-acidic fusion partners, such as the C-terminal peptide tails, were evaluated for their effects on the thermal stability and activity of APX1 from Jatropha curcas and Arabidopsis. The hyper-acidic fusion partners efficiently improved the thermostability and prevented thermal inactivation of APX1 in both plant species with an elevated heat tolerance of at least 2 °C. These hyper-acidified thermostable APX1 fusion variants are of considerable biotechnological potential and can provide a new route to enhance the heat tolerance of plant species especially of inherent thermo-sensitivity.
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http://dx.doi.org/10.1007/s10529-014-1754-4DOI Listing
April 2015

Cancer drug development in China: recent advances and future challenges.

Drug Discov Today 2015 Jun 20;20(6):766-71. Epub 2014 Nov 20.

Quintiles China, Beijing 100006, China.

Over the past 10 years, the Chinese Government, academic organizations, and biopharmaceutical companies have tried to transition the nation from a consumer of generic drugs into a developer of innovative therapies. Here, we present a timeline of recent innovative cancer drug development, with a particular focus on four case studies that have reshaped perceptions of what can be done in China. We present metrics comparing China with other countries alongside analysis of what national authorities are doing to close the gap in areas where China still lags behind the West.
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http://dx.doi.org/10.1016/j.drudis.2014.11.005DOI Listing
June 2015

Visceral adiposity index and insulin secretion and action in first-degree relatives of subjects with type 2 diabetes.

Diabetes Metab Res Rev 2015 Mar 4;31(3):315-21. Epub 2015 Feb 4.

Second Affiliated Hospital of Harbin Mecical University, Department of Endocrinology and Metabolism, Harbin, Heilongjiang, China; Yiwu Affiliated Hospital, Zhejiang University School of Medicine, Department of Endocrinology and Metabolism, Hangzhou, Zhengjiang, China.

Background: To explore the predictive performance of the newly established visceral adiposity index for diabetes and prediabetes, as well as the relationships between the visceral adiposity index and the parameters of insulin secretion and action.

Methods: Eight hundred twenty-four first-degree relatives of individuals with type 2 diabetes who had no known history of abnormal glucose regulation were selected. Diabetes and prediabetes were diagnosed using the standard oral glucose tolerance test.

Results: The visceral adiposity index values were greater for the subjects with prediabetes and diabetes than for those with normal glucose regulation. Among the subjects with normal glucose regulation, the visceral adiposity index was higher for those whose levels were above the median value of the incremental area under the curve for glucose than for the subjects whose levels fell below the median value. The visceral adiposity index was negatively correlated with the homeostasis model assessment of the β-cell function index (Homa-β) and with the insulinogenic index (ΔI30 /ΔG30 ). The visceral adiposity index was found to be a valuable predictor of diabetes, but it was not superior to triglyceride levels, waist circumference, or lipid accumulation production.

Conclusions: The first degree relatives of people with type 2 DM who have prediabetes or diabetes have progressively higher visceral adiposity index in association with progressive hyperglycemia, and it was found to correlate with the Homa-β and the ΔI30 /ΔG30 .
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http://dx.doi.org/10.1002/dmrr.2615DOI Listing
March 2015

A genome-wide scan for selection signatures in Yorkshire and Landrace pigs based on sequencing data.

Anim Genet 2014 Dec 19;45(6):808-16. Epub 2014 Oct 19.

Department of Animal Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China; Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai, 200240, China.

Pigs have experienced dramatic selection due to domestication, which has led to many different phenotypes when compared to their wild counterparts, especially in the last several decades. Currently, genome-wide scans in both cattle and humans showing positive selection footprints have been investigated. However, few studies have focused on porcine selection footprints, particularly on a genome-wide scale. Surveying for selection footprints across porcine genomes can be quite valuable for revealing the genetic mechanisms of phenotypic diversity. Here, we employed a medium sequencing depth (5-20x/site per individual, on average) approach called genotyping by genome reducing and sequencing (GGRS) to detect genome-wide selection signatures of two domestic pig breeds (Yorkshire and Landrace) that have been under intensive selection for traits of muscle development, growth and behavior. The relative extended haplotype homozygosity test, which identifies selection signatures by measuring the characteristics of haplotypes' frequency distribution within a single population, was also applied to identify potential positively selected regions. As a result, signatures of positive selection were found in each breed. However, most selection signatures were population specific and related to genomic regions containing genes for biological categories including brain development, metabolism, growth and olfaction. Furthermore, the result of the gene set enrichment analysis indicated that selected regions of the two breeds presented a different over-representation of genes in the Gene Ontology annotations and Kyoto Encyclopedia of Genes and Genomes pathways. Our results revealed a genome-wide map of selection footprints in pigs and may help us better understand the mechanisms of selection in pig breeding.
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http://dx.doi.org/10.1111/age.12229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276287PMC
December 2014

A new genotype imputation method with tolerance to high missing rate and rare variants.

PLoS One 2014 27;9(6):e101025. Epub 2014 Jun 27.

School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai, China.

We report a novel algorithm, iBLUP, to impute missing genotypes by simultaneously and comprehensively using identity by descent and linkage disequilibrium information. The simulation studies showed that the algorithm exhibited drastically tolerance to high missing rate, especially for rare variants than other common imputation methods, e.g. BEAGLE and fastPHASE. At a missing rate of 70%, the accuracy of BEAGLE and fastPHASE dropped to 0.82 and 0.74 respectively while iBLUP retained an accuracy of 0.95. For minor allele, the accuracy of BEAGLE and fastPHASE decreased to -0.1 and 0.03, while iBLUP still had an accuracy of 0.61.We implemented the algorithm in a publicly available software package also named iBLUP. The application of iBLUP for processing real sequencing data in an outbred pig population was demonstrated.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0101025PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074155PMC
October 2015

Structures and antioxidant and intestinal disaccharidase inhibitory activities of A-type proanthocyanidins from peanut skin.

J Agric Food Chem 2013 Sep 9;61(37):8814-20. Epub 2013 Sep 9.

School of Life Sciences, Inner Mongolian University , Huhhot, China.

Nine compounds including a new A-type proanthocyanidin trimer, epicatechin-(2β→O→7,4β→8)-[catechin-(6→4β)]-epicatechin (8), and a known trimer, epicatechin-(4β→8)-epicatechin-(2β→O→7,4β→8)-catechin (9), being reported for peanut skin for the first time, were isolated and purified. Their structures were determined by spectroscopic methods and by degradation reactions with L-cysteine in acidic conditions. The DPPH radical scavenging activity and the inhibitory activity on maltase and sucrase of the isolated compounds were investigated. All compounds showed strong DPPH scavenging activities (EC₅₀ < 20 μg/mL). Compound 8 showed the strongest inhibitory activity on maltase with an IC₅₀ value of 0.088 mg/mL, while compound 9 exhibited the strongest inhibition on sucrase with an IC₅₀ value of 0.091 mg/mL.
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http://dx.doi.org/10.1021/jf402518kDOI Listing
September 2013