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MicroRNA-24 promotes pancreatic beta cells toward dedifferentiation to avoid endoplasmic reticulum stress-induced apoptosis

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Journal of Molecular Cell Biology 2019年第9期11卷 747-760页

作者： Yunxia Zhu Yi Sun Yuncai Zhou Yan Zhang Tao Zhang Yating Li Weiyan You Xiaoai Chang Li Yuan Xiao Han Key Laboratory of Human Functional Genomics of Jiangsu Province Department of Biochemistry and Molecular BiologyNanjing Medical UniversityNanjing 210029China

Current research indicates that beta cell loss in type 2 diabetes may be attributed to beta cell dedifferentiation rather than apoptosis;however,the mechanisms by which this occurs remain poorly understood.Our previous study demonstrated that elevation of microRNA-24(miR-24)in a diabetic setting caused beta cell dysfunction and replicative deficiency.In this study,we focused on the role of miR-24 in beta cell apoptosis and dedifferentiation under endoplasmic reticulum(ER)stress conditions.We found that miR-24 overabundance protected beta cells from thapsigargin-induced apoptosis at the cost of accelerating the impairment of glucosestimulated insulin secretion(GSIS)and enhancing the presence of dedifferentiation markers.Ingenuity?Pathway Analysis(IPA)revealed that elevation of miR-24 had an inhibitory effect on XBP1 and ATF4,which are downstream effectors of two key branches of ER stress,by inhibiting its direct target,Irela.Notably,elevated miR-24 initiated another pathway that targeted Mafa and decreased GSIS function in surviving beta cells,thus guiding their dedifferentiation under ER stress conditions.Our results demonstrated that the elevated miR-24,to the utmost extent,preserves beta cell mass by inhibiting apoptosis and inducing dedifFerentiation.This study not only provides a novel mechanism by which miR-24 dominates beta cell turnover under persistent metabolic stress but also offers a therapeutic consideration for treating diabetes by inducing dedifferentiated beta cells to re-differentiation.

关键词： microRNA-24 ER stress apoptosis dedifferentiation type 2 diabetes pancreatic beta cells

Differential expression, molecular cloning,and characterization of porcine beta defensin 114

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Journal of Animal Science and Biotechnology 2019年第4期10卷 884-894页

作者： Guoqi Su Kunhong Xie Daiwen Chen Bing Yu Zhiqing Huang Yuheng Luo Xiangbing Mao Ping Zheng Jie Yu Junqiu Luo Jun He Animal Nutrition Institute Sichuan Agricultural UniversityChengdu 611130People’s Republic of China Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education Sichuan Agricultural UniversityChengdu 625014People’s Republic of China

Background:β-defensins have attracted considerable research interest because of their roles in protecting hosts from various pathogens.This study was conducted to investigate the expression profiles of the porcineβ-defensin114(PBD114)in different breeds and in response to infections.Moreover,the function of PBD114 protein was partially investigated.Methods:Six Tibetan pigs(TP)and six DLY(Duroc×Landrace×Yorkshire)pigs were slaughtered to explore the expression profiles of PBD114 in different breeds and tissues.For infection models,sixteen DLY pigs were divided into two groups and challenged either with sterile saline or E.coli K88.The recombinant protein PBD114(r PBD114)was obtained by using a heterologous expression system in E.coli.Results:PBD114 gene was highly expressed in tissues such as the intestine,liver,spleen,and thymus.Interestingly,the expression level of PBD114 gene was higher in the TP pigs than in the DLY pigs(Pbetan and DLY pigs was identical,and both showed a 210-bp open reading frame encoding a 69-amino acid mature peptide.To explaore the function of PBD114 protein,PBD114 gene was successfully expressed in E.coli Origami B(DE3)and the molecular weight of the r PBD114 was estimated by SDS-PAGE to be 25 k Da.The r PBD114 was purified and mass spectrometry verified the protein as PBD114.Importantly,r PBD114 showed antimicrobial activities against E.coli DH5αand E.coli K88,and the minimal inhibitory concentrations(MICs)were 64 and 128μg/m L,respectively.Hemolytic and cytotoxicity assays showed that r PBD114 did not affect cell viability under physiological concentrations.Conclusions:PBD114 is an infection response gene that is differentially-expressed between different porcine breeds and tissues.The antimicrobial activity of PBD114 protein,against pathogens such as the E.coli K88,suggested that it may serve as a candidate for the substitution of conventionally used antibiotics.

关键词： Antimicrobial activity DLY E.coli Porcine beta defensin 114 Tibetan

Modeling hot deformation behavior of low-cost Ti-2Al-9.2Mo-2Fe beta titanium alloy using a deep neural network

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Journal of Materials Science & Technology 2019年第5期35卷 907-916页

作者： Cheng-Lin Li P.L.Narayana N.S.Reddy Seong-Woo Choi Jong-Taek Yeom Jae-Keun Hong Chan Hee Park Advanced Metals Division Korea Institute of Materials Science Changwon 51508 Republic of Korea School of Materials Science and Engineering Gyeongsang National University Jinju 52828 Republic of Korea

Ti-2 Al-9.2 Mo-2 Fe is a low-cost β titanium alloy with well-balanced strength and ductility, but hot working of this alloy is complex and unfamiliar. Understanding the nonlinear relationships among the strain,strain rate, temperature, and flow stress of this alloy is essential to optimize the hot working process.In this study, a deep neural network(DNN) model was developed to correlate flow stress with a wide range of strains(0.025–0.6), strain rates(0.01–10 s^-1) and temperatures(750–1000℃). The model, which was tested with 96 unseen datasets, showed better performance than existing models, with a correlation coefficient of 0.999. The processing map constructed using the DNN model was effective in predicting the microstructural evolution of the alloy. Moreover, it led to the optimization of hot-working conditions to avoid the formation of brittle precipitates(temperatures of 820–1000℃ and strain rates of 0.01-0.1 s^-1).

关键词： Deep neural networks Back propagation Processing map Recrystallization beta titanium

A new method for position-sensitive measurement of beta surface contamination

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Nuclear Science and Techniques 2017年第2期28卷 49-56页

作者： Yan-Tao Qu Hui Wang Yang Liu Ling Chen Jie Hou Zhe Liu Ji-Zeng Ma Department of Radiation Protection China Institute of Atomic Energy Beijing 102413 China Nuclear and Radiation Safety Center Ministry of Environment Protection Beijing 100082 China Occupational Radiation Protection Unit Radiation Safety and Monitoring Section NSRW IAEA PO Box 1001400 Vienna Austria

In this paper, we propose a new method for position-sensitive measurement of beta surface contamination. With a position-sensitive detector of enlarged sensitive detection area, accurate information of the contamination distribution can be obtained. The positionsensitive detection is based on a large-area plastic scintillator and the wavelength shifting(WLS) fibers and adopts the ‘‘light center of gravity'' method. Optical transmission of the detector is simulated with a preliminary detector model, and feasibility of the detector design and measurement method is evaluated using an experiment system.The simulation and experiment results at different beta-ray incident points on the scintillator surface show that there is a polynomial relationship between the average amplitude ratio of the output pulses from the two parallel WLS fibers in the same fiber layer and the relative distance from the incident point to the WLS fiber.

关键词： beta surface contamination Position-sensitive measurement Wavelength shifting fibers Plastic scintillator

Prognostic value of hypoxia-inducible factor-1 alpha and prolyl 4-hydroxylase beta polypeptide overexpression in gastric cancer

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World Journal of Gastroenterology 2018年第22期24卷 2381-2391页

作者： Jun Zhang Yue Wu Yu-Hang Lin Shuai Guo Pei-Fang Ning Zhi-chao Zheng Yue Wang Yan Zhao Department of Gastric Cancer Liaoning Cancer Hospital and Institute (Cancer Hospital of China Medical University) Department of Emergency Sheng Jing Hospital of China Medical University Department of Pancreatic and Thyroid Surgery Sheng Jing Hospital of China Medical University Department of Pathology Liaoning Cancer Hospital and Institute (Cancer Hospital of China Medical University)

AIM To investigate the relationship between hypoxia-inducible factor-1α(HIF-1α), prolyl 4-hydroxylase beta(P4 HB) expression, and clinicopathologic parameters, as well as the prognostic value of these genes for patients with gastric cancer(Gc).METHODS Hypoxia is a critical factor that shapes the Gc microenvironment. In previous reports, we have demonstrated that P4 HB is a potential target of HIF-1α. In the present study, gene expression profiling interactive analysis(GEPIA) was used to analyze the relationship between P4 HB and hypoxia-associated genes. To this end, 428 Gc tissue samples were used to analyze the expression of HIF-1α and P4 HB via immunohistochemical staining. Patient samples were classified as having weak-expression or over-expression both in terms of HIF-1α and P4 HB. Correlations between biomarkers and clinicopathological factors were analyzed to predict survival. RESULTS P4 HB demonstrated a positive correlation with hypoxiaassociated genes(P 0.05).CONCLUSION Overexpression of HIF-1α and P4 HB is associated with poor prognosis in patients with Gc. Thus, these genes may be potential prognostic biomarker candidates in GC.

关键词： Gastric cancer Hypoxia inducible factor-1α Prolyl 4-hydroxylase beta polypeptide Overall survival Clinicopathological predictors Disease free survival

Etherification of HMF to biodiesel additives: The role of NH4+ confinement in beta zeolites

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Journal of Energy Chemistry 2019年第9期28卷 114-121页

作者： Paola Lanzafame Georgia Papanikolaou Katia Barbera Gabriele Centi Siglinda Perathoner Departments of ChiBioFarAm and MIFT-Section of Industrial Chemistry University of Messina ERIC aisbl and CASPE-INSTM

The role of NH4^+ ion confinement in the catalytic etherification of HMF(5-hydroxymethylfurfural) with ethanol to biodiesel additives was evidenced by studying the catalytic behavior of NH4^+-beta zeolites with SiO2/Al2O3 ratios of 25 and 75.In order to affect the strength and distribution of the acidic sites, as well as the mobility of NH4^+ ions in the zeolites cages, a secondary level of porosity was introduced in the NH4^+-beta, presenting a different stability versus alkaline treatment, by using a thermal or an ultrasound assisted method.By analyzing the catalytic behavior in these two series of samples with respect to the changes in porosity by nonlocal density functional theory, structure by XRD, amount of acid sites by FT-IR and mobility of NH4^+ cations by measurements of reversible NH4^+ exchange capacity, was evidenced a decrease in catalytic performances both in terms of rate of HMF depletion and productivity to the main products, when confinement of the ammonium ions is lost due to the introduction of mesoporosity.The high capability of ammonium ions release, associated to the mono-dentate configuration,and the minor confinement effect inside the zeolite pore system, due to the more opened pores structure of mesoporous zeolites, hinders both the direct etherification of HMF to EMF [5-(ethoxymethyl)furan-2-carbaldehyde] and the parallel reaction pathway via acetalization, favoring the rapid desorption of the HMFDEA [5-(hydroxymethyl)furfural diethyl acetal] product out of the crystal and the consequent inhibition of the consecutive reactions to EMFDEA [5-(ethoxymethyl)furfural diethyl acetal] and EMF.

关键词： Ammonium ion beta zeolite HMF etherification Confinement effect 5-(ethoxymethyl)furan-2-carbaldehyde

Bioinformatic identification of key candidate genes and pathways in axon regeneration after spinal cord injury in zebrafish

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Neural Regeneration Research 2020年第1期15卷 103-111页

作者： Jia-He Li Zhong-Ju Shi Yan Li Bin Pan Shi-Yang Yuan Lin-Lin Shi Yan Hao Fu-Jiang Cao Shi-Qing Feng Department of Orthopedics Tianjin Medical University General HospitalTianjinChina Department of Orthopedics the Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina Tianjin Neurological Institute Key Laboratory of Post-Neuroinjury Neurorepair and Regeneration in Central Nervous SystemMinistry of Education and Tianjin CityTianjinChina

Zebrafish and human genomes are highly homologous;however,despite this genomic similarity,adult zebrafish can achieve neuronal proliferation,regeneration and functional restoration within 6–8 weeks after spinal cord injury,whereas humans cannot.To analyze differentially expressed zebrafish genes between axon-regenerated neurons and axon-non-regenerated neurons after spinal cord injury,and to explore the key genes and pathways of axonal regeneration after spinal cord injury,microarray GSE56842 was analyzed using the online tool,GEO2R,in the Gene Expression Omnibus database.Gene ontology and protein-protein interaction networks were used to analyze the identified differentially expressed genes.Finally,we screened for genes and pathways that may play a role in spinal cord injury repair in zebrafish and mammals.A total of 636 differentially expressed genes were obtained,including 255 up-regulated and 381 down-regulated differentially expressed genes in axon-regenerated neurons.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were also obtained.A protein-protein interaction network contained 480 node genes and 1976 node connections.We also obtained the 10 hub genes with the highest correlation and the two modules with the highest score.The results showed that spectrin may promote axonal regeneration after spinal cord injury in zebrafish.Transforming growth factor beta signaling may inhibit repair after spinal cord injury in zebrafish.Focal adhesion or tight junctions may play an important role in the migration and proliferation of some cells,such as Schwann cells or neural progenitor cells,after spinal cord injury in zebrafish.Bioinformatic analysis identified key candidate genes and pathways in axonal regeneration after spinal cord injury in zebrafish,providing targets for treatment of spinal cord injury in mammals.

关键词： axonal regeneration differentially expressed genes focal adhesions Gene Ontology Kyoto Encyclopedia of Genes and Genomes neural regeneration protein-protein interaction network signaling pathway spectrin tight junctions transforming growth factor beta Wnt signaling pathway

Transplantation of primary and reversibly immortalized human liver cells and other gene therapies in acute liver failure and decompensated chronic liver disease

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World Journal of Gastroenterology 2000年第5期6卷 636-642页

作者： Stephen M.Riordan Roger Williams Institute of Hepatology University College London and University College London HospitalsLondonEngland Department of GastroenterologyThe Prince of Wales HospitalSydneyAustralia Institute of Hepatology University College London and University College London HospitalsLondonEngland

Studies performed in experimental small animalswith hepatic-based metabolic disorders but nostructural liver disease,including Gunn andanalbuminaemic rats and rabbits with inherited low-density lipoprotein receptor deficiency,have shownthat up to 95% of hepatocytes transplanted into thespleen or liver remain in these sites,withimprovement in metabolic function

关键词： liver failure acute liver diseases liver transplantation gene therapy animals laboratory transfering growth factor beta

Protective mechanism of testosterone on cognitive impairment in a rat model of Alzheimer's disease

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Neural Regeneration Research 2019年第4期14卷 649-657页

作者： Xu-Sheng Yan Zhan-Jun Yang Jian-Xin Jia Wei Song Xin Fang Zhi-Ping Cai Dong-Sheng Huo He Wang Department of Human Anatomy Baotou Medical College School of Health Sciences University of NewcastleNewcastle Australia

Cognitive dysfunction in Alzheimer's disease is strongly associated with a reduction in synaptic plasticity, which may be induced by oxidative stress. Testosterone is beneficial in learning and memory, although the underlying protective mechanism of testosterone on cognitive performance remains unclear. This study explored the protective mechanism of a subcutaneous injection of 0.75 mg testosterone on cognitive dysfunction induced by bilateral injections of amyloid beta 1–42 oligomers into the lateral ventricles of male rats. Morris water maze test results demonstrated that testosterone treatment remarkably reduced escape latency and path length in Alzheimer's disease rat models. During probe trials, testosterone administration significantly elevated the percentage of time spent in the target quadrant and the number of platform crossings. However, flutamide, an androgen receptor antagonist, inhibited the protective effect of testosterone on cognitive performance in Alzheimer's disease rat models. Nissl staining, immunohistochemistry, western blot assay, and enzyme-linked immunosorbent assay results showed that the number of intact hippocampal pyramidal cells, the dendritic spine density in the hippocampal CA1 region, the immune response and expression level of postsynaptic density protein 95 in the hippocampus, and the activities of superoxide dismutase and glutathione peroxidase were increased with testosterone treatment. In contrast, testosterone treatment reduced malondialdehyde levels. Flutamide inhibited the effects of testosterone on all of these indicators. Our data showed that the protective effect of testosterone on cognitive dysfunction in Alzheimer's disease is mediated via androgen receptors to scavenge free radicals, thereby enhancing synaptic plasticity.

关键词： nerve regeneration Alzheimer’s disease testosterone cognitive dysfunction synaptic plasticity free radicals Morris water maze androgen receptor flutamide postsynaptic density protein 95 amyloid beta 1–42 neurodegenerative change neural regeneration