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Lipidomics reveals carnitine palmitoyltransferase 1C protects cancer cells from lipotoxicity and senescence

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Journal of Pharmaceutical Analysis 2021年第3期11卷 340-350页

作者： Huizhen Zhang Yongtao wang Lihuan guan Yixin Chen Panpan Chen Jiahong Sun Frank J.Gonzalez min Huang Huichang Bi guangdong Provincial Key Laboratory of New Drug Design and Evaluation School of Pharmaceutical SciencesSun Yat-Sen UniversityGuangzhou510006China Laboratory of Metabolism Center for Cancer ResearchNational Cancer InstituteNational Institutes of HealthBethesdaMD20892USA

Lipotoxicity, caused by intracellular lipid accumulation, accelerates the degenerative process of cellular senescence, which has implications in cancer development and therapy. Previously, carnitine palmitoyltransferase 1C(CPT1C), a mitochondrial enzyme that catalyzes carnitinylation of fatty acids, was found to be a critical regulator of cancer cell senescence. However, whether loss of CPT1C could induce senescence as a result of lipotoxicity remains unknown. An LC/MS-based lipidomic analysis of PANC-1,MDA-MB-231, HCT-116 and A549 cancer cells was conducted after siRNA depletion of CPT1C. Cellular lipotoxicity was further confirmed by lipotoxicity assays. Significant changes were found in the lipidome of CPT1C-depleted cells, including major alterations in fatty acid, diacylglycerol, triacylglycerol, oxidative lipids, cardiolipin, phosphatidylglycerol, phosphatidylcholine/phosphatidylethanolamine ratio and sphingomyelin. This was coincident with changes in expressions of mRNAs involved in *** and biochemical analyses revealed higher lipid accumulation and increased malondialdehyde and reactive oxygen species, signatures of lipid peroxidation and oxidative stress. Reduction of ATP synthesis, loss of mitochondrial transmembrane potential and down-regulation of expression of mitochondriogenesis gene m RNAs indicated mitochondrial dysfunction induced by lipotoxicity, which could further result in cellular senescence. Taken together, this study demonstrated CPT1C plays a critical role in the regulation of cancer cell lipotoxicity and cell senescence, suggesting that inhibition of CPT1C may serve as a new therapeutic strategy through induction of tumor lipotoxicity and senescence.

关键词： Lipidomics Lipid accumulation Lipid peroxidation Oxidative stress Mitochondrial dysfunction Anticancer target

Desymmetrization of Cyclic 1,3-Diketones under N-Heterocyclic Carbene Organocatalysis:Access to Organofluorines with Multiple Stereogenic Centers

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Research 2021年第1期2021卷 1495-1507页

作者： guanjie wang min Zhang Yezhi guan Ye Zhang Xianfang Hong Chenlong Wei Pengcheng Zheng Donghui Wei Zhenqian Fu Yonggui Robin Chi Wei Huang Key Laboratory of Flexible Electronics(KLOFE)&Institute of Advanced Materials(IAM)Nanjing Tech University(NanjingTech) 30 South Puzhu RoadNanjing 211816China College of Chemistry and Green Catalysis Center Zhengzhou UniversityZhengzhouHenan 450001China School of Chemistry and Molecular Engineering Nanjing Tech University(NanjingTech)30 South Puzhu RoadNanjing 211816China Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering Key Laboratory of Green Pesticide and Agricultural BioengineeringMinistry of EducationGuizhou UniversityHuaxi DistrictGuiyang 550025China Division of Chemistry&Biological Chemistry School of Physical&Mathematical SciencesNanyang Technological UniversitySingaporeSingapore 637371 Frontiers Science Center for Flexible Electronics(FSCFE)&Shaanxi Institute of Flexible Electronics(SIFE) Northwestern Polytechnical University(NPU)127 West Youyi RoadXi’an 710072China

Symmetric 1,3-diketones with fluorine or fluorinated substituents on the prochiral carbon remain to be ***,we have developed a novel prochiral fluorinated oxindanyl 1,3-diketone and successfully applied these substrates in carbene-catalyzed asymmetric ***,a versatile strategy for asymmetric generation of organofluorines with fluorine or fluorinated methyl groups has been *** stereogenic centers were selectively constructed with satisfactory *** diverse enantioenriched organofluorines were generated with excellent results in terms of yields,diastereoselectivities,and ***,exchanging fluorinated methyl groups to fluorine for this prochiral 1,3-diketones leads to switchable *** aspects and origin of stereoselectivity were studied by DFT ***,some of the prepared organofluorines demonstrated competitive antibacterial activities.

关键词： fluorine chiral asymmetric

Epigenetic and post-translational modifications in autophagy:biological functions and therapeutic targets

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Signal Transduction and Targeted Therapy 2023年第2期8卷 581-603页

作者： Feng Shu Han Xiao Qiu-Nuo Li Xiao-Shuai Ren Zhi-Gang Liu Bo-Wen Hu Hong-Sheng wang Hao wang guan-min Jiang Department of Clinical Laboratory The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhaiGuangdongChina Cancer Center Affiliated Dongguan HospitalSouthern Medical UniversityDongguanGuangdongChina Department of Urology The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhaiGuangdongChina guangdong Key Laboratory of Chiral Molecule and Drug Discovery School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhouGuangdongChina Department of Clinical Laboratory The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhuiChina

Autophagy is a conserved lysosomal degradation pathway where cellular components are dynamically degraded and re-processed to maintain physical ***,the physiological effect of autophagy appears to be *** the one hand,autophagy functions as a cytoprotective mechanism,protecting against multiple diseases,especially tumor,cardiovascular disorders,and neurodegenerative and infectious ***,autophagy may also play a detrimental role via pro-survival effects on cancer cells or cell-killing effects on normal body *** disorder onset and progression,the expression levels of autophagy-related regulators and proteins encoded by autophagy-related genes(ATGs)are abnormally regulated,giving rise to imbalanced autophagy ***,the detailed mechanisms and molecular events of this process are quite ***,including DNA methylation,histone modifications and miRNAs,and post-translational modifications,including ubiquitination,phosphorylation and acetylation,precisely manipulate gene expression and protein function,and are strongly correlated with the occurrence and development of multiple *** is substantial evidence that autophagy-relevant regulators and machineries are subjected to epigenetic and post-translational modulation,resulting in alterations in autophagy levels,which subsequently induces disease or affects the therapeutic effectiveness to *** this review,we focus on the regulatory mechanisms mediated by epigenetic and post-translational modifications in disease-related autophagy to unveil potential therapeutic *** addition,the effect of autophagy on the therapeutic effectiveness of epigenetic drugs or drugs targeting post-translational modification have also been discussed,providing insights into the combination with autophagy activators or inhibitors in the treatment of clinical diseases.

关键词： therapeutic drugs protective

Mitochondrial variants may influence the phenotypic manifestation of Leber's hereditary optic neuropathy-associated ND4 G11778A mutation

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Journal of Genetics and Genomics 2008年第11期35卷 649-655页

作者： Wanshi Cai Qun Fu Xiangtian Zhou Jia Qu Yi Tong min-Xin guan Zhejiang Provincial Key Laboratory of Medical Genetics School of Life Sciences Wenzhou Medical College Wenzhou 325035 China School of Ophthalmology and Optometry Wenzhou Medical College Wenzhou 325003 China The Third Affiliated Hospital Xinxiang Medical College Xinxiang 453003 China The FirstAffiliated Hospital Fujian Medical University Fuzhou 350005 China Division of Human Genetics Cincinnati Children＇s Hospital Medical Center Cincinnati Ohio 45229 USA

We report here the characterization of a five-generation Han Chinese family with Leber＇s hereditary optic neuropathy （LHON）. Strik- ingly, this Chinese family displayed high penetrance and expressivity of visual loss. The average age-of-onset of vision loss was 18 years in this family. Nineteen （11 males/8 females） of 29 matrilineal relatives in this family developed visual loss with a wide range of severity, ranging from blindness to normal vision. Sequence analysis of mitochondrial genome in this pedigree revealed the presence of the ND4 G 11778A mutation and 44 other variants belonging to Asian haplogroup M7b. The G 11778A mutation is present at homoplasmy in matri- lineal relatives of this Chinese family. Of other variants, the C01 G6480A, ND5 T12811C and Cytb A15395G located at highly conserved residues of corresponding polypeptides. In fact, these variants were implicated to be involved in other clinical abnormalities. Here, these variants may act in synergy with the primary LHON-associated Gl1778A mutation. Thus, the mitochondrial dysfunction caused by the primary ND4 G11778A mutation may be worsened by these mitochondrial variants. The results imply that the G6480A, T12811C and A15395G variants might have a potential modifier role in increasing the penetrance and expressivity of the primary LHON-associated G11778A mutation in this Chinese family.

关键词： Leber's hereditary optic neuropathy mitochondrial DNA mutation haplotype vision loss modifier Chinese

Overexpression of a New Putative Membrane Protein Gene AtMRB1 Results in Organ Size Enlargement in Arabidopsis

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Journal of Integrative Plant Biology 2009年第2期51卷 130-139页

作者： Hua guan Dingming Kang min Fan Zhangliang Chen Li-Jia Qu College of Biological Sciences China Agricultural University Beijing 100094 China College of Agronomy and Biotechnology China Agricultural University Beijing 100094 China National Laboratory of Protein Engineering and Plant Genetic Engineering College of Life Sciences Peking University Beijing 100871 China

Arabidopsis AtMRB1 is predicted to encode a novel protein of 432 amino acid residues in length, with four putative transmembrane domains. In the present study, characterization of AtMRB1 is conducted. Green fluorescent protein （GFP） fusion protein assay showed that AtMRB1 was located in the plasma membrane. Transgenic lines overexpressing AtMRB1 driven by a CaMV 35S promoter were generated. Statistic analysis showed that, during the seedling stage, the organ sizes of the transgenic lines including hypocotyl length, root length and root weight were significantly larger than those of the wild type plants under both light and dark conditions. In the adult plant stage, the AtMRB1 overexpressor plants were found to have larger organ sizes in terms of leaf length and width, and increased number of cauline leaves and branches when bolting. Further observation indicated that the larger leaf size phenotype was due to a larger number of mesophyll cells, the size of which was not altered. Quantitative real-time polymerase chain reaction analysis showed that the transcription of ANT, ROT3 and GRF5 were upregulated in the *** plants. These data suggest that AtMRB1 is possibly a positive regulator of organ size development in Arabidopsis, mainly through cell number control.

关键词： Arabidopsis AtMRB1 cell number overexpressor lines organ size.

Gene transfection mediated by polyethyleneiminepolyethylene glycol nanocarrier prevents cisplatininduced spiral ganglion cell damage

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Neural Regeneration Research 2015年第3期10卷 425-431页

作者： guan-gui Chen min Mao Li-zi Qiu Qi-ming Liu Department of Otorhinolaryngology the Second Affiliated Hospital of Guangzhou Medical University

Polyethyleneimine-polyethylene glycol （PEI-PEG）, a novel nanocarrier, has been used for trans- fection and gene therapy in a variety of cells. In our previous study, we successfully carried out PEI-PEG-mediated gene transfer in spiral ganglion cells. It remains unclear whether PEI-PEG could be used for gene therapy with X-linked inhibitor of apoptosis protein （XIAP） in the inner ear. In the present study, we performed PEI-PEG-mediated XIAP gene transfection in the cochlea of Sprague-Dawley rats, via scala tympani fenestration, before daily cisplatin injections. Audito- ry brainstem reflex tests demonstrated the protective effects of XIAP gene therapy on auditory function. Immunohistochemical staining revealed XIAP protein expression in the cytoplasm of cells in the spiral ganglion, the organ of Corti and the stria vascularis. Reverse transcription-PCR detected high levels of XIAP mRNA expression in the cochlea. The present findings suggest that PEI-PEG nanocarrier-mediated XIAP gene transfection results in XIAP expression in the cochlea, prevents damage to cochlear spiral ganglion cells, and protects hearing.

关键词： nerve regeneration polyethyleneimine-polyethylene glycol spiral ganglion cells X-linkedinhibitor of apoptosis protein gene therapy nanocarrier cisplatin neural regeneration ototoxicity cochlea

Blind Recognition of Non-Binary LDPC Codes Based on Ant Colony Optimization

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China Communications 2024年第10期21卷 59-69页

作者： guan Mengsheng Gao Wanting Chen Qi Zhu min Bai Baoming State Key Laboratory of Integrated Services Networks Xidian UniversityXi'an 710071China

This paper introduces a novel blind recognition of non-binary low-density parity-check(LDPC)codes without a candidate set,using ant colony optimization(ACO)algorithm over additive white Gaussian noise(AWGN)***,the scheme that effectively combines the ACO algorithm and the non-binary elements over finite fields is ***,an improved,simplified elitist ACO algorithm based on soft decision reliability is introduced to recognize the parity-check matrix over noisy *** results show that the recognition rate continuously increases with an increased signalto-noise ratio(SNR)over the AWGN channel.

关键词： ACO blind recognition non-binary LDPC codes open-set

The Characterization of Graphs with No 2-connected Spanning Subgraph of V_(8)as a minor

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Acta Mathematicae Applicatae Sinica 2022年第4期38卷 902-915页

作者： Xiao-min ZHOU Xia-xia guan Cheng-fu QIN Wei-hua YANG Department of Mathematics Taiyuan University of TechnologyTaiyuan 030000China School of Mathematical Sciences Xiamen UniversityXiamen 361005China School of Mathematics Science Guangxi Teachers Education UniversityNanning 530001China

It is difficult to characterize graphs which contain no a 2-connected graph as a minor in graph *** V_(8)be a graph constructed from an 8-cycle by connecting the antipodal *** are thirteen 2-connected spanning subgraphs of V_(8).In particular,one of them is obtained from the Petersen graph by deleting two vertices and it is also a hard problem to characterize Petersen-minor-free *** this paper,we characterize internally 4-connected graphs which contain a 2-connected spanning subgraph of V_(8)as a forbidden minor.

关键词： V_(8) internally 4-connected graph minor-free 2-connected subgraph

Effect of Argon-Induced Porosity on Mechanical Properties of Powder Metallurgy Titanium Alloy Components using Hot Isostatic Pressing

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Acta Metallurgica Sinica(English Letters) 2021年第10期34卷 1386-1394页

作者： min Cheng Jie Wu Zheng-guan Lu Rui-Peng Guo Lei Xu Rui Yang College of Materials Science and Engineering Taiyuan University of TechnologyTaiyuan 030024China Institute of Metal Research Chinese Academy of SciencesShenyang 110016China

This work reported the Ar-induced porosity in powder metallurgy Ti-5 Al-2.5 Sn alloy prepared by hot isostatic pressing(HIPing).The obtained microstructures of powder compacts were studied through optical and scanning electron microscopes,X-ray tomography,and the mechanical properties evaluated through tensile and impact *** results showed that the Ar-induced porosity is related to the hollow powder with gas bubble and the Ar leakage of sealed container during the powder *** hollow powder with gas bubble shows no obvious effects on mechanical properties of as-HIPed powder *** Ar content decreases with the increasing shrinkage of encapsulated powder.0.7%Ar-induced porosity degrades the impact toughness,but no reductions of tensile properties were *** content test is an effective method to detect the powder compacts with Ar concentration.

关键词： Titanium alloys Hot isostatic pressing Argon concentration Porosity