Metabolic reprogramming and epigenetic modifications in cancer: from the impacts and mechanisms to the treatment potential

Xu Xuemeng,Peng Qiu,Jiang Xianjie,Tan Shiming,Yang Yiqing,Yang Wenjuan,Han Yaqian,Chen Yuyu,Oyang Linda,Lin Jinguan,Xia Longzheng,Peng Mingjing,Wu Nayiyuan,Tang Yanyan,Li Jinyun,Liao Qianjin,Zhou Yuju 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Metabolic reprogramming and epigenetic modifications are hallmarks of cancer cells. In cancer cells, metabolic pathway activity varies during tumorigenesis and cancer progression, indicating regulated metabolic plasticity. Metabolic changes are often closely related to epigenetic changes, such as alterations in the expression or activity of epigenetically modified enzymes, which may exert a direct or an indirect influence on cellular metabolism. Therefore, exploring the mechanisms underlying epigenetic modifications regulating the reprogramming of tumor cell metabolism is important for further understanding tumor pathogenesis. Here, we mainly focus on the latest studies on epigenetic modifications related to cancer cell metabolism regulations, including changes in glucose, lipid and amino acid metabolism in the cancer context, and then emphasize the mechanisms related to tumor cell epigenetic modifications. Specifically, we discuss the role played by DNA methylation, chromatin remodeling, noncoding RNAs and histone lactylation in tumor growth and progression. Finally, we summarize the prospects of potential cancer therapeutic strategies based on metabolic reprogramming and epigenetic changes in tumor cells.

PAPG: Private Aggregation Scheme based on Privacy-preserving Gene in Wireless Sensor Networks

( Weini Zeng ),( Peng Chen ),( Hairong Chen ),( Shiming He ) 한국인터넷정보학회 2016 KSII Transactions on Internet and Information Syst Vol.10 No.9

This paper proposes a privacy-preserving aggregation scheme based on the designed P-Gene (PAPG) for sensor networks. The P-Gene is constructed using the designed erasable data-hiding technique. In this P-Gene, each sensory data item may be hidden by the collecting sensor node, thereby protecting the privacy of this data item. Thereafter, the hidden data can be directly reported to the cluster head that aggregates the data. The aggregation result can then be recovered from the hidden data in the cluster head. The designed P-Genes can protect the privacy of each data item without additional data exchange or encryption. Given the flexible generation of the P-Genes, the proposed PAPG scheme adapts to dynamically changing reporting nodes. Apart from its favorable resistance to data loss, the extensive analyses and simulations demonstrate how the PAPG scheme efficiently preserves privacy while consuming less communication and computational overheads.

ANALYSIS AND OPTIMIZATION OF AN EXPANDING ENERGY ABSORBER WITH VARIABLE THICKNESS DISTRIBUTION TUBE UNDER AXIAL DYNAMIC LOADING

Yanqing Wang,Shiming Wang,Lin Hou,Yong Peng 한국자동차공학회 2022 International journal of automotive technology Vol.23 No.6

An expanding energy absorber with variable thickness distribution tube is proposed and studied in this work. At first, a uniform thickness tube structure finite element (FE) model was developed and then verified by the results of an impact test. The parametric study found that outer obliquity angle β and inner obliquity angle γ have positive influence on initial peak force (Fp). While as axial distribution ratio l less than 0.1, the l has significant positive effect on Fp. The non-monotonicity of specific energy absorption (SEA) with design parameters of β and γ was found. Increasing the parameter l could obviously improve the SEA. To obtain the optimal design, an integrated optimization methodology was applied. The Pareto fronts show that there is a lot of room for improvement of original design. The optimal compromising solution increased the SEA by 12.60 % with Fp decreased by 14.24 kN comparing with that of original design. At last, the optimization result were verified. The study stated that the proposed variable thickness distribution tube of expanding energy absorber is conducive to improving the crashworthiness of rail vehicles.

Functionalized benzothieno[3,2 b]thiophenes (BTTs) for high performance organic thin-film transistors (OTFTs)

Youn, Jangdae,Huang, Peng-Yi,Zhang, Shiming,Liu, Chiao-Wei,Vegiraju, Sureshraju,Prabakaran, Kumaresan,Stern, Charlotte,Kim, Choongik,Chen, Ming-Chou,Facchetti, Antonio,Marks, Tobin J. The Royal Society of Chemistry 2014 Journal of materials chemistry. C, Materials for o Vol.2 No.36

Cyano-substituted benzochalcogenadiazole-based polymer semiconductors for balanced ambipolar organic thin-film transistors

Shi, Shengbin,Wang, Hang,Chen, Peng,Uddin, Mohammad Afsar,Wang, Yuxi,Tang, Yumin,Guo, Han,Cheng, Xing,Zhang, Shiming,Woo, Han Young,Guo, Xugang The Royal Society of Chemistry 2018 Polymer chemistry Vol.9 No.28

<P>Due to their high-lying lowest unoccupied molecular orbitals (LUMOs), π-conjugated polymers based on benzothiadiazole and its derivatives typically are p-type. We report here the successful development of two narrow bandgap, ambipolar donor-acceptor copolymers, PDCNBT2T and PDCNBSe2T, which are based on new cyano-substituted strong electron acceptors, 4,7-dibromo-5,6-dicyano-2,1,3-benzothiadiazole (DCNBT) and 4,7-dibromo-5,6-dicyano-2,1,3-benzoselenadiazole (DCNBSe), respectively. Compared to their polymer analogues with fluorine substituents, the LUMO was lowered by a big margin of <I>ca.</I> 0.6 eV and the bandgap was reduced by 0.2-0.3 eV for the cyano-substituted polymers. Therefore, the cyano-substituted benzothiadiazole polymers showed very low-lying LUMO levels of <I>ca.</I> 4.3 eV. Benefiting from their narrow bandgaps of 1.1-1.2 eV and appropriately positioned LUMO levels, both polymers exhibit well balanced ambipolar transport characteristics in organic thin-film transistors, which differ from the p-type dominating transport properties of their fluorinated polymer analogues. A balanced hole/electron mobility of 0.59/0.47 cm<SUP>2</SUP> V<SUP>−1</SUP> s<SUP>−1</SUP> was achieved for polymer PDCNBT2T, and a reduced hole/electron mobility of 0.018/0.014 cm<SUP>2</SUP> V<SUP>−1</SUP> s<SUP>−1</SUP> was observed for the benzoselenadiazole-based PDCNBSe2T due to its lower crystallinity. These results show that the electron mobility can be enhanced by approximately two orders <I>versus</I> the electron mobility of the previously reported 4,7-di(thiophen-2-yl)-5,6-dicyano-2,1,3-benzothiadiazole-based polymer. This improvement was achieved by using the new acceptor units without additional electron-rich thiophene flanks, which allow a higher degree of freedom in selecting the donor co-unit and more effective tuning of energy levels of frontier molecular orbitals.</P>

Time-series transcriptomic analysis of the kelp grouper Epinephelus moara in response to low salinity stress

Quanxin Gao,Yanfeng Yue,Minghua Min,Shiming Peng,Zhaohong Shi,Jinbo Wang,Tao Zhang 한국통합생물학회 2018 Animal cells and systems Vol.22 No.4

The Kelp grouper Epinephelus moara is one of the most widely consumed and economically important marine fish in China. The species can tolerate a wide range of salinity, but genomic resources are not available, and the molecular mechanisms underlying adaptation to salinity at the transcriptomic level remain largely unclear. In this study, the transcriptomic responses of the liver of E. moara under low salinity were investigated using the Illumina digital gene expression system. After de novo assembly, 499,356 transcripts were generated and contributed 445,068 unigenes. A total of 14, 19, 33 and 3101 genes were differentially expressed following exposure to low salinity stress for 2, 6, 24 and 48 h, respectively. Only two genes were differentially expressed in all groups. Four genes related to metabolism and ambient salinity adaption were randomly selected to validate the differentially expressed genes (DEGs) by real-time PCR. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to analyse the functional significance of DEGs, including those responding to salinity through diverse biological processes, cellular components, molecular functions, and pathways associated with metabolic and osmotic responses. This work provides new insight into the response to salinity challenges in E. moara, and the findings expand our knowledge of the molecular basis of metabolic regulation mechanisms in this species. Additionally, the transcriptional data provide a valuable resource for future molecular and genetic studies on E. moara.

Cyano-Substituted Head-to-Head Polythiophenes: Enabling High-Performance n-Type Organic Thin-Film Transistors

Wang, Hang,Huang, Jun,Uddin, Mohammad Afsar,Liu, Bin,Chen, Peng,Shi, Shengbin,Tang, Yumin,Xing, Guichuan,Zhang, Shiming,Woo, Han Young,Guo, Han,Guo, Xugang American Chemical Society 2019 ACS APPLIED MATERIALS & INTERFACES Vol.11 No.10

<P>Polythiophenes, built on the electron-rich thiophene unit, typically possess high-lying energy levels of the lowest unoccupied molecular orbitals (LUMOs) and show hole-transporting properties. In this study, we develop a series of n-type polythiophenes, <B>P1</B>-<B>P3</B>, based on head-to-head-linked 3,3′-dialkoxy-4,4′-dicyano-2,2′-bithiophene (BTCNOR) with distinct side chains. The BTCNOR unit shows not only highly planar backbone conformation enabled by the intramolecular noncovalent sulfur-oxygen interaction but also significantly suppressed LUMO level attributed to the cyano-substitution. Hence, all BTCNOR-based polymer semiconductors exhibit low-lying LUMO levels, which are ∼1.0 eV lower than that of regioregular poly(3-hexylthiophene) (rr-P3HT), a benchmark p-type polymer semiconductor. Consequently, all of the three polymers can enable unipolar n-type transport characteristics in organic thin-film transistors (OTFTs) with low off-currents (<I>I</I><SUB>off</SUB>s) of 10<SUP>-10</SUP>-10<SUP>-11</SUP> A and large current on/off ratios (<I>I</I><SUB>on</SUB>/<I>I</I><SUB>off</SUB>s) at the level of 10<SUP>6</SUP>. Among them, polymer <B>P2</B> with a 2-ethylhexyl side chain offers the highest film ordering, leading to the best device performance with an excellent electron mobility (μ<SUB>e</SUB>) of 0.31 cm<SUP>2</SUP> V<SUP>-1</SUP> s<SUP>-1</SUP> in off-center spin-cast OTFTs. To the best of our knowledge, this is the first report of n-type polythiophenes with electron mobility comparable to the hole mobility of the benchmark p-type rr-P3HT and approaching the electron mobility of the most-studied n-type polymer, poly(naphthalene diimide-<I>alt</I>-bithiophene) (i.e., N2200). The change of charge carrier polarity from p-type (rr-P3HT) to n-type (<B>P2</B>) with comparable mobility demonstrates the obvious effectiveness of our structural modification. Adoption of <I>n</I>-hexadecyl (<B>P1</B>) and 2-butyloctyl (<B>P3</B>) side chains leads to reduced film ordering and results in 1-2 orders of magnitude lower μ<SUB>e</SUB>s, showing the critical role of side chains in optimizing device performance. This study demonstrates the unique structural features of head-to-head linkage containing BTCNOR for constructing high-performance n-type polymers, i.e., the alkoxy chain for backbone conformation locking and providing polymer solubility as well as the strong electron-withdrawing cyano group for lowering LUMO levels and enabling n-type performance. The design strategy of BTCNOR-based polymers provides useful guidelines for developing n-type polythiophenes.</P> [FIG OMISSION]</BR>

Head-to-Head Linked Dialkylbifuran-Based Polymer Semiconductors for High-Performance Organic Thin-Film Transistors with Tunable Charge Carrier Polarity

Shi, Shengbin,Wang, Hang,Uddin, Mohammad Afsar,Yang, Kun,Su, Mengyao,Bianchi, Luca,Chen, Peng,Cheng, Xing,Guo, Han,Zhang, Shiming,Woo, Han Young,Guo, Xugang American Chemical Society 2019 Chemistry of materials Vol.31 No.5

<P>A planar backbone conformation is essential for enabling polymer semiconductors with high charge carrier mobility in organic thin-film transistors. Benefiting from the smaller van der Waals radius of the O atom in furan (versus the S atom in thiophene), alkylated furan exerts a reduced steric hindrance on neighboring arene, and it was found that the head-to-head (HH)-linked 3,3′-dialkyl-2,2′-bifuran (<B>BFR</B>) can attain a high degree of backbone planarity. Hence, <B>BFR</B> should be a promising building block for constructing polymer semiconductors with a planar backbone conformation and hold distinctive advantages over a dialkylbithiophene-based analogue, which is typically highly twisted. The alkyl chains on the 3 and 3′ positions offer good solubility to the resulting polymers, which in combination with its planar backbone yields an improved molecular design window for developing high-performance polymer semiconductors, particularly those with a simple molecular structure and based on the acceptor co-unit without any solubilizing chains. When incorporated into polymer semiconductors, remarkably high hole and electron mobilities of 1.50 and 0.31 cm<SUP>2</SUP> V<SUP>-1</SUP> s<SUP>-1</SUP> are obtained for <B>BFR</B>-based polymers <B>FBFR-BO</B> and <B>CNBFR-C18</B> containing fluorinated and cyano-functionalized benzothiadiazole as the acceptor co-unit, respectively. Such mobilities are the highest values for HH-linked polymers and also among the best for furan-containing polymers. The results demonstrate that HH-linked dialkylbifuran is a highly promising building block for constructing organic and polymeric semiconductors, and this new approach by incorporating HH <B>BFR</B> offers several distinctive advantages for developing high-performance polymer semiconductors, including effective optoelectronic property tuning using a minimal number of aromatic rings, reduced structural complexity, facile material synthesis, good material solubility, and enriching the material library. In addition, the study offers important guidelines for future development of furan-based polymers and head-to-head linkage containing organic semiconductors.</P> [FIG OMISSION]</BR>