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Bioactive phlorotannin as autophagy modulator in cervical cancer cells and advanced glycation end products inhibitor in glucotoxic c. elegans

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ALGAL RESEARcH-BIOMASS BIOFUELS AND BIOPRODUcTS 2022年 67卷

作者： Kumar, Rai Sameer Gunaseelan, Sathaiah Sangeetha, Ramalingam Arunkumar, Malaisamy Shakambari, Ganeshan Ashokkumar, Balasubramaniem Varalakshmi, Perumal Madurai Kamaraj Univ Sch Biotechnol Dept Mol Microbiol Madurai 625021 Tamil Nadu India Madurai Kamaraj Univ Sch Biotechnol Dept Genet Engn Madurai 625021 Tamil Nadu India Int Ctr Genet Engn & Biotechnol ICGEB Transcript Regulat Grp New Delhi 110067 India

Brown algae produce varieties of potent metabolites in order to adapt to extreme environment. Among these metabolites, polyphenols comprised of phlorotannins serve as powerful multifaceted bioactive with vast phar-macological potentials against non-communicable diseases like cancer and diabetes. In this study, a new phlorotannin was extracted from Padina tetrastromatica and characterized by Fourier Transform-Infrared, Nuclear Magnetic Resonance & Electronspray Ionization-Mass Spectroscopy. The phlorotannin exhibited potent DPPH and nitric oxide radical-scavenging activity in in-vitro, which were better than the standard antioxidants and other phlorotannins, previously reported. Further, the novel phlorotannin explicitly inhibited advanced glycation end-products formation in both in-vitro and in-vivo studies using hyperglycaemic c. elegans as an animal model and confirmed by live-cell fluorescence imaging. In addition, a significant modulation in expression of stress -responsive genes daf-2 and daf-16 were observed in phlorotannin treated hyperglycemic c. elegans. Moreover, the cytotoxic potential of phlorotannin (2,4,6-trioxa-1,3,5(1,3) tribenzenacyclohexaphane-15,35,55-triol) was explored for the first time in human cervical cancer cells (HeLa) and interesting observation was made that the cancer cell death was induced by activation of autophagy and pro-apoptotic protein markers i.e., Lc3I/II, p21 and p53 that were confirmed by western-blot technique. Therefore, phlorotannin can be postulated as a potential bioactive for oxidative stress-mediated diseases, including diabetes and cancer.

关键词： Phlorotannin Autophagy Padina tetrastromatica Macroalgae c elegans Advanced glycation end products

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Identifying the Types and characterization of the Active Sites on M-X-c Single-Atom catalysts

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cHEMPHYScHEM 2020年第23期21卷 2486-2496页

作者： Yang, Jiarui Wang, Dingsheng Li, Yadong Tsinghua Univ Dept Chem Beijing 100084 Peoples R China

Single atom catalysts (SAcs) have attracted much attention in recent years. As an essential group in SAcs, M-X-c (X=nonmetallic element) materials have been demonstrated to be efficient in many reactions. However, identifying the active sites on M-X-c, especially under working conditions, is still challenging, which is crucial for chemists to further understand the mechanism underlying the reaction and better design proper SAcs for specific reactions. Herein, the types and characterization of M-X-c are comprehensively summarized and discussed in this review. In addition to the basic information above, the challenges and opportunities remaining in this field will be also proposed to present a perspective to the research on the next step.

关键词： active sites characterization M− X− c nanomaterials single-atom catalysts

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Sperm associated antigen 4 promotes SREBP1-mediated de novo lipogenesis via interaction with lamin A/c and contributes to tumor progression in hepatocellular carcinoma

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cANcER LETTERS 2022年 536卷 215642-215642页

作者： Liu, Tengfei Yu, Junming Ge, chao Zhao, Fangyu chen, Jing Miao, chunxiao Jin, Wenjiao Zhou, Qingqing Geng, Qin Lin, Hechun Tian, Hua chen, Taoyang Xie, Haiyang cui, Ying Yao, Ming Xiao, Xiuying Li, Jinjun Li, Hong Shanghai Jiao Tong Univ Renji Hosp Shanghai Canc Inst State Key Lab Oncogenes & Related GenesSch Med Shanghai 200032 Peoples R China Shanghai Jiao Tong Univ Rui jin Hosp Sch Med Dept Oncol Shanghai 200020 Peoples R China Qi Dong Liver Canc Inst Qi Dong 226200 Peoples R China Zhejiang Univ Affiliated Hosp 1 Sch Med Dept Gen Surg Hangzhou 310000 Peoples R China Canc Inst Guangxi Nanning 530027 Peoples R China Shanghai Jiao Tong Univ Ren ji Hosp Sch Med Dept Oncol Shanghai 200127 Peoples R China

Hepatocellular carcinoma (Hcc) is a highly malignant tumor and its progression is associated with altered lipid metabolism in precancerous lesions, such as non-alcoholic fatty liver disease. Here, we identified sperm associated antigen 4 (SPAG4), and explored its oncogenic role in Hcc progression. Database analysis and immunohistochemistry indicated increased level of SPAG4 in Hcc tissues which was of prognostic value. Gain/loss-offunction experiments showed that SPAG4 exerted oncogenic roles in Hcc growth both in vitro and in vivo. RNA sequencing revealed activation of a lipogenic state and SREBP1-mediated pathway following SPAG4 overexpression. Mechanistically, the N-terminal region of SPAG4 bound to lamin A/c, which increased SREBP1 expression, nuclear translocation, and transcriptional activity. Treatment with orlistat, a lipid synthesis inhibitor, reversed SPAG4-mediated oncogenic effects, and its efficacy varied with SPAG4 level. The effect of orlistat was further amplified when combined with sorafenib in tumor xenograft mouse models. Our study provides evidence that SPAG4 mediates Hcc progression by affecting lipid metabolism. Administration of orlistat combined with sorafenib reverses SPAG4-mediated oncogenesis in Hcc cells and ectopic xenograft tumors in mice, suggesting that this pathway represents a potential target for Hcc treatment.

关键词： Hepatocellular carcinoma SPAG4 Lipogenesis SREBP1 Lamin A c

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The Effect of cyclic Strain on Human Fibroblasts With Lamin A/c Mutations and Its Relation to Heart Disease

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JOURNAL OF BIOMEcHANIcAL ENGINEERING-TRANSAcTIONS OF THE ASME 2020年第6期142卷 061002页

作者： Tran, Richard D. H. Siemens, Mark Nguyen, cecilia H. H. Ochs, Alexander R. Zaragoza, Michael, V Grosberg, Anna Univ Calif Irvine Dept Biomed Engn Edwards Lifesci Ctr Adv Cardiovasc Technol Cardiovasc Modeling Lab 2131 Engn Hall Irvine Irvine CA 92697 USA Univ Calif Irvine Sch Med Dept Pediat Div Genet & Genom 2042 Hewitt Hall Irvine Irvine CA 92697 USA Dept Pediat Div Genet & Genom 2042 Hewitt Hall Irvine Irvine CA 92697 USA Univ Calif Irvine Sch Med Dept Biol Chem 2042 Hewitt Hall Irvine Irvine CA 92697 USA Univ Calif Irvine Dept Biomed Engn Ctr Complex Biol Syst Edwards Lifesci Ctr Adv Cardiovasc TechnolCardio 2418 Engn Hall Irvine Irvine CA 92697 USA Univ Calif Irvine Dept Chem & Biomol Engn 2418 Engn Hall Irvine Irvine CA 92697 USA

Although mutations in the Lamin A/c gene (LMNA) cause a variety of devastating diseases, the pathological mechanism is often unknown. Lamin A/c proteins play a crucial role in forming a meshwork under the nuclear membrane, providing the nucleus with mechanical integrity and interacting with other proteins for gene regulation. Most LMNA mutations result in heart diseases, including some types that primarily have heart disease as the main pathology. In this study, we used cells from patients with different LMNA mutations that primarily lead to heart disease. Indeed, it is a mystery why a mutation to the protein in every nucleus of the body manifests as a disease of primarily the heart in these patients. Here, we aimed to investigate if strains mimicking those within the myocardial environment are sufficient to cause differences in cells with and without the LMNA mutation. To test this, a stretcher device was used to induce cyclic strain upon cells, and viability/proliferation, cytoskeleton and extracellular matrix organization, and nuclear morphology were quantified. The properties of cells with Hutchinson-Gilford progeria syndrome (HGPS) were found to be significantly different from all other cell lines and were mostly in line with previous findings. However, the properties of cells from patients who primarily had heart diseases were not drastically different when compared to individuals without the LMNA mutation. Our results indicated that cyclic strain alone was insufficient to cause any significant differences that could explain the mechanisms that lead to heart diseases in these patients with LMNA mutations.

关键词： lamin A c laminopathies cyclic strain heart mechanics heart disease

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Insight into cations substitution on structural and electrochemical properties of nanostructured Li2FeSiO4/c cathodes

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JOURNAL OF THE AMERIcAN cERAMIc SOcIETY 2020年第3期103卷 1685-1697页

作者： Sivaraj, Pazhaniswamy Abhilash, Karuthedath Parameswaran Nalini, Balakrishnan Selvin, Paneerselvam christopher Goel, Sunkulp Yadav, Sudheer Kumar Bharathiar Univ Dept Phys Solid State Ion & Luminescence Lab Coimbatore 641046 Tamil Nadu India NGM Coll Dept Phys Mat Res Ctr Coimbatore Tamil Nadu India Nanjing Univ Sci & Technol Herbert Gleiter Inst Nanosci Nanjing Jiangsu Peoples R China Avinashilingam Inst Home Sci & Higher Educ Women Dept Phys Coimbatore 641043 Tamil Nadu India

Structural instability is the major obstacle in the Li2FeSiO4/c cathode during charge and discharge process, which can be improved by the substitution of cations in the host cage. In this study, the transition metal ions with different valence (Ag1+, Zn2+, cr3+, and Ti4+) have been substituted in Li2FeSiO4/c via modified sol-gel method and the impact on the structural, electrical, and electrochemical performances has been systematically explored. The Rietveld-refined XRD pattern and HR-TEM (SAED) result reveal that all the prepared samples maintain orthorhombic structure (S.G- Pmn2(1)). The FE-SEM and TEM micrographs of bare and doped Li2FeSiO4/c display nanoparticle formation with 20-40 nm size. Among different cation-substituted silicates, Li2Fe0.9Ti0.1SiO4/c sample exhibits an excellent total conductivity of 1.20 x 10(-4) S cm(-1) which is one order of magnitude higher than the bare Li2FeSiO4/c sample. The galvanostatic charge-discharge curves and cyclic voltammetric analysis reveal that the Li2Fe0.9Ti0.1SiO4/c material provides an excellent initial specific capacity of 242 mAh g(-1) and maintains a capacity of 226 mAh g(-1) after 50 cycles with capacity retention of 93.38%. The Ti doping is a promising strategy to overcome the capacity fading issues, by preventing the structural collapse during Li-ion intercalation/de-intercalation processes in the Li2FeSiO4/c electrode through the strong hybridization between the 3d and 4s orbitals in titanium and 2p orbital in oxygen.

关键词： doping electrochemical performance Li2FeSiO4 c lithium ion batteries nano cathode

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Preparation of high performance LiFePO4/c by extracting iron element from iron tailings by concentrated sulfuric acid hot dip method

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IONIcS 2020年第4期26卷 1645-1655页

作者： Wang, Yingling Wang, Yafeng Luo, Shaohua Liu, chengjun Teng, Fei chen, Huanhuan Shen, Huiliang Gao, Desheng Northeastern Univ Sch Met Shenyang 110819 Peoples R China Northeastern Univ Minist Educ Key Lab Ecol Met Multimetall Ores Shenyang 110819 Peoples R China Northeastern Univ Qinhuangdao Sch Resources & Mat Qinhuangdao 066004 Hebei Peoples R China Northeastern Univ Sch Mat Sci & Engn Shenyang 110819 Peoples R China

LiFePO4/c cathode materials are synthesized by carbothermal reduction process using FePO4 as iron and phosphorus source, and starch as carbon source. The FePO4 precursor was prepared by leaching iron tailings with concentrated sulfuric acid and then leaching with phosphoric acid and hydrogen peroxide. The morphology and structure of FePO4 precursors prepared under different pH conditions were studied by using thermogravimetric-differential analysis (TG-DTA), infrared analysis (FTIR), x-ray diffraction (XRD), and field emission scanning electron microscopy (FESEM). The effect of the FePO4 material on the properties of the synthesized LiFePO4 cathode was investigated by charge and discharge cycles. On this basis, the effects of different molar ratios of c and LiFePO4 on the performance of synthetic product LiFePO4/c were studied using starch as carbon source. The results show that the FePO4 precursor prepared under the condition of pH 2 is the raw material, and the LiFePO4/c cathode material synthesized by adding 45% carbon has the best performance. The first cycle discharge capacity reached 142.6 mAh g(-1) at a current density of 0.1 degrees c, reaching 83.9% of its theoretical capacity. This work proposes a novel and effective method to utilize the iron tailings.

关键词： cathode material LiFePO4 c Iron tailings concentrated sulfuric acid leaching FePO4 precursor

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Multimodal Stimulation in a Microfluidic Device Facilitates Studies of Interneurons in Sensory Integration in c. elegans

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SMALL 2020年第10期16卷 e1905852页

作者： cho, Yongmin Lee, Sol Ah chew, Yee Lian Broderick, Kirby Schafer, William R. Lu, Hang Georgia Inst Technol Sch Chem & Biomol Engn Atlanta GA 30332 USA Med Res Council Lab Mol Biol Div Neurobiol Cambridge CB2 0QH England Harvard Med Sch Dept Syst Biol Boston MA 02115 USA Univ Wollongong Mol Horizons Wollongong NSW 2522 Australia Univ Wollongong Sch Chem & Mol Biosci Wollongong NSW 2522 Australia Illawarra Hlth & Med Res Inst Wollongong NSW 2522 Australia

Animals' perception and behavior involve integration of multiple sensory modalities. caenorhabditis elegans is a useful model for studying multimodal sensory integration, as it has well-characterized neuronal circuits in a relatively simple nervous system. However, most studies based on functional imaging have only been conducted on single modal stimuli, because well-controlled multimodal experiments for c. elegans are technically difficult. For instance, no single systems currently deliver precise stimuli with spatial, temporal, and intensity control, despite prior hypotheses that interneurons do integrate these sensory inputs to control behavior. Here, a microfluidic platform that can easily deliver spatially and temporally controlled combination stimuli to c. elegans is presented. With this platform, both sensory and interneuron activity is measured in response to mechanical and chemical stimulations in a quantitative and high-throughput manner. It is found that the activity of command interneuron PVc can be modulated by prior stimulation both within the same and across different modalities. The roles of monoaminergic and peptidergic signaling are further examined on the process of multimodal integration through PVc activity. The approach exemplified here is envisioned to be broadly applicable in different contexts to elucidate underlying mechanisms and identify genes affecting multisensory integration.

关键词： c elegans microfluidics multisensory integration PVc interneurons

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Effect of FeSO4 purity on low temperature performance of LiFePO4/c

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IONIcS 2020年第9期26卷 4433-4442页

作者： Wang, Xiaoyan Wen, Lizhi Zheng, Yi Ren, Xin Li, Yongsheng Liang, Guangchuan Hebei Univ Technol Inst Power Source & Ecomat Sci Tianjin 300130 Peoples R China North China Univ Sci & Technol Qinggong Coll Tangshan 063000 Peoples R China Tianjin Sino German Univ Appl Sci Automobile & Rail Transportat Sch Tianjin 300350 Peoples R China Hebei Univ Technol Minist Educ Key Lab Special Funct Mat Ecol Environm & Informa Tianjin 300130 Peoples R China Hebei Univ Technol Key Lab New Type Funct Mat Hebei Prov Tianjin 300130 Peoples R China

LiFePO4/c was prepared by employing coprecipitation method and carbothermal reduction method using FeSO4 with different purity as the iron source. The purity of FeSO4 has a great influence on the morphology of FePO4, but has little effect on the morphology of LiFePO4/c. The cycling performance decreases with the decrease of purity, and purity has a significant effect on the specific discharge capacities at low temperature. The specific discharge capacities of the five samples at - 20 degrees c and 0.5 c were 85.3, 74.2, 65.5, 60.4, and 50.1 mAh g(-1), and the capacity retention rates were 53.3%, 47.1%, 42.9%, 38.7%, and 31.9%, respectively. Full battery low temperature performance test results validate the test results of coin cell. The Li+ diffusion coefficients are 4.53 x 10(-13), 2.02x 10(-13), 4.73 x 10(-14), 2.34x 10(-14), and 8.56 x 10(-15) cm(2) s(-1), respectively. D-Li(+) is reduced two orders of magnitude with reduction of raw material purity. This is mainly because the low-purity FeSO4 contains a large amount of Ti, which enters the LiFePO4/c crystal lattice, causing the lattice distortion to block the lithium ion diffusion channel. Therefore, improving the purity of raw materials is an important method to improve the low temperature performance of LiFePO4/c.

关键词： FeSO4 LiFePO4 c Purity Low temperature performance

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Genetic basis of thermal nociceptive sensitivity and brain weight in a BALB/c reduced complexity cross

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MOLEcULAR PAIN 2022年 18卷

作者： Beierle, Jacob A. Yao, Emily J. Goldstein, Stanley, I Scotellaro, Julia L. Sena, Katherine D. Linnertz, colton A. Willits, Adam B. Kader, Leena Young, Erin E. Peltz, Gary Emili, Andrew Ferris, Martin T. Bryant, camron D. Boston Univ Sch Med Program Biomol Pharmacol Boston MA 02118 USA Boston Univ Dept Pharmacol & Expt Therapeut & Psychiat Lab Addict Genet Sch Med Boston MA 02118 USA Boston Univ Ctr Network Syst Biol Dept Biol & Biochem Sch Med Boston MA 02118 USA Boston Univ Undergrad Res Opportun Program Boston MA 02118 USA Univ N Carolina Dept Genet Chapel Hill NC 27515 USA Univ Kansas Med Ctr Neurosci Program Kansas City KS 66103 USA Univ Kansas Med Ctr Dept Anesthesiol Kansas City KS 66103 USA Stanford Univ Sch Med Dept Anesthesiol Pain & Preoperat Med Stanford CA 94305 USA

Thermal nociception involves the transmission of temperature-related noxious information from the periphery to the cNS and is a heritable trait that could predict transition to persistent pain. Rodent forward genetics complement human studies by controlling genetic complexity and environmental factors, analysis of end point tissue, and validation of variants on appropriate genetic backgrounds. Reduced complexity crosses between nearly identical inbred substrains with robust trait differences can greatly facilitate unbiased discovery of novel genes and variants. We found BALB/cByJ mice showed enhanced sensitivity on the 53.5 degrees c hot plate and mechanical stimulation in the von Frey test compared to BALB/cJ mice and replicated decreased gross brain weight in BALB/cByJ versus BALB/cJ. We then identified a quantitative trait locus (QTL) on chromosome 13 for hot plate sensitivity (LOD = 10.7;p < 0.001;peak = 56 Mb) and a QTL for brain weight on chromosome 5 (LOD = 8.7;p < 0.001). Expression QTL mapping of brain tissues identified H2afy (56.07 Mb) as the top transcript with the strongest association at the hot plate locus (FDR = 0.0002) and spliceome analysis identified differential exon usage within H2afy associated with the same locus. Whole brain proteomics further supported decreased H2AFY expression could underlie enhanced hot plate sensitivity, and identified AcADS as a candidate for reduced brain weight. To summarize, a BALB/c reduced complexity cross combined with multiple-omics approaches facilitated identification of candidate genes underlying thermal nociception and brain weight. These substrains provide a powerful, reciprocal platform for future validation of candidate variants.

关键词： Thermal nociception hot plate von frey genetics BALB c reduced complexity cross brain weight H2afy

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Modeling Temperature-Dependent Vibration Damping in c/Sic Fiber-Reinforced ceramic-Matrix composites

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MATERIALS 2020年第7期13卷 1633页

作者： Li, Longbiao Nanjing Univ Aeronaut & Astronaut Coll Civil Aviat 29 Yudao St Nanjing 210016 Peoples R China

In this paper, the temperature-dependent vibration damping in c/Sic fiber-reinforced ceramic-matrix composites (cMcs) with different fiber preforms under different vibration frequencies is investigated. A micromechanical temperature-dependent vibration damping model is developed to establish the relationship between composite damping, material properties, internal damage mechanisms, and temperature. The effects of fiber volume, matrix crack spacing, and interface properties on temperature-dependent composite vibration damping of cMcs and interface damage are analyzed. The experimental temperature-dependent composite damping of 2D and 3D c/Sic composites is predicted for different loading frequencies. The damping of the c/Sic composite increases with temperature to the peak value and then decreases with temperature. When the vibration frequency increases from f = 1 to 10 Hz, the peak value of composite damping and corresponding temperature both decrease due to the decrease of interface debonding and slip range, and the damping of 2D c/Sic is much higher than that of 3D c/Sic at temperature range from room temperature to 400 degrees c. When the fiber volume and interface debonding energy increase, the peak value of composite damping and the corresponding temperature decreases, mainly attributed to the decrease of interface debonding and slip range.

关键词： ceramic-matrix composites (cMcs) c Sic damping temperature-dependent matrix cracking interface debonding

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