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Chemical screen identifies shikonin as a broad DNA damage response inhibitor that enhances chemotherapy through inhibiting ATM and ATR

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1339-1350页

作者： Fangfang Wang sora jin Franklin Mayca Pozo Danmei Tian Xiyang Tang Yi Dai Xinsheng Yao jinshan Tang Youwei Zhang Institute of Traditional Chinese Medicine and Natural Products College of PharmacyJinan UniversityGuangzhou 510632China Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drug Research Jinan UniversityGuangzhou 510632China Department of Pharmacology Case Comprehensive Cancer CenterCase Western Reserve University School of MedicineClevelandOH 44106USA

DNA damage response(DDR)is a highly conserved genome surveillance mechanism that preserves cell viability in the presence of chemotherapeutic ***,small molecules that inhibit DDR are expected to enhance the anti-cancer effect of *** a recent chemical library screen,we identified shikonin as an inhibitor that strongly suppressed DDR activated by various chemotherapeutic drugs in cancer cell lines derived from different ***,shikonin inhibited the activation of ataxia telangiectasia mutated(ATM),and to a lesser degree ATM and RAD3-related(ATR),two master upstream regulators of the DDR signal,through inducing degradation of ATM and ATR-interacting protein(ATRIP),an obligate associating protein of ATR,*** a result of DDR inhibition,shikonin enhanced the anti-cancer effect of chemotherapeutic drugs in both cell cultures and in mouse *** degradation of ATRIP is proteasome dependent,that of ATM depends on caspase-and lysosome-,but not *** of ATM significantly mitigated DDR inhibition and cell death induced by shikonin and chemotherapeutic *** novel findings reveal shikonin as a pan DDR inhibitor and identify ATM as a primary factor in determining the chemo sensitizing effect of *** data may facilitate the development of shikonin and its derivatives as potential chemotherapy sensitizers through inducing ATM degradation.

关键词： Chemical screen Shikonin DNA damage Response ATM ATR ATRIP Protein degradation Chemo sensitizing

Quantifying and managing regional greenhouse gas emissions: Waste sector of Daejeon, Korea

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Journal of Environmental Sciences 2014年第6期26卷 1249-1259页

作者： sora Yi Heewon Yang Seung Hoon Lee Kyoung-jin An Department of Urban Planning Research Daejeon Development Institute Department of Environmental Engineering Anyang University Faculty of Science & Technology The Technological and Higher Education Institute of Hong KongNew Territories Hong Kong China

A credible accounting of national and regional inventories for the greenhouse gas （GHG） reduction has emerged as one of the most significant current discussions. This article assessed the regional GHG emissions by three categories of the waste sector in Daejeon Metropolitan City （DMC）, Korea, examined the potential for DMC to reduce GHG emission, and discussed the methodology modified from Intergovernmental Panel on Climate Change and Korea national guidelines. During the last five years, DMC＇s overall GHG emissions were 239 thousand tons C02 eq./year from eleven public environmental infrastructure facilities, with a population of 1.52 million. Of the three categories, solid waste treatment/disposal contributes 68%, whilst wastewater treatment and others contribute 22% and 10% respectively. Among GHG unit emissions per ton of waste treatment, the biggest contributor was waste incineration of 694 kg CO2 eq./ton, followed by waste disposal of 483 kg CO2 eq./ton, biological treatment of solid waste of 209 kg CO2 eq./ton, wastewater treatment of 0.241 kg CO2 eq./m3, and public water supplies of 0.067 kg CO2 eq./m3. Furthermore, it is suggested that the potential in reducing GHG emissions from landfill process can be as high as 47.5% by increasing landfill gas recovery up to 50%. Therefore, it is apparent that reduction strategies for the main contributors of GHG emissions should take precedence over minor contributors and lead to the best practice for managing GHGs abatement.

关键词： Solid waste disposal biological treatment of solid waste waste incineration wastewater treatment public water supply

Accidental esophageal intubation via a large type C congenital tracheoesophageal fistula:A case report

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World Journal of Clinical Cases 2022年第30期10卷 11198-11203页

作者： Seong Min Hwang Myeong jin Kim sora Kim Saeyoung Kim Department of Anesthesiology and Pain Medicine School of MedicineKyungpook National UniversityDaegu 41944South Korea

BACKGROUND Tracheoesophageal fistula(TEF)is a congenital anomaly characterized by interruptions in esophageal continuity with or without fistulous communication to the *** management during TEF repair is challenging because of the difficulty of perioperative airway *** is important to determine the appropriate position of the endotracheal tube(ETT)for proper ventilation and to prevent excessive gastric ***,the tip of the ETT should be placed immediately below the fistula and above the *** SUMMARY A full-term,one-day-old,2.4 kg,50 cm male neonate was diagnosed with TEF type *** induction,an ETT was inserted using video laryngoscope and advanced deeply to ensure that the tip passed over the fistula,according to known *** passage of the ETT through the vocal cords was confirmed via video ***,after inflating the ETT cuff,breath sounds were not heard on bilateral lung ***,gastric sounds were *** that a large fistula(approximately 6.60 mm×4.54 mm)located 10.2mm above the carina was confirmed on preoperative tracheal computed tomography,the possibility of unintentional esophageal intubation was highly ***,we decided to uncuff and withdraw the ETT carefully for repositioning,while monitoring auscultation and end-tidal CO2 *** a certain point(9.5 cm from the lip),clear breath sounds and proper end-tidal CO_(2) readings were suddenly achieved,and adequate ventilation was *** Preanesthetic anatomical evaluation with imaging studies in TEF is necessary to minimize complications related to airway management.

关键词： Tracheoesophageal fistula Imaging study Anatomy Intubation Airway management Auscultation Case report

KoNA:Korean Nucleotide Archive as A New Data Repository for Nucleotide Sequence Data

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Genomics, Proteomics & Bioinformatics 2024年第1期22卷 161-167页

作者： Gunhwan Ko Jae Ho Lee Young Mi Sim Wangho Song Byung-Ha Yoon Iksu Byeon Bang Hyuck Lee Sang-Ok Kim jinhyuk Choi Insoo Jang Hyerin Kim jin Ok Yang Kiwon Jang sora Kim Jong-Hwan Kim Jongbum Jeon Jaeeun Jung Seungwoo Hwang Ji-Hwan Park Pan-Gyu Kim Seon-Young Kim Byungwook Lee Korea Bioinformation Center Korea Research Institute of Bioscience&BiotechnologyDaejeon 34141Republic of Korea

During the last decade,the generation and accumulation of petabase-scale high-throughput sequencing data have resulted in great challenges,including access to human data,as well as transfer,storage,and sharing of enormous amounts of *** promote data-driven biological research,the Korean government announced that all biological data generated from government-funded research projects should be deposited at the Korea BioData Station(K-BDS),which consists of multiple databases for individual data ***,we introduce the Korean Nucleotide Archive(KoNA),a repository of nucleotide sequence *** of July 2022,the Korean Read Archive in KoNA has collected over 477 TB of raw next-generation sequencing data from national genome *** ensure data quality and prepare for international alignment,a standard operating procedure was adopted,which is similar to that of the International Nucleotide Sequence Database *** standard operating procedure includes quality control processes for submitted data and metadata using an automated pipeline,followed by manual *** ensure fast and stable data transfer,a high-speed transmission system called GBox is used in ***,the data uploaded to or downloaded from KoNA through GBox can be readily processed using a cloud computing service called *** seamless coupling of KoNA,GBox,and Bio-Express enhances the data experience,including submission,access,and analysis of raw nucleotide *** not only satisfies the unmet needs for a national sequence repository in Korea but also provides datasets to researchers globally and contributes to advances in *** KoNA is available at https://***/kona/.

关键词： Korea BioData Station Nucleotide sequence Next-generation sequencing repository Genomics Deposition and access of big data

基于BLISS和PMA的多学科可靠性设计优化

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航空学报 2013年第10期34卷 2349-2356页

作者：刘云平张俊张冰孙瑾南京信息工程大学信息与控制学院江苏南京210044 山东水利职业学院机电工程系山东日照276826 中信建设有限责任公司北京100027

针对多学科设计优化(MDO)中考虑不确定性而带来的计算复杂性问题,采用序列优化与可靠性评估(sora)法的解耦思想,提出了基于两级集成系统综合(BLISS)策略和性能测量法(PMA)的多学科可靠性设计优化(RBMDO)方法。该方法将传统的3层嵌套循环... 详细信息

针对多学科设计优化(MDO)中考虑不确定性而带来的计算复杂性问题,采用序列优化与可靠性评估(sora)法的解耦思想,提出了基于两级集成系统综合(BLISS)策略和性能测量法(PMA)的多学科可靠性设计优化(RBMDO)方法。该方法将传统的3层嵌套循环的RBMDO方法过程解耦为顺序执行的确定性多学科设计优化(DMDO)和多学科可靠性分析(MRA),DMDO和MRA均采用BLISS策略进行计算,避免了每次多学科设计优化对完整可靠性分析模型的反复调用。飞机起落架缓冲器算例结果表明,文中方法的计算效率较其他两种方法分别提高了52.01%和26.51%,验证了方法的有效性。

关键词：两级集成系统综合性能测量法多学科可靠性设计优化可靠性缓冲器

18β-甘草次酸通过抑制信号传导与转录激活因子3的激活能够增强人肝癌细胞对索拉非尼的敏感性

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中华实验外科杂志 2018年第8期35卷 1445-1447页

作者：赵冬刘秋梦梁慧芳陈劲张必翔华中科技大学同济医学院附属武汉中心医院检验科武汉430014 华中科技大学同济医学院附属同济医院肝外科中心实验室武汉430030

目的观察18β-甘草次酸（GA）和索拉非尼单独和联合应用对人肝癌细胞株7402的增殖、凋亡和周期的影响，从对信号传导与转录激活因子3（STAT3）通路的影响探讨其可能的机制。方法用100 μmol/L的GA和10 μmol/L的索拉非尼单独和联合应用... 详细信息

目的观察18β-甘草次酸（GA）和索拉非尼单独和联合应用对人肝癌细胞株7402的增殖、凋亡和周期的影响，从对信号传导与转录激活因子3（STAT3）通路的影响探讨其可能的机制。方法用100 μmol/L的GA和10 μmol/L的索拉非尼单独和联合应用于肝癌细胞株7402，用细胞增殖活性检测（CCK-8）和平板克隆方法检测增殖，流式细胞术检测细胞周期凋亡，Western blot检测细胞周期蛋白（Cyclin D1）和STAT3通路的激活情况。结果CCK-8方法结果显示GA和索拉非尼单独处理7402后细胞生存率分别为（74.3±3.3）%和（56.7±5.0）%，联合给药细胞生存率为（42.6±2.8）%。联合给药比单独给药对细胞杀伤作用更加明显，差异均有统计学意义（P=0.000、0.000）。细胞凋亡结果显示，与对照组（5.31±1.53）%的凋亡率比较，GA和索拉非尼单独给药诱导的细胞凋亡率分别为（15.18±2.12）%和（19.18±1.30）%，联合给药细胞凋亡率为（28.29±2.58）%。与单独给药比较，联合给药能进一步增加细胞凋亡数量，差异有统计学意义（P=0.000、0.000）。机制实验中，与对照组比较，索拉非尼单独处理后磷酸化信号传导与转录激活因子3（p-STAT3）表达量变化不明显（t=2.449，P=0.070），而GA组p-STAT3表达量降低（t=34.080，P=0.000），联合给药组p-STAT3表达量显著降低（t=40.420，P=0.000）。结论GA能够通过抑制STAT3的激活增强人肝癌细胞对索拉非尼的敏感性。

关键词： 18β-甘草次酸肝癌增殖凋亡细胞周期信号传导与转录激活因子3