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Anti-proliferative effects of a small molecule inhibitor of CDKAT7519 on chronic myeloid leukemia (CML) cells through haltingthe transition of cells from G2/M phase of the cell cycle

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BIOCELL 2020年第2期44卷 183-192页

作者： MASOUMEH OGHABI AVA SAFAROGHLI-AZAR ATIEH POURBAGHERI-SIGAROODI MOHAMMAD SAYYADI MOHSEN HAMIDPOUR MOHAMMAD HOSSEIN MOHAMMADI DAVOOD BASHASH department of Hematology and Blood banking School of Allied Medical SciencesShahid Beheshti University of Medical SciencesTehranIran Student Research Committee Department of Hematology and Blood BankingSchool of Allied Medical SciencesShahid Beheshti University of Medical SciencesTehranIran School of Allied Medical Sciences Arak University of Medical SciencesArakIran

Pathogenesis of chronic myeloid leukemia(CML)has mostly been studied with regard to the oncogenic role of BCR/ABL fusion,however,recent disclosures have declared that the challenges with the treatment of CML patients would not be resolved until the role of other aberrancies is *** the involvement of cyclin-dependent kinases(CDKs)in the pathogenesis of CML,the present study aimed to investigate the effects of a multi-CDK inhibitor AT7519 on BCR/ABL-harboring CML-derived K562 *** results showed that AT7519 effectively reduced the survival of K562 and induced its anti-proliferative effect through the induction of G2/M arrest due to elevated p21 and *** resulting data also revealed that either direct or indirect suppression of c-Myc using specific c-Myc inhibitor 10058-F4 and selective PI3K inhibitor CAL-101 resulted in a superior cytotoxicity,suggesting that the activation of PI3K pathway could attenuate antileukemic effects of the inhibitor,at least partly,through a c-Mycdependent *** the best of our knowledge,to date,no study has addressed the effect of autophagy on CML cell response to AT7519,and,herein,we proposed for the first time that the suppression of autophagy boosted AT7519 cytotoxicity against ***,we suggested that selective CDK inhibitor AT7519 exerted antileukemic effect against CML cells and propose a novel therapeutic application for the inhibitor either as a single agent or in combination with c-Myc and/or PI3K inhibitors.

关键词： Chronic myeloid leukemia (CML) Cyclin-dependent kinase (CDK) AT7519 Autophagy PI3K c-Myc

Characteristics,treatment patterns,and glycemic control of older type 2 diabetes mellitus patients in China

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Chinese Medical Journal 2021年第23期134卷 2893-2895页

作者： Xiao-Ling Cai Jie Shen Bin-Qi Ye Qiang Li Douglas ASClark Li-Nong Ji department of Endocrinology and Metabolism Peking University People’s HospitalBeijing 100044China department of Medical Affairs Boehringer Ingelheim(China)Investment Co.Ltd.Shanghai 200040China department of Biostatistics&Data Sciences Asia Boehringer Ingelheim(China)Investment Co.Ltd.Shanghai 200040China department of Global Epidemiology Boehringer Ingelheim(China)Investment Co.Ltd.Beijing 100027China Boehringer Ingelheim International GmbH Binger Strasse 17355216 Ingelheim am RheinGermany.

To the Editor:The prevalence of type 2 diabetes mellitus(T2DM)in older Chinese adults(≥60 years)is over 20%.[1]In comparison to younger patients,older diabetes patients tend to have lower rate of adequate glycemic control(<7.0%hemoglobin A1c[HbA1c])and a higher risk of hypoglycemia.[2]Currently,there are limited data on the clinical characteristics and treatment patterns of older T2DM patients in *** conducted a nation-wide cross-sectional study to examine the clinical characteristics,anti-diabetic treatment patterns,and glycemic control in older(≥60 years)Chinese *** associated with poor glycemic control were identified with multivariate regression analysis.

关键词： patients T2DM diabetes

What's So Special about China's Producer Services?An Input–output Analysis

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China & World Economy 2014年第1期22卷 103-120页

作者： Dazhong Cheng Peter W.Daniels department of World Economy Institute for World Economyand Global Investment and Trade InstituteFudan University University of Birmingham

In the present study, five stylized facts about China ＂s producer services are established through international, intersectoral and intertemporal comparisons based on input --output tables. First, the overall service input ratio is the lowest in all the sample economies. Second, most producer services are supplied by the traditional labor-intensive sectors. Third, manufacturing is the biggest user of producer services, and service industry is the second, while the opposite is true for most of the other sample economies. Fourth, unlike other economies, China ＂s ＂R＆D＂ is characterized more by consumer services than producer services. Fifth, China has fairly lower service input ratios in almost all the industries. The backward and forward linkages coefficients are both smaller for ＂real estate activities＂ and ＂finance and insurance. ＂＂ Policy reform should focus not only on specific producer services but also on reducing obstacles that are inhibiting the balanced development of diverse producer services that will help China to optimize its economic structure.

关键词： Chinese economy input-output analysis producer services

Injury severities from heavy vehicle accidents:An exploratory empirical analysis

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Journal of Traffic and Transportation Engineering(English Edition) 2022年第6期9卷 991-1002页

作者： Hamsa Zubaidi Ali Alnedawi Ihsan Obaid Masoud Ghodrat Abadi Roads and Transport Engineering department College of EngineeringUniversity of Al-QadisiyahAl-DiwaniyaIraq investment Commission Endowment BaghdadIraq department of Civil Engineering California State UniversitySacramentoCA 95819USA

Despite the importance of heavy vehicles in Australia’s transportation system,little is known on the factors influencing injury severity from accidents involving a single heavy *** vehicular crashes have been one of the main causes of fatal injuries in Australia,and this raises safety concerns for transport authorities,insurance companies,and emergency *** there have been several potential attempts to identify the factors contributing to heavy vehicle crashes and injury severity,it is still necessary to reduce the number of traffic crashes and lower the fatality rate involving heavy *** aims of this study were investigating the effects of heavy trucks’presence in accidents on the injury severity level sustained by the vehicle driver and detecting the contributing factors that lead to specific injury severity ***-and random-parameter ordered probit and logit models were applied for predicting the likelihood of three injury severity categories severe,moderate,and no injury based on data from crashes caused by heavy trucks in Victoria,Australia in *** results showed that the random-parameter ordered probit model performed better than the other models *** variables(i.e.,factors)were found to be significant,and 12 of them were found to have random parameters that were normally *** some of the investigated factors had different effects on the type of injury severity in Australia,this paper does not recommend generalizing the findings from other case *** on the findings,Victoria state authorities can have insight and enhanced understanding of the specific factors that lead to various types of injury severity involving heavy ***,the safety of all road users,including heavy vehicle drivers,can be enhanced.

关键词： Heavy vehicle Injury severity Random parameter Ordered probit model

Degradation and resynthesis of chlorophyll during increased oxidative stress and prolonged darkness differ between annual and perennial flax(Linum L.)

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Oil Crop Science 2024年第2期9卷 121-130页

作者： Kenyon J. Nisbett Abida Alokozai Su Hyun Elizabeth Ko G. Adam Mott Jason C.L. Browna department of Biological Sciences University of Toronto ScarboroughTorontoONCanada department of Cell&Systems Biology University of TorontoTorontoONCanada Centre for the Analysis of Genome Evolution&Function University of TorontoTorontoONCanada

Among plants,there is considerable variation in lifespan:annuals live less than one year,whereas perennials live for several years,with the longest-living perennial having survived 43,600 *** proposed by the Disposable Soma Theory,this lifespan variation among plants likely reflects differential investment of limited energy and nutrient resources,with perennials investing more energy and nutrients into biomolecular maintenance compared to annuals in order to ensure persistence over multiple *** differential investment may be particularly important during periods of exogenous stress,which are known to accelerate biomolecular *** present study evaluated this hypothesis using annual and perennial flax(Linum L.)subjected to two exogenous stressors—increased oxidative stress(i.e.,foliar H2O2spraying)and complete prolonged *** chlorophyll has been shown to exhibit degradation in response to changes in environmental conditions,we utilized changes in chlorophyll levels during and after periods of exogenous stress to evaluate our *** predicted that i)perennials would exhibit a slower rate of chlorophyll degradation during exposure to exogenous stressors compared to annuals,and ii)perennials would exhibit a faster rate of chlorophyll resynthesis following such exposure compared to *** levels before,during,and after exposure to both exogenous stressors were measured in two separate trails,once using image colour analysis and once using *** chlorophyll degradation rates in response to oxidative stress did not differ between annuals and perennials,contrary to our predictions,chlorophyll resynthesis rates following such exposure were significantly higher in perennials,as *** plants were subjected to complete prolonged darkness,chlorophyll degradation rates were significantly lower in perennials than annuals,as predicted;however,when plants were subsequently reintroduced to natural photoperiod,ch

关键词： Ageing Life history Maximum lifespan Oxidative stress Somatic maintenance

Monetary Policy and Borrowers'Loan Defaults:Research Based on Data from Ren re ndai

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China & World Economy 2020年第1期28卷 94-121页

作者： Wenda Song Haiyang Zhang School of banking and Finance University of International Business and Economics School of banking and Finance University of International Business and Economicsand Institute of Digital FinancePeking University

This paper uses Renrendai data to study the relationship between monetaryj policy and the default behavior of borrowers,and analyzes the transmission *** research shows that tight monetary policy will lead to a significant increase in a borrower s probability to default,and this effect will continue for several *** may be two transmission channels:(i)monetary policy changes a debtor s liquidity through credit and balance sheet channels,which directly affects their current repayment behavior;and(ii)monetary policy may affect a borrower s investment,production and profitability,thus changing their long-term *** paper also finds that the repayment behavior of productive borrowers is more susceptible to monetary policy than consumptive borrowers,and that the default behavior of borrowers in coastal provinces is more susceptible to monetary policy than of borrowers in inland *** findings provide new evidence for understanding how monetary policy affects individual behavior and its transmission mechanisms.

关键词： default liquidity monetary policy online lending

Rank-dependent ppredictableforward performance processes

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Probability, Uncertainty and Quantitative Risk 2024年第2期9卷 181-218页

作者： Bahman Angoshtari Shida Duan department of Mathematics University of MiamiCoral Gables FL 33146USA

Predictable forward performance processes(PFPPs)are stochastic optimal control frameworks for an agent who controls a randomly evolving system but can only prescribe the system dynamics for a short period *** is a common scenario in which a controlling agent frequently re-calibrates her *** introduce a new class of PFPPs based on rank-dependent utility,generalizing existing models that are based on expected utility theory(EUT).We establish existence of rank-dependent PFPPs under a conditionally complete market and exogenous probability distortion functions which are updated *** show that their construction reduces to solving an integral equation that generalizes the integral equation obtained under EUT in previous *** then propose a new approach for solving the integral equation via theory of Volterra *** illustrate our result in the special case of conditionally complete Black-Scholes model.

关键词： Forward performance criteria Rank dependent utility Probability distortion Time consistency Inverse investment problems Volterra integral equations Completely monotonic inverse marginals

Energy Control of Plug-In Hybrid Electric Vehicles Using Model Predictive Control With Route Preview

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IEEE/CAA Journal of Automatica Sinica 2021年第12期8卷 1948-1955页

作者： Yang Zhao Yanguang Cai Qiwen Song department of Mechanical and Electrical Engineering Guangdong University of Science and TechnologyDongguan 523083China School of Automation Guangdong University of TechnologyGuangzhou 510006China Transport Infrastructure investment Company Guangzhou 510620China

The paper proposes an adoption of slope,elevation,speed and route distance preview to achieve optimal energymanagement of plug-in hybrid electric vehicles(PHEVs).Theapproach is to identify route features from historical and real-time traffic data,in which information fusion model and trafficprediction model are used to improve the information ***,dynamic programming combined with equivalent con-sumption minimization strategy is used to compute an optimalsolution for real-time energy *** solution is thereference for PHEV energy management control along the *** improve the system's ability of handling changing situation,the study further explores predictive control model in the real-time control of the energy.A simulation is performed to modelPHEV under above energy control strategy with route *** results show that the average fuel consumption of PHEValong the previewed route with model predictive control(MPC)strategy can be reduced compared with optimal strategy andbase control strategy.

关键词： Energy management model predictive control(MPC) optimal control plug-in hybrid electric vehicle(PHEV)

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

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World Journal of Gastroenterology 2024年第9期30卷 1237-1249页

作者： Yue-Hong Kong Mei-Ling Xu Jun-Jun Zhang Guang-Qiang Chen Zhi-Hui Hong Hong Zhang Xiao-Xiao Dai Yi-Fu Ma Xiang-Rong Zhao Chen-Yang Zhang Rong-Zheng Chen Peng-Fei Xing Li-Yuan Zhang Center for Cancer Diagnosis and Treatment The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina department of Radiotherapy&Oncology The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina Institution of Radiotherapy&Oncology Soochow UniversitySuzhou 215000Jiangsu ProvinceChina department of Radiology The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina department of Nuclear Medicine The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina department of Clinical Laboratory The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina department of Pathology The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line *** human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in *** SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 *** had not developed any grade 2 or above treatment-related adverse events at any *** of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no *** PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

关键词： Pancreatic ductal adenocarcinoma PRaG 3.0 therapy Human epidermal growth factor receptor 2 Novel combination therapy Case report