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br Acknowledgments I thank Takeshi
2021-11-25
Acknowledgments I thank Takeshi Sakaba for critical reading of the manuscript and helpful comments. This work was supported by JSPS/MEXT KAKENHI Grant Numbers 17K19466, 17H03548. Introduction The oral route of drug application is the main route in pharmacology since it is easy to handle and o
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9620 synthesis The synthesis of substituted pyrimidinone car
2021-11-25
The synthesis of 2-substituted pyrimidinone carboxamides – is outlined in , . Treatment of readily accessible nitriles with N-methylhydroxylamine hydrochloride in the presence of 9620 synthesis provided the adducts , which were subsequently reacted with diethyl acetylenedicarboxylate to afford ins
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br Conclusion br Introduction Gastric adenocarcinoma GA is t
2021-11-25
Conclusion Introduction Gastric adenocarcinoma (GA) is the fifth most commonly diagnosed malignancy and the third most common cause of death due to cancer worldwide. It is a highly aggressive cancer and 5-year survival rate (5YSR) is usually the late stages based on the endoscopic investigati
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br Acknowledgments br Introduction The
2021-11-25
Acknowledgments Introduction The incidence of cholangiocarcinoma (CCA), a malignant tumor found in both intra- and extra-hepatic biliary epithelia [1], has been increased worldwide over the past two decades [2]. The prognosis of CCA patients are generally poor, due to the lack of early detecti
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Anti apoptotic Bcl proteins have become attractive targets
2021-11-25
Anti-apoptotic Bcl-2 proteins have become attractive targets for anti-cancer agents development, because they are associated with progression of a wide variety of human cancers., , The small-molecular Bcl-2 inhibitor venetoclax (ABT-199) () has been approved recently for the treatment of patients w
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Under increased drug pressure more protease variants with mo
2021-11-25
Under increased drug pressure, more protease variants with more than one substitution will likely become clinically relevant. The accumulation of additional substitutions can allow RAS variants to emerge that alone are not viable, but in combination can rescue the viral fitness. We previously demons
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Protein structures determined in high resolution by X ray cr
2021-11-25
Protein structures determined in high resolution by X-ray crystallography and NMR techniques provide wealth of structural information on intra-domain and inter-domain protein interactions of small sized proteins. In addition, cryo-EM often provides low resolution structures of multi-component protei
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It is interesting that SEC significantly inhibited cell migr
2021-11-25
It is interesting that SEC significantly inhibited cell migration and EMT in PC3 cells expressing a low RKIP level and HEK293T RKIP−/− cells, while had no effect on HEK293T RKIP+/+ cells. These observations can be interpreted that the RKIP-ANXA7 association may block SEC-induced ANXA7 GTPase activat
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The hypothesis that genes involved in type
2021-11-24
The hypothesis that genes involved in type 2 diabetes evolved under changing selective pressures and may carry the signature of natural selection motivated us to describe patterns of sequence variation at CAPN10 and GPR35 in human populations. An initial population genetics study reported an unusual
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A number of synthetic GPR agonists have been
2021-11-24
A number of synthetic GPR119 agonists have been reported to date, several of which have advanced into clinical trials. Reported GPR119 agonists are often composed of three parts as depicted in : a piperidine or a piperazine ring -substituted with a carbamate or a heteroaryl group at the right side,
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Introduction CD T cell recovery after initiation of combinat
2021-11-24
Introduction CD4+ T cell recovery after initiation of combination antiretroviral therapy (cART) is essential for restoring immune function in HIV-positive individuals [1]. However, CD4 recovery is variable and is affected by factors such as biological sex [2], [3], race [4], BMI [5], geographic reg
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As discussed above both endogenous and
2021-11-24
As discussed above, both endogenous and exogenous lesions can lead to adverse health effects [43]. Damaged nucleobases can block DNA replication which is often lethal to cells [44]. The effectiveness of DNA restoration by DNA glycosylases should be closely monitored to gain an insight of the functio
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Histamine functions as a key neurotransmitter in
2021-11-24
Histamine functions as a key neurotransmitter in multiple circuits to control various behaviors. In Drosophila photoreceptor, GNE-317 is produced de novo by histidine decarboxylase (Burg et al., 1993); meanwhile, maintaining normal histamine content also depends on the histamine recycling pathway (
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br Author contribution br Declaration of
2021-11-24
Author contribution Declaration of interest Acknowledgements This work was supported by National Natural Science Foundation of China (Grants 81473093) and State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica (SIMM1601ZZ-02). Introduction Diabetes represents a majo
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KH CB19 Axons are the largest component of WM by volume
2021-11-24
Axons are the largest component of WM by volume and are a significant repository of intracellular glutamate that can be releases under ischemic conditions [1,3,4,29,117]. We have recently shown that the principle route by which mature myelinated KH CB19 release glutamate during acute ischemia is vi
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