Objective To study the strategic planning of drug regulatory science,the effectiveness and role of policy implementation in the United States so as to gain insights and make suggestions for further improving the strat...Objective To study the strategic planning of drug regulatory science,the effectiveness and role of policy implementation in the United States so as to gain insights and make suggestions for further improving the strategic planning of drug regulatory science in China.Methods Literature research method and comparative research method were used to compare and analyze the strategic planning of regulatory science in China and the United States.Results and Conclusion Drawing on the US experience,China should set goals based on mission and vision and identify problems,knowledge gaps,and key areas,then concrete measures can be taken to advance regulatory science.展开更多
The use of non-steroidal anti-inflammatory drugs(NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of dige...The use of non-steroidal anti-inflammatory drugs(NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of digestive system complications in the course of their use. Recent data suggests that the complications of the lower gastro-intestinal tract may be as frequent and severe as those of the upper tract. NSAIDs enteropathy is due to enterohepatic recycling of the drugs resulting in a prolonged and repeated exposure of the intestinal mucosa to the compound and its metabolites. Thus leading to so-called topical effects, which, in turn, lead to an impairment of the intestinal barrier. This process determines bacterial translocation and toxic substances of intestinal origin in the portal circulation, leading to an endotoxaemia. This condition could determine a liver inflammatory response and might promote the development of nonalcoholic steatohepatitis, mostly in patients with risk factors such as obesity, metabolic syndrome and a high fat diet, which may induce a small intestinal bacterial overgrowth and dysbiosis. This alteration of gut microbiota may contribute to nonalcoholic fatty liver disease and its related disorders in two ways: firstly causing a malfunction of the tight junctions that play a critical role in the increase of intestinal permeability, and then secondly leading to the development of insulin resistance, body weight gain, lipogenesis, fibrogenesis and hepatic oxidative stress.展开更多
The sulfide-based solid-state electrolytes(SEs)reactivity toward moisture and Li-metal are huge barriers that impede their large-scale manufactu ring and applications in all-solid-state lithium batteries(ASSLBs).Herei...The sulfide-based solid-state electrolytes(SEs)reactivity toward moisture and Li-metal are huge barriers that impede their large-scale manufactu ring and applications in all-solid-state lithium batteries(ASSLBs).Herein,we proposed an Al and O dual-doped strategy for Li_(3)PS_(4)SE to regulate the chemical/electrochemical stability of anionic PS_(4)^(3-)tetrahedra to mitigate structural hydrolysis and parasitic reactions at the SE/Li interface.The optimized Li_(3.08)A_(10.04)P_(0.96)S_(3.92)O_(0.08)SE presents the highestσLi+of 3.27 mS cm^(-1),which is~6.8 times higher than the pristine Li_(3)PS_(4)and excellently inhibits the structural hydrolysis for~25 min@25%humidity at RT.DFT calculations confirmed that the enhanced chemical stability was revealed to the intrinsically stable entities,e.g.,POS33-units.Moreover,Li_(3.08)Al_(0.04)P_(0.96)S_(3.92)O_(0.08)SE cycled stably in Li//Li symmetric cell over 1000 h@0.1 mA cm^(-2)/0.1 mA h cm^(-2),could be revealed to Li-Al alloy and Li_(2)Oat SE/Li interface impeding the growth of Li-dendrites during cycling.Resultantly,LNO@LCO/Li_(3.08)Al_(0.04)P_(0.96)S_(3.92)O_(0.08)/Li-In cell delivered initial discharge capacities of 129.8 mA h g^(-1)and 83.74%capacity retention over 300 cycles@0.2 C at RT.Moreover,the Li_(3.08)Al_(0.04)P_(0.96)S_(3.92)O_(0.08)SE presented>90%capacity retention over 200 and 300 cycles when the cell was tested with LiNi_(0.8)Co_(0.15)Al_(0.05)O_(2)(NCA)cathode material vs.5 and 10 mg cm^(-2)@RT.展开更多
Aim: To reveal the exonic and 3’UTR sequences of KRAS, TP53, APC, BRAF, PIK3CA genes in sporadic colorectal tumors and to investigate the clinical relevance of 3’UTR variations in miRNA profiles. Methods: In the stu...Aim: To reveal the exonic and 3’UTR sequences of KRAS, TP53, APC, BRAF, PIK3CA genes in sporadic colorectal tumors and to investigate the clinical relevance of 3’UTR variations in miRNA profiles. Methods: In the study, the exonic and 3’UTR sequences of five genes in 12 sporadic colorectal tumors were extracted by next generation sequencing. In tumors with variation in the 3’UTR region, the changes caused by the variation in the miRNA binding profile were detected. The expression profile of these miRNAs in colorectal and other solid tumors compared to normal tissue was determined. Pathway analysis was performed to determine which signaling pathways miRNAs affect. Results: Case-10 in our study was wild type KRAS and received cetuximab treatment and developed drug resistance. In this case, it was concluded that the expression of KRAS increased and tumorigenesis progressed due to miRNAs that do not bind to this region due to variations in the 3’UTR region. Among these miRNAs, hsa-miR-124-3p was found to have decreased expression in colorectal tumors and to be associated with the ECM-receptor interaction pathway. Conclusion: Variations in the 3’UTR regions of genes critical in the process of carsinogenesis are associated with drug resistance and the process of tumorigenesis.展开更多
Proceeding from natural amino acid L-asparagine and commercially available aldehydes a stereoselective synthesis was developed of (2S,4S)-2-alkyl(aryl)-3-(3-sulfanylpropanoyl)-6-oxohexahy- dropyrimidine-4-carboxylic a...Proceeding from natural amino acid L-asparagine and commercially available aldehydes a stereoselective synthesis was developed of (2S,4S)-2-alkyl(aryl)-3-(3-sulfanylpropanoyl)-6-oxohexahy- dropyrimidine-4-carboxylic acids, potential antihypertensive drugs, inhibitors of the angiotensin converting enzyme.展开更多
1.楼下那个人睡不着觉。[误]The downstairs man couldn’t go to sleep.[正]The man downstairs couldn’t go to sleep.[析]以today,here,there,downstairs,upstairs, below,above等作定语修饰名词时常放在名词之后。2我正想出去,铃...1.楼下那个人睡不着觉。[误]The downstairs man couldn’t go to sleep.[正]The man downstairs couldn’t go to sleep.[析]以today,here,there,downstairs,upstairs, below,above等作定语修饰名词时常放在名词之后。2我正想出去,铃响了。[误]I just went out when the bell rang.[正]I was just going out when the bell rang.[析]由when连接的两个分句,其中—个谓语动词是延续性,另一个谓语是终止性动词时,此处的when是并列连词,意为“这时 (突然)”,所以要将went out改为was going out.展开更多
I.单项选择:从A、B、C、D四个选项中,选出可以填入空白处的正确答案。1.Are you__ the 100-metre race today? A.on B.to C.for D.in2.I’m afraid you didn’t do your homework__ A.careful enough B.carefully enough C.enough caref...I.单项选择:从A、B、C、D四个选项中,选出可以填入空白处的正确答案。1.Are you__ the 100-metre race today? A.on B.to C.for D.in2.I’m afraid you didn’t do your homework__ A.careful enough B.carefully enough C.enough careful D.enough carefully3.They__a class meeting last Friday. A.hold B.held C.take D.took4.__Jack came a moment__ . -Why did he come__? A.late;later B.late;late C.later;late D.later;展开更多
1.你必须尽快把书还到图书馆。[误]You must return the book to the library as quickly as possible.[正]You must return the book to the library as soon as possible.[析]as quickly as possible与as soon as possible都可表“尽...1.你必须尽快把书还到图书馆。[误]You must return the book to the library as quickly as possible.[正]You must return the book to the library as soon as possible.[析]as quickly as possible与as soon as possible都可表“尽快”地,但前者是指做事的速度快,可以用as fast as possible来替换;而后者则指做事的时间尽可能早。展开更多
1.你明天能来吗?【误】Do you able to come tomorrow?【正】Are you able to come tomorrow?【析】able是个形容词,常放在be之后,构成beable to do sth.,表示“能做某事”;其疑问形式不需要用助动词do,而应将be提到主语之前。
基金supported by the Special Fund of Scientific Research Base for Drug Regulation of NMPA-Research Institute of Drug Regulatory Science of Shenyang Pharmaceutical University(2021jgkx004).
文摘Objective To study the strategic planning of drug regulatory science,the effectiveness and role of policy implementation in the United States so as to gain insights and make suggestions for further improving the strategic planning of drug regulatory science in China.Methods Literature research method and comparative research method were used to compare and analyze the strategic planning of regulatory science in China and the United States.Results and Conclusion Drawing on the US experience,China should set goals based on mission and vision and identify problems,knowledge gaps,and key areas,then concrete measures can be taken to advance regulatory science.
文摘The use of non-steroidal anti-inflammatory drugs(NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of digestive system complications in the course of their use. Recent data suggests that the complications of the lower gastro-intestinal tract may be as frequent and severe as those of the upper tract. NSAIDs enteropathy is due to enterohepatic recycling of the drugs resulting in a prolonged and repeated exposure of the intestinal mucosa to the compound and its metabolites. Thus leading to so-called topical effects, which, in turn, lead to an impairment of the intestinal barrier. This process determines bacterial translocation and toxic substances of intestinal origin in the portal circulation, leading to an endotoxaemia. This condition could determine a liver inflammatory response and might promote the development of nonalcoholic steatohepatitis, mostly in patients with risk factors such as obesity, metabolic syndrome and a high fat diet, which may induce a small intestinal bacterial overgrowth and dysbiosis. This alteration of gut microbiota may contribute to nonalcoholic fatty liver disease and its related disorders in two ways: firstly causing a malfunction of the tight junctions that play a critical role in the increase of intestinal permeability, and then secondly leading to the development of insulin resistance, body weight gain, lipogenesis, fibrogenesis and hepatic oxidative stress.
基金supported by the National Natural Science Foundation of China(Nos.21203008,21975025,12274025)the Hainan Province Science and Technology Special Fund(Nos.ZDYF2021SHFZ232,ZDYF2023GXJS022)the Hainan Province Postdoctoral Science Foundation(No.300333)。
文摘The sulfide-based solid-state electrolytes(SEs)reactivity toward moisture and Li-metal are huge barriers that impede their large-scale manufactu ring and applications in all-solid-state lithium batteries(ASSLBs).Herein,we proposed an Al and O dual-doped strategy for Li_(3)PS_(4)SE to regulate the chemical/electrochemical stability of anionic PS_(4)^(3-)tetrahedra to mitigate structural hydrolysis and parasitic reactions at the SE/Li interface.The optimized Li_(3.08)A_(10.04)P_(0.96)S_(3.92)O_(0.08)SE presents the highestσLi+of 3.27 mS cm^(-1),which is~6.8 times higher than the pristine Li_(3)PS_(4)and excellently inhibits the structural hydrolysis for~25 min@25%humidity at RT.DFT calculations confirmed that the enhanced chemical stability was revealed to the intrinsically stable entities,e.g.,POS33-units.Moreover,Li_(3.08)Al_(0.04)P_(0.96)S_(3.92)O_(0.08)SE cycled stably in Li//Li symmetric cell over 1000 h@0.1 mA cm^(-2)/0.1 mA h cm^(-2),could be revealed to Li-Al alloy and Li_(2)Oat SE/Li interface impeding the growth of Li-dendrites during cycling.Resultantly,LNO@LCO/Li_(3.08)Al_(0.04)P_(0.96)S_(3.92)O_(0.08)/Li-In cell delivered initial discharge capacities of 129.8 mA h g^(-1)and 83.74%capacity retention over 300 cycles@0.2 C at RT.Moreover,the Li_(3.08)Al_(0.04)P_(0.96)S_(3.92)O_(0.08)SE presented>90%capacity retention over 200 and 300 cycles when the cell was tested with LiNi_(0.8)Co_(0.15)Al_(0.05)O_(2)(NCA)cathode material vs.5 and 10 mg cm^(-2)@RT.
文摘Aim: To reveal the exonic and 3’UTR sequences of KRAS, TP53, APC, BRAF, PIK3CA genes in sporadic colorectal tumors and to investigate the clinical relevance of 3’UTR variations in miRNA profiles. Methods: In the study, the exonic and 3’UTR sequences of five genes in 12 sporadic colorectal tumors were extracted by next generation sequencing. In tumors with variation in the 3’UTR region, the changes caused by the variation in the miRNA binding profile were detected. The expression profile of these miRNAs in colorectal and other solid tumors compared to normal tissue was determined. Pathway analysis was performed to determine which signaling pathways miRNAs affect. Results: Case-10 in our study was wild type KRAS and received cetuximab treatment and developed drug resistance. In this case, it was concluded that the expression of KRAS increased and tumorigenesis progressed due to miRNAs that do not bind to this region due to variations in the 3’UTR region. Among these miRNAs, hsa-miR-124-3p was found to have decreased expression in colorectal tumors and to be associated with the ECM-receptor interaction pathway. Conclusion: Variations in the 3’UTR regions of genes critical in the process of carsinogenesis are associated with drug resistance and the process of tumorigenesis.
文摘Proceeding from natural amino acid L-asparagine and commercially available aldehydes a stereoselective synthesis was developed of (2S,4S)-2-alkyl(aryl)-3-(3-sulfanylpropanoyl)-6-oxohexahy- dropyrimidine-4-carboxylic acids, potential antihypertensive drugs, inhibitors of the angiotensin converting enzyme.
文摘1.楼下那个人睡不着觉。[误]The downstairs man couldn’t go to sleep.[正]The man downstairs couldn’t go to sleep.[析]以today,here,there,downstairs,upstairs, below,above等作定语修饰名词时常放在名词之后。2我正想出去,铃响了。[误]I just went out when the bell rang.[正]I was just going out when the bell rang.[析]由when连接的两个分句,其中—个谓语动词是延续性,另一个谓语是终止性动词时,此处的when是并列连词,意为“这时 (突然)”,所以要将went out改为was going out.
文摘I.单项选择:从A、B、C、D四个选项中,选出可以填入空白处的正确答案。1.Are you__ the 100-metre race today? A.on B.to C.for D.in2.I’m afraid you didn’t do your homework__ A.careful enough B.carefully enough C.enough careful D.enough carefully3.They__a class meeting last Friday. A.hold B.held C.take D.took4.__Jack came a moment__ . -Why did he come__? A.late;later B.late;late C.later;late D.later;
文摘1.你必须尽快把书还到图书馆。[误]You must return the book to the library as quickly as possible.[正]You must return the book to the library as soon as possible.[析]as quickly as possible与as soon as possible都可表“尽快”地,但前者是指做事的速度快,可以用as fast as possible来替换;而后者则指做事的时间尽可能早。
文摘1.你明天能来吗?【误】Do you able to come tomorrow?【正】Are you able to come tomorrow?【析】able是个形容词,常放在be之后,构成beable to do sth.,表示“能做某事”;其疑问形式不需要用助动词do,而应将be提到主语之前。
