Marine natural products(MNPs)are valuable resources for drug development.To date,17 drugs from marine sources are in clinical use,and 33 pharmaceutical compounds are in clinical trials.Presently the success of drug de...Marine natural products(MNPs)are valuable resources for drug development.To date,17 drugs from marine sources are in clinical use,and 33 pharmaceutical compounds are in clinical trials.Presently the success of drug development from the marine resources is higher than the industry average.It is a feasible strategy to conduct the discovery of druglead compounds based on marine chemical ecology by fully exploiting the pharmacological potential of marine chemical defense matters.In the search for bioactive MNPs,our group has constructed a biological resources library including more than 1500 strains of fungi.Focusing on the strategy of Blue Drug Library,we have discovered a series of novel MNPs with abundant biological functions.Highly efficient and scalable total synthesis of(+)-aniduquinolone A(44)and pesimquinolone I(48)have been completed,which will facilitate access to sufficient quantities of candidates for in vivo pharmacological and toxicological studies.As a nucleoprotein(NP)inhibitor,QLA(75)possesses significant anti-influenza A virus(IAV)activities both in vitro and in vivo.CHNQD-00803(76)is a potent and selective AMP-activated kinase(AMPK)activator that can effectively inhibit metabolic disorders and metabolic dysfunction-associated steatohepatitis(MASH)progression.Moreover,we identified two new candidate molecules with potent anti-hepatocellular carcinoma effects.Particularly,as a natural guanine-nucleotide exchange factors for ADP-ribosylation factor GTPases(Arf-GEFs)inhibitor prodrug,CHNQD-01255(78)is qualified to be developed as a targeted candidate anticancer drug,which may be promising to apply for cancer immunotherapy.Hence,it is evident that MNPs play an important role in drug development.展开更多
In order to reflect truly the damage evolution mechanism of weak muddy intercalation in dry-wet cycles, two typical weak muddy intercalations were selected for dry-wet cycles. The mineral changes of specimens were ana...In order to reflect truly the damage evolution mechanism of weak muddy intercalation in dry-wet cycles, two typical weak muddy intercalations were selected for dry-wet cycles. The mineral changes of specimens were analyzed via X-ray diffraction after dry-wet cycles. By combining in-situ SEM and digital image processing(DIP), the damage evolution process and damage characteristic parameters of each stage were obtained. The experimental results indicate that the hydration and dissolution of minerals can not be a determinant factor in structure damage. The micro-structural damage is due to disintegration of mineral aggregates, leading to changes in the number and size of cracks and pores. The damage degree of specimens is related to its initial structure, and the micro-structural damage intensifies and finally tends to stabilize with cycle times increased.展开更多
目的利用纤维束自动定量法探讨高血压对脑白质微结构的影响及其与认知功能的相关性。方法连续性收集2017年1月至2018年7月于南京大学医学院附属鼓楼医院就诊的受试者,分为不伴认知损害的高血压组(hypertension without cognitive impair...目的利用纤维束自动定量法探讨高血压对脑白质微结构的影响及其与认知功能的相关性。方法连续性收集2017年1月至2018年7月于南京大学医学院附属鼓楼医院就诊的受试者,分为不伴认知损害的高血压组(hypertension without cognitive impairment,HTN-nonCI;n=44)、伴认知损害的高血压组(hypertension with cognitive impairment,HTN-CI;n=50)及对照组(n=25)。收集受试者影像学资料及神经心理学量表测试结果,采用纤维束自动定量法得到全脑20条纤维束上各100个节点的弥散参数,比较对照组与HTN-nonCI组以及HTN-nonCI与HTN-CI组各纤维束弥散参数的差异性节段,对HTN-nonCI组与HTN-CI组具有显著差异的脑白质纤维束与各认知域进行相关性分析。结果三组脑白质纤维束的各向异性分数(fractional anisotropy,FA)均呈递减趋势,平均扩散系数(mean diffusivity,MD)均呈递增趋势。对对照组与HTN-nonCI组进行的比较显示,左侧丘脑放射束中点偏脑干侧、胼胝体膝部近脑干侧、胼胝体压部额部及近侧脑室处的FA值差异有统计学意义(P均<0.05);左侧丘脑放射束中部及近脑干部、右侧丘脑放射束近脑干部、左侧皮质脊髓束顶部及近脑干部、右侧扣带束海马中部、胼胝体膝部中部、胼胝体压部近侧脑室处、左侧钩束近额部的MD值差异有统计学意义(P均<0.05)。对HTN-nonCI组与HTN-CI组进行的比较显示,左侧扣带束扣带回的散在分布节段和左侧下额枕束近枕叶侧的FA值差异有统计学意义,其中左侧扣带束扣带回与蒙特利尔认知评估量表评分显著相关(标化β=0.268,P=0.029);右侧丘脑放射束近脑干部、胼胝体压部额部及近侧脑室处、右侧下纵束的散在分布节段的MD值差异有统计学意义,其中右侧下纵束与记忆力(标化β=-0.243,P=0.047)及执行功能(标化β=-0.284,P=0.021)显著相关。结论高血压患者普遍存在脑白质微结构完整性破坏,但部分节段更易受高血压影响。扣带束扣带回完整性与整体认知功能显著相关,下纵束完整性与执行功能及记忆力显著相关。展开更多
目的探讨MRI上总脑小血管病（cerebral small vessel disease, SVD）评分与总体及不同认知域认知功能的相关性。方法2017年1月至2018年6月，从南京大学医学院附属鼓楼医院神经内科门诊、病房以及社区招募纳入年龄45～80岁且无脑血管病...目的探讨MRI上总脑小血管病（cerebral small vessel disease, SVD）评分与总体及不同认知域认知功能的相关性。方法2017年1月至2018年6月，从南京大学医学院附属鼓楼医院神经内科门诊、病房以及社区招募纳入年龄45～80岁且无脑血管病和痴呆的受试者。应用相关量表对所有受试者进行总体认知功能、执行功能、处理速度、工作记忆、语言功能、视空间能力及抑郁评估。应用3.0 T MRI（T1加权成像、T2加权成像、弥散加权成像、液体衰减反转恢复序列和磁敏感加权成像）识别脑白质高信号、腔隙灶、微出血和血管周围间隙扩大，计算总SVD评分。结果共纳入217名受试者，其中正常中老年人24名，脑血管病高危者65名，影像学可见SVD改变者128名。多变量线性回归分析显示，校正可能的混杂因素后，总SVD评分与总体认知功能（β＝－0.105，95%可信区间－0.201～－0.010；P＝0.030）、执行功能（β＝－0.135，95%可信区间－0.216～－0.054；P＝0.001）和语言功能（β＝－0.095，95% CI －0.182～－0.008；P＝0.032）呈显著独立负相关。结论总SVD评分与总体认知功能、执行功能和语言功能损害呈负相关。展开更多
基金supported by the Shandong Province Special Fund ‘Frontier Technology and Free Exploration’ from Laoshan Laboratory (No. 8-01)the National Natural Science Foundation of China (No. 42376116)+3 种基金the Special Funds of Shandong Province for Qingdao National Laboratory of Marine Science and Technology (No. 2022QN LM030003)the State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University (No. CMEMR2023-B16)the National Key Research and Development Program of China (No. 2022YFC2601305)the Innovation Center for Academicians of Hainan Province, and the Fundamental Research Funds for the Central Universities (No. 202461059)
文摘Marine natural products(MNPs)are valuable resources for drug development.To date,17 drugs from marine sources are in clinical use,and 33 pharmaceutical compounds are in clinical trials.Presently the success of drug development from the marine resources is higher than the industry average.It is a feasible strategy to conduct the discovery of druglead compounds based on marine chemical ecology by fully exploiting the pharmacological potential of marine chemical defense matters.In the search for bioactive MNPs,our group has constructed a biological resources library including more than 1500 strains of fungi.Focusing on the strategy of Blue Drug Library,we have discovered a series of novel MNPs with abundant biological functions.Highly efficient and scalable total synthesis of(+)-aniduquinolone A(44)and pesimquinolone I(48)have been completed,which will facilitate access to sufficient quantities of candidates for in vivo pharmacological and toxicological studies.As a nucleoprotein(NP)inhibitor,QLA(75)possesses significant anti-influenza A virus(IAV)activities both in vitro and in vivo.CHNQD-00803(76)is a potent and selective AMP-activated kinase(AMPK)activator that can effectively inhibit metabolic disorders and metabolic dysfunction-associated steatohepatitis(MASH)progression.Moreover,we identified two new candidate molecules with potent anti-hepatocellular carcinoma effects.Particularly,as a natural guanine-nucleotide exchange factors for ADP-ribosylation factor GTPases(Arf-GEFs)inhibitor prodrug,CHNQD-01255(78)is qualified to be developed as a targeted candidate anticancer drug,which may be promising to apply for cancer immunotherapy.Hence,it is evident that MNPs play an important role in drug development.
基金Funded by the National Natural Science Foundation of China(No.51574201)the Research and Innovation Team of Provincial U niversities in Sichuan(18TD0014)the Excellent Youth Foundat ion of Sichuan Scientific Committee(2019JDJQ0037)
文摘In order to reflect truly the damage evolution mechanism of weak muddy intercalation in dry-wet cycles, two typical weak muddy intercalations were selected for dry-wet cycles. The mineral changes of specimens were analyzed via X-ray diffraction after dry-wet cycles. By combining in-situ SEM and digital image processing(DIP), the damage evolution process and damage characteristic parameters of each stage were obtained. The experimental results indicate that the hydration and dissolution of minerals can not be a determinant factor in structure damage. The micro-structural damage is due to disintegration of mineral aggregates, leading to changes in the number and size of cracks and pores. The damage degree of specimens is related to its initial structure, and the micro-structural damage intensifies and finally tends to stabilize with cycle times increased.
基金Project supported by the National Natural Science Foundation of China(No.81973460)the Foundation of Science and Technology Department of Sichuan Province(No.2018JY0186)the Xinglin Scholar Research Promotion Project of Chengdu University of Traditional Chinese Medicine(No.BSH2018008)。
文摘目的利用纤维束自动定量法探讨高血压对脑白质微结构的影响及其与认知功能的相关性。方法连续性收集2017年1月至2018年7月于南京大学医学院附属鼓楼医院就诊的受试者,分为不伴认知损害的高血压组(hypertension without cognitive impairment,HTN-nonCI;n=44)、伴认知损害的高血压组(hypertension with cognitive impairment,HTN-CI;n=50)及对照组(n=25)。收集受试者影像学资料及神经心理学量表测试结果,采用纤维束自动定量法得到全脑20条纤维束上各100个节点的弥散参数,比较对照组与HTN-nonCI组以及HTN-nonCI与HTN-CI组各纤维束弥散参数的差异性节段,对HTN-nonCI组与HTN-CI组具有显著差异的脑白质纤维束与各认知域进行相关性分析。结果三组脑白质纤维束的各向异性分数(fractional anisotropy,FA)均呈递减趋势,平均扩散系数(mean diffusivity,MD)均呈递增趋势。对对照组与HTN-nonCI组进行的比较显示,左侧丘脑放射束中点偏脑干侧、胼胝体膝部近脑干侧、胼胝体压部额部及近侧脑室处的FA值差异有统计学意义(P均<0.05);左侧丘脑放射束中部及近脑干部、右侧丘脑放射束近脑干部、左侧皮质脊髓束顶部及近脑干部、右侧扣带束海马中部、胼胝体膝部中部、胼胝体压部近侧脑室处、左侧钩束近额部的MD值差异有统计学意义(P均<0.05)。对HTN-nonCI组与HTN-CI组进行的比较显示,左侧扣带束扣带回的散在分布节段和左侧下额枕束近枕叶侧的FA值差异有统计学意义,其中左侧扣带束扣带回与蒙特利尔认知评估量表评分显著相关(标化β=0.268,P=0.029);右侧丘脑放射束近脑干部、胼胝体压部额部及近侧脑室处、右侧下纵束的散在分布节段的MD值差异有统计学意义,其中右侧下纵束与记忆力(标化β=-0.243,P=0.047)及执行功能(标化β=-0.284,P=0.021)显著相关。结论高血压患者普遍存在脑白质微结构完整性破坏,但部分节段更易受高血压影响。扣带束扣带回完整性与整体认知功能显著相关,下纵束完整性与执行功能及记忆力显著相关。
文摘目的探讨MRI上总脑小血管病（cerebral small vessel disease, SVD）评分与总体及不同认知域认知功能的相关性。方法2017年1月至2018年6月，从南京大学医学院附属鼓楼医院神经内科门诊、病房以及社区招募纳入年龄45～80岁且无脑血管病和痴呆的受试者。应用相关量表对所有受试者进行总体认知功能、执行功能、处理速度、工作记忆、语言功能、视空间能力及抑郁评估。应用3.0 T MRI（T1加权成像、T2加权成像、弥散加权成像、液体衰减反转恢复序列和磁敏感加权成像）识别脑白质高信号、腔隙灶、微出血和血管周围间隙扩大，计算总SVD评分。结果共纳入217名受试者，其中正常中老年人24名，脑血管病高危者65名，影像学可见SVD改变者128名。多变量线性回归分析显示，校正可能的混杂因素后，总SVD评分与总体认知功能（β＝－0.105，95%可信区间－0.201～－0.010；P＝0.030）、执行功能（β＝－0.135，95%可信区间－0.216～－0.054；P＝0.001）和语言功能（β＝－0.095，95% CI －0.182～－0.008；P＝0.032）呈显著独立负相关。结论总SVD评分与总体认知功能、执行功能和语言功能损害呈负相关。
