The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKS...The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully understood.Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic spines.However,the function of CNKSR2 in the cytoplasm remains to be elucidated.In this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2.Through a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome.We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290.Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2.When we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal genes.This manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and motility.Furthermore,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder.Our findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.展开更多
The intricate distribution of oil and water in tight rocks makes pinpointing oil layers challenging.While conventional identification methods offer potential solutions,their limited accuracy precludes them from being ...The intricate distribution of oil and water in tight rocks makes pinpointing oil layers challenging.While conventional identification methods offer potential solutions,their limited accuracy precludes them from being effective in their applications to unconventional reservoirs.This study employed nuclear magnetic resonance(NMR)spectrum decomposition to dissect the NMR T_(2)spectrum into multiple subspectra.Furthermore,it employed laboratory NMR experiments to ascertain the fluid properties of these sub-spectra,aiming to enhance identification accuracy.The findings indicate that fluids of distinct properties overlap in the T_(2)spectra,with bound water,movable water,bound oil,and movable oil appearing sequentially from the low-value zone to the high-value zone.Consequently,an oil layer classification scheme was proposed,which considers the physical properties of reservoirs,oil-bearing capacity,and the characteristics of both mobility and the oil-water two-phase flow.When applied to tight oil layer identification,the scheme's outcomes align closely with actual test results.A horizontal well,deployed based on these findings,has produced high-yield industrial oil flow,underscoring the precision and dependability of this new approach.展开更多
目的探究胰岛素分泌曲线和血糖谱在2型糖尿病选择胰岛素促泌剂中的价值,为临床胰岛素促泌剂选择提供依据。方法本研究为随机对照试验,选取2015年12月至2020年12月东营市第二人民医院根据降糖治疗需要选用胰岛素促泌剂的2型糖尿病患者12...目的探究胰岛素分泌曲线和血糖谱在2型糖尿病选择胰岛素促泌剂中的价值,为临床胰岛素促泌剂选择提供依据。方法本研究为随机对照试验,选取2015年12月至2020年12月东营市第二人民医院根据降糖治疗需要选用胰岛素促泌剂的2型糖尿病患者120例作为研究对象,采用随机数字表法分为观察组和对照组,各60例。观察组男38例、女22例,年龄(58.27±6.34)岁,病程(3.62±1.28)年;对照组男33例、女27例,年龄(59.04±7.82)岁,病程(3.55±1.17)年。观察组进行馒头餐试验并依据胰岛素分泌曲线选择胰岛素促泌剂;对照组依据血糖谱选择胰岛素促泌剂,两组均治疗24周。对比两组患者血糖控制达标平均天数、血糖达标率、住院天数、低血糖发生率及治疗前后胰岛素β细胞功能[空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、C肽(CP)水平]、血糖[空腹血糖(FPG)、餐后2 h血糖(2 h PBG)、糖化血红蛋白(HbA1c)]水平、不良反应发生情况。采用t检验、χ^(2)检验。结果观察组血糖控制达标平均天数、住院天数均短于对照组[(7.05±1.42)d比(8.39±1.86)d、(10.29±2.08)d比(11.35±2.17)d],血糖达标率高于对照组[86.67%(52/60)比71.67%(43/60)],差异均有统计学意义(t=4.436、2.732,χ^(2)=4.093;均P<0.05)。治疗后,观察组FINS、CP水平均高于对照组[(9.32±1.55)IU/L比(8.46±1.38)IU/L、(1.49±0.39)μg/L比(1.35±0.32)μg/L],HOMA-IR低于对照组[(1.92±0.43)比(2.37±0.84)],差异均有统计学意义(t=3.210、2.150、3.694,均P<0.05)。治疗后,观察组FPG、2 h PBG、HbA1c水平均低于对照组[(6.47±1.12)mmol/L比(7.35±0.94)mmol/L、(10.52±1.17)mmol/L比(11.83±1.59)mmol/L、(6.12±1.09)%比(6.79±1.35)%],差异均有统计学意义(t=4.662、5.140、2.991,均P<0.05)。观察组不良反应发生率为15.00%(9/60),与对照组[18.33%(11/60)]比较,差异无统计学意义(χ^(2)=0.240,P=0.624)。结论与血糖谱相比,经胰岛素分泌曲线选择胰岛素促泌剂具有较好的促胰岛素分泌效果和降糖效果,有利于缩短血糖控制达标时间和住院时间,提高血糖达标率。展开更多
The method of regularization factor selection determines stability and accuracy of the regularization method. A formula of regularization factor was proposed by analyzing the relationship between the improved SVD and ...The method of regularization factor selection determines stability and accuracy of the regularization method. A formula of regularization factor was proposed by analyzing the relationship between the improved SVD and regularization method. The improved SVD algorithm and regularization method could adapt to low SNR. The regularization method is better than the improved SVD in the case that SNR is below 30 and the improved SVD is better than the regularization method when SNR is higher than 30. The regularization method with the regularization factor proposed in this paper can be better applied into low SNR （5〈SNR） NMR logging. The numerical simulations and real NMR data process results indicated that the improved SVD algorithm and regularization method could adapt to the low signal to noise ratio and reduce the amount of computation greatly. These algorithms can be applied in NMR logging.展开更多
基金supported by the National Nature Science Foundation of China,No.32101020(to JL)the Natural Science Foundation of Shandong Province,Nos.ZR2020MC071(to JL),ZR2023MH327(to HZ)+1 种基金the Integrated Project of Major Research Plan of National Natural Science Foundation of China,No.92249303(to PL)the Natural Science Foundation of Qingdao,No.23-2-1-193-zyyd-jch(to HZ)。
文摘The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully understood.Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic spines.However,the function of CNKSR2 in the cytoplasm remains to be elucidated.In this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2.Through a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome.We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290.Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2.When we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal genes.This manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and motility.Furthermore,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder.Our findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.
基金funded by a major special project of PetroChina Company Limited(No.2021DJ1003No.2023ZZ2).
文摘The intricate distribution of oil and water in tight rocks makes pinpointing oil layers challenging.While conventional identification methods offer potential solutions,their limited accuracy precludes them from being effective in their applications to unconventional reservoirs.This study employed nuclear magnetic resonance(NMR)spectrum decomposition to dissect the NMR T_(2)spectrum into multiple subspectra.Furthermore,it employed laboratory NMR experiments to ascertain the fluid properties of these sub-spectra,aiming to enhance identification accuracy.The findings indicate that fluids of distinct properties overlap in the T_(2)spectra,with bound water,movable water,bound oil,and movable oil appearing sequentially from the low-value zone to the high-value zone.Consequently,an oil layer classification scheme was proposed,which considers the physical properties of reservoirs,oil-bearing capacity,and the characteristics of both mobility and the oil-water two-phase flow.When applied to tight oil layer identification,the scheme's outcomes align closely with actual test results.A horizontal well,deployed based on these findings,has produced high-yield industrial oil flow,underscoring the precision and dependability of this new approach.
文摘目的探究胰岛素分泌曲线和血糖谱在2型糖尿病选择胰岛素促泌剂中的价值,为临床胰岛素促泌剂选择提供依据。方法本研究为随机对照试验,选取2015年12月至2020年12月东营市第二人民医院根据降糖治疗需要选用胰岛素促泌剂的2型糖尿病患者120例作为研究对象,采用随机数字表法分为观察组和对照组,各60例。观察组男38例、女22例,年龄(58.27±6.34)岁,病程(3.62±1.28)年;对照组男33例、女27例,年龄(59.04±7.82)岁,病程(3.55±1.17)年。观察组进行馒头餐试验并依据胰岛素分泌曲线选择胰岛素促泌剂;对照组依据血糖谱选择胰岛素促泌剂,两组均治疗24周。对比两组患者血糖控制达标平均天数、血糖达标率、住院天数、低血糖发生率及治疗前后胰岛素β细胞功能[空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、C肽(CP)水平]、血糖[空腹血糖(FPG)、餐后2 h血糖(2 h PBG)、糖化血红蛋白(HbA1c)]水平、不良反应发生情况。采用t检验、χ^(2)检验。结果观察组血糖控制达标平均天数、住院天数均短于对照组[(7.05±1.42)d比(8.39±1.86)d、(10.29±2.08)d比(11.35±2.17)d],血糖达标率高于对照组[86.67%(52/60)比71.67%(43/60)],差异均有统计学意义(t=4.436、2.732,χ^(2)=4.093;均P<0.05)。治疗后,观察组FINS、CP水平均高于对照组[(9.32±1.55)IU/L比(8.46±1.38)IU/L、(1.49±0.39)μg/L比(1.35±0.32)μg/L],HOMA-IR低于对照组[(1.92±0.43)比(2.37±0.84)],差异均有统计学意义(t=3.210、2.150、3.694,均P<0.05)。治疗后,观察组FPG、2 h PBG、HbA1c水平均低于对照组[(6.47±1.12)mmol/L比(7.35±0.94)mmol/L、(10.52±1.17)mmol/L比(11.83±1.59)mmol/L、(6.12±1.09)%比(6.79±1.35)%],差异均有统计学意义(t=4.662、5.140、2.991,均P<0.05)。观察组不良反应发生率为15.00%(9/60),与对照组[18.33%(11/60)]比较,差异无统计学意义(χ^(2)=0.240,P=0.624)。结论与血糖谱相比,经胰岛素分泌曲线选择胰岛素促泌剂具有较好的促胰岛素分泌效果和降糖效果,有利于缩短血糖控制达标时间和住院时间,提高血糖达标率。
文摘The method of regularization factor selection determines stability and accuracy of the regularization method. A formula of regularization factor was proposed by analyzing the relationship between the improved SVD and regularization method. The improved SVD algorithm and regularization method could adapt to low SNR. The regularization method is better than the improved SVD in the case that SNR is below 30 and the improved SVD is better than the regularization method when SNR is higher than 30. The regularization method with the regularization factor proposed in this paper can be better applied into low SNR （5〈SNR） NMR logging. The numerical simulations and real NMR data process results indicated that the improved SVD algorithm and regularization method could adapt to the low signal to noise ratio and reduce the amount of computation greatly. These algorithms can be applied in NMR logging.
