The biological functions of the epitranscriptomic modification N^(6)-methyladenosine(m^(6)A)in plants are not fully understood.CPSF30-L is a predominant isoform of the polyadenylation factor CPSF30 and consists of CPS...The biological functions of the epitranscriptomic modification N^(6)-methyladenosine(m^(6)A)in plants are not fully understood.CPSF30-L is a predominant isoform of the polyadenylation factor CPSF30 and consists of CPSF30-S and an m^(6)A-binding YTH domain.Little is known about the biological roles of CPSF30-L and the molecular mechanism underlying its m^(6)A-binding function in alternative polyadenylation.Here,we charac-terized CPSF30-L as an Arabidopsis m^(6)A reader whose m^(6)A-binding function is required for the floral tran-sition and abscisic acid(ABA)response.We found that the m^(6)A-binding activity of CPSF30-L enhances the formation of liquid-like nuclear bodies,where CPSF30-L mainly recognizes m*A-modified far-upstream elements to control polyadenylation site choice.Deficiency of CPSF30-L lengthens the 3'untranslated region of three phenotypes-related transcripts,thereby accelerating their mRNA degradation and leading to late flowering and ABA hypersensitivity.Collectively,this study uncovers a new molecular mechanism for m^(6)A-driven phase separation and polyadenylation in plants.展开更多
WX-0593(Iruplinalkib)is a novel,highly selective oral ALK and ROS1 tyrosine kinase inhibitor(TKI).In this study,the safety,antitumor activity,and pharmacokinetics of WX-0593 were evaluated in advanced non-small cell l...WX-0593(Iruplinalkib)is a novel,highly selective oral ALK and ROS1 tyrosine kinase inhibitor(TKI).In this study,the safety,antitumor activity,and pharmacokinetics of WX-0593 were evaluated in advanced non-small cell lung cancer(NSCLC)patients with ALK or ROS1 rearrangement.In the dose-escalation phase and dose-expansion phase,patients were treated with WX-0593 until disease progression,unacceptable toxicity,or subject withdrawal.In the dose-escalation phase,the primary endpoints were maximum tolerated dose(MTD),dose-limiting toxicity(DLT),and safety assessed by investigators.In the dose-expansion phase,the primary endpoint was objective response rate(ORR)assessed by investigators.Between September 25,2017 and October 15,2018,a total of 153 patients received WX-0593 treatment.Two dose-limiting toxicities(DLTs)including one grade 3 QT interval prolonged and one grade 2 chronic heart failure were reported at the dose of 300 mg in one patient.MTD was not reached.Overall,140 of the 152(92%)patients experienced treatment-related adverse events(TRAEs)and 35 of the 152(23%)patients had TRAEs≥grade 3.The overall ORR was 59.3%(32 of 54)for the dose-escalation phase and 56.6%(56 of 99)for the dose-expansion phase.For patients who were ALK-rearranged and ALK TKI naive,the ORR were 81.0%(17 of 21)in the dose-escalation phase and 76.3%(29 of 38)in the dose-expansion phase,and for patients who previously received crizotinib as the only ALK TKI,the ORR were 38.1%(8 of 21)and 45.7%(21 of 46)for the two phases,respectively.For patients who were ROS1-rearranged,the ORR were 30.0%(3 of 10)in the dose-escalation phase and 44.4%(4 of 9)in the dose-expansion phase.WX-0593 showed favorable safety and promising antitumor activity in advanced NSCLC patients with ALK or ROS1 rearrangement.展开更多
目的构建中西医结合专业学位护理研究生与专科护士并轨实践教学模式,并进行实证研究。方法随机抽取2016、2017级护理专业学位(master of nursing specialist,MNS)研究生43名、随机分为对照组21名和观察组22名。对照组采用传统临床护理...目的构建中西医结合专业学位护理研究生与专科护士并轨实践教学模式,并进行实证研究。方法随机抽取2016、2017级护理专业学位(master of nursing specialist,MNS)研究生43名、随机分为对照组21名和观察组22名。对照组采用传统临床护理实践模式进行培养,观察组采用中西医结合护理研究生专业学位与专科护士并轨的新实践教学模式进行培养。采用360°评价法联合OSCE考试评价比较两组MNS研究生临床实践效果。结果观察组除职业道德外的临床实践能力360°评价结果以及OSCE考试成绩优秀人数均优于对照组,差异有统计学意义(P<0.05)。结论中西医结合护理研究生专业学位与专科护士并轨实践教学模式有利于护理专业学位研究生的临床实践能力的提高,促进MNS培养目标的顺利实现。展开更多
Background:Previous studies have reported associations of specific maternal and paternal lifestyle factors with offspring’s cognitive development during early childhood.This study aimed to investigate the prospective...Background:Previous studies have reported associations of specific maternal and paternal lifestyle factors with offspring’s cognitive development during early childhood.This study aimed to investigate the prospective associations between overall parental lifestyle and offspring’s cognitive performance during adolescence and young adulthood in China.Methods:We included 2531 adolescents aged 10-15 years at baseline in 2010 from the China Family Panel Studies.A healthy parental lifestyle score(ranged 0-5)was constructed based on the following five modifiable lifestyle factors:Smoking,drinking,exercise,sleep,and diet.Generalized estimating equation models were used to examine the association between baseline parental healthy lifestyle scores and offspring’s fluid and crystallized intelligence in subsequent years(2012,2014,2016,and 2018).Results:Offspring in the top tertile of parental healthy lifestyle scores performed better in overall fluid intelligence(multivariable-adjusted β=0.53,95%confidence interval[CI]:0.29-0.77)and overall crystallized intelligence(multivariable-adjusted β=0.35,95%CI:0.16-0.54)than those in the bottom tertile of parental healthy lifestyle scores.The results were similar after further adjustment for the offspring’s healthy lifestyle scores and persisted across the subgroups of parental socioeconomic status.Additionally,maternal and paternal healthy lifestyle scores were independently associated with better offspring’s cognitive performance,with significant contribution observed for paternal never-smoking,weekly exercise,and diversified diet.When both parents and offspring adhered to a healthier lifestyle,we observed the highest level of the offspring’s overall crystallized intelligence.Conclusions:Our study indicates that parental adherence to a healthier lifestyle is associated with significantly better offspring’s cognitive performance during adolescence and early adulthood,regardless of socioeconomic status.These findings highlight the potential cognitive benefits of promo展开更多
基金This work was supported by the National Natural Science Foundation of China(nos.21822702,21820102008,92053109,and 21432002)the National Basic Research Program of China(2017YFA0505201 and 2019YFA0802201).
文摘The biological functions of the epitranscriptomic modification N^(6)-methyladenosine(m^(6)A)in plants are not fully understood.CPSF30-L is a predominant isoform of the polyadenylation factor CPSF30 and consists of CPSF30-S and an m^(6)A-binding YTH domain.Little is known about the biological roles of CPSF30-L and the molecular mechanism underlying its m^(6)A-binding function in alternative polyadenylation.Here,we charac-terized CPSF30-L as an Arabidopsis m^(6)A reader whose m^(6)A-binding function is required for the floral tran-sition and abscisic acid(ABA)response.We found that the m^(6)A-binding activity of CPSF30-L enhances the formation of liquid-like nuclear bodies,where CPSF30-L mainly recognizes m*A-modified far-upstream elements to control polyadenylation site choice.Deficiency of CPSF30-L lengthens the 3'untranslated region of three phenotypes-related transcripts,thereby accelerating their mRNA degradation and leading to late flowering and ABA hypersensitivity.Collectively,this study uncovers a new molecular mechanism for m^(6)A-driven phase separation and polyadenylation in plants.
基金This study(NCT03389815)was funded by Qilu Pharmaceutical Co.,Ltd.and also supported in part by China National Major Project for New Drug Innovation(2017ZX09304015)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS)(2016-I2M-1-001).
文摘WX-0593(Iruplinalkib)is a novel,highly selective oral ALK and ROS1 tyrosine kinase inhibitor(TKI).In this study,the safety,antitumor activity,and pharmacokinetics of WX-0593 were evaluated in advanced non-small cell lung cancer(NSCLC)patients with ALK or ROS1 rearrangement.In the dose-escalation phase and dose-expansion phase,patients were treated with WX-0593 until disease progression,unacceptable toxicity,or subject withdrawal.In the dose-escalation phase,the primary endpoints were maximum tolerated dose(MTD),dose-limiting toxicity(DLT),and safety assessed by investigators.In the dose-expansion phase,the primary endpoint was objective response rate(ORR)assessed by investigators.Between September 25,2017 and October 15,2018,a total of 153 patients received WX-0593 treatment.Two dose-limiting toxicities(DLTs)including one grade 3 QT interval prolonged and one grade 2 chronic heart failure were reported at the dose of 300 mg in one patient.MTD was not reached.Overall,140 of the 152(92%)patients experienced treatment-related adverse events(TRAEs)and 35 of the 152(23%)patients had TRAEs≥grade 3.The overall ORR was 59.3%(32 of 54)for the dose-escalation phase and 56.6%(56 of 99)for the dose-expansion phase.For patients who were ALK-rearranged and ALK TKI naive,the ORR were 81.0%(17 of 21)in the dose-escalation phase and 76.3%(29 of 38)in the dose-expansion phase,and for patients who previously received crizotinib as the only ALK TKI,the ORR were 38.1%(8 of 21)and 45.7%(21 of 46)for the two phases,respectively.For patients who were ROS1-rearranged,the ORR were 30.0%(3 of 10)in the dose-escalation phase and 44.4%(4 of 9)in the dose-expansion phase.WX-0593 showed favorable safety and promising antitumor activity in advanced NSCLC patients with ALK or ROS1 rearrangement.
文摘目的构建中西医结合专业学位护理研究生与专科护士并轨实践教学模式,并进行实证研究。方法随机抽取2016、2017级护理专业学位(master of nursing specialist,MNS)研究生43名、随机分为对照组21名和观察组22名。对照组采用传统临床护理实践模式进行培养,观察组采用中西医结合护理研究生专业学位与专科护士并轨的新实践教学模式进行培养。采用360°评价法联合OSCE考试评价比较两组MNS研究生临床实践效果。结果观察组除职业道德外的临床实践能力360°评价结果以及OSCE考试成绩优秀人数均优于对照组,差异有统计学意义(P<0.05)。结论中西医结合护理研究生专业学位与专科护士并轨实践教学模式有利于护理专业学位研究生的临床实践能力的提高,促进MNS培养目标的顺利实现。
基金supported by grants from the Zhejiang University Education Foundation Global Partnership Fund(to CZY)the Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province(No.2020E10004).
文摘Background:Previous studies have reported associations of specific maternal and paternal lifestyle factors with offspring’s cognitive development during early childhood.This study aimed to investigate the prospective associations between overall parental lifestyle and offspring’s cognitive performance during adolescence and young adulthood in China.Methods:We included 2531 adolescents aged 10-15 years at baseline in 2010 from the China Family Panel Studies.A healthy parental lifestyle score(ranged 0-5)was constructed based on the following five modifiable lifestyle factors:Smoking,drinking,exercise,sleep,and diet.Generalized estimating equation models were used to examine the association between baseline parental healthy lifestyle scores and offspring’s fluid and crystallized intelligence in subsequent years(2012,2014,2016,and 2018).Results:Offspring in the top tertile of parental healthy lifestyle scores performed better in overall fluid intelligence(multivariable-adjusted β=0.53,95%confidence interval[CI]:0.29-0.77)and overall crystallized intelligence(multivariable-adjusted β=0.35,95%CI:0.16-0.54)than those in the bottom tertile of parental healthy lifestyle scores.The results were similar after further adjustment for the offspring’s healthy lifestyle scores and persisted across the subgroups of parental socioeconomic status.Additionally,maternal and paternal healthy lifestyle scores were independently associated with better offspring’s cognitive performance,with significant contribution observed for paternal never-smoking,weekly exercise,and diversified diet.When both parents and offspring adhered to a healthier lifestyle,we observed the highest level of the offspring’s overall crystallized intelligence.Conclusions:Our study indicates that parental adherence to a healthier lifestyle is associated with significantly better offspring’s cognitive performance during adolescence and early adulthood,regardless of socioeconomic status.These findings highlight the potential cognitive benefits of promo
