The privileged C_(2)-symmetric rigid phenol-type ligand is more attractive but challenging in asymmetric catalysis.Herein,we designed and synthesized a class of rigid-featured chiral tridentate Phenol-2NO ligands,that...The privileged C_(2)-symmetric rigid phenol-type ligand is more attractive but challenging in asymmetric catalysis.Herein,we designed and synthesized a class of rigid-featured chiral tridentate Phenol-2NO ligands,that incorporate the advantages of both the phenol skeleton and pyrroloimidazolone-based N-oxide moiety,from readily available L-prolinamides in operationally simple two steps and up to 44%overall yield.More importantly,using an achiral quinoline derivative as an additive,the newly developed Phenol-2NO ligand could serve as the anioic ligand upon deprotonative activation to coordinate to Zn(II)to form a highly enantioselective catalyst for the asymmetric Michael-type Friedel-Crafts alkylation reaction of indoles with 2,3-dioxopyrrolidines.Excellent yields(up to 90%)and high enantioselectivities(up to 99%ee)are obtained for a wide range of substrates under mild conditions.Experiments and DFT calculations revealed the reaction mechanism and the origins of the enantioselectivity.This also represented the first activation of phenol-type ligand/metal complex by an achiral organic base as the additive in asymmetric catalysis.展开更多
Background This study aimed to explore the relationship of 25-hydroxyvitamin D[25(OH)D]in three trimesters and at birth with neurodevelopment at 24 months of age.Methods From 2013 to 2016,pregnant women from the Shang...Background This study aimed to explore the relationship of 25-hydroxyvitamin D[25(OH)D]in three trimesters and at birth with neurodevelopment at 24 months of age.Methods From 2013 to 2016,pregnant women from the Shanghai Birth Cohort in China were recruited for the study.Altogether,649 mother-infant pairs were included.Serum 25(OH)D was measured with mass spectrometry in three trimesters,and cord blood was divided into deficiency(<20 and<12 ng/mL,respectively),insufficiency(20–30 and 12–20 ng/mL,respectively),and sufficiency(≥30 and≥20 ng/mL,respectively).Bayley-III scale was used to assess cognitive,language,motor,social-emotional,and adaptive behavior development at 24 months of age.The Bayley-III scores were grouped into quartiles,and scores within the lowest quartile were defined as suboptimal development.Results After adjusting for confounding factors,cord blood 25(OH)D in the sufficient group was positively correlated with cognitive[β=11.43,95%confidence interval(CI)=5.65–17.22],language(β=6.01,95%CI=1.67–10.3),and motor scores(β=6.43,95%CI=1.73–11.1);cord blood 25(OH)D in the insufficient group was also positively correlated with cognitive scores(β=9.42,95%CI=3.74–15.11).Additionally,sufficient vitamin D status in the four periods and persistent 25(OH)D≥30 ng/mL throughout pregnancy were associated with a lower risk of suboptimal cognitive development in adjusted models,although the effects were attenuated after applying the false discovery rate adjustment.Conclusions Cord blood 25(OH)D≥12 ng/mL has a significant positive association with cognitive,language,and motor development at 24 months of age.Sufficient vitamin D status in pregnancy might be a protective factor for suboptimal neurocognition development at 24 months of age.展开更多
Background： Placebo was defined as any therapy that is used for its nonspecific psychological and physiologic effect but has no specific pharmacologic impact on the condition being treated. Besides medication therapi...Background： Placebo was defined as any therapy that is used for its nonspecific psychological and physiologic effect but has no specific pharmacologic impact on the condition being treated. Besides medication therapies, studies have found that the optimal dietary approach as well as physical activity and education are useful to control hyperglycemia in patients with type 2 diabetes （T2DM）. The aim of this study was to evaluate the placebo effects ofantidiabetic therapies in Asian and Caucasian T2DM patients and make a comparison between the two ethnicities. Methods： A search using the MEDLINE database, EMBASE, and Cochrane Database was performed, from when recording began until December 2016. The main concepts searched in English were sulfonylurea （SU）; alpha glucosidase inhibitors （AGI）; metfornlin （MET）; thiazolidinediones （TZD）; dipeptidyl peptidase-4 inhibitors （DPP-4i）; sodium-glucose cotransporter 2 inhibitors （SGLT2i）; glucagon-like peptide- 1 receptor agonist （GLP- 1RA）; type 2 diabetes （T2DM）; placebo controlled; and randomized controlled trials. Using the Cochrane instrument, we evaluated the adequacy of randomization, allocation concealment procedures, and blinding. Results： This study included 63 studies with a total of 7096 Asian patients involved and 262 studies with a total of 27,477 Caucasian patients involved. In Caucasian population, the use of placebo led to significant redtlctions of glycosylated hemoglobin （HbAlc）, -0.683% （P - 0.008） in SU monotherapy treatment, -0.193% （P = 0.001） in DPP-4i treatment, and -0.230% （P 〈 0.001） in SGLT2i treatment, respectively. In Asian population, the use of placebo resulted in significant decreases ofHbA1c, 0.162% （P= 0.012） in DPP-4i treatment and -0.269% （P =0.028） in GLP-1RA add-on therapy, respectively. The placebo also significantly reduced body weight. In Caucasian population, placebo use resulted in 0.833 kg （P = 0.006） weight loss by SU treatment and 0.953 kg （P = 0.006） weight loss by GLP-I RA treatment. In Asian population, the placebo led to a weight change of0.612 kg （P 〈 0.001 ） by GLP-1 RA analog treatment. The changes of HbA I c and weight due to the placebo effect in other treatments were not significant in both Asian and Caucasian population. Comparisons of the placebo effect on HbAlc change and weight change in each treatment group indicated that no significant difference was found between Asian and Caucasian population. Conclusions： The overall differences of the placebo effect on HbAlc changes as well as on body weight changes were not significant between Asian and Caucasian T2DM patients. The placebo effect on HbA- 1 c changes and weight changes was not associated with baseline age, gender, baseline body mass index, baseline HbAlc, duration of diabetes, or study duration.展开更多
基金We thank financial support from NSFC(22061006)Guizhou Provincial Program(GCC[2023]047,GCC[2023]078,ZK[2023]043,ZK[2022]144,ZK[2022]480).
文摘The privileged C_(2)-symmetric rigid phenol-type ligand is more attractive but challenging in asymmetric catalysis.Herein,we designed and synthesized a class of rigid-featured chiral tridentate Phenol-2NO ligands,that incorporate the advantages of both the phenol skeleton and pyrroloimidazolone-based N-oxide moiety,from readily available L-prolinamides in operationally simple two steps and up to 44%overall yield.More importantly,using an achiral quinoline derivative as an additive,the newly developed Phenol-2NO ligand could serve as the anioic ligand upon deprotonative activation to coordinate to Zn(II)to form a highly enantioselective catalyst for the asymmetric Michael-type Friedel-Crafts alkylation reaction of indoles with 2,3-dioxopyrrolidines.Excellent yields(up to 90%)and high enantioselectivities(up to 99%ee)are obtained for a wide range of substrates under mild conditions.Experiments and DFT calculations revealed the reaction mechanism and the origins of the enantioselectivity.This also represented the first activation of phenol-type ligand/metal complex by an achiral organic base as the additive in asymmetric catalysis.
基金supported by the National Key Research and Development Program of China(No.2022YFC2705203)the National Natural Science Foundation of China(No.81773411)+4 种基金the Special Program for Women and Children Health(No.2020YJZX0212)Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(No.20152220)the Cultivation Project of Clinical Research from SCMC(No.LY-SCMC2020-06)Shanghai Children’s Health Services Capacity Program(No.GDEK201708)the Key Program for Clinical Nutrition(No.2019ZB0103)from Shanghai Municipal Health Commission.
文摘Background This study aimed to explore the relationship of 25-hydroxyvitamin D[25(OH)D]in three trimesters and at birth with neurodevelopment at 24 months of age.Methods From 2013 to 2016,pregnant women from the Shanghai Birth Cohort in China were recruited for the study.Altogether,649 mother-infant pairs were included.Serum 25(OH)D was measured with mass spectrometry in three trimesters,and cord blood was divided into deficiency(<20 and<12 ng/mL,respectively),insufficiency(20–30 and 12–20 ng/mL,respectively),and sufficiency(≥30 and≥20 ng/mL,respectively).Bayley-III scale was used to assess cognitive,language,motor,social-emotional,and adaptive behavior development at 24 months of age.The Bayley-III scores were grouped into quartiles,and scores within the lowest quartile were defined as suboptimal development.Results After adjusting for confounding factors,cord blood 25(OH)D in the sufficient group was positively correlated with cognitive[β=11.43,95%confidence interval(CI)=5.65–17.22],language(β=6.01,95%CI=1.67–10.3),and motor scores(β=6.43,95%CI=1.73–11.1);cord blood 25(OH)D in the insufficient group was also positively correlated with cognitive scores(β=9.42,95%CI=3.74–15.11).Additionally,sufficient vitamin D status in the four periods and persistent 25(OH)D≥30 ng/mL throughout pregnancy were associated with a lower risk of suboptimal cognitive development in adjusted models,although the effects were attenuated after applying the false discovery rate adjustment.Conclusions Cord blood 25(OH)D≥12 ng/mL has a significant positive association with cognitive,language,and motor development at 24 months of age.Sufficient vitamin D status in pregnancy might be a protective factor for suboptimal neurocognition development at 24 months of age.
文摘Background： Placebo was defined as any therapy that is used for its nonspecific psychological and physiologic effect but has no specific pharmacologic impact on the condition being treated. Besides medication therapies, studies have found that the optimal dietary approach as well as physical activity and education are useful to control hyperglycemia in patients with type 2 diabetes （T2DM）. The aim of this study was to evaluate the placebo effects ofantidiabetic therapies in Asian and Caucasian T2DM patients and make a comparison between the two ethnicities. Methods： A search using the MEDLINE database, EMBASE, and Cochrane Database was performed, from when recording began until December 2016. The main concepts searched in English were sulfonylurea （SU）; alpha glucosidase inhibitors （AGI）; metfornlin （MET）; thiazolidinediones （TZD）; dipeptidyl peptidase-4 inhibitors （DPP-4i）; sodium-glucose cotransporter 2 inhibitors （SGLT2i）; glucagon-like peptide- 1 receptor agonist （GLP- 1RA）; type 2 diabetes （T2DM）; placebo controlled; and randomized controlled trials. Using the Cochrane instrument, we evaluated the adequacy of randomization, allocation concealment procedures, and blinding. Results： This study included 63 studies with a total of 7096 Asian patients involved and 262 studies with a total of 27,477 Caucasian patients involved. In Caucasian population, the use of placebo led to significant redtlctions of glycosylated hemoglobin （HbAlc）, -0.683% （P - 0.008） in SU monotherapy treatment, -0.193% （P = 0.001） in DPP-4i treatment, and -0.230% （P 〈 0.001） in SGLT2i treatment, respectively. In Asian population, the use of placebo resulted in significant decreases ofHbA1c, 0.162% （P= 0.012） in DPP-4i treatment and -0.269% （P =0.028） in GLP-1RA add-on therapy, respectively. The placebo also significantly reduced body weight. In Caucasian population, placebo use resulted in 0.833 kg （P = 0.006） weight loss by SU treatment and 0.953 kg （P = 0.006） weight loss by GLP-I RA treatment. In Asian population, the placebo led to a weight change of0.612 kg （P 〈 0.001 ） by GLP-1 RA analog treatment. The changes of HbA I c and weight due to the placebo effect in other treatments were not significant in both Asian and Caucasian population. Comparisons of the placebo effect on HbAlc change and weight change in each treatment group indicated that no significant difference was found between Asian and Caucasian population. Conclusions： The overall differences of the placebo effect on HbAlc changes as well as on body weight changes were not significant between Asian and Caucasian T2DM patients. The placebo effect on HbA- 1 c changes and weight changes was not associated with baseline age, gender, baseline body mass index, baseline HbAlc, duration of diabetes, or study duration.
