Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregati...Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregation,and alleviates scopolamine-induced cognitive impairment,similar to the phase Ⅲ clinical drug resveratrol.In this study,we established a mouse model of Alzheimer's disease via intracerebroventricular injection of fibrillar amyloid-β to investigate the effect of D30 on fibrillar amyloid-β-induced neuropathology.Our results showed that D30 alleviated fibrillar amyloid-β-induced cognitive impairment,promoted fibrillar amyloid-β clearance from the hippocampus and cortex,suppressed oxidative stress,and inhibited activation of microglia and astrocytes.D30 also reversed the fibrillar amyloid-β-induced loss of dendritic spines and synaptic protein expression.Notably,we demonstrated that exogenous fibrillar amyloid-βintroduced by intracerebroventricular injection greatly increased galectin-3 expression levels in the brain,and this increase was blocked by D30.Considering the role of D30 in clearing amyloid-β,inhibiting neuroinflammation,protecting synapses,and improving cognition,this study highlights the potential of galectin-3 as a promising treatment target for patients with Alzheimer's disease.展开更多
The Ritter-type reaction, without relying on a pre-installed functional group, is a highly efficient tool forthe construction of amides. However, the intrinsic chemo-selectivity that determines the generation ofamides...The Ritter-type reaction, without relying on a pre-installed functional group, is a highly efficient tool forthe construction of amides. However, the intrinsic chemo-selectivity that determines the generation ofamides or byproducts limits the efficiency and yield of the reaction. From 68 different types of hydrates,we found that a coordinatively unsaturated inorganic salt hydrate, MgSO_(4)·2H_(2)O, controlled chemoselectivity and eliminated the shortcomings of other synthesis approaches. To rationalize the differencesin selectivity of inorganic salt hydrates, we analyzed their corresponding water content, alkalinity, anions,and cations. MgSO_(4)·2H_(2)O was used with diverse scaffolds and C–H oxygenations, which demonstratedits generality in synthetic utility. Because it is readily available and it significantly improves yield, we expectthat MgSO_(4)·2H_(2)O will have broad application for Ritter-type reactions.展开更多
基金supported by the Research Foundation for Talented Scholars of Fujian Medical University,No.XRCZX2018014(to DZ)Startup Fund for Scientific Research,Fujian Medical University,No.2019QH1017(to CW)the Natural Science Foundation of Fujian Province,China,Nos.2021J01693(to DZ),2021J02032(to ZCY)。
文摘Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregation,and alleviates scopolamine-induced cognitive impairment,similar to the phase Ⅲ clinical drug resveratrol.In this study,we established a mouse model of Alzheimer's disease via intracerebroventricular injection of fibrillar amyloid-β to investigate the effect of D30 on fibrillar amyloid-β-induced neuropathology.Our results showed that D30 alleviated fibrillar amyloid-β-induced cognitive impairment,promoted fibrillar amyloid-β clearance from the hippocampus and cortex,suppressed oxidative stress,and inhibited activation of microglia and astrocytes.D30 also reversed the fibrillar amyloid-β-induced loss of dendritic spines and synaptic protein expression.Notably,we demonstrated that exogenous fibrillar amyloid-βintroduced by intracerebroventricular injection greatly increased galectin-3 expression levels in the brain,and this increase was blocked by D30.Considering the role of D30 in clearing amyloid-β,inhibiting neuroinflammation,protecting synapses,and improving cognition,this study highlights the potential of galectin-3 as a promising treatment target for patients with Alzheimer's disease.
基金support from the Research Foundation for Talented Scholars of Fujian Medical University(grant number:XRCZX2018014)the Joint Funds for the Innovation of Science and Technology,Fujian province(grant number:2018Y9072)the Natural Science Foundation of Fujian Province,China(grant number:2021J01693).
文摘The Ritter-type reaction, without relying on a pre-installed functional group, is a highly efficient tool forthe construction of amides. However, the intrinsic chemo-selectivity that determines the generation ofamides or byproducts limits the efficiency and yield of the reaction. From 68 different types of hydrates,we found that a coordinatively unsaturated inorganic salt hydrate, MgSO_(4)·2H_(2)O, controlled chemoselectivity and eliminated the shortcomings of other synthesis approaches. To rationalize the differencesin selectivity of inorganic salt hydrates, we analyzed their corresponding water content, alkalinity, anions,and cations. MgSO_(4)·2H_(2)O was used with diverse scaffolds and C–H oxygenations, which demonstratedits generality in synthetic utility. Because it is readily available and it significantly improves yield, we expectthat MgSO_(4)·2H_(2)O will have broad application for Ritter-type reactions.
