Visible-Light-Promoted α-C(sp3)-H Amination of Ethers with Azoles and Amides.

A visible-light-induced highly efficient C(sp3)-H amination of ethers with amides and azoles has been presented under mild conditions via a nitrogen- and carbon-centered radical coupling process. This protocol successfully utilizes 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) and tert-butyl nitrite (TBN) as cocatalysts to deliver the aminated products of ethers under aerobic conditions. Notably, the developed reaction features the corresponding products in good yields (up to 93%) with a wide substrate scope. The mechanistic study indicates that C-N bond formation proceeds via a direct radical cross-coupling process. Preliminary biological activity analysis indicates that the resulting products have good and selective inhibitory activity on osteosarcoma (OS) cell lines and are promising for use as hits for drug discovery.

The association between alpha diversity of gut microbiota, neuroimaging markers and cognitive function in cerebral small vessel disease.

There is increasing recognition of gut microbial dysbiosis in cerebral small vessel disease (CSVD). The altered diversity in a single ecosystem - alpha diversity index of gut microbiota has attracted wide attention. Our study aims to determine whether the alpha diversity index differs among healthy control (HC), CSVD with and without cognitive impairment. Moreover, we investigate the correlation between the alpha diversity index, neuroimaging markers, and cognitive function. We recruited 40 HC, 43 CSVD patients without cognitive impairment (CSVD-NCI), and 35 CSVD patients with mild cognitive impairment (CSVD-MCI). Clinical and neuropsychological assessments, MRI scanning, and gut microbiota analysis were performed on all participants. The alpha diversity indexes Chao1 and Shannon were calculated to evaluate community richness and diversity in a sample, respectively. Individual neuroimaging markers of CSVD and the CSVD burden score were also evaluated. A significantly lower level of Chao 1 rather than the Shannon index was observed in the CSVD subgroups than in the HC group. The level of the Chao 1 index was negatively correlated with both CMB counts, a neuroimaging characteristic of CSVD, and CSVD burden score in patients with CSVD. Additionally, the Chao 1 index has been associated with general cognitive function, information processing speed, and language function in patients with CSVD. Remarkably, the increased CSVD burden score mediated the effects of decreased levels of Chao 1 on information processing speed and language function. Hence, the alterations in species richness may be associated with CSVD-related cognitive impairment and mediated by CSVD neuroimaging markers.

YKL-40 as a novel biomarker related to white matter damage and cognitive impairment in patients with cerebral small vessel disease.

YKL-40 is a novel neuroinflammatory marker associated with white matter damage and cognitive dysfunction. 110 CSVD patients, including 54 with mild cognitive impairment (CSVD-MCI), 56 with no cognitive impairment (CSVD-NCI), and 40 healthy controls (HCs) underwent multimodal magnetic resonance examination, serum YKL-40 level detection and cognitive function assessment to investigate the association between YKL-40 and white matter damage and cognitive impairment in cerebral small vessel disease (CSVD) patients. White matter hyperintensities volume was calculated using the Wisconsin White Matter Hyperintensity Segmentation Toolbox (W2MHS) for white matter macrostructural damage evaluation. For white matter microstructural damage evaluation, fractional anisotropy (FA) and mean diffusivity (MD) indices of the region of interest were analyzed based on diffusion tensor imaging (DTI) images using the Tract-Based Spatial Statistics (TBSS) pipeline. The serum YKL-40 level of CSVD was significantly higher than those of HCs, and the CSVD-MCI was higher than in HCs and CSVD-NCI. Furthermore, serum YKL-40 provided high diagnostic accuracy for CSVD and CSVD-MCI. The macroscopic and microstructure of white matter in CSVD-NCI and CSVD-MCI patients indicated different degrees of damage. Disruption of white matter macroscopic and microstructure was significantly associated with YKL-40 levels and cognition deficits. Moreover, the white matter damage mediated the associations between the increased serum YKL-40 levels and cognitive impairment. Our findings demonstrated that YKL-40 might be a potential biomarker of white matter damage in CSVD, whereas white matter damage was associated with cognitive impairment. Serum YKL-40 measurement provides complementary information regarding the neural mechanism of CSVD and its associated cognitive impairment.

Altered serum amyloid beta and cerebral perfusion and their associations with cognitive function in patients with subcortical ischemic vascular disease.

Subcortical ischemic vascular disease (SIVD) is one of the important causes of cognitive dysfunction, altered amyloid-beta (Aß) and cerebral perfusion may be involved in the pathophysiological mechanism of SIVD and are closely related to cognitive function. We aimed to investigate altered serum Aß and cerebral perfusion in patients with SIVD and their correlation with cognitive function. Seventy-four healthy controls (HCs) and 74 SIVD patients, including 38 SIVD patients with no cognitive impairment (SIVD-NCI) and 36 SIVD patients with mild cognitive impairment (SIVD-MCI) underwent the measurement of serum Aß40 and Aß42 levels, pseudo-continuous arterial spin labeling MRI scanning, and cognitive evaluation. Compared to the healthy controls (HCs), the level of serum Aß40 and Aß40/42 ratio increased and Aß42 decreased in SIVD patients. The serum Aß40 level and Aß40/42 ratio in patients with SIVD-MCI were significantly higher than those in the HCs and SIVD-NCI, and the level of Aß42 in the SIVD-MCI was lower than the HCs. In addition, the serum Aß40/42 ratio provided high diagnostic accuracy for SIVD and SIVD-MCI, it was further identified as an independent risk factor for cognitive impairment. Patients with SIVD-NCI and SIVD-MCI exhibited both increased and decreased cerebral blood flow (CBF) in regional. The Aß40/42 ratio was associated with global CBF, while altered global and regional CBF was associated with cognitive deficits. In addition, white matter hyperintensities volume (WMHV) correlated with Aß40/42 ratio, CBF, and cognition. The relationship between Aß40/42 ratio and cognition was partially mediated by altered CBF. Based on these results, we conclude that the serum Aß40/42 ratio may be a potential biomarker that can complement current methods for the prediction and diagnosis of cognitive impairment in SIVD patients. In addition, serum Aß may play a role in cognitive function by regulating CBF, which provides new insights into the intervention, treatment, and prevention of cognitive impairment in SIVD.