Transcriptional patterns of brain structural abnormalities in CSVD-related cognitive impairment

BackgroundBrain structural abnormalities have been associated with cognitive impairment in individuals with small cerebral vascular disease (CSVD). However, the molecular and cellular factors making the different brain structural regions more vulnerable to CSVD-related cognitive impairment remain largely unknown.Materials and methodsVoxel-based morphology (VBM) was performed on the structural magnetic resonance imaging data of 46 CSVD-related cognitive impairment and 73 healthy controls to analyze and compare the gray matter volume (GMV) between the 2 groups. Transcriptome-neuroimaging spatial correlation analysis was carried out in combination with the Allen Human Brain Atlas to explore gene expression profiles associated with changes in cortical morphology in CSVD-related cognitive impairment.ResultsVBM analysis demonstrated extensive decreased GMV in CSVD-related cognitive impairment in the bilateral temporal lobe and thalamus, especially the hippocampus, thalamus, parahippocampus, and fusiform, and the left temporal lobe showed a more severe atrophy than the right temporal lobe. These brain structural alterations were closely related to memory and executive function deficits in CSVD-related cognitive impairment. Furthermore, a total of 1,580 genes were revealed to be significantly associated with regional change in GMV. The negatively and positively GMV-linked gene expression profiles were mainly enriched in RNA polymerase II, catalytic activity acting on a nucleic acid, aminoacyltransferase activity, axonogenesis, Golgi membrane, and cell junction organization.ConclusionOur findings suggest that brain morphological abnormalities in CSVD-related cognitive impairment are linked to molecular changes involving complex polygenic mechanisms, highlighting the interplay between genetic influences and structural alterations relevant to CSVD-related cognitive impairment

Alteration and clinical potential in gut microbiota in patients with cerebral small vessel disease

BackgroundCerebral small vessel disease (CSVD) is a cluster of microvascular disorders with unclear pathological mechanisms. The microbiota-gut-brain axis is an essential regulatory mechanism between gut microbes and their host. Therefore, the compositional and functional gut microbiota alterations lead to cerebrovascular disease pathogenesis. The current study aims to determine the alteration and clinical value of the gut microbiota in CSVD patients.MethodsSixty-four CSVD patients and 18 matched healthy controls (HCs) were included in our study. All the participants underwent neuropsychological tests, and the multi-modal magnetic resonance imaging depicted the changes in brain structure and function. Plasma samples were collected, and the fecal samples were analyzed with 16S rRNA gene sequencing.ResultsBased on the alpha diversity analysis, the CSVD group had significantly decreased Shannon and enhanced Simpson compared to the HC group. At the genus level, there was a significant increase in the relative abundances of Parasutterella, Anaeroglobus, Megasphaera, Akkermansia, Collinsella, and Veillonella in the CSVD group. Moreover, these genera with significant differences in CSVD patients revealed significant correlations with cognitive assessments, plasma levels of the blood-brain barrier-/inflammation-related indexes, and structural/functional magnetic resonance imaging changes. Functional prediction demonstrated that lipoic acid metabolism was significantly higher in CSVD patients than HCs. Additionally, a composite biomarker depending on six gut microbiota at the genus level displayed an area under the curve of 0.834 to distinguish CSVD patients from HCs using the least absolute shrinkage and selection operator (LASSO) algorithm.ConclusionThe evident changes in gut microbiota composition in CSVD patients were correlated with clinical features and pathological changes of CSVD. Combining these gut microbiota using the LASSO algorithm helped identify CSVD accurately

Se(IV) chemistry in bioconjugation : small and single-atom modifications on tyrosine residues by a rational-designed selenoxide

Post-translational modifications are generally small but important because they substantially broaden protein function. Chemical protein modification can further expand the structural and functional diversity of modifications, but the introduction of small structural perturbations to proteins by chemical methods is difficult, due to the requirement for selectivity and the stringent restrictions on reaction conditions inherent to biological systems. Conventional protein modification methods typically rely on the combination of reactive residues and mild reagents to control the selectivity, which, however, creates a large, inconvertible substituent on the modified residue. While the small modification can be accomplished with small, reactive molecules, the control of selectivity can be challenging. The method presented here uses a rationally designed selenoxide reagent to form a versatile selenonium linchpin on tyrosine residues of peptides and small proteins, which can be subsequently converted to a series of small and single-atom substituents. Key to the design is the interplay of the water-resistant, intramolecular chalcogen and hydrogen bonds in the selenoxide, which enables the selective electrophilic aromatic substitution of tyrosine residues to form a weak C(sp2)–Se bond that can engage for further transformations. This new method extends the Se(IV) chemistry to the C–H functionalization of biomolecules and provides new insights into the use of heavy main-group elements in the field of bioconjugation

Master cylinder pressure reduction logic for cooperative work between electro-hydraulic brake system and anti-lock braking system based on speed servo system

As one feasible solution of brake-by-wire systems, electro-hydraulic brake system has been made available into production recently. Electro-hydraulic brake system must work cooperatively with the hydraulic control unit of anti-lock braking system. Due to the mechanical configuration involving electric motor + reduction gear, the electro-hydraulic brake system could be stiffer in contrast to a conventional vacuum booster. That is to say, higher pressure peaks and pressure oscillation could occur during an active anti-lock braking system control. Actually, however, electro-hydraulic brake system and anti-lock braking system are produced by different suppliers considering brake systems already in production. Limited signals and operations of anti-lock braking system could be provided to the supplier of electro-hydraulic brake system. In this work, a master cylinder pressure reduction logic is designed based on speed servo system for active pressure modulation of electro-hydraulic brake system under the anti-lock braking system–triggered situation. The pressure reduction logic comprises of model-based friction compensation, feedforward and double closed-loop feedback control. The pressure closed-loop is designed as the outer loop, and the motor rotation speed closed-loop is drawn into the inner loop of feedback control. The effectiveness of the proposed controller is validated by vehicle experiment in typical braking situations. The results show that the controller remains stable against parameter uncertainties in extreme condition such as low temperature and mismatch of friction model. In contrast to the previous methods, the comparison results display the improved dynamic cooperative performance of electro-hydraulic brake system and anti-lock braking system and robustness. </jats:p

Substrate-Controlled Transformation of Azobenzenes to Indazoles and Indoles via Rh(III)-Catalysis

Rh­(III)-catalyzed substrate-controlled transformation of azobenzenes to indazoles and 2-acyl (NH) indoles is achieved via C–H functionalization. Generally, good functional groups tolerance, satisfying yields, and excellent regio-selectivity are achieved in this reaction. Mechanistically, the reaction with acrylates undergoes β-hydride elimination, while the reaction with vinyl ketones or acrylamides undergoes nucleophilic addition. Copper acetate was supposed to play different roles in the β-hydride elimination to furnish indazoles and nucleophilic addition of C–Rh bond to deliver 2-acyl (NH) indoles