Astroglial GJC plays a significant role in MCAO-induced remote hippocampal damage and cognitive impairment. It might be possible to improve the cognition in patients with MCAO by manipulating interastrocytic communication via the gap junction channels.

Glucokinase (GK) is an important enzyme for regulating blood glucose levels and a potentially attractive target for diabetes of the young type 2 and persistent hyperinsulinemic hypoglycemia of infancy. To characterize the conformational transition of GK from the closed state to the superopen state, a series of conventional molecular dynamics (MD) and target MD (TMD) simulations were performed on both the wild-type enzyme and its mutants. Two 10-ns conventional MD simulations showed that, although the allosteric site of GK is Ϸ20 Å away from the active site, the activator is able to enhance the activity of the enzyme through conformational restriction. Fourteen TMD simulations on GK and five of its mutants revealed a reliably conformational transition pathway. The overall conformational transition includes three stages, and three likely stable intermediate states were identified by free energy scanning for the snapshots throughout the pathway. The conformational transition feature revealed by our TMD simulations rationalized several important mutagenesis and kinetic data. Remarkably, the TMD simulations predicted that Y61S, I159A, A201R, V203E, and V452S mutations, which have not been investigated so far, may facilitate the opening process of GK. These predictions also have been verified by mutagenesis and kinetic analyses in this study. These observations are beneficial to understanding the mechanism of GK regulation and designing the compounds for treating metabolic diseases. molecular dynamics ͉ mutagenesis

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AimCerebral venous sinus thrombosis (CVST) is a less common cerebrovascular disease that predominantly affects young patients. The incidence of CVST is 2–5/10 000 000/year, accounting for 0.5%–1% of all stroke. To reduce mortality and morbidity associated with CVST, Chinese Stroke Association commissioned the authors to write the current guideline on the management of CVST.MethodsPubMed (MEDLINE), CNKI and Wanfang database were searched for studies related to CVST from 1 January 1990 to 31 July 2019. Data were synthesised by evidence tables. Each recommendation was fully discussed by the writing group members and reviewed by Chinese Stroke Association Stroke Fellow Committees. Levels of evidence grading algorithm of Chinese Stroke Association was used to grade each recommendation.ResultsThis guideline mainly focuses on the diagnostic evaluation, therapeutic strategies and secondary prevention of CVST. CT/CTV and MRI/MRV are recommended in the initial imaging evaluation of patients with suspected CVST. Anticoagulation therapy with low-molecular weight heparin should be initiated in patients with CVST immediately. After the acute stage, warfarin is recommended for 3–6 months to prevent the recurrence of CVST and other venous thromboembolic events.ConclusionsThe guideline summarises the current evidence regarding the management of CVST, and provides references for diagnosis, treatment and secondary prevention of CVST in China.

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Background Previous studies have found widespread impairment of white matter (WM) integrity and disruption of structural network connectivity in cerebral small‐vessel disease, but have not evaluated these changes jointly in nondemented patients. Purpose To jointly investigate the microstructural impairment of WM and the related alterations of structural network topology in nondemented cerebral small‐vessel disease (CSVD‐ND). Study Type Prospective. Population Thirty‐seven CSVD‐ND patients and 34 elderly controls, who were age‐, sex‐, and education‐matched. Field Strength/Sequence 3.0T/diffusion tensor imaging (DTI). Assessment Clinical characteristics, lacunar infarct, and white matter hyperintensity (WMH) was assessed. A multiatlas likelihood fusion (MALF) algorithm was used for DTI‐based brain segmentation and network node defining. Then the alterations of WM integrity and structural network topology were investigated jointly. Statistical Tests Student's t‐test, chi‐square test, Mann–Whitney U‐test, linear regression, Pearson correlation, and multiple comparison correction. Results Decreased fractional anisotropy and increased trace values were observed in predefined structures (P < 0.05, familywise error rate‐corrected), including major commissural fibers, projection fibers, and some association fibers. Topologically, both groups showed small‐worldness. CSVD‐ND patients showed reduced global and local efficiency (P < 0.001). Despite widespread impairment of WM integrity, CSVD‐ND patients only showed reduced nodal efficiency in the right superior occipital gyrus and the right lingual gyrus (P < 0.05, familywise error rate‐corrected). The nodal local efficiency of the right precuneus was associated with the processing speed after adjusting the effect of lacunar infarct and WMH (r = –0.499, P = 0.038). Data Conclusion WM integrity was widely impaired in nondemented CSVD patients but structural network connectivity was relatively preserved. DTI may potentially provide information for the pathophysiology of CSVD in the nondemented phase. Level of Evidence: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:1162–1169.