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Receptor-interacting serine/threonine protein kinase 2 (RIPK2) has been demonstrated to be a promising target for treating inflammatory diseases. Herein, we describe the discovery and optimization of a series of RIPK2 inhibitors derived from an FLT3 inhibitor, CHMFL-FLT3-165. Compound

To identify abnormal functional connectivity of the default mode network in cingulate gyrus epilepsy, which may yield new information about the default mode network and suggest a new cingulate gyrus epilepsy biomarker. Fifteen patients with cingulate gyrus epilepsy (mean age = 21 years) and 15 healthy controls (mean age = 24 years) were studied in the resting state using magnetoencephalography. Twelve brain areas of interest in the default mode network were extracted and investigated with multifrequency signals that included alpha (α, 8–13 Hz), beta (β, 14–30 Hz), and gamma (γ, 31–80 Hz) band oscillations. Patients with cingulate gyrus epilepsy had significantly greater connectivity in all three frequency bands (α, β, γ). A frequency‐specific elevation of functional connectivity was found in patients compared to controls. The greater functional connectivity in the γ band was significantly more prominent than that of the α and β bands. Patients with cingulate gyrus epilepsy and controls differed significantly in functional connectivity between the left angular gyrus and left posterior cingulate cortex in the α, β, and γ bands. The results of the node degree analysis were similar to those of the functional connectivity analysis. Our findings reveal for the first time that brain activity in the γ band may play a key role in the default mode network in cingulate gyrus epilepsy. Altered functional connectivity of the left angular gyrus and left posterior cingulate cortex may be a new biomarker for cingulate gyrus epilepsy.

In this study, a novel batch of indazole containing 1,2,3-triazole agents were designed and synthesized. The antiproliferative activity of target compounds in four human cancer cells, PC-3 (human prostate cancer cell), MCF-7 (human breast cancer cell), HepG-2 (human hepatoma cell) and MGC-803 (human gastric cancer cell), was evaluated by thiazole blue (MTT). In the antiproliferative activity screening, we were surprised to find that most compounds have specific cytotoxicity to PC-3 cancer cells. In particular, 9a has an IC

Objective. Repetitive transcranial magnetic stimulation (rTMS) emerges as a useful therapy for autism spectrum disorder (ASD) clinically. Whereas the mechanisms of action of rTMS on ASD are not fully understood, and no biomarkers until now are available to reliably predict the follow-up rTMS efficacy in clinical practice. Approach. In the current work, the temporal variability was investigated in resting-state electroencephalogram of ASD patients, and the nonlinear complexity of related time-varying networks was accordingly evaluated by fuzzy entropy. Main results. The results showed the hyper-variability in the resting-state networks of ASD patients, while three week rTMS treatment alleviates the hyper fluctuations occurring in the frontal-parietal and frontal-occipital connectivity and further contributes to the ameliorative ASD symptoms. In addition, the changes in variability network properties are closely correlated with clinical scores, which further serve as potential predictors to reliably track the long-term rTMS efficacy for ASD. Significance. The findings consistently demonstrated that the temporal variability of time-varying networks of ASD patients could be modulated by rTMS, and related variability properties also help predict follow-up rTMS efficacy, which provides the potential for formulating individualized treatment strategies for ASD (ChiCTR2000033586).

Until recently, paroxysmal hypnogenic dyskinesia was thought to be a rare movement disorder characterized by intermittent dystonia and/or choreoathetoid movements that occur during non-rapid eye movement sleep, with consciousness preserved once the patient is awakened during the episodes. Recent investigations have revealed that most, but not all, paroxysmal hypnogenic dyskinesia cases are actually frontal lobe epilepsy. Here, we present two cases with paroxysmal choreoathetoid movements on waking during non-rapid eye movement sleep. Although they did not respond to antiepileptic drugs, they did respond to antidopaminergic drugs. This supports the opinion that non-epileptic paroxysmal hypnogenic dyskinesia does exist.

Background & Aims Levels of bile acid metabolic enzymes and membrane transporters have been reported to change in cholestasis. These alterations (e.g. CYP7A1 repression and MRP4 induction) are thought to be adaptive responses that attenuate cholestatic liver injury. However, the molecular mechanisms of these adaptive responses in human obstructive cholestasis due to gallstone biliary obstruction remain unclear. Methods We collected liver samples from cholestatic patients with biliary obstruction due to gallstones and from control patients without liver disease (n = 22 per group). The expression levels of bile acid synthetic and detoxification enzymes, membrane transporters, and the related nuclear receptors and transcriptional factors were measured. Results The levels of bile acid synthetic enzymes, CYP7B1 and CYP8B1, and the detoxification enzyme CYP2B6 were increased in cholestatic livers by 2.4-fold, 2.8-fold, and 1.9-fold, respectively (p