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Human long interspersed elements 1 (LINE-1 or L1) is the only autonomous non-LTR retroelement in humans and has been associated with genome instability, inherited genetic diseases, and the development of cancer. Certain human APOBEC3 family proteins are known to have LINE-1 restriction activity. The mechanisms by which APOBEC3 affects LINE-1 retrotransposition are not all well characterized; here, we confirm that both A3B and A3DE have a strong ability to inhibit LINE-1 retrotransposition. A3DE interacts with LINE-1 ORF1p to target LINE-1 ribonucleoprotein particles in an RNA-dependent manner. Moreover, A3DE binds to LINE-1 RNA and ORF1 protein in cell culture system. Fluorescence microscopy demonstrated that A3DE co-localizes with ORF1p in cytoplasm. Furthermore, A3DE inhibits LINE-1 reverse transcriptase activity in LINE-1 ribonucleoprotein particles in a cytidine deaminase-independent manner. In contrast, A3B has less inhibitory effects on LINE-1 reverse transcriptase activity despite its strong inhibition of LINE-1 retrotransposition. This study demonstrates that different A3 proteins have been evolved to inhibit LINE-1 activity through distinct mechanisms.

Engineered nanozymes have been developed to catalyze the production of reactive oxygen species (ROS) for cancer therapy, but currently, the ROS generation efficiency is still far from optimistic. In this study, a human self‐driven electrical stimulation enhanced catalytic system based on wearable triboelectric nanogenerator (TENG) and fully π‐conjugated covalent organic framework nanocages (hCOF) for improving cancer therapy is created. The fully π‐conjugated hCOF nanocage with high electron mobility under the self‐generated electric field can not only rearrange the local electric field for optimizing energy utilization, but also facilitates the access of electrolytes to optimize the utilization of the electric field. With the self‐powered wearable TENG, the peroxidase‐like activity of hCOF increased by 2.44‐fold and has electricity‐responsive doxorubicin delivery capacity for enhancing the therapeutic outcomes. The high‐efficient self‐driven electrical stimulation enhanced nanocatalytic system provides a new optimized model for the catalytic energy supply of nanozymes.

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Astragaloside IV is one of the main active ingredients of Radix astragali, which is a herbal remedy widely used in traditional Chinese medicine for the treatment of diabetes and cardiovascular diseases. However, its effects on vascular smooth muscle cell (VSMC), which plays a key role in the development of diabetic vascular complications, were not well studied. The present study was performed to examine the effects of astragaloside IV on proliferation, apoptosis and phenotypic modulation of VSMC under high D-glucose (25 mM). Application of astragaloside IV inhibited the proliferation and the rise of the proliferation index (PI) of VSMC induced by high glucose in a dose-dependent manner. Astragaloside IV induced apoptosis in VSMC under high glucose conditions, accompanied with typical morphological alterations and loss of mitochondrial membrane potential (Delta Psim). In addition, Western blot analysis revealed that astragaloside IV increased the expression of alpha-smooth muscle actin, an important phenotypic modulation marker. In conclusion, astragaloside IV could inhibit high glucose-induced VSMC proliferation through intervention with the cell cycle, promoting apoptosis and regulating phenotypic modulation of VSMC, which strongly suggest that astragaloside IV could hinder the process of pathological vascular remodeling in diabetic patients.

The death domain (DD) is a globular protein motif with a signature feature of an all-helical Greek-key motif. It is a primary mediator of a variety of biological activities, including apoptosis, cell survival and cytoskeletal changes, which are related to many neurodegenerative diseases, neurotrauma, and cancers. DDs exist in a wide range of signalling proteins including p75 neurotrophin receptor (p75 NTR ), a member of the tumour necrosis factor receptor superfamily. The specific signalling mediated by p75 NTR in a given cell depends on the type of ligand engaging the extracellular domain and the recruitment of cytosolic interactors to the intracellular domain, especially the DD, of the receptor. In solution, the p75 NTR -DDs mainly form a symmetric non-covalent homodimer. In response to extracellular signals, conformational changes in the p75 NTR extracellular domain (ECD) propagate to the p75 NTR -DD through the disulfide-bonded transmembrane domain (TMD) and destabilize the p75 NTR -DD homodimer, leading to protomer separation and exposure of binding sites on the DD surface. In this review, we focus on recent advances in the study of the structural mechanism of p75 NTR -DD signalling through recruitment of diverse intracellular interactors for the regulation and control of diverse functional outputs.

BACKGROUND AND PURPOSE:Individual assessment of the absolute risk of intracranial aneurysm rupture remains challenging. Emerging imaging techniques such as dynamic contrast-enhanced MR imaging and postcontrast vessel wall MR imaging may improve risk estimation by providing new information on aneurysm wall properties. The purpose of this study was to investigate the relationship between aneurysm wall permeability on dynamic contrast-enhanced MR imaging and aneurysm wall enhancement on postcontrast vessel wall MR imaging in unruptured intracranial aneurysms. MATERIALS AND METHODS:Patients with unruptured saccular intracranial aneurysms were imaged with vessel wall MR imaging before and after gadolinium contrast administration. Dynamic contrast-enhanced MR imaging was performed coincident with contrast injection using 3D T1-weighted spoiled gradient-echo imaging. The transfer constant (K trans ) was measured adjacent to intracranial aneurysm and adjacent to the normal intracranial artery. RESULTS:Twenty-nine subjects were analyzed (mean age, 53.9 Ϯ 13.5 years; 24% men; PHASES score: median, 8; interquartile range, 4.75-10). K trans was higher in intracranial aneurysms compared with the normal intracranial artery (median, 0.0110; interquartile range, 0.0060 -0.0390 versus median, 0.0032; interquartile range, 0.0018 -0.0048 min Ϫ1 ; P Ͻ .001), which correlated with intracranial aneurysm size (Spearman ϭ 0.54, P ϭ .002) and PHASES score ( ϭ 0.40, P ϭ .30). Aneurysm wall enhancement, detected in 19 (66%) aneurysms, was associated with intracranial aneurysm size and the PHASES score but not significantly with K trans (P ϭ .30). Aneurysms of 2 of the 9 patients undergoing conservative treatment ruptured during 1-year follow-up. Both ruptured aneurysms had increased K trans , whereas only 1 had aneurysm wall enhancement at baseline. CONCLUSIONS:Dynamic contrast-enhanced MR imaging showed increased K trans adjacent to intracranial aneurysms, which was independent of aneurysm wall enhancement on postcontrast vessel wall MR imaging. Increased aneurysm wall permeability on dynamic contrast-enhanced MR imaging provides new information that may be useful in intracranial aneurysm risk assessment. ABBREVIATIONS: AWEϭ aneurysm wall enhancement; DCE ϭ dynamic contrast-enhanced; IA ϭ intracranial aneurysm; IQR ϭ interquartile range; K trans ϭ transfer constant; PHASES ϭ Population, Hypertension, Age, Size, Earlier Subarachnoid Hemorrhage, and Site; WEI ϭ wall enhancement index Indicates open access to non-subscribers at www.ajnr.org http://dx.