Helicobacter pylori infection is a major etiological factor in gastric diseases. However, clinical antibiotic therapy for H. pylori is limited by continuously decreased therapeutic efficacy and side effects to symbiotic bacteria. Herein, we develop an in vivo activatable pH-responsive graphitic nanozyme, PtCo@Graphene (PtCo@G), for selective treatment of H. pylori. Such nanozymes can resist gastric acid corrosion, exhibit oxidase-like activity to stably generate reactive oxygen species only in acidic gastric milieu and demonstrate superior selective bactericidal property. C18-PEGn-Benzeneboronic acid molecules are modified on PtCo@G, improving its targeting capability. Under acidic gastric pH, graphitic nanozymes show notable bactericidal activity toward H. pylori, while no bacterial killing is observed under intestinal conditions. In mouse model, high antibacterial capability toward H. pylori and negligible side effects toward normal tissues and symbiotic bacteria are achieved. Graphitic nanozyme displays the desired enzyme-like activities at corresponding physiological sites and may address critical issues in clinical treatment of H. pylori infections.
Though vascular smooth muscle cell (VSMC) proliferation underlies all cardiovascular hyperplastic disorders, our understanding of the molecular mechanisms responsible for this cellular process is still incomplete. Here we report that SRSF1 (serine/arginine-rich splicing factor 1), an essential splicing factor, promotes VSMC proliferation and injury-induced neointima formation. Vascular injury in vivo and proliferative stimuli in vitro stimulate SRSF1 expression. Mice lacking SRSF1 specifically in SMCs develop less intimal thickening after wire injury. Expression of SRSF1 in rat arteries enhances neointima formation. SRSF1 overexpression increases, while SRSF1 knockdown suppresses the proliferation and migration of cultured human aortic and coronary arterial SMCs. Mechanistically, SRSF1 favours the induction of a truncated p53 isoform, Δ133p53, which has an equal proliferative effect and in turn transcriptionally activates Krüppel-like factor 5 (KLF5) via the Δ133p53-EGR1 complex, resulting in an accelerated cell-cycle progression and increased VSMC proliferation. Our study provides a potential therapeutic target for vascular hyperplastic disease.
Using exact quantum Monte Carlo calculations, we examine the interplay between localization of electronic states driven by many-body correlations and that by randomness in a two-dimensional system featuring linearly vanishing density of states at the Fermi level. A novel disorder-induced nonmagnetic insulating phase is found to emerge from the zero-temperature quantum critical point separating a semimetal and a Mott insulator. Within this phase, a phase transition from a gapless Anderson-like insulator to a gapped Mott-like insulator is identified. Implications of the phase diagram are also discussed.
Using exact quantum Monte Carlo method, we examine the recent novel electronic states seen in magic-angle graphene superlattices. From the Hubbard model on a double-layer honeycomb lattice with a rotation angle θ = 1.08 • , we reveal that an antiferromagnetically ordered Mott insulator emerges beyond a critical Uc at half filling, and with a small doping, the pairing with d+id symmetry dominates over other pairings at low temperature. The effective d + id pairing interaction strongly increase as the on-site Coulomb interaction increases, indicating that the superconductivity is driven by electron-electron correlation. Our non-biased numerical results demonstrate that the twisted bilayer graphene share the similar superconducting mechanism of high temperature superconductors, which is a new and ideal platform for further investigating the strongly correlated phenomena. arXiv:1804.06096v2 [cond-mat.supr-con]
The complex biological environments and multiple physiological barriers significantly impede efficient accumulation and penetration of nanomaterials within tumor tissue for therapy. In situ energy conversion of nanomotors features autonomous movements and improves cancer treatment. However, one of the key challenges is to prepare nanomotors with an adequately small size, good biocompatibility and precise positioning.Here, we demonstrate a simple, ultra-small, versatile, and real-time motion guidance strategy for magnetocatalytic CoPt@graphene navigators (MCGNs) that can enable highly efficient propulsion in the presence of H 2 O 2 or magnetic actuation. MCGNs act as highly diffusive delivery vehicles to promote tumor tissue targeting, and the amount of drug in the tumor was 3 times than without navigation. By engaging movements powered through in situ energy conversion, MCGNs gain considerable propulsion to penetrate a cell's membrane and enhance intracellular delivery.
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