AimTo evaluate the efficacy and safety of Entecavir (ETV) plus adefovir (ADV) for chronic hepatitis B (CHB) patients after multiple nucleos(t)ide analogue (NAs) failure treatment.MethodsHepatitis B e antigen (HBeAg)-positive patients who had a suboptimal response or developed resistance to two or more previous NAs treatments were included, and all subjects were treated with ETV in combination with ADV for ≥ 24 months. Complete virologic response (CVR) was defined as an undetectability of serum hepatitis B virus (HBV) DNA level during treatment. Safety assessment was based on the increasing of serum creatinine and creatine kinase levels.ResultsA total of 45 eligible patients were included. Twenty-five patients had been treated with lamivudine (LAM) or telbivudine (LdT) and developed genotypic resistance. Resistance to ADV was present in 18 patients and 4 patients had a suboptimal response to ETV. Two patients had a resistance to both LAM and ADV. The cumulative probabilities of CVR at 12 and 24 months of ETV + ADV treatment were 88.9% (40/45) and 97.8% (44/45), respectively. Although one patient failed to achieve CVR, its serum HBV DNA level decreased by 3.3 log copies/mL after 24 months of combination therapy. The cumulative probability of HBeAg seroconversion was 15.6% (7/45) and 26.7% (12/45) at 12 and 24 months of treatment, respectively. History of prior exposure to specific NAs did not make a difference to ETV + ADV treatment outcome. There were no significant adverse events related to ETV + ADV therapy observed in the study subjects.ConclusionETV + ADV can be used as an effective and safe rescue therapy in patients after multiple NA therapy failures, especially in the areas where tenofovir is not yet available.

Graphite is an attractive anode material for low‐cost potassium‐ion batteries (PIBs), which are highly promising in addressing the urgent demand for large‐scale energy storage systems. However, the large volume variation of graphite during the potassiation/depotassiation may lead to poor long‐term stability, which is unfavorable for commercialization. Herein, highly graphitic hollow spheres (HGHS) are designed by using D‐ribose as the carbon source and Fe‐based catalysts to address these issues, and the effect of graphitization degree on potassium storage performance is explored, which is rarely reported. Fe‐based catalysts can promote graphitization of carbon layer and function as a hard template for manufacturing hollow and spherical architecture. HGHS possess a high porosity, which provides good contact when the liquid electrolyte infiltrates throughout the material. HGHS synthesized with a suitable amount of Fe‐based catalysts display highly graphitic hollow carbon spheres and show a superior potassium storage performance (264 mAh g−1 at 100 mA g−1). The hollow carbon sphere structure and highly graphitic carbon layer endows HGHS with outstanding stability, retaining 87% of the capacity after 500 cycles at 200 mA g−1. This study provides an effective strategy in designing highly graphitic hollow nanostructures for addressing the instability issues of graphite anode in PIBs.

Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) cause neointimal hyperplasia after percutaneous vascular interventions. Nuclear receptor subfamily 1 group D member 1 (NR1D1), a crucial member of circadian clock, is involved in the regulation of atherosclerosis and cellular proliferation. However, whether NR1D1 affects vascular neointimal hyperplasia remains unclear. In this study, we found that activating NR1D1 reduced injury-induced vascular neointimal hyperplasia. Overexpression of NR1D1 reduced the number of Ki-67-positive VSMCs and migrated VSMCs after platelet-derived growth factor (PDGF)-BB treatment. Mechanistically, NR1D1 suppressed the phosphorylation of AKT and 2 main effectors of the mammalian target of rapamycin complex 1 (mTORC1), S6, and 4EBP1 in PDGF-BB-challenged VSMCs. Re-activation of mTORC1 by Tuberous sclerosis 1 siRNA (siTsc1) and re-activation of AKT by SC-79 abolished NR1D1-mediated inhibitory effects on proliferation and migration of VSMCs. Moreover, decreased mTORC1 activity induced by NR1D1 was also reversed by SC-79. Simultaneously, Tsc1 knockdown abolished the vascular protective effects of NR1D1 in vivo. In conclusion, NR1D1 reduces vascular neointimal hyperplasia by suppressing proliferation and migration of VSMCs in an AKT/mTORC1-dependent manner.