Near-Infrared Light-Responsive Nitric Oxide Delivery Platform for Enhanced Radioimmunotherapy

Radiotherapy(RT)is a widely used way for cancer treatment.However,the efficiency of RT may come with various challenges such as low specificity,limitation by resistance,high dose and so on.Nitric oxide(NO)is known a very effective radiosensitizer of hypoxic tumor.However,NO cannot circulate in body with high concentration.Herein,an NIR light-responsive NO delivery system is developed for controlled and precisely release of NO to hypoxic tumors during radiotherapy.Tert-Butyl nitrite,which is an efficient NO source,is coupled to Ag2S quantum dots(QDs).NO could be generated and released from the Ag2S QDs effectively under the NIR irradiation due to the thermal effect.In addition,Ag is also a type of heavy metal that can benefit the RT therapy.We demonstrate that Ag2S NO delivery platforms remarkably maximize radiotherapy effects to inhibit tumor growth in CT26 tumor model.Furthermore,immunosuppressive tumor microenvironment is improved by our NO delivery system,significantly enhancing the anti-PD-L1 immune checkpoint blockade therapy.100% survival rate is achieved by the radio-immune combined therapy strategy based on the Ag2S NO delivery platforms.Our results suggest the promise of Ag2S NO delivery platforms for multifunctional cancer radioimmunotherapy.

Annexin A5 derived from matrix vesicles protects against osteoporotic bone loss via mineralization

Matrix vesicles(MVs)have shown strong effects in diseases such as vascular ectopic calcification and pathological calcified osteoarthritis and in wound repair of the skeletal system due to their membranous vesicle characteristics and abundant calcium and phosphorus content.However,the role of MVs in the progression of osteoporosis is poorly understood.Here,we report that annexin A5,an important component of the matrix vesicle membrane,plays a vital role in bone matrix homeostasis in the deterioration of osteoporosis.We first identified annexin A5 from adherent MVs but not dissociative MVs of osteoblasts and found that it could be sharply decreased in the bone matrix during the occurrence of osteoporosis based on ovariectomized mice.We then confirmed its potential in mediating the mineralization of the precursor osteoblast lineage via its initial binding with collagen type I to achieve MV adhesion and the subsequent activation of cellular autophagy.Finally,we proved its protective role in resisting bone loss by applying it to osteoporotic mice.Taken together,these data revealed the importance of annexin A5,originating from adherent MVs of osteoblasts,in bone matrix remodeling of osteoporosis and provided a new strategy for the treatment and intervention of bone loss.

Tacrolimus combined with arsenic trioxide provides a three-in-one drug-eluting coronary stent integrating anti-restenosis,pro-endothelialization and anti-inflammation

The limitations of current drug-eluting stent technologies in selectively inhibiting vascular smooth muscle cell proliferation,which often leads to inflammation,call for innovative approaches in coronary artery disease treatment.In the present work,we propose a revolutionary solution:a three-in-one platform for vascular stents,combining arsenic trioxide(ATO)and tacrolimus(TAC)to address anti-proliferation,pro-endothelialization,and anti-inflammation aspects.Our findings demonstrate that the synergistic action of ATO and TAC effectively suppresses aberrant vascular smooth muscle cell proliferation and mitigates endothelial cell inflammation.Remarkably,the combination treatment of TAC/ATO enhances endothelial cell migration and adhesion abilities.Moreover,our TAC/ATO-eluting stent exhibits superior re-endothelialization and anti-restenosis effects in a rabbit and porcine stent implantation model.Both in vitro and in vivo results solidify the notion that the TAC/ATO-eluting stent ensures rapid re-endothelialization and significantly reduces the incidence of in-stent restenosis.Overall,this study represents a promising and novel multifunctional platform with immense potential in the therapy of coronary artery disease.

Optimization and improvement of ac resistance calculation method for multi-phase parallel-wiring cables

Parallel-wiring cables are often used in multi-phase AC aircraft Electrical Power Systems(EPSs).However,it complicates the ac resistance estimation.To solve this issue,an analytical resistance calculation method for parallel-wiring cables in multi-phase EPS was proposed.Firstly,the existing calculation formula of proximity factor was optimized,and the calculation error was reduced from 16%to 2%when two conductors are close to each other.Afterwards,the superposition effect on current density distribution between multi-conductors was considered based on orthogonal decomposition method,and the position of the equivalent charged points were easily determined.Finally,the ac resistance calculation formula was derived according to characteristics of parallel-wiring strategy,and the general ac resistance calculation methods of multi-phase parallel-wiring cables were presented.The proposed approach considerably enhances the applicability of ac resistance analytical calculation method for multi-conductor cables.Thanks to the accuracy of the proposed method,it can be used in many cases to avoid case-by-case simulation work and facilitate efficient system design and analysis.