Although photothermal therapy (PTT) has thrived as a promising treatment for drug-resistant bacterial infections by avoiding the abuse of antibiotics, the remaining challenges that limit the treatment efficiency are the poor targeting properties of infected lesions and low penetration to the cell membrane of Gram-negative bacteria. Herein, we developed a biomimetic neutrophil-like aggregation-induced emission (AIE) nanorobot (CM@AIE NPs) for precise inflammatory site homing and efficient PTT effects. Due to their surface-loaded neutrophil membranes, CM@AIE NPs can mimic the source cell and thus interact with immunomodulatory molecules that would otherwise target endogenous neutrophils. Coupled with the secondary near-infrared region absorption and excellent photothermal properties of AIE luminogens (AIEgens), precise localization, and treatment in inflammatory sites can be achieved, thereby minimizing damage to surrounding normal tissues. Moreover, CM@AIE NP-mediated PTT was stimulated in vivo by a 980 nm laser irradiation, which contributed to the extent of the therapeutic depth and limited the damage to skin tissues. The good biocompatibility and excellent in vitro and in vivo antibacterial effects prove that CM@AIE NPs can provide a strategy for broad-spectrum antibacterial applications.
The porcine epidemic diarrhea virus, PEDV, which causes diarrhea, vomiting and death in piglets, causes huge economic losses. Therefore, understanding how to induce mucosal immune responses in piglets is essential in the mechanism and application against PEDV infection with mucosal immunity. A method of treatment in our research was used to make an oral vaccine that packaged the inactive PEDV with microencapsulation, which consisted of sodium alginate and chitosan, and adapted the condition of the gut in mice. The in vitro release experiment of microcapsules showed that inactive PEDV was not only easily released in saline and acid solutions but also had an excellent storage tolerance, and was suitable for use as an oral vaccine. Interestingly, both experimental groups with different doses of inactive virus enhanced the secretion of specific antibodies in the serum and intestinal mucus, which caused the effective neutralization against PEDV in the Vero cell by both IgG and IgA, respectively. Moreover, the microencapsulation could stimulate the differentiation of CD11b+ and CD11c+ dendritic cells, which means that the microencapsulation was also identified as an oral adjuvant to help phagocytosis of dendritic cells in mice. Flow cytometry revealed that the B220+ and CD23+ of the B cells could significantly increase antibody production with the stimulation from the antigens' PEDV groups, and the microencapsulation could also increase the cell viability of B cells, stimulating the secretion of antibodies such as IgG and IgA in mice. In addition, the microencapsulation promoted the expression of anti-inflammatory cytokines, such as IL-10 and TGF-β. Moreover, proinflammatory cytokines, such as IL-1, TNF-α, and IL-17, were inhibited by alginate and chitosan in the microencapsulation groups compared with the inactivated PEDV group. Taken together, our results demonstrate that the microparticle could play the role of mucosal adjuvant, and release inactivated PEDV in the gut, which can effectively stimulate mucosal and systemic immune responses in mice.
Engineering equipmentpsilas rush repairs in battlefield optimal assignment model was established. Combining the features of job shop scheduling problems, described the complexity of this problem. In order to find global optimal results efficiently, traditional GAs were improved and used for study of this problem. Though genetic algorithm, as an effective global search method, had been used in many engineering problems, it had the disadvantages of slow convergence and poor stability in practical engineering. In order to overcome these problems, an improved genetic algorithm was proposed in terms of creation of the initial population, genetic operators, etc. At the end, the steps to solve the optimal model were put forward. With this model we had obtained ideal results. This shows that the method can offer a scientific and effective support for a decision maker in command automation of the engineering equipmentpsilas rush repairs in battlefield.
In this work, we developed multi-shelled hollow nanospheres [RGD@am-ZnO@CuO@Au@DOX HNSs] as multifunctional therapeutic agents to achieve effective and targeted Zn2+/Cu2+ therapy, induced drug delivery under low pH/red-light conditions, and enhanced phototherapy under single red-light. The photothermal and photodynamic performance of am-ZnO@CuO@Au HNSs was enhanced relative to that of am-ZnO nanoparticles (NPs) or am-ZnO@CuO HNSs by utilizing the resonance energy transfer process and broad red-light absorption. The pH-sensitive am-ZnO@CuO@Au HNSs were dissolved to Zn2+/Cu2+ in the acidic endosomes/lysosomes of cancer cells, resulting in a cancer cell killing effect. The release performance of doxorubicin (DOX) from RGD@am-ZnO@CuO@Au@DOX HNSs was evaluated under low pH and red-light-irradiated conditions, and targeting of HNSs was confirmed by dual-modal imaging (magnetic resonance/fluorescence) of the tumor area. Moreover, in vivo synergistic therapy using RGD@am-ZnO@CuO@Au@DOX HNSs was further evaluated in mice bearing human pulmonary adenocarcinoma (A549) cells, achieving a remarkable synergistic antitumor effect superior to that obtained by monotherapy. This study validated that RGD@am-ZnO@CuO@Au@DOX HNSs can be a promising candidate for efficient postoperative cancer therapy.
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