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Abstract Background Neural stem cells (NSCs) play a crucial role in the progress of ischemic stroke. Research on zebrafish embryonic demonstrates an association between Strawberry Notch 1 (Sbno1) and central nervous system development. However, the regulation and underlying mechanism of Sbno1 in NSCs have not been studied yet. Here, we investigated the role and the mechanism of Sbno1 in NSCs development and the potential therapeutic value of Sbno1 in ischemic stroke. Methods Adeno-associated virus (AAV) was used for overexpression or knockdown of Sbno1 in vitro or in vivo. A mouse model of MCAO was established to evaluate the neuroprotective effects of AAV-Sbno1, including balance beam test, rotarod test, and strength evaluation. H&E and immunofluorescence assessed neuronal impairment. Western blot and RT-qPCR were used to detect the expression of Sbno1 and its downstream target genes. RNA-seq and western blot were performed to explore further molecular mechanisms by which Sbno1 promoted endogenous repair of NSCs and macrophages M2 polarization. CCK8 was conducted to assess the effects of Sbno1 on NSCs proliferation. The impact of Sbno1 on NSCs apoptosis was evaluated by flow cytometry. NSCs derived from small extracellular vesicles (sEV) were obtained using ultracentrifugation and identified through nanoparticle tracking analysis (NTA) and western blot analysis. Results Our results showed that Sbno1 is highly expressed in the central nervous system, which plays a crucial role in regulating the proliferation of NSCs through the PI3k-Akt-GSK3β-Wnt/β-catenin signaling pathway. In addition, with overexpression of Sbno1 in the hippocampus, post-stroke behavioral scores were superior to the wild-type mice, and immunofluorescence staining revealed an increased number of newly generated neurons. sEV released by NSCs overexpressing Sbno1 inhibited neuroinflammation, which mechanistically impaired the activation of the microglial NF-κB and MAPK signaling pathways. Conclusions Our studies indicate that sbno1 promotes the proliferation of NSCs and enhances endogenous repairing through the PI3k-Akt-GSK3β-Wnt/β-catenin signaling pathway. Additionally, NSCs overexpressing sbno1 improve ischemic stroke recovery and inhibit neuroinflammation after ischemia by sEV through the MAPK and NF-κB signaling pathways.

Coxsackievirus B (CVB) is one of the major viral pathogens of human myocarditis and cardiomyopathy without any effective preventive measures; therefore, it is necessary to develop a safe and efficacious vaccine against CVB. Immunoinformatics methods are both economical and convenient as in-silico simulations can shorten the development time. Herein, we design a novel multi-epitope vaccine for the prevention of CVB by using immunoinformatics methods. With the help of advanced immunoinformatics approaches, we predicted different B-cell, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) epitopes, respectively. Subsequently, we constructed the multi-epitope vaccine by fusing all conserved epitopes with appropriate linkers and adjuvants. The final vaccine was found to be antigenic, non-allergenic, and stable. The 3D structure of the vaccine was then predicted, refined, and evaluated. Molecular docking and dynamics simulation were performed to reveal the interactions between the vaccine with the immune receptors MHC-I, MHC-II, TLR3, and TLR4. Finally, to ensure the complete expression of the vaccine protein, the sequence of the designed vaccine was optimized and further performed in-silico cloning. In conclusion, the molecule designed in this study could be considered a potential vaccine against CVB infection and needed further experiments to evaluate its safety and efficacy.

As a large and heterogeneous group of disorders, neurodegenerative diseases are characterized by the progressive loss of structure or function in neurons, finally leading to neuronal death. Neurodegenerative diseases cause serious threat to a patient’s quality of life and the most common are Alzheimer’s disease and Parkinson’s disease. Currently, little is known of the detailed etiology of these disorders; as such, there are no effective treatments available. Furthermore, the lack of targeted, effective, and resolvable therapy for neurodegenerative diseases, represents an expanding research field for the discovery of new therapeutic strategies. Investigations of the potential pathogenesis of neurodegenerative diseases will become the basis of preventing the occurrence and development of neurodegenerative diseases and finding effective therapies. Existing theories and mechanisms, such as genetic and environmental factors, abnormal protein accumulation, and oxidative stress, are intricately associated with each other. However, there is no molecular theory that can entirely explain the pathological processes underlying neurodegenerative diseases. Due to the development of experimental technology and the support of multidisciplinary integration, it has been possible to perform more in-depth research on potential targets for neurodegenerative diseases and there have been many exciting discoveries in terms of original theories and underlying mechanisms. With this review, we intend to review the existing literature and provide new insights into the molecular mechanisms underlying neurodegenerative diseases.

Recently, biomaterial scaffolds have been widely applied in the field of tissue engineering and regenerative medicine. Due to different production methods, unique types of three-dimensional (3D) scaffolds can be fabricated to meet the structural characteristics of tissues and organs, and provide suitable 3D microenvironments. The therapeutic effects of stem cell (SC) therapy in tissues and organs are considerable and have attracted the attention of academic researchers worldwide. However, due to the limitations and challenges of SC therapy, exosome therapy can be used for basic research and clinical translation. The review briefly introduces the materials (nature or polymer), shapes (hydrogels, particles and porous solids) and fabrication methods (crosslinking or bioprinting) of 3D scaffolds, and describes the recent progress in SC/exosome therapy with 3D scaffolds over the past 5 years (2016–2020). Normal SC/exosome therapy can improve the structure and function of diseased and damaged tissues and organs. In addition, 3D scaffold-based SC/exosome therapy can significantly improve the structure and function cardiac and neural tissues for the treatment of various refractory diseases. Besides, exosome therapy has the same therapeutic effects as SC therapy but without the disadvantages. Hence, 3D scaffold therapy provides an alternative strategy for treatment of refractory and incurable diseases and has entered a transformation period from basic research into clinical translation as a viable therapeutic option in the future.

This paper concentrates on the study of logic-based switching adaptive control. Two different cases will be considered. In the first case, the finite time stabilization problem for a class of nonlinear system is studied. Based on the recently developed adding a barrier power integrator technique, a new logic-based switching adaptive control method is proposed. In contrast with the existing results, finite time stability can be achieved when the considered systems contain both fully unknown nonlinearties and unknown control direction. Moreover, the proposed controller has a very simple structure and no approximation methods, e.g., neural networks/fuzzy logic, are needed. In the second case, the sampled-data control for a class of nonlinear system is investigated. New sampled-data logic-based switching mechanism is proposed. Compared with previous works, the considered nonlinear system has an uncertain linear growth rate. The control parameters and the sampling time can be adjusted adaptively to render the exponential stability of the closed loop system. Applications in robot manipulators are conducted to verify the proposed results.

This paper addresses the asynchronous stabilization problem of two typical stochastic switching systems, i.e., dual switching systems and semi-Markov jump systems. By dual switching, it means that the systems contain both deterministic and stochastic switching dynamics. New stability criteria are firstly proposed for these two switched systems, which can well handle the asynchronous phenomenon. The conditional expectation of Lyapunov functions is allowed to increase during some unmatched interval to reduce the conservatism. Next, we present numerically testable asynchronous controller design methods for the dual switching systems. The proposed method is suitable for the situation where the asynchronous modes come from both inaccurate mode detection and time varying delay. Meanwhile, the transition probabilities are both uncertain and partly accessible. Finally, novel asynchronous controller design methods are proposed for the semi-Markov jump systems. The sojourn time of the semi-Markov jump systems can have both lower and upper bounds, which could be more practical than previous scenarios. Examples are utilized to demonstrate the effectiveness of the proposed methods.