New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders.

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.

Comparison of ketamine/xylazine and isoflurane anesthesia on the establishment of mouse middle cerebral artery occlusion model.

The middle cerebral artery occlusion model (MCAO) is one of the most common stroke models in neuroscience research. The establishment of the mouse MCAO model in terms of animal survival depends on anesthesia, which is an important part of the entire surgical process. The 7-day survival rate of the MCAO model under isoflurane (ISO) anesthesia (35%) was lower than ketamine/xylazine (KX) anesthesia (70%), which demonstrated that the success rate of the MCAO model under KX anesthesia would be significantly higher than that under ISO anesthesia. As confirmed by TTC staining and MRI, the cerebral infarction area of mice successfully modeled under ISO anesthesia was significantly smaller than that of KX anesthesia. The diameter of cerebral blood vessels under ISO anesthesia was significantly larger than that under KX, and the blood perfusion volume was also significantly increased in the same area. ISO has proven to delay the coagulation time and affect the activation of coagulation factors. ISO anesthesia may cause bleeding, vasodilation, respiratory depression, and other phenomena that affect the success rate and death of diseased animal models. In conclusion, compared with ISO anesthesia, KX anesthesia is a safer and more suitable method for the establishment of a mouse MCAO model. The data will inform safer and more detailed anesthesia recommendations forthe establishment of animal models of vascular-related major injury diseases.

Designing a multi-epitope vaccine against coxsackievirus B based on immunoinformatics approaches.

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.

Asynchronous Stabilization for Two Classes of Stochastic Switching Systems with Applications on Servo Motors.

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.

Switching Adaptive Control with Applications on Robot Manipulators.

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.

Technological Advances of 3D Scaffold-Based Stem Cell/Exosome Therapy in Tissues and Organs.

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.

The Effect of SARS-CoV-2 on the Spleen and T Lymphocytes.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has infected millions of individuals in the world. However, the long-term effect of SARS-CoV-2 on the organs of recovered patients remains unclear. This study is to evaluate the impact of SARS-CoV-2 on the spleen and T lymphocytes. Seventy-six patients recovered from COVID-19, including 66 cases of moderate pneumonia and 10 cases of severe pneumonia were enrolled in the observation group. The control group consisted of 55 age-matched healthy subjects. The thickness and length of spleen were measured by using B-ultrasound and the levels of T lymphocytes were detected by flow cytometry. Results showed that the mean length of spleen in the observation group was 89.57 ± 11.49 mm, which was significantly reduced compared with that in the control group (103.82 ± 11.29 mm, p < 0.001). The mean thicknesses of spleen between observation group and control group were 29.97 ± 4.04 mm and 32.45 ± 4.49 mm, respectively, and the difference was significant (p < 0.001). However, no significant difference was observed in the size of spleen between common pneumonia and severe pneumonia (p > 0.05). In addition, the decreased count of T lymphocyte was observed in part of recovered patients. The counts of T suppressor lymphocytes in patients with severe pneumonia were significantly decreased compared with those with moderate pneumonia (p = 0.005). Therefore, these data indicate that SARS-CoV-2 infection affects the size of spleen and T lymphocytes.

UBE2W down-regulation promotes cell apoptosis and correlates with hypospermatogenesis.

Ubiquitin conjugating enzyme (E2) is crucial for mediating N-terminal ubiquitination. Recent study reports that UBE2W is involved in male infertility. However, the correlation between UBE2W expression and hypospermatogenesis is unclear. The present study is to explore the biological role of UBE2W and its association with hypospermatogenesis. Results showed that the sexpression levels of UBE2W in mouse testes were gradually elevated from 2 to 10 weeks, while were significantly deceased in the testes with hypospermatogenesis. When UBE2W expression was successfully down-regulated in spermatogenic cells, the rate of apoptosis was significantly increased and the P53/Bcl-2/caspase 6/caspase 9 signal pathways were activated. Thus, these data indicate that UBE2W down-regulation promotes cell apoptosis and correlates with hypospermatogenesis, which may be helpful for the diagnosis of male infertility.