白藜芦醇及其衍生物在TNF-α诱导的人脐静脉内皮细胞中的抗炎作用

二苯乙烯类化合物，自1940年首次从毛藜芦根中分离出白藜芦醇以来就对此进行了广泛研究。这类化合物存在于许多植物中并具有广泛的生理活性，主要有抗氧化、抗肿瘤、抗淤血综合征（如脑炎、动脉粥样硬化、慢性炎症）等。白藜芦醇（trans-3，5，4’-trihydroxystiibene），是从中药虎杖中提取出来的一种二苯乙烯类化合物，同时也是一种非常重要的植物内毒素，在近年来的实验研究中已充分证明其具有很多有益的药理作用，如抗癌、心血管保护、神经保护、抗衰老和抗炎等等。大量研究证实其在抗动脉粥样硬化中起着非常重要的作用。近年来随着白藜芦醇的类似物的不断出现，研究者们发现其中一些二苯乙烯类化合物同样具有许多与白藜芦醇相似的药理活性且某些化合物的活性、选择性及稳定性均要强于白藜芦醇，故成为目前研究的热点。为了探讨白藜芦醇类似物中甲基化白藜芦醇和自藜芦醇苷的抗炎效应并阐明其作用机制，同时与白藜芦醇进行比较，我们首先用细胞黏附实验测定其是否具有抗细胞黏附的能力，然后对其相关的黏附分子的表达及NF—κB进行考察。

Tetramethylpyrazine Nitrone Improved Motor Deficits and Alleviated Dystrophic Muscle Pathology in the <i>mdx</i>Mouse Model of Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive neuromuscular disorder caused by mutations in the dystrophin encoding gene, with the characteristics of a severe and progressive destruction of muscle structure and function. Skeletal muscle fibrosis is one of the pathological features of DMD. Tetramethylpyrazine (2,3,5,6-tetramethylpyrazine, TMP) has been demonstrated to reduce heart and liver fibrosis. Meanwhile, previous studies showed that Tetramethylpyrazine nitrone (TBN), a nitrone derivative of TMP, has promising therapeutic effects in several neurodegenerative models and is more potent than TMP. In this study, we investigated the potential effect of TBN on the mdx mouse model of DMD. Eight-week-old mdx mice were administered with TBN (30 mg/kg) intragastrically twice daily, with deflazacort (1 mg/kg) once a day as a positive control, for a total of 24 weeks. Behavioral tests including pole-climbing open-field test were monitored every 4 weeks. Histopathological assessment was conducted in the gastrocnemius and diaphragm muscles. The effects of TBN on protein levels of dysferlin were measured by immunohistochemistry. TBN significantly reduced the climbing time in pole test and increased the total distance moved in an open-field test of mdx mice. TBN attenuated fibrosis in the gastrocnemius and diaphragmatic muscles. In addition, TBN protected gastrocnemius muscle fibers via increasing expression of the dysferlin in mdx mice. In conclusion, this study demonstrated that TBN could improve the motor deficits and muscle pathology of mdx mouse, and it is worth further exploring the mechanism of action of TBN for DMD treatment.

Exact satisfiability and phase transition analysis of the regular(k,d)-CNF formula

1Introduction The satisfiability(SAT)problem has been considered the"seed"of other NP-complete problems.The regular partial exact(k,d)-SAT problem is an important extension of the SAT problem.For any(k,d)-CNF formula with a variable set V,V'is a proper subset of V,the problem involves determining whether a truth assignment set on V'exists such that only a literal in each clause is true.When V'=V,it is a regular exact(k,d)-SAT problem.Currently,both experimental verifications and theoretical analyses of k-SAT problem have shown that the ratioα(clause constraint density)of the number of clauses m to the number of variables n is an important parameter affecting the satisfiability of the formula[1].However,the regular(k,d)-SAT problem has the same clause constraint density d/k.

Maintaining the balance of TDP-43,mitochondria,and autophagy:a promising therapeutic strategy for neurodegenerative diseases

Mitochondria are the energy center of cell operations and are involved in physiological functions and maintenance of metabolic balance and homeostasis in the body.Alterations of mitochondrial function are associated with a variety of degenerative and acute diseases.As mitochondria age in cells,they gradually become inefficient and potentially toxic Acute injury can trigger the permeability of mitochondrial membranes,which can lead to apoptosis or necrosis.Transactive response DNA-binding protein 43 kDa(TDP-43)is a protein widely present in cells.It can bind to RNA,regulate a variety of RNA processes,and play a role in the formation of multi-protein/RNA complexes.Thus,the normal physiological functions of TDP-43 are particularly important for cell survival.Normal TDP-43 is located in various subcellular structures including mitochondria,mitochondrial-associated membrane,RNA particles and stress granules to regulate the endoplasmic reticulum-mitochondrial binding,mitochondrial protein translation,and mRNA transport and translation.Importantly,TDP-43 is associated with a variety of neurodegenerative diseases,including amyotrophic lateral sclerosis,frontotemporal dementia and Alzheimer's disease,which are characterized by abnormal phosphorylation,ubiquitination,lysis or nuclear depletion of TDP-43 in neurons and glial cells.Although the pathogenesis of TDP-43 proteinopathy remains unknown,the presence of pathological TDP-43 inside or outside of mitochondria and the functional involvement of TDP-43 in the regulation of mitochondrial morphology,transport,and function suggest that mitochondria are associated with TDP-43-related diseases.Autophagy is a basic physiological process that maintains the homeostasis of cells,including targeted clearance of abnormally aggregated proteins and damaged organelles in the cytoplasm;therefore,it is considered protective against neurodegenerative diseases.However,the combination of abnormal TDP-43 aggregation,mitochondrial dysfunction,and insufficient autophagy can lead to a variety of aging-related pathologies.In this review,we describe the current knowledge on the associations of mitochondria with TDP-43 and the role of autophagy in the clearance of abnormally aggregated TDP-43 and dysfunctional mitochondria.Finally,we discuss a novel approach for neurodegenerative treatment based on the knowledge.

An algorithm for solving satisfiability problem based on the structural information of formulas

1 Introduction The propositional satisfiability(SAT)problem is an important and prototypical NP-hard problem in theoretical computer science[1].Many efforts have been made for designing high-performance SAT solvers.The existing practical techniques for solving SAT problems are mainly divided into two categories:complete search technique and stochastic local search technique.

Satisfiability threshold of the random regular(s,c,k)-SAT problem

1Introduction The satisfiability(SAT)problem is always a core problem in the field of computer science.Its theoretical and applied research have long been the common attention of many scholars in the field of artificial intelligence and mathematical logic.In the real world,all issues related to combinatorial optimization and coordination verification are closely related to SAT problem.