Nanocarrier-mediated siRNA delivery:a new approach for the treatment of traumatic brain injury-related Alzheimer's disease

Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive deficits.Furthermore,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's disease.Nanocarriers offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug actions.This review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future directions.In principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various diseases.Among the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain barrier.Nanoparticles have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain diseases.They are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional therapy.The use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective approach.Although this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular targeted therapy and precision medicine for the treatment of Alzheimer's disease associated with traumatic brain injury.

Is China's agricultural enterprise growing steadily?Evidence from listed agricultural companies

Agricultural enterprises are integral for agricultural modernization,serving as a bridge between scattered small-scale farmers and modern markets.However,agricultural competitiveness is still weak in China.This paper uses the Technique for Order of Preference by Similarity to Ideal Solution(TOPSIS)method to measure the growth performance of China's listed agricultural companies and analyze its influencing factors based on Panel-Corrected Standard Errors(PCSE)to verify whether they are capable of achieving sustainable development.The findings confirm that first,listed Chinese agricultural companies have significantly increased profitability and scale in recent years but are still weak compared to other industries.The growth performance of such enterprises is generally stable,the difference between them is decreasing,and their growth ranking fluctuates greatly,with significant regional and industrial characteristics.Second,technological efficiency,scale,and age are positively related to the growth of listed agricultural companies.The diversification and expansion of business harm the profitability and development of enterprises.Currently,financial support can satisfy the short-term profit-seeking demands of enterprises but is inadequate to improve the ability of enterprises to grow.Third,China's listed agricultural companies need to devise policies through a forward-looking perspective and use them more effectively.Additionally,the transformation opportunities introduced by non agricultural capital into agriculture deserve attention.When agricultural enterprises realize technological progress via modern capital,they understand the importance of utilizing and integrating technological innovation and increase the efficiency of transforming new technology into productivity.Policy orientation should be attentive to the public welfare of these listed companies and take into account the demands of corporate profits to realize the long-term sustainable development of enterprises and regions.

<i>In vitro</i>differentiation of human umbilical cord-derived mesenchymal stem cells into CD34⁺cells via CD34 antibody

CD34+cells differentiated from mesenchymal stem cells (MSCs) have a strong biological function in cardiovascular regeneration. However, the molecular mechanisms of and the methods to improve the CD34+ cell differentiation from MSCs, especially from human MSCs (hUC-MSCs) are still unclear. In the current study, the effect of CD34 antibody on the CD34+ cell differentiation from human umbilical cord (UC)-derived MSCs (hUC-MSCs) is determined. The results have demonstrated that the expression of cd34 protein is significantly increased in hUC-MSCs treated with CD34 antibody. In addition, the cell proliferation is increased in hUC-MSCs after treatment with CD34 antibody. Moreover, the expression of PI3K, AKT, p-AKT proteins, which are signaling molecules related to stem cell differentiation, is increased by CD34 antibody. The results suggest that CD34 antibody could promote the differentiation of hUC-MSCs into CD34+ cells and PI3K/AKT may be involved in this important process.

Cage slip characteristics of a cylindrical roller bearing with a trilobe-raceway

Based on dynamic analysis of rolling bearings, the nonlinear dynamic differential equations of a cylindrical roller bearing with a trilobe-raceway were established and solved by the GSTIFF（gear stiff） integer algorithm with a variable step. The influences of structural parameters and the tolerance of the trilobe-raceway, working conditions of the bearing, and the outer ring installation method on cage slip characteristics were investigated. The results show that：（i） The cage slip ratio and bearing rating life of a cylindrical roller bearing with a trilobe-raceway would reduce when the low-radius（radius of the outer raceway contour at the lowest point） and D-value（difference value between the high and low points of the outer raceway contour） decrease, and the former（low-radius） contributes more significantly.（ii） The cage slip ratio of a cylindrical roller bearing with a trilobe-raceway rises with the increase of the bearing speed, and decreases with the increase of the radial force; the variation range increases with the increase of the low-radius.（iii） When the installation angle of the outer ring increases in a period, the cage slip ratio remains unchanged while the bearing rating life rises up a little. Therefore, when installing a cylindrical roller bearing with a trilobe-raceway, the location of the maximum radius shall be under that of the radial force to improve the bearing rating life.（iv） With the increase of the roundness of the base circle where the radius of the lowest points of the trilobe-raceway contour locates, the cage slip ratio rises gradually and the bearing rating life decreases.

Genetic evidence for asymmetric blocking of higher-order chromatin structure by CTCF/cohesin

Dear Editor,Similar to higher-order folding of polypeptide chains into functional proteins,linear DNA molecules are spatially folded in a hierarchical and dynamic manner into three-dimensional(3D)functional chromatin structures in eukaryotic nuclei(Huang and Wu,2016;Rowley and Corces,2018).This dynamic folding is closely related to many nuclear processes such as DNA replication and repair,chromosomal translo­cation,recombination,and segregation,as well as RNA transcription,splicing,and transport.In particular,dynamic long-distance chromatin looping interactions,which result in close spatial contacts between distal enhancers and target promoters,are thought to play a role in controlling precise spatiotemporal as well as cell-type specific gene expression during animal development(Rowley and Corces,2018).Mammalian genomes contain numerous noncoding regula­tory elements that regulate these dynamic long-distance chromatin looping interactions.