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The blood brain barrier (BBB) limits the application of most therapeutic drugs for neurological diseases (NDs). Hybrid cell membrane‐coated nanoparticles derived from different cell types can mimic the surface properties and functionalities of the source cells, further enhancing their targeting precision and therapeutic efficacy. Neuroinflammation has been increasingly recognized as a critical factor in the pathogenesis of various NDs, especially Alzheimer's disease (AD). In this study, a novel cell membrane coating is designed by hybridizing the membrane from platelets and chemokine (C–C motif) receptor 2 (CCR2) cells are overexpressed to cross the BBB and target neuroinflammatory lesions. Past unsuccessful endeavors in AD drug development underscore the challenge of achieving favorable outcomes when utilizing single‐mechanism drugs.Two drugs with different mechanisms of actions into liposomes are successfully loaded to realize multitargeting treatment. In a transgenic mouse model for familial AD (5xFAD), the administration of these drug‐loaded hybrid cell membrane liposomes results in a significant reduction in amyloid plaque deposition, neuroinflammation, and cognitive impairments. Collectively, the hybrid cell membrane‐coated nanomaterials offer new opportunities for precise drug delivery and disease‐specific targeting, which represent a versatile platform for targeted therapy in AD. [ABSTRACT FROM AUTHOR]

BackgroundIn eukaryotes, tRNA trafficking between the nucleus and cytoplasm is a complex process connected with cell cycle regulation. Such trafficking is therefore of fundamental importance in cell biology, and disruption of this process has grave consequences for cell viability and survival. To cope with harsh habitats, Artemia has evolved a special reproductive mode to release encysted embryos in which cell division can be maintained in a dormancy state for a long period.ResultsUsing Artemia as a peculiar model of the cell cycle, an La-related protein from Artemia, named Ar-Larp, was found to bind to tRNA and accumulate in the nucleus, leading to cell cycle arrest and controlling the onset of diapause formation in Artemia. Furthermore, exogenous gene expression of Ar-Larp could induce cell cycle arrest in cancer cells and suppress tumor growth in a xenograft mouse model, similar to the results obtained in diapause embryos of Artemia. Our study of tRNA trafficking indicated that Ar-Larp controls cell cycle arrest by binding to tRNAs and influencing their retrograde movement from the cytoplasm to the nucleus, which is connected to pathways involved in cell cycle checkpoints.ConclusionsThese findings in Artemia offer new insights into the mechanism underlying cell cycle arrest regulation, as well as providing a potentially novel approach to study tRNA retrograde movement from the cytoplasm to the nucleus.

Mining is gradually progressed toward the in-depth area of No.8 solid coal seam in No.3 panel of Baode Coal Mine. In order to secure safe mining in this area, a systematic analysis is conducted on the geological factors that influence gas occurrence. Based on the basic data actually measured at site, grey relational analysis (GRA) is adopted for predictive analysis of influencing factors (depth, coal seam thickness, metamorphic grade, sand to mud ratio of roof, sand to mud ratio of floor, geological structure and washout), followed by establishment of a grey relational model. Then, the relation degree among factors is calculated, thus identifying the main controlling factors of gas occurrence. The research result suggests: the main geological factors that influence gas occurrence in No.8 coal seam are geological structure and washout. A model equation is established for prediction of gas content using multiple regression method: y=3.2429+0.0047X1+0.0079X2-0.0180X3+0.0016X4-0.0215X5+0.4641X6+0.2001X7. This equation demonstrates high degree of fitting.

Aims: PRRT2 variants are associated with various paroxysmal disorders. To date, more than 90 PRRT2 variants have been reported in PRRT2‐related disorders. Lack of functional study in majority of missense variants makes their pathogenicity uncertain. We aim to evaluate the clinical significance of PRRT2 missense variants by performing in vitro experiments. Methods: We systematically reviewed PRRT2‐related disorders and summarized reported PRRT2 missense variants. Protein expression and subcellular localization of mutant PRRT2 were investigated in mammal cells. American College of Medical Genetics and Genomics (ACMG) guidelines were used to analyze the pathogenicity of PRRT2 missense variants. Results: A total of 29 PRRT2 missense variants were identified in PRRT2‐related disorders. Ten variants were observed to affect both subcellular localization and protein level, three variants only affect membrane localization, and two variants only affect protein level. According to ACMG guidelines, 15 variants were finally classified as "likely pathogenic", three as "benign", three as "likely benign", and eight as "uncertain significance" variants. The likely pathogenic variants were concentrated in the C‐terminal of PRRT2. Conclusions: The pathogenicity of eight uncertain significance variants needs further investigation. C‐terminal of PRRT2 is crucial for its physiological function. [ABSTRACT FROM AUTHOR]

Background: As a response to harsh environments, the crustacean artemia produces diapause gastrula embryos (cysts), in which cell division and embryonic development are totally arrested. This dormant state can last for very long periods but be terminated by specific environmental stimuli. Thus, artemia is an ideal model organism in which to study cell cycle arrest and embryonic development. Principal Finding: Our study focuses on the roles of H3K56ac in the arrest of cell cycle and development during artemia diapause formation and termination. We found that the level of H3K56ac on chromatin increased during diapause formation, and decreased upon diapause termination, remaining basal level throughout subsequent embryonic development. In both HeLa cells and artemia, blocking the deacetylation with nicotinamide, a histone deacetylase inhibitor, increased the level of H3K56ac on chromatin and induced an artificial cell cycle arrest. Furthermore, we found that this arrest of the cell cycle and development was induced by H3K56ac and dephosphorylation of the checkpoint protein, retinoblastoma protein. Conclusions/Significance: These results have revealed the dynamic change in H3K56ac on chromatin during artemia diapause formation and termination. Thus, our findings provide insight into the regulation of cell division during arrest of artemia embryonic development and provide further insight into the functions of H3K56ac. [ABSTRACT FROM AUTHOR]

To study the construction of yeast bioengineering strain which can degrade cellulosic waste, an endo-beta-glucanase III (EG III) cDNA gene of Trichoderma viride AS3.3711 was isolated with RT-PCR protocol. After sequencing it was constructed on S. cerevisiae induceable expression vector pYES2. A L9 (3(4)) orthogonal design was used to optimize yeast sonication assistant transformation. The expression of EG III gene was induced by 2% beta-D-glactose, the transcription and expression of it was detected by Northern blotting and Congo Red method respectively. The endo-beta-glucanase activity was assayed as CMCase activity with CMC-Na as a substrate. The results show that the ORF of EG III was 1254 bp, encoding 418 aa, deducing molecular weight 44.1 x 10(3), group 5 (sonication treat time 60 s, incubate 40 min, SS-DNA 150 microg, heat shock 5 min) was the optimum one of the orthogonal experiment, and EG III transformants can produced clear hydrolysis halos on the Congo-Red-CMC plate. The measure of the enzyme activity show that the expression product can be expressed in active forms and secreted to the medium. The enzyme activity was approached the highest level (0.041 U/mL) when the culture time was 60 h. The optimized enzyme reaction temperature was 50 degrees C and the optimized pH was 5.8.