Transcriptional and epigenetic dysregulation impairs generation of proliferative neural stem and progenitor cells during brain aging.

The decline in stem cell function during aging may affect the regenerative capacity of mammalian organisms; however, the gene regulatory mechanism underlying this decline remains unclear. Here we show that the aging of neural stem and progenitor cells (NSPCs) in the male mouse brain is characterized by a decrease in the generation efficacy of proliferative NSPCs rather than the changes in lineage specificity of NSPCs. We reveal that the downregulation of age-dependent genes in NSPCs drives cell aging by decreasing the population of actively proliferating NSPCs while increasing the expression of quiescence markers. We found that epigenetic deregulation of the MLL complex at promoters leads to transcriptional inactivation of age-dependent genes, highlighting the importance of the dynamic interaction between histone modifiers and gene regulatory elements in regulating transcriptional program of aging cells. Our study sheds light on the key intrinsic mechanisms driving stem cell aging through epigenetic regulators and identifies potential rejuvenation targets that could restore the function of aging stem cells.

A Pyrazolate Osmium(VI) Nitride Exhibits Anticancer Activity through Modulating Protein Homeostasis in HepG2 Cells.

Interest in the third-row transition metal osmium and its compounds as potential anticancer agents has grown in recent years. Here, we synthesized the osmium(VI) nitrido complex Na[OsVI(N)(tpm)2] (tpm = [5-(Thien-2-yl)-1H-pyrazol-3-yl]methanol), which exhibited a greater inhibitory effect on the cell viabilities of the cervical, ovarian, and breast cancer cell lines compared with cisplatin. Proteomics analysis revealed that Na[OsVI(N)(tpm)2] modulates the expression of protein-transportation-associated, DNA-metabolism-associated, and oxidative-stress-associated proteins in HepG2 cells. Perturbation of protein expression activity by the complex in cancer cells affects the functions of the mitochondria, resulting in high levels of cellular oxidative stress and low rates of cell survival. Moreover, it caused G2/M phase cell cycle arrest and caspase-mediated apoptosis of HepG2 cells. This study reveals a new high-valent osmium complex as an anticancer agent candidate modulating protein homeostasis.

Transformation of Plant to Resource Acquisition Under High Nitrogen Addition Will Reduce Green Roof Ecosystem Functioning.

Ecosystem engineering, such as green roof, provides numerous key ecosystem functions dependent on both plants and environmental changes. In the recent years, global nitrogen (N) deposition has become a hot topic with the intensification of anthropogenic disturbance. However, the response of green roof ecosystems to N deposition is still not clear. To explore the effects of N addition on plant ecological strategy and ecosystem functioning (biomass), we conducted a 3-month N addition simulation experiment using 12 common green roof species from different growth forms on an extensive green roof in Tianjin, China. The experiment included three different N addition treatments (0, 3.5, and 10.5 gN m-2 year-1). We found that plants with the resource-acquisitive strategy were more suitable to survive in a high N environment, since both aboveground and belowground traits exhibited synergistic effects. Moreover, N addition indirectly decreased plant biomass, indicating that ecosystem functioning was impaired. We highlight that there is a trade-off between the survival of green roof species and keeping the ecosystem functioning well in the future N deposition. Meanwhile, these findings also provide insights into how green roof species respond to global climate change and offer important information for better managing and protecting similar ecosystem engineering in the background of high N deposition.

Teachers Self-Efficacy and Employee Brand Based Equity: A Perspective of College Students.

Teachers working in institutions like to affiliate themselves with their organizations taking into account their efficacy toward jobs along with encouraging students in studies. The main objective of the present study is to identify the teachers' self-efficacy on collective self-efficacy, academic psychological capital, and students' engagement which consequently affect brand-based equity. The population taken in this study is college students across China, deriving a sample size of 316. The sample has been selected on the basis of the convenience sampling technique. Smart PLS 3.3.5 software has been used in the present study to analyze data for structural equation modeling. The findings of the study had shown that teachers' self-efficacy does not have any impact on employee-based brand equity, however, significantly affects collective self-efficacy, academic psychological capital, and student engagement. Further, strong and moderate mediations have also been confirmed in the study for collective self-efficacy, academic psychological capital, student engagement between the relationships between teachers self-efficacy and brand based equity, however, collective self-efficacy and academic psychological capital could not find any mediating significance. The results have identified the significant role of teachers' self-efficacy for collective self-efficacy, academic psychological capital, and student engagement. These empirical findings suggest policy implications for the retention of students in colleges across China.

Cbx3 maintains lineage specificity during neural differentiation.

Chromobox homolog 3 (Cbx3/heterochromatin protein 1γ [HP1γ]) stimulates cell differentiation, but its mechanism is unknown. We found that Cbx3 binds to gene promoters upon differentiation of murine embryonic stem cells (ESCs) to neural progenitor cells (NPCs) and recruits the Mediator subunit Med26. RNAi knockdown of either Cbx3 or Med26 inhibits neural differentiation while up-regulating genes involved in mesodermal lineage decisions. Thus, Cbx3 and Med26 together ensure the fidelity of lineage specification by enhancing the expression of neural genes and down-regulating genes specific to alternative fates.

Ephrin-A3 and ephrin-A4 contribute to microglia-induced angiogenesis in brain endothelial cells.

The association of microglia with brain vasculature during development and the reduced brain vascular complexity in microglia-deficient mice suggest the role of microglia in cerebrovascular angiogenesis. However, the underlying molecular mechanism remains unclear. Here, using an in vitro angiogenesis model, we found the culture supernatant of BV2 microglial cells significantly enhanced capillary-like tube formation and migration of brain microvascular endothelial cells (BMECs). The expression of angiogenic factors, ephrin-A3 and ephrin-A4, were specifically upregulated in BMECs exposed to BV2-derived culture supernatant. Knockdown of ephrin-A3 and ephrin-A4 in BMECs by siRNA significantly attenuated the enhanced angiogenesis and migration of BMECs induced by BV2 supernatant. Our further results indicated that the ability of BV2 supernatant to promote endothelial angiogenesis was caused by the soluble tumor necrosis factor α (TNF-α) released from BV2 microglial cells. Moreover, the upregulations of ephrin-A3 and ephrin-A4 in BMECs in response to BV2 supernatant were effectively abolished by neutralization antibody against TNF-α and TNF receptor 1, respectively. The present study provides evidence that microglia upregulates endothelial ephrin-A3 and ephrin-A4 to facilitate in vitro angiogenesis of brain endothelial cells, which is mediated by microglia-released TNF-α.