Search

Adult neurogenesis, arising from quiescent radial-glia-like neural stem cells (RGLs), occurs throughout life in the dentate gyrus. How neural stem cells are maintained throughout development to sustain adult mammalian neurogenesis is not well understood. Here, we show that milk fat globule-epidermal growth factor (EGF) 8 (Mfge8), a known phagocytosis factor, is highly enriched in quiescent RGLs in the dentate gyrus. Mfge8-null mice exhibit decreased adult dentate neurogenesis, and furthermore, adult RGL-specific deletion of Mfge8 leads to RGL overactivation and depletion. Similarly, loss of Mfge8 promotes RGL activation in the early postnatal dentate gyrus, resulting in a decreased number of label-retaining RGLs in adulthood. Mechanistically, loss of Mfge8 elevates mTOR1 signaling in RGLs, inhibition of which by rapamycin returns RGLs to quiescence. Together, our study identifies a neural-stem-cell-enriched niche factor that maintains quiescence and prevents developmental exhaustion of neural stem cells to sustain continuous neurogenesis in the adult mammalian brain.

Fluorescent imaging and biosensing in the near‐infrared‐II (NIR‐II) window holds great promise for non‐invasive, radiation‐free, and rapid‐response clinical diagnosis. However, it's still challenging to develop bright NIR‐II fluorophores. In this study, we report a new strategy to enhance the brightness of NIR‐II aggregation‐induced emission (AIE) fluorophores through intramolecular electrostatic locking. By introducing sulfur atoms into the side chains of the thiophene bridge in TSEH molecule, the molecular motion of the conjugated backbone can be locked through intramolecular interactions between the sulfur and nitrogen atoms. This leads to enhanced NIR‐II fluorescent emission of TSEH in both solution and aggregation states. Notably, the encapsulated nanoparticles (NPs) of TSEH show enhanced brightness, which is 2.6‐fold higher than TEH NPs with alkyl side chains. The in vivo experiments reveal the feasibility of TSEH NPs in vascular and tumor imaging with a high signal‐to‐background ratio and precise resection for tiny tumors. In addition, polystyrene nanospheres encapsulated with TSEH are utilized for antigen detection in lateral flow assays, showing a signal‐to‐noise ratio 1.9‐fold higher than the TEH counterpart in detecting low‐concentration antigens. This work highlights the potential for developing bright NIR‐II fluorophores through intramolecular electrostatic locking and their potential applications in clinical diagnosis and biomedical research. [ABSTRACT FROM AUTHOR]

SUMMARY: Carotenoids are photosynthetic pigments and antioxidants that contribute to different plant colors. However, the involvement of TOPLESS (TPL/TPR)‐mediated histone deacetylation in the modulation of carotenoid biosynthesis through ethylene‐responsive element‐binding factor‐associated amphiphilic repression (EAR)‐containing transcription factors (TFs) in apple (Malus domestica Borkh.) is poorly understood. MdMYB44 is a transcriptional repressor that contains an EAR repression motif. In the present study, we used functional analyses and molecular assays to elucidate the molecular mechanisms through which MdMYB44‐MdTPR1‐mediated histone deacetylation influences carotenoid biosynthesis in apples. We identified two carotenoid biosynthetic genes, MdCCD4 and MdCYP97A3, that were confirmed to be involved in MdMYB44‐mediated carotenoid biosynthesis. MdMYB44 enhanced β‐branch carotenoid biosynthesis by repressing MdCCD4 expression, whereas MdMYB44 suppressed lutein level by repressing MdCYP97A3 expression. Moreover, MdMYB44 partially influences carotenoid biosynthesis by interacting with the co‐repressor TPR1 through the EAR motif to inhibit MdCCD4 and MdCYP97A3 expression via histone deacetylation. Our findings indicate that the MdTPR1‐MdMYB44 repressive cascade regulates carotenoid biosynthesis, providing profound insights into the molecular basis of histone deacetylation‐mediated carotenoid biosynthesis in plants. These results also provide evidence that the EAR‐harboring TF/TPL repressive complex plays a universal role in histone deacetylation‐mediated inhibition of gene expression in various plants. Significance Statement: MdMYB44 regulated carotenoid biosynthesis partially by interacting with co‐repressor TPR1 via EAR motif to inhibit MdCCD4 and MdCYP97A3 expression through histone deacetylation, providing evidence that the EAR‐harboring TF/TPL repressive complex has a universal role in histone deacetylation‐mediated gene expression inhibition in various plants. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the role of Nkx1‐2, a transcription factor with the NK homeobox domain, in the regulation of fat production. Methods: Gene expression was analyzed using quantitative real‐time polymerase chain reaction or transcriptome sequencing. CRISPR/Cas9 technology was employed to generate nkx1.2 knockout zebrafish and nkx1.2‐deleted 3T3‐L1 cells. Lipid droplet production in zebrafish larvae was visually quantified using Nile red staining, whereas lipid droplets in 3T3‐L1 cells were stained with Oil red O. The binding of Nkx1‐2 to the promoter was verified through an electrophoretic mobility shift assay experiment. Results: Nkx1‐2 plays crucial roles in the regulation of fat production in zebrafish. Knockout of nkx1.2 in zebrafish leads to weight loss, accompanied by significantly reduced lipid droplet production and decreased visceral and liver fat content. Furthermore, genes related to lipid biosynthesis are significantly downregulated. In 3T3‐L1 preadipocytes, Nkx1‐2 induces differentiation into mature adipocytes by binding to the cebpa promoter, thereby activating its transcription. Additionally, the expression of nkx1.2 is regulated by the p38 MAPK, JNK, or Smad2/3 signaling pathways in 3T3‐L1 cells. Conclusions: Our findings suggest that Nkx1‐2 functions as a positive regulator of fat production, playing a critical role in adipocyte differentiation and lipid biosynthesis. [ABSTRACT FROM AUTHOR]

It remains a challenge for existing financial models to accurately capture the shapes of implied volatility (IV) of options with all maturities simultaneously. Inspired by Chen et al.'s empirical finding, 'the shorter the option expiry, the higher the IV is', we propose a novel and simple approach to solve this challenge, by introducing a term-structure-based correction (i.e. an exponential increase function of the options expiry) to the volatility of volatility (vol–vol) term of the classical Heston stochastic volatility model. We derive an approximate formula for the IV under the corrected model with the perturbation method and further apply the formula to predict the IVs of options written on the Shanghai Stock Exchange 50 ETF. Numerical experiments and empirical results show that the introduction of a term-structure-based correction function surely overcomes the deficiency of the classical Heston model in capturing the short-term IVs, thus improving notably its performance of IV forecasting. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is characterized by molecular heterogeneity with various immune cell infiltration patterns, which have been associated with therapeutic sensitivity and resistance. In particular, dendritic cells (DCs) are recently discovered to be associated with prognosis and survival in cancer. However, how DCs differ among ESCC patients has not been fully comprehended. Recently, the advance of single-cell RNA sequencing (scRNA-seq) enables us to profile the cell types, states, and lineages in the heterogeneous ESCC tissues. Here, we dissect the ESCC tumor microenvironment at high resolution by integrating 192,078 single cells from 60 patients, including 4379 DCs. We then used Scissor, a method that identifies cell subpopulations from single-cell data that are associated bulk samples with genomic and clinical information, to stratify DCs into Scissorhi and Scissorlow subtypes. We applied the Scissorhi gene signature to stratify ESCC scRNAseq patient, and we found that PD-L1, TIGIT, PVR and IL6 ligand-receptor-mediated cell interactions existed mainly in Scissorhi patients. Finally, based on the Scissor results, we successfully developed a validated prognostic risk model for ESCC and further validated the reliability of the risk prediction model by recruiting 40 ESCC clinical patients. This information highlights the importance of these genes in assessing patient prognosis and may help in the development of targeted or personalized therapies for ESCC. [ABSTRACT FROM AUTHOR]

In order to cultivate children's computational thinking, researchers have developed many excellent programming systems. Among them, the tangible programming systems combined with graphic output have been widely accepted because of the intuitive input method and diversified visual feedback. However, few of them support collaborative learning or programming. Little is known about children's experiences, emotional states and behaviours on collaborative programming. Motivated by this gap, we present a novel tangible and collaborative enabled programming system named Lighters, which designed for children aged 7–10 and had two types of collaboration modes (block-based and role-based). We conducted an user experiment with 24 children, and collected physiological (EDA), questionnaire, video recording and interview data for analysis. Based on our experiment results, Lighters are effective in helping children learn to program collaboratively. In addition, Lighters can mobilize children's positive emotions and enthusiasm to learn programming. Compared with block-based collaboration, role-based collaboration is more likely to stimulate children's emotional states and has a better effect on learning programming. [ABSTRACT FROM AUTHOR]