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Strong evidence from human genetic studies associates the thousand and one amino acid kinase 1 (TAOK1) gene with autism spectrum disorder (ASD). In this work, we discovered a de novo frameshifting mutation in TAOK1 within a Chinese ASD cohort. We found that Taok1 haploinsufficiency induces autistic-like behaviors in mice. Importantly, we observed a significant enrichment of Taok1 in the dorsal raphe nucleus (DRN). The haploinsufficiency of Taok1 considerably restrained the activation of DRN neurons during social interactions, leading to the aberrant phosphorylation of numerous proteins. Intriguingly, the genetic deletion of Taok1 in VGlut3-positive neurons of DRN resulted in mice exhibiting autistic-like behaviors. Ultimately, reintroducing wild-type Taok1, but not its kinase-dead variant, into the DRN of adult mice effectively mitigated the autistic-like behaviors associated with Taok1 haploinsufficiency. This work suggests that Taok1, through its influence in the DRN, regulates social interaction behaviors, providing critical insights into the etiology of ASD. [Display omitted] • Mice with Taok1 haploinsufficiency exhibit both macrocephaly and autistic-like behaviors • Taok1 haploinsufficiency leads to abnormal neural activity upon social interactions in DRN • Genetically deleting Taok1 in the DRN or VGlut3+ neurons in mice leads to ASD-like behaviors • Restoration of TAOK1, but not kinase-dead one, in the DRN rescues the ASD-like behaviors Appropriate neuronal excitability is essential for animal behavior. Wang et al. show that Taok1 haploinsufficiency leads to abnormal neural activity in the DRN, which subsequently leads to autistic-like behaviors in mice. In addition, the study identifies phosphoproteomics in the DRN of Taok1 deficient mice, providing a potential etiology for ASD. [ABSTRACT FROM AUTHOR]

Location has historically been vital to a restaurant's success. However, in the past decade, on-demand food delivery (ODFD) platforms like Meituan, Deliveroo, and Uber Eats have progressively increased their market shares, recently facilitated by the COVID-19 pandemic. Under the new circumstances, are restaurants still constrained by conventional locational factors, such as transport accessibility, customer proximity, and industrial agglomeration? How do ODFD platforms impact the geography of restaurants? This paper innovatively offers a comparative analysis of the different spatial distributions of brick-and-mortar and platform-dependent restaurants. Based on the case of Nanjing, China, robust empirical evidence demonstrates how platformization has spatially affected the catering sector. Using data from the most popular Chinese ODFD platform, Meituan, we analyze the following spatial characteristics of the catering sector in the urban core of Nanjing: transport accessibility, density pattern, agglomeration degree, and horizontal and vertical locational patterns. The findings suggest that platform-dependent restaurants have reduced dependence on transport accessibility. Compared with traditional brick-and-mortar restaurants, platform-dependent restaurants are more dispersed spatially, not only horizontally but also vertically. The digital turn in the catering sector is also noticeably associated with the rise of informal restaurants, such as ghost kitchens in vacant high-rise office spaces. • On-demand food delivery platforms reduce restaurants' dependence on location. • Platformization has spatially affected the catering sector. • Platform-dependent restaurants become less dependent on transport accessibility. • Platform-dependent restaurants are spatially dispersed horizontally and vertically. • Ghost kitchens or informal restaurants appear prevalent in office buildings in Nanjing, China. [ABSTRACT FROM AUTHOR]

[Display omitted] • CircPOLR2A was proved to promote GBM cell growth for the first time. • CeRNA mechanism of circPOLR2A/miR-2113/POU3F2 was first discovered in GBM cells. • POU3F2 activated SOX9 transcription to affect GBM cell growth was identified. Glioblastoma multiforme (GBM) is the most common cancer in nervous system around the world. Little advancement has been achieved in promoting prognosis of GBM patients. Circular RNAs (circRNAs) are suggested as crucial effectors in modulating GBM development. Hsa_circRNA_092437 (circPOLR2A), an up-regulated circRNA in GBM cells, has not been studied yet. In this study, RT-qPCR and western blot assays were applied to detect RNA and protein levels. Cell proliferation and apoptosis were analyzed via functional assays. Subcellular fractionation assay was carried out to determine circPOLR2A distribution in cells. Bioinformatics analysis and mechanism assays were done for detecting relationships among different factors. Rescue assays were performed to confirm validity of circPOLR2A/SOX9 axis. According to experimental results, circPOLR2A was up-regulated in GBM cells and promoted GBM cell proliferation while inhibiting GBM cell apoptosis. CircPOLR2A mainly existed in cell cytoplasm and sponged miR-2113 to positively regulate POU3F2 expression. POU3F2 activated the transcription of SOX9 through interacting with SOX9 promoter (1–500). Rescue assays validated that circPOLR2A influenced GBM cell proliferation and apoptosis via SOX9. To conclude, circPOLR2A enhanced the transcription of SOX9 through miR-2113/POU3F2 axis, thus exacerbating GBM cells growth. [ABSTRACT FROM AUTHOR]

The drug delivery nanosystems with weak acid-triggered surface charge reversal function should be promising for efficient chemotherapy due to the prolonged blood circulation and enhanced the cellular uptake. However, there are only limited reports up to now. In this study, we fabricated a hybrid nanocapsule with a negative-to-positive charge-reversal outer layer triggered by the weak acidity in tumor microenvironment. The short branched polyethylenimine (PEI) with positive charge and weak acid-sensitive hexahydrophthalic anhydride with negative charge were successively modified on the surface of small uniform thioether-bridged hollow mesoporous silica nanospheres with multiple cavities. The modification of PEI as a linker was more favorable for charge reversal than that of aminopropyl group. The constructed hybrid nanocapsules exhibited weak acid (pH 6.0)-triggered charge reversal and drug release behaviors, thus effectively inhibiting the growth of A549 cancer cells. The surface functionalization of hybrid nanocapsules opens new opportunities for the development of silica-based hybrid nanosystems for promising drug delivery. Thioether-bridged hollow mesoporous silica nanocapsules with weak acid-triggered charge reverse and drug release are designed and constructed for efficient tumor drug delivery. Image 1 • Branched PEI and hexahydrophthalic anhydride were modified on thioether-bridged mesoporous organosilica nanocapsules. • The constructed hybrid nanocapsules exhibited weak acid (pH 6.0)-triggered charged reversal and DOX release behaviors. [ABSTRACT FROM AUTHOR]