The nervous system is the most complex system in the human body, and the normal development of the central nervous system (CNS) is essential for maintaining the healthy life activities of the individual. CNS development requires the orchestration of multiple internal or external or direct or indirect factors to regulate neural stem cell fate specification. Here, we provide a broad overview of the regulatory system of nerve cell fate decisions and discuss the latest technological approaches to achieve neural regeneration.
View Article and Find Full Text PDFSonodynamic therapy (SDT) is a burgeoning and newfangled therapy modality with great application potential. Sonosensitizers are essential factors used to ensure the effectiveness of SDT. For the past few years, a lot of scientists have discovered many valid ways to refine and improve the performance of SDT.
View Article and Find Full Text PDFIntroduction: Immunotherapy has led to a paradigm shift in reinvigorating treatment of cancer. Nevertheless, tumor associated macrophages (TAMs) experience functional polarization on account of the generation of suppressive metabolites, contributing to impaired antitumor immune responses.
Methods: Hence, metabolic reprogramming of tumor microenvironment (TME) can synergistically improve the efficacy of anti-tumor immunotherapy.
Alzheimer's disease (AD) is a progressive neurodegenerative condition that has become an important public health problem of global concern, and the early diagnosis and etiological treatment of AD are currently the focus of research. In the course of clinical treatment, approved clinical drugs mainly serve to slow down the disease process by relieving patients' clinical symptoms. However, these drugs do not target the cause of the disease, and the lack of specificity of these drugs has led to undesirable side effects in treatment.
View Article and Find Full Text PDFRegulatory cell death is an important way to eliminate the DNA damage that accompanies the rapid proliferation of neural stem cells during cortical development, including pyroptosis, apoptosis, and so on. Here, the study reports that the absence of GSDMD-mediated pyroptosis results in defective DNA damage sensor pathways accompanied by aberrant neurogenesis and autism-like behaviors in adult mice. Furthermore, GSDMD is involved in organizing the mitochondrial electron transport chain by regulating the AMPK/PGC-1α pathway to target Aifm3.
View Article and Find Full Text PDFBlood vessels play a crucial role in maintaining the stem cell niche in both tumours and developing organs. Cell competition is critical for tumour progression. We hypothesise that blood vessels may act as a regulator of this process.
View Article and Find Full Text PDFThe reprogramming of tumor metabolism presents a substantial challenge for effective immunotherapy, playing a crucial role in developing an immunosuppressive microenvironment. In particular, the degradation of the amino acid L-tryptophan (Trp) to kynurenine (Kyn) by indoleamine-pyrrole 2,3-dioxygenase 1 (IDO1) is one of the most clinically validated pathways for immune suppression. Thus, regulating the Trp/Kyn metabolism by IDO1 inhibition represents a promising strategy for enhancing immunotherapy.
View Article and Find Full Text PDFAtg8 family proteins play crucial roles in autophagy to maintain cellular homeostasis. However, the physiological roles of Atg8 family proteins have not been systematically determined. In this study, we generated Atg8a and Atg8b (homologs of Atg8 in Drosophila melanogaster) knockout flies.
View Article and Find Full Text PDFThis study introduces a novel wash-type affinity-primed proximity labeling (WAPL) strategy for labeling and surface engineering of the MUC1 protein neighboring system. The strategy entails the utilization of peroxidase in conjunction with a MUC1-selective aptamer, facilitating targeted binding to MUC1 and inducing covalent labeling of the protein neighboring system. This study reveals a novel finding that the WAPL strategy demonstrates superior labeling efficiency in comparison to nonwash-type affinity-primed proximity labeling, marking the first instance of such observations.
View Article and Find Full Text PDFNanovaccines have emerged as promising agents for cancer therapy because of their ability to induce specific immune responses without off-target effects. However, inadequate cytotoxic T lymphocyte response and low antigen/adjuvant encapsulation remain major obstacles to vaccinating against cancer. Herein, we designed a stimulator of interferon genes (STING) pathway-activating nanovaccine based on hollow metal-organic frameworks (MOFs) for tumor treatment.
View Article and Find Full Text PDFMammalian neocortex formation follows a stereotypical pattern wherein the self-renew and differentiation of neural stem cells are coordinated with diverse organelle dynamics. However, the role of lysosomes in brain development has long been overlooked. Here, we demonstrate the highly dynamic lysosomal quantities, types, and localizations in developing brain.
View Article and Find Full Text PDFLipid raft-specific glycosylation has been implicated in many biological processes, including intracellular trafficking, cell adhesion, signal transduction, and host-pathogen interactions. The major predicament in lipid raft-specific glycosylation research is the unavailability of tools for tracking and manipulating glycans on lipid rafts at the microstructural level. To overcome this challenge, we developed a multifunctional proximity labeling (MPL) platform that relies on cholera toxin B subunit to localize horseradish peroxidase on lipid rafts.
View Article and Find Full Text PDFDNA walkers have been widely explored and applied as biosensor elements to detect disease-related biomarkers. Traditional interface-anchored DNA walkers typically have a fixed swing arm range and an orientation of the preset track, which might complicate the design of a sensor system and limit its application in more scenes. We propose a simple electrochemical aptasensor to accurately detect Alzheimer's disease (AD) based on a nicking enzyme-powered DNA walker.
View Article and Find Full Text PDFARID1A, an SWI/SNF chromatin-remodeling gene, is commonly mutated in cancer and hypothesized to be a tumor suppressor. Recently, loss-of-function of ARID1A gene has been shown to cause intellectual disability. Here we generate Arid1a conditional knockout mice and investigate Arid1a function in the hippocampus.
View Article and Find Full Text PDFCancer cell receives extracellular signal inputs to obtain a stem-like status, yet how tumor microenvironmental (TME) neural signals steer cancer stemness to establish the hierarchical tumor architectures remains elusive. Here, a pan-cancer transcriptomic screening for 10852 samples of 33 TCGA cancer types reveals that cAMP-responsive element (CRE) transcription factors are convergent activators for cancer stemness. Deconvolution of transcriptomic profiles, specification of neural markers and illustration of norepinephrine dynamics uncover a bond between TME neural signals and cancer-cell CRE activity.
View Article and Find Full Text PDFThe regulation of neural stem cell (NSC) proliferation and differentiation during brain development is a precisely controlled process, with the production of different neuronal subtypes governed by strict timelines. Glutamate is predominantly used as a neurotransmitter by the subtypes of neurons in the various layers of the cerebral cortex. The expression pattern of BCAT1, a gene involved in glutamate metabolism, in the different layers of neurons has yet to be fully understood.
View Article and Find Full Text PDFDuring brain development, the proliferation and differentiation of neural stem cells (NSCs) are precisely regulated. Defects in embryonic brain development can lead to serious developmental disorders. The cerebral cortex is the most evolved and complicated structure in the mammalian brain.
View Article and Find Full Text PDFThe vascular system and the neural system processes occur simultaneously, the interaction among them is fundamental to the normal development of the central nervous system. Arid1a (AT-rich interaction domain 1A), which encodes an epigenetic subunit of the SWI/SNF chromatin-remodelling complex, is associated with promoter-mediated gene regulation and histone modification. However, the molecular mechanism of the interaction between cerebrovascular and neural progenitor cells (NPCs) remains unclear.
View Article and Find Full Text PDFMicroglia are the primary source of transglutaminase 2 (TGM2) in the brain; however, the roles of microglial TGM2 in neural development and disease are still not well known. The aim of this study is to elucidate the role and mechanisms of microglial TGM2 in the brain. A mouse line with a specific knockout of Tgm2 in microglia was generated.
View Article and Find Full Text PDFTraumatic brain injury usually results in neuronal loss and cognitive deficits. Promoting endogenous neurogenesis has been considered as a viable treatment option to improve functional recovery after TBI. However, neural stem/progenitor cells (NSPCs) in neurogenic regions are often unable to migrate and differentiate into mature neurons at the injury site.
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