Metabolic changes in neuroendocrine neoplasms.

Neuroendocrine neoplasms (NENs) are a group of highly heterogeneous neoplasms originating from neuroendocrine cells with a gradually increased incidence. Metabolic change is one of the recognized markers of tumor progression, which has been extensively and systematically studied in other malignant tumors. However, metabolic change in NENs has been relatively poorly studied, and systematic reviews are lacking.

Reducing Excessive Screen Time Among Primary School-aged Children Through Caregivers' Parenting Behaviors: A Feasibility Pilot Study in China.

Objective: Given the well-documented associations between excessive screen time (ST) and adverse health outcomes, this pilot study aimed to examine the applicability and effectiveness of a multicomponent intervention that combined strategies to enhance caregivers' screen-related parenting practices with efforts to create a supportive community environment to reduce children's ST in a county in China.

Methods: A 2-arm, cluster-randomized, wait-list controlled design was used. Eight communities and 336 caregivers of primary school-aged children were randomly assigned to intervention and control groups.

Scutellarin Attenuates Pro-Inflammatory Foam Cell Formation and Facilitates M2 Polarization in Microglia during Copper Homeostasis Imbalance via the MAPK Signaling Pathway.

Background: Clinical and experimental evidence indicates that copper has the ability to promote the progressive development of demyelinating diseases such as multiple sclerosis. Microglia-mediated neuroinflammation is believed to play a crucial role in this process. Scutellarin, a flavonoid compound, has anti-inflammatory, antioxidative, and neuroprotective effects.

Btbd8 deficiency exacerbates bleomycin-induced pulmonary fibrosis in mice by enhancing myofibroblast accumulation and inflammatory responses.

BTBD8 contributes to the pathogenesis of inflammatory bowel disease through regulating intestinal barrier integrity and inflammation. However, its role in idiopathic pulmonary fibrosis (IPF) remains unknown. Here we investigated whether BTBD8 plays a role in bleomycin-induced pulmonary fibrosis.

-induced promotes the malignant progression of pancreatic neuroendocrine neoplasms through -mediated lipid metabolism.

N6-methyladenosine (m6A) is considered the most prevalent RNA epigenetic regulator in cancer. FTO, an m6A demethylase, has been implicated in contributing to the progression of various cancers by up-regulating the expression of multiple oncogenes. However, studies exploring its impact on lipid metabolism in cancer, especially in pNENs, remain scarce.

ERK phosphorylates ESRRB to regulate the self-renewal and differentiation of mouse embryonic stem cells.

MEK (mitogen-activated protein kinase) inhibitor is widely used for culturing pluripotent stem cells, while prolonged MEK inhibition compromises the developmental potential of mouse embryonic stem cells (ESCs), implying a dual role of MEK/ERK (extracellular signal-regulated kinase) signaling in pluripotency maintenance. To better understand the mechanism of MEK/ERK in pluripotency maintenance, we performed quantitative phosphoproteomic analysis and identified 169 ERK substrates, which are enriched for proteins involved in stem cell population maintenance, embryonic development, and mitotic cell cycle. Next, we demonstrated that ERK phosphorylates a well-known pluripotency factor ESRRB on Serine 42 and 43.

DDX18 coordinates nucleolus phase separation and nuclear organization to control the pluripotency of human embryonic stem cells.

Pluripotent stem cells possess a unique nuclear architecture characterized by a larger nucleus and more open chromatin, which underpins their ability to self-renew and differentiate. Here, we show that the nucleolus-specific RNA helicase DDX18 is essential for maintaining the pluripotency of human embryonic stem cells. Using techniques such as Hi-C, DNA/RNA-FISH, and biomolecular condensate analysis, we demonstrate that DDX18 regulates nucleolus phase separation and nuclear organization by interacting with NPM1 in the granular nucleolar component, driven by specific nucleolar RNAs.

DCP1A, a MEK substrate, regulates the self-renewal and differentiation of mouse embryonic stem cells.

Mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors are widely applied to maintain pluripotency, while prolonged MEK inhibition compromises the developmental potential of mouse embryonic stem cells (ESCs). To understand the mechanism of MEK in pluripotency maintenance, we first demonstrated that MEK regulates gene expression at post-transcriptional steps. Consistently, many of the 66 MEK substrates identified by quantitative phosphoproteomics analysis are involved in RNA processing.

Lactylation of Hdac1 regulated by Ldh prevents the pluripotent-to-2C state conversion.

Background: Cellular metabolism regulates the pluripotency of embryonic stem cells (ESCs). Yet, how metabolism regulates the transition among different pluripotent states remains elusive. It has been shown that protein lactylation, which uses lactate, a metabolic product of glycolysis, as a substrate, plays a critical role in various biological events.

Hypoxia drives CBR4 down-regulation promotes gastroenteropancreatic neuroendocrine tumors via activation mammalian target of rapamycin mediated by fatty acid synthase.

Hypoxia has been highly proven a hallmark of tumor micro-environment, promoting the malignant phenotypes, playing a crucial role from tumor initiation, progression, invasion, and intravasation to metastatic dissemination and outgrowth. Increasing evidence also showed that hypoxia mediated the abnormal lipid metabolism in cancer by regulating various oncogenic signal pathways. However, it is still unclear but attractive how hypoxia specifically functioned and changed the condition of the tumor micro-environment.

Novel role for Ddx39 in differentiation and telomere length regulation of embryonic stem cells.

Erk signaling is indispensable for the self-renewal and differentiation of mouse embryonic stem cells (ESCs), as well as telomere homeostasis. But how Erk regulates these biological processes remains unclear. We identified 132 Erk2 interacting proteins by co-immunoprecipitation and mass spectrometric analysis, and focused on Ddx39 as a potential Erk2 substrate.

deficiency reduces susceptibility to colitis by enhancing intestinal barrier function and suppressing inflammation.

Introduction: has been identified as a susceptible gene for inflammatory bowel diseases (IBD). However, the function of in normal development and IBD pathogenesis remains unknown.

Methods: We administered drinking water with 3% dextran sodium sulfate (DSS) to wild-type (WT) and knockout (KO) mice for seven consecutive days to induce IBD.

Glycolysis-Stimulated Esrrb Lactylation Promotes the Self-Renewal and Extraembryonic Endoderm Stem Cell Differentiation of Embryonic Stem Cells.

Embryonic stem cells (ESCs) favor glycolysis over oxidative phosphorylation for energy production, and glycolytic metabolism is critical for pluripotency establishment, maintenance, and exit. However, an understanding of how glycolysis regulates the self-renewal and differentiation of ESCs remains elusive. Here, we demonstrated that protein lactylation, regulated by intracellular lactate, contributes to the self-renewal of ESCs.

The NR2B-targeted intervention alleviates the neuronal injuries at the sub-acute stage of cerebral ischemia: an exploration of stage-dependent strategy against ischemic insults.

Stroke is reported to be the second leading cause of death worldwide, among which ischemic stroke has fourfold greater incidence than intracerebral hemorrhage. Excitotoxicity induced by NMDAR plays a central role in ischemic stroke-induced neuronal death. However, intervention targeted NMDARs against ischemic stroke has failed, which may result from the complex composition of NMDARs and the dynamic changes of their subunits.

Hbxip is essential for murine embryogenesis and regulates embryonic stem cell differentiation through activating mTORC1.

HBXIP, also named LAMTOR5, has been well characterized as a transcriptional co-activator in various cancers. However, the role of Hbxip in normal development remains unexplored. Here, we demonstrated that homozygous knockout of Hbxip leads to embryonic lethality, with retarded growth around E7.

Homozygous Loss of , but not its Haploinsufficiency, Leads to Male Infertility and Fertilization Failure.

The gene has been associated with male infertility. Male chimera mice were infertile, supporting the prevailing view that haploinsufficiency causes male infertility. In this study, we identified a heterozygous mutation on , c.

The lupus autoantigen La/Ssb is an Xist-binding protein involved in Xist folding and cloud formation.

Using the programmable RNA-sequence binding domain of the Pumilio protein, we FLAG-tagged Xist (inactivated X chromosome specific transcript) in live mouse cells. Affinity pulldown coupled to mass spectrometry was employed to identify a list of 138 candidate Xist-binding proteins, from which, Ssb (also known as the lupus autoantigen La) was validated as a protein functionally critical for X chromosome inactivation (XCI). Extensive XCI defects were detected in Ssb knockdown cells, including chromatin compaction, death of female mouse embryonic stem cells during in vitro differentiation and chromosome-wide monoallelic gene expression pattern.

lncRNA 5430416N02Rik Promotes the Proliferation of Mouse Embryonic Stem Cells by Activating Mid1 Expression through 3D Chromatin Architecture.

Both 3D chromatin architecture and long non-coding RNAs (lncRNAs) play essential roles in pluripotency maintenance. However, whether lncRNAs are involved in organizing 3D chromatin structure remains largely unexplored. We identified 39 lncRNAs bound by Klf4, among which we further revealed the 5430416N02Rik promoter is a chromatin interaction hub.

Cops5 safeguards genomic stability of embryonic stem cells through regulating cellular metabolism and DNA repair.

The highly conserved COP9 signalosome (CSN), composed of 8 subunits (Cops1 to Cops8), has been implicated in pluripotency maintenance of human embryonic stem cells (ESCs). Yet, the mechanism for the CSN to regulate pluripotency remains elusive. We previously showed that Cops2, independent of the CSN, is essential for the pluripotency maintenance of mouse ESCs.

Live-Cell Imaging and Functional Dissection of Xist RNA Reveal Mechanisms of X Chromosome Inactivation and Reactivation.

We double-tagged Xist (inactivated X chromosome-specific transcript), a prototype long non-coding RNA pivotal for X chromosome inactivation (XCI), using the programmable RNA sequence binding domain of Pumilio protein, one tag for live-cell imaging and the other replacing A-repeat (a critical domain of Xist) to generate "ΔA mutant" and to tether effector proteins for dissecting Xist functionality. Based on the observation in live cells that the induced XCI in undifferentiated embryonic stem (ES) cells is counteracted by the intrinsic X chromosome reactivation (XCR), we identified Kat8 and Msl2, homologs of Drosophila dosage compensation proteins, as players involved in mammalian XCR. Furthermore, live-cell imaging revealed the obviously undersized ΔA Xist cloud signals, clarifying an issue regarding the previous RNA fluorescence in situ hybridization results.

Antitumor effects of anlotinib in thyroid cancer.

There is no effective treatment for patients with poorly differentiated papillary thyroid cancer or anaplastic thyroid cancer (ATC). Anlotinib, a multi-kinase inhibitor, has already shown antitumor effects in various types of carcinoma in a phase I clinical trial. In this study, we aimed to better understand the effect and efficacy of anlotinib against thyroid carcinoma cells in vitro and in vivo.

COPS2 Antagonizes OCT4 to Accelerate the G2/M Transition of Mouse Embryonic Stem Cells.

Proper regulation of the cell cycle is essential to safeguard the genomic integrity of embryonic stem cells (ESCs) while maintaining the fast proliferation rate. The pluripotency factor OCT4 has been shown to inhibit CDK1 activation, thus preventing mitotic entry and facilitating the maintenance of genomic integrity. Yet, how ESCs enter mitosis in the presence of OCT4 remains unclear.