Additionally, an accumulation of amphisomes greater than 10 μm2 in area were observed in aging oocytes, and this accumulation was mimicked in oocytes treated with lysosomal inhibitor chloroquine. Overall, these findings implicate lysosomal dysfunction as a prominent mechanism by which these age-related changes may occur and highlight the importance of macroautophagy in maintaining mouse pre-ovulatory oocyte quality. This provides a basis for further investigation of dysfunctional autophagy in poor oocyte quality and for the development of therapeutic or preventative strategies to aid in the maintenance of pre-ovulatory oocyte health.

This study aims to investigate the underlying mechanisms of KAT2A/MCT1 axis in renal cell carcinoma (RCC), providing potential therapeutic targets.

We obtained the expression data of KAT2A and MCT1 from The Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) and International Cancer Genome Consortium (ICGC) databases. Differential analysis was conducted via the limma package. The CCK8 assay, soft agar assay, clone formation assay, and patients-derived organoid models were used to detect cell growth. The transwell and wound-healing assays were utilized to detect cell migration. The

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assays were further conducted to assess the oncogenic roles of KAT2A. The transcriptome sequencing and chromatin immunoprecipitation (ChIP) sequencing were conducted to screen KAT2A downstream targets. CRT0066101 research buy The dose-effect curves were used to detect the 50% inhibiting concentration (IC50) of AZD3965. Data analysis was performed in the Graphpad Prism (Version 8.3.0) and R software (Version 3.6.1).

Our study found that KAT2A was highly expressed in RCC versus normal samples. Prognostic analysis indicated that a high KAT2A was an independent biomarker and associated with poor survival outcomes. KAT2A could promote RCC proliferation and distal metastasis

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. Transcriptome analysis and ChIP-seq were combined to find that KAT2A mainly regulated the glycolytic process. Validation and rescue assays revealed that MCT1 was the downstream target of KAT2A, and KAT2A depended on MCT1 to promote RCC malignant phenotypes. Lastly, MCT1 inhibitor (AZD3965) was effective to treat KAT2A-induced RCC progression.

Our study indicated that KAT2A was an oncogenic chromatin modifier that promotes RCC progression by inducing MCT1 expression. We proposed that MCT1 inhibitor (AZD3965) was useful for suppressing RCC.

Our study indicated that KAT2A was an oncogenic chromatin modifier that promotes RCC progression by inducing MCT1 expression. We proposed that MCT1 inhibitor (AZD3965) was useful for suppressing RCC.Zebrafish have superior regenerative capacity in the central nervous system (CNS) compared to mammals. In contrast, medaka were shown to have low regenerative capacity in the adult heart and larval retina, despite the well-documented high tissue regenerative ability of teleosts. Nevertheless, medaka and zebrafish share similar brain structures and biological features to those of mammals. Hence, this study aimed to compare the neural stem cell (NSC) responses and regenerative capacity in the optic tectum of adult medaka and zebrafish after stab wound injury. Limited neuronal differentiation was observed in the injured medaka, though the proliferation of radial glia (RG) was induced in response to tectum injury. Moreover, the expression of the pro-regenerative transcriptional factors ascl1a and oct4 was not enhanced in the injured medaka, unlike in zebrafish, whereas expression of sox2 and stat3 was upregulated in both fish models. Of note, glial scar-like structures composed of GFAP+ radial fibers were observed in the injured area of medaka at 14 days post injury (dpi). Altogether, these findings suggest that the adult medaka brain has low regenerative capacity with limited neuronal generation and scar formation. Hence, medaka represent an attractive model for investigating and evaluating critical factors for brain regeneration.Acephalic spermatozoa syndrome is a rare genetic and reproductive disease. Recent studies have shown that approximately 33-47% of patients with acephalic spermatozoa syndrome have SUN5 mutations, but the molecular mechanism underlying this phenomenon has not been elucidated. In this study, we generated Sun5 knockout mice and found that the head-to-tail linkage was broken in Sun5-/- mice, which was similar to human acephalic spermatozoa syndrome. Furthermore, ultrastructural imaging revealed that the head-tail coupling apparatus (HTCA) and the centrosome were distant from the nucleus at steps 9-10 during spermatid elongation. With the manchette disappearing at steps 13-14, the head and the tail segregated. To explore the molecular mechanism underlying this process, bioinformatic analysis was performed and showed that Sun5 may interact with Nesprin3. Further coimmunoprecipitation (Co-IP) and immunofluorescence assays confirmed that Sun5 and Nesprin3 were indeed bona fide interaction partners that formed the lin-tail connection.T cell protein tyrosine phosphatase (TCPTP), a vital regulator in glucose metabolism, inflammatory responses, and tumor processes, is increasingly considered a promising target for disease treatments and illness control. This review discusses the structure, substrates and main biological functions of TCPTP, as well as its regulatory effect in glucose metabolism, as an attempt to be referenced for formulating treatment strategies of metabolic disorders. Given the complicated regulation functions in different tissues and organs of TCPTP, the development of drugs inhibiting TCPTP with a higher specificity and a better biocompatibility is recognized as a promising therapeutic strategy for diabetes or obesity. Besides, treatments targeting TCPTP in a specific tissue or organ are suggested to be considerably promising.Sensorineural hearing loss (SNHL) is a dominant public health issue affecting millions of people around the globe, which is correlated with the irreversible deterioration of the hair cells and spiral ganglion neurons (SGNs) within the cochlea. Strategies using bioactive molecules that regulate neurite regeneration and neuronal survival to reestablish connections between auditory epithelium or implanted electrodes and SGN neurites would become attractive therapeutic candidates for SNHL. As an intracellular second messenger, cyclic guanosine-3′,5′-monophosphate (cGMP) can be synthesized through activation of particulate guanylate cyclase-coupled natriuretic peptide receptors (NPRs) by natriuretic peptides, which in turn modulates multiple aspects of neuronal functions including neuronal development and neuronal survival. As a cardiac-derived hormone, atrial natriuretic peptide (ANP), and its specific receptors (NPR-A and NPR-C) are broadly expressed in the nervous system where they might be involved in the maintenance of diverse neural functions.