Smad7 enables STAT3 activation and promotes pluripotency independent of TGF-β signaling

TGF-β and related growth factors critically regulate cell potency and functions. Smad7 is induced by TGF-βs and inhibits the physiological functions of TGF-β signaling. This study describes an unexpected finding that Smad7 promotes self-renewal of embryonic stem cells (ESCs) in a manner independent of its inhibition on TGF-β signaling. Instead, Smad7 acts to induce activation of transcription factor signal transducers and activators of transcription 3 (STAT3) in ESCs. Smad7 activates STAT3 through its direct binding to the cytokine receptor upstream of STAT3 activation. In agreement with the role of STAT3 in maintaining ESC pluripotency, Smad7 promotes ESC self-renewal and induced pluripotent stem cell reprogramming. This finding illustrates a regulatory mechanism for Smad7 in maintaining pluripotency, and likely in cancer and inflammation

PIK3C2A is a prognostic biomarker that is linked to immune infiltrates in kidney renal clear cell carcinoma

BackgroundPhosphoinositide 3-kinases (PI3Ks) are lipid enzymes that regulate a wide range of intracellular functions. In contrast to Class I and Class III PI3K, which have more detailed descriptions, Class II PI3K has only recently become the focus of functional research. PIK3C2A is a classical member of the PI3Ks class II. However, the role of PIK3C2A in cancer prognosis and progression remains unknown.MethodsThe expression pattern and prognostic significance of PIK3C2A in human malignancies were investigated using multiple datasets and scRNA-seq data. The PIK3C2A expression in renal clear cell carcinoma (KIRC) was then validated utilizing Western blot. The functional role of PIK3C2A in KIRC was assessed using combined function loss experiments with in vitro experiments. Furthermore, the correlation of PIK3C2A expression with tumor immunity was investigated in KIRC. The TCGA database was employed to investigate PIK3C2A functional networks.ResultsSignificant decrease in PIK3C2A expression in KIRC, demonstrated that it potentially influences the prognosis of diverse tumors, particularly KIRC. In addition, PIK3C2A was significantly correlated with the T stage, M stage, pathologic stage, and histologic grade of KIRC. Nomogram models were constructed and used to predict patient survival based on the results of multivariate Cox regression analysis. PIK3C2A knockdown resulted in significantly increased KIRC cell proliferation. Of note, PIK3C2A expression demonstrated a significant correlation with the infiltrating levels of primary immune cells in KIRC.ConclusionThese findings support the hypothesis that PIK3C2A is a novel biomarker for tumor progression and indicates dynamic shifts in immune infiltration in KIRC. Furthermore, aberrant PIK3C2A expression can influence the biological activity of cancer cells

Amorphous V–O–C composite nanofibers electrospun from solution precursors as binder- and conductive additive-free electrodes for supercapacitors with outstanding performance

Flexible V–O–C composite nanofibers were fabricated from solution precursors via electrospinning and were investigated as free-standing and additive-free film electrodes for supercapacitors. Specifically, composite nanofibers (V0, V5, V10 and V20) with different vanadyl acetylacetonate (VO(acac)2) contents of 0, 5, 10 and 20 wt% with respect to polyacrylonitrile (PAN) were prepared. The composite nanofibers were comparatively studied using XRD, Raman spectroscopy, XPS, N2 adsorption–desorption, FE-SEM, TEM and S-TEM. The vanadium element was found to be well-dispersed in the carbon nanofibers, free from the formation of an aggregated crystalline phase, even in the case of V20. A specific surface area of 587.9 m2 g-1 was reached for V10 after calcination, which is approximately twice that of the vanadium-free carbon nanofibers (V0, 300.9 m2 g-1). To perform as an electrode for supercapacitors in an aqueous electrolyte, the V10 film delivered a specific capacitance of 463 F g-1 at 1 A g-1. V10 was also able to retain a specific capacitance of 380 F g-1, even at a current density of 10 A g-1. Additionally, very stable cycling stability was achieved, maintaining an outstanding specific capacitance of 400 F g-1 at 5 A g-1 after charge–discharge cycling 5000 times. Thus, V–O–C composite nanofibers are highly attractive electrode materials for flexible, high-power, thin film energy storage devices and applications

Correction: Xia et al. Resveratrol Alleviates Zearalenone-Induced Intestinal Dysfunction in Mice through the NF-κB/Nrf2/HO-1 Signalling Pathway. <i>Foods</i> 2024, <i>13</i>, 1217

In the original publication [...

How the Innate Immune DNA Sensing cGAS&ndash;STING Pathway Is Involved in Autophagy

The cGAS&ndash;STING pathway is a key component of the innate immune system and exerts crucial roles in the detection of cytosolic DNA and invading pathogens. Accumulating evidence suggests that the intrinsic cGAS&ndash;STING pathway not only facilitates the production of type I interferons (IFN-I) and inflammatory responses but also triggers autophagy. Autophagy is a homeostatic process that exerts multiple effects on innate immunity. However, systematic evidence linking the cGAS&ndash;STING pathway and autophagy is still lacking. Therefore, one goal of this review is to summarize the known mechanisms of autophagy induced by the cGAS&ndash;STING pathway and their consequences. The cGAS&ndash;STING pathway can trigger canonical autophagy through liquid-phase separation of the cGAS&ndash;DNA complex, interaction of cGAS and Beclin-1, and STING-triggered ER stress&ndash;mTOR signaling. Furthermore, both cGAS and STING can induce non-canonical autophagy via LC3-interacting regions and binding with LC3. Subsequently, autophagy induced by the cGAS&ndash;STING pathway plays crucial roles in balancing innate immune responses, maintaining intracellular environmental homeostasis, alleviating liver injury, and limiting tumor growth and transformation

Identification and tissue distribution of a novel rat glucocorticoid receptor splice variant

Glucocorticoid receptor (GR) is a steroid hormone receptor that has been shown to play important roles in diverse cellular and physiological processes. More and more evidence has revealed that the effects of glucocorticoids are mediated by the glucocorticoid receptor through genomic or nongenomic mechanisms. A growing number of glucocorticoid receptor splice variants have been identified in human tissues, but few are known in rat tissues. In this work, a novel rGR cDNA, called rGRβ, was cloned from Sprague Dawlay (SD) rat liver. Sequence analysis revealed that the rGRβ mRNA was 39 base pairs (bp) shorter than the rGR mRNA reported earlier. The deleted segment is located in exon 1 and encodes 13 repeated glutamine residues. Both the rGR and rGRβ mRNAs were quantitated by Northern blot hybridization using non-homologous glucocorticoid cDNA probes. Results showed that the rGR and rGRβ mRNAs were most abundant in the lung, the least abundant in the heart, and there were more rGR and rGRβ mRNAs in the kidney than in the liver. The identification of rGRβ may contribute to the understanding of the genomic or nongenomic effects of glucocorticoids

Disc degeneration promotes regional inhomogeneity in the trabecular morphology of loaded rat tail vertebrae

Summary: Background: There is a close relationship between the vertebral trabecular morphology and the condition of the associated disc. Objective: The relationship between disc degeneration and vertebral trabecular inhomogeneity is unclear. This study aimed to analyse the regional changes of vertebral trabecular morphology after disc degeneration. Methods: Thirty male Sprague–Dawley rats were randomly assigned to five groups. Group 1 served as an experimental group for the assessment of disc degeneration induced by needle puncture. Group 2 served as a sham group for trabecular morphology analysis. In Group 3, rats had their tail bent between the eighth and tenth coccygeal vertebrae. In Group 4, the tail of rats was bent with a compression load of 4.5 N. In Group 5, rats first underwent disc degeneration induced by a needle puncture before their tail was bent with a compressive load of 4.5 N. Magnetic resonance imaging was performed on all groups, and histological examination was performed on rodents from Group 1. The ninth coccygeal vertebrae of rats from Groups 2–5 were scanned by Micro-computed tomography. Trabecular morphologic changes were assessed in the concave and convex regions by bone volume fraction, trabecular number, trabecular thickness and trabecular separation. Results: Vertebral trabecular morphology in the concave region improved significantly, whereas the convex region was of significantly lower trabecular morphologic parameters with disc degeneration. The difference in trabecular morphologic parameters between the convex and concave regions increased significantly after disc degeneration. Conclusion: Disc degeneration promotes regional inhomogeneity in the vertebral trabecular morphology, with the convex region of the vertebrae having the worse trabecular bone morphology than the concave region. The translational potential of this article: Our study indicates that disc degeneration promotes regional inhomogeneity in the vertebral trabecular morphology. Regional variations in trabecular microarchitecture are helpful to predict vertebral fragility. This may help to elucidate the mechanisms by which disc degeneration contributes to vertebral fracture. Keywords: Animal model, Disc degeneration, Regional inhomogeneity, Trabecular morpholog

Shared metabolic shifts in endothelial cells in stroke and Alzheimer’s disease revealed by integrated analysis

Abstract Since metabolic dysregulation is a hallmark of both stroke and Alzheimer’s disease (AD), mining shared metabolic patterns in these diseases will help to identify their possible pathogenic mechanisms and potential intervention targets. However, a systematic integration analysis of the metabolic networks of the these diseases is still lacking. In this study, we integrated single-cell RNA sequencing datasets of ischemic stroke (IS), hemorrhagic stroke (HS) and AD models to construct metabolic flux profiles at the single-cell level. We discovered that the three disorders cause shared metabolic shifts in endothelial cells. These altered metabolic modules were mainly enriched in the transporter-related pathways and were predicted to potentially lead to a decrease in metabolites such as pyruvate and fumarate. We further found that Lef1, Elk3 and Fosl1 may be upstream transcriptional regulators causing metabolic shifts and may be possible targets for interventions that halt the course of neurodegeneration