The forkhead box O3 (FOXO3): a key player in the regulation of ischemia and reperfusion injury.

Forkhead box O3 is a protein encoded by the FOXO3 gene expressed throughout the body. FOXO3 could play a crucial role in longevity and many other pathologies, such as Alzheimer's disease, glioblastoma, and stroke. This study is a comprehensive review of the expression of FOXO3 under ischemia and reperfusion (IR) and the molecular mechanisms of its regulation and function. We found that the expression level of FOXO3 under ischemia and IR is tissue-specific. Specifically, the expression level of FOXO3 is increased in the lung and intestinal epithelial cells after IR. However, FOXO3 is downregulated in the kidney after IR and in the skeletal muscles following ischemia. Interestingly, both increased and decreased FOXO3 expression have been reported in the brain, liver, and heart following IR. Nevertheless, these contribute to stimulating ischemia and reperfusion injury via the induction of inflammatory response, apoptosis, autophagy, mitophagy, pyroptosis, and oxidative damage. These results suggest that FOXO3 could play protective effects in some organs and detrimental effects in others against IR injury. Most importantly, these findings indicate that controlling FOXO3 expression, genetically or pharmacologically, could contribute to preventing or treating ischemia and reperfusion damage.

Parallel implement of real-time delta-sigma modulation for digital mobile fronthaul.

We propose and experimentally demonstrate a novel FPGA-based parallel architecture for delta-sigma modulation (DSM) for digital mobile fronthaul employing the DSM interface. This architecture breaks the limitations of the feedback loop in DSM, is not constrained by critical paths, and supports fully parallel processing, so it can deal with high sampling rates at low hardware operating speeds. In contrast to other parallel schemes, the proposed bit-by-bit quantization DSM avoid significant storage resources requirements for buffering. A real-time experimental system using Xilinx Kintex Ultrascale FPGA was implemented to validate the feasibility of the proposed architecture. 14 carrier aggregated orthogonal frequency division multiplexing (OFDM) signals are digitized by DSM into a 5Gb/s PAM4 signal and transmitted over a 20 km single-mode fiber (SMF). As a waveform-agnostic digitization interface, we also experimentally demonstrated the DSM with 14 carrier aggregated filter-bank-multicarrier (FBMC) signals, which can achieve better EVM performance.

Glucocorticoid Regulates the Synthesis of Porcine Muscle Protein through m6A Modified Amino Acid Transporter SLC7A7.

The occurrence of stress is unavoidable in the process of livestock production, and prolonged stress will cause the decrease of livestock productivity. The stress response is mainly regulated by the hypothalamic-pituitary-adrenal axis (HPA axis), which produces a large amount of stress hormones, namely glucocorticoids (GCs), and generates a severe impact on the energy metabolism of the animal body. It is reported that m6A modification plays an important role in the regulation of stress response and also participates in the process of muscle growth and development. In this study, we explored the effect of GCs on the protein synthesis procession of porcine skeletal muscle cells (PSCs). We prove that dexamethasone affects the expression of SLC7A7, a main amino acid transporter for protein synthesis by affecting the level of m6A modification in PSCs. In addition, we find that SLC7A7 affects the level of PSC protein synthesis by regulating the conduction of the mTOR signaling pathway, which indicates that the reduction of SLC7A7 expression may alleviate the level of protein synthesis under stress conditions.

Mechanisms of microRNA-132 in central neurodegenerative diseases: A comprehensive review.

MicroRNA-132 (miR-132) is a highly conserved molecule that plays a crucial regulatory role in central nervous system (CNS) disorders. The expression levels of miR-132 exhibit variability in various neurological disorders and have been closely linked to disease onset and progression. The expression level of miR-132 in the CNS is regulated by a diverse range of stimuli and signaling pathways, including neuronal migration and integration, dendritic outgrowth, and complexity, synaptogenesis, synaptic plasticity, as well as inflammation and apoptosis activation. The aberrant expression of miR-132 in various central neurodegenerative diseases has garnered widespread attention. Clinical studies have revealed altered miR-132 expression levels in both chronic and acute CNS diseases, positioning miR-132 as a potential biomarker or therapeutic target. An in-depth exploration of miR-132 holds the promise of enhancing our understanding of the mechanisms underlying CNS diseases, thereby offering novel insights and strategies for disease diagnosis and treatment. It is anticipated that this review will assist researchers in recognizing the potential value of miR-132 and in generating innovative ideas for clinical trials related to CNS degenerative diseases.

Hydrogen sulfide and its donors for the treatment of cerebral ischaemia-reperfusion injury: A comprehensive review.

As an endogenous gas signalling molecule, hydrogen sulfide (H2S) is frequently present in a variety of mammals and plays a significant role in the cardiovascular and nervous systems. Reactive oxygen species (ROS) are produced in large quantities as a result of cerebral ischaemia-reperfusion, which is a very serious class of cerebrovascular diseases. ROS cause oxidative stress and induce specific gene expression that results in apoptosis. H2S reduces cerebral ischaemia-reperfusion-induced secondary injury via anti-oxidative stress injury, suppression of the inflammatory response, inhibition of apoptosis, attenuation of cerebrovascular endothelial cell injury, modulation of autophagy, and antagonism of P2X7 receptors, and it plays an important biological role in other cerebral ischaemic injury events. Despite the many limitations of the hydrogen sulfide therapy delivery strategy and the difficulty in controlling the ideal concentration, relevant experimental evidence demonstrating that H2S plays an excellent neuroprotective role in cerebral ischaemia-reperfusion injury (CIRI). This paper examines the synthesis and metabolism of the gas molecule H2S in the brain as well as the molecular mechanisms of H2S donors in cerebral ischaemia-reperfusion injury and possibly other unknown biological functions. With the active development in this field, it is expected that this review will assist researchers in their search for the potential value of hydrogen sulfide and provide new ideas for preclinical trials of exogenous H2S.

TBENet:A two-branch boundary enhancement Network for cerebrovascular segmentation.

Cerebrovascular segmentation in digital subtraction angiography (DSA) images is the gold standard for clinical diagnosis. However, owing to the complexity of cerebrovascular, automatic cerebrovascular segmentation in DSA images is a challenging task. In this paper, we propose a CNN-based Two-branch Boundary Enhancement Network (TBENet) for automatic segmentation of cerebrovascular in DSA images. The TBENet is inspired by U-Net and designed as an encoder-decoder architecture. We propose an additional boundary branch to segment the boundary of cerebrovascular and a Main and Boundary branches Fusion Module (MBFM) to integrate the boundary branch outcome with the main branch outcome to achieve better segmentation performance. The TBENet was evaluated on HMCDSA (an in-house DSA cerebrovascular dataset), and reaches 0.9611, 0.7486, 0.7152, 0.9860 and 0.9556 in Accuracy, F1 score, Sensitivity, Specificity, and AUC, respectively. Meanwhile, we tested our TBENet on the public vessel segmentation benchmark DRIVE, and the results show that our TBENet can be extended to diverse vessel segmentation tasks.

Effect of Enrichment Items on the Physiology and Behavior of Sows in the Third Trimester of Pregnancy.

Modern intensive pig breeding harms animal welfare, which is especially noticeable for pregnant sows kept in confinement stalls. This study aimed to evaluate the effects of enrichment items on the movement and physiological parameters of sows in the third trimester of pregnancy. A total of 30 large white pregnant sows were randomly divided into three equal treatment groups (n = 10): control, pine wood, and scented wood groups. Interestingly, compared with the control group, the sows in the pine wood or scented wood groups showed less ventral lying and more lateral lying behavior (p < 0.01), coupled with significant reduction in the frequency of scratching and sham-chewing (p < 0.01), but with no significant difference in the degree of preference for these enrichment items (p > 0.05). Additionally, the sows in the pine wood or scented wood groups also decreased significantly in the concentration of immunoglobulin A (IgA) (p < 0.01) and the concentration of tumor necrosis factor-α (TNF-α) (p < 0.05) throughout the late pregnancy period. Overall, adding enrichment items to confinement stalls can alleviate the chronic stress and the stereotypic behavior of sows, suggesting their potential to reduce welfare compromise.

Regulation of morphological differentiation in S. coelicolor by RNase III (AbsB) cleavage of mRNA encoding the AdpA transcription factor.

RNase III family enzymes, which are perhaps the most widely conserved of all ribonucleases, are known primarily for their role in the processing and maturation of small RNAs. The RNase III gene of Streptomyces coelicolor, which was discovered initially as a global regulator of antibiotic production in this developmentally complex bacterial species and named absB (antibiotic biosynthesis gene B), has subsequently also been found to modulate the cellular abundance of multiple messenger RNAs implicated in morphological differentiation. We report here that regulation of differentiation-related mRNAs by the S. coelicolor AbsB/RNase III enzyme occurs largely by ribonucleolytic cleavage of transcripts encoding the pleiotropic transcription factor, AdpA, and that AdpA and AbsB participate in a novel feedback-control loop that reciprocally regulates the cellular levels of both proteins. Our results reveal a previously unsuspected mechanism for global ribonuclease-mediated control of gene expression in streptomycetes.

Glucocorticoid Receptor Alpha Targets SLC2A4 to Regulate Protein Synthesis and Breakdown in Porcine Skeletal Muscle Cells.

In the presence of stress, the hypothalamic-pituitary-adrenal (HPA) axis activity can be enhanced to promote the secretion of a large amount of glucocorticoids (GCs), which play an important role in the anabolism and catabolism of skeletal muscle. When the endogenous and exogenous glucocorticoids are deficient or excessive, the body will produce stress-related resistance and change the protein metabolism. In this study, we investigated the effect of GC receptor GRα on protein breakdown and synthesis in porcine skeletal muscle cells (PSCs). Overexpression of GRα was shown to increase the expression of protein degradation-related genes, while knockdown of GRα decreased the expression of these genes. Additionally, we found a relationship between GRα and solute carrier family 2 member 4 (SLC2A4), SLC2A4 expression level increases when stress occurs, suggesting that increasing SLC2A4 expression can partially alleviate stress-induced damage, and we found that there is a combination between them via luciferase reporter assays, which still needs to be confirmed in further studies.

Autoregulation of AbsB (RNase III) expression in Streptomyces coelicolor by endoribonucleolytic cleavage of absB operon transcripts.

The Streptomyces coelicolor absB gene encodes an RNase III family endoribonuclease and is normally essential for antibiotic biosynthesis. Here we report that AbsB controls its own expression by sequentially and site specifically cleaving stem-loop segments of its polycistronic transcript. Our results demonstrate a ribonucleolytic regulatory role for AbsB in vivo.

Involvement of caspase-3 and p38 mitogen-activated protein kinase in cobalt chloride-induced apoptosis in PC12 cells.

Our previous study showed that cobalt chloride (CoCl2) could induce PC12 cell apoptosis and that the CoCl2-treated PC12 cells may serve as a simple in vitro model for the study of the mechanism of hypoxia-linked neuronal disorders. The aim of this study is to elucidate the mechanism of CoCl2-induced apoptosis in PC12 cells. Caspases are known to be involved in the apoptosis induced by various stimuli in many cell types. To investigate the involvement of caspases in CoCl2-induced apoptosis in PC12 cells, we generated PC12 cells that stably express the viral caspases inhibitor gene p35 and analyzed the effect of p35 on the process of apoptosis induced by CoCl2. We also examined the effect of cell-permeable peptide inhibitors of caspases. The results showed that the baculovirus p35 gene and the general caspases inhibitor Z-VAD-FMK significantly block apoptosis induced by CoCl2, confirming that caspase is involved in CoCl2-induced apoptosis. Further investigation showed that in this process the caspase-3-like activity is increased, as indicated by the cells' ability to cleave the fluorogenic peptide substrate Ac-Asp-Glu-Val-Asp-7-AMC and to degrade the DNA-repairing enzyme poly-(ADP-ribose) polymerase (PARP), an endogenous caspase-3 substrate. At the same time, caspase-3-specific inhibitors, namely, the peptide Ac-DEVD-CHO, Ac-DEVD-FMK, partially inhibit CoCl2-induced apoptosis. These findings suggested that caspase-3 or caspase-3-like proteases are involved in the apoptosis induced by CoCl2 in PC12 cells. Additionally, we have observed that another apoptotic marker, p38 mitogen-activated protein kinase (MAPK), is significantly activated in this process in a time-dependent manner and that a selective p38 MAPK inhibitor, SB203580, partially inhibits this cell death. The addition of SB203580 also partially suppresses caspase-3-like activity. All these results confirm that the CoCl2-treated PC12 cell is a useful in vitro model with which to study hypoxia-linked neuronal disorders. Furthermore, the results showing that the baculovirus p35 gene and caspase inhibitors possess a remarkable ability to rescue PC12 cells from CoCl2-induced cell death may have implications for future neuroprotective therapeutic approaches for the hypoxia-associated disorders.

Ref-1 protein enhances the IL-2-stimulated telomerase activity.

Telomerase is an important ribonucleoprotein enzyme involved in cellular proliferation and senescence. Activation of telomerase has been detected in a vast majority of human cancer cells. In this article, we demonstrated that Interleukin-2 (IL-2) which is the pivotal cytokine in the immune system could stimulate the activity of telomerase in the cultured BA/F3beta cells. It was also found that the level of IL-2-induced telomerase activity was decreased by the treatment with chemical oxidant in vitro. Since IL-2 stimulation produces a oxidative shift of the intracellular environment, the activation and maintenance of telomerase in this oxidative circumstance requires particular protection. Here we proved the redox factor-1 (Ref-1) protein was involved in this process. The addition of GST-Ref-1 protein increased the level of IL-2-induced telomerase activity in the TRAP assay, while elimination of the endogenous Ref-1 protein by immunodepletion decreased it. Consistent with these in vitro results, IL-2-induced telomerase activity could be enhanced by transient overexpression of Ref-1 protein in BA/F3beta cells. Taken together, these findings proved that Ref-1 protein benefits the activation of telomerase activity in the oxidative microenvironment of the BA/F3beta cells stimulated by IL-2.

Geldanamycin, a heat shock protein 90-binding agent, disrupts Stat5 activation in IL-2-stimulated cells.

The 90-kDa heat shock protein (Hsp90) is the most abundant molecular chaperone in eukaryotic cells. Hsp90 plays a critical role in regulating signal transduction pathways that control cell proliferation since its chaperone function is restricted to a subset of proteins including some signal molecules. Improper function of these proteins can be induced by an anti-tumor agent geldanamycin (GA) which is the specific inhibitor of Hsp90. In this study, it was demonstrated that GA interferes with IL-2-stimulated proliferation of murine CTLL-2 cells. As to the signaling mechanisms underlying this inhibitory effect, we discovered GA disrupts the IL-2-stimulated activation and phosphorylation of the transcription factor Stat5, indicating the proper function of Hsp90 is indispensable for Stat5 activation. This conclusion is validated by the observation that Hsp90 interacts with Stat5 in the immunoprecipitation assay and GA interrupts their interaction. Furthermore, by constructing deletion mutants, we identified the c-terminal half of Stat5 coiled-coil region is responsible for binding with Hsp90.