In this work, nickel phyllosilicate was prepared through the hydrothermal reaction of rice husk-derived silica (SR) and nickel nitrate. Owing to the loss of surface silanol group on SR during the ...calcination process, a small amount of Ni-phyllosilicate with Ni content of 10.2 wt% was obtained on N220/SR, which was prepared under a very severe hydrothermal condition of 220 °C for 48 h. After the addition of urea, the dense flower-like nanosheets attributing to Ni-phyllosilicate were observed on the surface of N180/SR-U-24 with high Ni content of 22.6 wt%, which was prepared under a much milder hydrothermal temperature of 180 °C and a shorter reaction time of 24 h. This was because urea could facilitate the formation of an important intermediate (Ni(OH)2) and leaching of SiO2, resulting in the quick formation of Ni-phyllosilicate. N180/SR-U-24 exhibited both good catalytic activity and high long-term stability for CO2 methanation due to the relatively high Ni content, fine Ni particles and the strong metal-support interaction derived from Ni-phyllosilicate.
Display omitted
•Renewable rice-husk-derived SiO2 was prepared.•Ni-phyllosilicate was synthesized using two hydrothermal methods with or without urea.•Urea-assisted hydrothermal method was efficient for synthesis of Ni-phyllosilicate.•Urea could facilitate the formation of Ni(OH)2 and leaching of SiO2.
RLR-mediated type I IFN production plays a pivotal role in elevating host immunity for viral clearance and cancer immune surveillance. Here, we report that glycolysis, which is inactivated during RLR ...activation, serves as a barrier to impede type I IFN production upon RLR activation. RLR-triggered MAVS-RIG-I recognition hijacks hexokinase binding to MAVS, leading to the impairment of hexokinase mitochondria localization and activation. Lactate serves as a key metabolite responsible for glycolysis-mediated RLR signaling inhibition by directly binding to MAVS transmembrane (TM) domain and preventing MAVS aggregation. Notably, lactate restoration reverses increased IFN production caused by lactate deficiency. Using pharmacological and genetic approaches, we show that lactate reduction by lactate dehydrogenase A (LDHA) inactivation heightens type I IFN production to protect mice from viral infection. Our study establishes a critical role of glycolysis-derived lactate in limiting RLR signaling and identifies MAVS as a direct sensor of lactate, which functions to connect energy metabolism and innate immunity.
Display omitted
•Lactate inhibits RLR-mediated interferon production•This regulation occurs through direct sensing of lactate by MAVS•MAVS associates with hexokinase, but this association is disrupted by RIG-I•Targeting LDHA enhances type I IFN production and viral clearance
Lactate acts as a regulator of the adaptor MAVS, allowing a cross-regulation between antiviral signaling and energy metabolism
Abstract
Extracellular cytokines are enriched in the tumor microenvironment and regulate various important properties of cancers, including autophagy. However, the precise molecular mechanisms ...underlying the link between autophagy and extracellular cytokines remain to be elucidated. In the present study, we demonstrate that IL-6 activates autophagy through the IL-6/JAK2/BECN1 pathway and promotes chemotherapy resistance in colorectal cancer (CRC). Mechanistically, IL-6 triggers the interaction between JAK2 and BECN1, where JAK2 phosphorylates BECN1 at Y333. We demonstrate that BECN1 Y333 phosphorylation is crucial for BECN1 activation and IL-6-induced autophagy by regulating PI3KC3 complex formation. Furthermore, we investigate BECN1 Y333 phosphorylation as a predictive marker for poor CRC prognosis and chemotherapy resistance. Combination treatment with autophagy inhibitors or pharmacological agents targeting the IL-6/JAK2/BECN1 signaling pathway may represent a potential strategy for CRC cancer therapy.
An impregnated Ni/CeO2 catalyst with an array structure and a phyllosilicate-based Ni/SiO2 catalyst prepared by hydrothermal method were designed for CO2 methanation. The as-synthetized Ni/SiO2 ...catalyst exhibits a high Ni content of 25.9 wt%, while its CO2 conversion at low temperature is far lower than that of Ni/CeO2, whose Ni content is only 10.0 wt%. TEM and XRD results show that the Ni/CeO2 catalyst possesses very tiny Ni particle size of around 1.2 nm, which leads to large H2 uptake capacity. XPS and Raman analyses indicate that Ni/CeO2 obtains more oxygen vacancies resulting in promotion of the CO2 activation. The combined effect of the Ni/CeO2 catalyst to enhance chemisorption of H2 and CO2 leads to high low-temperature activity.
Display omitted
•The catalytic activity of Ni/CeO2 and Ni/SiO2 was compared for CO2 methanation.•The Ni/CeO2 catalyst possessed smaller Ni particle size and larger H2 chemisorption capacity.•The Ni/CeO2 catalyst exhibited more oxygen vacancies and enhanced CO2 activation property.•Enhanced H2 and CO2 activation properties of Ni/CeO2 led to higher activity.
SMAD3 plays a central role in cancer metastasis, and its hyperactivation is linked to poor cancer outcomes. Thus, it is critical to understand the upstream signaling pathways that govern SMAD3 ...activation. Here, we report that SMAD3 underwent methylation at K53 and K333 (K53/K333) by EZH2, a process crucial for cell membrane recruitment, phosphorylation, and activation of SMAD3 upon TGFB1 stimulation. Mechanistically, EZH2-triggered SMAD3 methylation facilitated SMAD3 interaction with its cellular membrane localization molecule (SARA), which in turn sustained SMAD3 phosphorylation by the TGFB receptor. Pathologically, increased expression of EZH2 expression resulted in the accumulation of SMAD3 methylation to facilitate SMAD3 activation. EZH2-mediated SMAD3 K53/K333 methylation was upregulated and correlated with SMAD3 hyperactivation in breast cancer, promoted tumor metastasis, and was predictive of poor survival outcomes. We used 2 TAT peptides to abrogate SMAD3 methylation and therapeutically inhibit cancer metastasis. Collectively, these findings reveal the complicated layers involved in the regulation of SMAD3 activation coordinated by EZH2-mediated SMAD3 K53/K333 methylation to drive cancer metastasis.
Renal tubular epithelial cell (RTEC) apoptosis is important in acute kidney injury (AKI). Calcium/calmodulin-dependent protein kinase II (CaMKII) plays an important role in cell apoptosis, but its ...potential role in AKI remains unknown.
Using co-immunoprecipitation, immunofluorescence, immunohistochemistry, western blotting, flow cytometry, and cell transfection, this study aimed to verify whether CaMKII is involved in RTEC apoptosis and to explore the underlying mechanism.
We found that CaMKII was involved in RTEC apoptosis. In adriamycin-induced AKI mice, serum creatinine levels, cell apoptosis, CaMKII activity, and nuclear factor of activated T cells 2 (NFAT2) levels increased, whereas nuclear Yes-associated protein (YAP) expression decreased; inhibition of CaMKII activity reversed these changes. Phosphorylated CaMKII could bind to phosphorylated YAP in the cytoplasm and block it from entering the nucleus, thereby failing to inhibit NFAT2-mediated cell apoptosis. Sequestrated phosphorylated YAP in the RTEC cytoplasm was finally degraded by ubiquitination.
CaMKII may regulate RTEC apoptosis through YAP/NFAT2 in AKI mice. CaMKII may be a potent molecular target for AKI treatment.
Highly efficient drug delivery systems with excellent tumor selectivity and minimal toxicity to normal tissues remain challenging for tumor treatment. Although great effort has been made to prolong ...the blood circulation and improve the delivery efficiency to tumor sites, nanomedicines are rarely approved for clinical application. Bacteria have the inherent properties of homing to solid tumors, presenting themselves as promising drug delivery systems. Escherichia coli Nissle 1917 (EcN) is a commonly used probiotic in clinical practice. Its facultative anaerobic property drives it to selectively colonize in the hypoxic area of the tumor for survival and reproduction. EcN can be engineered as a bacteria-based microrobot for molecular imaging, drug delivery, and gene delivery. This review summarizes the progress in EcN-mediated tumor imaging and therapy and discusses the prospects and challenges for its clinical application. EcN provides a new idea as a delivery vehicle and will be a powerful weapon against cancer.
In recent years, delivery systems based on the incorporation of thiols/disulfides have been extensively explored to promote the intracellular delivery of biological cargoes. However, it remains ...unclear about the detailed processes of thiol-disulfide exchanges taking place on the cell surface and how the exchange reactions promote the cellular uptake of cargoes bearing thiols or disulfide bonds. In this work, we report the rational design of biscysteine motif-containing peptide probes with substantially different ring-closing property and how these peptide probes were employed to explore the thiol-disulfide exchanges on the cell surface. Our results show that extensive thiol-disulfide exchanges between peptides and exofacial protein thiols/disulfides are involved in the cellular uptake of these peptide probes, and importantly glutathione (GSH) exported from the cytosols participates extensively in the exchange reactions. Cysteine-glycine-cysteine (CGC)-containing peptide probes can be more efficiently taken up by cells compared to other probes, and we suggested that the driving force for the superior cellular uptake arises from very likely the unique propensity of the CGC motif in forming doubly bridged disulfide bonds with exofacial proteins. Our probe-based strategy provides firsthand information on the detailed processes of the exchange reactions, which would be of great benefit to the development of delivery systems based on the extracellular thiol-disulfide exchanges for intracellular delivery of biologics.
Alcoholic liver disease (ALD) is a chronic alcohol-induced disorder of the liver for which there are few effective therapies for severe forms of ALD and for those who do not achieve alcohol ...abstinence. In this study, we used a systematic drug-repositioning bioinformatics approach querying a large compendium of gene-expression profiles to identify candidate U.S. Food and Drug Administration (FDA)-approved drugs to treat ALD. One of the top compounds predicted to be therapeutic for ALD by our approach was dimethyl fumarate (DMF), an nuclear factor erythroid 2-related factor 2 (NRF2) inducer. We experimentally validated DMF in liver cells and in vivo. Our work demonstrates that DMF is able to significantly upregulate the NRF2 protein level, increase NRF2 phosphorylation, and promote NRF2 nuclear localization in liver cells. DMF also reduced the reactive oxygen species (ROS) level, lipid peroxidation, and ferroptosis. Furthermore, DMF treatment could prevent ethanol-induced liver injury in ALD mice. Our results provide evidence that DMF might serve as a therapeutic option for ALD in humans, and support the use of computational repositioning to discover therapeutic options for ALD.
Three novel cyclic hexapeptides, sclerotides C-E (
-
), and a new lipodepsipeptide, scopularide I (
), together with a known cyclic hexapeptide sclerotide A (
), were isolated from fermented rice ...cultures of a soft coral-derived fungus:
SCSIO 41031. The structures of the new peptides were determined by 1D and 2D NMR spectroscopic analysis, Marfey's method, ESIMS/MS analysis, and single crystal X-ray diffraction analysis. Scopularide I (
) exhibited acetylcholinesterase inhibitory activity with an IC
value of 15.6 μM, and weak cytotoxicity against the human nasopharyngeal carcinoma cell line HONE-EBV with IC
value of 10.1 μM.
PDF
