LRRC1 knockdown downregulates MACF1 to inhibit the malignant progression of acute myeloid leukemia by inactivating ß-catenin/c-Myc signaling.

Acute myeloid leukemia (AML) is a hematologic disease associated with genetic abnormalities. This study aimed to explore the role of leucine-rich repeat-containing protein 1 (LRRC1) in the malignant activities of AML and to reveal the molecular mechanism related to microtubule actin cross-linking factor 1 (MACF1). GEPIA database was used to analyze the expression of LRRC1 in bone marrow tissues of AML patients and the correlation between LRRC1 expression and survival analysis. LRRC1 was knocked down to assess the change of AML cell proliferation, cell cycle and apoptosis using CCK-8 assay and flow cytometry. Besides, the contents of extracellular acidification and oxygen consumption rates were measured to evaluate the glycolysis. Additionally, the interaction between LRRC1 and MACF1 predicted by MEM database and was verified by co-immunoprecipitation (Co-IP) assay. Then, MACF1 was overexpressed to conduct the rescue experiments. Expression of proteins in ß-catenin/c-Myc signaling was detected by western blot. Finally, AML xenograft mouse model was established to observe the impacts of LRRC1 silencing on the tumor development. Notably upregulated LRRC1 expression was observed in bone marrow tissues of AML patients and AML cells, and patients with the higher LRRC1 expression displayed the lower overall survival. LRRC1 depletion promoted cell cycle arrest and apoptosis and inhibited the glycolysis. Co-IP confirmed the interaction between LRRC1 and MACF1. MACF1 upregulation relieved the impacts of LRRC1 knockdown on the malignant activities of AML cells. Moreover, LRRC1 silencing inhibited the development of xenograft tumor growth of HL-60 cells in nude mice, suppressed MACF1 expression and inactivated the ß-catenin/c-Myc signaling. Collectively, LRRC1 knockdown suppressed proliferation, glycolysis and promoted apoptosis in AML cells by downregulating MACF1 expression to inactivate ß-catenin/c-Myc signaling.

Enhanced oxygen evolution reaction via the tunability of spin polarization and electronic states in a flexible van der Waals membranous catalyst.

The response of the magnetic field and strain engineering in an electrochemical process, such as the oxygen evolution reaction (OER), not only provides a strategy for enhancing catalytic performance through external fields and mechanical stress but also serves as a platform for revealing the functionality of multiple degrees of freedom in catalysts. The perovskite transition metal oxide (TMO) thin film with precise stoichiometry and lattice ordering enables atomic-level catalysis mechanisms in various electrochemical processes, thereby facilitating the design and engineering of promising catalysts. However, the perplexing dominance of spin in an OER process is still a puzzle due to the strong correlation between transition metal d and oxygen p orbitals. In this study, we utilized La0.7Sr0.3MnO3 (LSMO) manganite as a ferromagnetic OER catalyst, which was directly deposited onto a flexible mica substrate. By subjecting LSMO to a tensile stress, we observed an enhanced OER, and the OER performance of LSMO improved by 30% with a +0.2% strain due to the weakened chemisorption of Mn-O. Moreover, it has been observed that the OER performance can be improved by approximately 87%, while the overpotential can be reduced by around 22% through the combination of a 5 kOe magnetic field and +0.2% strain. The OER performance of LSMO changed by ∼153% under 4% strain and 5 kOe magnetic field. Our experiments indicate that the primary source of the observed magnetic response is derived from the triplet state of O2, in which spin-polarized d and oxygen p orbitals decrease the spin potential within OER. This study provides experimental evidence for understanding the spin degree and electronic state regulation in the OER process, thereby facilitating further design and engineering of flexible magnetic electrochemistry catalysts with promising potential.

Magnetic Field-Enhanced Oxygen Evolution Reaction via the Tuneability of Spin Polarization in a Half-Metal Catalyst.

The magnetic field response of an electrochemistry process, such as the oxygen evolution reaction (OER), provides not only a strategy for enhanced catalytic activity by applying an external field but also a platform for revealing the functionality of the multiple degrees of freedom of the catalyst. However, the mechanism of the magnetic field tuneable OER is controversial. The strong correlation between the d and p orbitals of transition metal and oxygen still puzzles the dominant role of spin in an OER process. Here in this study, we have employed the manganite La0.7Sr0.2Ca0.1MnO3 as the ferromagnetic OER catalyst, which has a ferromagnetic/paramagnetic transition (TC) around the room temperature. It is found that the overpotential can be reduced by ∼18% after applying a 5 kOe magnetic field. Furthermore, this magnetic field can trigger a further improvement of the OER performance, and it demonstrates a strong temperature dependence which is incongruent with its magnetoresistive behavior. So our experiments suggest that the observed magnetic response originates dominantly from the triplet state of the O2, where the spin-polarized d and oxygen p orbitals lower the Gibbs free energy for every reaction step in OER. This study offers experimental evidence on comprehending the spin degree in the OER process, meanwhile benefiting the further design and engineering of the promising magnetic electrochemistry catalysts.

Experimental demonstration of a skyrmion-enhanced strain-mediated physical reservoir computing system.

Physical reservoirs holding intrinsic nonlinearity, high dimensionality, and memory effects have attracted considerable interest regarding solving complex tasks efficiently. Particularly, spintronic and strain-mediated electronic physical reservoirs are appealing due to their high speed, multi-parameter fusion and low power consumption. Here, we experimentally realize a skyrmion-enhanced strain-mediated physical reservoir in a multiferroic heterostructure of Pt/Co/Gd multilayers on (001)-oriented 0.7PbMg1/3Nb2/3O3-0.3PbTiO3 (PMN-PT). The enhancement is coming from the fusion of magnetic skyrmions and electro resistivity tuned by strain simultaneously. The functionality of the strain-mediated RC system is successfully achieved via a sequential waveform classification task with the recognition rate of 99.3% for the last waveform, and a Mackey-Glass time series prediction task with normalized root mean square error (NRMSE) of 0.2 for a 20-step prediction. Our work lays the foundations for low-power neuromorphic computing systems with magneto-electro-ferroelastic tunability, representing a further step towards developing future strain-mediated spintronic applications.

The modulated oxygen evolution reaction performance of LaFeO3 with abundant electronic structures via a design of stoichiometry offset.

Transition metal oxides have been widely employed as electrocatalysts in various electrochemical processes such as oxygen evolution reaction (OER) owing to their designable adsorption/desorption ability of water intermediates by engineering their electronic structures. However, the coexistence of multiple chemical valences of the transition metal always hides the realization of the functional active phase in OER. In this study, we have performed the OER measurements on LaFeO3 (LFO) catalysts to reveal the complex relationships between 3d electronic structure and its OER responses; herein, several electronic statuses, including t42ge2g (S = 2), t52ge1g (S = 1), or t62ge0g (S = 0) of Fe ions, can be dominantly achieved by the design of stoichiometry offset in LFO. It is found that the current density of LFO at 1.9 V shows a volcanic dependence on the oxygen content. After the comprehensive characterization of Fe and oxygen ions in LFO by X-ray photoelectron spectroscopy and magnetic hysteresis measurements, we have found the OH- adsorption capacity and exchange interaction of Fe ions jointly determine the OER performance. Our research provides a stepwise evolution of the multiple spin states in LFO, and their subsequent OER responses are demonstrated, which can benefit the fundamental understanding of the link between 3d electronic structure and OER performance and the design for further promising transition metal oxide catalysts.

Strain Modified Oxygen Evolution Reaction Performance in Epitaxial, Freestanding, and Van Der Waals Manganite Thin Films.

In perovskite complex oxides, the strain has been established as a promising approach for tuning the oxygen evolution reaction (OER) performance by the manipulated electronic structure and interaction/coupling. In this study, we have employed rigid epitaxial, flexible freestanding, and van der Waals La2/3Sr1/3MnO3 (LSMO) to investigate the strain effects on OER, which are different in stress strength and range via lattice mismatch and curvature change. It was found that the OER performances as a function of strain exhibited volcano and monotonous trends in rigid and flexible LSMO, respectively. The findings suggest that distinguished oxygen activation energy in varied lattice fields also plays a crucial role in the epitaxial LSMO in contrast to the pure strain effect in the flexible LSMO. Our results not only fundamentally clarify the effort of strain but also technologically provide an effective route to engineer the electronic structure for modified OER performance by perovskite complex oxides.

ADSC-Exosomes Alleviate MTX-induced Rat Neuronal Damage by Activating Nrf2-ARE Pathway.

The aim of this study was to analyze the efficacy and underlying mechanism of adipose-derived mesenchymal stem cell exosome (ADSC-exosomes)-mediated protection on methotrexate (MTX)-induced neuronal damage. We established a H2O2-induced oxidative stress model in vitro, as well as an MTX-induced neuronal damage rat model in vivo. We analyzed the effects of ADSC-exosomes on neuronal damage and Nrf2-ARE signaling pathway in rats and related mechanisms. The morphological and functional recovery of rat hippocampal neurons by ADSC-exosomes was examined by Nissl staining and modified neurological severity score (mNSS) score. The activation of Nrf2-ARE pathway effectively inhibited H2O2-induced oxidative stress. ADSC-exosomes treatment restored the activity of hippocampal neuronal cells, reduced ROS production, and inhibited hippocampal neuronal cells apoptosis. In in vivo experiments, ADSC-exosomes ameliorates MTX-induced hippocampal neuron damage by triggering Nrf2-ARE pathway, decreasing IL-6, IFN-, and TNF-a levels and TUNEL positive cells in hippocampus, and repairing hippocampal neuronal cell damage. ADSC-exosomes ameliorated MTX-induced neuronal damage and suppressed oxidative stress induced by neuronal damage through the activation of Nrf2-ARE signaling pathway.

Surface Atomic Decoration of a Manganite to a Modulable Oxygen Evolution Reaction.

Aiming at the fundamental understanding of oxygen evolution reaction (OER) in epitaxial perovskite transition metal oxide (TMO) thin films, we evaluate the surface decoration conditions, including lattice orientation and surface morphology, of La2/3Sr1/3MnO3 (LSMO) related to its modulable OER performance. The LSMOs with orientations of (001), (110), and, (111) exhibit different OER activities owing to the discrepant surface density of Mn. Furthermore, tuning of the surface atomic terrace width of LSMO shows a more efficient path to modulate the OER performance by introducing a high-valence Mn state owing to the surface dangling bonds of LSMO. As the electrochemical process is dominated by the interface of the TMO surface and electrolyte, our investigation can approach the fundamental understanding of a perovskite-type TMO surface state and its OER performance while highlighting the role of the nonbulk electron state in a promising TMO electrocatalyst in abundant electrochemical processes.

The cytomegalovirus UL146 gene product vCXCL1 promotes the resistance of hepatic cells to CD8+ T cells through up-regulation of PD-L1.

The HCMV (human cytomegalovirus) encodes numerous proteins which function to evade the immune response, which allows the virus to replicate. Exploring the mechanisms of HCMV immune escape helps to find the strategy to inhibit HCMV replicate. CD8+ T cells play a critical role in the immune response to viral pathogens. However, the mechanisms of HCMV to evade the attack by CD8+ T cells remain largely unknown. Viral CXCL1 (vCXCL1) is the production of HCMV UL146 gene. Here, we found that vCXCL1 promoted the resistance of hepatic cells to CD8+ T cells. vCXCL1 increased the levels of PD-L1 protein expression and mRNA expression. VCXCL1 enhanced the binding of STAT3 transcription factor to the promoter of PD-L1 and increased the activity of PD-L1 promoter. Furthermore, down-regulation of PD-L1 reduced the effects of vCXCL1 on the resistance of hepatic cells to CD8+ T cells. Taken together, vCXCL1 promotes the resistance of hepatic cells to CD8+ T cells through up-regulation of PD-L1. This finding might provide a new mechanism of HCMV immune escape.

Association of asparaginase-associated pancreatitis and ULK2 gene polymorphism.

The purpose of the study was to analyze the clinical characteristics and the course of diagnosis and therapy of asparaginase-associated pancreatitis (AAP) in childhood, improve the ability of diagnosis and treatment, and evaluate ULK2 gene polymorphism as a predictive factor for AAP. Data of 12 patients with childhood AAP were reviewed. Sanger sequencing of ULK2 gene was performed in AAP group (n=12) and control group (n=146). The main symptoms of AAP were abdominal pain and vomiting. Generally, the levels of amylase and lipase in the serum peaked within 72 h. Abdominal ultrasonography was performed in 11 patients; seven patients exhibited findings of pancreatic enlargement. Computed tomography was performed in 9 patients. Five patients exhibited findings of pancreatic enlargement and peri-pancreatic exudation. All patients were managed by fasting at the early stage, and seven patients underwent placement of a nasojejunal tube to receive enteral nutrition. One patient underwent endoscopic retrograde cholangiopancreatography (revealing dilation of the pancreatic duct) and endoscopic retrograde pancreatic drainage. Another patient developed signs of shock and received continuous renal replacement. There were no deaths caused by AAP. Therefore, early identification of patients at risk of AAP is of great importance. In addition, repeated elevation in the levels of pancreatic enzymes is indicative of complications. Sanger sequencing analysis of ULK2 gene showed that there was a significant difference of EXON1: -493C>T and EXON1: -308C>G between the AAP group and control group (P<0.0001). Thus, ULK2 gene polymorphism may be associated with the development of AAP. However, more validation of this finding is needed.

Effect of Pt doping on the preferred orientation enhancement in FeCo/SiO2 nanocomposite films.

We prepared FeCoPt/SiO2 thin films by sol-gel spin-coating technique. As-prepared composite films were reduced in hydrogen to induce texture growth. Structural, magnetic property and surface morphology of the films were characterized by X-ray diffraction (XRD), vibrating sample magnetometer (VSM) and scanning electron microscope (SEM). These experimental data indicate that integrated intensity ratio I(200)/I(110) of diffraction peaks (200) and (110) of FeCo firstly increases and then decreases, while the coercivity first decreases and then increases with increasing Pt doping content. The specimen with less Pt doping content has a large I(200)/I(110) value and small coervicity value, which is closely related with strong (200) texture in FeCo thin film. These results indicate that fcc-Pt is also in favor of promoting (200) FeCo texture like Al or Cu elements, and this similar trends of Pt and Al originate from their similar atomic radius and crystal cell volume.