A New Strategy for the High-Throughput Characterization of Materials' Mechanical Homogeneity Based on the Effect of Isostatic Pressing on Surface Microstrain.

A new strategy for the high-throughput characterization of the mechanical homogeneity of metallurgical materials is proposed. Based on the principle of hydrostatic transmission and the synergistic analysis of the composition, microstructure, defects, and surface profile of the chosen material, the microstrain characteristics and changes in surface roughness after isostatic pressing were analyzed. After isostatic pressing, two types of microstrains were produced: low microstrain (surface smoothening with decreasing roughness) and large microstrain (surface roughening with increasing roughness). Furthermore, the roughness of the roughened microregions could be further classified based on the strain degree. The phenomenon of weak-interface damage with a large microstrain (plastic deformation, cleavage fracture, and tearing near nonmetallic inclusions) indicated that the surface microstrain analysis could be a new method of high-throughput characterization for microregions with relatively poor micromechanical properties. In general, the effect of isostatic pressing on the surface microstrain of heat-resistant steel provides a promising strategy for achieving high-throughput screening and statistically characterizing microregions with poor micromechanical properties, such as microregions containing microcracks, nonmetallic inclusions, pores, and other surface defects.

Magnetism and electronic properties of ConMoP (n = 1 ~ 5) cluster: a DFT study.

CONTEXT: Hydrogen has emerged as a promising clean energy carrier, underscoring the imperative need to comprehend its adsorption mechanisms. This study delves into the magnetic and electronic properties of Co-Mo-P clusters, aiming to unveil their catalytic potential in hydrogen production. Employing density functional theory (DFT), we optimized cluster configurations and scrutinized their magnetic behaviors. Our investigation unveiled 16 stable configurations of the ConMoP (n = 1 ~ 5) cluster, predominantly in steric forms. The magnetic attributes were primarily ascribed to the d orbitals of Co metal atoms, with Co3MoP exhibiting exceptional magnetic characteristics. Analysis of density of state diagrams revealed the prevalence of spin-up α-electrons in d orbitals, while spin-down ß-electrons attenuated overall magnetic properties. Localized orbital (LOL) analysis highlighted stable covalent bonds within the clusters, affirming their catalytic potential. Orbital delocalization index (ODI) analysis revealed diverse spatial distribution ranges for orbitals across different configurations, suggesting a progressive attenuation of off-domain properties with increasing cluster size. Furthermore, infrared spectroscopy unveiled distinct vibrational peaks in various configurations, indicative of unique infrared activities. These findings contribute to a nuanced theoretical understanding of Co-Mo-P clusters and pave the path for future research aimed at augmenting their catalytic efficiency in hydrogen production. This study underscores the viability of Co-Mo-P clusters as alternatives to conventional Pt catalysts, offering insights into the design of novel materials for sustainable energy applications. Further research is warranted to explore the behavior of the Co-Mo-P system under diverse reaction conditions, fostering advancements in materials and energy science. METHODS: In this study, we harnessed the ConMoP (n = 1 ~ 5) cluster as a simulation platform for probing the local structure of the material. Our aim was to scrutinize the magnetism, electronic characteristics influenced by the varying metal atoms within these clusters. A systematic exploration involved incrementing the number of metal atoms and expanding the cluster size to elucidate the corresponding property variations. Density functional theory (DFT) calculations were pivotal to our methodology, employing the B3LYP hybrid functional implemented in the Gaussian 16 software package. The ConMoP (n = 1 ~ 5) cluster underwent optimization calculations and vibrational analysis at the def2-tzvp quantization level, yielding optimized configurations with diverse spin multiplet degrees. To comprehensively characterize and visually represent the stability, electronic features, and catalytic attributes of these configurations, we employed a suite of computational tools. Specifically, quantum chemistry software GaussView and wave function analysis software Multiwfn played integral roles. Through the integrated use of these computational tools, we acquired valuable insights into the magnetism, electronic characteristics of the ConMoP (n = 1 ~ 5) cluster, shedding light on their dependency on distinct metal atoms.

Seeding ductile nanophase in ceramic grains.

Transgranular brittle fracture is the dominant failure mode of brittle materials, including ceramics and ceramic matrix composites. However, strengthening these materials without sacrificing their toughness has been a big challenge. In this study, an innovative approach is proposed to achieve coordinated strengthening and toughening of ceramics-based composites by introducing specific ductile coherent nanoparticles into ceramic grains. As an example, the WC-Co cemented tungsten carbides were used to demonstrate how this brittle material can achieve ultrahigh strength without losing toughness by seeding metallic nanoparticles inside WC grains. The mechanisms for inducing the formation and modulating the amount, size, and distribution of such nanophase within the ceramic grains were disclosed. The fraction of transgranular ruptures of the brittle ceramic phase was reduced significantly due to the presence of the ductile coherent in-grain nanoparticles. Both the strength and strain limit of the cemented carbides were remarkably increased compared to their counterparts reported in the literature. The coordinated strengthening and toughening strategy proposed in this work is applicable to a broad range of ceramics and ceramic matrix composites to obtain superior comprehensive mechanical properties.

Comparative analysis of electronic, magnetic, catalytic properties of clusters (PS4, CrnPS4, AlnPS4, GanPS4, n = 1 ~ 3) based on density functional theory.

CONTEXT: The article presents a comparative study of the electronic, magnetic and catalytic properties of CrPS4, AlPS4, GaPS4 and their expanded structures. It is finally found that: When n = 2, 3, the internal electron mobility of the configurations is stronger than when n = 0,1. When n = 1, the five configurations, except configuration 1Cr(4), are susceptible to both electrophilic and nucleophilic reactions at the same time. The configurations are more prone to nucleophilic reactions when n = 2 and 3, and the reaction sites are mainly located on the metal atoms; the more metal atoms, the more nucleophilic reaction sites. When the M atoms in the configuration are Al and Ga atoms, there is no big difference between the contribution of metal atoms and non-metal atoms to the magnetism in the configuration, while in the configuration containing Cr atoms, the metal atoms contribute more to the magnetism and mainly originate from the d-orbitals, which has better magnetic properties and greater application value. Configuration 2Cr(4) and configuration 1Cr(2) have better catalytic and adsorption activities and are most suitable as catalysts. METHODS: In the article, based on topological principles, density functional theory, B3LYP functional and def2-tzvp basis group and Gaussian16 quantum chemistry software were used to optimise the calculations of the clusters CrPS4, AlPS4, GaPS4 and their expanded configurations, with the most stable structure selected for each cluster, and finally, with the help of Multiwfn program, the required analytical data were obtained by assisting the calculations.

Density functional theory studies on properties of cluster ConMoS (n=1 ~ 5): interatomic interactions, electronic properties, frontier orbitals.

CONTEXT: To comprehend the microscopic property alterations within the ConMoS cluster (n=1-5), this study investigates its internal interactions, electronic characteristics, and orbital correlations employing density functional theory. Structural optimization and theoretical analysis of the cluster are conducted using the Gaussian09 software package, considering various spin multiplicities and employing the B3LYP/def2tzvp quantum chemical method as the computational standard. The outcomes reveal the optimization of the cluster, resulting in 21 stable configurations while continually acquiring energy from the external environment. Analysis of the interaction region indicator functions, the independent gradient model based on Hirshfeld partition, the localized orbital indicator functions, and the electron localization function reveals a trend toward chemical bonding interactions within the interatomic interaction regions. Moreover, the interatomic forces exhibit a high likelihood of engaging in covalent bonding interactions. Both Co and Mo atoms display greater electron delocalization, facilitating the exchange of electrons with the external environment. The paper discuss electron space range, hardness and softness, polarizability, dipole moment, Mulliken population analysis, density of states, HOMO-LUMO diagram, and UV-Vis spectra. Configuration 5a exhibits the broadest electron delocalization and the highest reactivity. It maintains structural stability in external conditions and displays the most polarized molecules. Metal atoms in this cluster exhibit superior mobility compared to non-metal atoms. We elucidate the electron density aggregation region within the cluster. Configuration 1a demonstrates the highest correlation with molar absorption coefficient for its peak. Analyzing the HOMO and LUMO orbital delocalization index and center-of-mass distances revealed that the front orbits of configuration 5a exhibited a broad distribution in space and the minimum center-of-mass distance. METHODS: This study presents a theoretical investigation of Co-Mo-S clusters employing density functional theory (DFT). DFT is a prevalent method for exploring the electronic structure and characteristics of atoms, molecules, and solids. The paper examines cluster attributes encompassing interatomic interactions, electronic properties, and frontier orbitals. Gaussian09 software is employed for optimizing cluster structures, while the analysis is augmented using Multiwfn wave function analysis software. By harnessing these theoretical and computational tools, it aims to delve deeper into cluster properties, yielding valuable insights.

Stability, electronic and catalytic properties of ConMoP(n = 1 ~ 5) clusters: A DFT study.

CONTEXT: The investigation of the stability, electronic properties, and catalytic activity of clusters ConMoP holds significant applications and implications in catalyst design, materials science, energy conversion and storage, and environmental protection. The study aims to delve into the unique features of the clusters ConMoP(n = 1 ~ 5), aiming to drive advancements in these related fields. The results obtained from the analysis revealed the stable configurations of the ten clusters, primarily characterized by steric structures. Furthermore, the energy of the clusters was found to increase continuously during growth, as indicated by calculations of atomic fragmentation energy and atomic binding energy. The researchers conducted an analysis of the Natural Population Analysis(NPA) charge, which revealed that Co atoms acted as electron donors, while P and Mo atoms acted as electron acceptors within the clusters. Additionally, an examination of the electrostatic potential indicated that Co and Mo atoms displayed nucleophilic tendencies, while P atoms exhibited electrophilic characteristics. Moreover, the density of states curves, HOMO and LUMO orbitals, and Kooperman's theorem were applied to the clusters ConMoP(n = 1 ~ 5).Through this study, a deeper understanding of the properties and behavior of clusters ConMoP has been achieved, shedding light on their potential as catalysts. The findings contribute to the existing knowledge of these clusters and provide a basis for further research and exploration in this field. METHODS: In this study, we employed the clusters ConMoP(n = 1 ~ 5) to simulate the local structure of the material, enabling us to investigate the stability, electronic properties, and catalytic properties influenced by the metal atoms. By systematically increasing the number of metal atoms and expanding the cluster size, we explored the variations in these properties. Density functional theory (DFT) calculations were performed using the B3LYP hybrid functional implemented in the Gaussian09 software package. The clusters ConMoP(n = 1 ~ 5) underwent optimization calculations and vibrational analysis at the def2-tzvp quantization level, resulting in optimized configurations with different spin multiplet degrees. For data characterization and graphical representation of the stability, electronic properties, and catalytic properties of the optimized configurations, we utilized a range of computational tools. Specifically, the quantum chemistry software GaussView, wave function analysis software Multiwfn were employed. Through the comprehensive utilization of these computational tools, we gained valuable insights into the stability, electronic properties, and catalytic properties of the clusters ConMoP(n = 1 ~ 5) and their dependence on different metal atoms.

Application of density functional theory to study the electronic structure and magnetic behavior of clusters MnPS3 (M = Fe, Co, Ni; n = 0 ~ 3).

CONTEXT: The article explores and compares the electronic structure and magnetic properties of transition metal phosphate materials, namely FePS3, CoPS3, and NiPS3. RESEARCH FINDINGS: Analysis of the optimized configuration reveals significant insights into the electronic properties of MnPS3 clusters. Electrons within the cluster exhibit a flow from the metal atom M and the non-metal atom P to the non-metal atom S. The S atom serves as the primary site for electrophilic reactions within the cluster, while the metal atom hosts the main site for nucleophilic reactions. Configurations 2a(2), 2b(2), 3a(4), 3b(3), and 3c(2) exhibit enhanced electron mobility and optimal electronic properties. Moreover, the analysis of the magnetic properties of the optimized configurations demonstrates that the magnetic behavior of MnPS3 clusters is influenced by the spin motion of α electrons in the p orbital. Metal atoms make a relatively significant contribution to the magnetic properties of MnPS3 clusters. Configurations 1b(3), 2c(4), and 3a(4) exhibit comparatively higher magnetic properties compared to other configurations of the same size. This study identifies the optimal configuration for the magnetic and electronic properties of transition metal phosphorothioate materials. It also elucidates the trends in magnetic and electronic properties as the number of metal atoms varies, thereby providing valuable theoretical support for the application of these materials in the fields of magnetic materials and electronic devices. METHODS: In this study, the Fe-based transition elements, namely Fe, Co, and Ni, are selected as the metal atoms M. The cluster MPS3 is used to simulate the local structure of the material, allowing for an investigation into the influence of the metal atoms on its electronic and magnetic properties. By increasing the number of metal atoms and expanding the cluster size, the variations in these properties are explored. Density functional theory (DFT) calculations are performed using the B3LYP functional within the Gaussian09 software package. The MnPS3 cluster is subjected to optimal calculations and vibrational analysis at the def2-tzvp quantization level, resulting in optimized configurations with different spin multiplet degrees. Quantum chemistry software GaussView, wave function analysis software Multiwfn, and plotting software Origin are utilized for data characterization and graphical representation of the magnetic and electronic properties of the optimized configurations. Through the employment of these computational tools, valuable insights into the magnetic and electronic properties of the MnPS3 cluster and its dependency on different metal atoms are obtained.

E2F2 modulates cell adhesion through the transcriptional regulation of PECAM1 in multiple myeloma.

Multiple myeloma (MM) is the second most common haematological malignancy. Despite the development of new drugs and treatments in recent years, the therapeutic outcomes of patients are not satisfactory. It is necessary to further investigate the molecular mechanism underlying MM progression. Herein, we found that high E2F2 expression was correlated with poor overall survival and advanced clinical stages in MM patients. Gain- and loss-of-function studies showed that E2F2 inhibited cell adhesion and consequently activated cell epithelial-to-mesenchymal transition (EMT) and migration. Further experiments revealed that E2F2 interacted with the PECAM1 promoter to suppress its transcriptional activity. The E2F2-knockdown-mediated promotion of cell adhesion was significantly reversed by the repression of PECAM1 expression. Finally, we observed that silencing E2F2 significantly inhibited viability and tumour progression in MM cell models and xenograft mouse models respectively. This study demonstrates that E2F2 plays a vital role as a tumour accelerator by inhibiting PECAM1-dependent cell adhesion and accelerating MM cell proliferation. Therefore, E2F2 may serve as a potential independent prognostic marker and therapeutic target for MM.

Overexpression of PvBiP2 improved biomass yield and cadmium tolerance in switchgrass (Panicum virgatum L.).

Switchgrass (Panicum virgatum L.), the prime bioenergy feedstock crop, is one ideal candidate for phytoremediation of cadmium (Cd). The absorption of Cd imposes severe endoplasmic reticulum (ER)-stress in plants. ER chaperone binding proteins (BiPs) are important modulators in ER-stress responses. The objective of this study was to characterize one Cd-responsive BiP gene, PvBiP2, in switchgrass for its roles in Cd tolerance and plant growth. PvBiP2 was up-regulated by Cd and the ER-stress inducer, dithiothreitol (DTT) and could be trans-activated by one Cd-responsive heat shock transcription factor PvHsfA4. Overexpression of PvBiP2 in switchgrass significantly increased its plant growth with higher height, stem diameter, leaf width, internode length, and tiller numbers than those of the wildtype (WT) plants under non-stress conditions. After 30 days of Cd treatment, the PvBiP2 over-expression transgenic lines showed 40-45% higher dry biomass accumulation with net photosynthesis rate (Pn), but lower electrolyte leakage (EL), malondialdehyde (MDA), and glutathione (GSH) levels than WT. Moreover, over-expressing PvBiP2 led to ∼90-140% Cd accumulation in plants but 46-57% lower Cd translocation rates to shoots. Together, the PvHSFA4-PvBiP2 module acted as positive regulators in plant Cd tolerance, and over-expressing PvBiP2 promoted plant vegetative growth as well as Cd tolerance making it an ideal molecular target for genetic improvement in switchgrass in the future.

A sustainable recycling process for end-of-life vehicle plastics: A case study on waste bumpers.

End-of-life vehicle (ELV) recycling has considerable potential value and a wide range of applications. Plastics form an increasing percentage of the total weight of automobiles as their lightweight. Recycling plastics from automobiles is important for achieving the overall recycling goal from a sustainability standpoint. In this study, the whole recycling process of automotive plastic parts was explored, using waste bumpers as an example, in which paint removal and recycled polypropylene (RPP) modification were the important links. First, LS-Dyna was used to run simulations to determine the best paint removal process parameters for surface coating treatment, and experiments were then conducted to confirm the paint removal effect. Second, component, morphological, and Gel Permeation Chromatography (GPC) analyses were conducted. As per the results, the degradation was primarily caused by surface oxidation of the ELV bumper, and the molecular weight of RPP was lower than that of new PP. Finally, the thermal and mechanical properties of RPP, modified RPP, and the new bumper were compared. The addition of nano-montmorillonite(nano-MMT), virgin PP, and a compatibilizer could improve the thermal and mechanical properties of RPP while satisfying the application requirements of the new bumper. This process provides a valuable idea for the sustainable recycling of used ELV plastics.

Dual-Mode Fluorescence and Visual Fluorescent Test Paper Detection of Copper Ions and EDTA.

In this study, blue-emission carbon dots were prepared from the legumes of the vegetable Pisum sativum Linn. by one-step carbonization. The fluorescence of a carbon dot (CDs) solution can be quenched by copper ions and recovered by ethylenediaminetetraacetic acid (EDTA). In addition, two kinds of visual fluorescent filter papers were prepared. Finally, a dual-mode fluorescence and visual fluorescent test paper was employed for the detection of copper ions and EDTA. The simple synthesis method and the high safety enable this material to have more application possibilities.

MicroRNA­93 knockdown inhibits acute myeloid leukemia cell growth via inactivating the PI3K/AKT pathway by upregulating DAB2.

Acute myeloid leukemia (AML) is associated with a poor prognosis in elderly adults and currently lacks optimal treatment strategies. MicroRNAs (miRNAs or miRs) have increasingly been reported to be associated with AML progression; however, the mechanisms of action of miR­93 in AML with the involvement of disabled 2 (DAB2) are currently unknown. In the present study, miR­93 expression was assessed in patients with AML and in AML cell lines. The association between miR­93 expression and the pathological characteristics of patients with AML was analyzed. AML cells were then transfected to knockdown or overexpress miR­93 in order to elucidate its function in AML progression. The target gene of miR­93 was assessed using a dual­luciferase reporter gene assay. The expression levels of miR­93, DAB2 and phosphatidylinositol 3­kinase (PI3K)/protein kinase B (AKT) pathway­related proteins were measured and in vivo experiments were conducted to confirm the results. It was observed that miR­93 was highly expressed in patients with AML and in AML cells. The knockdown of miR­93 in HL­60 cells inhibited AML cell proliferation and resistance to apoptosis, while the overexpression of miR­93 in THP­1 cells led to contrasting results. Moreover, miR­93 targeted DAB2 to inactivate the PI3K/AKT pathway, and the overexpression of DAB2 reversed the effects of miR­93 on THP­1 cell growth. Tumor volume, tumor weight, and the positive expression of Ki67, survivin and p53 were increased in THP­1 cells overexpressing miR­93. On the whole, the present study demonstrates that miR­93 is highly expressed in AML cells, and that the suppression of miR­93 inhibits AML cell growth by targeting DAB2 and inhibiting the PI3K/AKT pathway.

Ethyl Acetate Fraction of Amomum villosum var. xanthioides Attenuates Hepatic Endoplasmic Reticulum Stress-Induced Non-Alcoholic Steatohepatitis via Improvement of Antioxidant Capacities.

Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH), affects 25% of the global population. Despite the prevalence of NAFLD worldwide, effective therapeutics are currently lacking. Amomum villosum var. xanthioides (Wall. ex Baker) T.L.Wu & S.J.Chen (AX) is a medicinal herb traditionally used for treating digestive tract disorders in countries across Asia. We aimed to examine the pharmacological effects of the ethyl acetate fraction of AX (AXEF) against tunicamycin (TM)-induced ER stress in a NASH mouse model using C57/BL6J male mice. Following TM injections (2 mg/kg), the mice were orally administrated AXEF (12.5, 25, or 50 mg/kg), silymarin (50 mg/kg), or distilled water daily for 5 days, and the outcomes for fatty liver, inflammation, and oxidative stress were measured in serum or liver tissue levels. AXEF drastically attenuated hepatic ER stress-induced NASH as indicated by decreases in lipid droplet accumulations, serum liver enzymes, hepatic inflammations, and cell death signals in the hepatic tissue and/or serum levels. Interestingly, AXEF showed potent antioxidant effects by quenching reactive oxidative stress and its final product lipid peroxide in the hepatic tissue, specifically an increase in metallothionein (MT). To confirm the underlying actions of AXEF, we observed that AXEF increases MT1 gene promoter activities in the physiological levels. Collectively, AXEF showed antioxidant properties on TM-induced ER stress in a NASH mice model through the improvement of MTs.

A high throughput dynamic method for characterizing thermodynamic properties of catalyzed magnesium hydrides by thermogravimetric analysis.

The use of the conventional pressure-composition-temperature (PCT) method to determine the thermodynamics of metal hydrides is a time-consuming process. This work presents an efficient method based on thermogravimetric analysis (TGA), to characterize the thermodynamic parameters. Through cycling catalyzed magnesium hydride in a TGA apparatus under a flowing gas with a constant hydrogen partial pressure, TGA curves can be used to determine absorption/desorption equilibrium temperatures. Based on the van't Hoff analysis, the reaction enthalpies and entropies can be derived from the equilibrium temperatures as a function of hydrogen pressure. Using the results of this work we calculated the hydrogenation and dehydrogenation enthalpies, which are 79.8 kJ per mol per H2 and 76.5 kJ per mol per H2, respectively. These values are in good agreement with those reported values using the PCT method. These results demonstrate that the TGA can be an efficient and effective method for measuring thermodynamic parameters of metal hydrides.

A Regulatory Loop Involving Notch and Wnt Signaling Maintains Leukemia Stem Cells in T-Cell Acute Lymphoblastic Leukemia.

Leukemia-initiating cells play critical role in relapse, resistance to therapies and metastases but the mechanism remains largely elusive. We report that ß-catenin is over-expressed in almost all T-ALL patients and flow sorted ß-cateninhigh fractions are highly resistant to therapy, leading to liver metastases in nude mice as well as dysregulated lncRNAs. Pharmacological inhibition through XAV-939 as well as si-RNA mediated inhibition of ß-catenin is initially effective in re-sensitization to therapy, however, prolonged inhibition shifts dependency from ß-catenin to Notch signaling, with particularly high levels of receptors Notch 1 and Notch 2. The results are verifiable in a cohort of T-ALL patients comprising of responders vs. those who have progressed, with ß-catenin, Notch 1 and Notch 2 elevated in progressed patients. Further, in patients-derived cells, silencing of Notch 1 or Notch 2 does not counter resistance to ß-catenin inhibition, rather pharmacological pan-Notch inhibition is needed to overcome resistance and its effect on in vitro tumor sphere formations as well as in vivo liver metastases. Thus, wnt and Notch signaling are part of a regulatory loop mutually compensating for each other in T-ALL, while ensuring the maintenance of stem cell phenotype.

Sestrin Proteins Protect Against Lipotoxicity-Induced Oxidative Stress in the Liver via Suppression of C-Jun N-Terminal Kinases.

BACKGROUND & AIMS: Sestrin 1/2/3 (Sesn1/2/3) belong to a small family of proteins that have been implicated in the regulation of metabolic homeostasis and oxidative stress. However, the underlying mechanisms remain incompletely understood. The aim of this work was to illustrate the collective function of Sesn1/2/3 in the protection against hepatic lipotoxicity. METHODS: We used Sesn1/2/3 triple knockout (TKO) mouse and cell models to characterize oxidative stress and signal transduction under lipotoxic conditions. Biochemical, histologic, and physiological approaches were applied to illustrate the related processes. RESULTS: After feeding with a Western diet for 8 weeks, TKO mice developed remarkable metabolic associated fatty liver disease that was manifested by exacerbated hepatic steatosis, inflammation, and fibrosis compared with wild-type counterparts. Moreover, TKO mice exhibited higher levels of hepatic lipotoxicity and oxidative stress. Our biochemical data revealed a critical signaling node from sestrins to c-Jun N-terminal kinases (JNKs) in that sestrins interact with JNKs and mitogen-activated protein kinase kinase 7 and suppress the JNK phosphorylation and activity. In doing so, sestrins markedly reduced palmitate-induced lipotoxicity and oxidative stress in both mouse and human hepatocytes. CONCLUSIONS: The data from this study suggest that Sesn1/2/3 play an important role in the protection against lipotoxicity-associated oxidative stress and related pathology in the liver.

HDAC8 promotes daunorubicin resistance of human acute myeloid leukemia cells via regulation of IL-6 and IL-8.

The chemoresistance is one of the major challenges for acute myeloid leukemia (AML) treatment. We found that the expression of histone deacetylase 8 (HDAC8) was increased in daunorubicin (DNR) resistant AML cells, while targeted inhibition of HDAC8 by its specific siRNA or inhibitor can restore sensitivity of DNR treatment . Further, targeted inhibition of HDAC8 can suppress expression of interleukin 6 (IL-6) and IL-8. While recombinant IL-6 (rIL-6) and rIL-8 can reverse si-HDAC8-resored DNR sensitivity of AML cells. Mechanistical study revealed that HDAC8 increased the expression of p65, one of key components of NF-κB complex, to promote the expression of IL-6 and IL-8. It might be due to that HDAC8 can directly bind with the promoter of p65 to increase its transcription and expression. Collectively, our data suggested that HDAC8 promotes DNR resistance of human AML cells via regulation of IL-6 and IL-8.

Piezo1 impairs hepatocellular tumor growth via deregulation of the MAPK-mediated YAP signaling pathway.

Accumulating evidence has revealed the mechanosensitive ion channel protein Piezo1 is contributing to tumorigenesis. However, its role in hepatocellular carcinoma (HCC) remains unexplored. In this study, we demonstrated that Piezo1 was expressed in the HepG2 cell line and depletion of Piezo1 impaired proliferation and migration, as well as increased apoptosis in these cells. Using a Piezo1-specific activator, Yoda1, we identified that calcium entry induced by Yoda1 resulted in phosphorylation of JNK, p38, and ERK, thereby activating the mitogen-activated protein kinase (MAPK) pathway, in a dose- and time-dependent manner. More strikingly, Piezo1 activation integrated with YAP signaling to control the nuclear translocation of YAP and regulation of its target genes. JNK, p38, and ERK (MAPK signaling) regulated Yoda1-induced YAP activation. Consistent with the association of calpain with Piezo1, we also found that calpain activity was decreased by siRNA-mediated knockdown of Piezo1. In addition, the growth of HCC tumors was inhibited in Piezo1 haploinsufficient mice. Together, our findings establish that the Piezo1/MAPK/YAP signaling cascade is essential for HepG2 cell function. These results highlight the importance of Piezo1 in HCC and the potential utility of Piezo1 as a biomarker and therapeutic target.

The depletion of Circ-PRKDC enhances autophagy and apoptosis in T-cell acute lymphoblastic leukemia via microRNA-653-5p/Reelin mediation of the PI3K/AKT/mTOR signaling pathway.

A range of circular (Circ) RNAs have been demonstrated to be of therapeutic significance for the treatment of acute lymphoblastic leukemia (ALL). Here, we investigated the mechanisms underlying the action of Circ-PRKDC and the microRNA-653-5p/Reelin (miR-653-5p/RELN) axis in T-cell ALL (T-ALL).Clinical specimens were obtained from patients with T-ALL (n = 39) and healthy controls (n = 30). In each specimen, we determined the expression levels of Circ-PRKDC, miR-653-5p, and RELN. Human T-ALL cells (Jurkat) were transfected with Circ-PRKDC- or miR-653-5p-related sequences to investigate cell proliferation, apoptosis, and autophagy. We also determined the levels of Circ-PRKDC, miR-653-5p, RELN, and signaling proteins related to phosphoinositide 3-kinase (PI3K), AKT, and mammalian target of rapamycin (mTOR). Finally, we decoded the interactions between Circ-PRKDC, miR-653-5p, and RELN. The expression levels of Circ-PRKDC and RELN were upregulated in T-ALL tissues and cells while the levels of miR-653-5p were downregulated. Thereafter, then silencing of Circ-PRKDC, or the enforced expression of miR-653-5p, repressed the expression of RELN and the activation of the PI3K/AKT/mTOR signaling pathway, thus enhancing cell autophagy and apoptosis, and disrupting cell proliferation. Circ-PRKDC acted a sponge for miR-653-5p while miR-653-5p targeted RELN. The knockdown of miR-653-5p abrogated the silencing of Circ-PRKDC-induced effects in T-ALL cells. The depletion of Circ-PRKDC elevated miR-653-5p to silence RELN-mediated PI3K/AKT/mTOR signaling activation, thereby enhancing autophagy and apoptosis in T-ALL cells.

Synthesis of blue fluorescent carbon dots and their application in detecting mercury and iodine based on "off-on" mode.

In this study, a type of blue-emission fluorescent carbon dot was synthesized using malic acid, urea, and water. This material demonstrates strong stability to heat, ionic strength, and time. It was found that mercury ions can quench the blue fluorescence of the material, and using iodine ions, the fluorescence can be recovered. Hence, we designed an "off-on" mode to detect mercury and iodine ions using the carbon dots. The results showed that this material exhibits good selectivity and recovery rate. Concurrently, imaging experiments showed that this material demonstrates low cytotoxicity and can be used in cell fluorescence imaging. The study concludes that this material has wider application prospects in the future.