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1.
Blood ; 142(23): 2002-2015, 2023 12 07.
Article in English | MEDLINE | ID: mdl-37738460

ABSTRACT

Acute myeloid leukemia (AML) with TP53 mutation is one of the most lethal cancers and portends an extremely poor prognosis. Based on in silico analyses of druggable genes and differential gene expression in TP53-mutated AML, we identified pololike kinase 4 (PLK4) as a novel therapeutic target and examined its expression, regulation, pathogenetic mechanisms, and therapeutic potential in TP53-mutated AML. PLK4 expression was suppressed by activated p53 signaling in TP53 wild-type AML and was increased in TP53-mutated AML cell lines and primary samples. Short-term PLK4 inhibition induced DNA damage and apoptosis in TP53 wild-type AML. Prolonged PLK4 inhibition suppressed the growth of TP53-mutated AML and was associated with DNA damage, apoptosis, senescence, polyploidy, and defective cytokinesis. A hitherto undescribed PLK4/PRMT5/EZH2/H3K27me3 axis was demonstrated in both TP53 wild-type and mutated AML, resulting in histone modification through PLK4-induced PRMT5 phosphorylation. In TP53-mutated AML, combined effects of histone modification and polyploidy activated the cGAS-STING pathway, leading to secretion of cytokines and chemokines and activation of macrophages and T cells upon coculture with AML cells. In vivo, PLK4 inhibition also induced cytokine and chemokine expression in mouse recipients, and its combination with anti-CD47 antibody, which inhibited the "don't-eat-me" signal in macrophages, synergistically reduced leukemic burden and prolonged animal survival. The study shed important light on the pathogenetic role of PLK4 and might lead to novel therapeutic strategies in TP53-mutated AML.


Subject(s)
Histones , Leukemia, Myeloid, Acute , Animals , Mice , Histones/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Mutation , Methylation , Nucleotidyltransferases/metabolism , Leukemia, Myeloid, Acute/pathology , Immunity , Polyploidy
2.
Chemistry ; 30(25): e202304296, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38380537

ABSTRACT

Sodium/potassium-ion batteries (NIBs and KIBs) are considered the most promising candidates for lithium-ion batteries in energy storage fields. Tin sulfide (SnS2) is regarded as an attractive negative candidate for NIBs and KIBs thanks to its superior power density, high-rate performance and natural richness. Nevertheless, the slow dynamics, the enormous volume change and the decomposition of polysulfide intermediates limit its practical application. Herein, microcubes SnS2 were prepared through sacrificial MnCO3 template-assisted and a facile solvothermal reaction strategy and their performance was investigated in Na and K-based cells. The unique hollow cubic structure and well-confined SnS2 nanosheets play an important role in Na+/K+ rapid kinetic and alleviating volume change. The effect of the carbon additives (Super P/C65) on the electrochemical properties were investigated thoroughly. The in operando and ex-situ characterization provide a piece of direct evidence to clarify the storage mechanism of such conversion-alloying type negative electrode materials.

3.
Adv Exp Med Biol ; 1442: 45-64, 2023.
Article in English | MEDLINE | ID: mdl-38228958

ABSTRACT

Hematopoietic stem cells (HSCs) are multipotent stem cells that can self-renew and generate all blood cells of different lineages. The system is under tight control in order to maintain a precise equilibrium of the HSC pool and the effective production of mature blood cells to support various biological activities. Cell metabolism can regulate different molecular activities, such as epigenetic modification and cell cycle regulation, and subsequently affects the function and maintenance of HSC. Upon malignant transformation, oncogenic drivers in malignant hematopoietic cells can remodel the metabolic pathways for supporting the oncogenic growth. The dysregulation of metabolism results in oncogene addiction, implying the development of malignancy-specific metabolism-targeted therapy. In this chapter, we will discuss the significance of different metabolic pathways in hematopoiesis, specifically, the distinctive metabolic dependency in hematopoietic malignancies and potential metabolic therapy.


Subject(s)
Hematologic Neoplasms , Hematopoiesis , Humans , Hematopoiesis/physiology , Hematopoietic Stem Cells , Hematologic Neoplasms/metabolism , Multipotent Stem Cells , Epigenesis, Genetic , Cell Differentiation
4.
Molecules ; 26(6)2021 Mar 11.
Article in English | MEDLINE | ID: mdl-33799697

ABSTRACT

Lithium metal batteries have achieved large-scale application, but still have limitations such as poor safety performance and high cost, and limited lithium resources limit the production of lithium batteries. The construction of these devices is also hampered by limited lithium supplies. Therefore, it is particularly important to find alternative metals for lithium replacement. Sodium has the properties of rich in content, low cost and ability to provide high voltage, which makes it an ideal substitute for lithium. Sulfur-based materials have attributes of high energy density, high theoretical specific capacity and are easily oxidized. They may be used as cathodes matched with sodium anodes to form a sodium-sulfur battery. Traditional sodium-sulfur batteries are used at a temperature of about 300 °C. In order to solve problems associated with flammability, explosiveness and energy loss caused by high-temperature use conditions, most research is now focused on the development of room temperature sodium-sulfur batteries. Regardless of safety performance or energy storage performance, room temperature sodium-sulfur batteries have great potential as next-generation secondary batteries. This article summarizes the working principle and existing problems for room temperature sodium-sulfur battery, and summarizes the methods necessary to solve key scientific problems to improve the comprehensive energy storage performance of sodium-sulfur battery from four aspects: cathode, anode, electrolyte and separator.

5.
Cell Biol Int ; 44(1): 317-326, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31498515

ABSTRACT

Acute lung injury (ALI) caused by sepsis occurs early and the condition is severe, and is also an important reason for accelerating the death of patients. Increasing evidence has identified long non-coding RNA (lncRNA) metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) as a regulator of ALI. However, the potential mechanism underlying MALAT1 on ALI still needs further identification. To explore the mechanisms of gene regulation expression mediated by MALAT1 through miR-149/MyD88 in lung injury inflammation, we constructed a lung injury inflammatory model using the lipopolysaccharides (LPS)-induced method and quantificated the cytokines and signaling cascade molecules as well as miR-149. The MALAT1, myeloid differentiation factor 88 (MyD88), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 levels were significantly increased, and the nuclear factor-κB (NF-κB) pathway was activated, but the miR-149 level was decreased in the LPS-induced ALI model. miR-149 directly targeted both lncRNA MALAT1 and the MyD88 gene. Knockdown of MALAT1 down-regulated the levels of MyD88, TNF-α, IL-1ß, and IL-6, and inhibited the NF-κB pathway. However, MALAT1 knockdown up-regulated the expression of miR-149. Overexpression of miR-149 down-regulated MyD88, TNF-α, IL-1ß, and IL-6 levels, and inhibited the NF-κB pathway. MALAT1 acts as a pro-inflammatory factor in ALI via the miR-149/MyD88/NF-κB axis and is therefore a potential novel therapeutic target for ALI treatment.

6.
Clin Exp Hypertens ; 42(6): 519-526, 2020 Aug 17.
Article in English | MEDLINE | ID: mdl-31973589

ABSTRACT

Hypoxic pulmonary hypertension (HPH) is a fatal disease with limited therapeutic strategies. Combination therapy is regarded as the standard of care in PH and becoming widely used in clinical practice. However, many PH patients treated with combinations of available clinical drugs still have a poor prognosis. Therefore, identifying innovative therapeutic strategies is essential for PH. This study is designed to examine the effects of combined prevention with resveratrol and SR1001 on HPH in rats. The effects of combined prevention with resveratrol and SR1001 and each mono-prevention on the development of HPH, Th17 cells differentiation, expression of guanine nucleotide exchange factor-H1 (GEF-H1), Ras homolog gene family member A (RhoA) and Phosphorylated myosin phosphatase target subunit (MYPT1) were examined. HPH and RV hypertrophy occurred in rats exposed to hypoxia. Compared with normoxia group, the hypoxia group showed significantly increased ratio of Th17 cells. After treatment with resveratrol, HPH rats showed an obvious reduction of Th17 cells. SR1001 significantly reduced the increased p-MYPY1, RhoA, and GEF-H1 expression in the hypoxic rats. The mono-prevention with resveratrol or SR1001 significantly inhibited the Th17 cells differentiation, p-STAT3, p-MYPY1, RhoA, and GEF-H1 protein expression, which was further inhibited by their combination prevention. The combination of resveratrol and SR1001 has a synergistic interaction, suggesting that combined use of these pharmacological targets may be an alternative to exert further beneficial effects on HPH.


Subject(s)
Hypertension, Pulmonary , Resveratrol/pharmacology , Sulfonamides/pharmacology , Thiazoles/pharmacology , Animals , Drug Synergism , Drug Therapy, Combination , Enzyme Inhibitors/pharmacology , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/metabolism , Hypertension, Pulmonary/prevention & control , Hypoxia/complications , Hypoxia/metabolism , Male , Protein Phosphatase 1/metabolism , Pulmonary Artery/drug effects , Rats , Th17 Cells/drug effects , Th17 Cells/physiology , Treatment Outcome , rhoA GTP-Binding Protein/metabolism
7.
BMC Plant Biol ; 19(1): 106, 2019 Mar 19.
Article in English | MEDLINE | ID: mdl-30890145

ABSTRACT

BACKGROUND: MADS-box genes play important roles in vegetative growth and reproductive development and are essential for the correct development of plants (particularly inflorescences, flowers, and fruits). However, this gene family has not been identified nor their functions analyzed in Brassica oleracea. RESULTS: In this study, we performed a whole-genome survey of the complete set of MADS-box genes in B. oleracea. In total, 91 MADS-box transcription factors (TFs) were identified and categorized as type I (Mα, Mß, Mγ) and type II (MIKCC, MIKC*) groups according to the phylogeny and gene structure analysis. Among these genes, 59 were randomly distributed on 9 chromosomes, while the other 23 were assigned to 19 scaffolds and 9 genes from NCBI had no location information. Both RNA-sequencing and quantitative real-time-PCR analysis suggested that MIKC genes had more active and complex expression patterns than M type genes and most type II genes showed high flowering-related expression profiles. Additional quantitative real-time-PCR analysis of pedicel and four flower whorls revealed that the structure of the B.oleracea MIKC genes was conserved, but their homologues showed variable expression patterns compared to those in Arabidopsis thaliana. CONCLUSION: This paper gives a detailed overview of the BolMADS genes and their expression patterns. The results obtained in this study provide useful information for understanding the molecular regulation of flower development and further functional characterization of MADS-box genes in B. oleracea.


Subject(s)
Brassica/genetics , Flowers/growth & development , Genome, Plant , MADS Domain Proteins/genetics , Brassica/growth & development , Brassica/metabolism , Chromosomes, Plant , Flowers/metabolism , MADS Domain Proteins/metabolism , Phylogeny
8.
Zhonghua Zhong Liu Za Zhi ; 37(11): 868-72, 2015 Nov.
Article in Zh | MEDLINE | ID: mdl-26887521

ABSTRACT

OBJECTIVE: To analyze the clinical efficacy and toxicity of vitamin support in lung adenocarcinoma patients treated with pemetrexed second-line chemotherapy. METHODS: Two hundred and eighty-three patients with stage 3/4 lung adenocarcinoma treated at our hospital from August 2010 to August 2013 were included in this study. The lung adenocarcinomas in all the 283 patients were confirmed by pathology or cytology, all were EGFR-negative, and all patients received pemetrexed second line chemotherapy. The 283 patients were randomly divided into two groups: the improved treatment group (142 cases) and the conventional treatment group (141 cases). The patients of conventional treatment group received 400 µg folic acid per os daily for 7 days before the first dose of pemetrexed, and continued until 21 days after the last dose of pemetrexed. Besides, they received 1000 µg vitamin B12 injection at 7 days before the first dose of pemetrexed, and once per cycle of pemetrexed for 3 cycles after the last dose of pemetrexed. The patients of the improved treatment group took 400 µg folic acid daily per os from the day before the first dose to 21 days after the last dose of pemetrexed. They also received 500 µg vitamin B12 by injection one day before the first dose, and one day before each therapy cycle of pemetrexed therapy. RESULTS: The mean number of cycles of pemetrexed chemotherapy was 4 in both groups. In the 142 patients of improved treatment group, complete response (CR) was observed in two cases, partial remission (PR) in 28, stable disease (SD) in 21, and progressive disease (PD) in 91 cases, with a total effective rate of 21.1%. While in the conventional treatment group, CR was observed in one case, PR in 27 cases, SD in 23 cases, and PD in 90 cases, with a total effective rate of 19.9%. The median progression-free survival (PFS) was 3.8 months in the improved treatment group and 4.2 months in the conventional treatment group (P=0.143). The toxicity of chemotherapy was mild in both groups, with no significant difference between the two groups (P>0.05). The most common side effects of hematological system were leukopenia and neutropenia, and the most common side effects of non-blood system were nausea and vomiting. The most common grade 3-4 toxic reaction in both groups was leukopenia and neutropenia, with no significant difference between the two groups (P>0.05). Multivariate analysis showed that the age of patients was an independent factor of grade 3-4 chemotherapy toxic reaction (P<0.05), while gender, the baseline level of PS score or blood system had no significant effect on the grade 3-4 chemotherapy toxic reaction (P>0.05). CONCLUSIONS: Compared with the conventional treatment scheme, the improved treatment scheme has similar therapeutic effects and could be used more conveniently, while the toxic effects of chemotherapy are not increased at the same time. Our results indicate that pemetrexed-based chemotherapy does not need to delay the chemotherapy because of vitamin support treatment.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Agents/therapeutic use , Folic Acid/therapeutic use , Lung Neoplasms/drug therapy , Pemetrexed/therapeutic use , Vitamin B 12/therapeutic use , Vitamin B Complex/therapeutic use , Adenocarcinoma of Lung , Disease-Free Survival , Humans , Treatment Outcome
9.
Materials (Basel) ; 17(11)2024 May 29.
Article in English | MEDLINE | ID: mdl-38893893

ABSTRACT

The development of low-cost, high-performance oxygen electrocatalysts is of great significance for energy conversion and storage. As a potential substitute for precious metal electrocatalysts, the construction of efficient and cost-effective oxygen electrocatalysts is conducive to promoting the widespread application of zinc-air batteries. Herein, CoxNiyMOF nanoparticles encapsulated within a carbon matrix were synthesized and employed as cathode catalysts in zinc-air batteries. Co0.5Ni0.5MOF exhibits superior oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) performance and durability. The zinc-air battery assembled with Co0.5Ni0.5MOF as the air cathode exhibits a maximum power density of 138.6 mW·cm-2. These improvements are mainly attributed to the optimized metal composition of the cobalt-nickel alloy, which increases the specific surface area of the material and optimizes its pore structure. Significantly, the optimization of the electronic structure and active sites within the material has led to amplified ORR/OER activity and better zinc-air battery performance. This study underscores the immense promise of Co0.5Ni0.5MOF catalysts as feasible substitutes for commercial Pt/C catalysts in zinc-air batteries.

10.
Adv Mater ; 35(13): e2206228, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36004772

ABSTRACT

Batteries with a Li-metal anode have recently attracted extensive attention from the battery communities owing to their high energy density. However, severe dendrite growth hinders their practical applications. More seriously, when Li dendrites pierce the separators and trigger short circuit in a highly flammable organic electrolyte, the results would be catastrophic. Although the issues of growth of Li dendrites have been almost addressed by various methods, the highly flammable nature of conventional organic liquid electrolytes is still a lingering fear facing high-energy-density Li-metal batteries given the possibility of thermal runaway of the high-voltage cathode. Recently, various kinds of nonflammable liquid- or solid-state electrolytes have shown great potential toward safer Li-metal batteries with minimal detrimental effect on the battery performance or even enhanced electrochemical performance. In this review, recent advances in developing nonflammable electrolyte for high-energy-density Li-metal batteries including high-concentration electrolyte, localized high-concentration electrolyte, fluorinated electrolyte, ionic liquid electrolyte, and polymer electrolyte are summarized. Then, the solvation structure of different kinds of nonflammable liquid and polymer electrolytes are analyzed to provide insight into the mechanism for dendrite suppression and fire extinguishing. Finally, guidelines for future design of nonflammable electrolyte for safer Li-metal batteries are provided.

11.
ACS Nano ; 17(22): 22227-22239, 2023 Nov 28.
Article in English | MEDLINE | ID: mdl-37965727

ABSTRACT

Green hydrogen production from renewably powered water electrolysis is considered as an ideal approach to decarbonizing the energy and industry sectors. Given the high-cost supply of ultra-high-purity water, as well as the mismatched distribution of water sources and renewable energies, combining seawater electrolysis with coastal solar/offshore wind power is attracting increasing interest for large-scale green hydrogen production. However, various impurities in seawater lead to corrosive and toxic halides, hydroxide precipitation, and physical blocking, which will significantly degrade catalysts, electrodes, and membranes, thus shortening the stable service life of electrolyzers. To accelerate the development of seawater electrolysis, it is crucial to widen the working potential gap between oxygen evolution and chlorine evolution reactions and develop flexible and highly efficient seawater purification technologies. In this review, we comprehensively discuss present challenges, research efforts, and design principles for direct/indirect seawater electrolysis from the aspects of materials engineering and system innovation. Further opportunities in developing efficient and stable catalysts, advanced membranes, and integrated electrolyzers are highlighted for green hydrogen production from both seawater and low-grade water sources.

12.
Comput Math Methods Med ; 2022: 4597087, 2022.
Article in English | MEDLINE | ID: mdl-35126623

ABSTRACT

OBJECTIVE: To explore the possibility of microRNA miR-31-3p as a biomarker for bone metastasis of non-small-cell lung cancer (NSCLC) and its molecular mechanism to the invasion and metastasis of NSCLC cells. METHODS: Real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of miR-31-3p and forkhead box 1 (FOXO1) in NSCLC tissues, serum, and cells to analyze the correlation between the expression levels of miR-31-3p and the clinicopathology of NSCLC. After interference with or overexpressing miR-31-3p, NSCLC cell proliferation, apoptosis, invasion ability, and migration ability were detected by MTT, flow cytometry, Transwell, and scratch experiment, respectively. The interaction between miR-31-3p and FOXO1 was further verified by the dual-luciferase reporter experiment. Western blot was performed to detect the protein expression of FOXO1 in tissues and FOXO1, RhoA, p-RhoA, ROCK-2, and p-ROCK-2 in cells. RESULTS: In tissues, serum, and NSCLC cell line A549 of the NSCLC patients, the expression of FOXO1 was notably lower, and the miR-31-3p expression was significantly higher. Overexpression of miR-31-3p could distinctly improve the proliferation, invasion, and migration of A549 cells, meanwhile inhibit cell apoptosis, and activate the RhoA/ROCK-2 signaling pathway, while interfering with the expression of miR-31-3p has the opposite function. Besides, bioinformatics analysis and luciferase reporter assay confirmed that FOXO1 was a target gene of miR-31-3p. Overexpressing FOXO1 could inhibit the proliferation and metastasis of A549 cells, but overexpressing miR-31-3p reverses the results. CONCLUSION: This study confirmed that miR-31-3p promotes the proliferation, invasion, and migration of NSCLC cells and inhibits apoptosis through targeted regulating FOXO1 and be a potential therapeutic targets for the treatment of NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Forkhead Box Protein O1/antagonists & inhibitors , Forkhead Box Protein O1/genetics , Lung Neoplasms/genetics , MicroRNAs/genetics , A549 Cells , Adult , Apoptosis/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/secondary , Case-Control Studies , Cell Movement/genetics , Cell Proliferation/genetics , Computational Biology , Female , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , MicroRNAs/metabolism , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathology , Neoplasm Metastasis/genetics , Signal Transduction/genetics , Young Adult , rho-Associated Kinases/metabolism , rhoA GTP-Binding Protein/metabolism
13.
ACS Appl Mater Interfaces ; 14(21): 24447-24461, 2022 Jun 01.
Article in English | MEDLINE | ID: mdl-35604016

ABSTRACT

The integration of nickel (Ni) nanoparticle (NP)-embedded carbon layers (Ni@C) into the three-dimensional (3D) hierarchically porous carbon architectures, where ultrahigh boron (B) and nitrogen (N) doping is a potential methodology for boosting Ni catalysts' water splitting performances, was achieved. In this study, the novel 3D ultrafine Ni NP-embedded and B- and N-codoped hierarchically porous carbon nanowires (denoted as Ni@BNPCFs) were successfully synthesized via pyrolysis of the corresponding 3D nickel acetate [Ni(AC)2·4H2O]-hydroxybenzeneboronic acid-polyvinylpyrrolidone precursor networks woven by electrospinning. After optimizing the pyrolysis temperatures, various structural and morphological characterization analyses indicate that the optimal Ni@BNPCFs-900 networks own a large surface area, abundant micro/mesopores, and vast carbon edges/defects, which boost doping a large amount of B (5.81 atom %) and N (5.84 atom %) dopants into carbon frameworks with 6.36 atom % of BC3, pyridinic-N (pyridinic-N-Ni), and graphitic-N active sites. Electrochemical measurements demonstrate that Ni@BNPCFs-900 reveals the best hydrogen evolution reaction (HER) and oxygen reduction reaction catalytic activities in an alkaline solution. The HER potential at 10 mA cm-2 [E10 = -164.2 mV vs reversible hydrogen electrode (RHE)] of the optimal Ni@BNPCFs-900 is just 96.2 mV more negative than that of the state-of-the-art 20 wt % Pt/C (E10 = -68 mV vs RHE). In particular, the OER E10 and Tafel slope of the optimal Ni@BNPCFs-900 (1.517 V vs RHE and 19.31 mV dec-1) are much smaller than those of RuO2 (1.557 V vs RHE and 64.03 mV dec-1). For full water splitting, the catalytic current density achieves 10 mA cm-2 at a low cell voltage of 1.584 V for the (-) Ni@BNPCFs-900||Ni@BNPCFs-900 (+) electrolysis cell, which is 10 mV smaller than that of the (-) 20 wt % Pt/C||RuO2 (+) benchmark (1.594 V) under the same conditions. The synergistic effects of 3D hierarchically porous structures, advanced charge transport ability, and abundant active centers [such as Ni@BNC, BC3, pyridinic-N (pyridinic-N-Ni), and graphitic-N] are responsible for the excellent water-splitting catalytic activity of the Ni@BNPCFs-900 networks. Especially, because of the remarkable structural and chemical stabilities of 3D hierarchically porous Ni@BNPCFs-900 networks, the (-) Ni@BNPCFs-900||Ni@BNPCFs-900 (+) water electrolysis cell displays an excellent stability.

14.
ACS Appl Mater Interfaces ; 14(11): 13280-13294, 2022 Mar 23.
Article in English | MEDLINE | ID: mdl-35263074

ABSTRACT

Along with the widespread applications of various energy storage and conversion devices, the prices of precious metal platinum (Pt) and transition-metal cobalt/nickel keep continuously growing. In the future, designing high-efficiency nonprecious-metal catalysts based on low-cost iron (Fe) and manganese (Mn) metals for hydrogen evolution reaction (HER) and oxygen reduction reaction (ORR) is fairly critical for commercial applications of hydrogen fuel cells. In this study, for the first time, we design novel three-dimensional (3D) hybrid networks consisting of manganese oxide (MnO)-modified, iron carbide (Fe3C)-embedded, and boron (B)/nitrogen (N) codoped hierarchically porous carbon nanofibers (denoted FeMn@BNPCFs). After optimizing the pyrolysis temperatures, the optimal FeMn@BNPCFs-900 catalyst displays the best HER and ORR catalytic activities in an alkaline solution. As expected, the HER onset potential (Eonset) and the potential at a current density of -10 mA cm-2 for FeMn@BNPCFs-900 in 1.0 M KOH are just 36 and 194 mV more negative than the state-of-the-art 20 wt % Pt/C catalyst with more superior stability. In particular, the FeMn@BNPCFs-900 catalyst shows excellent ORR catalytic activity with a more positive Eonset (0.946 V vs RHE), a more positive half-wave potential (E1/2 = 0.868 V vs RHE), better long-term stability, and higher methanol tolerance surpassing the commercial 20 wt % Pt/C (Eonset = 0.943 V vs RHE, E1/2 = 0.854 V vs RHE) and most previously reported precious-metal-free catalysts in 0.1 M KOH. The synergistic effects of 3D hierarchically macro-/mesoporous architectures, advanced charge transport capacity, abundant carbon defects/edges, abundant B (2.3 atom %) and N (4.9 atom %) dopants, uniformly dispersed Fe3C@BNC NPs, and MnO nanocrystallines are responsible for the excellent HER/ORR catalytic activities of the FeMn@BNPCFs-900 catalyst.

15.
Leukemia ; 36(8): 1990-2001, 2022 08.
Article in English | MEDLINE | ID: mdl-35624145

ABSTRACT

Gain-of-function kinase mutations are common in AML and usually portend an inferior prognosis. We reported a novel mechanism whereby kinase mutants induced intracellular alkalization characteristic in oncogenesis. Thirteen kinases were found to activate sodium/hydrogen exchanger (NHE1) in normal hematopoietic progenitors, of which FLT3-ITD, KRASG12D, and BTK phosphorylated NHE1 maintained alkaline intracellular pH (pHi) and supported survival of AML cells. Primary AML samples with kinase mutations also showed increased NHE1 phosphorylation and evidence of NHE1 addiction. Amiloride enhanced anti-leukemic effects and intracellular distribution of kinase inhibitors and chemotherapy. Co-inhibition of NHE1 and kinase synergistically acidified pHi in leukemia and inhibited its growth in vivo. Plasma from patients taking amiloride for diuresis reduced pHi of leukemia and enhanced cytotoxic effects of kinase inhibitors and chemotherapy in vitro. NHE1-mediated intracellular alkalization played a key pathogenetic role in transmitting the proliferative signal from mutated-kinase and could be exploited for therapeutic intervention in AML.


Subject(s)
Amiloride , Antineoplastic Agents , Leukemia, Myeloid, Acute , Amiloride/pharmacology , Amiloride/therapeutic use , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Gain of Function Mutation , Humans , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/pathology , Mutation , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Protein Kinases/genetics , Protein Kinases/metabolism , Protons , Signal Transduction , fms-Like Tyrosine Kinase 3/genetics , fms-Like Tyrosine Kinase 3/therapeutic use
16.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(8): 1134-1140, 2020 Aug 30.
Article in Zh | MEDLINE | ID: mdl-32895184

ABSTRACT

OBJECTIVE: To explore whether thrombopoietin (TPO) can rescue megakaryopoiesis by protecting bone marrowderived endothelial progenitor cells (BM-EPCs) in patients receiving chemotherapy for hematological malignancies. METHODS: Bone marrow samples were collected from 23 patients with hematological malignancies 30 days after chemotherapy and from 10 healthy volunteers. BM-EPCs isolated from the samples were identified by staining for CD34, CD309 and CD133, and their proliferation in response to treatment with TPO was assessed using CCK8 assay. DiL-Ac-LDL uptake and FITC-UEA-I binding assay were performed to evaluate the amount of BM-EPCs from the subjects. Tube-formation and migration experiments were used for functional assessment of the BM-EPCs. The BM-EPCs with or without TPO treatment were co-cultured with human megakaryocytes, and the proliferation of the megakaryocytes was detected with flow cytometry. RESULTS: Flow cytometry indicated that the TPO-treated cells had high expressions of CD34, CD133, and CD309. CCK8 assay demonstrated that TPO treatment enhanced the proliferation of the BM-EPCs, and the optimal concentration of TPO was 100 µg/L. Double immunofluorescence assay indicated that the number of BM-EPC was significantly higher in TPO-treated group than in the control group. The TPO-treated BM-EPCs exhibited stronger tube-formation and migration abilities (P < 0.05) and more significantly enhanced the proliferation of co-cultured human megakaryocytes than the control cells (P < 0.05). CONCLUSIONS: TPO can directly stimulate megakaryopoiesis and reduce hemorrhage via protecting the function of BM-EPCs in patients following chemotherapy for hematological malignancies.


Subject(s)
Bone Marrow , Hematologic Neoplasms , Bone Marrow Cells , Cells, Cultured , Humans , Megakaryocytes , Thrombopoietin
17.
Mol Med Rep ; 22(6): 4485-4491, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33173966

ABSTRACT

In December 2019, an emergence of pneumonia was detected in patients infected with a novel coronavirus (CoV) in Wuhan (Hubei, China). The International Committee on Taxonomy of Viruses named the virus severe acute respiratory syndrome­CoV­2 and the disease CoV disease­19 (COVID­19). Patients with COVID­19 present with symptoms associated with respiratory system dysfunction and hematological changes, including lymphopenia, thrombocytopenia and coagulation disorders. However, to the best of our knowledge, the pathogenesis of COVID­19 remains unclear. Therefore, understanding the mechanisms underlying the hematological changes that manifest during COVID­19 may aid in the development of treatments and may improve patient prognosis.


Subject(s)
Betacoronavirus , Coronavirus Infections/blood , Pneumonia, Viral/blood , Antibodies, Viral/immunology , Antigen-Antibody Complex/immunology , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Betacoronavirus/immunology , COVID-19 , Cellular Microenvironment , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Coronavirus Infections/therapy , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/prevention & control , Cytokines/blood , Diagnostic Tests, Routine , Endothelium, Vascular/pathology , Hematologic Tests , Hematopoiesis/drug effects , Hematopoietic Stem Cells/pathology , Humans , Hypoalbuminemia/etiology , Liver/physiopathology , Lung/physiopathology , Lymphopenia/etiology , Lymphopenia/physiopathology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Pneumonia, Viral/therapy , Reperfusion Injury/etiology , SARS-CoV-2 , Thrombocytopenia/etiology , Thrombocytopenia/physiopathology , Thrombophilia/etiology , COVID-19 Drug Treatment
18.
Thromb Res ; 193: 110-115, 2020 09.
Article in English | MEDLINE | ID: mdl-32535232

ABSTRACT

Corona Virus Disease 2019 (COVID-19) is caused by the novel coronavirus SARS-CoV-2. Emerging genetic and clinical evidence suggests similarities between COVID-19 patients and those with severe acute respiratory syndrome and Middle East respiratory syndrome. Hematological changes such as lymphopenia and thrombocytopenia are not rare in COVID-19 patients, and a smaller population of these patients had leukopenia. Thrombocytopenia was detected in 5-41.7% of the patients with COVID-19. Analyzing the dynamic decrease in platelet counts may be useful in the prognosis of patients with COVID-19. However, the mechanisms underlying the development of thrombocytopenia remain to be elucidated. This review summarizes the hematological changes in patients infected with SARS-CoV-2 and possible underlying mechanisms of thrombocytopenia development.


Subject(s)
Blood Platelets/pathology , Coronavirus Infections/complications , Pneumonia, Viral/complications , Thrombocytopenia/etiology , Animals , Betacoronavirus/isolation & purification , Blood Coagulation , Blood Platelets/virology , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Humans , Pandemics , Platelet Count , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Prognosis , SARS-CoV-2 , Thrombocytopenia/blood , Thrombocytopenia/diagnosis , Thrombocytopenia/virology
19.
ACS Appl Mater Interfaces ; 10(49): 42796-42803, 2018 Dec 12.
Article in English | MEDLINE | ID: mdl-30461257

ABSTRACT

Sodium-ion batteries are regarded as one of the most promising energy storage systems, but the choice of anode material is still facing great challenges. Biomass carbon materials were explored for their low cost and wide range of sources. Here, a hard carbon material with a "honeycomb" structure using pine pollen (PP) as a precursor was successfully prepared and applied as an anode. The initial discharge capacity can reach 370 mA h g-1 at a current density of 0.1 A g-1. After cycling 200 times, the reversible capacity also stabled at 203.3 mA h g-1 with the retention rate of 98%. We further studied the sodium storage mechanism by different methods, especially the Na+ diffusivity coefficient ( DNa+) calculated by galvanostatic intermittent titration technique, which was more accurate. Interestingly, the trend of DNa+ coincides with cyclic voltammetry curves. Carbonized PP exhibited excellent electrochemical properties because of its three-dimensional structure and larger layer spacing (∼0.41 nm), which reduces the resistance of sodium ions to intercalation and deintercalation.

20.
Nanoscale ; 10(6): 2983-2989, 2018 Feb 08.
Article in English | MEDLINE | ID: mdl-29372212

ABSTRACT

The cycling stability of Li-O2 batteries has been impeded by the lack of high-efficiency, and durable oxygen cathodes for the oxygen-reduction reaction (ORR) and the oxygen-evolution reaction (OER). Herein we report a novel TiN nanorod array-based cathode, which was firstly prepared by growing a TiN nanorod array on carbon paper (CP), and then followed by depositing MnO2 ultrathin sheets or Ir nanoparticles on the TiN nanorods to form well-ordered, three-dimensional (3D), and free-standing structured cathodes: TiN@MnO2/CP and TiN@Ir/CP. Both cathodes exhibited good specific capacity and excellent cycling stability. Their specific discharge capacities were up to 2637 and 2530 mA h g-1, respectively. After 200 cycles for 2000 h at a current density of 100 mA g-1, no obvious decays were observed for TiN@MnO2/CP and TiN@Ir/CP cathodes, while significant decreases were observed after the 80th and 30th cycles for the Pt/C and TiN/CP cathodes, respectively. Such high performance can be ascribed to the 3D array structure with enough microspace and high surface area, which facilitated the high dispersion of active components and prevented the formation of large/irreversible Li2O2.

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