Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations

Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2), are present in most gliomas and secondary glioblastomas, but are rare in other neoplasms. IDH1/2 mutations are heterozygous, and affect a single arginine residue. Recently, IDH1 mutations were identified in 8% of acute myelogenous leukemia (AML) patients. A glioma study revealed that IDH1 mutations cause a gain-of-function, resulting in the production and accumulation of 2-hydroxyglutarate (2-HG). Genotyping of 145 AML biopsies identified 11 IDH1 R132 mutant samples. Liquid chromatography-mass spectrometry metabolite screening revealed increased 2-HG levels in IDH1 R132 mutant cells and sera, and uncovered two IDH2 R172K mutations. IDH1/2 mutations were associated with normal karyotypes. Recombinant IDH1 R132C and IDH2 R172K proteins catalyze the novel nicotinamide adenine dinucleotide phosphate (NADPH)–dependent reduction of α-ketoglutarate (α-KG) to 2-HG. The IDH1 R132C mutation commonly found in AML reduces the affinity for isocitrate, and increases the affinity for NADPH and α-KG. This prevents the oxidative decarboxylation of isocitrate to α-KG, and facilitates the conversion of α-KG to 2-HG. IDH1/2 mutations confer an enzymatic gain of function that dramatically increases 2-HG in AML. This provides an explanation for the heterozygous acquisition of these mutations during tumorigenesis. 2-HG is a tractable metabolic biomarker of mutant IDH1/2 enzyme activity

Experimental investigation of AC two-channel gliding arcs discharge plasma driven kerosene cracking

To improve the ignition and combustion performance of aviation kerosene, two-channel gliding arcs plasma was adopted to crack kerosene into active components, such as gaseous light hydrocarbons and H2. The influence of carrier gas flow rate on discharge characteristics and cracking effects were investigated. Experimental results indicate that, compared to single channel discharge, the power of two-channel gliding arcs discharge is greater while the arcs cover twice as much area as that of single channel discharge. The cracking rate of two-channel discharge plasma is greater than that of single channel discharge while it shows an upward trend with greater carrier gas flow rate. Among the main components of cracking gas, the molar percentage of hydrogen is the highest and exceeds 50%. Greater carrier gas flow rate would result in lower molar percentage of hydrogen. Interestingly, the ethyl group prefers to form C2H2 as the carrier gas flow rate increases in the two-channel gliding arcs discharge while the molar percentage of C2H2 and C2H4 changes inconspicuously in the single channel discharge

Time-Varying Wear Calculation Method for Fractal Rough Surfaces of Friction Pairs

For the wear problem of the real rough surface during sliding friction, based on fractal theory and Hertz contact theory, a 3-D fractal rough surface with random characteristics is constructed, and the relationship between the wear deformation depth of the rough peak and its real contact area during the wear process is derived. Furthermore, considering the peak wear and pit scratch phenomena of rough surfaces in different contact states, the time-varying wear calculation model of the worn surface and the compensation wear calculation model of the unworn surface are established, respectively, and the relationship between the instantaneous wear amount and the dynamic change in the rough surface topography is comprehensively characterized. Combined with image digitization technology, the 3-D rough surface is converted into a 2-D discrete plane with 3-D information. According to the dynamic real-time update of the graph data, the iterative calculation of the wear cycle is completed, the time-varying wear calculation method for fractal rough surfaces of friction pairs is proposed, and the dynamic change in the wear amount and surface topography of the rough surface is simulated. The simulation results are experimentally verified and the influence of friction parameters on the surface topography is analyzed. The results show that after the wear simulation, the profile height of the rough surface is reduced, and the average wear depth is 0.02 mm. Increases in rotational speeds and external loads can exacerbate surface wear, surface topography tends to be flattened, and surface carrying capacity increases. This provides theoretical guidance for the development and manufacture of friction pairs

The Characteristics of Gliding Arc Plasma and Its Activating Effect for Ramjet Combustion

In order to improve the combustion performance of a ramjet under low temperature and pressure, a gliding arc plasma actuator was designed based on a typical evaporation flameholder. The discharge characteristics, as well as the activating effect of single-channel and three-channel gliding arc plasma under different carrier gas flow rates, were studied. Results show that with the increase in the carrier gas flow rate, the average duration of the gliding arc discharge becomes shorter, while the average power increases, and the specific input energy decreases. Compared with single-channel discharge, three-channel discharge has higher discharge power and energy injection rate, which makes a bigger actuated space. Through gliding arc plasma, the kerosene is cracked and H2, CH4, C2H2, C2H4, C3H6 and other small molecule components are produced. For three-channel gliding arc discharge, the effective cracking rate and the production rate of each component are higher than those of the single-channel discharge; both of them gradually increase with the increase in the carrier gas flow rate. The experiment results indicate that three-channel gliding arc plasma can effectively widen the ignition boundary and improve the combustion efficiency of ramjet combustion. The ignition pressure boundary is expanded from 60 kPa to 50 kPa under 390 K; the combustion efficiency is increased from 76% to 82%

The Characteristics of Gliding Arc Plasma and Its Activating Effect for Ramjet Combustion

In order to improve the combustion performance of a ramjet under low temperature and pressure, a gliding arc plasma actuator was designed based on a typical evaporation flameholder. The discharge characteristics, as well as the activating effect of single-channel and three-channel gliding arc plasma under different carrier gas flow rates, were studied. Results show that with the increase in the carrier gas flow rate, the average duration of the gliding arc discharge becomes shorter, while the average power increases, and the specific input energy decreases. Compared with single-channel discharge, three-channel discharge has higher discharge power and energy injection rate, which makes a bigger actuated space. Through gliding arc plasma, the kerosene is cracked and H2, CH4, C2H2, C2H4, C3H6 and other small molecule components are produced. For three-channel gliding arc discharge, the effective cracking rate and the production rate of each component are higher than those of the single-channel discharge; both of them gradually increase with the increase in the carrier gas flow rate. The experiment results indicate that three-channel gliding arc plasma can effectively widen the ignition boundary and improve the combustion efficiency of ramjet combustion. The ignition pressure boundary is expanded from 60 kPa to 50 kPa under 390 K; the combustion efficiency is increased from 76% to 82%

Genetic analysis of a pedigree with MECP2 duplication syndrome in China

Abstract Background MECP2 duplication syndrome (MDS) is a rare X-linked genomic disorder that primarily affects males. It is characterized by delayed or absent speech development, severe motor and cognitive impairment, and recurrent respiratory infections. MDS is caused by the duplication of a chromosomal region located on chromosome Xq28, which contains the methyl CpG binding protein-2 (MECP2) gene. MECP2 functions as a transcriptional repressor or activator, regulating genes associated with nervous system development. The objective of this study is to provide a clinical description of MDS, including imaging changes observed from the fetal period to the neonatal period. Methods Conventional G-banding was employed to analyze the chromosome karyotypes of all pedigrees under investigation. Subsequently, whole exome sequencing (WES), advanced biological information analysis, and pedigree validation were conducted, which were further confirmed by copy number variation sequencing (CNV-seq). Results Chromosome karyotype analysis revealed that a male patient had a chromosome karyotype of 46,Y,dup(X)(q27.2q28). Whole-exon duplication in the MECP2 gene was revealed through WES results. CNV-seq validation confirmed the presence of Xq27.1q28 duplicates spanning 14.45 Mb, which was inherited from a mild phenotype mother. Neither the father nor the mother's younger brother carried this duplication. Conclusion In this study, we examined a male child in a family who exhibited developmental delay and recurrent respiratory tract infections as the main symptoms. We conducted thorough family investigations and genetic testing to determine the underlying causes of the disease. Our findings will aid in early diagnosis, genetic counseling for male patients in this family, as well as providing prenatal diagnosis and reproductive guidance for female carriers

A Novel FOXL2 Mutation Implying Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome Type I

Background/Aims: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal dominant disease caused by FOXL2 gene mutations, and it is clinically characterized by an eyelid malformation associated (type I) or not (type II) with premature ovarian failure (POF). Functional study of novel mutations is especially critical for female patients, as it may allow the prediction of infertility and early planning of an appropriate therapy. Methods: A clinical and molecular genetic investigation was performed in all members of a Chinese family with BPES. Genomic DNA was extracted, and the FOXL2 coding region was sequenced. Subcellular localization was performed by confocal microscopy. Transactivation studies were performed by real-time PCR, dual luciferase reporter assays and electrophoretic mobility shift assays. Results: A novel deletion mutation (C.634_641 del, CCCATGC) between the forkhead domain and the polyalanine domain was found, resulting in a frameshift mutation and a truncated protein. Functional studies showed a strong cytoplasmic mislocalization and abnormal transactivation activity, implying a type I kind mutation with a large chance of infertility. Conclusion: This study identifies that this mutation indicates the probability of developing into POF and shows the importance and necessity of early recognition of BPES type through mutation testing for female patients. Prompt personalized therapy and follow-up is of great clinical significance for female patients carrying this kind of mutation