A group of low-cost Fe40Ni(50-x)Cr10Mox high-entropy alloys (HEAs) without the Co element were proposed. The microstructure and properties were investigated. With the increase of Mo content, the ...microstructure changes from FCC single-phase to two-phase divorced eutectic, divorced eutectic + hypoeutectic, hypoeutectic, eutectic and hypereutectic, in which the two-phase is composed of FCC phase + σ phase. The yield strength of alloy increases with the increase of Mo content. Its strengthening mechanism transforms from solution strengthening to second phase strengthening and grain boundary strengthening. Mo-20 and Mo-22.5 have comprehensive mechanical properties, and their yield strength, fracture strength and plastic strain are 1103.1 MPa and 1127.9 MPa, 1924.5 MPa and 1881.7 MPa, 30.4% and 28.7% respectively. In addition, the revised equivalent Cr content (ECC) is proposed in the FeNiCrMo HEAs, ECC = at.%Cr+8/3 × at.%Mo. The eutectic composition can be precisely designed through the revised ECC and atomic content ratio (RI/F) of the intermetallic forming elements to the FCC forming elements in FeNiCrMo HEAs system. When 20 at.%≤Fe and Ni ≤ 40 at.%, and RI/F = ECC/x × at.%Fe + y × at.%Ni = 1.05 ± 0.3, FexNiyCrmMon is the eutectic high-entropy alloy.
L-carnitine (LC) is generally believed to transport long-chain acyl groups from fatty acids into the mitochondrial matrix for ATP generation via the citric acid cycle. Based on Warburg's theory that ...most cancer cells mainly depend on glycolysis for ATP generation, we hypothesize that, LC treatment would lead to disturbance of cellular metabolism and cytotoxicity in cancer cells. In this study, Human hepatoma HepG2, SMMC-7721 cell lines, primary cultured thymocytes and mice bearing HepG2 tumor were used. ATP content was detected by HPLC assay. Cell cycle, cell death and cell viability were assayed by flow cytometry and MTS respectively. Gene, mRNA expression and protein level were detected by gene microarray, Real-time PCR and Western blot respectively. HDAC activities and histone acetylation were detected both in test tube and in cultured cells. A molecular docking study was carried out with CDOCKER protocol of Discovery Studio 2.0 to predict the molecular interaction between L-carnitine and HDAC. Here we found that (1) LC treatment selectively inhibited cancer cell growth in vivo and in vitro; (2) LC treatment selectively induces the expression of p21(cip1) gene, mRNA and protein in cancer cells but not p27(kip1); (4) LC increases histone acetylation and induces accumulation of acetylated histones both in normal thymocytes and cancer cells; (5) LC directly inhibits HDAC I/II activities via binding to the active sites of HDAC and induces histone acetylation and lysine-acetylation accumulation in vitro; (6) LC treatment induces accumulation of acetylated histones in chromatin associated with the p21(cip1) gene but not p27(kip1) detected by ChIP assay. These data support that LC, besides transporting acyl group, works as an endogenous HDAC inhibitor in the cell, which would be of physiological and pathological importance.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Three‐dimensional unmanned aerial vehicle (UAV) oblique photogrammetric data were used to infer mountainous gravel braided river lithofacies, lithofacies associations and architectural elements. ...Hierarchical architecture and lithofacies associations with detailed lithofacies characterizations were comprehensively described to document the architectural model, architectural element scale and gravel particle scale. (1) Nine lithofacies (i.e., Gmm, Gcm, Gcc, Gci, Gcl, Ss, Sm, Fsm and Fl) were identified and classified as gravel, sand and fine matrix deposits. These are typical depositional features of a mountainous dryland gravel‐braided river. (2) Three architectural elements were identified, including channel (CH), gravel bar (GB) and overbank (OB). CH can be further divided into flow channel and abandoned channel, while GB consists of Central Gravel bar (CGB) and Margin Gravel bar (MGB). (3) The gravel bar is the key architectural element of the gravel braided river, with its geological attributes. The dimensions of GBs and their particles are various, but exhibit good relationships with each other. The grain size of GB decreases downstream, but the dimensions of GB do not. The bank erosion affects the GB dimensions, whereas channel incision and water flow velocity influence the grain size of GB. The conclusions can be applied to the dryland gravel braided river studies in tectonically active areas.
Real-time simulation of modular multilevel converter (MMC)-based HVDC is one of the most important and difficult technologies in the area of utility-scale power electronics research. This paper ...describes an efficient modeling approach for real-time simulation of MMC-HVDC. Taking advantages of the full parallel architecture of the field-programmable gate array (FPGA), more than 1500 submodules are able to be simulated in a single FPGA. The design details of the physical MMC control system are also presented. The presented MMC-HVDC real-time simulator and physical control system are successfully performed in the Nan-ao Island MMC-HVDC project, which is the world's first three-terminal MMC-HVDC system for research on operation and fault characteristics. The results validate the accuracy of proposed approach and real-time MMC simulator.
Recently, the definition of extensively drug-resistant TB (XDR-TB) has been revised. In this study, we conducted a descriptive and retrospective study to determine the prevalence of XDR-TB in a ...Chinese multidrug-resistant TB (MDR-TB) cohort.
Broth microdilution method was performed to determine in vitro susceptibilities of Mycobacterium tuberculosis (MTB) isolates to (FQs), bedaquiline (BDQ) and linezolid (LZD). The putative drug target genes conferring drug resistance were screened by DNA sequencing.
A total of 425 MDR-TB isolates were included from 13 pilots in China. LZD and BDQ resistance were noted in 30 (7.1%) and 10 (2.4%) isolates. On the basis of latest definitions, 114 (26.8%) were MDR-TB, 282 (66.4%) were pre-XDR-TB, and 29 (6.8%) were XDR-TB. Among 311 FQ-resistant isolates, 265 harbored genetic mutations within QRDRs. The most common mutations were observed at codon 94 of gyrA, accounting for 47.2% of FQ-resistant MTB isolates. Only mutations within the Rv0678 gene were found to confer BDQ resistance in our cohort, conferring 40.0% of BDQ resistance. For LZD resistance, 53.3% of LZD-resistant isolates carried genetic mutations in rplC or 23S rRNA. The most frequent mutation was Cys154Arg in the rplC gene. In addition, we recorded two MDR-TB patients with resistance to both BDQ and LZD, of which one patient experienced continuous positive culture of MTB despite inclusion of efficacious moxifloxacin.
Our results demonstrate that the low prevalence of XDR-TB holds great promise for MDR-TB treatment with WHO-endorsed regimens containing BDQ-LZD combination, whereas the high prevalence of FQ-resistance in MDR-TB patients warrants national attention.
In this study, we utilized whole genome sequencing (WGS) of clinical extremely drug-resistant tuberculosis (EDR-TB) strains collected during 2014–2020 in Beijing to detect clustered strains.
A ...retrospective cohort study was conducted by inclusion of EDR-TB patients with positive cultures in Beijing between 2014 and 2020.
A total of 95 EDR-TB patients were included in our analysis. Up on the WGS based genotyping, 94 (94/95, 98.9%) out of 95 were identified as lineage 2 (East Asia). The pairwise genomic distance analysis identified 7 clusters, ranging in size from 2 to 5 isolates. The clustering rate of EDR-TB was 21.1%; while no patients had significantly higher odds of clustering. All isolates harbor rpoB RRDR mutations that confer RIF resistance and katG or inhA promoter mutations that confer INH resistance. Of 95 EDR-TB isolates, a total of 15 mutation types were recorded in the transcriptional regulator mmpR5. In vitro susceptibility testing results revealed that 14 (14/15, 93.3%) out of 15 mutation types were resistant to CFZ; whereas only 3 (3/15, 20.0%) showed resistance to BDQ. Interestingly, 12 isolates harbored mutations within rrl locus, whereas only mutations at positions 2294 and 2296 conferred CLA resistance. Favorable outcomes of EDR-TB patients were positively associated with more effective drugs in the regimes.
WGS data demonstrate limited transmission of EDR-TB in this metropolis city. WGS-based drug susceptibility predictions will bring benefits to EDR-TB patients to formulate optimal therapeutic regimens.
Over the years, shale oil has been at the leading edge of oil exploration and also become the hotspot of reserve increases for various oil fields. The Permian Lucaogou Formation in the Jimsar Sag has ...been less extensively researched in terms of, among others, lithologic interpretation of fine-grained mixosedimentite, identification and classification of sedimentary microfacies, and sweet spot evaluation. The present study identifies the classification of sedimentary microfacies, characteristic distribution of sedimentary reservoir, and spatial configuration distribution of facies-controlled sweet spot body based on core logging, cutting logging, and data while drilling, combined with logging information, experimental analysis data, and production data with respect to formation test and production test and through the lithology identification based on element logging. This study indicated the following: 1) Microfacies of the reservoir body include a shallow lacustrine sand bar, mixing beach, and dolomitic flat. Different microfacies are adapted to different lithologies or lithological associations. 2) The lower sweet spots P
2
l
1
2−3
, P
2
l
1
2−2,
and P
2
l
1
2−1
evolved into the dolomitic flat from mixing beach from NE to W. Also, the dolomitic flat is mostly developed in the west of the work area, and the mixing beach is better developed in the east. The shallow lacustrine sand bar is highly developed in the middle location, and the mixing beach and shallow lacustrine sand bar are highly developed on the northern and southern sides. 3) Sedimentary microfacies have evident controls over sweet spots. The upper sweet spots P
2
l
2
2−3
and P
2
l
2
2−2
are dominated by Class I sweet spots followed by Class II and IV sweet spots, which are major sweet spot reservoirs. The upper sweet spot P
2
l
2
2−1
is mainly suffused with Class IV sweet spots, and the Class I reservoir is feldspathic litharenite (shallow lacustrine sand bar microfacies accordingly).
Gambogic acid (GA) is a natural compound derived from Chinese herbs that has been approved by the Chinese Food and Drug Administration for clinical trials in cancer patients; however, its molecular ...targets have not been thoroughly studied. Here, we report that GA inhibits tumor proteasome activity, with potency comparable to bortezomib but much less toxicity. First, GA acts as a prodrug and only gains proteasome-inhibitory function after being metabolized by intracellular CYP2E1. Second, GA-induced proteasome inhibition is a prerequisite for its cytotoxicity and anticancer effect without off-targets. Finally, because expression of the CYP2E1 gene is very high in tumor tissues but low in many normal tissues, GA could therefore produce tissue-specific proteasome inhibition and tumor-specific toxicity, with clinical significance for designing novel strategies for cancer treatment.
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► GA is metabolized by CYP2E1 to produce a metabolite proteasome inhibitor ► Proteasome inhibition is required for GA’s cytotoxicity and anticancer activity ► GA is a more tissue-specific proteasome inhibitor than bortezomib/velcade ► GA is nontoxic to peripheral white blood cells compared to bortezomib
Although the proteasome inhibitor bortezomib has shown significant benefit for multiple myeloma treatment in clinical trials, its effectiveness and administration have been limited by toxic side effects and the development of drug resistance. Dou, Liu, and colleagues demonstrate that gambogic acid is able to selectively inhibit tumor proteasome activity, with potency comparable to bortezomib but less toxicity. Compared with bortezomib, gambogic acid could produce tissue-specific proteasome inhibition and tumor-specific toxicity because of the differential distribution of CYP2E1 in normal and tumor tissues.
The measurements of iron, beryllium and carbon sphere neutron leakage spectra using BC501A detector by DT neutron source are presented. The experiments were carried out in Institute of Nuclear ...Physics and Chemistry (INPC), China. Neutron leakage spectra in a wide energy range at angles of 0° and 30° from the direction of incident deuteron beam were obtained. The results show the leakage neutron flux decreases notably with the spherical shell increasing when neutron energy >10MeV. When neutron energy <6MeV the leakage neutron distribution tends to lower energy side with the shell increase. The total uncertainty evaluation of the neutron spectra is also provided: in the high-energy parts the uncertainty is about 5–7%, while in the low-energy parts the uncertainty is about 7–9%. In order to compare the experiment results a Monte-carlo calculation was made using the MCNP5 Code with the ENDF/B-VII.1 nuclear data files.
•Neutron leakage spectra of Fe, Be and C from spherical benchmark in 0° and 30° were obtained.•Leakage neutrons decrease notably with iron thickness increasing above 10MeV.•The lower threshold of neutron energy could be extended to 0.4MeV.•The experiment and calculation of leakage neutron spectra agree well.•Total uncertainty of neutron spectra was evaluated.
Extracellular adenosine (ADE) interacts with cells by two pathways: by activating cell surface receptors at nanomolar/micromolar concentrations; and by interfering with the homeostasis of the ...intracellular nucleotide pool at millimolar concentrations. Ade shows both cytotoxic and cytoprotective effects; however, the underlying mechanisms remain unclear. In the present study, the effects of adenosine-mediated ATP on cell viability were investigated. Adenosine treatment was found to be cytoprotective in the low intracellular ATP state, but cytotoxic under the normal ATP state. Adenosine-mediated cytotoxicity and cytoprotection rely on adenosine-derived ATP formation, but not via the adenosine receptor pathway. Ade enhanced proteasome inhibition-induced cell death mediated by ATP generation. These data provide a new pathway by which adenosine exerts dual biological effects on cell viability, suggesting an important role for adenosine as an ATP precursor besides the adenosine receptor pathway.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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