Effect of Initial Microstructure on the Hot Deformation Behavior and Microstructure Evolution of Aluminum Alloy AA2060

Chaoyang Li,Guangjie Huang,Lingfei Cao,Ruoxi Zhang,Yu Cao,Bin Liao,Lin Lin 대한금속·재료학회 2022 METALS AND MATERIALS International Vol.28 No.7

The microstructure evolution and hot deformation behavior of a Li-containing aluminum alloy AA2060 with different initialmicrostructure (homogenized vs. pre-rolled) were studied by isothermal hot deformation. The tests were performed within awide range of deformation temperatures of 370–490 ℃ and strain rates of 0.01–10 s−1. Results show that the stress drop ratioof the pre-rolled specimen is higher than that of the homogenized one under the same deformation condition. Microstructurewere analyzed on the thermal processing maps in unstable and optimum processing domain, and a higher dynamic recrystallizationfraction can be observed in the pre-rolled specimen that has more substructures and smaller grains. Four typesof the dynamic recrystallization were observed and the mechanism for deformation softening was discussed in this work.

In vitro selection and identifcation of a cold‑tolerant variant in pineapple (Ananas comosus)

Yafen Zhang,Zhiqiang Xu,Tao Xie,Wei Zhang,Yehua He,Chaoyang Liu 한국원예학회 2022 Horticulture, Environment, and Biotechnology Vol.63 No.2

Cold stress is an important factor limiting the growth and distribution of pineapple. Breeding cold-resistant germplasm is an efective way to cope with this problem. In vitro selection for the somaclonal variation using diferent selection agents has been used for crop improvement in stress tolerance. In this study, the pineapple cold-tolerant variant was developed through in vitro cold selection of somaclonal variations. Low temperature was used as the selected agent, and the extreme lethal condition for the in vitro pineapple cultures was determined to be 0 °C for 72 h. The morphology changes of the in vitro cultures during the cold selection were observed and analyzed. The cold-tolerant variant line was fnally obtained through three consecutive selections with cold shock treatments, based on the established high-efciency culture system for pineapple embryogenic calli. The genetic variations at the molecular level in the cold-tolerant variant were verifed by ISSR analysis. The signifcantly improved cold tolerance in our selected variant was mainly refected by the higher survival rate, increased proline content, and elevated SOD activity under cold stress compared to these qualities in the control plants. This study demonstrated the feasibility of in vitro selection for cold tolerance in pineapple. The cold-tolerant variant could be valuable for future pineapple breeding programs and for cold tolerance research.

TGF-β promotes pericyte-myofibroblast transition in subretinal fibrosis through the Smad2/3 and Akt/mTOR pathways

Zhao Zhenzhen,Zhang Yumeng,Zhang Chaoyang,Zhang Jingting,Luo Xueting,Qiu Qinghua,Luo Dawei,Zhang Jingfa 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Subretinal fibrosis remains a major obstacle to the management of neovascular age-related macular degeneration. Choroidal pericytes were found to be a significant source of subretinal fibrosis, but the underlying mechanisms of pericyte-myofibroblast transition (PMT) remain largely unknown. The goal of this study was to explore the role and potential mechanisms by which PMT contributes to subretinal fibrosis. Choroidal neovascularization (CNV) was induced by laser photocoagulation in transgenic mice with the collagen1α1-green fluorescent protein (Col1α1-GFP) reporter, and recombinant adeno-associated virus 2 (rAAV2)-mediated TGF-β2 (rAAV2-TGF-β2) was administered intravitreally to further induce PMT. Primary mouse choroidal GFP-positive pericytes were treated with TGF-β2 in combination with siRNAs targeting Smad2/3, the Akt inhibitor MK2206 or the mTOR inhibitor rapamycin to examine cell proliferation, migration, and differentiation into myofibroblasts. The involvement of the Akt/mTOR pathway in PMT in subretinal fibrosis was further investigated in vivo. Intraocular TGF-β2 overexpression induced GFP-positive pericyte infiltration and PMT in subretinal fibrosis, which was mimicked in vitro. Knockdown of Smad2/3 or inhibition of Akt/mTOR decreased cell proliferation, PMT and migration in primary mouse pericytes. Combined inhibition of Smad2/3 and mTOR showed synergistic effects on attenuating α-smooth muscle actin (α-SMA) expression and cell proliferation. In mice with laser-induced CNV, the administration of the Akt/mTOR inhibitors suppressed pericyte proliferation and alleviated the severity of subretinal fibrosis. Our results showed that PMT plays a pivotal role in subretinal fibrosis, which was induced by TGF-β2 through the Smad2/3 and Akt/mTOR pathways. Thus, inhibiting PMT may be a novel strategy for the treatment of subretinal fibrosis.

Prediction of Surface Settlement with Ultra-shallow-burial and Large Rectangular Cross-section Urban Underpass

Chaoyang Heng,Song Sun,Zhi Zhou,Jiantao Zhang 대한토목학회 2019 KSCE JOURNAL OF CIVIL ENGINEERING Vol.23 No.11

Based on the actual measured surface settlement of two super-shallow buried large rectangular-section urban underpass, a settlement fitting function is established. The superposition curve used the reduction of settlement trough. By comparing the results of fitting analysis with Peck formula result, settlement characteristics and simple prediction method for super-shallow and large rectangular section urban underpass are proposed, including: 1) The settlement trough is a superposition of three normal distribution curves, with the maximum surface settlement appeared above the central line of each single passage; 2) The depth and width of the middle passage settlement trough should be uniformly reduced. The reduction coefficient is calculated based on the ratio of the middle passage width to the side passage; 3) The loss rate of the side passage is 0.7% − 1.0%, while it is 0.4% − 0.6% for the middle passage, 4) If the underpass is excavated in staggered sequence, the peck formula can be used to calculate the surface settlement. The surface settlement of a single passage is calculated firstly, and then the surface settlement of three passages is superimposed to obtain the final settlement.

Calculation Method of Underground Passage Excavation on Interactive Effects among Pipe-Roof, Steel Bracing and Foundation Soil

Chaoyang Heng,Song Sun,Jiantao Zhang,Zhi Zhou 대한토목학회 2022 KSCE JOURNAL OF CIVIL ENGINEERING Vol.26 No.1

The ultra-shallow buried excavation technology, utilizing pipe-roof steel arches as main supporting structure, has broad application prospects. Current mainstream pipe-roof design schemes often adopt simple beam theory or engineering analogy methods, which do not take into account the cumulative deformation and have high engineering disaster risk. Based on the beam Winkler model of elastic foundation, this paper studies the method on interactive effects among pipe-roof, steel bracing and foundation soil. The calculation model of the ultra-shallow buried pipe-roof and steel bracing is established with theoretical derivation. And a new supporting design method of ultra-shallow buried excavation under interactive effects is proposed. Firstly, an optimal method for determining the elasticity coefficient of steel arch and foundation soil is put forward on interactive effects among pipe-roof, steel bracing and foundation. Secondly, considering the enhancement effect of concrete wall, a procedure of determining the elasticity coefficient of fulcrum is described. That is, the first steel arch, which is adjacent to underground passage tunnel face, returns to the 1.5H (H is the height of the hole) range as an enhanced transition section, and the elasticity coefficient of fulcrum varies linearly with its position. Furthermore, the key issue is the deformation of the inlet section increases to a stable level in a certain range, while the ground settlement does not exceed the threshold. The selection of pipe-roof is controlled by calculated deformation. If the deformation meets the requirements, the internal force will be far enough to meet the requirements. Only two sections need to be considered when calculating the ultra-shallow buried underground passage, the entrances 2.0H and the central across section. Finally, the accuracy of the interactive effects calculated method is validated by using the measured data of a practical example.

An experimental investigation on the normal force behavior of magnetorheological suspensions

Guo, Chaoyang,Gong, Xinglong,Xuan, Shouhu,Zhang, Yanli,Jiang, Wanquan 한국유변학회 2012 Korea-Australia rheology journal Vol.24 No.3

In this work the normal force behavior of magnetorheological suspensions are systematically investigated. Four magnetorheological suspensions with different volume fractions (10%, 20%, 30%, and 40%) are prepared and both the static and dynamic normal forces of the samples are measured by using a commercial plate-plate magneto-rheometer under constant and sweeping magnetic field. A positive normal force will be generated when the applied magnetic field exceeds a critical value. The normal force firstly increases with the increasing of magnetic field strength and then reaches a saturation value. A magnetization model is utilized to represent this mechanism. The oscillatory dynamic normal forces with time are studied and their changes with shear rates are dependent on the volume fraction. Comparisons between static and dynamic normal forces show that the differences between them are dependent on the volume fraction and magnetic filed. The temperature effect on the normal force is studied and under high magnetic field the normal force would increase slightly with the increasing of temperature.

BRD4 Inhibition Is Synthetic Lethal with PARP Inhibitors through the Induction of Homologous Recombination Deficiency

Sun, Chaoyang,Yin, Jun,Fang, Yong,Chen, Jian,Jeong, Kang Jin,Chen, Xiaohua,Vellano, Christopher P.,Ju, Zhenlin,Zhao, Wei,Zhang, Dong,Lu, Yiling,Meric-Bernstam, Funda,Yap, Timothy A.,Hattersley, Mauree Cell Press 2018 CANCER CELL Vol. No.

<P><B>Summary</B></P> <P>Poly(ADP-ribose) polymerase inhibitors (PARPi) are selectively active in cells with homologous recombination (HR) deficiency (HRD) caused by mutations in <I>BRCA1</I>, <I>BRCA2</I>, and other pathway members. We sought small molecules that induce HRD in HR-competent cells to induce synthetic lethality with PARPi and extend the utility of PARPi. We demonstrated that inhibition of bromodomain containing 4 (BRD4) induced HRD and sensitized cells across multiple tumor lineages to PARPi regardless of <I>BRCA1/2</I>, <I>TP53</I>, <I>RAS</I>, or <I>BRAF</I> mutation status through depletion of the DNA double-stand break resection protein CtIP (C-terminal binding protein interacting protein). Importantly, BRD4 inhibitor (BRD4i) treatment reversed multiple mechanisms of resistance to PARPi. Furthermore, PARPi and BRD4i are synergistic in multiple <I>in vivo</I> models.</P> <P><B>Highlights</B></P> <P> <UL> <LI> BRD4 inhibition decreases homologous recombination competency by decreasing CtIP </LI> <LI> PARP and BRD4 inhibitors demonstrate synergy in multiple cancer lineages </LI> <LI> CtIP rescues DNA end resection and HR defect caused by BRD4 inhibition </LI> <LI> BRD4 inhibition resensitizes cells with acquired PARPi resistance to PARPi </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>

Rational combination therapy with PARP and MEK inhibitors capitalizes on therapeutic liabilities in <i>RAS</i> mutant cancers

Sun, Chaoyang,Fang, Yong,Yin, Jun,Chen, Jian,Ju, Zhenlin,Zhang, Dong,Chen, Xiaohua,Vellano, Christopher P.,Jeong, Kang Jin,Ng, Patrick Kwok-Shing,Eterovic, Agda Karina B.,Bhola, Neil H.,Lu, Yiling,Wes American Association for the Advancement of Scienc 2017 Science translational medicine Vol.9 No.392

<P>Mutant <I>RAS</I> has remained recalcitrant to targeted therapy efforts. We demonstrate that combined treatment with poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors and mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitors evokes unanticipated, synergistic cytotoxic effects in vitro and in vivo in multiple <I>RAS</I> mutant tumor models across tumor lineages where <I>RAS</I> mutations are prevalent. The effects of PARP and MEK inhibitor combinations are independent of <I>BRCA1/2</I> and <I>p53</I> mutation status, suggesting that the synergistic activity is likely to be generalizable. Synergistic activity of PARP and MEK inhibitor combinations in <I>RAS</I> mutant tumors is associated with (i) induction of BIM-mediated apoptosis, (ii) decrease in expression of components of the homologous recombination DNA repair pathway, (iii) decrease in homologous recombination DNA damage repair capacity, (iv) decrease in DNA damage checkpoint activity, (v) increase in PARP inhibitor–induced DNA damage, (vi) decrease in vascularity that could increase PARP inhibitor efficacy by inducing hypoxia, and (vii) elevated PARP1 protein, which increases trapping activity of PARP inhibitors. Mechanistically, enforced expression of FOXO3a, which is a target of the RAS/MAPK pathway, was sufficient to recapitulate the functional consequences of MEK inhibitors including synergy with PARP inhibitors. Thus, the ability of mutant <I>RAS</I> to suppress FOXO3a and its reversal by MEK inhibitors accounts, at least in part, for the synergy of PARP and MEK inhibitors in <I>RAS</I> mutant tumors. The rational combination of PARP and MEK inhibitors warrants clinical investigation in patients with <I>RAS</I> mutant tumors where there are few effective therapeutic options.</P>

Cloning and expression of lin-28 homolog B gene in the onset of puberty in Duolang sheep

Feng Xing,Chaoyang Zhang,Zhengquan Kong 아세아·태평양축산학회 2019 Animal Bioscience Vol.32 No.1

Objective: Recent studies have demonstrated that lin-28 homolog B (LIN28B)/miRNA let-7 (let-7) plays a role in the regulation of pubertal onset in mammals. However, the role of LIN28B/let-7 in the onset of ovine puberty remains unknown. We cloned the Duolang sheep Lin28B cDNA sequence, detected the expression change of LIN28B, let-7a and let-7g in hypothalamus, pituitary and ovary tissues at three different pubertal stages. Methods: The reverse transcriptase polymerase chain reaction (RT-PCR) was used to clone the cDNA sequence of LIN28B gene from Duolang sheep and the bioinformatics methods were applied to analyze the amino acid sequence of LIN28B protein. The mRNA expression levels of the LIN28B gene at different pubertal stages were examined by real time RT-PCR. Results: LIN28B cDNA of Duolang sheep was cloned, and two transcripts were obtained. The amino acid sequence of transcript 1 shares 99.60%, 98.78%, and 94.80% identity with those of goat, wild yak and pig, respectively. Strong LIN28B mRNA expression was detected in the hypothalamus, pituitary, ovary, oviduct and uterus, while moderate expression was found in the liver, kidney, spleen and heart, weak expression was observed in the heart. No expression was found in the lungs. Quantitative real-time PCR (QPCR) and western-blot analysis revealed that the LIN28B was highly expressed in the hypothalamus and ovary at prepuberty stages, and this expression significantly decreased from the prepuberty to puberty stages (p<0.05). Markedly increased levels of mRNA expression were detected in the pituitary from prepuberty to puberty (p<0.05) and then significantly decreased from puberty to postpuberty (p<0.05). The expression levels of let-7a and let-7g showed no significant changes among different pubertal stages (p>0.05). Conclusion: These results provided a foundation for determining the functions of LIN28B/let-7 and their role in the onset of sheep puberty.

Coexistence of nonvolatile unipolar and volatile threshold resistive switching in the Pt/LaMnO3/Pt heterostructures

Yin Yanfeng,Kang Chaoyang,Jia Caihong,Zhang Weifeng 한국물리학회 2021 Current Applied Physics Vol.31 No.-

Coexistence of nonvolatile unipolar and volatile threshold resistive switching is observed in the Pt/LaMnO3 (LMO)/Pt heterostructures. The nonvolatile unipolar memory is achieved by applying a negative bias, while the volatile threshold resistive switching is obtained under a positive bias. Additionally, the pristine low resistance state (LRS) could be switched to high resistance state (HRS) by the positive voltage sweeping, which is attributed to the conduction mechanism of Schottky emission. Subsequently, the insulator-to-metal transition in the LMO film due to formation of ferromagnetic metallic phase domain contributes to the volatile threshold resistive switching. However, the nonvolatile unipolar switching under the negative bias is ascribed to the formation/ rupture of oxygen-vacancy conducting filaments. The simultaneously controllable transition between nonvolatile and volatile resistance switching by the polarity of the applied voltage exhibits great significance in the applications of in-memory computing technology.