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"Yang, P"
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\"With the aid of Kelvin, a dinosaur from the past, Amber must save her father--and the rest of us--from the very same danger that caused the dinosaurs to flee--and from the dinosaurs themselves as they return to Earth\"-- Back cover.
Book
Lattice distortion enabling enhanced strength and plasticity in high entropy intermetallic alloy
Intermetallic alloys have traditionally been characterized by their inherent brittleness due to their lack of sufficient slip systems and absence of strain hardening. However, here we developed a single-phase B2 high-entropy intermetallic alloy that is both strong and plastic. Unlike conventional intermetallics, this high-entropy alloy features a highly distorted crystalline lattice with complex chemical order, leading to multiple slip systems and high flow stress. In addition, the alloy exhibits a dynamic hardening mechanism triggered by dislocation gliding that preserves its strength across a wide range of temperatures. As a result, this high-entropy intermetallic circumvents precipitous thermal softening, with extensive plastic flows even at high homologous temperatures, outperforming a variety of both body-centered cubic and B2 alloys. These findings reveal a promising direction for the development of intermetallic alloys with broad engineering applications.
Intermetallics are traditionally characterised by their inherent brittleness due to a lack of sufficient slip systems and the absence of strain hardening. Here authors show that a single-phase distorted high entropy B2 intermetallic alloy displays notable strength and plasticity at room temperature, along with stable plastic flow at high homologous temperatures.
Journal Article
CYP2C9 polymorphism analysis in Han Chinese populations: building the largest allele frequency database
Genetic polymorphisms of
CYP2C9
significantly influence the pharmacokinetics and pharmacodynamics of some drugs, which might result in adverse drug effects and therapeutic failure. Several studies have been performed on
CYP2C9
genetic polymorphisms in Han Chinese populations. However, these studies only focused on two commonly investigated alleles,
*2
and
*3
, in relatively small sample sizes. To scale up the gene-scanning region and determine relatively precise data on the genetic distribution pattern in Chinese populations, unrelated healthy Han Chinese volunteers from Zhejiang Province (
n
=1127) and Hebei (
n
=1000) Province were recruited as subjects for the direct sequencing of all exons of
CYP2C9
. As a result, 14 previously reported alleles were detected in this work, and 8 of these alleles (
*14
,
*16
,
*19
,
*23
,
*27
,
*29
,
*33
and
*34
) were described for the first time in Chinese populations. In addition, 37 novel mutations were also detected, of which 22 variants were non-synonymous, and 21 new alleles,
*36-*56
, were designated by the Human CYP Allele Nomenclature Committee.
In vitro
functional analysis of these 22 novel CYP2C9 variants revealed that 17 mutations had a significant influence on the protein’s catalytic activity. Our study provides the most accurate data on
CYP2C9
polymorphisms in Han Chinese populations and detects the largest number of novel allelic variants existing to date. These new alleles will greatly enrich the current knowledge of naturally occurring
CYP2C9
variants in Chinese populations.
Journal Article
Potential ecological risk assessment and prediction of soil heavy-metal pollution around coal gangue dump
The aim of the present study is to evaluate the potential ecological risk and trend of soil heavy-metal pollution around a coal gangue dump in Jilin Province (Northeast China). The concentrations of Cd, Pb, Cu, Cr and Zn were monitored by inductively coupled plasma mass spectrometry (ICP-MS). The potential ecological risk index method developed by Hakanson (1980) was employed to assess the potential risk of heavy-metal pollution. The potential ecological risk in the order of ER(Cd) > ER(Pb) > ER(Cu) > ER(Cr) > ER(Zn) have been obtained, which showed that Cd was the most important factor leading to risk. Based on the Cd pollution history, the cumulative acceleration and cumulative rate of Cd were estimated, then the fixed number of years exceeding the standard prediction model was established, which was used to predict the pollution trend of Cd under the accelerated accumulation mode and the uniform mode. Pearson correlation analysis and correspondence analysis are employed to identify the sources of heavy metals and the relationship between sampling points and variables. These findings provided some useful insights for making appropriate management strategies to prevent or decrease heavy-metal pollution around a coal gangue dump in the Yangcaogou coal mine and other similar areas elsewhere.
Journal Article
Low-order moments of the velocity gradient in homogeneous compressible turbulence
We derive from first principles analytic relations for the second- and third-order moments of $\\boldsymbol{\\mathsf{m}}$, the spatial gradient of fluid velocity $\\boldsymbol{u}$, $\\boldsymbol{\\mathsf{m}} = \\nabla \\boldsymbol{u}$, in compressible turbulence, which generalize known relations in incompressible flows. These relations, although derived for homogeneous flows, hold approximately for a mixing layer. We also discuss how to apply these relations to determine all the second- and third-order moments of the velocity gradient experimentally for isotropic compressible turbulence.
Journal Article
Cytosolic PKM2 stabilizes mutant EGFR protein expression through regulating HSP90–EGFR association
Secondary mutation of epidermal growth factor receptor (EGFR) resulting in drug resistance is one of the most critical issues in lung cancer therapy. Several drugs are being developed to overcome EGFR tyrosine kinase inhibitor (TKI) resistance. Here, we report that pyruvate kinase M2 (PKM2) stabilized mutant EGFR protein by direct interaction and sustained cell survival signaling in lung cancer cells. PKM2 silencing resulted in markedly reduced mutant EGFR expression in TKI-sensitive or -resistant human lung cancer cells, and in inhibition of tumor growth in their xenografts, concomitant with downregulation of EGFR-related signaling. Mechanistically, PKM2 directly interacted with mutant EGFR and heat-shock protein 90 (HSP90), and thus stabilized EGFR by maintaining its binding with HSP90 and co-chaperones. Stabilization of EGFR relied on dimeric PKM2, and the protein half-life of mutant EGFR decreased when PKM2 was forced into its tetramer form. Clinical levels of PKM2 positively correlated with mutant EGFR expression and with patient outcome. These results reveal a previously undescribed non-glycolysis function of PKM2 in the cytoplasm, which contribute to EGFR-dependent tumorigenesis and provide a novel strategy to overcome drug resistance to EGFR TKIs.
Journal Article
GSK3β controls epithelial–mesenchymal transition and tumor metastasis by CHIP-mediated degradation of Slug
Glycogen synthase kinase 3 beta (GSK3β) is highly inactivated in epithelial cancers and is known to inhibit tumor migration and invasion. The zinc-finger-containing transcriptional repressor, Slug, represses E-cadherin transcription and enhances epithelial–mesenchymal transition (EMT). In this study, we find that the GSK3β-pSer9 level is associated with the expression of Slug in non-small cell lung cancer. GSK3β-mediated phosphorylation of Slug facilitates Slug protein turnover. Proteomic analysis reveals that the carboxyl terminus of Hsc70-interacting protein (CHIP) interacts with wild-type Slug (wtSlug). Knockdown of CHIP stabilizes the wtSlug protein and reduces Slug ubiquitylation and degradation. In contrast, nonphosphorylatable Slug-4SA is not degraded by CHIP. The accumulation of nondegradable Slug may further lead to the repression of E-cadherin expression and promote cancer cell migration, invasion and metastasis. Our findings provide evidence of a
de novo
GSK3β-CHIP-Slug pathway that may be involved in the progression of metastasis in lung cancer.
Journal Article
Quantum-limit Chern topological magnetism in TbMn6Sn6
The quantum-level interplay between geometry, topology and correlation is at the forefront of fundamental physics
1
–
15
. Kagome magnets are predicted to support intrinsic Chern quantum phases owing to their unusual lattice geometry and breaking of time-reversal symmetry
14
,
15
. However, quantum materials hosting ideal spin–orbit-coupled kagome lattices with strong out-of-plane magnetization are lacking
16
–
21
. Here, using scanning tunnelling microscopy, we identify a new topological kagome magnet, TbMn
6
Sn
6
, that is close to satisfying these criteria. We visualize its effectively defect-free, purely manganese-based ferromagnetic kagome lattice with atomic resolution. Remarkably, its electronic state shows distinct Landau quantization on application of a magnetic field, and the quantized Landau fan structure features spin-polarized Dirac dispersion with a large Chern gap. We further demonstrate the bulk–boundary correspondence between the Chern gap and the topological edge state, as well as the Berry curvature field correspondence of Chern gapped Dirac fermions. Our results point to the realization of a quantum-limit Chern phase in TbMn
6
Sn
6
, and may enable the observation of topological quantum phenomena in the RMn
6
Sn
6
(where R is a rare earth element) family with a variety of magnetic structures. Our visualization of the magnetic bulk–boundary–Berry correspondence covering real space and momentum space demonstrates a proof-of-principle method for revealing topological magnets.
Scanning tunnelling microscopy is used to reveal a new topological kagome magnet with an intrinsic Chern quantum phase, which shows a distinct Landau fan structure with a large Chern gap.
Journal Article
Structure and role of the pressure Hessian in regions of strong vorticity in turbulence
Amplification of velocity gradients, a key feature of turbulent flows, is affected by the non-local character of the incompressible fluid equations expressed by the second derivative (Hessian) of the pressure field. By analysing the structure of the flow in regions where the vorticity is the highest, we propose an approximate expression for the pressure Hessian in terms of the local vorticity, consistent with the existence of intense vortex tubes. Contrary to the often used simplification of an isotropic form for the pressure Hessian, which in effect inhibits vortex stretching, the proposed approximate form of the pressure Hessian enables much stronger vortex stretching. The prediction of the approximation proposed here is validated with results of direct numerical simulations of turbulent flows.
Journal Article
The multifaceted role of GCM1 during trophoblast differentiation in the human placenta
Remodeling of the uterine vasculature by invasive extravillous trophoblasts (EVTs) is a critical aspect of human placentation. Insufficient EVT invasion can lead to severe obstetrical complications like preeclampsia, intrauterine growth restriction, and preterm birth. Glial cells missing-1 (GCM1) is a transcription factor that is crucial for proper placentation in mice, and is highly expressed in human syncytiotrophoblast (ST) and EVTs. GCM1 is classically considered a master regulator of ST formation, but little is known about its contribution to the development and function of EVTs. Therefore, in this study we test the hypothesis that GCM1 is a critical regulator of both EVT and ST development and function. We show that GCM1 is highly expressed in human trophoblast stem (TS) cells differentiated into either ST or EVTs. Knockdown of GCM1 in TS cells hindered differentiation into both ST and EVT pathways. When placed in ST media, GCM1-knockdown cells formed small, unstable clusters; when placed in EVT media, cells had altered morphology and transcript profiles resembling cells trapped in an intermediate state between CT and EVT, and invasive capacity through matrix was reduced. RNA sequencing analysis of GCM1-deficient TS cells revealed downregulation of EVT-associated genes and enrichment in transcripts related to WNT signaling, which was linked to decreased expression of the EVT master regulator ASCL2 and the WNT antagonist NOTUM. Our findings reveal an essential role of GCM1 during ST and EVT development, and suggest that GCM1 regulates differentiation of human TS cells into EVTs by inducing expression of ASCL2 and NOTUM.
Journal Article