Retraction notice to "Design, synthesis, and biological evaluation of heterotetracyclic quinolinone derivatives as anticancer agents targeting topoisomerases" [Eur. J. Med. Chem. 190 (2020) 112074].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the authors. The authors regret to inform that they would like to withdraw this accepted article, due to serious errors in authorship, affiliations, material sources and supporting grant names/numbers. The authors sincerely apologize for these oversights and miscommunications the study caused.

VHL-HIF-2α axis-induced SMYD3 upregulation drives renal cell carcinoma progression via direct trans-activation of EGFR.

It has been well established that the von Hippel-Lindau/hypoxia-inducible factor α (VHL-HIFα) axis and epidermal growth factor receptor (EGFR) signaling pathway play a critical role in the pathogenesis and progression of renal cell carcinoma (RCC). However, few studies have addressed the relationship between the two oncogenic drivers in RCC. SET and MYND domain-containing protein 3 (SMYD3) is a histone methyltransferase involved in gene transcription and oncogenesis, but its expression and function in RCC remain unclear. In the present study, we found that SMYD3 expression was significantly elevated in RCC tumors and correlated with advanced tumor stage, histological and nuclear grade, and shorter survival. Depletion of SMYD3 inhibited RCC cell proliferation, colony numbers, and xenograft tumor formation, while promoted apoptosis. Mechanistically, SMYD3 cooperates with SP1 to transcriptionally promote EGFR expression, amplifying its downstream signaling activity. TCGA data analyses revealed a significantly increased SMYD3 expression in primary RCC tumors carrying the loss-of-function VHL mutations. We further showed that HIF-2α can directly bind to the SMYD3 promoter and subsequently induced SMYD3 transcription and expression. Taken together, we identify the VHL/HIF-2α/SMYD3 signaling cascade-mediated EGFR hyperactivity through which SMYD3 promotes RCC progression. Our study suggests that SMYD3 is a potential therapeutic target and prognostic factor in RCC.

Electric-Controlled Valley Pseudomagnetoresistance in Graphene with Y-Shaped Kekulé Lattice Distortion.

We propose a new method for regulating valley pseudomagnetoresistance in ballistic graphene-based valley field-effect transistors by taking into account the Y-shaped Kekulé lattice distortion and electric barrier. The device involves valley injection and valley detection by ferromagnetic-strain source and drain. The valley manipulation in the channel is achieved via the Y-shaped Kekulé lattice distortion and electric barrier. The central mechanism of these devices lies on Y-shaped Kekulé lattice distortion in graphene can induce a valley precession, thus controlling the valley orientation of channel electrons and hence the current collected at the drain. We found that the tuning external bias voltage makes the valley pseudomagnetoresistance oscillate between positive and negative values and colossal tunneling valley pseudomagnetoresistance of over 30,000% can be achieved. Our results suggest that the synergy of valleytronics and digital logics may provide new paradigms for valleytronic-based information processing and reversible computing.

Design, synthesis, and biological evaluation of heterotetracyclic quinolinone derivatives as anticancer agents targeting topoisomerases.

A series of thiochromeno[2,3-c]quinolin-12-one derivatives with various substitutions were synthesized and evaluated as topoisomerase (Topo) inhibitors. Six (8, 10, 12, 14, 19, and 26) of 23 compounds showed strong inhibitory activities against Topo-mediated DNA relaxation and proliferation of five human cell lines including breast (MDA-MB-231, MDA-MB-468 and MCF7), colorectal (HCT116) and non-small cell lung (H1299) cancers. Among these, compounds 14 and 26 exhibited full inhibitory activities against Topo I at 3 µM and Topo IIα at 1 µM. Cancer cells treated with 26 accumulated DNA damage and were arrested at the G2/M phase. With time, cells proceeded to apoptosis, as revealed by increased amounts of cells with fragmented DNA and cleavage of caspase-8 and -9. In contrast, normal breast epithelial cells showed low sensitivity to 26. Taken together, our study identifies 26 as a potent Topo dual-inhibitor with low toxicity to normal cells, and elucidates that the terminal amino group of N-2-aminoethylamino or N-3-aminopropylamino at the 6th position and 8,10-di-halogen substituents on thiochromeno[2,3-c]quinolin-12-one are critical for the Topo-inhibiting and cancer-killing activities.

Electric Field Controlled Indirect-Direct-Indirect Band Gap Transition in Monolayer InSe.

Electronic structures of monolayer InSe with a perpendicular electric field are investigated. Indirect-direct-indirect band gap transition is found in monolayer InSe as the electric field strength is increased continuously. Meanwhile, the global band gap is suppressed gradually to zero, indicating that semiconductor-metal transformation happens. The underlying mechanisms are revealed by analyzing both the orbital contributions to energy band and evolution of band edges. These findings may not only facilitate our further understanding of electronic characteristics of layered group III-VI semiconductors, but also provide useful guidance for designing optoelectronic devices.

Tunable Dirac points and high spin polarization in ferromagnetic-strain graphene superlattices.

Spin-dependent energy bands and transport properties of ferromagnetic-strain graphene superlattices are studied. The high spin polarization appears at the Dirac points due to the presence of spin-dependent Dirac points in the energy band structure. A gap can be induced in the vicinity of Dirac points by strain and the width of the gap is enlarged with increasing strain strength, which is beneficial for enhancing spin polarization. Moreover, a full spin polarization can be achieved at large strain strength. The position and number of the Dirac points corresponding to high spin polarization can be effectively manipulated with barrier width, well width and effective exchange field, which reveals a remarkable tunability on the wavevector filtering behavior.

Helical edge states and edge-state transport in strained armchair graphene nanoribbons.

A helical type edge state, which is generally supported only on graphene with zigzag boundaries, is found to also appear in armchair graphene nanoribbons in the presence of intrinsic spin-orbit coupling and a suitable strain. At a critical strain, there appears a quantum phase transition from a quantum spin Hall state to a trivial insulator state. Further investigation shows that the armchair graphene nanoribbons with intrinsic spin-orbit coupling, Rashba spin-orbit coupling, effective exchange fields and strains also support helical-like edge states with a unique spin texture. In such armchair graphene nanoribbons, the spin directions of the counterpropogating edge states on the same boundary are always opposite to each other, while is not conserved and the spins are canted away from the -direction due to the Rashba spin-orbit coupling, which is different from the case of the zigzag graphene nanoribbons. Moreover, the edge-state energy gap is smaller than that in zigzag graphene nanoribbons, even absent in certain cases.

Valley precession and valley polarization in graphene with inter-valley coupling.

We theoretically investigate the valley precession and valley polarization in graphene under inter-valley coupling. Our results show that the inter-valley coupling can induce valley polarization in graphene and also precess valleys in real space in a manner similar to the Rashba spin-orbit interaction rotating spins. Moreover, using strain modulation, we can achieve high valley polarization with large valley-polarized currents. These findings provide a new way to create and manipulate valley polarization in graphene.

Edge states and quantum phase transition in graphene under in-plane effective exchange fields.

We investigated the edge states and quantum phase transition in graphene under an in-plane effective exchange field. The result shows that the combined effects of the in-plane effective exchange field and a staggered sublattice potential can induce zero-energy flat bands of edge states. Such flat-band edge states can evolve into helical-like ones in the presence of intrinsic spin-orbit coupling, with a unique spin texture. We also find that the bulk energy gap induced by the spin-orbit coupling and staggered sublattice potential can be closed and reopened with the in-plane effective exchange field, and the reopened bulk gap can be even larger than that induced by only the spin-orbit coupling and staggered sublattice potential, which is different from the case of an out-of-plane effective exchange field. The calculated spin-dependent Chern numbers suggest that the bulk gap closing and reopening is accompanied by a quantum phase transition from a trivial insulator phase across a metal phase into a spin-dependent quantum Hall phase.

[Expression of miR-550a-5p in Myelodysplastic Syndrome and Its Prediction of Target Genes].

OBJECTIVE: To investigate the expression of miR-550a-5p in bone marrow of patients with myelodysplastic syndrome (MDS), and to predict its target genes and function by bioinformatics analyses, so as to provide the evidence to furthre explore the role of miR-550a-5p and its target genes in pathogenesis of MDS. METHODS: Real-time PCR was used to detect the expression of miR-550a-5p in 54 MDS patients, 16 acute myeloid leukemia transformed from MDS (sfAML) and 19 healthy controls, and the correlation between the expression of miR-550a-5p and clinical pathologic characteristics of MDS, including chromosome, percentage of marrow blasts, absolute neutrophil count, platelet count and hemoglobin levels were analyzed. The sequence of miR-550 was searched in miRBase database. Target genes of miR-550a-5p were predicted by Microcosm,Miranda and Targetscan, and the predective results were collected, then the enrichment analyses of target gene function(GO) and signalling pathway(pathway of miR-550a-5p) were carried out by using gene ontology darabase and KEGG database. RESULTS: The expression of miR-550a-5p in bone marrow of all MDS patients was higher than that in controls: the expression level of miR-550a-5p in low risk MDS and middl risk 1 MDS was 1.7 times of controls (P=1.23×10-10); the expression of miR-550a-5p in midde risk 2 MDS and high risk MDS was 1.9 times of controls (P=1.20×10-10); the expression of miR-550a-5p in tAML was 2.0 times of controls (P=5.61×10-10). The miR-550a-5p expression level was up-regulated gradually with the enhancement of disease risk of MDS, but there was no correlation between the expression level of miR-550a-5p and clinical pathologic characteristics of MDS(chromosome: Normal: 1.11±0.19, Abnormal:1.26±0.15, P>0.05; Percentage of Marrow Blasts: r=0.29,P=0.07; absolute neutrophil count: r=-0.02,P=0.89; hemoglobin level: r=0.09,P=0.57; platelet count: r=0.25,P=0.08). The sequence of miR-550 was conservative among different species, and the prediced results indicated that there were 19 target genes in intersection. The functions of target genes were enriched in regulation of stress-activated cascade, MAPK pathway, regulation of muscle organ development, regulation of protein homodimerization activity and other biological processes; they participated in some molecular functions including enzyme activity, combination processes of some molecules as protein, cAMP and domain existed in cell junction, synapse, coated vesicle, dendrite and other cellular components. Two of them-PDLIM2 and PSME1 were selected which might play a role in pathologic mechanism of MDS regulated by miR-550a-5p. CONCLUSION: The expression of miR-550a-5p in bone marrow of MDS patients increases specifically, and miR-550a-5p may play a role in the pathogenesis of MDS through regulation of target genes, PDLIM2 and PSME1.

Full Valley and Spin Polarizations in Strained Graphene with Rashba Spin Orbit Coupling and Magnetic Barrier.

We propose a graphene-based full valley- and spin-polarization device based on strained graphene with Rashba spin orbit coupling and magnetic barrier. The underlying mechanism is the coexistence of the valley and single spin band gaps in a certain Fermi energy. By aligning the Fermi energy in the valley and single spin band gaps, remarkable valley- and spin-polarization currents can be accessed.