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1.
Cancer Lett ; 587: 216703, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341127

RESUMO

Gallbladder cancer (GBC) is a highly malignant and rapidly progressing tumor of the human biliary system, and there is an urgent need to develop new therapeutic targets and modalities. Non-POU domain-containing octamer-binding protein (NONO) is an RNA-binding protein involved in the regulation of transcription, mRNA splicing, and DNA repair. NONO expression is elevated in multiple tumors and can act as an oncogene to promote tumor progression. Here, we found that NONO was highly expressed in GBC and promoted tumor cells growth. The dysregulation of RNA splicing is a molecular feature of almost all tumor types. Accordingly, mRNA-seq and RIP-seq analysis showed that NONO promoted exon6 skipping in DLG1, forming two isomers (DLG1-FL and DLG1-S). Furthermore, lower Percent-Spliced-In (PSI) values of DLG1 were detected in tumor tissue relative to the paraneoplastic tissue, and were associated with poor patient prognosis. Moreover, DLG1-S and DLG1-FL act as tumor promoters and tumor suppressors, respectively, by regulating the YAP1/JUN pathway. N6-methyladenosine (m6A) is the most common and abundant RNA modification involved in alternative splicing processes. We identified an m6A reader, IGF2BP3, which synergizes with NONO to promote exon6 skipping in DLG1 in an m6A-dependent manner. Furthermore, IP/MS results showed that RBM14 was bound to NONO and interfered with NONO-mediated exon6 skipping of DLG1. In addition, IGF2BP3 disrupted the binding of RBM14 to NONO. Overall, our data elucidate the molecular mechanism by which NONO promotes DLG1 exon skipping, providing a basis for new therapeutic targets in GBC treatment.


Assuntos
Proteínas de Ligação a DNA , Neoplasias da Vesícula Biliar , Humanos , Proteínas de Ligação a DNA/genética , Neoplasias da Vesícula Biliar/genética , Fatores de Transcrição/genética , Splicing de RNA , Proliferação de Células , RNA Mensageiro/genética , Linhagem Celular Tumoral , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Proteína 1 Homóloga a Discs-Large/genética , Proteína 1 Homóloga a Discs-Large/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
2.
Phys Rev Lett ; 131(23): 236002, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38134785

RESUMO

Recently, the bilayer perovskite nickelate La_{3}Ni_{2}O_{7} has been reported to show evidence of high-temperature superconductivity (SC) under a moderate pressure of about 14 GPa. To investigate the superconducting mechanism, pairing symmetry, and the role of apical-oxygen deficiencies in this material, we perform a random-phase approximation based study on a bilayer model consisting of the d_{x^{2}-y^{2}} and d_{3z^{2}-r^{2}} orbitals of Ni atoms in both the pristine crystal and the crystal with apical-oxygen deficiencies. Our analysis reveals an s^{±}-wave pairing symmetry driven by spin fluctuations. The crucial role of pressure lies in that it induces the emergence of the γ pocket, which is involved in the strongest Fermi-surface nesting. We further found the emergence of local moments in the vicinity of apical-oxygen deficiencies, which significantly suppresses the T_{c}. Therefore, it is possible to significantly enhance the T_{c} by eliminating oxygen deficiencies during the synthesis of the samples.

3.
J Colloid Interface Sci ; 652(Pt A): 989-996, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37639929

RESUMO

The design and development of high-performance, low-cost catalysts with long-term durability are crucial for hydrogen generation from water electrolysis. Interfacial engineering is an appealing strategy to boost the catalytic performance of electrode materials toward hydrogen evolution reaction (HER). Herein, we report a simple phosphidation followed by sulfidation treatment to construct heterogeneous cobalt phosphide-cobalt sulfide nanowire arrays on carbon cloth (CoP/CoS2/CC). When evaluated as catalysts toward the HER, the resultant CoP/CoS2/CC exhibits efficient pH-universal hydrogen production due to the heterostructure, synergistic contribution of CoP and CoS2, and conductive substrate. To attain a current density of 10 mA cm-2, overpotentials of only 111.2, 58.1, and 182.9 mV for CoP/CoS2/CC are required under alkaline, acidic, and neutral conditions, respectively. In particular, the as-prepared CoP/CoS2/CC shows markedly improved HER electroactivity in 1.0 M KOH, even outperforming commercial Pt-C/CC at a current density of >50 mA cm-2. In addition, the self-assembled CoP/CoS2||NiFe layered double hydroxide electrolyzer demonstrates efficient catalytic performance and long-time stability, excelling the benchmark Pt-C||IrO2. These findings indicate an effective pathway for the fabrication of high-performance heterogeneous electrocatalysts for hydrogen production in the future.

4.
Phytomedicine ; 114: 154785, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37002972

RESUMO

BACKGROUND: Gallbladder cancer (GBC) is the most aggressively malignant tumor in the bile duct system. The prognosis for patients with GBC is extremely poor. Ponicidin is a diterpenoid compound extracted and purified from the traditional Chinese herb Rabdosia rubescens, and showed promising anti-cancer effects in a variety of tumors. However, Ponicidin has not been investigated in GBC. METHODS: CCK-8, colony formation assay and EdU-488 DNA synthesis assay were performed to investigate the effect of Ponicidin on GBC cells proliferation. Cell invasion and migration assays and wound-healing assay were used to explore the effect of Ponicidin on invasion and migration ability of GBC cells. mRNA-seq was adopted to explore the underlying mechanisms. Western blot and immunohistochemical staining were conducted to detect the protein level. CHIP assay and dual-luciferase assay were used to validate binding motif. Nude mouse model of GBC was used to assess the anti-tumor effect and safety of Ponicidin. RESULTS: Ponicidin inhibited the proliferation and cell invasion and migration of GBC cells in vitro. Moreover, Ponicidin exerted anti-tumor effects by down-regulating the expression of MAGEB2. Mechanically, Ponicidin upregulated the FOXO4 expression and promoted it to accumulate in nucleus to inhibit the transcript of MAGEB2. Furthermore, Ponicidin suppressed tumor growth in the nude mouse model of GBC with excellent safety. CONCLUSION: Ponicidin may be a promising agent for the treatment of GBC effectively and safely.


Assuntos
Diterpenos , Neoplasias da Vesícula Biliar , Animais , Camundongos , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/patologia , Linhagem Celular Tumoral , Camundongos Nus , Diterpenos/farmacologia , Proliferação de Células , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Proteínas de Ciclo Celular/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Antígenos de Neoplasias , Proteínas de Neoplasias/metabolismo
5.
Proc Natl Acad Sci U S A ; 119(51): e2211193119, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36520670

RESUMO

An interplay of geometrical frustration and strong quantum fluctuations in a spin-1/2 triangular-lattice antiferromagnet (TAF) can lead to exotic quantum states. Here, we report the neutron-scattering, magnetization, specific heat, and magnetocaloric studies of the recently discovered spin-1/2 TAF Na2BaCo(PO4)2, which can be described by a spin-1/2 easy axis XXZ model. The zero-field neutron diffraction experiment reveals an incommensurate antiferromagnetic ground state with a significantly reduced ordered moment of about 0.54(2) µB/Co. Different magnetic phase diagrams with magnetic fields in the ab plane and along the easy c-axis were extracted based on the magnetic susceptibility, specific heat, and elastic neutron-scattering results. In addition, two-dimensional (2D) spin dispersion in the triangular plane was observed in the high-field polarized state, and microscopic exchange parameters of the spin Hamiltonian have been determined through the linear spin wave theory. Consistently, quantum critical behaviors with the universality class of d = 2 and νz = 1 were established in the vicinity of the saturation field, where a Bose-Einstein condensation (BEC) of diluted magnons occurs. The newly discovered quantum criticality and fractional magnetization phase in this ideal spin-1/2 TAF present exciting opportunities for exploring exotic quantum phenomena.

6.
Nano Lett ; 22(24): 9891-9899, 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36519735

RESUMO

Layered ferromagnets with strong magnetic anisotropy energy (MAE) have special applications in nanoscale memory elements in electronic circuits. Here, we report a strain tunability of perpendicular magnetic anisotropy in van der Waals (vdW) ferromagnets VI3 using magnetic circular dichroism measurements. For an unstrained flake, the M-H curve shows a rectangular-shaped hysteresis loop with a large coercivity (1.775 T at 10 K) and remanent magnetization. Furthermore, the coercivity can be enhanced to a maximum of 2.6 T under a 3.8% external in-plane tensile strain. Our DFT calculations show that the increased MAE under strain contributes to the enhancement of coercivity. Meanwhile, the strain tunability on the coercivity of CrI3, with a similar crystal structure, is limited. The main reason is the strong spin-orbit coupling in V3+ in VI6 octahedra in comparison with that in Cr3+. The strain tunability of coercivity in VI3 flakes highlights its potential for integration into vdW heterostructures.

7.
Nanoscale ; 14(15): 5851-5858, 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35357377

RESUMO

The research on two-dimensional (2D) van der Waals (vdW) magnets has promoted the development of ultrahigh-density data storage and nanoscale spintronic devices. However, the soft ferromagnetic behavior in most 2D magnets, which means the absence of remanent magnetization, severely limits their applications in realistic devices. Here, we report a layer-controlled ferromagnetic behavior in atomically thin CrSiTe3 flakes, where a transition from the soft to the hard ferromagnetic state occurs as the thickness of samples decreases down to several nanometers. Phenomenally, in contrast to the negligible hysteresis loop in the bulk counterparts, atomically thin CrSiTe3 shows a rectangular loop with finite magnetization and coercivity as the thickness decreases down to ∼8 nm, indicative of a single-domain and out-of-plane ferromagnetic order. We find that the stray field is weakened with decreasing thickness, which suppresses the formation of the domain wall. In addition, thickness-dependent ferromagnetic properties also reveal a crossover from 3 dimensional to 2 dimensional Ising ferromagnets, accompanied by a drop of the Curie temperature from 33 K for bulk to ∼17 K for the 4 nm sample. Our study paves the way towards exploring and learning much more about atomically thin and layered intrinsic ferromagnets.

8.
J Integr Plant Biol ; 63(12): 2123-2135, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34655280

RESUMO

Pear has an S-RNase-based gametophytic self-incompatibility (SI) system. Nuclear DNA degradation is a typical feature of incompatible pollen tube death, and is among the many physiological functions of vacuoles. However, the specific changes that occur in vacuoles, as well as the associated regulatory mechanism in pear SI, are currently unclear. Although research in tobacco has shown that decreased activity of diacylglycerol kinase (DGK) results in the morphological change of pollen tube vacuole, whether DGK regulates the pollen tube vacuole of tree plants and whether it occurs in SI response, is currently unclear. We found that DGK activity is essential for pear pollen tube growth, and DGK4 regulates pollen tube vacuole morphology following its high expression and deposition at the tip and shank edge of the pollen tube of pear. Specifically, incompatible S-RNase may induce cytoplasmic acidification of the pollen tube by inhibiting V-ATPase V0 domain a1 subunit gene expression as early as 30 min after treatment, when the pollen tube is still alive. Cytoplasmic acidification induced by incompatible S-RNase results in reduced DGK4 abundance and deposition, leading to morphological change of the vacuole and fragmentation of nuclear DNA, which indicates that DGK4 is a key factor in pear SI response.


Assuntos
Pyrus , DNA/metabolismo , Diacilglicerol Quinase/genética , Diacilglicerol Quinase/metabolismo , Concentração de Íons de Hidrogênio , Tubo Polínico/metabolismo , Pyrus/genética , Pyrus/metabolismo , Vacúolos/metabolismo
9.
Nano Lett ; 21(19): 7946-7952, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34533027

RESUMO

Despite recent advances in layered ferromagnets, ferromagnetic interactions in these materials are rather weak. Here, we report pressure-enhanced ferromagnetism in layered CrSiTe3 flakes revealed by high-pressure magnetic circular dichroism measurements. Below ∼3 GPa, CrSiTe3 undergoes a paramagnetic-to-ferromagnetic phase transition at ∼32 K, and the field-induced spin-flip in the ferromagnetic phase produces nearly zero hysteresis loops, demonstrating soft ferromagnetism. Above ∼4 GPa, a soft-to-hard ferromagnetic transition occurs, signaled by rectangular-shaped hysteresis loops with finite coercivity and remanent magnetization. Interestingly, as pressure increases, the Curie temperature and coercivity dramatically increase up to ∼138 K and 0.17 T at 7.8 GPa, respectively, in contrast to ∼36 K and 0.02 T at 4.6 GPa. It indicates a remarkable influence of pressure on exchange interactions, which is consistent with DFT calculations. The effective interaction between magnetic couplings and external pressure offers new opportunities in pursuit of high-temperature layered ferromagnets.

10.
Nat Commun ; 12(1): 3048, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34031422

RESUMO

Beyond the absence of long-range magnetic orders, the most prominent feature of the elusive quantum spin liquid (QSL) state is the existence of fractionalized spin excitations, i.e., spinons. When the system orders, the spin-wave excitation appears as the bound state of the spinon-antispinon pair. Although scarcely reported, a direct comparison between similar compounds illustrates the evolution from spinon to magnon. Here, we perform the Raman scattering on single crystals of two quantum kagome antiferromagnets, of which one is the kagome QSL candidate Cu3Zn(OH)6FBr, and another is an antiferromagnetically ordered compound EuCu3(OH)6Cl3. In Cu3Zn(OH)6FBr, we identify a unique one spinon-antispinon pair component in the E2g magnetic Raman continuum, providing strong evidence for deconfined spinon excitations. In contrast, a sharp magnon peak emerges from the one-pair spinon continuum in the Eg magnetic Raman response once EuCu3(OH)6Cl3 undergoes the antiferromagnetic order transition. From the comparative Raman studies, we can regard the magnon mode as the spinon-antispinon bound state, and the spinon confinement drives the magnetic ordering.

11.
Phys Rev Lett ; 127(26): 267202, 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-35029499

RESUMO

One favorable situation for spins to enter the long-sought quantum spin liquid (QSL) state is when they sit on a kagome lattice. No consensus has been reached in theory regarding the true ground state of this promising platform. The experimental efforts, relying mostly on one archetypal material ZnCu_{3}(OH)_{6}Cl_{2}, have also led to diverse possibilities. Apart from subtle interactions in the Hamiltonian, there is the additional degree of complexity associated with disorder in the real material ZnCu_{3}(OH)_{6}Cl_{2} that haunts most experimental probes. Here we resort to heat transport measurement, a cleaner probe in which instead of contributing directly, the disorder only impacts the signal from the kagome spins. For ZnCu_{3}(OH)_{6}Cl_{2}, we observed no contribution by any spin excitation nor obvious field-induced change to the thermal conductivity. These results impose strong constraints on various scenarios about the ground state of this kagome compound: while certain quantum paramagnetic states other than a QSL may serve as natural candidates, a QSL state, gapless or gapped, must be dramatically modified by the disorder so that the kagome spin excitations are localized.

12.
J Phys Chem Lett ; 11(17): 7313-7319, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32787290

RESUMO

We investigated the evolution of ferromagnetism in layered Fe3GeTe2 flakes under different pressures and temperatures using in situ magnetic circular dichroism (MCD) spectroscopy. We found that the rectangular shape of the hysteresis loop under an out-of-plane magnetic field sweep can be sustained below 7 GPa. Above that pressure, an intermediate state appears in the low-temperature region signaled by an 8-shaped skewed hysteresis loop. Meanwhile, the coercive field and Curie temperature decrease with increasing pressures, implying the decrease of the exchange interaction and the magneto-crystalline anisotropy under pressures. The intermediate phase has a labyrinthine domain structure, which is attributed to the increase of the ratio of exchange interaction to magneto-crystalline anisotropy based on Jagla's theory. Moreover, our calculations reveal a weak structural transition around 6 GPa that corresponds to a significant change in the FeI-FeI bond length, which has strong influences on magnetic interaction. Detailed analysis on exchange interaction and magneto-crystalline anisotropy with pressure shows a consistent trend with experiments.

13.
ACS Appl Mater Interfaces ; 12(22): 25135-25142, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32338493

RESUMO

Topological Hall effect is an abnormal Hall response arising from the scalar spin chirality of chiral magnetic textures. Up to now, such an effect is only observed in certain special materials, but rarely in traditional ferromagnets. In this work, we have implemented the molecular beam epitaxy technique to successfully embed black-phosphorus-like bismuth nanosheets with strong spin-orbit coupling into the bulk of chromium telluride Cr2Te3, as evidenced by atomically resolved energy dispersive X-ray spectroscopy mapping. Distinctive from pristine Cr2Te3, these Bi-embedded Cr2Te3 epitaxial films exhibit not only pronounced topological Hall effects, but also magnetoresistivity anomalies and differential magnetic susceptibility plateaus. All these experimental features point to the possible emergence of magnetic skyrmions in Bi-embedded Cr2Te3, which is further supported by our numerical simulations with all input parameters obtained from the first-principle calculations. Therefore, our work demonstrates a new efficient way to induce skyrmions in ferromagnets, as well as the topological Hall effect by embedding nanosheets with strong spin-orbit couplings.

14.
Nano Lett ; 20(5): 3160-3168, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32207627

RESUMO

How an interfacial superconductivity emerges during the nucleation and epitaxy is of great importance not only for unveiling the physical insights but also for finding a feasible way to tune the superconductivity via interfacial engineering. In this work, we report the nanoscale creation of a robust and relatively homogeneous interfacial superconductivity (TC ≈ 13 K) on the epitaxial FeTe surface, by van der Waals epitaxy of single-quintuple-layer topological insulator Bi2Te3. Our study suggests that the superconductivity in the Bi2Te3/FeTe heterostructure is generated at the interface and that the superconductivity at the interface does not enhance or weaken with the increase of the Bi2Te3 thickness beyond 1 quintuple layer (QL). The observation of the topological surface states crossing Fermi energy in the Bi2Te3/FeTe heterostructure with the average Bi2Te3 thickness of about 20 QL provides further evidence that this heterostructure may potentially host Majorana zero modes.

15.
BMC Cancer ; 19(1): 740, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31357957

RESUMO

BACKGROUND: Emerging evidence has shown that miR-1275 plays a critical role in tumour metastasis and the progression of various types of cancer. In this study, we analysed the role and mechanism of miR-1275 in the progression and prognosis of gastric cancer (GC). METHODS: Target genes of miR-1275 were identified and verified by luciferase assay and Western blotting. The function of miR-1275 in invasion and metastasis was analysed in vitro and in vivo in nude mice. The signal pathway regulated by miR-1275 was examined by qRT-PCR, Western blotting and chromatin immunoprecipitation analyses. The expression of miR-1275and JAZF1 were measured in specimens of GC and adjacent non cancerous tissues. RESULTS: We identified JAZF1 as a direct miR-1275 target. miR-1275 supresses migration and invasion of GC cells in vitro and in vivo, which was restored by JAZF1 overexpression. Moreover, JAZF1 was recognized as a direct regulator of Vimentin. Knocking-down miR-1275 or overexpressing JAZF1 resulted in upregulation of Vimentin but downregulation of E-cadherin. Meanwhile, we validated in 120 GC patients specimens that low miR-1275expression and high JAZF1 mRNA expression levels were closely associated with lymph node metastasis and poor prognosis. The expression of JAZF1 in protein level displayed the correlations with Vimentin but inversely with E-cadherin. CONCLUSIONS: Increased miR-1275 expression inhibited GC metastasis by regulating vimentin/E-cadherin via direct suppression of JAZF1expression, suggesting that miR-1275 is a tumour-suppressor miRNA with the potential as a prognostic biomarker or therapeutic target in GC.


Assuntos
Antígenos CD/metabolismo , Caderinas/metabolismo , Movimento Celular , Proteínas Correpressoras/metabolismo , Proteínas de Ligação a DNA/metabolismo , MicroRNAs/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Vimentina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proteínas Correpressoras/genética , Proteínas de Ligação a DNA/genética , Modelos Animais de Doenças , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfonodos/patologia , Metástase Linfática , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Neoplasias Gástricas/cirurgia , Transfecção
16.
Nanoscale ; 11(3): 955-961, 2019 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-30652715

RESUMO

Dichotomy between local spins and conjugated electrons spawns various exotic physical phenomena, however, it has mostly been reported in three-dimensional (3D) inorganic systems. We show, for the first time, that a rare 2D metal-organic framework exhibits intriguing dichotomy behavior, which can be directly identified through scanning tunneling microscopy/spectroscopy (STM/STS). In a newly synthesized Cu-hexaiminobenzene [Cu3(HAB)2], on the one hand, the Cu2+ ions form an ideal S - 1/2 antiferromagnetic (AFM) kagome lattice; on the other hand, the conjugated-electrons from the organic ligands produce a frustrated πx,y model on a honeycomb lattice, giving rise to completely dispersionless energy bands around the Fermi level that favour the ferromagnetic (FM) state. Remarkably, the frustrated local spins and conjugated electrons interact through a strong FM Hund's coupling, giving rise to a wide range of intriguing quantum phases. Furthermore, we propose that this dichotomy can be directly characterized through STM/STS measurements due to its special 2D nature, which provides a unique exciting platform to investigate the dichotomy of frustrated spins and electrons in a single lattice.

17.
Phys Chem Chem Phys ; 20(33): 21693-21698, 2018 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-30101264

RESUMO

Herbertsmithite and Zn-doped barlowite are two compounds for experimental realization of two-dimensional kagome spin liquids. Theoretically, it has been proposed that charge doping a quantum spin liquid gives rise to exotic metallic states, such as high-temperature superconductivity. However, one recent experiment on herbertsmithite with successful Li-doping surprisingly showed an insulating state even under a heavily doped scenario, which cannot be explained by previous theories. Using first-principles calculations, we performed a comprehensive study on the Li intercalation doping effect of these two compounds. For the Li-doped herbertsmithite, we identified the optimized Li position at the Cl-(OH)3-Cl pentahedron site instead of the previously speculated Cl-(OH)3 tetrahedral site. With increasing Li doping concentration, saturation magnetization decreases linearly due to charge transfer from Li to Cu ions. Moreover, we found that Li forms chemical bonds with nearby (OH)- and Cl- ions, which lowers the surrounding chemical potential and traps electrons, as evidenced by the localized charge distribution, explaining the insulating behavior measured experimentally. Though a different structure from herbertsmithite, Zn-doped barlowite shows the same features upon Li doping. We conclude that Li doping this family of kagome spin liquids cannot realize exotic metallic states, and other methods should be further explored, such as element substitution with those having different valence electrons.

18.
J Cancer ; 9(8): 1448-1454, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29721055

RESUMO

Objective: Mammalian target of rapamycin complex 1 (mTORC1) plays an important role in maintaining proper cellular functions in gastric cancer (GC). Previous studies demonstrated genetic variants within mTORC1 genes were associated with GC risk. However, no studies reported the associations between genetic variants within mTORC1 genes and GC prognosis. Herein, we firstly assessed the associations of genetic variants of mTORC1 genes with overall survival (OS) of GC in Chinese populations. Methods: We genotyped eight single nucleotide polymorphisms (SNPs) in mTORC1 genes (i.e., rs2536 T>C and rs1883965 G>A for mTOR, rs3160 T>C and rs26865 A>G for MLST8, rs3751934 C>A, rs1062935 T>C, rs3751932 T>C and rs12602885 G>A for RPTOR) by the TaqMan method in 197 Chinese GC patients who had surgical resection in Xinhua Hospital. We conducted Kaplan-Meier survival plots and Cox hazards regression analysis to explore the associations of these SNPs with OS. Results: The single-locus analysis indicated that RPTOR rs1062935 T>C was associated with an increased risk of poor GC prognosis (CC vs. TT/TC: adjusted Hazard ratio (HR) = 1.71, 95% confidence interval (CI) = 1.04-2.82). The combined analysis of all eight SNPs showed that patients with more than three risk genotypes significantly increased risk of death (adjusted HR = 2.44, 95% CI = 1.30-4.58), when compared to those with three or less risk genotypes. Conclusions: Our findings indicated that genetic variants within mTORC1 genes may predict GC prognosis in Chinese populations. The results need to be validated in future studies with larger sample sizes.

19.
Cell Death Dis ; 9(3): 410, 2018 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-29540696

RESUMO

Gallbladder carcinoma (GBC), the most common malignant tumour of the bile duct, is highly aggressive and has a poor prognosis. MicroRNA-30a-5p (miR-30a-5p) is an important tumour suppressor that participates in many aspects of carcinogenesis and cancer development. However, the role of miR-30a-5p in GBC development remains to be determined, as do the mechanisms underlying its effects in GBC. Using samples collected from 42 subjects with gallbladder carcinoma (GBC), we showed decreased miR-30a-5p expression in the primary lesions vs. non-tumour adjacent tissues (NATs). Decreased miR-30a-5p was associated with shorter disease-free survival (DFS) and overall survival (OS). Inhibiting miR-30a-5p expression in 2 representative GBC cell lines (GBC-SD and NOZ) increased cell proliferation, migration, invasiveness, as well as ß-catenin nuclear translocation, vice versa. In nude mice, NOZ cells transfected with miR-30a-5p mimics grew slower (vs. miR-NC) upon subcutaneous inoculation, and had lower rate of hepatic metastasis upon spleen inoculation. Dual luciferase assay confirmed that E2F transcription factor 7 (E2F7) was a direct target of miR-30a-5p and antagonized the effects induced by miR-30a-5p downregulation in GBC cells. MiR-30a-5p attenuates the EMT and metastasis in GBC cells by targeting E2F7, suggesting miR-30a-5p is a tumour suppressor that may serve as a novel potential prognostic biomarker or molecular therapeutic target for GBC.


Assuntos
Fator de Transcrição E2F7/genética , Neoplasias da Vesícula Biliar/genética , MicroRNAs/metabolismo , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Fator de Transcrição E2F7/metabolismo , Feminino , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/fisiopatologia , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Pessoa de Meia-Idade , Metástase Neoplásica
20.
Phys Rev Lett ; 120(3): 037204, 2018 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-29400534

RESUMO

We describe electron spin resonance in a quantum spin liquid with significant spin-orbit coupling. We find that the resonance directly probes spinon continuum, which makes it an efficient and informative probe of exotic excitations of the spin liquid. Specifically, we consider spinon resonance of three different spinon mean-field Hamiltonians, obtained with the help of projective symmetry group analysis, which model a putative quantum spin liquid state of the triangular rare-earth antiferromagnet YbMgGaO_{4}. The band of absorption is found to be very broad and exhibit strong van Hove singularities of single spinon spectrum as well as pronounced polarization dependence.

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