ABSTRACT
Triple-negative breast cancer (TNBC) exhibits heightened aggressiveness compared with other breast cancer (BC) subtypes, with earlier relapse, a higher risk of distant metastasis, and a worse prognosis. Transcription factors play a pivotal role in various cancers. Here, we found that factor forkhead box M1 (FOXM1) expression was significantly higher in TNBC than in other BC subtypes and normal tissues. Combining the findings of Gene Ontology (GO) enrichment analysis and a series of experiments, we found that knockdown of the FOXM1 gene attenuated the ability of TNBC cells to proliferate and metastasize both in vivo and in vitro. In addition, Spearman's test showed that FOXM1 significantly correlated with glycolysis-related genes, especially centromere protein A (CENPA) in datasets (GSE76250, GSE76124, GSE206912, and GSE103091). The effect of silencing FOXM1 on the inhibition of CENPA expression, TNBC proliferation, migration, and glycolysis could be recovered by overexpression of CENPA. According to MeRIP, the level of m6A modification on FOMX1 decreased in cells treated with cycloleucine (a m6A inhibitor) compared with that in the control group. The increase in FOXM1 expression caused by YTHDC1 overexpression could be reversed by the m6A inhibitor, which indicated that YTHDC1 enhanced FOXM1 expression depending on m6A modification. Therefore, we concluded that the YTHDC1-m6A modification/FOXM1/CENPA axis plays an important role in TNBC progression and glycolysis.
Subject(s)
Cell Proliferation , Disease Progression , Forkhead Box Protein M1 , Gene Expression Regulation, Neoplastic , Glycolysis , Triple Negative Breast Neoplasms , Animals , Female , Humans , Mice , Adenosine/analogs & derivatives , Adenosine/metabolism , Cell Line, Tumor , Cell Movement , Chromosomal Proteins, Non-Histone/metabolism , Chromosomal Proteins, Non-Histone/genetics , Forkhead Box Protein M1/metabolism , Forkhead Box Protein M1/genetics , Mice, Nude , RNA Splicing Factors/metabolism , RNA Splicing Factors/genetics , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/metabolismABSTRACT
PURPOSE: In patients with first-line advanced breast cancer (ABC), the correlation between ctDNA variant allele frequency (VAF) and tumor disease burden, and its prognostic value remains poorly investigated. METHODS: This study included patients with ABC diagnosed at Peking University Cancer Hospital who performed ctDNA test before receiving first-line treatment. Baseline plasma samples were collected for assessing ctDNA alterations and VAF with next-generation sequencing. The sum of tumor target lesion diameters (SLD) was measured with imaging methods according to RECIST 1.1 criteria. RESULTS: The final cohort included 184 patients. The median age of the cohort was 49.4 (IQR: 42.3-56.8) years. The median VAF was 15.6% (IQR: 5.4%-33.7%). VAF showed positive correlation with SLD in patients with relatively large tumor lesions (r = 0.314, p = 0.003), but not in patients with small tumor lesions (p = 0.226). VAF was associated with multiple metastasis sites (p = 0.001). Multivariate Cox regression analysis showed that high VAF was associated with shorter overall survival (OS) (HR: 3.519, 95% confidence interval (CI): 2.149-5.761), and first-line progression-free survival (PFS) (HR: 2.352, 95%CI: 1.462-3.782). Combined VAF and SLD improved prediction performance, both median OS and PFS of patients in VAF(H)/SLD(H) group were significantly longer than VAF(L)/SLD(L) group (mOS: 49.3 vs. 174.1 months; mPFS: 9.6 vs. 25.3 months). CONCLUSION: ctDNA VAF associated with tumor disease burden, and was a prognostic factor for patients with ABC. A combination of ctDNA test and radiographic imaging might enhance tumor burden evaluation, and improve prognosis stratification in patients with ABC.
Subject(s)
Breast Neoplasms , Circulating Tumor DNA , Lung Neoplasms , Humans , Adult , Middle Aged , Female , Circulating Tumor DNA/genetics , Tumor Burden , Breast Neoplasms/genetics , Breast Neoplasms/therapy , Biomarkers, Tumor/genetics , Prognosis , Lung Neoplasms/genetics , Gene Frequency , MutationABSTRACT
Improving visible light absorption plays an important role in the utilization of solar power for photocatalysis. Using first-principles calculations within the HSE06 functional, we propose that the semiconductor heterojunction BiOI/LaOXIãIXã extends the optical absorption to the near-infrared range, boosts the absorption coefficient from 1.28 × 105 cm-1 to above 2.20 × 105 cm-1 in the visible light range, and increases the conversion efficiency of solar power up to 9.48%. The enhanced optical absorption derives from the significant interlayer transition and excitonic effect which benefit from polarized LaOXI with a flat band in the highest valence band (VB). In BiOI/LaOClIãICl ã, the electrostatic potential difference (ΔΦ) modifies the band edge positions to meet the requirements for photocatalytic overall water splitting, while the polarized electric field (Ep) accelerates the separation of photogenerated carriers and regulates the overpotentials of photogenerated carriers following a direct Z-scheme strategy. In addition, BiOI/LaOXIãIXã is dynamically and thermodynamically stable. Furthermore, only a low external potential is needed to drive the redox reaction. Our theoretical results suggest that BiOI/LaOXIãIXã could be a potential photocatalyst for overall water splitting with enhanced visible light absorption.
ABSTRACT
This study used the DNA of Bacillus amyloliquefaciens Ba168 as a template to amplify the flagellin BP8-2 gene and ligate it into the fusion expression vector pCAMBIA1300-35S-EGFP after digestion for the construction of the expression vector pCAMBIA1300-EGFP-BP8-2. Next, using Nicotiana benthamiana as receptor material, transient expression was carried out under the mediation of Agrobacterium tumefaciens C58C1. Finally, the transient expression and subcellular localisation of flagellin BP8-2 protein were analysed using the imaging of co-transformed GFP under laser confocal microscopy. The results showed that flagellin BP8-2 was localised in the cell membrane and nucleus, and the RT-PCR results showed that the BP8-2 gene could be stably expressed in tobacco leaf cells. Furthermore, there was stronger antiviral activity against tobacco mosaic virus (TMV) infection in Nicotiana glutinosa than in BP8-2 and ningnanmycin, with an inhibitory effect of 75.91%, protective effect of 77.45%, and curative effect of 68.15%. TMV movement and coat protein expression were suppressed, and there was a high expression of PR-1a, PAL, and NPR1 in BP8-2-treated tobacco leaf. These results suggest that flagellin BP8-2 inhibits TMV by inducing resistance. Moreover, BP8-2 has low toxicity and is easily biodegradable and eco-friendly. These results further enrich our understanding of the antiviral mechanisms of proteins and provide alternatives for controlling viral diseases in agriculture.
Subject(s)
Antiviral Agents , Flagellin , Genetic Vectors , Nicotiana , Tobacco Mosaic Virus , Flagellin/pharmacology , Flagellin/metabolism , Flagellin/genetics , Nicotiana/virology , Nicotiana/genetics , Nicotiana/metabolism , Tobacco Mosaic Virus/drug effects , Antiviral Agents/pharmacology , Plant Leaves/virology , Plant Leaves/metabolism , Plant Diseases/virology , Plant Diseases/geneticsABSTRACT
To provide a desirable number of parallel subnetworks as required to reach a robust inference in an active modulation diffractive deep neural network, a random micro-phase-shift dropvolume that involves five-layer statistically independent dropconnect arrays is monolithically embedded into the unitary backpropagation, which does not require any mathematical derivations with respect to the multilayer arbitrary phase-only modulation masks, even maintaining the nonlinear nested characteristic of neural networks, and generating an opportunity to realize a structured-phase encoding within the dropvolume. Further, a drop-block strategy is introduced into the structured-phase patterns designed to flexibly configure a credible macro-micro phase dropvolume allowing for convergence. Concretely, macro-phase dropconnects concerning fringe griddles that encapsulate sparse micro-phase are implemented. We numerically validate that macro-micro phase encoding is a good plan to the types of encoding within a dropvolume.
ABSTRACT
BACKGROUND: To compare the clinical value of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and pegylated rhG-CSF(PEG-rhG-CSF) in early-stage breast cancer (EBC) patients receiving adjuvant chemotherapy, compare the efficacy of PEG-rhG-CSF with different dose and explore the timing of rhG-CSF rescue treatment. METHODS: Patients in two PEG-rhG-CSF subgroups were given 3 mg or 6 mg PEG-rhG-CSF within 24 ~ 48 h after chemotherapy for preventing myelosuppression, while patients in the rhG-CSF group were given rhG-CSF. Observation indicators include the incidence of febrile neutropenia (FN) and grade 3/4 chemotherapy-induced-neutropenia (CIN), the overall levels and nadir values of white blood cells (WBC) and absolute neutrophil count (ANC), comparison of WBC and ANC curves over time, the incidence of CIN-related complications, the incidence of adverse events in each group and the timing of rescue treatment for rhG-CSF. RESULTS: There was no significant difference in the incidence of FN in the first cycle among the groups (P = 0.203). But the incidence of ≥ 3 grade CIN in two PEG-rhG-CSF subgroups was significantly lower than that in the rhG-CSF group (P < 0.001). The overall WBC and ANC levels in the PEG-rhG-CSF group were significantly higher than those in the rhG-CSF group (P < 0.001). In terms of CIN-related complications, less chemotherapy delay rate (1.1 vs. 7.5%, P = 0.092), less dose reduction rate (6.9 vs. 7.5%, P = 1.000), less antibiotic use rate (3.4 vs. 17.5%, P = 0.011) and less proportion of rhG-CSF rescue therapy (24.1 vs. 85.0%, P < 0.001) in the PEG-rhG-CSF group, and there were no significant differences between PEG-rhG-CSF subgroups. In the incidence of adverse events among the groups, there were no statistical differences. All patients undergoing rhG-CSF rescue treatment were mainly 4 grade (63.6%) and 3 grade (25.5%) CIN, and 10.9% of patients with 1 ~ 2 grade CIN who had high infection risk or had been infected. CONCLUSION: PEG-rhG-CSF has better efficacy and equal tolerance compared with rhG-CSF in preventing CIN in EBC patients receiving EC regimen. Moreover, a half-dose 3 mg PEG-rhG-CSF also had good efficacy. Last, patients with ≥ 3 grade CIN and others who have been assessed to be at high risk of infection or have co-infection should consider rhG-CSF or even antibiotic rescue treatment.
Subject(s)
Antineoplastic Agents , Breast Neoplasms , Neutropenia , Female , Humans , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/etiology , Granulocyte Colony-Stimulating Factor , Neutropenia/chemically induced , Neutropenia/prevention & control , Recombinant Proteins/adverse effects , Recombinant Proteins/therapeutic useABSTRACT
The rapid industrial development has contributed to worsening global pollution, necessitating the urgent development of highly sensitive, cost-effective, and portable gas sensors. In this work, the adsorption of CO, CO2, H2S, NH3, NO, NO2, O2, and SO2 gas molecules on pristine and Cu- and Al-decorated monolayer TiSe2 has been investigated based on first-principles calculations. First, the results of the phonon spectrum and ab initio molecular dynamics simulations demonstrated that TiSe2 is dynamically stable. In addition, compared to pristine TiSe2 (-0.029 to -0.154 eV), the adsorption energy of gas molecules (excluding CO2) significantly decreased after decorated with Cu or Al (-0.212 to -0.977 eV in Cu-decorated TiSe2, -0.438 to -2.896 eV in Al-decorated TiSe2). Among them, NH3 and NO2 have the lowest adsorption energies in Cu and Al-decorated TiSe2, respectively. Further research has shown that the decrease in adsorption energy of gas molecules is mainly due to orbital hybridization and charge transfer between decorated Cu and Al atoms and gas molecules. These findings suggest that TiSe2 decorated with Cu and Al can effectively improve its sensitivity to NH3 and NO2, respectively, making it promising in gas sensing applications.
ABSTRACT
Transthyretin (TTR) amyloidosis is a hereditary life-threatening disease characterized by deposition of amyloid fibrils. The main causes of TTR amyloidosis are mutations in the TTR gene that lead to the production of misfolded TTR protein. Reducing the production of toxic protein in the liver is a validated strategy to treat TTR amyloidosis. In this study, we established a humanized mouse model that expresses mutant human TTR (hTTR; V30M) protein in the liver to model TTR amyloidosis. Then, we compared the efficiency of reducing the expression of mutant hTTR by dual adeno-associated virus 8 (AAV8)-mediated split SpCas9 with that by single AAV8-mediated Nme2Cas9 in this model. With two gRNAs targeting different exons, dual AAV-mediated split SpCas9 system achieved efficiencies of 37% and 34% reduction of hTTR mRNA and reporter GFP expression, respectively, in the liver. Surprisingly, single AAV-mediated Nme2Cas9 treatment resulted in 65% and 71% reduction of hTTR mRNA and reporter GFP, respectively. No significant editing was identified in predicted off-target sites in the mouse and human genomes after Nme2Cas9 targeting. Thus, we provide proof of principle for using single AAV-mediated CRISPR-Nme2Cas9 to effectively reduce mutant hTTR expression in vivo, which may translate into gene therapy for TTR amyloidosis.
Subject(s)
Amyloid Neuropathies, Familial , Amyloid , Amyloid Neuropathies, Familial/genetics , Amyloid Neuropathies, Familial/therapy , Animals , Disease Models, Animal , Mice , Mice, Transgenic , Prealbumin/geneticsABSTRACT
Constructing metal-semiconductor interfaces by loading metal atoms onto two-dimensional material to build atomically dispersed single-atom catalysts (SACs) has emerged as a new frontier for improving atom utilization and designing multifunctional electrocatalysts. Nowadays, studies on black phosphorus nanosheets in electrocatalysis have received much attention and the successful preparation of metal nanoparticle/black phosphorus (BP) hybrid electrocatalysts indicates BP nanosheets can serve as a potential support platform for SACs. Herein, by using large-scale ab initio calculations, we explored a large composition space of SACs with transition metal atoms supported on BP monolayer (M-BP) and built a comprehensive picture of activity trend, stability, and electronic origin towards oxygen reduction and evolution reaction (ORR and OER) and hydrogen evolution reaction (HER). The results show that the catalytic activity can be widely tuned by reasonable regulation of metal atoms. Ni-, Pd-, and Pt-BP could effectively balance the binding strength of the target intermediates, thus achieving efficient bifunctional activity for OER and ORR. Favorable bifunctional catalytic performance for OER and HER can be realized on Rh-BP. Especially, Pt-BP exhibits promising trifunctional activity towards OER, ORR, and HER. Multiple-level corrections among overpotential, Gibbs free energy, orbital population, and d-band center reveal that the trend and origin of catalytic activity are intrinsically determined by the d-band center of metal sites. The thermodynamic and dynamic stability simulations demonstrate that the active metal centers are firmly anchored on BP substrate with intact M-P bonds. These findings provide a theoretical basis for the rational design of BP-based SACs toward promising multifunctional activity.
ABSTRACT
BACKGROUND: The correlations between circulating tumour DNA (ctDNA)-derived genomic markers and treatment response and survival outcome in Chinese patients with advanced breast cancer (ABC) have not been extensively characterized. METHODS: Blood samples from 141 ABC patients who underwent first-line standard treatment in Peking University Cancer Hospital were collected. A next-generation sequencing based liquid biopsy assay (PredicineCARE) was used to detect somatic mutations and copy number variations (CNVs) in ctDNA. A subset of matched blood samples and tumour tissue biopsies were compared to evaluate the concordance. RESULTS: Overall, TP53 (44.0%) and PIK3CA (28.4%) were the top two altered genes. Frequent CNVs included amplifications of ERBB2 (24.8%) and FGFR1 (8.5%) and deletions of CDKN2A (3.5%). PIK3CA/TP53 and FGFR1/2/3 variants were associated with drug resistance in hormone receptor-positive (HR +) and human epidermal growth factor receptor 2-positive (HER2 +) patients. The comparison of genomic variants across matched tumour tissue and ctDNA samples revealed a moderate to high concordance that was gene dependent. Triple-negative breast cancer (TNBC) patients harbouring TP53 or PIK3CA alterations had a shorter overall survival than those without corresponding mutations (P = 0.03 and 0.008). A high ctDNA fraction was correlated with a shorter progression-free survival (PFS) (P = 0.005) in TNBC patients. High blood-based tumor mutation burden (bTMB) was associated with a shorter PFS for HER2 + and TNBC patients (P = 0.009 and 0.05). Moreover, disease monitoring revealed several acquired genomic variants such as ESR1 mutations, CDKN2A deletions, and FGFR1 amplifications. CONCLUSIONS: This study revealed the molecular profiles of Chinese patients with ABC and the clinical validity of ctDNA-derived markers, including the ctDNA fraction and bTMB, for predicting treatment response, prognosis, and disease progression. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03792529. Registered January 3rd 2019, https://clinicaltrials.gov/ct2/show/NCT03792529 .
Subject(s)
Breast Neoplasms , Circulating Tumor DNA , Triple Negative Breast Neoplasms , Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Circulating Tumor DNA/genetics , Class I Phosphatidylinositol 3-Kinases/genetics , DNA Copy Number Variations , Female , High-Throughput Nucleotide Sequencing , Humans , Mutation/genetics , PrognosisABSTRACT
Tussilago farfara is of vital medical value. A new leaf spot disease was observed on T. farfara leaves, in Dingxi, Gansu Province, China, in October 2019. In order to research the pathogen, the diseased samples were collected for isolation and identification. The isolate KD3 was verified by pathogenicity test, as the pathogen causing the T. farfara leaf spot disease. Its morphological characteristics were consistent with Alternaria alternata, the colony color gray-green with concentric rings, conidia fusiform and pear-shaped, brown, with 1-7 septa and 0-3 longitudinal septa, conidia size (19. 62-44.49) µm × (6.97-10.53) µm, beak length (1.35-10.03) µm × (1.01-3.63) µm, and the spore phenotype was a dwarf tree-like chain of short conidia. Multilocus sequences analysis manifested that the internal transcribed spacer (ITS), Alternaria major allergen (Alta1), and Calcium barine (CAL) sequences of strain KD3 were most closely to A. alternata (A23), with the homology of 99.47%, 99.56% and 98.28%, respectively. Based on morphological and molecular characteristics, strain KD3 was identified as A. alternata. OA was the optimal medium for its growth and PCA medium was the optimal for sporulation. This is the first report of A. alternata causing T. farfara leaf spots in China.
Subject(s)
Alternaria , Tussilago , Alternaria/genetics , Calcium , China , AllergensABSTRACT
The formulation and training of unitary neural networks is the basis of an active modulation diffractive deep neural network. In this Letter, an optical random phase DropConnect is implemented on an optical weight to manipulate a jillion of optical connections in the form of massively parallel sub-networks, in which a micro-phase assumed as an essential ingredient is drilled into Bernoulli holes to enable training convergence, and malposed deflections of the geometrical phase ray are reformulated constantly in epochs, allowing for enhancement of statistical inference. Optically, the random micro-phase-shift acts like a random phase sparse griddle with respect to values and positions, and is operated in the optical path of a projective imaging system. We investigate the performance of the full-drilling and part-drilling phenomena. In general, random micro-phase-shift part-drilling outperforms its full-drilling counterpart both in the training and inference since there are more possible recombinations of geometrical ray deflections induced by random phase DropConnect.
Subject(s)
Neural Networks, ComputerABSTRACT
General solutions to the quantum Rabi model involve subspaces with an unbounded number of photons. However, for the multiqubit multimode case, we find special solutions with at most one photon for an arbitrary number of qubits and photon modes. Such solutions exist for arbitrary single qubit-photon coupling strength with constant eigenenergy, while still being qubit-photon entangled states. Taking advantage of their peculiarities and the reach of the ultrastrong coupling regime, we propose an adiabatic scheme for the fast and deterministic generation of a two-qubit Bell state and arbitrary single-photon multimode W states with nonadiabatic error less than 1%. Finally, we propose a superconducting circuit design to catch and release the W states, and shows the experimental feasibility of the multimode multiqubit quantum Rabi model.
ABSTRACT
Taking advantage of their ability to integrate their genomes into the host genome, lentiviruses have been used to rapidly produce transgenic mice in biomedical research. In most cases, transgenes delivered by lentiviral vectors have resisted silencing mediated by epigenetic modifications in mice. However, some studies revealed that methylation caused decreased transgene expression in mice. Therefore, there is conflicting evidence regarding the methylation-induced silencing of transgenes delivered by lentiviral transduction in mice. In this study, we present evidence that the human TTR transgene was silenced by DNA methylation in the liver of a transgenic mouse model generated by lentiviral transduction. The density of methylation on the transgene was increased during reproduction, and the expression of the transgene was completely silenced in mice of the F2 generation. Interestingly, 5-azacytidine (5-AzaC), a methyltransferase inhibitor, potently reactivated the silenced genes in neonatal mice whose hepatocytes were actively proliferating and led to stable transgene expression during development. However, 5-AzaC did not rescue liver transgene expression when administered to adult mice. Moreover, 5-AzaC at the given dose had low developmental toxicity in the newborn mice. In summary, we demonstrate the methylation-induced silencing of an exogenous gene in the liver of a mouse model generated by lentiviral transduction and show that the silenced transgene can be safely and efficiently reactivated by 5-AzaC treatment, providing an alternative way to obtain progeny with stable transgene expression in the case of the methylation of exogenous genes in transgenic mice generated by lentiviral transduction.
Subject(s)
DNA Methylation/genetics , Lentivirus/genetics , Prealbumin/genetics , Transgenes/genetics , Animals , Animals, Newborn , Azacitidine/pharmacology , DNA Methylation/drug effects , Gene Expression Regulation, Developmental/drug effects , Genetic Vectors/drug effects , Humans , Lentivirus/drug effects , Mice , Mice, Transgenic/geneticsABSTRACT
By means of quotient-graph associated crystal prediction method, a new graphyne allotrope with unique Dirac nodal grid state is reported in this work. It is named as 191-E24Y24-1 according to its hexagonal lattice (with P6/mmm symmetry, No. 191) containing 24 sp2-hybridized carbon atoms and 24 sp-hybridized ones. The first-principles results show that the total energy of 191-E24Y24-1 is more favorable than that of recent synthesizedß-graphdiyne and carbon ene-yne. It is also demonstrated to be dynamically, thermally, and mechanically stable. Interestingly, the 191-E24Y24-1 harbors intrinsic semimetal features showing intriguing hexagonal Dirac nodal grid state in the reciprocal space. Such unique electronic state is stable against small external tensile strains, and it is tunable under compression strains which will transform to new triangle Dirac nodal grid state. Moreover, a new metastable graphyne allotrope named 191-E12Y36-4 with Dirac nodal loop state is also observed in the process of stretching 191-E24Y24-1 with large tensile strains. The results presented in this work reveal two novel graphyne allotropes with exotic electronic properties. These discoveries are not only physical interesting, but also provide potential material candidates for carbon-based high performance electronic nanodevices.
ABSTRACT
We performed density functional theory calculations to investigate the electronic and magnetic properties of h-BN/MoS2 heterostructures intercalated with 3d transition-metal (TM) atoms, including V, Cr, Mn, Fe, Co, and Ni atoms. It was found that metal and magnetic semiconductor characteristics are induced in the h-BN/MoS2 heterostructures after intercalating TMs. In addition, the results demonstrate that h-BN sheets could promote charge transfer between the TMs and the heterogeneous structure. Specifically, the h-BN/MoS2 heterostructure transforms from an indirect semiconductor to a metal after intercalating V or Cr atoms in the interlayers. For Mn, Fe, and Co atoms, the bandgaps of the intercalated heterojunction systems become smaller when the spin polarization is 100% at the highest occupied molecular orbital level. However, the system intercalated with Ni atoms exhibits no spin polarization and non-magnetic character. Strong covalent-bonding interactions emerged between the intercalated TMs and the nearest S atom of the h-BN/MoS2 heterostructure. In addition, the magnetic moments of the TM atoms show a decreasing trend for all the interstitial intercalated heterostructures compared with their free-standing states. These results reveal that h-BN/MoS2 heterostructures with intercalated TMs are promising candidates for application in multifarious spintronic devices.
ABSTRACT
Thermal anisotropy/isotropy is one of the fundamental characteristics of the thermal properties of a material, playing a significant role in the high-performance thermal management in micro-/nanoelectronics. It has been well documented in the literature that the symmetry of geometric structures governs the anisotropy/isotropy of thermal transport. However, the fundamental correlation and the underlying mechanism remain unclear. In this paper, using a new two-dimensional (2D) van der Waals (vdW) phosphorus nanotube array as a case study, we show that the lattice thermal conductivity can be abnormally almost isotropic although the geometric structure presents remarkable anisotropy, which contradicts the previous consensus. The key factor for the abnormal isotropic thermal conductivity is mainly the essentially analogous group velocities along the intratube and intertube directions. Compared with a carbon-nanotube array, a traditional vdW system, a microscopic picture is established to underpin the underlying mechanism. The quasi-bond (non-covalent bonding, but far stronger than the vdW interatomic interaction) between the phosphorus nanotubes is found to be responsible for such diverse isotropic transport phenomena. The findings in this paper are expected to deepen our understanding of the anisotropy/isotropy thermal transport of materials and are also helpful for future thermal management technology.
ABSTRACT
Thousands of lncRNAs have been identified but few have been functionally characterized in triple negative breast cancer (TNBC). LINC00152 was known as cytoskeleton regulator RNA (CYTOR) and expressed in various cancers including breast cancer. But the underlying molecular mechanism of LINC00152 in pathogenesis of TNBC have not been elucidated. In our study, we identified that LINC00152 expression was dramatically elevated in TNBC tissue and cells. Inhibition or overexpression of LINC00152 obviously increased or suppressed PTEN protein expression but did not affect the mRNA expression level. Our further experiments showed up-regulated LINC00152 in TNBC obviously enhanced NEDD4-1 mediated ubiquitination and degradation of PTEN protein. Finally, we demonstrated that YY1 bound with LINC00152 promotor and mostly inhibited the transcription of LINC00152. Furthermore, analysis of clinical samples resource retrieved from databases suggested high LINC00152 expression was correlated with ER or PR negative expression, late TNM stage and lymphatic invasion, as well as shorter overall survival time in patients. Consequently, this study firstly reveals that up-regulated LINC00152 mediates PTEN protein stability attenuation in TNBC.
Subject(s)
Gene Expression Regulation, Neoplastic , PTEN Phosphohydrolase/genetics , RNA, Long Noncoding/genetics , Triple Negative Breast Neoplasms/genetics , YY1 Transcription Factor/genetics , Binding Sites , Cell Line, Tumor , Cell Movement , Cell Proliferation , Disease Progression , Female , Genes, Reporter , Humans , Luciferases/genetics , Luciferases/metabolism , Lymphatic Metastasis , Nedd4 Ubiquitin Protein Ligases/genetics , Nedd4 Ubiquitin Protein Ligases/metabolism , PTEN Phosphohydrolase/metabolism , Protein Binding , Protein Stability , Proteolysis , RNA, Long Noncoding/antagonists & inhibitors , RNA, Long Noncoding/metabolism , Signal Transduction , Survival Analysis , Triple Negative Breast Neoplasms/diagnosis , Triple Negative Breast Neoplasms/mortality , Triple Negative Breast Neoplasms/pathology , Ubiquitination , YY1 Transcription Factor/metabolismABSTRACT
Metastasis-associated protein 2 (MTA2) is overexpressed in certain malignancies, and plays important roles in tumour metastasis and progression. The present study highlights the function of MTA2 in pancreatic carcinoma through its role as a deacetylator of hypoxia-inducible factor-1α (HIF-1α) and a cotranscriptional factor for E-cadherin expression. We found that overexpression of MTA2 promoted, and knockdown of MTA2 inhibited, the invasion and proliferation of pancreatic carcinoma cells both in vitro and in xenograft models in vivo. We also found that MTA2 is transcriptionally upregulated by HIF-1α through a hypoxia response element (HRE) of the MTA2 promoter in response to hypoxia. Reciprocally, MTA2 deacetylates HIF-1α and enhances its stability through interacting with histone deacetylase 1 (HDAC1). Consequently, HIF-1α recruits MTA2 and HDAC1 to the HRE of the E-cadherin promoter, by which E-cadherin transcription is repressed. In agreement with these experimental results, MTA2 is positively associated with HIF-1α, but inversely correlated with E-cadherin, in pancreatic carcinoma samples. Moreover, data from The Cancer Genome Atlas on 172 pancreatic carcinomas indicate an association between high expression of MTA2 and short overall survival. Taken together, our study identifies MTA2 as a critical hub and potential therapeutic target to inhibit the progression and metastasis of pancreatic carcinoma. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Subject(s)
Adenocarcinoma/metabolism , Antigens, CD/metabolism , Cadherins/metabolism , Histone Deacetylases/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Pancreatic Neoplasms/metabolism , Repressor Proteins/metabolism , Acetylation , Adenocarcinoma/genetics , Adenocarcinoma/secondary , Animals , Antigens, CD/genetics , Cadherins/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation , Down-Regulation , Epithelial-Mesenchymal Transition , Female , Gene Expression Regulation, Neoplastic , Histone Deacetylase 1/metabolism , Histone Deacetylases/genetics , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Mice, Inbred BALB C , Neoplasm Invasiveness , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Protein Processing, Post-Translational , Protein Stability , Repressor Proteins/genetics , Response Elements , Signal Transduction , Transcription, Genetic , Tumor BurdenABSTRACT
The energy landscape of carbon is exceedingly complex, hosting diverse and important metastable phases, including diamond, fullerenes, nanotubes, and graphene. Searching for structures, especially those with large unit cells, in this landscape is challenging. Here we use a combined stochastic search strategy employing two algorithms (ab initio random structure search and random sampling strategy combined with space group and graph theory) to apply connectivity constraints to unit cells containing up to 100 carbon atoms. We uncover three low energy carbon polymorphs (Pbam-32, P6/mmm, and I4[over ¯]3d) with new topologies, containing 32, 36, and 94 atoms in their primitive cells, respectively. Their energies relative to diamond are 96, 131, and 112 meV/atom, respectively, which suggests potential metastability. These three carbon allotropes are mechanically and dynamically stable, insulating carbon crystals with superhard mechanical properties. The I4[over ¯]3d structure possesses a direct band gap of 7.25 eV, which is the widest gap in the carbon allotrope family. Silicon, germanium, and tin versions of Pbam-32, P6/mmm, and I4[over ¯]3d also show energetic, dynamical, and mechanical stability. The computed electronic properties show that they are potential materials for semiconductor and photovoltaic applications.