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If a bulk material can withstand a high load without any irreversible damage (such as plastic deformation), it is usually brittle and can fail catastrophically1,2. This trade-off between strength and fracture toughness also extends into two-dimensional materials space3-5. For example, graphene has ultrahigh intrinsic strength (about 130 gigapascals) and elastic modulus (approximately 1.0 terapascal) but is brittle, with low fracture toughness (about 4 megapascals per square-root metre)3,6. Hexagonal boron nitride (h-BN) is a dielectric two-dimensional material7 with high strength (about 100 gigapascals) and elastic modulus (approximately 0.8 terapascals), which are similar to those of graphene8. Its fracture behaviour has long been assumed to be similarly brittle, subject to Griffith's law9-14. Contrary to expectation, here we report high fracture toughness of single-crystal monolayer h-BN, with an effective energy release rate up to one order of magnitude higher than both its Griffith energy release rate and that reported for graphene. We observe stable crack propagation in monolayer h-BN, and obtain the corresponding crack resistance curve. Crack deflection and branching occur repeatedly owing to asymmetric edge elastic properties at the crack tip and edge swapping during crack propagation, which intrinsically toughens the material and enables stable crack propagation. Our in situ experimental observations, supported by theoretical analysis, suggest added practical benefits and potential new technological opportunities for monolayer h-BN, such as adding mechanical protection to two-dimensional devices.
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AIMS: This study aims to explore the function and mechanism of G Protein-coupled receptor class C group 5 member A (GPRC5A) in docetaxel-resistance and liver metastasis of breast cancer. METHODS: Single-cell RNA transcriptomic analysis and bioinformatic analysis are used to screen relevant genes in breast cancer metastatic hepatic specimens. MeRIP, dual-luciferase analysis and bioinformation were used to detect m6A modulation. Mass spectrometry (MS), co-inmunoprecipitation (co-IP) and immunofluorescence colocalization were executed to explore the mechanism of GPRC5A in breast cancer cells. RESULT: GPRC5A was upregulated in triple-negative breast cancer (TNBC) and was associated with a poor prognosis. In vitro and in vivo experiments demonstrated that knockdown of GPRC5A alleviated metastasis and resistance to docetaxel in TNBC. Overexpression of GPRC5A had the opposite effects. The m6A methylation of GPRC5A mRNA was modulated by METTL3 and YTHDF1, which facilitates its translation. GPRC5A inhibited the ubiquitination-dependent degradation of LAMTOR1, resulting in the recruitment of mTORC1 to lysosomes and activating the mTORC1/p70s6k signaling pathway. CONCLUSION: METTL3/YTHDF1 axis up-regulates GPRC5A expression by m6A methylation. GPRC5A activates mTORC1/p70s6k signaling pathway by recruiting mTORC1 to lysosomes, consequently promotes docetaxel-resistance and liver metastasis.
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Neoplasias Hepáticas , Neoplasias de Mama Triplo Negativas , Humanos , Docetaxel/farmacologia , Docetaxel/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Proteínas Quinases S6 Ribossômicas 70-kDa , Transdução de Sinais , Metilação , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Receptores Acoplados a Proteínas G/genética , Serina-Treonina Quinases TOR/genética , Alvo Mecanístico do Complexo 1 de Rapamicina , MetiltransferasesRESUMO
Intracellular gene transfers (IGTs) between the nucleus and organelles, including plastids and mitochondria, constantly reshape the nuclear genome during evolution. Despite the substantial contribution of IGTs to genome variation, the dynamic trajectories of IGTs at the pangenomic level remain elusive. Here, we developed an approach, IGTminer, that maps the evolutionary trajectories of IGTs using collinearity and gene reannotation across multiple genome assemblies. We applied IGTminer to create a nuclear organellar gene (NOG) map across 67 genomes covering 15 Poaceae species, including important crops. The resulting NOGs were verified by experiments and sequencing data sets. Our analysis revealed that most NOGs were recently transferred and lineage specific and that Triticeae species tended to have more NOGs than other Poaceae species. Wheat (Triticum aestivum) had a higher retention rate of NOGs than maize (Zea mays) and rice (Oryza sativa), and the retained NOGs were likely involved in photosynthesis and translation pathways. Large numbers of NOG clusters were aggregated in hexaploid wheat during 2 rounds of polyploidization, contributing to the genetic diversity among modern wheat accessions. We implemented an interactive web server to facilitate the exploration of NOGs in Poaceae. In summary, this study provides resources and insights into the roles of IGTs in shaping interspecies and intraspecies genome variation and driving plant genome evolution.
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Oryza , Poaceae , Poaceae/genética , Triticum/genética , Genoma de Planta/genética , Oryza/genética , Zea mays/genética , Evolução MolecularRESUMO
BACKGROUND: The repair of facial skin and soft tissue defects remains a clinical challenge. The author introduced a novel "table tennis racquet" random skin flap for wound repair after facial skin cancer excision and discussed its survival mechanisms. METHODS: A lateral mandibular neck skin flap shaped like a table tennis racquet with no well-known blood vessels at the narrow pedicle was designed in 31 cases to repair tissue defects. Among them, there were 8 cases of skin carcinoma in the frontotemporal area and 23 cases of skin carcinoma in the cheek. The flap area was 8.0 × 7.0 cm at maximum and 3.0 × 2.5 cm at minimum, with a pedicle width of 1.0-2.0 cm and a pedicle length of 2.0-6.0 cm. RESULTS: All 31 "table tennis racquet" random skin flaps survived, although there were 3 cases with delayed healing of distal flap bruising. All of them had an ideal local shape after repair with a concealed donor area and inconspicuous scars. CONCLUSIONS: This flap has a "table tennis racquet" shape with a pedicle without well-known blood vessels and has a length-to-width ratio that exceeds that of conventional random flaps, making it unconventional. Because of its long and narrow pedicle, it not only has a large rotation and coverage area but also can be designed away from the defect area, avoiding the defect of no donor tissue being localized near the defect. Overall, this approach is an ideal option for repairing tissue defects after enlarged excision of facial skin carcinoma.
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Neoplasias Faciais , Procedimentos de Cirurgia Plástica , Neoplasias Cutâneas , Retalhos Cirúrgicos , Humanos , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Faciais/cirurgia , Idoso , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos/irrigação sanguínea , Resultado do Tratamento , Transplante de Pele/métodos , Adulto , Cicatrização/fisiologia , Idoso de 80 Anos ou mais , Sobrevivência de EnxertoRESUMO
The blood-brain barrier (BBB) is essential for maintaining central nervous system (CNS) stability, and neuroinflammation may cause the dysfunction of the BBB. MicroRNA-146a (miR-146a) is closely associated with neuroinflammation, which showed significant upregulation in response to lipopolysaccharide (LPS) induction. Elucidating the relationship between LPS-induced miR-146a expression and the BBB could decipher the mechanism of many neurological diseases. Here, we constructed an in vitro microfluidic human-BBB (µF-hBBB) chip consisting of human umbilical vein vascular endothelial cells (HUVECs) and human astrocyte (HAs) cells. A tetrahedral DNA framework (TDF-3MB) nanoprobe was used to label miR-146a in HUVECs on µF-hBBB chips before and after LPS induction, and the study revealed a significant increase in miR-146a expression after LPS induction. We believe that such a µF-hBBB chip is a promising in vitro platform for further use in understanding CNS diseases.
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Lipopolissacarídeos , MicroRNAs , Humanos , Lipopolissacarídeos/farmacologia , MicroRNAs/genética , MicroRNAs/metabolismo , Barreira Hematoencefálica/metabolismo , Doenças Neuroinflamatórias , Microfluídica , Inflamação/induzido quimicamente , Inflamação/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , DNARESUMO
Accurate germplasm characterization is a vital step for accelerating crop genetic improvement, which remains largely infeasible for crops such as bread wheat (Triticum aestivum L.), which has a complex genome that undergoes frequent introgression and contains many structural variations. Here, we propose a genomic strategy called ggComp, which integrates resequencing data with copy number variations and stratified single-nucleotide polymorphism densities to enable unsupervised identification of pairwise germplasm resource-based Identity-By-Descent (gIBD) blocks. The reliability of ggComp was verified in wheat cultivar Nongda5181 by dissecting parental-descent patterns represented by inherited genomic blocks. With gIBD blocks identified among 212 wheat accessions, we constructed a multi-scale genomic-based germplasm network. At the whole-genome level, the network helps to clarify pedigree relationship, demonstrate genetic flow, and identify key founder lines. At the chromosome level, we were able to trace the utilization of 1RS introgression in modern wheat breeding by hitchhiked segments. At the single block scale, the dissected germplasm-based haplotypes nicely matched with previously identified alleles of "Green Revolution" genes and can guide allele mining and dissect the trajectory of beneficial alleles in wheat breeding. Our work presents a model-based framework for precisely evaluating germplasm resources with genomic data. A database, WheatCompDB (http://wheat.cau.edu.cn/WheatCompDB/), is available for researchers to exploit the identified gIBDs with a multi-scale network.
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Melhoramento Vegetal , Triticum , Pão , Variações do Número de Cópias de DNA , Polimorfismo de Nucleotídeo Único/genética , Reprodutibilidade dos Testes , Triticum/genéticaRESUMO
We developed a mobile superconducting strip photon detector (SSPD) system operated in a liquid-helium Dewar. By adopting highly disordered NbTiN thin films, we successfully enhanced the detection performance of superconducting strips at higher operation temperatures and realized SSPDs with nearly saturated detection efficiency at 4.2â K. Then we customized a compact liquid-helium Dewar and a battery-based electronic module to minimize the SSPD system. A mobile SSPD system was integrated, which showed a system detection efficiency of 72% for a 1550â nm wavelength with a dark count rate of 200 cps and a timing jitter of 67.2 ps. The system has a weight of 40â kg and a power consumption of 500â mW, which can work continuously for 20 hours. The metrics can be further optimized in accordance with the various practical application platforms, such as aircraft, drones, etc.
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BACKGROUND: Histone chaperones (HCs) are crucial for governing genome stability and gene expression in multiple cancers. However, the functioning of HCs in the tumor microenvironment (TME) is still not clearly understood. METHODS: Self-tested single-cell RNA-seq data derived from 6 breast cancer (BC) patients with brain and liver metastases were reanalyzed by nonnegative matrix factorization (NMF) algorithm for 36 HCs. TME subclusters were observed with BC and immunotherapy public cohorts to assess their prognosis and immune response. The biological effect of HSPA8, one of the HCs, was verified by transwell assay and wound-healing assays. RESULTS: Cells including fibroblasts, macrophages, B cells, and T cells, were classified into various subclusters based on marker genes. Additionally, it showed that HCs might be strongly associated with biological and clinical features of BC metastases, along with the pseudotime trajectory of each TME cell type. Besides, the results of bulk-seq analysis revealed that TME cell subclusters mediated by HCs distinguished significant prognostic value for BC patients and were relevant to patients' immunotherapy responses, especially for B cells and macrophages. In particular, CellChat analysis exhibited that HCs-related TME cell subclusters revealed extensive and diverse interactions with malignant cells. Finally, transwell and wound-healing assays exhibited that HSPA8 deficiency inhibited BC cell migration and invasion. CONCLUSIONS: Collectively, our study first dissected HCs-guided intercellular communication of TME that contribute to BC metastases.
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Graphene sitting on hexagonal boron nitride (h-BN) always exhibits excellent electrical properties. And the properties of graphene onh-BN are often dominated by its domain size and boundaries. Chemical vapor deposition (CVD) is a promising approach to achieve large size graphene crystal. However, the CVD growth of graphene onh-BN still faces challenges in increasing coverage of monolayer graphene because of a weak control on nucleation and vertical growth. Here, an auxiliary source strategy is adapted to increase the nucleation density of graphene onh-BN and synthesis continuous graphene films. It is found that both silicon carbide and organic polymer e.g. methyl methacrylate can assist the nucleation of graphene, and then increases the coverage of graphene onh-BN. By optimizing the growth temperature, vertical accumulation of graphitic materials can be greatly suppressed. This work provides an effective approach for preparing continuous graphene film onh-BN, and may bring a new sight for the growth of high quality graphene.
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The hydration of perfluorinated sulfonic-acid ionomers is the most important phenomenon that determines their transport and electrical properties. To bridge the gap between the macroscopic electrical properties and the microscopic water-uptake mechanism, we investigated the hydration process of a Nafion membrane using ambient-pressure x-ray photoelectron spectroscopy (APXPS) from vacuum up to â¼90% relative humidity at room temperature. The O 1s and S 1s spectra provided a quantitative analysis of the water content (λ) and the transformation of the sulfonic acid group (-SO3H) to its deprotonated type (-SO3 -) during the water-uptake process. Taking advantage of a specially designed two-electrode cell, the conductivity of the membrane was determined by electrochemical impedance spectroscopy before APXPS measurements with the same conditions, thereby establishing the connection between the electrical properties and the microscopic mechanism. By means of ab initio molecular dynamics simulations based on density functional theory, the core-level binding energies of O- and S-containing species in the Nafion + H2O system were obtained.
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BACKGROUND: Reproductive tract infections influenced a series of inflammatory processes which involved in the development of breast cancer, while the processes were largely affected by estrogen. The present study aimed to explore the associations of breast cancer risk and prognosis with reproductive tract infections and the modification effects of estrogen exposure. METHODS: We collected history of reproductive tract infections, menstruation and reproduction from 1003 cases and 1107 controls and a cohort of 4264 breast cancer patients during 2008-2018 in Guangzhou, China. We used logistic regression model to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for risk; Cox model was applied to estimate the hazard ratios (HRs) and 95% CIs for progression-free survival (PFS) and overall survival (OS). RESULTS: It was found that previous reproductive tract infections were negatively associated with breast cancer risk (OR = 0.80, 95%CI, 0.65-0.98), particularly for patients with more menstrual cycles (OR = 0.74, 95%CI, 0.57-0.96). Patients with previous reproductive tract infections experienced better OS (HR = 0.61; 95% CI, 0.40-0.94) and PFS (HR = 0.84; 95% CI, 0.65-1.09). This protective effect on PFS was only found in patients with more menstrual cycles (HR = 0.52, 95% CI:0.34-0.79, Pinteraction = 0.015). CONCLUSIONS: The findings suggested that reproductive tract infections may be protective for the initiation and development of breast cancer, particularly for women with a longer interval of lifetime estrogen exposure.
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Neoplasias da Mama , Infecções do Sistema Genital , Humanos , Feminino , Neoplasias da Mama/epidemiologia , Mama , Estrogênios/uso terapêutico , PrognósticoRESUMO
The present study collected data on traditional Chinese medicine(TCM) compounds effective in relieving pain from the patent database of the State Intellectual Property Office(SIPO), sorted out the TCM compounds against pain in patents, and analyzed the medication rules to provide references for the research and development of new TCM drugs against pain. The data were subjected to frequency statistics, association rules, cluster analysis, and complex network analysis by IBM SPSS Modeler 18.3 and SPSS Statistical 26.0. The results showed that among the 101 oral prescriptions included in the statistics, the top 5 drugs were Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Paeoniae Radix Alba, Chuanxiong Rhizoma, and Salviae Miltiorrhizae Radix et Rhizoma, and among the 49 external prescriptions included in the statistics, the top 5 drugs were Myrrha, Olibanum, Angelicae Dahuricae Radix, Borneolum Syntheticum, and Chuanxiong Rhizoma. Whether oral or external prescriptions, the drugs were mainly warm in nature, and bitter, pungent, and sweet in flavor. According to TCM complex network analysis, the core drugs were Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Paeoniae Radix Alba, and Chuanxiong Rhizoma in oral prescriptions, and Olibanum, Myrrha, Glycyrrhizae Radix et Rhizoma, Chuanxiong Rhizoma, and Angelicae Sinensis Radix in external prescriptions. Overall, the therapeutic principles of oral prescriptions were mainly replenishing Qi, nourishing blood, and promoting Qi and blood circulation, while those of external prescriptions were activating blood, resolving stasis, promoting Qi flow, and relieving pain on the basis of the oral prescriptions. In the future research and development of TCM compounds against pain, the prescriptions should be modified with mind-tranquilizing and depression-relieving drugs. With the modernization of TCM, the development of new pain-relieving TCM compound patents based on ancient methods and clinical experience adhering to the guidance of TCM treatment based on syndrome differentiation can meet the new demand for pain treatment in the current society and give full play to the advantages of TCM in pain treatment.
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Besouros , Franquincenso , Paeonia , Animais , Medicina Tradicional Chinesa , DorRESUMO
PURPOSE: Results of the associations between weight change after breast cancer diagnosis and prognosis were inconsistent. The modification effects of menopausal status and endocrine therapy on the associations remain poorly understood. METHODS: A total of 2016 breast cancer patients were recruited between October 2008 and January 2018 and followed up until December 31, 2019 in Guangzhou. Multivariate Cox models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for progression-free survival (PFS) in association with weight change after diagnosis. RESULTS: Weight loss at 2 years (HR = 1.34, 95% CI 0.87-2.06) or more than 2 years (HR = 1.95, 95% CI 1.22-3.10) after diagnosis increased risk of breast cancer progression. The adverse effect of weight loss was significantly more pronounced in post-menopausal than pre-menopausal women, particularly for weight loss at 2 years after diagnosis, with the HRs and 95% CIs of 2.41 (1.25-4.63) and 0.90 (0.49-1.64), respectively. Weight gain tended to reduce the risk of disease progression among patients with endocrine therapy but not for those with non-endocrine therapy; the significant interaction between weight gain at 2 years after diagnosis and endocrine therapy was observed (Pinteraction = 0.042). CONCLUSION: Our finding suggested that weight loss was detrimental to breast cancer prognosis, particularly for post-menopausal women, while weight gain may be a potential beneficial indicator for the patients with endocrine therapy but not for those with non-endocrine therapy.
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Neoplasias da Mama , Mama , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Feminino , Humanos , Prognóstico , Aumento de Peso , Redução de PesoRESUMO
The integrated in-plane growth of graphene nanoribbons (GNRs) and hexagonal boron nitride (h-BN) could provide a promising route to achieve integrated circuitry of atomic thickness. However, fabrication of edge-specific GNRs in the lattice of h-BN still remains a significant challenge. Here we developed a two-step growth method and successfully achieved sub-5-nm-wide zigzag and armchair GNRs embedded in h-BN. Further transport measurements reveal that the sub-7-nm-wide zigzag GNRs exhibit openings of the bandgap inversely proportional to their width, while narrow armchair GNRs exhibit some fluctuation in the bandgap-width relationship. An obvious conductance peak is observed in the transfer curves of 8- to 10-nm-wide zigzag GNRs, while it is absent in most armchair GNRs. Zigzag GNRs exhibit a small magnetic conductance, while armchair GNRs have much higher magnetic conductance values. This integrated lateral growth of edge-specific GNRs in h-BN provides a promising route to achieve intricate nanoscale circuits.
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BACKGROUND: The efficiency of capecitabine has been proven in early-stage triple negative breast cancer (eTNBC) with residue invasive tumor (non-pCR) after standard neoadjuvant chemotherapy (NACT). However, for those unselected eTNBC patients without screening from NACT (i.e., newly diagnosed eTNBC patients undergoing breast surgery followed by adjuvant systemic therapy), the value of capecitabine has still remains unclear. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate whether additional capecitabine in eTNBC patients could improve clinical outcomes. METHODS: Seven RCTs (USO 01062, FinXX, GEICAM/2003, CREATE-X, CIBOMA/2004, CBCSG-010 and SYSUCC-001) were identified in online databases until December 2020 and included in the meta-analysis. We extracted the survival data including disease/relapse-free survival (DFS/RFS) and overall survival (OS), and utilized the STATA software to calculate the summarized hazard ratios (HRs) and 95% confidence intervals (95%CIs). RESULTS: A total of 3329 eTNBC patients were enrolled in this meta-analysis, with 1640 receiving standard neo-/adjuvant chemo-regimes alone, and the other 1689 receiving an additional capecitabine use, respectively. Both DFS and OS were significantly improved with the addition of capecitabine, and the benefits remained consistent in those unselected eTNBC patients without screening from NACT. Subgroup analysis further proved that this improvement in DFS was significant in both nodal negative and positive patients. Similar benefits are also found across menopausal status (both pre- and post-menopause). Regarding toxicity, the hand-foot syndrome and neutropenia are the most common capecitabine related adverse events, and are mostly tolerable. CONCLUSIONS: The present meta-analysis of RCTs demonstrates for the first time that adding capecitabine to standard chemo-regimens could improve both DFS and OS in unselected eTNBC patients, and this benefit remains consistent regardless of nodal status and menopausal status, which may lead eTNBC therapy into a new era.
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Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Intervalo Livre de Doença , Feminino , Humanos , Terapia Neoadjuvante/métodos , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Human epidermal growth factor receptor 2-positive breast cancer (HER2+BC) is a common malignancy that is prone to recurrence and metastasis in the early stages, resulting in a poor prognosis for patients. Many studies have suggested that targeted therapy promotes clinical outcomes in HER2+BC. With the introduction of trastuzumab in 1998, the prognosis of patients with early HER2+BC has improved significantly. However, owing to obstinate drug resistance and adverse events, the addition of new agents in standardized treatment has become a research hotspot. These promising agents include antibodies, antibody-drug conjugates, tyrosine kinase inhibitors, and anti-HER2 combined therapies. This article provides a brief description of the biology of BC and the expression of HER2, with the aim to provide an overview of the therapeutic landscape of HER2+BC by reviewing research results and introducing the latest evidence to provide a reference for clinical treatment.
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Neoplasias da Mama , Neoplasias da Mama/patologia , Feminino , Humanos , Terapia de Alvo Molecular , Receptor ErbB-2/metabolismo , Trastuzumab/uso terapêuticoRESUMO
Metastatic tumor is a major contributor to death caused by breast cancer. However, effective and targeted therapy for metastatic breast cancer remains to be developed. Initially, we exploited a feasible biological rationale of the association between metastatic status and tumor-initiating properties in metastatic breast cancer stem cells (BCSCs). Further, we explored that circular RNA RANBP2-like and GRIP domain-containing protein 6 (circRGPD6) regulates the maintenance of stem cell-like characteristics of BCSCs. Targeted expression of circRGPD6 via human telomerase reverse transcriptase (hTERT) promoter-driven VP16-GAL4-woodchuck hepatitis virus post-transcriptional regulatory element (WPRE)-integrated systemic amplifier delivery composite vector (TV-circRGPD6) significantly inhibited expression of stem-cell marker CD44 and increased expression of the DNA damage marker p-H2AX. Furthermore, we determined TV-circRGPD6, alone or synergized with docetaxel, displays significant therapeutic responses on metastatic BCSCs. Mechanistic analyses exploited that TV-circRGPD6 suppresses BCSC-mediated metastasis via the microRNA (miR)-26b/YAF2 axis. Clinically, for the first time, we observed that expressions of circRGPD6 and YAF2 predict a favorable prognosis in patients with breast cancer, whereas expression of miR-26b is an unfavorable prognostic factor. Overall, we have developed a TV-circRGPD6 nanoparticle that selectively expresses circRGPD6 in metastatic BCSCs to eradicate breast cancer metastasis, therefore providing a novel avenue to treat breast cancers.
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Neoplasias da Mama/genética , Vetores Genéticos/genética , MicroRNAs/genética , Proteínas Musculares/genética , Nanopartículas , Células-Tronco Neoplásicas/metabolismo , RNA Circular/genética , Proteínas Repressoras/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Expressão Gênica , Técnicas de Transferência de Genes , Humanos , Interferência de RNARESUMO
The forkhead box O (FOXO) transcription factors (TFs) family are frequently mutated, deleted, or amplified in various human cancers, making them attractive candidates for therapy. However, their roles in pan-cancer remain unclear. Here, we evaluated the expression, prognostic value, mutation, methylation, and clinical features of four FOXO family genes (FOXO1, FOXO3, FOXO4, and FOXO6) in 33 types of cancers based on the Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases. We used a single sample gene set enrichment analysis (ssGSEA) algorithm to establish a novel index called "FOXOs score". Moreover, we investigated the association between the FOXOs score and tumor microenvironment (TME), the responses to multiple treatments, along with drug resistance. We found that the FOXO family genes participated in tumor progression and were related to the prognosis in various types of cancer. We calculated the FOXOs score and found that it was significantly correlated with multiple malignant pathways in pan-cancer, including Wnt/beta-catenin signaling, TGF-beta signaling, and hedgehog signaling. In addition, the FOXOs score was also associated with multiple immune-related characteristics. Furthermore, the FOXOs score was sensitive for predicting the efficacy of diverse treatments in multiple cancers, especially immunotherapy. In conclusion, FOXO family genes were vital in pan-cancer and were strongly correlated with the TME. A high FOXOs score indicated an excellent immune-activated TME and sensitivity to multiple treatments. Hence, the FOXOs score might potentially be used as a biomarker in patients with a tumor.
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Resistencia a Medicamentos Antineoplásicos , Fatores de Transcrição Forkhead , Multiômica , Neoplasias , Humanos , Fatores de Transcrição Forkhead/genética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Microambiente TumoralRESUMO
Monometallic cyanide clusterfullerenes (CYCFs) represent a unique branch of endohedral clusterfullerenes with merely one metal atom encapsulated, offering a model system for elucidating structure-property correlation, while up to now only C82 and C76 cages have been isolated for the pristine CYCFs. C84 is one of the most abundant fullerenes and has 24 isomers obeying the isolated pentagon rule (IPR), among which 14 isomers have been already isolated, whereas the C2v(17)-C84 isomer has lower relative energy than several isolated isomers but never been found for empty and endohedral fullerenes. Herein, four novel C84-based pristine CYCFs with variable encapsulated metals and isomeric cages, including MCN@C2(13)-C84 (M = Y, Dy, Tb) and DyCN@C2v(17)-C84, have been synthesized and isolated, fulfilling the first identification of the missing C2v(17)-C84 isomer, which can be interconverted from the C2(13)-C84 isomer through two steps of Stone-Wales transformation. The molecular structures of these four C84-based CYCFs are determined unambiguously by single-crystal X-ray diffraction. Surprisingly, although the ionic radii of Y3+, Dy3+, and Tb3+ differ slightly by only 0.01 Å, such a subtle difference leads to an obvious change in the metal-cage interactions, as inferred from the distance between the metal atom and the nearest hexagon center of the C2(13)-C84 cage. On the other hand, upon altering the isomeric cage from DyCN@C2(13)-C84 to DyCN@C2v(17)-C84, the Dy-cage distance changes as well, indicating the interplay between the encapsulated DyCN cluster and the outer cage. Therefore, we demonstrate that the metal-cage interactions within CYCFs can be steered via both internal and external routes.
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Superconducting nanowire single-photon detectors (SNSPDs) have attracted remarkable interest for visible and near-infrared single-photon detection due to their outstanding performance. However, conventional SNSPDs are generally used as binary photon-counting detectors. Another important characteristic of light, i.e., polarization, which can provide additional information of the object, has not been resolved using the standalone SNSPD. In this work, we present a first prototype of the polarimeter based on a four-pixel superconducting nanowire array, capable of resolving the polarization state of linearly-polarized light at the single-photon level. The detector array design is based on a division of focal plane configuration in which the orientation of each nanowire division (pixel) is offset by 45°. Each single nanowire pixel operates as a combination of a photon detector and almost linear polarization filter, with an average polarization extinction ratio of â¼10. The total system detection efficiency of the array is â¼1% at a total dark count rate of 680 cps, with a timing jitter of 126 ps, when the detector array is free-space coupled and illuminated with 1550-nm photons. The mean errors of the measured angle of polarization and degree of linear polarization were about -3° and 0.12, respectively. Furthermore, we successfully demonstrated polarization imaging at low-light level using the proposed detector. Our results pave the way for the development of a single-photon sensitive, fast, and large-scale integrated polarization polarimeter or imager. Such detector may find promising application in photon-starved polarization resolving and imaging with high spatial and temporal resolution.