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Rechargeable magnesium batteries (RMBs) are considered as one of the most promising candidates for next-generation batteries. However, the popularization of RMBs is seriously plagued due to the lack of suitable non-nucleophilic electrolytes and the passivation of Mg anode. Herein, a novel non-nucleophilic electrolyte is developed by introducing (s)-1-methoxy-2-propylamine (M4) into themagnesium aluminum chloride complex (MACC)-like electrolyte. The as-synthesizes Mg(AlCl4 )2 -IL-DME-M4 electrolyte enables robust reversible cycling of Mg plating/stripping with low overpotential, high anodic stability, and ionic conductivity (8.56 mS cm-1 ). These features should be mainly attributed to the in situ formation of an MgF2 containing Mg2+ -conducting interphase, which dramatically suppresses the passivation and parasitic reaction of Mg anode with electrolyte. Remarkably, the Mg/S batteries assemble with as-synthesize electrolyte and a new type MoS2 @CMK/S cathode deliver unprecedented electrochemical performance. Specifically, the Mg/S battery exhibited the highest reversible capacity up to 1210 mAh g-1 at 0.1 C, excellent rate capability and satisfactory long-term cycling stability with a reversible capacity of 370 mAh g-1 (coulombic efficiency of ≈100%) at 1.0 C for 600 cycles. The study findings provide a novel strategy and inspiration for designing efficient non-nucleophilic Mg electrolyte and suitable sulfur-host materials for practical Mg/S battery applications.
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Mn-based cathode material Li1.20Mn0.52Ni0.20Co0.08O2 was proposed and ameliorated by surface-coating poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) and doping Ga3+. X-ray diffraction and high-resolution transmission electron microscopy studies revealed that part of Ga3+ replacing the Ni site could reduce the Li+/Ni2+ mixing by forming a well-ordered layered structure and a homogeneous coating layer of PEDOT:PSS is covered on the surface of Li1.20Mn0.52Ni0.19Co0.08Ga0.01O2. The results of the electrochemical studies demonstrated the higher initial charging-discharging Coulombic efficiency, and outstanding rate capabilities and cyclic performance were obtained for the PEDOT:PSS-covered and Ga3+-doped samples. Especially, 2 wt % PEDOT:PSS-coated Li1.20Mn0.52Ni0.19Co0.08Ga0.01O2 delivered 38.3 mAh g-1, which is larger than the pristine cathode at a 5C high rate. Meanwhile, it could retain 189.6 mAh g-1 (90.3% of its initial discharge capacity at 45 °C) after 300 cycles with a 1C rate, while the pristine cathode only delivered 149.7 mAh g-1 with 80.7% cycling retention left. The results strongly suggested that such PEDOT:PSS-coated and Ga3+-doped Mn-based layered structure materials demonstrated high potential as a cathode candidate especially for high-energy applications.
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AIMS: Hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome is caused by germline mutations in the Fumarate hydratase (FH) gene. In young women, the syndrome often presents with symptomatic uterine leiomyomas, leading to myomectomy or hysterectomy. In this study, we aimed to investigate the incidence and mutational profiles of FH-negative leiomyomas from young patients, thus allowing for early identification and triage of syndromic patients for surveillance. METHODS AND RESULTS: We evaluated 153 cases of uterine leiomyomas from women aged up to 30 years for loss of FH expression by tissue microarray (TMA)-based immunohistochemical staining. Mutational analysis of tumours with loss of FH was carried out by polymerase chain reaction (PCR) amplification of 10 exons within the FH gene and subsequent Sanger sequencing. The status of promoter methylation was assessed by bisulphite sequencing. Loss of FH protein expression was detected in seven (4.6%) of 153 tested uterine leiomyomas from young patients. All FH-negative leiomyomas displayed staghorn vasculature and fibrillary/neurophil-like cytoplasm. We found that six (86%) of seven FH-negative tumours detected by immunohistochemistry harboured FH mutations, 50% of which contained germline mutations. In particular, the germline mutational rate in FH gene was 2.0% (three of 153 cases). Bisulphite sequencing analysis failed to detect promoter methylation in any of the seven tumours. CONCLUSION: Our study showed a relatively high rate of FH germline mutation in FH-negative uterine leiomyomas from patients aged up to 30 years. While genetic mutations confer protein expression loss, epigenetic regulation of the FH gene appears to be unrelated to this phenotype.
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Fumarato Hidratase/genética , Leiomioma/genética , Leiomiomatose/genética , Síndromes Neoplásicas Hereditárias/genética , Neoplasias Cutâneas/genética , Neoplasias Uterinas/genética , Adolescente , Adulto , Análise Mutacional de DNA , Feminino , Fumarato Hidratase/metabolismo , Mutação em Linhagem Germinativa , Humanos , Imuno-Histoquímica , Leiomioma/enzimologia , Leiomioma/patologia , Leiomiomatose/enzimologia , Leiomiomatose/patologia , Mutação , Síndromes Neoplásicas Hereditárias/enzimologia , Síndromes Neoplásicas Hereditárias/patologia , Prevalência , Estudos Retrospectivos , Neoplasias Cutâneas/enzimologia , Neoplasias Cutâneas/patologia , Análise Serial de Tecidos , Neoplasias Uterinas/enzimologia , Neoplasias Uterinas/patologia , Adulto JovemRESUMO
Hexamerin was originally identified as a storage protein but later confirmed to be involved in many physiological processes. In the present study, we cloned and characterized a novel hexamerin complementary DNA sequence from the Chinese oak silkworm, Antheraea pernyi (Ap-hexamerin), which shows high homology with reported insect methionine-rich hexamerins. The tissue distribution and time course of expression demonstrated that Ap-hexamerin was predominantly synthesized in the fat body and the expression level was significantly increased in response to the microbial challenge, suggesting the relevance of Ap-hexamerin to immune responses. In further immune functional studies, Ap-hexamerin was confirmed to take part in the upregulation of prophenoloxidase (PPO) activation in A. pernyi haemolymph triggered by pathogen-associated molecular patterns (PAMPs). Additional molecular interaction analysis revealed that Ap-hexamerin is capable of binding the PAMPs used in the phenoloxidase assay, suggesting hexamerin in A. pernyi may positively regulate haemolymph PPO activation, acting as a pattern recognition protein.
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Imunidade Inata/genética , Proteínas de Insetos/genética , Mariposas/genética , Mariposas/imunologia , Sequência de Aminoácidos , Animais , Catecol Oxidase/metabolismo , DNA Complementar/genética , Precursores Enzimáticos/metabolismo , Proteínas de Insetos/química , Proteínas de Insetos/imunologia , Larva , Filogenia , Alinhamento de SequênciaRESUMO
A 53-yr-old woman who presented with elevated renal indices was discovered to have a 4.5 cm right renal mass and an incidental 9.7 cm left ovarian mass on imaging studies. She underwent a partial nephrectomy and bilateral salpingo-oophorectomy, revealing a chromophobe renal cell carcinoma and an unusual ovarian neoplasm with epithelioid cells displaying prominent signet ring cell-like morphology. Immunohistochemical analysis of the ovarian neoplasm demonstrated that the tumor cells were diffusely immunoreactive for smooth muscle markers and negative for all tested cytokeratins and epithelial membrane antigen. On the basis of these results, the tumor was interpreted as an unusual epithelioid smooth muscle neoplasm with extensive signet ring cell-like features. Along with primary ovarian signet ring stromal tumors and sclerosing stromal tumors, this example adds epithelioid smooth muscle neoplasms with unusual cytologic alterations to the list of uncommon nonepithelial tumors that can simulate metastatic signet ring cell carcinoma (Krukenberg tumor) in the ovary.
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Carcinoma de Células em Anel de Sinete/patologia , Células Epitelioides/patologia , Neoplasias Ovarianas/patologia , Tumor de Músculo Liso/patologia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Primary osteosarcoma (OS) of the uterus is distinctly rare. We report a case of primary uterine OS with pulmonary metastasis in a 74-yr-old woman. Histopathologic features of the uterine tumor were in keeping with a pure chondroblastic OS composed of neoplastic cells with osteoblastic/chondroblastic differentiation and neoplastic bone formation. Despite treatment with Doxorubicin and Olaratumab and later with palliative radiation therapy, the patient died 7 mo after hysterectomy due to multiple distant metastases. A targeted next-generation sequencing assay based on a 637-gene panel was performed to analyze genetic alterations in this highly aggressive tumor, but no somatic mutations that are amenable to targeted therapy were detected. Rather, a 51-nucleotide deletion mutation including partial exon 2 of mediator complex subunit 12 (MED12), a gene commonly mutated in leiomyoma, breast fibroadenoma and phyllodes tumor, was identified. Given the MED12 mutation in this uterine OS, we propose possible mechanisms that account for the origin and development of this tumor.
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Complexo Mediador/genética , Mutação , Osteossarcoma/patologia , Neoplasias Uterinas/patologia , Idoso , Feminino , Humanos , Neoplasias Pulmonares/secundário , Osteossarcoma/genética , Osteossarcoma/terapia , Neoplasias Uterinas/genética , Neoplasias Uterinas/terapiaRESUMO
Protein marker levels in formalin-fixed, paraffin-embedded tissue sections traditionally have been assayed by chromogenic immunohistochemistry and evaluated visually by pathologists. Pathologist scoring of chromogen staining intensity is subjective and generates low-resolution ordinal or nominal data rather than continuous data. Emerging digital pathology platforms now allow quantification of chromogen or fluorescence signals by computer-assisted image analysis, providing continuous immunohistochemistry values. Fluorescence immunohistochemistry offers greater dynamic signal range than chromogen immunohistochemistry, and combined with image analysis holds the promise of enhanced sensitivity and analytic resolution, and consequently more robust quantification. However, commercial fluorescence scanners and image analysis software differ in features and capabilities, and claims of objective quantitative immunohistochemistry are difficult to validate as pathologist scoring is subjective and there is no accepted gold standard. Here we provide the first side-by-side validation of two technologically distinct commercial fluorescence immunohistochemistry analysis platforms. We document highly consistent results by (1) concordance analysis of fluorescence immunohistochemistry values and (2) agreement in outcome predictions both for objective, data-driven cutpoint dichotomization with Kaplan-Meier analyses or employment of continuous marker values to compute receiver-operating curves. The two platforms examined rely on distinct fluorescence immunohistochemistry imaging hardware, microscopy vs line scanning, and functionally distinct image analysis software. Fluorescence immunohistochemistry values for nuclear-localized and tyrosine-phosphorylated Stat5a/b computed by each platform on a cohort of 323 breast cancer cases revealed high concordance after linear calibration, a finding confirmed on an independent 382 case cohort, with concordance correlation coefficients >0.98. Data-driven optimal cutpoints for outcome prediction by either platform were reciprocally applicable to the data derived by the alternate platform, identifying patients with low Nuc-pYStat5 at ~3.5-fold increased risk of disease progression. Our analyses identified two highly concordant fluorescence immunohistochemistry platforms that may serve as benchmarks for testing of other platforms, and low interoperator variability supports the implementation of objective tumor marker quantification in pathology laboratories.
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Biomarcadores Tumorais/análise , Neoplasias da Mama/metabolismo , Imunofluorescência/métodos , Processamento de Imagem Assistida por Computador/métodos , Feminino , Humanos , Reprodutibilidade dos TestesRESUMO
The molecular mechanisms underlying progression of prostate cancer (PCa) to castrate-resistant (CR) and metastatic disease are poorly understood. Our previous mechanistic work shows that inhibition of transcription factor Stat5 by multiple alternative methods induces extensive rapid apoptotic death of Stat5-positive PCa cells in vitro and inhibits PCa xenograft tumor growth in nude mice. Furthermore, STAT5A/B induces invasive behavior of PCa cells in vitro and in vivo, suggesting involvement of STAT5A/B in PCa progression. Nuclear STAT5A/B protein levels are increased in high-grade PCas, CR PCas, and distant metastases, and high nuclear STAT5A/B expression predicts early disease recurrence and PCa-specific death in clinical PCas. Based on these findings, STAT5A/B represents a therapeutic target protein for advanced PCa. The mechanisms underlying increased Stat5 protein levels in PCa are unclear. Herein, we demonstrate amplification at the STAT5A/B gene locus in a significant fraction of clinical PCa specimens. STAT5A/B gene amplification was more frequently found in PCas of high histologic grades and in CR distant metastases. Quantitative in situ analysis revealed that STAT5A/B gene amplification was associated with increased STAT5A/B protein expression in PCa. Functional studies showed that increased STAT5A/B copy numbers conferred growth advantage in PCa cells in vitro and as xenograft tumors in vivo. The work presented herein provides the first evidence of somatic STAT5A/B gene amplification in clinical PCas.
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Amplificação de Genes , Neoplasias da Próstata/genética , Fator de Transcrição STAT5/genética , Proteínas Supressoras de Tumor/genética , Animais , Variações do Número de Cópias de DNA , DNA de Neoplasias/genética , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Hibridização in Situ Fluorescente , Masculino , Camundongos , Camundongos Nus , Gradação de Tumores , Transplante de Neoplasias , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Recidiva , Fator de Transcrição STAT5/biossíntese , Transplante Heterólogo , Células Tumorais Cultivadas , Proteínas Supressoras de Tumor/biossínteseRESUMO
Although great success has been achieved in various computer vision tasks, deep neural networks (DNNs) suffer dramatic performance degradation when evaluated on out-of-distribution data. Domain generalization (DG) is proposed to handle this problem by learning domain-agnostic information from multiple source domains to generalize well on unseen target domains. Several methods resort to Fourier transform due to its simplicity and efficiency. They argue that amplitude spectra imply domain-specific information, which should be suppressed, while phase counterparts imply domain-agnostic information, which should be preserved. However, these methods only suppress the domain-specific information in source domains and neglect the relationship with target domains, leading to the persistence of the domain gap. Besides, these methods preserve domain-agnostic information by keeping phase components unchanged, causing them to be underutilized. In this paper, we propose Dual Branch Augmentation Module (DBAM) by leveraging Fourier transform and taking advantage of both amplitude and phase spectra. For the amplitude branch, we propose Inner-domain Amplitude Distribution Rectification (IADR) and Cross-domain Amplitude Dirichlet Mixup (CADM) to stabilize the training process and explore more feature space. In addition, we propose Test-time Amplitude Prototype Calibration (TAPC) to construct the connection between source and target domains during evaluation to further mitigate the domain gap. For the phase branch, we propose Random Symmetric Phase Perturbation (RSPP) to enhance the robustness for recognizing domain-agnostic information. With the combined contributions of the two branches, DBAM significantly surpasses other state-of-the-art (SOTA) methods. Extensive experiments on four benchmarks and further analysis demonstrate the effectiveness of DBAM.
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Generalização Psicológica , Aprendizagem , Benchmarking , Calibragem , Redes Neurais de ComputaçãoRESUMO
Domain generalization (DG) aims to generalize from a large amount of source data that are fully annotated. However, it is laborious to collect labels for all source data in practice. Some research gets inspiration from semi-supervised learning (SSL) and develops a new task called semi-supervised domain generalization (SSDG). Unlabeled source data is trained jointly with labeled one to significantly improve the performance. Nevertheless, different research adopts different settings, leading to unfair comparisons. Moreover, the initial annotation of unlabeled source data is random, causing unstable and unreliable training. To this end, we first specify the training paradigm, and then leverage active learning (AL) to handle the issues. We further develop a new task called Active Semi-supervised Domain Generalization (ASSDG), which consists of two parts, i.e., SSDG and AL. We delve deep into the commonalities of SSL and AL and propose a unified framework called Gradient-Similarity-based Sample Filtering and Sorting (GSSFS) to iteratively train the SSDG and AL parts. Gradient similarity is utilized to select reliable and informative unlabeled source samples for these two parts respectively. Our methods are simple yet efficient, and extensive experiments demonstrate that our methods can achieve the best results on the DG datasets in the low-data regime without bells and whistles.
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Generalização Psicológica , Aprendizagem Baseada em Problemas , Transporte Proteico , Aprendizado de Máquina SupervisionadoRESUMO
Peptidoglycan recognition proteins (PGRPs) are a family of pattern recognition receptors that play a critical role in the immune response of invertebrates and vertebrates. Herein, the short ApPGRP-D gene was cloned from the model lepidopteran Antheraea pernyi. Quantitative PCR (qPCR) confirmed that ApPGRP-D is an immune-related protein and that the expression of ApPGRP-D can be induced by microorganisms. ApPGRP-D is a broad-spectrum pattern recognition protein that activates the prophenoloxidase cascade activation system and promotes the agglutination of microbial cells. Likely due to its amidase activity, ApPGRP-D can inhibit the growth of E. coli and S. aureus. In addition, we demonstrated for the first time that zinc ions, as important metal coenzymes, could promote multiple functions of ApPGRP-D but not its amidase activity.
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Proteínas de Transporte , Imunidade Humoral , Proteínas de Insetos , Mariposas , Animais , Mariposas/imunologia , Mariposas/genética , Mariposas/metabolismo , Mariposas/microbiologia , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Escherichia coli , Staphylococcus aureus , Sequência de Aminoácidos , Antibacterianos/farmacologia , Catecol Oxidase/metabolismo , Clonagem Molecular , Zinco/metabolismo , Precursores EnzimáticosRESUMO
Groundwater environments are complex, and traditional advanced oxidation technologies mainly based on free radicals have limitations such as poor selectivity and low interference resistance, making it difficult to efficiently degrade target pollutants in groundwater. Therefore, we developed a sludge-based biochar-supported FeMg-layered double hydroxide catalyst (BC@FeMg-LDH) for the catalytic degradation of 2, 4-dichlorophenol (2, 4-DCP) using persulfate (PDS) as an oxidant. The removal efficiency of the catalyst exceeded 95%, showing high oxidation activity in a wide pH range while being almost unaffected by reducing substances and ions in the environment. Meanwhile, under neutral conditions, the leaching of metal ions from BC@FeMg-LDH was minimal, thereby eliminating the risk of secondary pollution. According to quenching experiments and electron paramagnetic resonance spectroscopy, the main active species during BC@FeMg-LDH/PDS degradation of 2, 4-DCP is 1O2, indicating a non-radical reaction mechanism dominated by 1O2. Characterization techniques, including X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy, revealed that the carbonyl (C = O) and metal hydroxyl (M-OH) groups on the material surface were the main reactive sites mediating 1O2 generation. The 1O2 generation mechanism during the reaction involved ketone-like activation of carbonyl groups on the biochar surface and complexation of hydroxyl groups on the material surface with PDS, resulting in the formation of O2·- and further generation of 1O2. 1O2 exhibited high selectivity toward electron-rich organic compounds such as 2, 4-DCP and demonstrated strong interference resistance in complex groundwater environments. Therefore, BC@FeMg-LDH holds promising applications for the remediation of organic-contaminated groundwater.
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Água Subterrânea , Hidróxidos , Hidróxidos/química , Carvão Vegetal/química , Metais , FenóisRESUMO
INTRODUCTION: Emerging evidence in estrogen receptor-positive breast cancer supports the notion that prolactin-Stat5 signaling promotes survival and maintenance of differentiated luminal cells, and loss of nuclear tyrosine phosphorylated Stat5 (Nuc-pYStat5) in clinical breast cancer is associated with increased risk of antiestrogen therapy failure. However, the molecular mechanisms underlying loss of Nuc-pYStat5 in breast cancer remain poorly defined. METHODS: We investigated whether moderate extracellular acidosis of pH 6.5 to 6.9 frequently observed in breast cancer inhibits prolactin-Stat5 signaling, using in vitro and in vivo experimental approaches combined with quantitative immunofluorescence protein analyses to interrogate archival breast cancer specimens. RESULTS: Moderate acidosis at pH 6.8 potently disrupted signaling by receptors for prolactin but not epidermal growth factor, oncostatin M, IGF1, FGF or growth hormone. In breast cancer specimens there was mutually exclusive expression of Nuc-pYStat5 and GLUT1, a glucose transporter upregulated in glycolysis-dependent carcinoma cells and an indirect marker of lactacidosis. Mutually exclusive expression of GLUT1 and Nuc-pYStat5 occurred globally or regionally within tumors, consistent with global or regional acidosis. All prolactin-induced signals and transcripts were suppressed by acidosis, and the acidosis effect was rapid and immediately reversible, supporting a mechanism of acidosis disruption of prolactin binding to receptor. T47D breast cancer xenotransplants in mice displayed variable acidosis (pH 6.5 to 6.9) and tumor regions with elevated GLUT1 displayed resistance to exogenous prolactin despite unaltered levels of prolactin receptors and Stat5. CONCLUSIONS: Moderate extracellular acidosis effectively blocks prolactin signaling in breast cancer. We propose that acidosis-induced prolactin resistance represents a previously unrecognized mechanism by which breast cancer cells may escape homeostatic control.
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Acidose/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Prolactina/metabolismo , Fator de Transcrição STAT5/metabolismo , Microambiente Tumoral , Animais , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Modelos Animais de Doenças , Espaço Extracelular/metabolismo , Feminino , Glucose/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Glicólise , Xenoenxertos , Humanos , Fosforilação , Transporte Proteico , Receptores da Prolactina/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: Prolactin (PRL) is essential for normal mammary gland development. PRL promotes mammary tumor formation in rodents and elevated serum prolactin is associated with increased risk of estrogen-receptor positive breast cancer in women. On the other hand, PRL may also exert pro-differentiation effects and act to suppress invasive features of established breast cancer. Previously published limited global transcript profiling analyses of prolactin-regulated gene expression in human breast cancer cells have exclusively been performed in vitro. The present study aimed to shed new light on how PRL modulates estrogen receptor (ER)-positive breast cancer through global transcript profiling of a human breast cancer xenograft model in vivo. METHODS: The prolactin-responsive human T47D breast cancer cell line was xenotransplanted into nude mice and global transcript profiling was carried out following treatment with or without human PRL for 48 h. A subset of PRL-modulated transcripts was further validated using qRT-PCR and immunohistochemistry. RESULTS: The in vivo analyses identified 130 PRL-modulated transcripts, 75 upregulated and 55 downregulated, based on fold change >1.6 and P-value <0.05. From this initial panel of transcripts, a subset of 18 transcripts with established breast cancer-relevance were selected and validated by qRT-PCR. Some but not all of the transcripts were also PRL-modulated in vitro. The selected PRL-modulated transcripts were tested for dependence on Stat5, Jak1 or Jak2 activation, and for co-regulation by 17ß-estradiol (E2). The protein encoded by one of the PRL-regulated transcripts, PTHrP, was examined in a panel of 92 human breast cancers and found by in situ quantitative immunofluorescence analysis to be highly positively correlated with nuclear localized and tyrosine phosphorylated Stat5. Gene Ontology analysis revealed that PRL-upregulated genes were enriched in pathways involved in differentiation. Finally, a gene signature based on PRL-upregulated genes was associated with prolonged relapse-free and metastasis-free survival in breast cancer patients. CONCLUSIONS: This global analysis identified and validated a panel of PRL-modulated transcripts in an ER-positive human breast cancer xenotransplant model, which may have value as markers of relapse-free and metastasis-free survival. Gene products identified in the present study may facilitate ongoing deciphering of the pleiotropic effects of PRL on human breast cancer.
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Neoplasias da Mama/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Prolactina/farmacologia , Animais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Estradiol/farmacologia , Feminino , Ontologia Genética , Humanos , Janus Quinase 1/metabolismo , Janus Quinase 2/metabolismo , Camundongos Nus , Metástase Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos , Proteína Relacionada ao Hormônio Paratireóideo/metabolismo , Fosfotirosina/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes , Fator de Transcrição STAT5/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
This work reports the design and preparation of novel organic (polyvinyl alcohol, PVA)-inorganic (neodymium nitrate, Nd(NO3)3) hybrid coatings on micro-arc oxidation (MAO) coating for magnesium (Mg) alloy corrosion protection. X-ray diffractometer, X-ray photoelectron spectroscopy, fourier transform infrared spectroscopy, field emission scanning electron microscope, Energy Dispersive X-ray spectrometer and surface roughness were applied to characterize the chemical composition and surface morphology of the coatings. The corrosion resistance of the coatings was evaluated by electrochemical and salt spray tests. The results suggested that the formation of PVA-Nd3+ and PVA-Mg2+ complexes promoted the enrichment of Nd3+ on the surface, and thereby improved the sealing quality and compactness of the coating. Interestingly, when the coating was damaged, the Nd3+ ions were transformed to their carbonates and covered the active sites, and thus exhibiting self-healing function. Further, the corrosion resistance of PVA-Nd3+ modified MAO composite coating on AZ31 Mg alloy was improved.
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Rapid corrosion and bacterial infection are obstacles to put into use biodegradable magnesium (Mg) alloy as biomedical materials. In this research, an amorphous calcium carbonate (ACC)@curcumin (Cur) loaded poly-methyltrimethoxysilane (PMTMS) coating prepared by self-assembly method on micro-arc oxidation (MAO) coated Mg alloy has been proposed. Scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy are adopted to analyze the morphology and composition of the obtained coatings. The corrosion behaviour of the coatings is estimated by hydrogen evolution and electrochemical tests. The spread plate method without or with 808 nm near-infrared irradiation is applied to evaluate the antimicrobial and photothermal antimicrobial ability of the coatings. Cytotoxicity of the samples is tested by 3-(4,5)-dimethylthiahiazo(-z-y1)-2,5-di- phenytetrazoliumromide (MTT) and live/dead assay culturing with MC3T3-E1 cells. Results show that the MAO/ACC@Cur-PMTMS coating exhibited favourable corrosion resistance, dual antibacterial ability, and good biocompatibility. Cur was employed as an antibacterial agent and photosensitizer for photothermal therapy. The core of ACC significantly improved the loading of Cur and the deposition of hydroxyapatite corrosion products during degradation, which greatly promoted the long-term corrosion resistance and antibacterial activity of Mg alloys as biomedical materials.
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Curcumina , Corrosão , Antibacterianos , Ligas , Materiais Biocompatíveis , Magnésio , Carbonato de Cálcio , Materiais Revestidos BiocompatíveisRESUMO
INTRODUCTION: Signal transducer and activator of transcripton-5a (Stat5a) and its close homologue, Stat5b, mediate key physiological effects of prolactin and growth hormone in mammary glands. In breast cancer, loss of nuclear localized and tyrosine phosphorylated Stat5a/b is associated with poor prognosis and increased risk of antiestrogen therapy failure. Here we quantify for the first time levels of Stat5a and Stat5b over breast cancer progression, and explore their potential association with clinical outcome. METHODS: Stat5a and Stat5b protein levels were quantified in situ in breast-cancer progression material. Stat5a and Stat5b transcript levels in breast cancer were correlated with clinical outcome in 936 patients. Stat5a protein was further quantified in four archival cohorts totaling 686 patients with clinical outcome data by using multivariate models. RESULTS: Protein levels of Stat5a but not Stat5b were reduced in primary breast cancer and lymph node metastases compared with normal epithelia. Low tumor levels of Stat5a but not Stat5b mRNA were associated with poor prognosis. Experimentally, only limited overlap between Stat5a- and Stat5b-modulated genes was found. In two cohorts of therapy-naïve, node-negative breast cancer patients, low nuclear Stat5a protein levels were an independent marker of poor prognosis. Multivariate analysis of two cohorts treated with antiestrogen monotherapy revealed that low nuclear Stat5a levels were associated with a more than fourfold risk of unfavorable outcome. CONCLUSIONS: Loss of Stat5a represents a new independent marker of poor prognosis in node-negative breast cancer and may be a predictor of response to antiestrogen therapy if validated in randomized clinical trials.
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Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Fator de Transcrição STAT5/metabolismo , Adulto , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Núcleo Celular/metabolismo , Terapia Combinada , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Avaliação de Resultados da Assistência ao Paciente , Fosforilação , Prognóstico , Transporte Proteico , Resultado do Tratamento , Carga TumoralRESUMO
A novel l-histidine based ionic liquid (LHIL) was developed and successfully synthesized. Its structure was confirmed by Fourier-transform infrared spectroscopy, UV-vis spectroscopy, X-ray photoelectron spectroscopy, 1H-NMR and high-resolution mass spectrometry. The outstanding corrosion inhibition effect of the LHIL on mild steel in 1 M hydrochloric acid was thoroughly evaluated by Tafel plots, electrochemical impedance spectroscopy, and localized electrochemical strategies. The results revealed that the corrosion of mild steel was effectively suppressed by the adsorption of LHIL on its surface, and the best inhibition efficiency reached 98.8%. The adsorption behavior of LHIL on steel obeyed the Langmuir adsorption isotherm, which involved both chemisorption and physisorption. Theoretical calculations indicated the strong chemisorption of LHIL on steel, as proved by the low energy gap (ΔE = 0.0522 eV) and high binding energy (E binding = 303.47 kcal mol-1), which clearly confirmed the effectiveness of LHIL for steel protection.
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In unsupervised domain adaptation (UDA), many efforts are taken to pull the source domain and the target domain closer by adversarial training. Most methods focus on aligning distributions or features between the source domain and the target domain. However, little attention is paid to the interaction between finer-grained levels, such as classes or samples of the two domains. In contrast to UDA, another transfer learning task, i.e., few-shot learning (FSL), takes full advantage of the finer-grained-level alignment. Many FSL methods implement the interaction between samples of support sets and query sets, leading to significant improvements. We wonder whether we can get some inspiration from these methods and bring such ideas of FSL to UDA. To this end, we first take a closer look at the differences between FSL and UDA and bridge the gap between them by high-confidence sample selection (HCSS). Then we propose cross-attention map generation module (CAMGM) to interact samples selected by HCSS. Moreover, we propose a simple but efficient method called cross-attention-map-based regularization (CAMR) to regularize the feature maps generated by the feature extractor. Experiments on three challenging datasets demonstrate that CAMR can bring solid improvements when added to the original objective. More specifically, the proposed CAMR can outperform original methods by 1% to 2% in most tasks without bells and whistles.
Assuntos
Atenção , AprendizagemRESUMO
Embedding two-dimension micro/nanocontainers containing corrosion inhibitors into organic coating is a well-established concept to impart the coating with enhanced barrier and self-healing feature. Herein, a versatile nanoemulsion assembly approach was used to synthesis nanocarriers combing mesoporous polydopamine nanoparticles (MPDA) with reduced graphene oxide (GO), which was employed to encapsulate corrosion inhibitors (benzotriazole, BTA) to improve the anticorrosion performance of waterborne epoxy coating. The BTA release profiles from synthesized GO with MPDA (PDAG) demonstrated the rapid pH-triggered activities to acidic corrosion environment. With the addition of BTA-loaded PDAG, the composited epoxy coatings presented self-repairing behavior and enhanced corrosion resistance during long-term immersion. The outstanding anticorrosion performance is attributed to dual-protection mechanism provided by BTA-loaded PDAG: (1) MPDA endows GO with satisfactory interface compatibilities and thus provides impermeable barrier to delay the penetration process of corrosive electrolyte; (2) corrosion inhibitors including BTA and polydopamine form the adsorption layers on bare steel surface to resist continuous corrosion at metal/coating interface.