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In situ exsolution of metal nanoparticles (NPs) is emerging as an alternative technique to deliver thermally stable and evenly dispersed metal NPs, which exhibit excellent adhesion with conducting perovskite oxide supports. Here we provide the first demonstration that Ni metal NPs with high areal density (â¼175 µm-2) and fine size (â¼38.65 nm) are exsolved from an A-site-deficient perovskite stannate support (La0.2Ba0.7Sn0.9Ni0.1O3-δ (LBSNO)). The NPs are strongly anchored and impart coking resistance, and the Ni-exsolved stannates show exceptionally high electrical conductivity (â¼700 S·cm-1). The excellent conductivity is attributed to conduction between delocalized Sn 5s orbitals along with structural improvement toward ABO3 stoichiometry in the stannate support. We also reveal that experimental conditions with strong interaction must be optimized to obtain Ni exsolution without degrading the perovskite stannate framework. Our finding suggests a unique process to induce the formation of metal NPs embedded in stannate with excellent electrical properties.
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Caveolin-1 (Cav-1), a major structural component of cell membrane caveolae, is involved in a variety of intracellular signaling pathways as well as transmembrane transport. Cav-1, as a scaffolding protein, modulates signal transduction associated with cell cycle progression, cellular senescence, cell proliferation and death, lipid homeostasis, etc. Cav-1 is also thought to regulate the expression or activity of oncoproteins, such as Src family kinases, H-Ras, protein kinase C, epidermal growth factor, extracellular signal-regulated kinase, and endothelial nitric oxide synthase. Because of its frequent overexpression or mutation in various tumor tissues and cancer cell lines, Cav-1 has been speculated to play a role as an oncoprotein in cancer development and progression. In contrast, Cav-1 may also function as a tumor suppressor, depending on the type of cancer cells and/or surrounding stromal cells in the tumor microenvironment as well as the stage of tumors.
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Caveolina 1/metabolismo , Neoplasias/patologia , Transdução de Sinais , Microambiente Tumoral , Cavéolas/metabolismo , Transformação Celular Neoplásica , HumanosRESUMO
OBJECTIVE: This study examined social, cultural, and appraisal factors associated with Korean-American cancer patients' and their family caregivers' quality of life (QOL) and depression. METHODS: Data were from Korean-American cancer patients and their family caregivers (N = 60 dyads) living in the United States. Study aims were examined using descriptive statistics and multiple regression. RESULTS: For patients, higher social support and lower negative appraisal of illness predicted higher patient QOL; negative appraisal of illness also predicted higher patient depression. For caregivers, older age, having fewer traditional Korean values, and more modern (individualistic) values predicted higher caregiver QOL. Caregivers who held more modern values also had less depression. CONCLUSIONS: Higher support and less negative appraisal predicted better QOL in patients. For caregivers however, the type of cultural values they held (tradition or modern) was a key factor that predicted level of QOL and depression. Assessment of support and appraisal as well as attention to cultural values may enhance their QOL and reduce depression.
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Asiático/psicologia , Cuidadores/psicologia , Depressão/psicologia , Neoplasias/psicologia , Qualidade de Vida/psicologia , Adulto , Idoso , Atitude Frente a Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Apoio Social , Inquéritos e Questionários , Estados UnidosRESUMO
Hydrogen, the smallest and the lightest atomic element, is reversibly incorporated into interstitial sites in vanadium dioxide (VO2), a correlated oxide with a 3d(1) electronic configuration, and induces electronic phase modulation. It is widely reported that low hydrogen concentrations stabilize the metallic phase, but the understanding of hydrogen in the high doping regime is limited. Here, we demonstrate that as many as two hydrogen atoms can be incorporated into each VO2 unit cell, and that hydrogen is reversibly absorbed into, and released from, VO2 without destroying its lattice framework. This hydrogenation process allows us to elucidate electronic phase modulation of vanadium oxyhydride, demonstrating two-step insulator (VO2)-metal (HxVO2)-insulator (HVO2) phase modulation during inter-integer d-band filling. Our finding suggests the possibility of reversible and dynamic control of topotactic phase modulation in VO2 and opens up the potential application in proton-based Mottronics and novel hydrogen storage.
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BACKGROUND: The challenges of advanced cancer have health implications for patients and their family caregivers from diagnosis through end of life. The nature of the patient/caregiver experience suggests that their mental and physical health maybe interdependent, but limited empirical evidence exists. PURPOSE: This study used social cognitive theory as a framework to investigate individual and interpersonal influences on patients' and their family caregivers' mental health, physical health, and self-efficacy as individuals to manage the challenges of advanced disease over time. METHODS: Patients and caregivers (484 patient-caregiver dyads) completed surveys at baseline, 3 and 6 months. Longitudinal dyadic analysis techniques were used to examine (i)the influence that patients and caregivers had on their own mental health, physical health, and self-efficacy (actor effects)and (ii) the influence that they had on each other's health outcomes (partner effects). We also examined the influence of self-efficacy on mental and physical health over time. RESULTS: Consistent with our hypotheses, each person's mental health, physical health, and self-efficacy had significant effects on their own outcomes over time (actor effects). Patients and caregivers influenced one another's mental and physical health (partner effects), but not their self-efficacy. In addition, patients and caregivers with higher self-efficacy had better mental health, and their partners had better physical health. CONCLUSIONS: Patients' and caregivers' mental and physical health were interdependent. Each person's cancer-related self-efficacy influenced their own mental and physical health. However, a person's self-efficacy did not influence the other person's self-efficacy.
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Cuidadores/psicologia , Relações Interpessoais , Saúde Mental , Neoplasias/psicologia , Autoeficácia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Teoria Psicológica , Qualidade de Vida/psicologia , Inquéritos e Questionários , Adulto JovemRESUMO
PURPOSE: To understand the sources of social support and perceptions of cancer and the caregiving role for Korean American patients with cancer and their family caregivers. PARTICIPANTS & SETTING: Using convenience sampling, Korean American patients with cancer and their family caregivers were recruited from Korean American churches and community health agencies. METHODOLOGIC APPROACH: Semistructured interviews guided by the sociocultural stress and coping model were conducted with 12 dyads (N = 24) of Korean American patients with cancer and their family caregivers. Data were analyzed using thematic analysis. FINDINGS: Patients' social support sources included Korean cancer support programs, family or friends, and religion. Family caregivers' sources of social support were limited to religion and friends. IMPLICATIONS FOR NURSING: Nurses can encourage patients with cancer in racial and ethnic minority groups to attend cancer support programs offered in their primary language to enhance their quality of life during cancer survivorship. Culturally tailored interventions are needed to support the patients' family caregivers.
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Neoplasias , Qualidade de Vida , Humanos , Etnicidade , Asiático , Cuidadores , Grupos Minoritários , Apoio Social , FamíliaRESUMO
The stemness of bone marrow mesenchymal stem cells (BMSCs) is maintained by hypoxia. The oxygen level increases from vessel-free cartilage to hypoxic bone marrow and, furthermore, to vascularized bone, which might direct the chondrogenesis to osteogenesis and regenerate the skeletal system. Hence, oxygen was diffused from relatively low to high levels throughout a three-dimensional chip. When we cultured BMSCs in the chip and implanted them into the rabbit defect models of low-oxygen cartilage and high-oxygen calvaria bone, (i) the low oxygen level (base) promoted stemness and chondrogenesis of BMSCs with robust antioxidative potential; (ii) the middle level (two times ≥ low) pushed BMSCs to quiescence; and (iii) the high level (four times ≥ low) promoted osteogenesis by disturbing the redox balance and stemness. Last, endochondral or intramembranous osteogenesis upon transition from low to high oxygen in vivo suggests a developmental mechanism-driven solution to promote chondrogenesis to osteogenesis in the skeletal system by regulating the oxygen environment.
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Medula Óssea , Cartilagem , Animais , Coelhos , Osteogênese , Oxigênio , Hipóxia , Células da Medula Óssea , Células Cultivadas , Diferenciação CelularRESUMO
This paper describes a temperature-controllable bead affinity chromatography (BAC) in a microsystem for biomarker detection, and preparing samples for matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) analysis. Cancer marker proteins were captured in the microsystem by BAC with RNA aptamer-immobilized microbeads. The captured proteins were then denatured and released from the microbeads by controlling temperature. The microsystem consists of a microreactor for trapping microbeads and a temperature control unit for thermal treatment of the trapped beads. We used polymethylsilxoane or single crystalline silicon in fabricating two different types of reaction chamber to compare the differences in performance originated from the materials. Carcinoembryonic antigen was concentrated and purified from human serum using the microsystem and detected by MALDI-TOF MS to demonstrate the usefulness of the microsystem. The microsystem simplifies a sample preparation process required for protein analysis and cancer biomarker detection, which will accelerate the process of cancer research.
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Biomarcadores/sangue , Cromatografia de Afinidade/instrumentação , Neoplasias/diagnóstico , Temperatura , Sequência de Aminoácidos/genética , Humanos , Dados de Sequência Molecular , Compostos de Organossilício/química , Peptídeos/química , Peptídeos/genética , Polietilenoglicóis/química , Silanos/química , Propriedades de SuperfícieRESUMO
Mott threshold switching, which is observed in quantum materials featuring an electrically fired insulator-to-metal transition, calls for delicate control of the percolative dynamics of electrically switchable domains on a nanoscale. Here, we demonstrate that embedded metallic nanoparticles (NP) dramatically promote metastability of switchable metallic domains in single-crystal-like VO2 Mott switches. Using a model system of Pt-NP-VO2 single-crystal-like films, interestingly, the embedded Pt NPs provide 33.3 times longer 'memory' of previous threshold metallic conduction by serving as pre-formed 'stepping-stones' in the switchable VO2 matrix by consecutive electical pulse measurement; persistent memory of previous firing during the application of sub-threshold pulses was achieved on a six orders of magnitude longer timescale than the single-pulse recovery time of the insulating resistance in Pt-NP-VO2 Mott switches. This discovery offers a fundamental strategy to exploit the geometric evolution of switchable domains in electrically fired transition and potential applications for non-Boolean computing using quantum materials.
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The epitaxial growth of functional oxides using a substrate with a graphene layer is a highly desirable method for improving structural quality and obtaining freestanding epitaxial nanomembranes for scientific study, applications, and economical reuse of substrates. However, the aggressive oxidizing conditions typically used in growing epitaxial oxides can damage graphene. Here, we demonstrate the successful use of hybrid molecular beam epitaxy for SrTiO3 growth that does not require an independent oxygen source, thus avoiding graphene damage. This approach produces epitaxial films with self-regulating cation stoichiometry. Furthermore, the film (46-nm-thick SrTiO3) can be exfoliated and transferred to foreign substrates. These results open the door to future studies of previously unattainable freestanding oxide nanomembranes grown in an adsorption-controlled manner by hybrid molecular beam epitaxy. This approach has potentially important implications for the commercial application of perovskite oxides in flexible electronics and as a dielectric in van der Waals thin-film electronics.
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All-in-one treatments represent a paradigm shift in future medicine. For example, inflammatory bowel disease (IBD) is mainly diagnosed by endoscopy, which could be applied for not only on-site monitoring but also the intestinal lesion-targeted spray of injectable hydrogels. Furthermore, molecular conjugation to the hydrogels would program both lesion-specific adhesion and drug-free therapy. This study validated this concept of all-in-one treatment by first utilizing a well-known injectable hydrogel that underwent efficient solution-to-gel transition and nanomicelle formation as a translatable component. These properties enabled spraying of the hydrogel onto the intestinal walls during endoscopy. Next, peptide conjugation to the hydrogel guided endoscopic monitoring of IBD progress upon adhesive gelation with subsequent moisturization of inflammatory lesions, specifically by nanomicelles. The peptide was designed to mimic the major component that mediates intestinal interaction with Bacillus subtilis flagellin during IBD initiation. Hence, the peptide-guided efficient adhesion of the hydrogel nanomicelles onto Toll-like receptor 5 (TLR5) as the main target of flagellin binding and Notch-1. The peptide binding potently suppressed inflammatory signaling without drug loading, where TLR5 and Notch-1 operated collaboratively through downstream actions of tumor necrosis factor-alpha. The results were produced using a human colorectal cell line, clinical IBD patient cells, gut-on-a-chip, a mouse IBD model, and pig experiments to validate the translational utility.
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The current paradigm of cancer medicine focuses on patient- and/or cancer-specific treatments, which has led to continuous progress in the development of patient representatives (e.g., organoids) and cancer-targeting carriers for drug screening. As breakthrough concepts, i) living cancer tissues convey intact profiles of patient-specific microenvironmental signatures. ii) The growth mechanisms of cancer mass with intense cell-cell interactions can be harnessed to develop self-homing nano-targeting by using cancer cell-derived nanovesicles (CaNVs). Hence, a tissueoid model of ovarian cancer (OC) is developed by culturing OC patient tissues in a 3D gel chip, whose microchannel networks enable perfusion to maintain tissue viability. A novel model of systemic cancer responses is approached by xenografting OC tissueoids into ischaemic hindlimbs in nude mice. CaNVs are produced to carry general chemotherapeutics or new drugs under pre/clinical studies that target the BRCA mutation or energy metabolism, thereby increasing the test scope. This pioneer study cross-validates drug responses from the OC clinic, tissueoid, and animal model by demonstrating the alignment of results in drug type-specific efficiency, BRCA mutation-dependent drug efficiency, and metabolism inhibition-based anti-cancer effects. Hence, this study provides a directional foundation to accelerate the discovery of patient-specific drugs with CaNV application towards future precision medicine.
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Antineoplásicos/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Medicina de Precisão/métodos , Adulto , Idoso , Animais , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Modelos Animais de Doenças , Portadores de Fármacos/administração & dosagem , Feminino , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Organoides/efeitos dos fármacosRESUMO
The regeneration potential of implantable organ model hydrogels is applied to treat a loss of ovarian endocrine function in women experiencing menopause and/or cancer therapy. A rat ovariectomy model is used to harvest autologous ovary cells while subsequently producing a layer-by-layer form of follicle spheroids. Implantation of a microchannel network hydrogel with cell spheroids [vascularized hydrogel with ovarian spheroids (VHOS)] into an ischemic hindlimb of ovariectomized rats significantly aids the recovery of endocrine function with hormone release, leading to full endometrium regeneration. The VHOS implantation effectively suppresses the side effects observed with synthetic hormone treatment (i.e., tissue overgrowth, hyperplasia, cancer progression, deep vein thrombosis) to the normal levels, while effectively preventing the representative aftereffects of menopause (i.e., gaining fatty weight, inducing osteoporosis). These results highlight the unprecedented therapeutic potential of an implantable VHOS against menopause and suggest that it may be used as an alternative approach to standard hormone therapy.
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Hidrogéis , Ovário , Animais , Feminino , Hormônios , Humanos , Ovariectomia , Ratos , Esferoides CelularesRESUMO
Electronic phase modulation based on hydrogen insertion/extraction is kinetically limited by the bulk hydrogen diffusion or surface exchange reaction, so slow hydrogen kinetics has been a fundamental challenge to be solved for realizing faster solid-state electrochemical switching devices. Here we accelerate electronic phase modulation that occurs by hydrogen insertion in VO2 through vertically aligned 2D defects induced by symmetry mismatch between epitaxial films and substrates. By using domain-matching epitaxial growth of monoclinic VO2 films with lattice rotation and twinning on hexagonal Al2O3 substrates, the domain boundaries naturally align vertically; they provide a "highway" for hydrogen diffusion and surface exchange in VO2 films and overcome the limited rates of bulk diffusion and surface reaction. From the quantitative analysis of the deuterium (2H) isotope tracer exchange, it is confirmed that the tracer diffusion coefficient (D*) and surface exchange coefficient (k*) were increased by several orders of magnitude in VO2 films that had domain boundaries. These results yield fundamental insights into the mechanism by which mobile ions are inserted along extended defects and provide a strategy to overcome a limitation to switching speed in electrochemical devices that exploit ion insertion.
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Dynamically reconfigurable nanoscale tuning of visible light properties is one of the ultimate goals both in the academic field of nanophotonics and the optics industry demanding compact and high-resolution display devices. Among various efforts incorporating actively reconfigurable optical materials into metamaterial structures, phase-change materials have been in the spotlight owing to their optical tunability in wide spectral regions including the visible spectrum. However, reconfigurable modulation of visible light intensity has been limited with small modulation depth, reflective schemes, and a lack of profound theoretical background for universal design rules. Here, all-dielectric phase-change Fano metasurface gratings are demonstrated for strong dynamic full-space (reflection and transmission) modulation of visible intensities based on Fano resonances. By judicious periodic couplings between densely arranged meta-atoms containing VO2, phase-change induced thermo-optic modulation of full-space intensities is highly enhanced in the visible spectrum. By providing intuitive design rules, we envision that the proposed study would contribute to nanophotonics-enabled optoelectronics technologies for imaging and sensing.
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We report two types of signal enhancement strategy derived from the origin of mechanical response, surface stress and mass, of the dynamic mode microcantilever for the detection of PSA at low picogram scales (low femtomolar concentration). The PSA detection at extremely low concentration levels is crucial to the early detection of relapses of prostate cancer after the radical prostatectomy and the detection of breast cancer in patient's serum. There is a clear need for the ultrasensitive detection of PSA via simple and rapid diagnostic tools. From the motives, to increase the sensitivity of the microcantilever, PSA polyclonal antibody (PSA pAb) as an additional surface stress inducer and PSA polyclonal antibody-conjugated silica nanoparticles (pAb-SiNPs) as a mass inducer have been applied to the PSA-captured microcantilevers. From two types of sandwich assay, we could confirm the sensitivity enhancement effects (2 approximately 4 times enhanced at the same concentrations) enough to detect PSA at low picogram levels (LOD of 1 pg/mL or below). Moreover, surface stress due to steric interactions between epitope-specific monoclonal antibodies was assessed to support a signal amplification strategy by stress inducer, and the reduction of signal enhancement due to stiffness increase by the mass inducer was studied to clarify the sensitivity enhancement of the microcantilever by mass inducer.
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Antígeno Prostático Específico/análise , Anticorpos Monoclonais/química , Campos Eletromagnéticos , Humanos , Masculino , Nanopartículas , Nanotecnologia , Prostatectomia , Dióxido de Silício , Estresse Mecânico , Propriedades de SuperfícieRESUMO
BACKGROUND: The ginsenoside Rg3, one of active components of red ginseng, has chemopreventive and anticancer potential. Cancer stem cells retain self-renewal properties which account for cancer recurrence and resistance to anticancer therapy. In our present study, we investigated whether the standardized Korean Red Ginseng extract (RGE) and Rg3 could modulate the manifestation of breast cancer stem cell-like features through regulation of self-renewal activity. METHODS: The effects of RGE and Rg3 on the proportion of CD44high/CD24low cells, as representative characteristics of stem-like breast cancer cells, were determined by flow cytometry. The mammosphere formation assay was performed to assess self-renewal capacities of breast cancer cells. Aldehyde dehydrogenase activity of MCF-7 mammospheres was measured by the ALDEFLUOR assay. The expression levels of Sox-2, Bmi-1, and P-Akt and the nuclear localization of hypoxia inducible factor-1α in MCF-7 mammospheres were verified by immunoblot analysis. RESULTS: Both RGE and Rg3 decreased the viability of breast cancer cells and significantly reduced the populations of CD44high/CD24low in MDA-MB-231 cells. RGE and Rg3 treatment attenuated the expression of Sox-2 and Bmi-1 by inhibiting the nuclear localization of hypoxia inducible factor-1α in MCF-7 mammospheres. Suppression of the manifestation of breast cancer stem cell-like properties by Rg3 was mediated through the blockade of Akt-mediated self-renewal signaling. CONCLUSION: This study suggests that Rg3 has a therapeutic potential targeting breast cancer stem cells.
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Hydrogen spillover is a catalytic process that occurs by surface reaction and subsequent diffusion to reversibly provide a massive amount of hydrogen dopants in correlated oxides, but the mechanism at the surface of correlated oxides with metal catalyst are not well understood. Here we show that a significant amount of oxygen is released from the surface of correlated VO2 films during hydrogen spillover, contrary to the well-established observation of the formation of hydrogen interstitials in the bulk part of VO2 films. By using ambient-pressure X-ray photoelectron spectroscopy, we prove that the formation of surface oxygen vacancies is a consequence of a favorable reaction for the generation of weakly adsorbed H2O from surface O atoms that have low coordination and weak binding strength. Our results reveal the importance of in situ characterization to prove the dynamic change during redox reaction and present an opportunity to control intrinsic defects at the surface.
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Cancer stem cells (CSCs) are responsible for tumor initiation, metastasis and recurrence. Caveolin-1 (Cav-1) is a major protein of caveolae, which participates in various cellular functions, such as vesicle trafficking, cholesterol homeostasis, tumor progression, etc. In the present study, we investigated a role for Cav-1 in regulating the stemness of human breast cancer (MDA-MB-231) cells. Cav-1 expression was significantly lower in tumorspheres than in adherent cells. The silencing of Cav-1 enhanced stemness of MDA-MB-231â¯cells. Mechanistically, Cav-1 silencing was accompanied by enhanced expression of Bmi-1, which is a representative self-renewal regulator, and promoted epithelial-mesenchymal transition. In a CSC-like state, reduced Cav-1 depends on its destabilization through ubiquitin-proteasome degradation. We further found that Src-mediated phosphorylation of Cav-1 at the Tyr 14 residue is essential for its degradation. Taken together, these findings suggest that Cav-1 destabilization by Src may play a pivotal role in manifestation and maintenance of stemness in breast cancer cells.
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Neoplasias da Mama/patologia , Caveolina 1/química , Caveolina 1/metabolismo , Células-Tronco Neoplásicas/patologia , Quinases da Família src/metabolismo , Animais , Neoplasias da Mama/metabolismo , Caveolina 1/genética , Adesão Celular , Linhagem Celular Tumoral , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Células MCF-7 , Camundongos , Transplante de Neoplasias , Células-Tronco Neoplásicas/metabolismo , Fosforilação , Complexo Repressor Polycomb 1/metabolismo , Proteólise , UbiquitinaçãoRESUMO
Overproduction of prostaglandin E2 (PGE2) has been linked to enhanced tumor cell proliferation, invasiveness and metastasis as well as resistance to apoptosis. 15-Keto prostaglandin E2 (15-keto PGE2), a product formed from 15-hydroxyprostaglandin dehydrogenase-catalyzed oxidation of PGE2, has recently been shown to have anti-inflammatory and anticarcinogenic activities. In this study, we observed that 15-keto PGE2 suppressed the phosphorylation, dimerization and nuclear translocation of signal transducer and activator of transcription 3 (STAT3) in human mammary epithelial cells transfected with H-ras (MCF10A-ras). 15-Keto PGE2 inhibited the migration and clonogenicity of MCF10A-ras cells. In addition, subcutaneous injection of 15-keto PGE2 attenuated xenograft tumor growth and phosphorylation of STAT3 induced by breast cancer MDA-MB-231â¯cells. However, a non-electrophilic analogue, 13,14-dihydro-15-keto PGE2 failed to inhibit STAT3 signaling and was unable to suppress the growth and transformation of MCF10A-ras cells. These findings suggest that the α,ß-unsaturated carbonyl moiety of 15-keto PGE2 is essential for its suppression of STAT3 signaling. We observed that the thiol reducing agent, dithiothreitol abrogated 15-keto PGE2-induced STAT3 inactivation and disrupted the direct interaction between 15-keto PGE2 and STAT3. Furthermore, a molecular docking analysis suggested that Cys251 and Cys259 residues of STAT3 could be preferential binding sites for this lipid mediator. Mass spectral analysis revealed the covalent modification of recombinant STAT3 by 15-keto PGE2 at Cys259. Taken together, thiol modification of STAT3 by 15-keto PGE2 inactivates STAT3 which may account for its suppression of breast cancer cell proliferation and progression.