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Distinct viral gene expression characterizes Epstein-Barr virus (EBV) infection in EBV-producing marmoset B-cell (B95-8) and EBV-associated gastric carcinoma (SNU719) cell lines. CCCTC-binding factor (CTCF) is a structural chromatin factor that coordinates chromatin interactions in the EBV genome. Chromatin immunoprecipitation followed by sequencing against CTCF revealed 16 CTCF binding sites in the B95-8 and SNU719 EBV genomes. The biological function of one CTCF binding site (S13 locus) located on the BamHI A right transcript (BART) miRNA promoter was elucidated experimentally. Microscale thermophoresis assay showed that CTCF binds more readily to the stable form than the mutant form of the S13 locus. EBV BART miRNA clusters encode 22 miRNAs, whose roles are implicated in EBV-related cancer pathogenesis. The B95-8 EBV genome lacks a 11.8-kb EcoRI C fragment, whereas the SNU719 EBV genome is full-length. ChIP-PCR assay revealed that CTCF, RNA polymerase II, H3K4me3 histone, and H3K9me3 histone were more enriched at S13 and S16 (167-kb) loci in B95-8 than in the SNU719 EBV genome. 4C-Seq and 3C-PCR assays using B95-8 and SNU719 cells showed that the S13 locus was associated with overall EBV genomic loci including 3-kb and 167-kb region in both EBV genomes. We generated mutations in the S13 locus in bacmids with or without the 11.8-kb BART transcript unit (BART(+/-)). The S13 mutation upregulated BART miRNA expression, weakened EBV latency, and reduced EBV infectivity in the presence of EcoRI C fragment. Another 3C-PCR assay using four types of BART(+/-)·S13(wild-type(Wt)/mutant(Mt)) HEK293-EBV cells revealed that the S13 mutation decreased DNA associations between the 167-kb region and 3-kb in the EBV genome. Based on these results, CTCF bound to the S13 locus along with the 11.8-kb EcoRI C fragment is suggested to form an EBV 3-dimensional DNA loop for coordinated EBV BART miRNA expression and infectivity.
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Infecciones por Virus de Epstein-Barr , Infección Latente , MicroARNs , Humanos , Infecciones por Virus de Epstein-Barr/genética , Factor de Unión a CCCTC/genética , Herpesvirus Humano 4/genética , Histonas/genética , Células HEK293 , MicroARNs/genética , Cromatina , Sitios de UniónRESUMEN
Non-small-cell lung cancer (NSCLC) frequently harbors mutations in the epidermal growth factor receptor (EGFR), with exon 20 insertions comprising 1-10% of these mutations. EGFR exon 20 insertions are less responsive to conventional tyrosine kinase inhibitors (TKIs), leading to the development of targeted agents. This review explores key therapeutic agents, such as Amivantamab, Mobocertinib, Poziotinib, Zipalertinib, and Sunvozertinib, which have shown promise in treating NSCLC with EGFR exon 20 insertions. Amivantamab, a bispecific antibody-targeting EGFR and c-MET, demonstrates significant efficacy, particularly when combined with chemotherapy. Mobocertinib, a TKI, selectively targets EGFR exon 20 mutations but faces limitations in efficacy. Poziotinib, another oral TKI, shows mixed results due to mutation-specific responses. Zipalertinib and Sunvozertinib have emerged as potent TKIs with promising clinical data. Despite these advances, challenges in overcoming resistance mutations and improving central nervous system penetration remain. Future research should focus on optimizing first-line combination therapies and enhancing diagnostic strategies for comprehensive mutation profiling.
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Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Exones , Neoplasias Pulmonares , Terapia Molecular Dirigida , Inhibidores de Proteínas Quinasas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/genética , Receptores ErbB/antagonistas & inhibidores , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Exones/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Mutagénesis Insercional , Mutación , Antineoplásicos/uso terapéuticoRESUMEN
Skeletal muscle atrophy can be defined as a decrease of muscle volume caused by injury or lack of use. This condition is associated with reactive oxygen species (ROS), resulting in various muscular disorders. We acquired 2D and 3D images using micro-computed tomography in gastrocnemius and soleus muscles of sciatic-denervated mice. We confirmed that sciatic denervation-small animal model reduced muscle volume. However, the intraperitoneal injection of Oenothera odorata root extract (EVP) delayed muscle atrophy compared to a control group. We also investigated the mechanism of muscle atrophy's relationship with ROS. EVP suppressed expression of SOD1, and increased expression of HSP70, in both H2O2-treated C2C12 myoblasts and sciatic-denervated mice. Moreover, EVP regulated apoptotic signals, including caspase-3, Bax, Bcl-2, and ceramide. These results indicate that EVP has a positive effect on reducing the effect of ROS on muscle atrophy.
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Músculo Esquelético/efectos de los fármacos , Atrofia Muscular/tratamiento farmacológico , Oenothera/química , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Caspasa 3/genética , Caspasa 3/metabolismo , Línea Celular , Ceramidas/metabolismo , Desnervación/efectos adversos , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Proteínas HSP70 de Choque Térmico/agonistas , Proteínas HSP70 de Choque Térmico/genética , Proteínas HSP70 de Choque Térmico/metabolismo , Inyecciones Intraperitoneales , Masculino , Ratones , Ratones Endogámicos C57BL , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Atrofia Muscular/etiología , Atrofia Muscular/metabolismo , Atrofia Muscular/patología , Mioblastos/citología , Mioblastos/efectos de los fármacos , Mioblastos/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Nervio Ciático/cirugía , Superóxido Dismutasa/antagonistas & inhibidores , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa-1 , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismoRESUMEN
We report our hydrodynamic and energy analyses of droplet coalescence on water repellent surfaces including hydrophobic, superhydrophobic and oil-infused superhydrophobic surfaces. The receding contact angle has significant effects on the contact line dynamics since the contact line dissipation was more significant during the receding mode than advancing. The contact line dynamics is modeled by the damped harmonic oscillation equation, which shows that the damping ratio and angular frequency of merged droplets decrease as the receding contact angle increases. The fast contact line relaxation and the resulting decrease in base area during coalescence were crucial to enhance the mobility of coalescing sessile droplets by releasing more surface energy with reducing dissipation loss. The superhydrophobic surface converts â¼42% of the released surface energy to the kinetic energy via coalescence before the merged droplet jumps away from the surface, while oil-infused superhydrophobic and hydrophobic surfaces convert â¼30% and â¼22%, respectively, for the corresponding time. This work clarifies the mechanisms of the contact line relaxation and energy conversion during the droplet coalescence on water repellent surfaces, and helps develop water repellent condensers.
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NF-κB is one of the key transcription factors activated by receptor activator of NF-κB ligand (RANKL) during osteoclast differentiation. The 8-kDa dynein L chain (LC8) was previously identified as a novel NF-κB regulator. However, its physiological role as an NF-κB inhibitor remains elusive. In this study, we showed the inhibitory role of LC8 in RANKL-induced osteoclastogenesis and signaling pathways and its protective role in osteolytic animal models. LC8 suppressed RANKL-induced osteoclast differentiation, actin ring formation, and osteoclastic bone resorption. LC8 inhibited RANKL-induced phosphorylation and subsequent degradation of IκBα, the expression of c-Fos, and the consequent activation of NFATc1, which is a pivotal determinant of osteoclastogenesis. LC8 also inhibited RANKL-induced activation of JNK and ERK. LC8-transgenic mice exhibited a mild osteopetrotic phenotype. Moreover, LC8 inhibited inflammation-induced bone erosion and protected against ovariectomy-induced bone loss in mice. Thus, our results suggest that LC8 inhibits osteoclast differentiation by regulating NF-κB and MAPK pathways and provide the molecular basis of a new strategy for treating osteoporosis and other bone diseases.
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Resorción Ósea/prevención & control , Dineínas Citoplasmáticas/fisiología , Osteoclastos/patología , Osteólisis/prevención & control , Ligando RANK/antagonistas & inhibidores , Transducción de Señal/fisiología , Actinas/análisis , Animales , Diferenciación Celular , Dineínas Citoplasmáticas/genética , Dineínas Citoplasmáticas/toxicidad , Evaluación Preclínica de Medicamentos , Activación Enzimática , Regulación de la Expresión Génica/fisiología , Genes fos , Humanos , Proteínas I-kappa B/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Macrófagos/citología , Macrófagos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Inhibidor NF-kappaB alfa , FN-kappa B/metabolismo , Factores de Transcripción NFATC/biosíntesis , Factores de Transcripción NFATC/genética , Osteólisis/fisiopatología , Osteopetrosis/genética , Osteoporosis Posmenopáusica/fisiopatología , Osteoporosis Posmenopáusica/prevención & control , Fosforilación , Procesamiento Proteico-Postraduccional , Proteínas Proto-Oncogénicas c-fos/biosíntesis , Proteínas Recombinantes de Fusión/fisiología , Proteínas Recombinantes de Fusión/toxicidadRESUMEN
Bone mineralization is a normal physiological process, whereas ectopic calcification of soft tissues is a pathological process that leads to irreversible tissue damage. We have established a coxsackievirus B3 (CVB3)-infected mouse model that manifests both osteoporosis and ectopic calcification specifically in heart, pancreas, and lung. The CVB3-infected mice showed increased serum concentrations of both cytokines including IL-1ß, TNF-α, and the receptor activator of NF-κB ligand (RANKL) that stimulate osteoclast formation and of the osteoclast-derived protein tartrate-resistant acid phosphatase 5b. They exhibited more osteoclasts in bone, with no change in the number of osteoblasts, and a decrease in bone formation and the serum concentration of osteoblast-produced osteocalcin. These results indicate that CVB3-induced osteoporosis is likely due to upregulation of osteoclast formation and function, in addition to decreased osteoblast activity. In addition, the serum in the CVB3-infected mice contained a high inorganic phosphate content, which causes ectopic calcification. RANKL treatment induced an increase in the in vitro cardiac fibroblast calcification by inorganic phosphate via the upregulation of osteogenic BMP2, SPARC, Runx2, Fra-1, and NF-κB signaling. We finally observed that i.p. administration of RANK-Fc, a recombinant antagonist of RANKL, prevented bone loss as well as ectopic calcification in CVB3-infected mice. Thus, our results indicate that RANKL may contribute to both abnormal calcium deposition in soft tissues and calcium depletion in bone. In addition, our animal model should provide a tool for the development of new therapeutic agents for calcium disturbance in soft and hard tissues.
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Calcinosis/prevención & control , Infecciones por Coxsackievirus/metabolismo , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteoporosis/metabolismo , Osteoporosis/prevención & control , Ligando RANK/metabolismo , Receptor Activador del Factor Nuclear kappa-B/metabolismo , Animales , Calcinosis/patología , Calcinosis/virología , Infecciones por Coxsackievirus/inmunología , Infecciones por Coxsackievirus/patología , Modelos Animales de Enfermedad , Células HeLa , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Osificación Heterotópica/metabolismo , Osificación Heterotópica/patología , Osificación Heterotópica/virología , Osteoblastos/patología , Osteoblastos/virología , Osteoclastos/patología , Osteoclastos/virología , Osteoporosis/virología , Ligando RANK/antagonistas & inhibidores , Ratas , Ratas Sprague-Dawley , Receptor Activador del Factor Nuclear kappa-B/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/genéticaRESUMEN
Low-level laser therapy/treatment (LLLT) using a minimally invasive laser needle system (MILNS) might enhance bone formation and suppress bone resorption. In this study, the use of 405 nm LLLT led to decreases in bone volume and bone mineral density (BMD) of tibial trabecular bone in wild-type (WT) and Per2 knockout (KO) mice. Bone volume and bone mineral density of tibial trabecular bone was decreased by 405 nm LLLT in Per2 KO compared to WT mice at two and four weeks. To determine the reduction in tibial bone, mRNA expressions of alkaline phosphatase (ALP) and Per2 were investigated at four weeks after 405 nm laser stimulation using MILNS. ALP gene expression was significantly reduced in the LLLT-stimulated right tibial bone of WT and Per2 KO mice compared to the non-irradiated left tibia (p < 0.001). Per2 mRNA expression in WT mice was significantly reduced in the LLLT-stimulated right tibial bone compared to the non-irradiated left tibia (p < 0.001). To identify the decrease in tibial bone mediated by the Per2 gene, levels of runt-related transcription factor 2 (Runx2) and ALP mRNAs were determined in non-irradiated WT and Per2 KO mice. These results demonstrated significant downregulation of Runx2 and ALP mRNA levels in Per2 KO mice (p < 0.001). Therefore, the reduction in tibial trabecular bone resulting from 405 nm LLLT using MILNS might be associated with Per2 gene expression.
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Densidad Ósea , Huesos/metabolismo , Huesos/patología , Terapia por Luz de Baja Intensidad , Proteínas Circadianas Period/genética , Tibia/metabolismo , Tibia/patología , Animales , Huesos/efectos de la radiación , Regulación de la Expresión Génica/efectos de la radiación , Masculino , Ratones , Ratones Noqueados , Modelos Animales , Proteínas Circadianas Period/metabolismo , Tibia/efectos de la radiación , Microtomografía por Rayos XRESUMEN
Active matrix metalloproteinase-3 (MMP-3) is a prognostic marker of rheumatoid arthritis (RA). We recently developed an MMP-3 probe that can specifically detect the active form of MMP-3. The aim of this study was to investigate whether detection and monitoring of active MMP-3 could be useful to predict therapeutic drug responses in a collagen-induced arthritis (CIA) model. During the period of treatment with drugs such as methotrexate (MTX) or infliximab (IFX), MMP-3 mRNA and protein levels were correlated with fluorescence signals in arthritic joint tissues and in the serum of CIA mice. Also, bone volume density and erosion in the knee joints and the paws of CIA mice were measured with microcomputed tomography (micro-CT), X-ray, and histology to confirm drug responses. In joint tissues and serum of CIA mice, strong fluorescence signals induced by the action of active MMP-3 were significantly decreased when drugs were applied. The decrease in RA scores in drug-treated CIA mice led to fluorescence reductions, mainly as a result of down-regulation of MMP-3 mRNA or protein. The micro-CT, X-ray, and histology results clearly showed marked decreases in bone and cartilage destruction, which were consistent with the reduction of fluorescence by down-regulation of active MMP-3 in drug-treated CIA mice. We suggest that the MMP-3 diagnostic kit could be used to detect and monitor the active form of MMP-3 in CIA mice serum during a treatment course and thereby used to predict the drug response or resistance to RA therapies at an earlier stage. We hope that monitoring of active MMP-3 levels in arthritis patients using the MMP-3 diagnostic kit will be a promising tool for drug discovery, drug development, and monitoring of drug responses in RA therapy.
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Antirreumáticos/uso terapéutico , Colágeno/toxicidad , Metaloproteinasa 3 de la Matriz/metabolismo , Sondas Moleculares/metabolismo , Animales , Anticuerpos Monoclonales/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/enzimología , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/enzimología , Modelos Animales de Enfermedad , Infliximab , Metotrexato/uso terapéutico , RatonesRESUMEN
On superhydrophobic (SHPo) surfaces, either of two wetting states-the Cassie state (i.e., nonwetted state) and the Wenzel state (i.e., wetted state)-can be observed depending on the thermodynamic energy of each state and external conditions. Each wetting state leads to quite a distinctive dynamic characteristic of the water drop on SHPo surfaces, and it has been of primary interest to understand or induce the desirable wetting state for relevant thermofluid engineering applications. In this study, we investigate how the wetting state of microstructured SHPo surfaces influences the water-harvesting performance via dewing by testing two different patterns, including posts and grates with varying structural parameters. On grates, the observed Cassie wetting state during condensation is well described by the thermodynamic energy criteria, and small condensates can be efficiently detached from the surfaces because of the small contact line pinning force of Cassie droplets. Meanwhile, on posts, the observed wetting state is dominantly the Wenzel state regardless of the thermodynamic energy of each state, and the condensates are shed only after they grow to a sufficiently large size to overcome the much larger pinning force of the Wenzel state. On the basis of the mechanical force balance model and energy barrier consideration, we attribute the difference in the droplet shedding characteristics to the different dynamic pathway from the Wenzel state to the Cassie state between posts and grates. Overall, the faster droplet shedding helps to enhance the water-harvesting performance of the SHPo surfaces by facilitating condensation on the droplet-free area, as evidenced by the best water-harvesting performance of grates on the Cassie state among the tested surfaces.
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[Purpose] The present study analyzed the effect of the Togu exercise program on the lumbar back strength of middle-aged women who did not perform regular exercise, and presents an effective exercise method for middle-aged women with chronic low back pain symptom. [Subjects] The subjects were 16 women with chronic low back pain attending N University, Chungcheong-do, Korea. [Methods] Height, weight, body fat, and body mass index (BMI) were measured using a body composition analyzer (Inbody 720, Biospace, Korea), which utilizes bioelectrical impedance analysis. Using isokinetic lumbar muscle strength measurement equipment [Isomed 2000, Back system, (Germany)], peak torque/body weight, total work and average power of flexion and extension of the lumbar region were measured. For lumbar stabilization exercises, an air cushion (Germany), jumper (Germany), and aero step (Germany) were employed. First, warm-up exercise was conducted for 10 minutes, followed by 10 sets of the 3 main exercises using the above tools with 10-second rest intervals. The main exercise was done for 40 minutes in total. [Results] The paired sample t-test showed significant in the Togu exercise group peak torque of flexion, peak torque of extension, total work of flexion, total work of extension, average power of flexion, average power of extension, after the exercise showed a significant difference in the Togu exercise group. [Conclusion] The trunk muscle actiation program for middle-aged women had a significant effect on muscle strength and low back pain. Therefore the trunk muscle activation program is effective at increasing muscular strength of middle-aged women, and the results suggest improve muscle strength is effectively stabilizaties the lumbar region.
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Although carboxylate-based frameworks are commonly used architectures in metal-organic frameworks (MOFs), liquid/glass MOFs have thus far mainly been obtained from azole- or weakly coordinating ligand-based frameworks. This is because strong coordination bonds of carboxylate ligands to metals block the thermal vitrification pathways of carboxylate-based MOFs. In this study, we present the example of carboxylate-based melt-quenched MOF glasses comprising Mg2+ or Mn2+ with an aliphatic carboxylate ligand, adipate. These MOFs have a low melting temperature (Tm) of 284 °C and 238 °C, respectively, compared to zeolitic-imidazolate framework (ZIF) glasses, and superior mechanical properties in terms of hardness and elastic modulus. The low Tm may be attributed to the flexibility and low symmetry of the aliphatic carboxylate ligand, which raises the entropy of fusion (ΔSfus), and the lack of crystal field stabilization energy on metal ions, reducing enthalpy of fusion (ΔHfus). This research will serve as a cornerstone for the integration of numerous carboxylate-based MOFs into MOF glasses.
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BACKGROUND: Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is a subset of gastric cancers linked to EBV infection. While the role of male hormones in cancers such as prostate, breast, and ovarian cancers is well-studied, their impact on EBVaGC remains less understood. This study aims to examine the effect of dihydrotestosterone (DHT) on EBVaGC, particularly focusing on its influence on the immune response. METHODS: The study utilized the SNU719 EBVaGC cell line. Cells were treated with DHT to assess androgen receptor (AR) expression and the activation of signaling pathways, including NF-κB. The expression of MHC class I polypeptide-related sequence A (MICA) and its interaction with the NKG2D receptor on NK and T cells was evaluated. Cytotoxicity assays were conducted to determine DHT's effect on NK and T cell-mediated cytotoxicity, and proinflammatory cytokine gene expression was analyzed. RESULTS: DHT significantly increased AR expression in EBVaGC cells and activated the NF-κB pathway, which led to increased transcription of target genes such as MICA and EBNA1. These changes enhanced the interaction with receptors on NK and T cells, thereby boosting their cytotoxicity against EBVaGC cells. Importantly, DHT did not upregulate proinflammatory cytokine genes. CONCLUSION: DHT enhances the immune response against EBVaGC by upregulating MICA and activating NK and T cells. These findings suggest potential therapeutic strategies targeting androgen signaling to improve anti-tumor immunity in EBVaGC.
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Methylene blue (MB) has recently completed a Phase-3 clinical trial as leuco-methylthioninium (LMT) bis(hydromethanesulfonate) for treating Alzheimer's disease. Herein, we investigated the mechanism underlying the MB inhibition of tubulin-associated unit (tau) aggregation by focusing on tau monomers. We found that MB causes disulfide bond formation, resulting in strong nuclear magnetic resonance chemical shift perturbations in a large area of tau proteins. The oxidized form of MB, namely methylthioninium (MT+), specifically catalyzed the oxidation of cysteine residues in tau proteins to form disulfide bonds directly using O2. This process is independent of the MT+-to-LMT redox cycle. Moreover, MT+ preferentially oxidized C291 and C322 in the lysine-rich R2 and R3 domains. Under in vivo brain physoxia conditions, LMT may convert to MT+, possibly interfering with tau fibrillation via disulfide bond formation.
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BACKGROUND: Hwangryun-haedok-tang (HRT) is traditional herbal medicine used to treat inflammatory-related diseases in Asia. However, its effect on osteoclastogenesis and bone loss is still unknown. In this study, we evaluated the effect of HRT and its fermented product (fHRT) on the receptor activator for the nuclear factor-κB ligand-induced osteoclastogenesis using murine bone marrow-derived macrophages and postmenopausal bone loss using an ovariectomy (OVX) rat model. METHODS: Tartrate resistant acid phosphatase (TRAP) staining was employed to evaluate osteoclast formation. mRNA level of transcription factor and protein levels of signaling molecules were determined by real-time quantitative polymerase chain reaction and Western blot analysis, respectively. Effect of HRT or fHRT on OVX-induced bone loss was evaluated using OVX rats orally administered HRT, or fHRT with 300 mg/kg for 12 weeks. Micro-CT analysis of femora was performed to analyze bone parameter. RESULTS: HRT or fHRT treatment significantly decreased TRAP activity and the number of TRAP positive multinuclear cells on osteoclastogenesis. Interestingly, these inhibitory effects of HRT were enhanced by fermentation. Furthermore, fHRT significantly inhibited mRNA and protein expression of nuclear factor of activated T cells cytoplasmic 1, which leads to down-regulation of NFATc1-regulated mRNA expressions such as TRAP, the d2 isoform of vacuolar ATPase V(0) domain, and cathepsin K. Administration of fHRT significantly inhibited the decrease of bone mineral density, and improved bone parameter of femora more than that of HRT and vehicle in OVX rats. CONCLUSIONS: This study demonstrated that lactic bacterial fermentation fortifies the inhibitory effect of HRT on osteoclastogenesis and bone loss. These results suggest that fermented HRT might have the beneficial potential on osteoporosis by inhibiting osteoclastogenesis.
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Densidad Ósea/efectos de los fármacos , Huesos/efectos de los fármacos , Medicamentos Herbarios Chinos/uso terapéutico , Lactobacillus , Osteoclastos/efectos de los fármacos , Osteoporosis Posmenopáusica/tratamiento farmacológico , Fitoterapia , Animales , Resorción Ósea/metabolismo , Resorción Ósea/prevención & control , Huesos/citología , Huesos/metabolismo , Regulación hacia Abajo , Medicamentos Herbarios Chinos/metabolismo , Femenino , Fémur , Fermentación , Humanos , Lactobacillus/metabolismo , Macrófagos/efectos de los fármacos , Ratones , Factores de Transcripción NFATC/metabolismo , Osteoporosis Posmenopáusica/metabolismo , Ovariectomía , Ligando RANK/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
There has been significant research focused on the development of stretchable materials that can provide a large area with minimal material usage for use in solar cells and displays. However, most materials exhibit perpendicular shrinkage when stretched, which is particularly problematic for polymer-based substrates commonly used in stretchable devices. To address this issue, biaxial strain-controlled substrates have been proposed as a solution to increase device efficiency and conserve material resources. In this study, we present the design and fabrication of a biaxial strain-controlled substrate with a re-entrant honeycomb structure and a negative Poisson's ratio. Using a precisely machined mold with a shape error of less than 0.15%, we successfully fabricated polydimethylsiloxane substrates with a 500 µm thick re-entrant honeycomb structure, resulting in a 19.1% reduction in perpendicular shrinkage. This improvement translates to a potential increase in device efficiency by 9.44% and an 8.60% reduction in material usage for substrate fabrication. We demonstrate that this design and manufacturing method can be applied to the fabrication of efficient stretchable devices, such as solar cells and displays.
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Amyloid generation plays essential roles in various human diseases, biological functions, and nanotechnology. However, developing efficient chemical and biological candidates for regulating amyloid fibrillation remains difficult because information on the molecular actions of modulators is insufficient. Thus, studies are needed to understand how the intermolecular physicochemical properties of the synthesised molecules and amyloid precursors influence amyloidogenesis. In this study, we synthesised a novel amphiphilic sub-nanosized material, arginine-arginine (RR)-bile acid (BA), by conjugating positively charged RR to hydrophobic BA. The effects of RR-BA on amyloid formation were investigated on α-synuclein (αSN) in Parkinson's disease and on K18 and amyloid-ß (1-42) (Aß42) in Alzheimer's disease. RR-BA showed no appreciable effect on the kinetics of K18 and Aß42 amyloid fibrillation because of their weak and non-specific interactions. However, RR-BA specifically bound to αSN with moderate binding affinity through electrostatic interactions between the positively charged RR and the negatively charged cluster in the C-terminus of αSN. In addition, hydrophobic BA in the αSN-RR-BA complex transiently condensed αSN for primary nucleation, thereby accelerating αSN amyloid fibrillation. We propose an electrostatic binding and hydrophobic condensation model of RR-BA-driven amyloid formation of αSN, which will contribute to the rational design and development of molecules for controlling amyloid aggregation in diverse fields.
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Enfermedad de Alzheimer , Enfermedad de Parkinson , Humanos , alfa-Sinucleína/química , Enfermedad de Parkinson/metabolismo , Amiloide/química , Enfermedad de Alzheimer/metabolismo , Péptidos beta-AmiloidesRESUMEN
Hwangryun-haedok-tang (HRT) is the common recipe in traditional Asian medicine, and microbial fermentation is used for the conventional methods for processing traditional medicine. We investigated the inhibitory effect of the n-butanol fraction of HRT (HRT-BU) and fHRT (fHRT-BU) on the RANKL-induced osteoclastogenesis in bone-marrow-derived macrophages. mRNA expression of osteoclastogenesis-related genes were evaluated by real-time QPCR. The activation of signaling pathways was determined by western blot analysis. The marker compounds of HRT-BU and fHRT-BU were analyzed by HPLC. The inhibitory effect of HRT or fHRT on ovariectomy-induced bone loss were evaluated using OVX rats with orally administered HRT, fHRT (300, 1000 mg/kg), or its vehicle for 12 weeks. fHRT-BU significantly inhibited RANKL-induced osteoclastogenesis, and phosphorylation of p38, IKKα/ß, and NF-κBp65 compared to HRT-BU. In addition, fHRT-BU also significantly inhibited the mRNA expression of Nfκb2, TNF-α, NFATc1, TRAP, ATPv0d2, and cathepsin K. Furthermore, administration of fHRT had a greater effect on the increase of BMD, and greater improved bone microstructure of the femora than that of HRT in ovariectomy rats. This study demonstrated that bacterial fermentation enhances the inhibitory effect of HRT on osteoclastogenesis and bone loss. These results suggest that fermented HRT might have the beneficial effects on bone disease by inhibiting osteoclastogenesis.
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Owing to its exceptional physicochemical properties, graphene has demonstrated unprecedented potential in a wide array of scientific and industrial applications. By exploiting its chemically inert surface endowed with unique barrier functionalities, we herein demonstrate antiadhesive monolayer graphene films for realizing a peel-and-pick transfer process of target materials from the donor substrate. When the graphene antiadhesion layer (AAL) is inserted at the interface between the metal and the arbitrary donor substrate, the interfacial interactions can be effectively weakened by the weak interplanar van der Waals forces of graphene, enabling the effective release of the metallic electrode from the donor substrate. The flexible embedded metallic electrode with graphene AAL exhibited excellent electrical conductivity, mechanical durability, and chemical resistance, as well as excellent performance in flexible heater applications. This study afforded an effective strategy for fabricating high-performance and ultraflexible embedded metallic electrodes for applications in the field of highly functional flexible electronics.
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Recently, lubricant-impregnated surfaces (LIS) have emerged as a promising condenser surface by facilitating the removal of condensates from the surface. However, LIS has the critical limitation in that lubricant oil is depleted along with the removal of condensates. Such oil depletion is significantly aggravated under high condensation heat transfer. Here we propose a brushed LIS (BLIS) that can allow the application of LIS under high condensation heat transfer indefinitely by overcoming the previous oil depletion limit. In BLIS, a brush replenishes the depleted oil via physical contact with the rotational tube, while oil is continuously supplied to the brush by capillarity. In addition, BLIS helps enhance heat transfer performance with additional route to droplet removal by brush sweeping. By applying BLIS, we maintain the stable dropwise condensation mode for > 48 hours under high supersaturation levels along with up to 61% heat transfer enhancement compared to hydrophobic surfaces.
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Superhydrophobic (SHPo) surfaces can provide high condensation heat transfer due to facilitated droplet removal. However, such high performance has been limited to low supersaturation conditions due to surface flooding. Here, we quantify flooding resistance defined as the rate of increase in the fraction of water-filled cavities with respect to the supersaturation level. Based on the quantitative understanding of surface flooding, we suggest effective anti-flooding strategies through tailoring the nanoscale coating heterogeneity and structure length scale. Experimental verification is conducted using CuO nanostructures having different length scales combined with hydrophobic coatings with different nanoscale heterogeneities. The proposed anti-flooding SHPo can provide a â¼130% enhanced average heat transfer coefficient with â¼14% larger supersaturation range for droplet jumping compared to a previous CuO SHPo. The proposed anti-flooding parameter and the scalable SHPo will help develop high-performance condensers for real-world applications operating in a wide range of supersaturation levels.