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[This corrects the article DOI: 10.1016/j.radcr.2023.12.017.].
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Granular cell tumor (GCT) is a rare neoplasm. Its diagnosis is based on imaging and pathological findings. There are only a few reported cases of GCT of the breast (GCTB) in the literature. We present a case of a female patient diagnosed with GCTB and perform a review on the prevalence, diagnosis, histology, treatment, and prognosis.
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Mucocele-like lesions of the breast are rare, usually presenting themselves as suspicious findings on imaging, warranting biopsies. It can be associated with several degrees of hyperplasia, including atypical ductal hyperplasia and ductal carcinoma in situ, historically being considered a high-risk lesion. It also can be an underestimated invasive carcinoma in a percutaneous biopsy. When facing a histologic diagnosis of a mucocele-lesion in a percutaneous biopsy, it is important to be aware of these lesions' significance to make the most appropriate interpretation, recommendation, and management. The purpose of this work is to present some cases of breast mucocele-like lesions from our Institution and perform a review of the literature.
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Microbial CO2 electroreduction (mCO2ER) offers a promising approach for producing high-value multicarbon reductants from CO2 by combining CO2 fixing microorganisms with conducting materials (i. e., cathodes). However, the solubility and availability of CO2 in an aqueous electrolyte pose significant limitations in this system. This study demonstrates the efficient production of long-chain multicarbon reductants, specifically carotenoids (~C40), within a wet amine-based catholyte medium during mCO2ER. Optimizing the concentration of the biocompatible CO2 absorbent, monoethanolamine (MEA), led to enhanced CO2 fixation in the electroautotroph bacteria. Molecular biological analyses revealed that MEA in the catholyte medium redirected the carbon flux towards carotenoid biosynthesis during mCO2ER. The faradaic efficiency of mCO2ER with MEA for carotenoid production was 4.5-fold higher than that of the control condition. These results suggest the mass transport bottleneck in bioelectrochemical systems could be effectively addressed by MEA-assissted mCO2ER, enabling highly efficient production of valuable products from CO2.
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Dióxido de Carbono , Oxirredução , Dióxido de Carbono/química , Catálise , Eletrodos , Etanolamina/química , Eletroquímica , Aminas/química , Carotenoides/química , Eletrólitos/químicaRESUMO
Hydrogen energy production through photoelectrochemical (PEC) water splitting has great potential in the field of renewable energy. This study focuses on the hydration enthalpy difference of cations (Li+ , Na+ , and K+ ) in an aqueous solution for the chemical self-oxidation process without an external applied bias. The thickness of the cation/H2 O double layer is controlled. The starting materials are low-cost copper foil and the synthesis uses alkali cation-engineered chemical self-oxidation. Li+ ions are strongly attracted to water molecules. This forms a sufficient OH- layer on the Cu foil surface. By accelerating the oxidation reaction, a large surface area of Cu(OH)x nanowires (NWs) with high purity and a uniform shape are obtained. This optimal p-type Cu2 O NWs photocathode is CuO-free, has the highest conductivity, and is fabricated through phase transition using precise vacuum annealing. The other alkali cations produce the Cu2 O/CuO mixed or CuO phases that degrade the PEC performances with severe corrosive reactions. The Cu/Li : Cu2 O/AZO/TiO2 /Pt photocathode has a 50â h stability with a photocurrent density of 8.4â mA cm-2 at 0â VRHE . The fabricated photoelectrode did not structurally collapse after stability measurements during this period. The captured hydrogen production was in agreement with the calculated faradaic efficiency.
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OBJECTIVE: This study aimed to determine whether completion thyroidectomy is necessary based on long-term follow-up oncological results according to various clinical and pathological characteristics of patients with papillary thyroid carcinoma (PTC) who underwent lobectomy. MATERIALS AND METHODS: We enrolled 1815 patients with PTC who underwent thyroid lobectomy from January 2003 to December 2014. Various clinical and pathological characteristics were reviewed retrospectively, and clinicopathologic characteristics and recurrence rates were analyzed. RESULTS: Eighty-two (4.5%) patients showed locoregional recurrence during the average 10.2-year follow-up period. There was no significant difference in tumor size, multifocality, lymphovascular invasion (LVI), microscopic or strap muscle-extrathyroidal extension, and central neck lymph node (LN) micrometastasis between the recurrence and non-recurrence groups. The gross strap muscle-extrathyroidal extension group was associated with older age (p < 0.001), larger tumor size (p < 0.001), more capsular invasion (p < 0.001), and more LVI (p < 0.001) than the negative extrathyroidal extension group; there was no significant difference in recurrence between the groups (p = 0.096). Patients with five or more central LN micrometastases were associated with younger age (p = 0.006), larger tumor size (p = 0.04), and presence of LVI (p = 0.033) than patients with less than five central LN metastases; there was no significant difference in recurrence between the groups (p = 0.867). All patients with recurrence were cured through reoperation after recurrence was confirmed. CONCLUSION: After thyroid lobectomy, PTC patients with multifocality, LVI, extrathyroidal extension to the strap muscles, or five or more central LN micrometastases may not require immediate completion thyroidectomy.
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Carcinoma Papilar , Neoplasias da Glândula Tireoide , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Humanos , Linfonodos/patologia , Linfonodos/cirurgia , Músculos/patologia , Micrometástase de Neoplasia , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodosRESUMO
A novel and facile synthesis is made of cotton-like three-dimensional (3D) fibrous scaffold containing spatiotemporally defined patterns of simvastatin (SIM) optimized for angiogenesis-coupled osteogenesis. Herein, we demonstrate the 3D fiber deposition mechanism in detail during the electrospinning process via computer simulation. The 3D fibrous scaffolds were functionalized with hydroxyapatite nanoparticles (HA - NPs) to induce the biomineralization process mimicking the natural apatite layer. The morphology, physiochemical properties, biomimetic mineralization, and drug release of the as-fabricated 3D fibrous scaffolds of simvastatin-loaded poly (É-caprolactone) poly (glycerol-sebacate) hydroxyapatite nanoparticles (3D - PGHS) were investigated. The effects of simvastatin on the osteogenic differentiation of human mesenchymal stem cells (hMSCs) and angiogenesis in human umbilical vein endothelial cells (HUVECs) were assessed. The results showed that the 3D - PGHS both enhanced the expression of osteogenic markers including ALP, RUNX2, and COLA1 in hMSCs, and promoted the migration and tube formation of HUVECs. This finding demonstrates the potential of 3D scaffold-loaded SIM as a putative point-of-care therapy for tightly controlled tissue regeneration.
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Células-Tronco Mesenquimais , Osteogênese , Diferenciação Celular , Simulação por Computador , Liberação Controlada de Fármacos , Durapatita/química , Durapatita/farmacologia , Células Endoteliais , Humanos , Sinvastatina/química , Engenharia Tecidual , Alicerces Teciduais/químicaRESUMO
Air filters effectively filtrate external contaminants including pathogenic bioaerosols; however, they also act as culture sites for the pathogenic bacteria captured in nutrient organic pollutants. Although many researchers have applied various antibacterial coatings to filters, the coating application inevitably increased the pressure drop, leading to the low efficiency and high energy consumption of the purification system. Herein, we report a simple nanostructured zinc oxide (ZnO) coating technique to confer a polypropylene nonwoven filter with superior antibacterial, antifouling and anti-biofilm properties without an additional pressure drop. For aerodynamic coating designs, filters were directly immersed into low concentration precursor solutions to enable the sedimentation of the ZnO sol-gel particles on the filter fibers according to fluid dynamic. The precursor concentration affected the surface topology and so properties of the as-fabricated coating. 0.07 M precursor solution produced a rose-like nanostructured coating exhibiting no pressure-drop increase. The large specific surface area and hydrophobic surface killed and then repelled the attached bacteria effectively. As a result, the bare filter promoted the growth and consequent biofilm formation of the surface bacteria in a favorable environment for the growth of microorganisms, while the coated filter successfully suppressed biofilm development.
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Filtros de Ar , Incrustação Biológica , Óxido de Zinco , Antibacterianos/farmacologia , Biofilmes , Incrustação Biológica/prevenção & controle , Óxido de Zinco/farmacologiaRESUMO
Parkinson's disease (PD) is the second-most common neurodegenerative chronic disease affecting both cognitive performance and motor functions in aged people. Yet despite the prevalence of this disease, the current therapeutic options for the management of PD can only alleviate motor symptoms. Research has explored novel substances for naturally derived antioxidant phytochemicals with potential therapeutic benefits for PD patients through their neuroprotective mechanism, targeting oxidative stress, neuroinflammation, abnormal protein accumulation, mitochondrial dysfunction, endoplasmic reticulum stress, neurotrophic factor deficit, and apoptosis. The aim of the present study is to perform a comprehensive evaluation of naturally derived antioxidant phytochemicals with neuroprotective or therapeutic activities in PD, focusing on their neuropharmacological mechanisms, including modulation of antioxidant and anti-inflammatory activity, growth factor induction, neurotransmitter activity, direct regulation of mitochondrial apoptotic machinery, prevention of protein aggregation via modulation of protein folding, modification of cell signaling pathways, enhanced systemic immunity, autophagy, and proteasome activity. In addition, we provide data showing the relationship between nuclear factor E2-related factor 2 (Nrf2) and PD is supported by studies demonstrating that antiparkinsonian phytochemicals can activate the Nrf2/antioxidant response element (ARE) signaling pathway and Nrf2-dependent protein expression, preventing cellular oxidative damage and PD. Furthermore, we explore several experimental models that evaluated the potential neuroprotective efficacy of antioxidant phytochemical derivatives for their inhibitory effects on oxidative stress and neuroinflammation in the brain. Finally, we highlight recent developments in the nanodelivery of antioxidant phytochemicals and its neuroprotective application against pathological conditions associated with oxidative stress. In conclusion, naturally derived antioxidant phytochemicals can be considered as future pharmaceutical drug candidates to potentially alleviate symptoms or slow the progression of PD. However, further well-designed clinical studies are required to evaluate the protective and therapeutic benefits of phytochemicals as promising drugs in the management of PD.
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Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/prevenção & controle , Compostos Fitoquímicos/uso terapêutico , Animais , Humanos , Masculino , Compostos Fitoquímicos/farmacologia , RatosRESUMO
Renal fibrosis is a common end point for kidney injury and many chronic kidney diseases. Fibrogenesis depends on the sustained activation of myofibroblasts, which deposit the extracellular matrix that causes progressive scarring and organ failure. Here, we showed that the transcription factor SOX9 was associated with kidney fibrosis in humans and required for experimentally induced kidney fibrosis in mice. From genome-wide analysis, we identified Neuron navigator 3 (NAV3) as acting downstream of SOX9 in kidney fibrosis. NAV3 increased in abundance and colocalized with SOX9 after renal injury in mice, and both SOX9 and NAV3 were present in diseased human kidneys. In an in vitro model of renal pericyte transdifferentiation into myofibroblasts, we demonstrated that NAV3 was required for multiple aspects of fibrogenesis, including actin polymerization linked to cell migration and sustained activation of the mechanosensitive transcription factor YAP1. In summary, our work identifies a SOX9-NAV3-YAP1 axis involved in the progression of kidney fibrosis and points to NAV3 as a potential target for pharmacological intervention.
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Nefropatias , Miofibroblastos , Animais , Fibrose , Rim , Nefropatias/genética , Nefropatias/patologia , Camundongos , Miofibroblastos/patologia , Transdução de SinaisRESUMO
Polyhydroxyalkanoates (PHA) are appealing as an important alternative to replace synthetic plastics owing to its comparable physicochemical properties to that of synthetic plastics, and biodegradable and biocompatible nature. This review gives an inclusive overview of the current research activities dealing with PHA production by utilizing different waste fluxes generated from food, milk and sugar processing industries. Valorization of these waste fluxes makes the process cost effective and practically applicable. Recent advances in the approaches adopted for waste treatment, fermentation strategies, and genetic engineering can give insights to the researchers for future direction of waste to bioplastics production. Lastly, synthesis and application of PHA-nanocomposites, research and development challenges, future perspectives for sustainable and cost-effective PHB production are also discussed. In addition, the review addresses the useful information about the opportunities and confines associated with the sustainable PHA production using different waste streams and their evaluation for commercial implementation within a biorefinery.
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Poli-Hidroxialcanoatos , Fermentação , Alimentos , Plásticos , Poli-Hidroxialcanoatos/metabolismoRESUMO
BACKGROUND: Although ultrasound guidance has significantly improved the success rate of radial artery catheterization, the failure rate in children is still high. For the further improvement of success rate, we prospectively evaluated the factors that make ultrasound-guided radial artery catheterization difficult in children under two years old. METHODS: From October 2018 to September 2019, patients who required radial artery catheterization for surgery were enrolled. After collecting the anatomical characteristics of the radial artery using ultrasound at the puncture site, ultrasound-guided radial artery catheterization was performed by one experienced anaesthesiologist. The primary outcome was to identify the factors related to the first attempt failure. The factors associated with the total duration of the procedure until success were also evaluated. RESULTS: A total of 183 children were included in the analysis. A radial artery cross-sectional area of ≤1 mm2 (odds ratio [OR] = 5.26; 95% confidence interval [CI], 2.48-11.18; P < .0001) and the presence of an anomalous radial artery branch (OR = 3.37; 95% CI, 1.43-7.95; P = .005) were independent predictors of first-attempt failure during ultrasound-guided radial artery catheterization. The total procedure time was also negatively associated with the small cross-sectional area (P < .001). CONCLUSIONS: A cross-sectional area of ≤ 1 mm2 and the presence of an anomalous branch of radial artery significantly increased the difficulty of ultrasound-guided radial artery catheterization in children under two years old. In patients of these ages, pre-procedural ultrasound scanning to find an optimal site for catheterization may increase the first-attempt success rate although further studies are needed to verify our results. TRIAL REGISTRATION: Clinical Research Information Service (https://crits.nih.go.kr, October 6, 2018 [KCT0003239]; Principle investigator: Jong-Hwan Lee).
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Cateterismo Periférico , Artéria Radial , Criança , Humanos , Lactente , Estudos Prospectivos , Artéria Radial/diagnóstico por imagem , Ultrassonografia , Ultrassonografia de IntervençãoRESUMO
The Dendropanax genus is a kind of flowering plant in the family of Araliaceae that encompasses approximately 91 to 95 species. Several Dendropanax species are used as traditional medicinal plants, extensively used Korea and South America and other parts of the world. Almost every part of the plant, including the leaves, bark, roots, and stems, can be used as traditional medicine for the prevention and management of a broad spectrum of health disorders. This paper sought to summarizes the ethnopharmacological benefits, biological activities, and phytochemical investigations of plants from the genus Dendropanax, and perhaps to subsequently elucidate potential new perspectives for future pharmacological research to consider. Modern scientific literature suggests that plants of the Dendropanax genus, together with active compounds isolated from it, possess a wide range of therapeutic and pharmacological applications, including antifungal, anti-complement, antioxidant, antibacterial, insect antifeedant, cytotoxic, anti-inflammatory, neuroprotective, anti-diabetic, anti-cancer, and anti-hypouricemic properties. The botanical descriptions of approximately six to 10 species are provided by different scientific web sources. However, only six species, namely, D. morbiferus, D. gonatopodus, D. dentiger, D. capillaris, D. chevalieri, and D. arboreus, were included in the present investigation to undergo phytochemical evaluation, due to the unavailability of data for the remaining species. Among these plant species, a high concentration of variable bioactive ingredients was identified. In particular, D. morbifera is a traditional medicinal plant used for the multiple treatment purposes and management of several human diseases or health conditions. Previous experimental evidence supports that the D. morbifera species could be used to treat various inflammatory disorders, diarrhea, diabetes, cancer, and some microbial infections. It has recently been reported, by our group and other researchers, that D. morbifera possesses a neuroprotective and memory-enhancing agent. A total of 259 compounds have been identified among six species, with 78 sourced from five of these species reported to be bioactive. However, there is no up-to-date information concerning the D. morbifera, its different biological properties, or its prospective benefits in the enhancement of human health. In the present study, we set out to conduct a comprehensive analysis of the botany, traditional medicinal history, and medicinal resources of species of the Dendropanax genus. In addition, we explore several phytochemical constituents identified in different species of the Dendropanax genus and their biological properties. Finally, we offer comprehensive analysis findings of the phytochemistry, medicinal uses, pharmacological actions, and a toxicity and safety evaluation of the D. morbifera species and its main bioactive ingredients for future consideration.
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Green-emitting CsPbBr3 perovskite nanocrystals were synthesized by the modified hot-injection method using three different solvents. The produced nanocrystals showed a narrow green emission band centered at 515-520 nm with full width at half-maximum (FWHM) values of approximately 18-20 nm. The highest photoluminescence quantum yield (PLQY) was obtained for the nanocrystal sample synthesized using a paraffin liquid solvent, with a value of 70.1% under excitation at 450 nm. The CsPbBr3 nanocrystals film light-emitting diodes (LED) chip module showed a luminous efficacy of 40.7lm/Wrad. The white LED (WLED) with green CsPbBr3 and red CsPbI3 nanocrystal films emitted bluish-white light with a high color rendering index of 89, and the luminous efficacy of the WLED reached 16.3lm/Wrad.
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The discovery of several revitalizing molecules that can stop or reduce the pathology of a wide range of diseases will be considered a major breakthrough of the present time. Available synthetic compounds may provoke side effects and health issues, which heightens the need for molecules from plants and other natural resources under discovery as potential methods of replacing synthetic compounds. In traditional medicinal therapies, several plant extracts and phytochemicals have been reported to impart remedial effects as better alternatives. Murraya koenigii (M. koenigii) belongs to the Rutaceae family, which is commonly used as a medicinally important herb of Indian origin in the Ayurvedic system of medicine. Previous reports have demonstrated that the leaves, roots, and bark of this plant are rich sources of carbazole alkaloids, which produce potent biological activities and pharmacological effects. These include antioxidant, antidiabetic, anti-inflammatory, antitumor, and neuroprotective activities. The present review provides insight into the major components of M. koenigii and their pharmacological activities against different pathological conditions. The review also emphasizes the need for more research on the molecular basis of such activity in various cellular and animal models to validate the efficacy of M. koenigii and its derivatives as potent therapeutic agents.
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Parkinson's disease (PD) is a commonly reported age-related neurodegenerative disorder. Microglial-mediated neuroinflammation is one of the cardinal hallmarks of various neurodegenerative disorders, including PD progression. Inadequate therapeutic strategies and substantial adverse effects of well-established drug candidates demand new therapeutic leads to treat PD. Dendropanax morbifera (DM) is an endemic plant species of South Korea, and it has been used extensively as traditional medicine to treat numerous clinical complications. In this study, we conducted an initial profiling of the few major phytoconstituents of aqueous DM leaf extracts (DML) and quantified the same using high-performance liquid chromatography tandem mass spectrometry with electrospray ionization (HPLC-ESI-MS/MS). We subsequently evaluated the antineuroinflammatory activity and ameliorative potential of DML in both in vitro and in vivo experimental PD models. The prophylactic treatment of DML effectually improved the behavioral deficits, curbed the microglial-mediated neuroinflammation, and protected dopaminergic (DA) neuronal loss by restoring tyrosine hydroxylase (TH) levels in brain tissue of the MPTP-induced PD mouse model. We conducted chromatographic profiling and identified chlorogenic acid (CA) as a major constituent (19.5 mg/g of BuOH fraction), which has been well documented as an antioxidant and anti-inflammatory agent. This was found to be in harmony with our in vitro results, where DML suppressed the level of inflammatory mediators and allied the signaling pathway in LPS-stimulated microglial cells. The results of our study indicate that DML and its bioactive constituents can be developed as potential therapeutic candidates against progressive PD complications.
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1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Doença de Parkinson/tratamento farmacológico , Extratos Vegetais/química , Folhas de Planta/química , Animais , Anti-Inflamatórios/farmacologia , Modelos Animais de Doenças , Masculino , Camundongos , Doenças Neurodegenerativas/patologiaRESUMO
OBJECTIVES: The role of autophagy in the pathophysiology of otitis media with effusion (OME) remains unclear, particularly regarding the difference between pediatric and adult patients. The present study analyzed the expression levels of autophagy-associated mRNAs in effusion fluids obtained from pediatric and adult patients with OME. MATERIALS AND METHODS: Middle ear fluid samples were collected from 76 pediatric patients and 41 adult patients with OME, and the levels of mRNAs encoding autophagy-related genes were measured using real-time reverse transcription-polymerase chain reaction. The relationships between the levels of autophagy-associated mRNAs and the frequency of ventilation tube insertion, the characteristics of middle ear fluid, and the results of bacterial culture were analyzed. RESULTS: Autophagy-associated mRNAs were present in the effusion fluid of all patients. The level of Beclin-1 mRNA was significantly lower in pediatric than in adult patients, regardless of the frequency of surgery or fluid characteristics (p < 0.05). CONCLUSION: Autophagy-associated mRNAs were expressed in effusion fluids of both pediatric and adult patients with OME. However, the level of Beclin-1 mRNA was significantly lower in the effusion fluid of pediatric than adult patients.
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Proteína Beclina-1/genética , Otite Média com Derrame/genética , RNA Mensageiro/genética , Adulto , Idoso , Autofagia/genética , Criança , Pré-Escolar , Orelha Média/patologia , Orelha Média/cirurgia , Exsudatos e Transudatos/metabolismo , Exsudatos e Transudatos/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ventilação da Orelha Média/efeitos adversos , Ventilação da Orelha Média/métodos , Otite Média/complicações , Otite Média/patologia , Otite Média/cirurgia , Otite Média com Derrame/diagnóstico , Otite Média com Derrame/microbiologia , Otite Média com Derrame/cirurgia , Reação em Cadeia da Polimerase em Tempo Real/métodosRESUMO
Bio-mimicking the underwater sensors has tremendous potential in soft robotics, under water exploration and human interfaces. Pinniped are semiaquatic carnivores that use their whiskers to sense food by tracking the vortices left by potential prey. To detect and track the vortices inside the water, a fully 3D printed pinniped inspired multi-material whisker sensor is fabricated and characterized. The fabricated whisker is composed of a polyurethane rod with a length-to-diameter ratio (L/d) of 20:1 with four graphene patterns (length × diameter: 60 × 0.3 mm) perpendicular to each other. The graphene patterns are further connected with output signal wires via copper tape. The displacement (â¼5 mm) of the whisker rod in any direction (0-360°) causes the change in resistance [Formula: see text] because of generated tensile. The analog signals (resistance change) are digitalized by using analog to digital modules and fed to a microcontroller to detect the vortex. A virtual environment is designed such that it consists of a 3D printed fish fin, a water tank, a camera, and data loggers to study the response of fabricated whisker. The underwater sensitivity of the whisker sensor in any direction is detectable and remarkably high ([Formula: see text]% â¼1180). The mechanical reliability of the whisker sensor is tested by bending it up to 2000 cycles. The fabricated whisker's structure and material are unique, and no one has fabricated them by using cost-effective 3D printing methods earlier. This fully 3D printable flexible whisker sensor should be applicable to a wide range of soft robotic applications.
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Biomimética/instrumentação , Técnicas Biossensoriais/instrumentação , Impressão Tridimensional/instrumentação , Animais , Caniformia/fisiologia , Cobre , Grafite , RobóticaRESUMO
Soft actuators with complex range of motion lead to strong interest in applying devices like biomedical catheters and steerable soft pipe inspectors. To facilitate the use of soft actuators in devices where controlled, complex, precise, and fast motion is required, a structurally controlled Omni directional soft cylindrical actuator is fabricated in a modular way using multilayer composite of polylactic acid based conductive Graphene, shape memory polymer, shape memory alloy, and polyurethane. Multiple fabrication techniques are discussed step by step that mainly include fused deposition modeling based 3D printing, dip coating, and UV curing. A mathematical control model is used to generate patterned electrical signals for the Omni directional deformations. Characterizations like structural control, bending, recovery, path, and thermal effect are carried out with and without load (10 g) to verify the new cylindrical design concept. Finally, the application of Omni directional actuator as a steerable catheter is explored by fabricating a scaled version of carotid artery through 3D printing using a semitransparent material.
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Materiais Biomiméticos , Biomimética/instrumentação , Catéteres , Sistemas Microeletromecânicos/instrumentação , Desenho de Equipamento , Impressão Tridimensional , RobóticaRESUMO
Fibrosis and organ failure is a common endpoint for many chronic liver diseases. Much is known about the upstream inflammatory mechanisms provoking fibrosis and downstream potential for tissue remodeling. However, less is known about the transcriptional regulation in vivo governing fibrotic matrix deposition by liver myofibroblasts. This gap in understanding has hampered molecular predictions of disease severity and clinical progression and restricted targets for antifibrotic drug development. In this study, we show the prevalence of SOX9 in biopsies from patients with chronic liver disease correlated with fibrosis severity and accurately predicted disease progression toward cirrhosis. Inactivation of Sox9 in mice protected against both parenchymal and biliary fibrosis, and improved liver function and ameliorated chronic inflammation. SOX9 was downstream of mechanosignaling factor, YAP1. These data demonstrate a role for SOX9 in liver fibrosis and open the way for the transcription factor and its dependent pathways as new diagnostic, prognostic, and therapeutic targets in patients with liver fibrosis.