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BACKGROUND AND AIM: Bifidobacterium breve was the first bacteria isolated in the feces of healthy infants and is a dominant species in the guts of breast-fed infants. Some strains of B. breve have been shown to be effective at relieving intestinal inflammation, but the modes of action have yet to be elucidated. In this study, we investigated the mechanisms of action of B. breve CBT BR3 isolated from South Korean infant feces in relieving colitis in vitro and in vivo. METHODS: Colitis was induced in mice with dextran sodium sulfate (DSS) and dinitrobenzene sulfonic acid (DNBS). Quantitative reverse-transcription polymerase chain reaction, in vitro FITC-dextran flux permeability assay, and aryl hydrocarbon receptor (AhR) luciferase assay are performed using Caco-2 cells and HT29-Lucia™ AhR cells. RESULTS: B. breve CBT BR3 was orally administered. B. breve CBT BR3 improved colitis symptoms in both DSS- and DNBS-induced colitis models. B. breve CBT BR3 increased the number of goblet cells per crypt. B. breve increased the mRNA expressions of Notch, Spdef, Muc5, and Il22. The mRNA expressions of Occludin, which encodes a membrane tight-junction protein, and Foxo3, which encodes a protein related to butyrate metabolism, were also increased in the DSS- and DNBS-induced colitis models. B. breve CBT BR3 protected inflammation-induced epithelial cell permeability and improved goblet cell function by inducing aryl hydrocarbon receptor in vitro. CONCLUSIONS: These results indicate that B. breve CBT BR3 is effective at relieving intestinal inflammation by augmenting goblet cell regeneration.
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Bifidobacterium breve , Colite , Humanos , Animais , Camundongos , Células Caliciformes/metabolismo , Bifidobacterium breve/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Células CACO-2 , Colite/induzido quimicamente , Colite/terapia , Colite/metabolismo , Inflamação/terapia , Inflamação/metabolismo , RNA Mensageiro/genética , Regeneração , Sulfato de Dextrana , Mucosa Intestinal , Modelos Animais de Doenças , Camundongos Endogâmicos C57BLRESUMO
INTRODUCTION: Hyperhidrosis, causing excessive sweat, can be treated with Botulinum neurotoxin injection. Botulinum toxin, an effective and safe treatment for hyperhidrosis, unfortunately involves significant pain due to multiple injections. This study aims to propose a more efficient and less painful approach to nerve blocks for relief, by identifying optimal injection points to block the median nerve, thereby enhancing palmar hyperhidrosis treatment. METHODS: This study, involving 52 Korean cadaver arms (mean age 73.5 years), measured the location of the median nerve relative to the transverse line at the pisiform level to establish better nerve block injection sites. RESULTS: In between the extensor carpi radialis and palmaris longus, the median nerve was located at an average distance of 47.39 ± 6.43 mm and 29.39 ± 6.43 mm from the transverse line at the pisiform level. DISCUSSION: To minimize discomfort preceding the botulinum neurotoxin injection, we recommend the optimal injection site for local anesthesia to be located 4 cm distal to the transverse line of the pisiform, within the tendons of the palmaris longus and flexor carpi radialis muscles.
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Toxinas Botulínicas Tipo A , Hiperidrose , Humanos , Idoso , Anestesia Local/efeitos adversos , Nervo Mediano , Mãos , Hiperidrose/tratamento farmacológico , Hiperidrose/complicações , Dor/etiologiaRESUMO
Current drug delivery systems are hampered by poor delivery to tumors, in part reflecting poor encapsulation stability of nanocarriers. Although nanocarriers such as polymeric micelles have high colloidal stability and do not aggregate or precipitate in bulk solution, nanocarriers with low encapsulation stability can lose their cargo during circulation in blood due to interactions with blood cells, cellular membranes, serum proteins, and other biomacromolecules. The resulting premature drug release from carriers limits the therapeutic efficacy at target sites. Herein, we report a simple and robust technique to improve encapsulation stability of drug delivery systems. Specifically, we show that installation of disulfide cross-linked noncovalent polymer gatekeepers onto mesoporous silica nanoparticles with a high loading capacity for hydrophobic drugs enhances in vivo therapeutic efficacy by preventing premature release of cargo. Subsequent release of drug cargos was triggered by cleavage of disulfide cross-linking by glutathione, leading to improved antitumor activity of doxoroubicin in mice. These findings provide novel insights into the development of nanocarriers with high encapsulation stability and improved in vivo therapeutic efficacy.
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Nanocápsulas/química , Animais , Antineoplásicos/administração & dosagem , Coloides/química , Reagentes de Ligações Cruzadas/química , Doxorrubicina/administração & dosagem , Feminino , Células HeLa , Humanos , Camundongos , Camundongos Nus , Micelas , Nanocápsulas/efeitos adversos , Nanocápsulas/normas , Dióxido de Silício/químicaRESUMO
BACKGROUND: Current practice guidelines recommend surgical repair of large thoracic aortic aneurysms to prevent fatal aortic dissection or rupture, but limited natural history data exist to support clinical criteria for timely intervention. METHODS AND RESULTS: Of 3247 patients with thoracic aortic aneurysm registered in our institutional Thoracic Aortic Center Database, we identified and reviewed 257 nonsyndromic patients (age, 72.4±10.5 years; 143 female) with descending thoracic or thoracoabdominal aortic aneurysm without a history of aortic dissection in whom surgical intervention was not undertaken. The primary end point was a composite of aortic dissection/rupture and sudden death. Baseline mean maximal aortic diameter was 52.4±10.8 mm, with 103 patients having diameters ≥55 mm. During a median follow-up of 25.1 months (quartiles 1-3, 8.3-56.4 months), definite and possible aortic events occurred in 19 (7.4%) and 31 (12.1%) patients, respectively. On multivariable analyses, maximal aortic diameter at baseline emerged as the only significant predictor of aortic events (hazard ratio=1.12; 95% confidence interval, 1.08-1.15). Estimated rates of definite aortic events within 1 year were 5.5%, 7.2%, and 9.3% for aortic diameters of 50, 55, and 60 mm, respectively. Receiver-operating characteristic curves for discriminating aortic events were higher for indexed aortic sizes referenced by body size (area under the curve=0.832-0.889) but not significantly different from absolute maximal aortic diameter (area under the curve=0.805). CONCLUSIONS: Aortic size was the principal factor related to aortic events in unrepaired descending thoracic or thoracoabdominal aortic aneurysm. Although the risk of aortic events started to increase with a diameter >5.0 to 5.5 cm, it is uncertain whether repair of thoracic aortic aneurysms in this range leads to overall benefit, and the threshold for repair requires further evaluation.
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Aorta Torácica/ultraestrutura , Aneurisma da Aorta Torácica/epidemiologia , Dissecção Aórtica/epidemiologia , Ruptura Aórtica/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Dissecção Aórtica/patologia , Dissecção Aórtica/cirurgia , Aneurisma da Aorta Torácica/patologia , Aneurisma da Aorta Torácica/cirurgia , Doenças da Aorta/epidemiologia , Ruptura Aórtica/patologia , Ruptura Aórtica/cirurgia , Aterosclerose/epidemiologia , Bases de Dados Factuais , Morte Súbita/epidemiologia , Morte Súbita/etiologia , Diabetes Mellitus/epidemiologia , Dilatação Patológica/epidemiologia , Feminino , Seguimentos , Humanos , Hiperlipidemias/epidemiologia , Hipertensão/epidemiologia , Masculino , Massachusetts/epidemiologia , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Curva ROC , Risco , Fumar/epidemiologiaRESUMO
We have designed a reflective composite sheet consisting of a birefringent polymer matrix and isolated isotropic or minimally birefringent fibers. The optical properties of the sheet have been investigated in terms of the width, spacing, and thickness of the individual fibers. Commercial software (FDTD Solution) was used to simulate the reflectance of the proposed sheet, and conventional processes such as cast-film extrusion in combination with solid-state drawing were used to manufacture the multilayer composite sheet. The measured and simulated reflectance spectra confirm the feasibility of employing the sheet as a reflective polarizer.
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This article presents free-floating three-dimensional (3D) microstructure fabrication in a microfluidic channel using direct fine-tuned grayscale image lithography. The image is designed as a freeform shape and is composed of gray shades as light-absorbing features. Gray shade levels are modulated through multiple reflections of light in a digital micromirror device (DMD) to produce different height formations. Whereas conventional photolithography has several limitations in producing grayscale colors on photomask features, our method focuses on a maskless, single-shot process for fabrication of freeform 3D micro-scale shapes. The fine-tuned gray image is designed using an 8-bit grayscale color; thus, each pixel is capable of displaying 256 gray shades. The pattern of the UV light reflecting on the DMD is transferred to a photocurable resin flowing through a microfluidic channel. Here, we demonstrate diverse free-floating 3D microstructure fabrication using fine-tuned grayscale image lithography. Additionally, we produce polymeric microstructures with locally embedded gray encoding patterns, such as grayscale-encoded microtags. This functional microstructure can be applied to a biophysical detection system combined with 3D microstructures. This method would be suitable for fabricating 3D microstructures that have a specific morphology to be used for particular biological or medical applications.
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Peptide-functionalized nanomedicine, which addresses the challenges of specificity and efficacy in drug delivery, is emerging as a pivotal approach for cancer therapy. Globally, cancer remains a leading cause of mortality, and conventional treatments, such as chemotherapy, often lack precision and cause adverse effects. The integration of peptides into nanomedicine offers a promising solution for enhancing the targeting and delivery of therapeutic agents. This review focuses on the three primary applications of peptides: cancer cell-targeting ligands, building blocks for self-assembling nanostructures, and elements of stimuli-responsive systems. Nanoparticles modified with peptides improved targeting of cancer cells, minimized damage to healthy tissues, and optimized drug delivery. The versatility of self-assembled peptide structures makes them an innovative vehicle for drug delivery by leveraging their biocompatibility and diverse nanoarchitectures. In particular, the mechanism of cell death induced by self-assembled structures offers a novel approach to cancer therapy. In addition, peptides in stimuli-responsive systems enable precise drug release in response to specific conditions in the tumor microenvironment. The use of peptides in nanomedicine not only augments the efficacy and safety of cancer treatments but also suggests new research directions. In this review, we introduce systems and functionalization methods using peptides or peptide-modified nanoparticles to overcome challenges in the treatment of specific cancers, including breast cancer, lung cancer, colon cancer, prostate cancer, pancreatic cancer, liver cancer, skin cancer, glioma, osteosarcoma, and cervical cancer.
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Cancer remains a major global health challenge, necessitating the development of innovative treatment strategies. This review focuses on the functionalization of porous nanoparticles for combination therapy, a promising approach to enhance cancer treatment efficacy while mitigating the limitations associated with conventional methods. Combination therapy, integrating multiple treatment modalities such as chemotherapy, phototherapy, immunotherapy, and others, has emerged as an effective strategy to address the shortcomings of individual treatments. The unique properties of mesoporous silica nanoparticles (MSN) and other porous materials, like nanoparticles coated with mesoporous silica (NP@MS), metal-organic frameworks (MOF), mesoporous platinum nanoparticles (mesoPt), and carbon dots (CDs), are being explored for drug solubility, bioavailability, targeted delivery, and controlled drug release. Recent advancements in the functionalization of mesoporous nanoparticles with ligands, biomaterials, and polymers are reviewed here, highlighting their role in enhancing the efficacy of combination therapy. Various research has demonstrated the effectiveness of these nanoparticles in co-delivering drugs and photosensitizers, achieving targeted delivery, and responding to multiple stimuli for controlled drug release. This review introduces the synthesis and functionalization methods of these porous nanoparticles, along with their applications in combination therapy.
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Strain-controlled low cycle fatigue (LCF) tests were conducted on conventionally grained (CG) and ultrafine-grained (UFG) Al-Mg-Si alloys treated under various aging conditions. In the cyclic stress response (CSR) curves, CG peak-aged (PA) alloys showed initial cyclic hardening and subsequent saturation, whereas CG over-aged (OA) alloys displayed cyclic softening behavior close to saturation. The UFG materials exhibited continuous cyclic softening except for UFG 3; it originates from the microstructural stability of the UFG materials processed by severe plastic deformation (SPD). Using a strain-based criterion, the LCF behavior and life of the CG and UFG materials were analyzed and evaluated; the results are discussed in terms of strengthening mechanisms and microstructural evolution. In the CG materials, the LCF life changed markedly owing to differences in deformation inhomogeneity depending on the precipitate state. However, the UFG materials displayed a decreasing LCF life as cyclic softening induced by dynamic recovery became more severe; additionally, a relationship between the microstructural stability of the UFG materials and the cyclic strain hardening exponent n' was suggested.
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Gold nanorods (GNRs) have received much attention as potential drug-delivery vehicles because of their various advantages such as good biocompatibility, passive targeting, responsiveness to stimuli, and easy post-functionalization by surface modification. However, the drug structure might be changed for loading into GNRs, making it difficult to load various drugs, and the space to contain drugs is small, making it difficult to deliver sufficient drugs required for treatment compared with other porous materials. Herein, we report an amphiphilic polymer-coated GNR platform for chemo- and photothermal combination therapy. Amphiphilic polymers comprise hydrophobic alkyl chains for drug encapsulation, polyethylene glycol for biocompatibility, and folic acid for cancer targeting. GNRs generate heat energy under near-infrared light irradiation, promoting controlled drug release, and inducing cellular uptake by deforming the cell membrane. On-demand release behavior was traced with Nile red, and targeting and delivery efficiency were confirmed with paclitaxel through cellular experiments. This GNR-based platform enables combination therapy with passive and active targeting to enhance the efficacy of cancer treatment.
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The ELISA is the most worldwide method for immunoassay. However, the ELISA is losing ground due to low reproducibility of manual experimental processes in both R&D and IVD areas. An automated platform is a good solution, but there are still limitations owning to extremely high cost and requiring large space to set up especially for a small size laboratory. Here, we present a novel all-in-one platform called "VEUS" settable on the laboratory table that offers comprehensive automation of the entire multiplex immunoassay process by exploiting antibody conjugated magnetic particles, quality control and then immunoanalytical reaction, thereby enhancing detection sensitivity and high reproducibility. As a proof of concept, the system exhibits a sensitive LOD of 0.6 and 3.1 pg mL-1 within 1 h run, comparable precision that of molecular diagnostic systems based on PCR method, enabling rapid multiplex diagnosis of Influenza A, Influenza B, and COVID-19 viruses with similar symptoms. Through automation by the all-in-one system, it can be used by novice users, something innovative for immunoassays, relying heavily on user experience. Furthermore, it can contribute to streamline entire immunoassay processes of diverse biomarkers with high reproducibility and convenience in laboratories.
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SARS-CoV-2 , Humanos , Imunoensaio/métodos , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Anticorpos Imobilizados/imunologia , Anticorpos Imobilizados/química , Reprodutibilidade dos Testes , COVID-19/diagnóstico , COVID-19/virologia , Ensaio de Imunoadsorção Enzimática/métodos , Vírus da Influenza A/imunologia , Vírus da Influenza B/imunologia , Automação Laboratorial/métodos , Limite de DetecçãoRESUMO
A high-performance semiconductor metal oxide gas sensing strategy is proposed for efficient sensor-based disease prediction by integrating a machine learning methodology with complementary sensor arrays composed of SnO2- and WO3-based sensors. The six sensors, including SnO2- and WO3-based sensors and neural network algorithms, were used to measure gas mixtures. The six constituent sensors were subjected to acetone and hydrogen environments to monitor the effect of diet and/or irritable bowel syndrome (IBS) under the interference of ethanol. The SnO2- and WO3-based sensors suffer from poor discrimination ability if sensors (a single sensor or multiple sensors) within the same group (SnO2- or WO3-based) are separately applied, even when deep learning is applied to enhance the sensing operation. However, hybrid integration is proven to be effective in discerning acetone from hydrogen even in a two-sensor configuration through the synergistic contribution of supervised learning, i.e., neural network approaches involving deep neural networks (DNNs) and convolutional neural networks (CNNs). DNN-based numeric data and CNN-based image data can be exploited for discriminating acetone and hydrogen, with the aim of predicting the status of an exercise-driven diet and IBS. The ramifications of the proposed hybrid sensor combinations and machine learning for the high-performance breath sensor domain are discussed.
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Acetona , Síndrome do Intestino Irritável , Humanos , Algoritmos , Hidrogênio , Aprendizado de MáquinaRESUMO
The genus Gelanes Horstmann is recorded from South Korea for the first time. Eight species of the genus are found to occur in this country. Four species, G dentator sp. nov., G protritus sp. nov., G provectus sp. nov. and G verendus sp. nov., are described as new, three species, G belokobylskii, G cuspidatus and G simillimus, also occur in the Russian Far East, and G gubarevae was previously known only from Europe. A key to the South Korean species of Gelanes is provided.
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Vespas/anatomia & histologia , Vespas/classificação , Animais , Demografia , Feminino , República da Coreia , Especificidade da EspécieRESUMO
Magnesium and its alloys have been restricted in their industrial applications due to problems related to their formability. To overcome this issue, controlling the crystallographic texture is important, and the texture formation mechanism should be investigated in relation to factors including deformation conditions and solute atoms. In particular, the effects of solute atoms on the texture formation behavior should be further analyzed because they can considerably affect the deformation behavior. Thus, in this study, to clarify the effect of aluminum concentration on the texture formation behavior and microstructure, high-temperature uniaxial compression tests were conducted on three types of AZ-series magnesium alloys (AZ31, AZ61, and AZ91). Compression was conducted at 673 K and 723 K, with strain rates of 0.05 s-1 and 0.005 s-1, up to a true strain of -1.0. Cylindrical specimens were prepared from a rolled plate that had a (0001) basal texture and was compressed parallel to the c-axis of the grains. Consequently, work softening and fiber texture formation were observed in all the specimens. During the deformation, the development of grain boundaries, which is a typical characteristic of continuous dynamic recrystallization (CDRX), was observed, and the (0001) texture was highly developed with increasing Al content. Although each alloy was associated with the same deformation conditions and mechanisms, the AZ31 alloy exhibited a non-basal texture component. The stacking fault energy contributed to the generation of slip systems and gliding, and it was seen as the main reason for texture variation.
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For a wide industrial application of magnesium alloys, a method for imparting high damping properties while maintaining mechanical properties is required. Controlling the crystallographic texture seems to be useful, because dislocations are known to have a significant influence on the damping characteristics of magnesium alloys. In addition, textures are affected by the microstructure and texture variation when the deformation or annealing is applied. However, there were less reports about their effect on damping capacity. Therefore, the effect of twinning and annealing, which can affect the recrystallization, were investigated in this study. An AZ31 alloy was hot rolled at 673 K with a reduction ratio of 10% and 50%, and then annealed at 673 K and 723 K for 0.5, 1, 2, and 3 h, respectively. SEM-EBSD was used to examine the microstructure and texture. In addition, each specimen's hardness and internal friction were contemporarily measured. As a result, hot rolling produced tensile twins and their fraction increased with internal friction when the reduction ratio increased. Due to annealing, a discontinuous type of static recrystallization occurred within the twinning grains, and was highly activated along with the increasing annealing temperature and the fraction of twinning. In the samples annealed at 723 K, the internal friction continuously increased over the annealing time, whereas in the samples annealed at 673 K, the decrease in dislocation density was delayed while the internal friction showed a relatively low value.
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The blood-brain barrier (BBB) is one of the most selective endothelial barriers that protect the brain and maintains homeostasis in neural microenvironments. This barrier restricts the passage of molecules into the brain, except for gaseous or extremely small hydrophobic molecules. Thus, the BBB hinders the delivery of drugs with large molecular weights for the treatment of brain cancers. Various methods have been used to deliver drugs to the brain by circumventing the BBB; however, they have limitations such as drug diversity and low delivery efficiency. To overcome this challenge, microbubbles (MBs)-based drug delivery systems have garnered a lot of interest in recent years. MBs are widely used as contrast agents and are recently being researched as a vehicle for delivering drugs, proteins, and gene complexes. The MBs are 1-10 µm in size and consist of a gas core and an organic shell, which cause physical changes, such as bubble expansion, contraction, vibration, and collapse, in response to ultrasound. The physical changes in the MBs and the resulting energy lead to biological changes in the BBB and cause the drug to penetrate it, thus enhancing the therapeutic effect. Particularly, this review describes a state-of-the-art strategy for fabricating MB-based delivery platforms and their use with ultrasound in brain cancer therapy.
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An effective approach to accelerating wound healing is through a smart delivery platform that releases drugs according to the needs of different healing periods. With the growing demand for wound care and treatment, electrospun nanofibers have attracted considerable attention owing to their simple and versatile method of manufacturing, unique structure, and biological functions similar to those of the extracellular matrix. Moreover, nanofibers can be loaded with active substances that promote targeted wound healing. In this study, we investigated the performance of a core-shell nanofiber platform loaded with two drugs in the core and shell, respectively. The shell polymer, poly-l-lactic acid, initially releases the encapsulated drug into an aqueous solution at room temperature. Gold nanorods with near-infrared absorbance were incorporated in the core polymer poly(N-isopropylacrylamide) to produce localized heat by plasmon resonance when exposed to light. This allows the thermally responsive core polymer to swell and shrink for programmable drug release. Our study provides a versatile platform for controlled and safe drug delivery to wound sites and could be applied to the treatment of other topical diseases.
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Nanofibras , Nanofibras/química , Liberação Controlada de Fármacos , Cicatrização , Sistemas de Liberação de Medicamentos , Polímeros/farmacologiaRESUMO
To enhance the formability of magnesium alloys, inhibition of basal texture development by the particle-stimulated nucleation (PSN) effect has attracted significant interest. However, its contribution to texture development is not easily observed due to the separation of texture from the conventional deformation behavior. This study aims to separate the Ca texture from the deformation behavior of AZX611 alloy and quantify it using scanning electron microscopy with electron backscatter diffraction (SEM-EBSD). Since Ca in the AZ61 magnesium alloy precipitated as Al2Ca, the hot-rolled magnesium alloys AZ31, AZ61, and AZX611 were used. High temperature compression was conducted at 723 K, the strain rate 0.05/s and 0.005/s and the true strain up to -1.0. Dynamic recrystallization was observed in each specimen and the Ca-free alloys showed dislocation glide at high strain rates and solute drag at low strain rates. When the dislocation glide dominated, basal texture was strengthened. In contrast, solute drag caused non-basal texture development. Precipitation hardening caused AZ61 to have higher flow stress than those of the Ca-free alloys by the PSN effect; its texture was observed separately because the PSN grain growth around the precipitation and orientation was specific, similar to the one developed at the solute atom drag.
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Dermal delivery, which delivers drugs and cosmetics through the skin, has attracted significant attention due to its non-invasive and simple administration compared with oral or injectable administration. However, delivery of the ingredients through the skin barrier is difficult because the primary function of the skin is to protect the human body by preventing the invasion of contaminants. Although various techniques have been developed to overcome skin barriers, chemical toxicity, complicated processes, and expensive equipment still remain as obstacles. Moreover, green chemistry, which minimizes or eliminates the use of toxic chemicals, is required in the cosmetic industry. Thus, the development of a new method for dermal delivery is required. In this study, we provide a new method for dermal delivery using nanobubbles (NBs). NBs generated in oil improve the delivery effect of the active ingredients through the high Brownian motion and charge-balancing effect. Franz cell experiments and depigmentation experiments using the B16F10 melanoma cells were conducted to confirm the enhanced delivery effects. The system using NBs will contribute to the advancement of the dermal delivery of drugs and cosmetics.
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The use of cellular structures has led to unprecedented outcomes in various fields involving optical and mechanical cloaking, negative thermal expansion, and a negative Poisson's ratio. The unique characteristics of periodic cellular structures primarily originate from the interconnectivity, periodicity, and unique design of the unit cells. However, the periodicity often induces unfavorable mechanical behaviors such as a "post-yielding collapse", and the mechanical performance is often limited by the design of the unit cells. Therefore, we propose a novel structure called a meta grain structure (MGS), which is inspired by a polycrystalline structure, to enhance flexibility in design and mechanical reliability. A total of 138 different MGSs were built and tested numerically, and the correlations between the design parameters (e.g., the relative density) and mechanical properties of the MGSs were rigorously analyzed. A systematic design methodology was developed to obtain the optimal design of the MGS with the target Young's modulus. This methodology makes it possible to build a unique structure that offers various design options and overcomes the current limitations of cellular structures. Furthermore, a systematic inverse design methodology makes it possible to produce an MGS that satisfies the required mechanical performance.