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INTRODUCTION: Cholangiocarcinoma (CCC) still has a high mortality rate despite improvements in diagnostic and therapeutic techniques. The role of the human microbiome in CCC is poorly understood, and a recent metagenomic analysis demonstrated a significant correlation between microbiome-associated carcinogenesis and CCC. This study aimed to investigate changes in microbiome composition associated with CCC and its metabolic signature by integrating taxonomic and functional information with metabolomics data and in vitro experimental results. METHODS: From February 2019 to January 2021, this study included patients who underwent endoscopic retrograde cholangiopancreatography (ERCP), both with and without a diagnosis of CCC. Bile samples were collected via endoscopic nasobiliary drainages (ENBD) and subjected to DNA extraction, PCR amplification of the bacterial 16S rRNA gene V3-V4 region, and data analysis using QIIME2. In vitro Carboxyfluorescein succinimidyl ester (CFSE) proliferation and Annexin V/PI apoptosis assays were performed to investigate the effects of metabolites on CCC cells. RESULTS: A total of 24 patients were included in the study. Bile fluid analysis revealed a significantly higher abundance of Escherichia coli in the CCC group. Alpha diversity analyses exhibited significant differences between the CCC and non-CCC groups, and Nuclear Magnetic Resonance (NMR) spectroscopy metabolic profiling identified 15 metabolites with significant concentration differences; isoleucine showed the most notable difference. In vitro experiments demonstrated that isoleucine suppressed CCC cell proliferation but did not induce apoptosis. CONCLUSIONS: This research underlines the significance of biliary dysbiosis and specific bile metabolites, such as isoleucine, in influencing the development and progression of CCC.
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A taxonomic study of Spilonota Stephens, 1834, in Korea is conducted, and S. prognathana (Snellen, 1883) which had previously been merged with S. albicana (Motschulsky, 1866) is separated again. Additionally, as a result of research based on materials from Incheon National University two new species; S. samseong Choi, Bae & Nasu, S. laticucullusa Choi, Bae & Nasu proposed from Korea. The study provides brief descriptions of Spilonota species in Korea, with illustrations of the adult and genital morphology. Identification key for the known species reported from Korea is included.
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Lepidópteros , Mariposas , Humanos , Animais , Genitália , UniversidadesRESUMO
Development of coating technologies for electrochemical sensors that consistently exhibit antifouling activities in diverse and complex biological environments over extended time is vital for effective medical devices and diagnostics. Here, we describe a micrometer-thick, porous nanocomposite coating with both antifouling and electroconducting properties that enhances the sensitivity of electrochemical sensors. Nozzle printing of oil-in-water emulsion is used to create a 1 micrometer thick coating composed of cross-linked albumin with interconnected pores and gold nanowires. The layer resists biofouling and maintains rapid electron transfer kinetics for over one month when exposed directly to complex biological fluids, including serum and nasopharyngeal secretions. Compared to a thinner (nanometer thick) antifouling coating made with drop casting or a spin coating of the same thickness, the thick porous nanocomposite sensor exhibits sensitivities that are enhanced by 3.75- to 17-fold when three different target biomolecules are tested. As a result, emulsion-coated, multiplexed electrochemical sensors can carry out simultaneous detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid, antigen, and host antibody in clinical specimens with high sensitivity and specificity. This thick porous emulsion coating technology holds promise in addressing hurdles currently restricting the application of electrochemical sensors for point-of-care diagnostics, implantable devices, and other healthcare monitoring systems.
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Incrustação Biológica , Técnicas Biossensoriais , Nanocompostos , Porosidade , Emulsões , Anticorpos , Técnicas EletroquímicasRESUMO
INTRODUCTION: Common bile duct (CBD) stones are a health concern for 10-20% of individuals with symptomatic gallstones, leading to health complications and placing a burden on healthcare systems. This study was initiated to investigate the changes in microbiome compositions and the metabolic signature associated with CBD stones. The research approach integrated taxonomic and functional data with metabolomics data, complemented by in vivo experiments. METHODS: In a single tertiary healthcare institution, a total of 25 patients were enrolled who had undergone endoscopic retrograde cholangiopancreatography (ERCP) between February 2019 and January 2021. We harvested DNA from bile samples acquired from these individuals. The amplification of the bacterial 16S rRNA gene V3-V4 region was conducted through polymerase chain reaction (PCR), followed by sequencing. We utilized QIIME2 for a comprehensive data analysis. Furthermore, we performed a metabolomic analysis of the bile samples using nuclear magnetic resonance (NMR) spectroscopy. For the assessment of functional gene enrichment, we employed MetaboAnalyst 5.0. Lastly, we executed in vivo experiments on C57BL/6 mice and undertook histological examinations of tissue samples. RESULTS: Out of the 25 study subjects, 17 underwent ERCP due to CBD stones (the CBD stone group), while the remaining 8 had the procedure for different reasons (the non-CBD stone group). An alpha diversity analysis showed a significantly greater microbial diversity in the bile samples of the non-CBD stone group (p < 0.01), and a beta diversity analysis confirmed the greater microbial compositional abundance in the gut microbiomes in this group (p = 0.01). A taxonomic analysis revealed that the abundances of Enterococcaceae and Enterococcus were higher in the bile microbiomes of the CBD stone group. A metabolic profile analysis showed that the acetate, formate, and asparagine levels were higher in the CBD stone group. A pathway enrichment analysis showed the metabolic pathways (Arginine and Proline Metabolism, Aspartate Metabolism, Glycine, and Serine Metabolism, and Ammonia Recycling pathways) that were associated with these differences. Preclinical experiments demonstrated systemic inflammation and extracellular trap formation in the CBD stone group. CONCLUSIONS: Our study highlights the importance of biliary dysbiosis and bile metabolites, specifically acetate and formate, in CBD stone development and progression. These findings have implications for the development of diagnostic and therapeutic strategies using microbiomes for CBD stones.
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Two new species, Stericta jaeshini Kim & Bae, sp. nov. and S. atroaurantiaca Kim & Bae, sp. nov. are described from Southeast Asia. About 50 species of the genus Stericta have been recorded from Southeast Asia, but it has not been recorded to occur in Laos and Cambodia previously. We record the presence of this genus in these two countries for the first time in this study. Illustrations of adults and genitalia of examined species are provided. v.
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Lepidópteros , Mariposas , Animais , Laos , Camboja , Distribuição Animal , GenitáliaRESUMO
Liposomes have been extensively adopted in drug delivery systems with clinically approved formulations. However, hurdles remain in terms of loading multiple components and precisely controlling their release. Herein, we report a vesosomal carrier composed of liposomes encapsulated inside the core of another liposome for the controlled and sustained release of multiple contents. The inner liposomes are made of lipids with different compositions and are co-encapsulated with a photosensitizer. Upon induction of reactive oxygen species (ROS), the contents of the liposomes are released, with each type of liposome displaying distinct kinetics due to the variance in lipid peroxidation for differential structural deformation. In vitro experiments demonstrated immediate content release from ROS-vulnerable liposomes, followed by sustained release from ROS-nonvulnerable liposomes. Moreover, the release trigger was validated at the organismal level using Caenorhabditis elegans. This study demonstrates a promising platform for more precisely controlling the release of multiple components.
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Portadores de Fármacos , Lipossomos , Lipossomos/química , Preparações de Ação Retardada/farmacologia , Espécies Reativas de Oxigênio , Sistemas de Liberação de MedicamentosRESUMO
A two-dimensional (2D) atomic crystalline transition metal dichalcogenides has shown immense features, aiming for future nanoelectronic devices comparable to conventional silicon (Si). 2D molybdenum ditelluride (MoTe2) has a small bandgap, appears close to that of Si, and is more favorable than other typical 2D semiconductors. In this study, we demonstrate laser-induced p-type doping in a selective region of n-type semiconducting MoTe2 field effect transistors (FET) with an advance in using the hexagonal boron nitride as passivation layer from protecting the structure phase change from laser doping. A single nanoflake MoTe2-based FET, exhibiting initial n-type and converting to p-type in clear four-step doping, changing charge transport behavior in a selective surface region by laser doping. The device shows high electron mobility of about 23.4 cm2V-1s-1 in an intrinsic n-type channel and hole mobility of about 0.61 cm2V-1s-1 with a high on/off ratio. The device was measured in the range of temperature 77-300 K to observe the consistency of the MoTe2-based FET in intrinsic and laser-dopped region. In addition, we measured the device as a complementary metal-oxide-semiconductor (CMOS) inverter by switching the charge-carrier polarity of the MoTe2 FET. This fabrication process of selective laser doping can potentially be used for larger-scale MoTe2 CMOS circuit applications.
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Background: Ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) are used to treat patients with asymptomatic or mildly symptomatic gallstone disease. This study was conducted to evaluate the efficacy of gallbladder (GB) stone dissolution by UDCA/CDCA and the impact of treatment on gut microbial profiles. Methods: Fifteen treatment-naive patients with GB stones were initially included, but two dropped out during the treatment period. UDCA/CDCA was administered for 6 months. Abdominal ultrasonography was performed to evaluate response to treatment. In addition, fecal samples were collected before and after treatment for gut microbiome profiling. Then, 16S ribosomal RNA gene sequencing was carried out on fecal samples obtained before and after treatment, and results were compared with those of forty healthy controls. Results: Eight (62%) of the thirteen evaluable patients treated with UDCA/CDCA responded to treatment (four achieved complete GB stone resolution and four partial dissolution). Taxonomic compositions of fecal samples at the phylum level showed a significantly lower relative abundance of the Proteobacteria phylum in the pre-UDCA/CDCA group than in the healthy control group (p = 0.024). At the genus level, the relative abundances of five bacteria (Faecalibacterium, Roseburia, Lachnospira, Streptococcus, and Alistipes) differed in the control and pre-UDCA/CDCA group. Interestingly, the abundance of Roseburia was restored after 6 months of UDCA/CDCA treatment. Conclusion: Gut microbial dysbiosis was observed in GB stone patients and partially reversed by UDCA/CDCA treatment, which also effectively dissolved GB stones.
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Histone deacetylases (HDACs) deacetylate histones H3 and H4. An imbalance between histone acetylation and deacetylation can lead to various diseases. HDAC2 is present in the nucleus. It plays a critical role in modifying chromatin structures and regulates the expression of various genes by functioning as a transcriptional regulator. The roles of HDAC2 in tumorigenesis and anti-cancer drug resistance are discussed in this review. Several reports suggested that HDAC2 is a prognostic marker of various cancers. The roles of microRNAs (miRNAs) that directly regulate the expression of HDAC2 in tumorigenesis are also discussed in this review. This review also presents HDAC2 as a valuable target for developing anti-cancer drugs.
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Soft pressure sensors play key roles as input devices of electronic skin (E-skin) to imitate real human skin. For efficient data acquisition according to stimulus types such as detailed pressure images or macroscopic strength of stimuli, soft pressure sensors can have variable spatial resolution, just like the uneven spatial distribution of pressure-sensing receptors on the human body. However, previous methods on soft pressure sensors cannot achieve such tunability of spatial resolution because their sensor materials and read-out electrodes need to be elaborately patterned for a specific sensor density. Here, we report a universal soft pressure-sensitive platform based on anisotropically self-assembled ferromagnetic particles embedded in elastomer matrices whose spatial resolution can be facilely tuned. Various spatial densities of pressure-sensing receptors of human body parts can be implemented by simply sandwiching the film between soft electrodes with different pitches. Since the anisotropically aligned nickel particles form independent filamentous conductive paths, the pressure sensors show spatial sensing ability without crosstalk, whose spatial resolution up to 100 dpi can be achieved from a single platform. The sensor array shows a wide dynamic range capable of detecting various pressure levels, such as liquid drops (â¼30 Pa) and plantar (â¼300 kPa) pressures. Our universal soft pressure-sensing platform would be a key enabling technology for actually imitating the receptor systems of human skin in robot and biomedical applications.
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Dispositivos Eletrônicos Vestíveis , Humanos , Pele , Condutividade ElétricaRESUMO
Liquid metal is being regarded as a promising material for soft electronics owing to its distinct combination of high electrical conductivity comparable to that of metals and exceptional deformability derived from its liquid state. However, the applicability of liquid metal is still limited due to the difficulty in simultaneously achieving its mechanical stability and initial conductivity. Furthermore, reliable and rapid patterning of stable liquid metal directly on various soft substrates at high-resolution remains a formidable challenge. In this work, meniscus-guided printing of ink containing polyelectrolyte-attached liquid metal microgranular-particle in an aqueous solvent to generate semi-solid-state liquid metal is presented. Liquid metal microgranular-particle printed in the evaporative regime is mechanically stable, initially conductive, and patternable down to 50 µm on various substrates. Demonstrations of the ultrastretchable (~500% strain) electrical circuit, customized e-skin, and zero-waste ECG sensor validate the simplicity, versatility, and reliability of this manufacturing strategy, enabling broad utility in the development of advanced soft electronics.
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Transition metal dichalcogenides (TMDs) are of great interest owing to their unique properties. However, TMD materials face two major challenges that limit their practical applications: contact resistance and surface contamination. Herein, a strategy to overcome these problems by inserting a monolayer of hexagonal boron nitride (h-BN) at the chromium (Cr) and tungsten disulfide (WS2 ) interface is introduced. Electrical behaviors of direct metal-semiconductor (MS) and metal-insulator-semiconductor (MIS) contacts with mono- and bilayer h-BN in a four-layer WS2 field-effect transistor (FET) are evaluated under vacuum from 77 to 300 K. The performance of the MIS contacts differs based on the metal work function when using Cr and indium (In). The contact resistance is significantly reduced by approximately ten times with MIS contacts compared with that for MS contacts. An electron mobility up to ≈115 cm2 V-1 s-1 at 300 K is achieved with the insertion of monolayer h-BN, which is approximately ten times higher than that with MS contacts. The mobility and contact resistance enhancement are attributed to Schottky barrier reduction when h-BN is introduced between Cr and WS2 . The dependence of the tunneling mechanisms on the h-BN thickness is investigated by extracting the tunneling barrier parameters.
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Exposure to ambient particulate matter (PM) is associated with adverse health effects. Yet, due to the complexity of its chemical composition, the molecular effects of PM exposure and the mechanism of PM-mediated toxicity remain largely unknown. Here, we show that water-soluble inorganics such as nitrate and sulfate ions, rather than PM itself, rapidly penetrate the lung surfactant barrier to the alveolar region and perturb gene expression in the lungs. Through high-throughput sequencing of lung adenocarcinoma cells, we find that exposure to nitrate and sulfate ions activates the cholesterol biosynthetic metabolism and induces the expression of genes related to tumorigenesis. Transcriptome analysis of mouse lungs exposed to nitrate/sulfate aerosols reveals interferon gamma-associated immune response. Interestingly, we find that exposure to a nitrate/sulfate mixture leads to a unique gene expression pattern that is not observed when nitrate or sulfate is treated alone. Our work suggests that the water-soluble ions are a potential source of PM-mediated toxicity and provides a roadmap to unveil the molecular mechanism of health hazards from PM exposure.
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Poluentes Atmosféricos , Material Particulado , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Animais , Pulmão/metabolismo , Camundongos , Nitratos/análise , Material Particulado/análise , Sulfatos/análise , Água/análiseRESUMO
Iminosemiquinone-linker-based conductive metal-organic frameworks (c-MOFs) have attracted much attention as next-generation electronic materials due to their high electrical conductivity combined with high porosity. However, the utility of such c-MOFs in high-performance devices has been limited to date by the lack of high-quality MOF thin-film processing. Herein, a technique known as the microfluidic-assisted solution shearing combined with post-synthetic rapid crystallization (MASS-PRC) process is introduced to generate a high-quality, flexible, and transparent thin-film of Ni3 (hexaiminotriphenylene)2 (Ni3 (HITP)2 ) uniformly over a large-area in a high-throughput manner with thickness controllability down to tens of nanometers. The MASS-PRC process utilizes: 1) a micromixer-embedded blade to simultaneously mix and continuously supply the metal-ligand solution toward the drying front during solution shearing to generate an amorphous thin-film, followed by: 2) immersion in amine solution for rapid directional crystal growth. The as-synthesized c-MOF film has transparency of up to 88.8% and conductivity as high as 37.1 S cm-1 . The high uniformity in conductivity is confirmed over a 3500 mm2 area with an arithmetic mean roughness (Ra ) of 4.78 nm. The flexible thin-film demonstrates the highest level of transparency for Ni3 (HITP)2 and the highest hydrogen sulfide (H2 S) sensing performance (2,085% at 5 ppm) among c-MOFs-based H2 S sensors, enabling wearable gas-sensing applications.
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Photosynthetic organisms are exposed to various environmental sources of oxidative stress. Land plants have diverse mechanisms to withstand oxidative stress, but how microalgae do so remains unclear. Here, we characterized the Chlamydomonas reinhardtii basic leucine zipper (bZIP) transcription factor BLZ8, which is highly induced by oxidative stress. Oxidative stress tolerance increased with increasing BLZ8 expression levels. BLZ8 regulated the expression of genes likely involved in the carbon-concentrating mechanism (CCM): HIGH-LIGHT ACTIVATED 3 (HLA3), CARBONIC ANHYDRASE 7 (CAH7), and CARBONIC ANHYDRASE 8 (CAH8). BLZ8 expression increased the photosynthetic affinity for inorganic carbon under alkaline stress conditions, suggesting that BLZ8 induces the CCM. BLZ8 expression also increased the photosynthetic linear electron transfer rate, reducing the excitation pressure of the photosynthetic electron transport chain and in turn suppressing reactive oxygen species (ROS) production under oxidative stress conditions. A carbonic anhydrase inhibitor, ethoxzolamide, abolished the enhanced tolerance to alkaline stress conferred by BLZ8 overexpression. BLZ8 directly regulated the expression of the three target genes and required bZIP2 as a dimerization partner in activating CAH8 and HLA3. Our results suggest that a CCM-mediated increase in the CO2 supply for photosynthesis is critical to minimize oxidative damage in microalgae, since slow gas diffusion in aqueous environments limits CO2 availability for photosynthesis, which can trigger ROS formation.
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Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Carbono/metabolismo , Chlamydomonas reinhardtii/fisiologia , Estresse Oxidativo/fisiologia , Fatores de Transcrição de Zíper de Leucina Básica/genética , Anidrases Carbônicas/metabolismo , Chlamydomonas reinhardtii/citologia , Regulação da Expressão Gênica , Peroxidação de Lipídeos , Estresse Oxidativo/genética , Complexo de Proteína do Fotossistema II/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
One new species of Olethreutes Hübner, 1822 species, O. oculata Kim, Byun & Bae, sp. nov., is described, and two related species, O. captiosana (Falkovitsh, 1960) and O. subtilana (Falkovitsh, 1959), are redescribed from Korea. Color figures of adults and images of genitalia are provided. [Zoobank registrations: Olethreutes oculata Kim, Byun & Bae, new species: LSID: urn:lsid:zoobank.org:act:814E618C-C13D-4FAC-A669-C3AD8673227F].
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Lepidópteros , Mariposas , Animais , GenitáliaRESUMO
The paper contains the description of two new Meganola Dyar, 1898 species (M. canaliculata Cha Bae, sp. n. and M. phuana Cha Bae, sp. n.) and a new record of M. tetrodon (de Joannis, 1928) from Laos. Color figures of adults and genitalia of the examined species are provided.
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Mariposas , Animais , Genitália , LaosRESUMO
Electronic skin (E-skin) based on tactile sensors has great significance in next-generation electronics such as biomedical application and artificial intelligence that requires interaction with humans. To mimic the properties of human skin, high flexibility, excellent sensing capability, and sufficient spatial resolution through high-level sensor integration are required. Here, we report a highly sensitive pressure sensor matrix based on a piezoresistive cellulose/single-walled carbon nanotube-entangled fiber network, which forms its own porous structure enabling a superior pressure sensor with a high sensitivity (9.097 kPa-1), a fast response speed (<2 ms), and orders of magnitude detection range with a detection limit of 1 Pa. Furthermore, the remarkable device expandability based on the ease of patterning and scalability allows easy implementation of a large-area pressure sensor matrix which has 2304 (48 × 48) pixels. Combined with a real-time pressure distribution monitoring system, a flexible 3D touch sensor that simultaneously displays plane coordinates and pressure information and a scanning device that detects the morphology of the soft body 3D surface are successfully demonstrated.
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Heat dissipation materials in which fillers are dispersed in a polymer matrix typically do not exhibit both high thermal conductivity (k) and processability due to a trade-off. In this paper, we fabricate heat dissipation composites which overcome the trade-off using liquid metal (LM). By exceeding the conventional filler limit, ten times higher k is achieved for a 90 vol% LM composite compared with k of 50 vol% LM composite. Further, an even higher k is achieved by introducing h-BN between the LM droplets, and the highest k in this study was 17.1 W m-1 K-1. The LM composite is processable at room temperature and used as inks for 3D printing. This combination of high k and processability not only allows heat dissipation materials to be processed on demand under ambient conditions but it also increases the surface area of the LM composite, which enables rapid heat dissipation.
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The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has arisen as a global pandemic affecting the respiratory system showing acute respiratory distress syndrome (ARDS). However, there is no targeted therapeutic agent yet and due to the growing cases of infections and the rising death tolls, discovery of the possible drug is the need of the hour. In general, the study for discovering therapeutic agent for SARS-CoV-2 is largely focused on large-scale screening with fragment-based drug discovery (FBDD). With the recent advancement in cryo-electron microscopy (Cryo-EM), it has become one of the widely used tools in structural biology. It is effective in investigating the structure of numerous proteins in high-resolution and also had an intense influence on drug discovery, determining the binding reaction and regulation of known drugs as well as leading the design and development of new drug candidates. Here, we review the application of cryo-EM in a structure-based drug design (SBDD) and in silico screening of the recently acquired FBDD in SARS-CoV-2. Such insights will help deliver better understanding in the procurement of the effective remedial solution for this pandemic.