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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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Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Carbono/metabolismo , Chlamydomonas reinhardtii/fisiología , Estrés Oxidativo/fisiología , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Anhidrasas Carbónicas/metabolismo , Chlamydomonas reinhardtii/citología , Regulación de la Expresión Génica , Peroxidación de Lípido , Estrés Oxidativo/genética , Complejo de Proteína del Fotosistema II/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
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 , Liposomas , Liposomas/química , Preparaciones de Acción Retardada/farmacología , Especies Reactivas de Oxígeno , Sistemas de Liberación de MedicamentosRESUMEN
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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Endoplasmic reticulum (ER) stress is caused by the stress-induced accumulation of unfolded proteins in the ER. Here, we identified proteins and lipids that function downstream of the ER stress sensor INOSITOL-REQUIRING ENZYME1 (CrIRE1) that contributes to ER stress tolerance in Chlamydomonas (Chlamydomonas reinhardtii). Treatment with the ER stress inducer tunicamycin resulted in the splicing of a 32-nucleotide fragment of a basic leucine zipper 1 (bZIP1) transcription factor (CrbZIP1) mRNA by CrIRE1 that, in turn, resulted in the loss of the transmembrane domain in CrbZIP1, and the translocation of CrbZIP1 from the ER to the nucleus. Mutants deficient in CrbZIP1 failed to induce the expression of the unfolded protein response genes and grew poorly under ER stress. Levels of diacylglyceryltrimethylhomoserine (DGTS) and pinolenic acid (18:3Δ5,9,12) increased in the parental strains but decreased in the crbzip1 mutants under ER stress. A yeast one-hybrid assay revealed that CrbZIP1 activated the expression of enzymes catalyzing the biosynthesis of DGTS and pinolenic acid. Moreover, two lines harboring independent mutant alleles of Chlamydomonas desaturase (CrDES) failed to synthesize pinolenic acid and were more sensitive to ER stress than were their parental lines. Together, these results indicate that CrbZIP1 is a critical component of the ER stress response mediated by CrIRE1 in Chlamydomonas that acts via lipid remodeling.
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Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Chlamydomonas reinhardtii/genética , Estrés del Retículo Endoplásmico , Metabolismo de los Lípidos , Alelos , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Núcleo Celular/metabolismo , Chlamydomonas reinhardtii/fisiología , Retículo Endoplásmico/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Ácidos Linolénicos/metabolismo , Mutación , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , ARN Mensajero/genética , ARN de Planta/genética , Triglicéridos/metabolismo , Tunicamicina/farmacología , Respuesta de Proteína Desplegada/efectos de los fármacosRESUMEN
Protein cage nanoparticles have a unique spherical hollow structure that provides a modifiable interior space and an exterior surface. For full application, it is desirable to utilize both the interior space and the exterior surface simultaneously with two different functionalities in a well-combined way. Here, we genetically engineered encapsulin protein cage nanoparticles (Encap) as modular nanoplatforms by introducing a split-C-intein (IntC) fragment and SpyTag into the interior and exterior surfaces, respectively. A complementary split-N-intein (IntN) was fused to various protein cargoes, such as NanoLuc luciferase (Nluc), enhanced green fluorescent protein (eGFP), and Nluc-miniSOG, individually, which led to their successful encapsulation into Encaps to form Cargo@Encap through split intein-mediated protein ligation during protein coexpression and cage assembly in bacteria. Conversely, the SpyCatcher protein was fused to various protein ligands, such as a glutathione binder (GST-SC), dimerizing ligands (FKBP12-SC and FRB-SC), and a cancer-targeting affibody (SC-EGFRAfb); subsequently, they were displayed on Cargo@Encaps through SpyTag/SpyCatcher ligation to form Cargo@Encap/Ligands in a mix-and-match manner. Nluc@Encap/glutathione-S-transferase (GST) was effectively immobilized on glutathione (GSH)-coated solid supports exhibiting repetitive and long-term usage of the encapsulated luciferases. We also established luciferase-embedded layer-by-layer (LbL) nanostructures by alternately depositing Nluc@Encap/FKBP12 and Nluc@Encap/FRB in the presence of rapamycin and applied enhanced green fluorescent protein (eGFP)@Encap/EGFRAfb as a target-specific fluorescent imaging probe to visualize specific cancer cells selectively. Modular functionalization of the interior space and the exterior surface of a protein cage nanoparticle may offer the opportunity to develop new protein-based nanostructured devices and nanomedical tools.
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Nanopartículas , Neoplasias , Colorantes Fluorescentes , Humanos , Inteínas , LigandosRESUMEN
Capillary rise is important in many aspects of physical phenomena from transport in porous media to biotechnology. It is typically described by the Lucas-Washburn-Rideal equation (LWRE), but discrepancy between some experiments and the model still remains elusive. In this paper, we show that the discrepancy is simply from the contact angle change during the capillary rise with no help of any specific models, such as dynamic contact angle (DCA) models. To demonstrate this, we directly measure the contact angle change in the capillary rise for glycerol and carboxymethyl cellulose solutions as examples of Newtonian and non-Newtonian liquids. Unlike previous studies that used DCA models to explain the discrepancy, when the contact angle change is directly applied to the LWRE for all four tested fluids, the model agrees well with experimental data. The estimated contact angle from the capillary rise as a function of time is in good agreement with the directly measured contact angle within a narrow margin of error. To pinpoint the conditions for the discrepancy, we propose a new time scale when contact angle dynamics dominates. The contact angle dynamics that can be obtained from the macroscopic capillary rise may provide useful information for capillary flow in a more complicated geometry such as porous media.
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In many eukaryotes, endoplasmic reticulum (ER) stress activates the unfolded protein response (UPR) via the transmembrane endoribonuclease IRE1 to maintain ER homeostasis. The ER stress response in microalgae has not been studied in detail. Here, we identified Chlamydomonas reinhardtii IRE1 (CrIRE1) and characterized two independent knock-down alleles of this gene. CrIRE1 is similar to IRE1s identified in budding yeast, plants, and humans, in terms of conserved domains, but differs in having the tandem zinc-finger domain at the C terminus. CrIRE1 was highly induced under ER stress conditions, and the expression of a chimeric protein consisting of the luminal N-terminal region of CrIRE1 fused to the cytosolic C-terminal region of yeast Ire1p rescued the yeast ∆ire1 mutant. Both allelic ire1 knock-down mutants ire1-1 and ire1-2 were much more sensitive than their parental strain CC-4533 to the ER stress inducers tunicamycin, dithiothreitol and brefeldin A. Treatment with a low concentration of tunicamycin resulted in growth arrest and cytolysis in ire1 mutants, but not in CC-4533 cells. Furthermore, in the mutants, ER stress marker gene expression was reduced, and reactive oxygen species (ROS) marker gene expression was increased. The survival of ire1 mutants treated with tunicamycin improved in the presence of the ROS scavenger glutathione, suggesting that ire1 mutants failed to maintain ROS levels under ER stress. Together, these results indicate that CrIRE1 functions as an important component of the ER stress response in Chlamydomonas, and suggest that the ER stress sensor IRE1 is highly conserved during the evolutionary history.
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Chlamydomonas reinhardtii/metabolismo , Estrés del Retículo Endoplásmico , Proteínas de Plantas/metabolismo , Alelos , Chlamydomonas reinhardtii/genética , Secuencia Conservada/genética , Regulación de la Expresión Génica de las Plantas/genética , Técnicas de Silenciamiento del Gen , Genes de Plantas/genética , Genes de Plantas/fisiología , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/fisiología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Helicobacter pylori is a pathogenic flagellated bacterium that infects the gastroduodenal mucosa and causes peptic ulcers in humans. FliD caps the distal end of the flagellar filament and is essential in filament growth. Moreover, FliD has been studied to diagnose and prevent H. pylori infection. Here, we report structure-based molecular studies of H. pylori FliD (hpFliD). A crystal structure of hpFliD at 2.6â¯Å resolution presents a four-domain (D2-D5) structure, where the D3 domain forms a central platform surrounded by the other three domains (D2, D4, and D5). hpFliD domains D2 and D3 structurally resemble those of FliD orthologs, whereas the D4 and D5 domains are exclusive to hpFliD. Moreover, our ELISA analysis using anti-H. pylori antibodies demonstrated that the hpFliD-specific D4 and D5 domains are highly antigenic compared to the D2 and D3 domains. Collectively, our structural and serological analyses underscore the structural role of hpFliD domains and provide a molecular basis for vaccine and diagnosis development.
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Proteínas Bacterianas/química , Flagelos/química , Infecciones por Helicobacter/microbiología , Helicobacter pylori/química , Cristalografía por Rayos X , Humanos , Modelos Moleculares , Conformación Proteica , Dominios ProteicosRESUMEN
Actin bundling protein 34 (ABP34) is the one of 11 actin-crosslinking proteins identified in Dictyostelium discoideum, a novel model organism for the study of actin-associated neurodegenerative disorders such as Alzheimer's disease and Huntington's disease. ABP34 localizes at the leading and trailing edges of locomotory cells, i.e., at the cell cortex, filopodia, and pseudopodia. Functionally, it serves to stabilize membrane-associated actin at sites of cell-cell contact. In addition, this small crosslinking protein is involved in actin bundle formation, and its bundling activity is regulated by the concentration of calcium ion. Several studies have sought to determine the mechanism underlying the calcium-regulated actin bundling activity of ABP34, but it remains unclear. Using several mutational and structural analyses, we revealed that calcium binding to the EF2 motif disrupts the inter-domain interaction between the N- and C-domains, thereby inhibiting the actin bundling activity of ABP34. This finding provides clues about the pathogenesis of neurodegenerative disorders related to actin bundling.
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Actinas/metabolismo , Calcio/metabolismo , Proteínas de Microfilamentos/antagonistas & inhibidores , Factor 2 de Elongación Peptídica/metabolismo , Proteínas Protozoarias/antagonistas & inhibidores , Sitios de Unión , Cromatografía en Gel , Dictyostelium/química , Dictyostelium/metabolismo , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Factor 2 de Elongación Peptídica/química , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismoRESUMEN
Fabrication of functional nanostructures is a prominent issue in nanotechnology, because they often exhibit unique properties that are different from the individual building blocks. Protein cage nanoparticles are attractive nanobuilding blocks for constructing nanostructures due to their well-defined symmetric spherical structures, polyvalent nature, and functional plasticity. Here, a lumazine synthase protein cage nanoparticle is genetically modified to be used as a template to generate functional nanobuilding blocks and covalently display enzymes (ß-lactamase) and protein ligands (FKBP12/FRB) on its surface, making dual-functional nanobuilding blocks. Nanoreaction clusters are subsequently created by ligand-mediated alternate deposition of two complementary building blocks using layer-by-layer (LbL) assemblies. 3D nanoreaction clusters provide enhanced enzymatic activity compared with monolayered building block arrays. The approaches described here may provide new opportunities for fabricating functional nanostructures and nanoreaction clusters, leading to the development of new protein nanoparticle-based nanostructured biosensor devices.
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Nanoestructuras/química , Nanotecnología/métodos , Secuencia de Aminoácidos , Proteínas Bacterianas/metabolismo , Ligandos , Nanoestructuras/ultraestructura , Péptidos/química , Multimerización de Proteína , Pteridinas/metabolismo , Sirolimus/farmacología , Proteína 1A de Unión a Tacrolimus/metabolismoRESUMEN
A graphene-MoS2 (GM) heterostructure based diode is fabricated using asymmetric contacts to MoS2, as well as an asymmetric top gate (ATG). The GM diode exhibits a rectification ratio of 5 from asymmetric contacts, which is improved to 105 after the incorporation of an ATG. This improvement is attributed to the asymmetric modulation of carrier concentration and effective Schottky barrier height (SBH) by the ATG during forward and reverse bias. This is further confirmed from the temperature dependent measurement, where a difference of 0.22 eV is observed between the effective SBH for forward and reverse bias. Moreover, the rectification ratio also depends on carrier concentration in MoS2 and can be varied with the change in temperature as well as back gate voltage. Under laser light illumination, the device demonstrates strong opto-electric response with 100 times improvement in the relative photo current, as well as a responsivity of 1.9 A W-1 and a specific detectivity of 2.4 × 1010 Jones. These devices can also be implemented using other two dimensional (2D) materials and suggest a promising approach to incorporate diverse 2D materials for future nano-electronics and optoelectronics applications.
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BACKGROUND: The striped field mouse, Apodemus agrarius, is the most common mammal in Korea. Although microsatellite loci for the species have been identified from populations in southwestern China, amplification of those markers for Korean populations have been unsuccessful. The complicated taxonomy of Korean striped field mouse including populations on Jeju Island (A. a chejuensis) necessitates identification of additional molecular markers. FINDINGS: We applied 454 pyrosequencing systems to develop a suite of microsatellite markers. Muscle tissue was harvested and sequenced from 30 Jeju striped field mouse specimens which yielded 12,165 reads with a mean length per read of 287 bp. From these reads, we identified 17 microsatellite loci for A. a. chejuensis and tested these new markers against samples of both A. a chejuensis and A. a coreae, the mainland taxon. All 17 loci were amplified successfully for both taxa. Of the total 17 loci, one locus failed to amplify for a population on Heuksan Island. The cross-species transferability was also tested with the allied taxon, A. peninsulae and confirmed successful for 12 loci. CONCLUSIONS: These newly developed markers will benefit studies of genetic structure, evolution, and resolving taxonomic problems of striped field mice and allied taxa in Korea.
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Genética de Población , Repeticiones de Microsatélite , Murinae/genética , Animales , Marcadores Genéticos , Genotipo , República de Corea , Análisis de Secuencia de ADNRESUMEN
Fatty acids, the building blocks of biological lipids, are synthesized in plastids and then transported to the endoplasmic reticulum (ER) for assimilation into specific lipid classes. The mechanism of fatty acid transport from plastids to the ER has not been identified. Here we report that AtABCA9, an ABC transporter in Arabidopsis thaliana, mediates this transport. AtABCA9 was localized to the ER, and atabca9 null mutations reduced seed triacylglycerol (TAG) content by 35% compared with WT. Developing atabca9 seeds incorporated 35% less (14)C-oleoyl-CoA into TAG compared with WT seeds. Furthermore, overexpression of AtABCA9 enhanced TAG deposition by up to 40%. These data strongly support a role for AtABCA9 as a supplier of fatty acid substrates for TAG biosynthesis at the ER during the seed-filling stage. AtABCA9 may be a powerful tool for increasing lipid production in oilseeds.
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Transportadoras de Casetes de Unión a ATP/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Retículo Endoplásmico/metabolismo , Ácidos Grasos/metabolismo , Lípidos/biosíntesis , Transportadoras de Casetes de Unión a ATP/genética , Centrifugación , Cartilla de ADN/genética , Perfilación de la Expresión Génica , Técnicas de Inactivación de Genes , Semillas/químicaRESUMEN
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 Nocturnas , Humanos , Animales , Genitales , UniversidadesRESUMEN
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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Incrustaciones Biológicas , Técnicas Biosensibles , Nanocompuestos , Porosidad , Emulsiones , Anticuerpos , Técnicas ElectroquímicasRESUMEN
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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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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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.