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Ruegeria atlantica and Pseudoalteromonas neustonica are fish gut bacteria that have been isolated from the guts of Pagrus major and Acanthopagrus schlegelii, respectively. A total of 22 compounds (1-22) were isolated from these two bacteria; 16 compounds (1-16) from R. atalantica and 6 compounds (17-22) from P. neustonica. Their chemical structures were elucidated by spectroscopic and spectrometric data analysis and chemical synthesis. Compounds 11 and 13 showed strong collagenase inhibitory activity, with 31.91% and 36.43% at 20 µM, respectively, comparable to or surpassing that of the positive control epigallocatechin gallate (EGCG, 34.66%). Also, compounds 11 and 14 exhibited a mild tyrosinase inhibitory effect of 6.73% and 13.68%, respectively. All of the tested compounds displayed no significant antibacterial activity against Escherichia coli and Bacillus subtilis up to 100 µM. The collagenase- and tyrosinase-inhibitory compound 11, cyclo(l-Pro-d-Leu), was found to be stable under heat (50 °C) and UV light (254 and 365 nm) for up to 6 days. These results indicate that compound 11 could be developed into a cosmeceutical with antiaging effects.
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Myristica fragrans Houtt. is rich in lignans, neolignans, and diarylnonanoids, with well-documented anti-inflammatory properties. However, there is limited research on the conjugated forms of diarylnonanoids, neolignans, monoterpenes, and others and their anti-inflammatory effects. Our study isolated 33 new compounds (2-7, 9-22, and 41-52), including two neolignans, alongside various neolignan-diarylnonanoid, propenylbenzene-diarylnonanoid, 2,3-dimethylbutane-type lignan-diarylnonanoid, and monoterpene-diarylnonanoid conjugates, along with previously reported compounds (1, 8, and 23-40). Their chemical structures were determined via spectroscopic analyses. Compounds 2, 4, 9, 11, 12, 14, 17, and 18 exhibited potent inhibition of NF-κB/AP1 and IRF signaling induced by TLR agonists. Notably, stereoisomers showed distinct behavior, while 10R,11R-isomers induced cytotoxicity, and 10S,11R-isomers produced contrasting effects, especially within group-I compounds.
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A family of pyrazinone metabolites (1-11) were characterized from Staphylococcus xylosus ATCC 29971. Six of them were hydroxylated or methoxylated, which were proposed to be produced by the rare noncatalytic oxa-Michael addition reaction with a water or methanol molecule. It was confirmed that isopropyl alcohol can also be the Michael donor of the reaction. 1-7 and the synthetic precursor 2a showed significant inhibition of breast cancer cell migration.
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Pirazinas , Staphylococcus , Humanos , Movimiento Celular/efectos de los fármacos , Estructura Molecular , Pirazinas/química , Pirazinas/farmacología , Staphylococcus/efectos de los fármacosRESUMEN
In atomically thin van der Waals materials, grain boundaries-the line defects between adjacent crystal grains with tilted in-plane rotations-are omnipresent. When the tilting angles are arbitrary, the grain boundaries form inhomogeneous sublattices, giving rise to local electronic states that are not controlled. Here we report on epitaxial realizations of deterministic MoS2 mirror twin boundaries (MTBs) at which two adjoining crystals are reflection mirroring by an exactly 60° rotation by position-controlled epitaxy. We showed that these epitaxial MTBs are one-dimensionally metallic to a circuit length scale. By utilizing the ultimate one-dimensional (1D) feature (width ~0.4 nm and length up to a few tens of micrometres), we incorporated the epitaxial MTBs as a 1D gate to build integrated two-dimensional field-effect transistors (FETs). The critical role of the 1D MTB gate was verified to scale the depletion channel length down to 3.9 nm, resulting in a substantially lowered channel off-current at lower gate voltages. With that, in both individual and array FETs, we demonstrated state-of-the-art performances for low-power logics. The 1D epitaxial MTB gates in this work suggest a novel synthetic pathway for the integration of two-dimensional FETs-that are immune to high gate capacitance-towards ultimate scaling.
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Polycyclic aromatic hydrocarbons (PAHs), notably benzo[a]pyrene (BaP), are environmental contaminants with multiple adverse ecological implications. Numerous studies have suggested the use of BaP biodegradation using various bacterial strains to remove BaP from the environment. This study investigates the BaP biodegradation capability of Pigmentiphaga kullae strain KIT-003, isolated from the Nak-dong River (South Korea) under specific environmental conditions. The optimum conditions of biodegradation were found to be pH 7.0, 35°C, and a salinity of 0â¯%. GC-MS analysis suggested alternative pathways by which KIT-003 produced catechol from BaP through several intermediate metabolites, including 4-formylchrysene-5-carboxylic acid, 5,6-dihydro-5,6-dihydroxychrysene-5-carboxylic acid (isomer: 3,4-dihydro-3,4-dihydroxychrysene-4-carboxylic acid), naphthalene-1,2-dicarboxylic acid, and 2-hydroxy-1-naphthoic acid. Proteomic profiles indicated upregulation of enzymes associated with aromatic compound degradation, such as nahAc and nahB, and of those integral to the tricarboxylic acid cycle, reflecting the strain's adaptability to and degradation of BaP. Lipidomic analysis of KIT-003 demonstrated that BaP exposure induced an accumulation of glycerolipids such as diacylglycerol and triacylglycerol, indicating their crucial role in bacterial adaptation mechanisms under BaP stress. This study provides significant scientific knowledge regarding the intricate mechanisms involved in BaP degradation by microorganisms.
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Benzo(a)pireno , Biodegradación Ambiental , Benzo(a)pireno/metabolismo , Benzo(a)pireno/toxicidad , República de Corea , Proteómica , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/toxicidad , Cromatografía de Gases y Espectrometría de Masas , Catecoles/metabolismo , Ríos/química , Ríos/microbiología , MultiómicaRESUMEN
During the last decade, the generation and accumulation of petabase-scale high-throughput sequencing data have resulted in great challenges, including access to human data, as well as transfer, storage, and sharing of enormous amounts of data. To promote data-driven biological research, the Korean government announced that all biological data generated from government-funded research projects should be deposited at the Korea BioData Station (K-BDS), which consists of multiple databases for individual data types. Here, we introduce the Korean Nucleotide Archive (KoNA), a repository of nucleotide sequence data. As of July 2022, the Korean Read Archive in KoNA has collected over 477 TB of raw next-generation sequencing data from national genome projects. To ensure data quality and prepare for international alignment, a standard operating procedure was adopted, which is similar to that of the International Nucleotide Sequence Database Collaboration. The standard operating procedure includes quality control processes for submitted data and metadata using an automated pipeline, followed by manual examination. To ensure fast and stable data transfer, a high-speed transmission system called GBox is used in KoNA. Furthermore, the data uploaded to or downloaded from KoNA through GBox can be readily processed using a cloud computing service called Bio-Express. This seamless coupling of KoNA, GBox, and Bio-Express enhances the data experience, including submission, access, and analysis of raw nucleotide sequences. KoNA not only satisfies the unmet needs for a national sequence repository in Korea but also provides datasets to researchers globally and contributes to advances in genomics. The KoNA is available at https://www.kobic.re.kr/kona/.
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Bases de Datos de Ácidos Nucleicos , República de Corea , Humanos , Secuenciación de Nucleótidos de Alto Rendimiento/métodosRESUMEN
Mesenchymal stem cells (MSC) are an appealing therapeutic cell type for many diseases. However, patients with poor health or advanced age often have MSCs with poor regenerative properties. A major limiter of MSC therapies is cellular senescence, which is marked by limited proliferation capability, diminished multipotency, and reduced regenerative properties. In this work, we explored the ability of applied mechanical forces to reduce cellular senescence in MSCs. Our studies revealed that mechanical conditioning caused a lasting enhancement in proliferation, overall cell culture expansion potential, multipotency, and a reduction of senescence in MSCs from aged donors. Mechanistic studies suggested that these functional enhancements were mediated by oxidative stress and DNA damage repair signaling with mechanical load altering the expression of proteins of the sirtuin pathway, the DNA damage repair protein ATM, and antioxidant proteins. In addition, our results suggest a biophysical mechanism in which mechanical stretch leads to improved recognition of damaged DNA in the nucleus. Analysis of the cells through RNA-seq and ATAC-seq, demonstrated that mechanical loading alters the cell's genetic landscape to cause broad shifts in transcriptomic patterns that related to senescence. Overall, our results demonstrate that mechanical conditioning can rejuvenate mesenchymal stem cells derived from aged patients and improve their potential as a therapeutic cell type.
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Clopidol is extensively used in livestock farming and residues of this antibiotic can persist in animal tissues, posing a risk to humans and the environment. In this study, we investigated the depletion of clopidol in various edible tissues of chickens (muscle, liver, kidney, fat, and eggs) using liquid chromatography-tandem mass spectrometry after the administration of a clopidol-contaminated diet (at 250 mg kg-1 for the high (1x) dose). After 14 d of exposure, the clopidol concentrations were highest in eggs (median: 9.83 mg/kg), followed by liver (3.56 mg/kg), kidney (3.01 mg/kg), muscle (1.56 mg/kg), and fat (0.727 mg/kg) at low exposure group, indicating that clopidol accumulated primarily in eggs rather than the other edible tissues. In addition, the maternal transfer ratios were estimated, and the transfer efficiencies of clopidol in muscle (egg-to-tissue ratio, ETR:1.81) and fat (2.06-58.2) were higher than those in liver (0.731-31.1) and kidney (0.832-38.9). Furthermore, we conducted a cumulative risk assessment for clopidol in edible chicken tissues using the hazard quotient (HQ) method. This assessment revealed that the exposure levels for Korean consumers pose an acceptable risk. However, for eggs from the 1x dose exposure group, the HQ values were greater than 1 for all age groups, particularly for young children (<18 y), suggesting that the higher daily consumption of eggs combined with the higher clopidol residues in eggs resulted in higher HQ values, which requires further attention. The findings of this study can assist in the management and monitoring of clopidol residues in chicken tissues and eggs.
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Pollos , Contaminación de Alimentos , Animales , Medición de Riesgo , Contaminación de Alimentos/análisis , Humanos , Huevos/análisis , Riñón/química , Riñón/metabolismo , Espectrometría de Masas en Tándem , Hígado/química , Hígado/metabolismoRESUMEN
Moiré superlattices of transition metal dichalcogenides offer a unique platform to explore correlated exciton physics with optical spectroscopy. Whereas the spatially modulated potentials evoke that the exciton resonances are distinct depending on a site in a moiré supercell, there have been no clear demonstration how the moiré excitons trapped in different sites dynamically interact with the doped carriers; so far the exciton-electron dynamic interactions were presumed to be site-dependent. Thus, the transient emergence of nonequilibrium correlations are open questions, but existing studies are limited to steady-state optical measurements. Here we report experimental fingerprints of site-dependent exciton correlations under continuous-wave as well as ultrashort optical excitations. In near-zero angle-aligned WSe2/WS2 heterobilayers, we observe intriguing polarization switching and strongly enhanced Pauli blocking near the Mott insulating state, dictating the dominant correlation-driven effects. When the twist angle is near 60°, no such correlations are observed, suggesting the strong dependence of atomic registry in moiré supercell configuration. Our studies open the door to largely unexplored nonequilibrium correlations of excitons in moiré superlattices.
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Transcriptional regulation controls cellular functions through interactions between transcription factors (TFs) and their chromosomal targets. However, understanding the fate conversion potential of multiple TFs in an inducible manner remains limited. Here, we introduce iTF-seq as a method for identifying individual TFs that can alter cell fate toward specific lineages at a single-cell level. iTF-seq enables time course monitoring of transcriptome changes, and with biotinylated individual TFs, it provides a multi-omics approach to understanding the mechanisms behind TF-mediated cell fate changes. Our iTF-seq study in mouse embryonic stem cells identified multiple TFs that trigger rapid transcriptome changes indicative of differentiation within a day of induction. Moreover, cells expressing these potent TFs often show a slower cell cycle and increased cell death. Further analysis using bioChIP-seq revealed that GCM1 and OTX2 act as pioneer factors and activators by increasing gene accessibility and activating the expression of lineage specification genes during cell fate conversion. iTF-seq has utility in both mapping cell fate conversion and understanding cell fate conversion mechanisms.
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Diferenciación Celular , Factores de Transcripción , Animales , Ratones , Diferenciación Celular/genética , Linaje de la Célula/genética , Perfilación de la Expresión Génica/métodos , Células Madre Embrionarias de Ratones/metabolismo , Células Madre Embrionarias de Ratones/citología , Multiómica , ARN Citoplasmático Pequeño/genética , ARN Citoplasmático Pequeño/metabolismo , RNA-Seq/métodos , Análisis de Secuencia de ARN/métodos , Análisis de Expresión Génica de una Sola Célula , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , TranscriptomaRESUMEN
Pesticides are indispensable tools in modern agriculture for enhancing crop productivity. However, the inherent toxicity of pesticides raises significant concerns regarding human exposure, particularly among agricultural workers. This study investigated the exposure and associated risks of two commonly used pesticides in open-field pepper cultivation, namely, chlorothalonil and flubendiamide, in the Republic of Korea. We used a comprehensive approach, encompassing dermal and inhalation exposure measurements in agricultural workers during two critical scenarios: mixing/loading and application. Results revealed that during mixing/loading, dermal exposure to chlorothalonil was 3.33 mg (0.0002% of the total active ingredient [a.i.]), while flubendiamide exposure amounted to 0.173 mg (0.0001% of the a.i.). Conversely, dermal exposure increased significantly during application to 648 mg (chlorothalonil) and 93.1 mg (flubendiamide), representing 0.037% and 0.065% of the total a.i., respectively. Inhalation exposure was also evident, with chlorothalonil and flubendiamide exposure levels varying across scenarios. Notably, the risk assessment using the Risk Index (RI) indicated acceptable risk of exposure during mixing/loading but raised concerns during application, where all RIs exceeded 1, signifying potential risk. We suggest implementing additional personal protective equipment (PPE) during pesticide application, such as gowns and lower-body PPE, to mitigate these risks.
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Fluorocarburos , Nitrilos , Plaguicidas , Ftalimidas , Piper nigrum , Sulfonas , Humanos , Agricultores , Medición de Riesgo , Benzamidas , Plaguicidas/toxicidadRESUMEN
In the field of natural product research, the rediscovery of already-known compounds is one of the significant issues hindering new drug development. Recently, an innovative approach called bioactivity-HiTES has been developed to overcome this limitation, and several new bioactive metabolites have been successfully characterized by this method. In this study, we applied bioactivity-HiTES to Corynebacterium matruchotii, the human oral bacterium, with 3120 clinical drugs as potential elicitors. As a result, we identified two cryptic metabolites, methylindole-3-acetate (MIAA) and indole-3-acetic acid (IAA), elicited by imidafenacin, a urinary antispasmodic drug approved by the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). MIAA showed weak antibacterial activity against a pulmonary disease-causing Mycobacterium conceptionense with an IC50 value of 185.7 µM. Unexpectedly, we also found that C. matruchotii metabolized fludarabine phosphate, a USFDA-approved anticancer drug, to 2-fluoroadenine which displayed moderate antibacterial activity against both Bacillus subtilis and Escherichia coli, with IC50 values of 8.9 and 20.1 µM, respectively. Finally, acelarin, a prodrug of the anticancer drug gemcitabine, was found to exhibit unreported antibacterial activity against B. subtilis with an IC50 value of 33.6 µM through the bioactivity-HiTES method as well. These results indicate that bioactivity-HiTES can also be applied to discover biotransformed products in addition to finding cryptic metabolites in microbes.
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Antineoplásicos , Corynebacterium , Humanos , Antibacterianos/farmacología , Antibacterianos/metabolismo , Antineoplásicos/metabolismo , Bacterias/efectos de los fármacos , Bacterias/metabolismo , Corynebacterium/efectos de los fármacos , Corynebacterium/metabolismoRESUMEN
Considering the recent increase in the number of colorectal cancer (CRC) cases in South Korea, we aimed to clarify the molecular characteristics of CRC unique to the Korean population. To gain insights into the complexities of CRC and promote the exchange of critical data, RNA-sequencing analysis was performed to reveal the molecular mechanisms that drive the development and progression of CRC; this analysis is critical for developing effective treatment strategies. We performed RNA-sequencing analysis of CRC and adjacent normal tissue samples from 214 Korean participants (comprising a total of 381 including 169 normal and 212 tumor samples) to investigate differential gene expression between the groups. We identified 19,575 genes expressed in CRC and normal tissues, with 3,830 differentially expressed genes (DEGs) between the groups. Functional annotation analysis revealed that the upregulated DEGs were significantly enriched in pathways related to the cell cycle, DNA replication, and IL-17, whereas the downregulated DEGs were enriched in metabolic pathways. We also analyzed the relationship between clinical information and subtypes using the Consensus Molecular Subtype (CMS) classification. Furthermore, we compared groups clustered within our dataset to CMS groups and performed additional analysis of the methylation data between DEGs and CMS groups to provide comprehensive biological insights from various perspectives. Our study provides valuable insights into the molecular mechanisms underlying CRC in Korean patients and serves as a platform for identifying potential target genes for this disease. The raw data and processed results have been deposited in a public repository for further analysis and exploration.
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Neoplasias Colorrectales , Perfilación de la Expresión Génica , Humanos , Perfilación de la Expresión Génica/métodos , Neoplasias Colorrectales/metabolismo , Regulación Neoplásica de la Expresión Génica , Biología Computacional/métodos , ARNRESUMEN
During human pregnancy, extravillous trophoblasts play crucial roles in placental invasion into the maternal decidua and spiral artery remodeling. However, regulatory factors and their action mechanisms modulating human extravillous trophoblast specification have been unknown. By analyzing dynamic changes in transcriptome and enhancer profile during human trophoblast stem cell to extravillous trophoblast differentiation, we define stage-specific regulators, including an early-stage transcription factor, TFAP2C, and multiple late-stage transcription factors. Loss-of-function studies confirm the requirement of all transcription factors identified for adequate differentiation, and we reveal that the dynamic changes in the levels of TFAP2C are essential. Notably, TFAP2C pre-occupies the regulatory elements of the inactive extravillous trophoblast-active genes during the early stage of differentiation, and the late-stage transcription factors directly activate extravillous trophoblast-active genes, including themselves as differentiation further progresses, suggesting sequential actions of transcription factors assuring differentiation. Our results reveal stage-specific transcription factors and their inter-connected regulatory mechanisms modulating extravillous trophoblast differentiation, providing a framework for understanding early human placentation and placenta-related complications.
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Trofoblastos Extravellosos , Placenta , Embarazo , Humanos , Femenino , Trofoblastos , Diferenciación Celular/genética , Factores de Transcripción/genética , Células MadreRESUMEN
We reveal the critical effect of ultrashort dephasing on the polarization of high harmonic generation in Dirac fermions. As the elliptically polarized laser pulse falls in or slightly beyond the multiphoton regime, the elliptically polarized high harmonic generation is produced and exhibits a characteristic polarimetry of the polarization ellipse, which is found to depend on the decoherence time T2. T2 could then be determined to be a few femtoseconds directly from the experimentally observed polarimetry of high harmonics. This shows a sharp contrast with the semimetal regime of higher pump intensity, where the polarimetry is irrelevant to T2. An access to the dephasing dynamics would extend the prospect of high harmonic generation into the metrology of a femtosecond dynamic process in the coherent quantum control.
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Spin nematic is a magnetic analogue of classical liquid crystals, a fourth state of matter exhibiting characteristics of both liquid and solid1,2. Particularly intriguing is a valence-bond spin nematic3-5, in which spins are quantum entangled to form a multipolar order without breaking time-reversal symmetry, but its unambiguous experimental realization remains elusive. Here we establish a spin nematic phase in the square-lattice iridate Sr2IrO4, which approximately realizes a pseudospin one-half Heisenberg antiferromagnet in the strong spin-orbit coupling limit6-9. Upon cooling, the transition into the spin nematic phase at TC ≈ 263 K is marked by a divergence in the static spin quadrupole susceptibility extracted from our Raman spectra and concomitant emergence of a collective mode associated with the spontaneous breaking of rotational symmetries. The quadrupolar order persists in the antiferromagnetic phase below TN ≈ 230 K and becomes directly observable through its interference with the antiferromagnetic order in resonant X-ray diffraction, which allows us to uniquely determine its spatial structure. Further, we find using resonant inelastic X-ray scattering a complete breakdown of coherent magnon excitations at short-wavelength scales, suggesting a many-body quantum entanglement in the antiferromagnetic state10,11. Taken together, our results reveal a quantum order underlying the Néel antiferromagnet that is widely believed to be intimately connected to the mechanism of high-temperature superconductivity12,13.
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Von Hippel-Lindau (VHL) is a tumor suppressor that functions as the substrate recognition subunit of the CRL2VHL E3 complex. While substrates of VHL have been identified, its tumor suppressive role remains to be fully understood. For further determination of VHL substrates, we analyzed the physical interactome of VHL and identified the histone H3K9 methyltransferase SETBD1 as a novel target. SETDB1 undergoes oxygen-dependent hydroxylation by prolyl hydroxylase domain proteins and the CRL2VHL complex recognizes hydroxylated SETDB1 for ubiquitin-mediated degradation. Under hypoxic conditions, SETDB1 accumulates by escaping CRL2VHL activity. Loss of SETDB1 in hypoxia compared with that in normoxia escalates the production of transposable element-derived double-stranded RNAs, thereby hyperactivating the immune-inflammatory response. In addition, strong derepression of TEs in hypoxic cells lacking SETDB1 triggers DNA damage-induced death. Our collective results support a molecular mechanism of oxygen-dependent SETDB1 degradation by the CRL2VHL E3 complex and reveal a role of SETDB1 in genome stability under hypoxia.
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Inestabilidad Genómica , N-Metiltransferasa de Histona-Lisina , Hipoxia , Humanos , Genes Supresores de Tumor , N-Metiltransferasa de Histona-Lisina/metabolismo , Hipoxia/genética , Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Oxígeno/metabolismo , Ubiquitina-Proteína Ligasas/genética , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genética , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/metabolismoRESUMEN
To gain deeper insights into transcriptomes and epigenomes of organoids, liver organoids from two states (expandable and more differentiated) were subjected to single-cell RNA-seq (scRNA-seq) and single-cell ATAC-seq (scATAC-seq) analyses. Mitochondrial gene expression was higher in differentiated than in non-differentiated hepatocytes, with ATAC-seq peaks increasing near the mitochondrial control region. Differentiation of liver organoids resulted in the expression of transcription factors that act as enhancers and repressors. In addition, epigenetic mechanisms regulating the expression of alpha-fetoprotein (AFP) and albumin (ALB) differed in liver organoids and adult liver. Knockdown of PDX1, an essential transcription factor for pancreas development, led to the hepatic maturation of liver organoids through regulation of AFP and ALB expression. This integrative analysis of the transcriptomes and epigenomes of liver organoids at the single-cell level may contribute to a better understanding of the regulatory networks during liver development and the further development of mature in vitro human liver models.
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This paper presents a system that utilizes vision transformers and multimodal feedback modules to facilitate navigation and collision avoidance for the visually impaired. By implementing vision transformers, the system achieves accurate object detection, enabling the real-time identification of objects in front of the user. Semantic segmentation and the algorithms developed in this work provide a means to generate a trajectory vector of all identified objects from the vision transformer and to detect objects that are likely to intersect with the user's walking path. Audio and vibrotactile feedback modules are integrated to convey collision warning through multimodal feedback. The dataset used to create the model was captured from both indoor and outdoor settings under different weather conditions at different times across multiple days, resulting in 27,867 photos consisting of 24 different classes. Classification results showed good performance (95% accuracy), supporting the efficacy and reliability of the proposed model. The design and control methods of the multimodal feedback modules for collision warning are also presented, while the experimental validation concerning their usability and efficiency stands as an upcoming endeavor. The demonstrated performance of the vision transformer and the presented algorithms in conjunction with the multimodal feedback modules show promising prospects of its feasibility and applicability for the navigation assistance of individuals with vision impairment.