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Accumulation of DNA damage in the lung induces cellular senescence and promotes age-related diseases such as idiopathic pulmonary fibrosis (IPF). Hence, understanding the mechanistic regulation of DNA damage repair is important for anti-aging therapies and disease control. Here, we identified an m6A-independent role of the RNA-binding protein YTHDC1 in counteracting stress-induced pulmonary senescence and fibrosis. YTHDC1 is primarily expressed in pulmonary alveolar epithelial type 2 (AECII) cells and its AECII expression is significantly decreased in AECIIs during fibrosis. Exogenous overexpression of YTHDC1 alleviates pulmonary senescence and fibrosis independent of its m6A-binding ability, while YTHDC1 deletion enhances disease progression in mice. Mechanistically, YTHDC1 promotes the interaction between TopBP1 and MRE11, thereby activating ATR and facilitating DNA damage repair. These findings reveal a noncanonical function of YTHDC1 in delaying cellular senescence, and suggest that enhancing YTHDC1 expression in the lung could be an effective treatment strategy for pulmonary fibrosis.
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Senescencia Celular , Fibrosis Pulmonar Idiopática , Proteínas del Tejido Nervioso , Factores de Empalme de ARN , Animales , Ratones , Envejecimiento/genética , Fibrosis Pulmonar Idiopática/genética , Fibrosis Pulmonar Idiopática/inducido químicamente , Fibrosis Pulmonar Idiopática/metabolismo , Pulmón/metabolismo , Factores de Empalme de ARN/metabolismo , Proteínas del Tejido Nervioso/metabolismoRESUMEN
An unprecedented O-fused ring 5,7-dihydroxy-4-methyl-2,2,3-triphenylbenzofuran-6(2H)-one (3) was first time synthesized. Further, a series of novel dialkyl/fluoroalkyl derivatives of compound 3, 5,7-dialkoxy/fluoroalkoxy-4-methyl-2,2,3-triphenylbenzofuran-6(2H)-one, were obtained with noninvasive fluorescence switching characteristics and aggregation-induced emission properties. Compared with fluoroalkyl derivatives, the alkyl analogs exhibited a significant bathochromic shift in solid-state fluorescence emission. Notably, these noninvasive fluorescent molecular switches could be facilely tuned through light and heat stimulation, which successfully achieved high contrast and reversible fluorescent emission between orange and yellow endowing them with potential applications in data encryption materials. In addition, the single crystal data of compounds 3 and 7-CF3 displayed weak intermolecular interactions in different directions, resulting in twisted conformation and antiparallel slip stacking. Interestingly, the polymer dimethyl silicone film doped with 7-C3F7 also showed an evident light-responsive behavior, meeting the criterion for fluorescent materials in the optical field.
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Cyclophilin A (CypA), the first member of cyclophilins, is distributed extensively in eukaryotic and prokaryotic cells, primarily localized in the cytoplasm. In addition to acting as an intracellular receptor for cyclosporin A (CSA), CypA plays a crucial role in diseases such as aging and tumorigenesis. Apoptosis, a form of programmed cell death, is able to balance the rate of cell viability and death. In this review, we focus on the effects of CypA on apoptosis and the relationship between specific mechanisms of CypA promoting or inhibiting apoptosis and diseases, including tumorigenesis, cardiovascular diseases, organ injury, and microbial infections. Notably, the process of CypA promoting or inhibiting apoptosis is closely related to disease development. Finally, future prospects for the association of CypA and apoptosis are discussed, and a comprehensive understanding of the effects of CypA on apoptosis in relation to diseases is expected to provide new insights into the design of CypA as a therapeutic target for diseases. KEY POINTS: ⢠Understand the effect of CypA on apoptosis. ⢠CypA affects apoptosis through specific pathways. ⢠The effect of CypA on apoptosis is associated with a variety of disease processes.
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Ciclofilina A , Ciclosporina , Humanos , Ciclofilina A/metabolismo , Ciclosporina/metabolismo , Proteínas Portadoras , Apoptosis , CarcinogénesisRESUMEN
To assess the health of river ecosystems, it is essential to quantify the ecological risk of heavy metals in river sediments and the structure of microbial communities. As important tributaries of the Tuo River in the upper reaches of the Yangtze River, the Mianyuan River and the Shiting River, are closely related to the economic development and human daily life in the region. This study assessed the ecological risks of heavy-metal-polluted river sediments, the heavy-metal-driven bacterial communities were revealed, and the relationships between the ecological risks and the identical bacterial communities were discussed. The Cd content was significantly greater than the environmental background value, leading to a serious pollution and very high ecological risk at the confluence of the two rivers and the upper reaches of the Mianyuan River. Microbial community analysis showed that Rhodobacter, Nocardioides, Sphingomonas, and Pseudarthrobacter were the dominant bacterial genera in the sediments of the Shiting River. However, the dominant bacterial genera in the Mianyuan River were Kouleothrix, Dechloromonas, Gaiella, Pedomicrobium, and Hyphomicrobium. Mantel test results showed (r = 0.5977, P = 0.005) that the Cd, As, Zn, Pb, Cr, and Cu were important factors that influenced differences in the distribution of sediment bacterial communities Mianyuan and Shiting rivers. A correlation heatmap showed that heavy metals were negatively correlated for most bacterial communities, but some bacterial communities were tolerant and showed a positive correlation. Overall, the microbial structure of the river sediments showed a diverse spatial distribution due to the influence of heavy metals. The results will improve the understanding of rivers contaminated by heavy metals and provide theoretical support for conservation and in situ ecological restoration of river ecosystems.
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Metales Pesados , Microbiota , Contaminantes Químicos del Agua , Humanos , Ríos/química , Cadmio , Sedimentos Geológicos/química , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente , Metales Pesados/toxicidad , Metales Pesados/análisis , Medición de Riesgo , ChinaRESUMEN
A novel transition metal tellurate single-crystal BaNi2TeO6 with layered honeycomb lattices has been successfully synthesized. The crystal structure of BaNi2TeO6 reveals that there are the Ni2+ honeycomb lattice layers and Te6+ triangle lattice layers in the ab plane. BaNi2TeO6 shows an antiferromagnetic (AFM) transition at â¼25 K, which is almost the same temperature as the Curie-Weiss temperature θ â¼ -27 K, indicating the presence of the AFM interactions without obvious magnetic frustration in the system. However, the field-induced successive magnetic transitions observed at Hc1 â¼ 16.2 T and Hc2 â¼ 42.2 T show the complicated spin structure in BaNi2TeO6. Compared with the isostructural Na2Ni2TeO6, the various magnetic properties indicate that the intercalated ions (Ba2+) can significantly affect the magnetic properties of the layered honeycomb lattices, which may be useful for exploring the spin-liquid state and valence bond liquid state in the layered honeycomb lattice compounds.
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We report for the first time the coupling of activated thioamides with alcohols to efficiently form thionoesters via a palladium-catalyzed C-N cleavage strategy. The new approach employs thioamides as a thioacylating reagent to give thionoesters in moderate to good yields. Notably, this methodology demonstrates a broad substrate scope, as alkyl/aryl alcohols are well tolerated, and this process might facilitate the synthesis of sulfur-containing compounds under simple and mild conditions.
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Veterinary antibiotics in swine wastewater has drawn great public attention. The removal processes of sulfamethizole (SMZ), enrofloxacin (ENR) and chlortetracycline (CTC) were investigated in the high-rate anaerobic process. The continuous experiments demonstrated that in 3 L working volume and with the organic loading rate 5 kg/(m3·d) rised to 20 kg/(m3·d), the average removal efficiencies of the high-rate anaerobic bioreactor for SMZ, ENR and CTC were 0, 54 and 100%, respectively. By using fixed-bed adsorption models, the saturation time of SMZ, ENR and CTC were 4 hydraulic retention time (HRT) (24 h), 8 HRT (48 h) and 372 HRT (2,232 h). In the batch experiments, the adsorption and biodegradation characteristics of anaerobic granular sludge were determined. In the high-rate anaerobic bioreactor, SMZ removal process mainly relied on the adsorption but it was very weak; ENR removal process was based on the adsorption and biodegradation; CTC removal process was based to a large extent on the adsorption because of the big capacity of AnGS. These results were helpful to create a rational basis for designing more suitable treatment systems as feasible barriers to the release of antibiotics into the environment.
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Clortetraciclina , Aguas del Alcantarillado , Anaerobiosis , Animales , Antibacterianos , Reactores Biológicos , Enrofloxacina , Sulfametizol , Porcinos , Eliminación de Residuos Líquidos/métodos , Aguas ResidualesRESUMEN
Inflammatory diseases are sometimes devastating and notoriously difficult to treat. Precisely modulating inflammatory signaling pathways is a promising approach for treating inflammatory diseases. Herein, a multifunctional nanosystem is developed for active targeting, activatable imaging and on-demand therapy against inflammatory diseases through modulating inflammatory pathways. A chromophore-drug dyad (QBS-FIS) is synthesized by linking a chromophore and a Nrf2 (nuclear factor E2-related factor) activator fisetin through boronate bond which serves as fluorescence quencher and ROS (reactive oxygen species)-responsive linker. QBS-FIS molecules form nanoparticles in water and are coated with macrophage cell membrane to ensure active targeting toward inflammation site. To further improve therapeutic efficacy, a NF-kB (nuclear-factor kappa-light-chain-enhancer of activated B cells) inhibitor thalidomide is co-encapsulated to afford the nanosystem (QBS-FIS&Thd@MM). Upon administration into mice, the nanosystem migrates to inflammatory site and pathological ROS therein cleaves the boronate bonds, thereby activating the chromophore for imaging liver/kidney inflammatory diseases for disease diagnosis and recovery evaluation via fluorescence and optoacoustic imaging as well as releasing the active drugs for treating acute liver inflammation through activating Nrf2 pathway and inhibiting NF-kB pathway. The 3D multispectral optoacoustic tomography imaging is applied to precisely locate the inflammatory foci in a spatiotemporal manner.
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Factor 2 Relacionado con NF-E2 , FN-kappa B , Animales , Inflamación , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Especies Reactivas de Oxígeno , Transducción de SeñalRESUMEN
Two cobalt oxyfluoride antiferromagnets CoMOF5(pyz)(H2O)2 (M = Nb 1, Ta 2; pyz = pyrazine) have been synthesized via conventional hydrothermal methods and characterized by thermogravimetric (TGA) analysis, FTIR spectroscopy, electron spin resonance (ESR), magnetic susceptibility, and magnetization measurements at both static low field and pulsed high field. The single-crystal X-ray diffraction indicates both compounds 1 and 2 are isostructural and crystallize in the monoclinic space group C2/m with a two-dimensional Co2+ triangular lattice in the ab plane, separated by the nonmagnetic MOF5 (M = Nb 1, Ta 2) octahedra along the c-axis with large intertriangular-lattice Co···Co distance. Because of low dimensionality together with frustrated triangular lattice, compounds 1 and 2 exhibit no long-range antiferromagnetic order until â¼3.7 K. Moreover, a spin flop transition is observed in the magnetization curves at 2 K for both compounds, which is further confirmed by ESR spectra. In addition, the ESR spectra suggest the presence of a zero-field spin gap in both compounds. The high field magnetization measured at 2 K saturates at â¼7 T with Ms = 1.55 µB for 1 and 1.71 µB for 2, respectively, after subtracting the Van Vleck paramagnetic contribution, which is usually observed for Co2+ ions with pseudospin spin of 1/2 at low temperature. Powder-averaged magnetic anisotropy of g = 3.10 for 1 (3.42 for 2) and magnetic superexchange interaction J/kB = -3.2 K for 1 (-3.6 K for 2) are obtained.
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Multifunctional transformation of amide C-N bond cleavage is reported. The protocol applies to benzamide, thioamide, alcohols, and mercaptan under similar reaction conditions catalyzed by NaOTs. It is noteworthy that NaOTs can not only be recycled and reused for up to three cycles without significant loss in catalytic activity, but also catalyze gram-grade reactions. This study provides a novel solution with mild conditions and a simple procedure for transformation of multiple amides.
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The precise location of tumor and completeness of surgical resection are critical to successful tumor surgery; thus, the method capable of preoperatively locating a tumor site and intraoperatively determining tumor margins would be highly ideal. Herein, an activatable nanocomposite probe was developed for preoperatively locating orthotopic hepatic tumor via multispectral optoacoustic tomography imaging and for intraoperative navigation via near-IR-1 (NIR-I) and NIR-II fluorescence imaging. The molecular probe comprises an electronic donor, an acceptor, and a recognition moiety and forms the nanocomposite probe with bovine serum albumin. The probe specifically responds to nitroreductase overexpressed in tumor cells, which transforms the aromatic nitro group into an electron-donating amino group and thus activates the probe. The activated probe with the aggregation-induced emission feature generates strong NIR-I/NIR-II fluorescence and optoacoustic signals for dual-mode imaging. Owing to the in situ response toward nitroreductase in tumor cells in the hepatic region, the probe is found capable of detecting early stage orthotopic liver tumors. Furthermore, with the nanocomposite probe, we can obtain the 3D MSOT images to accurately locate orthotopic liver tumors preoperatively and the NIR-I/NIR-II fluorescence images to provide intraoperative guidance for tumor resection surgery.
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Neoplasias Hepáticas/diagnóstico por imagen , Sondas Moleculares/química , Nanocompuestos/química , Imagen Óptica/métodos , Animales , Bovinos , Línea Celular Tumoral , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Masculino , Ratones , Ratones Desnudos , Nitrorreductasas/metabolismo , Técnicas Fotoacústicas , Albúmina Sérica Bovina/química , Espectroscopía Infrarroja Corta , Trasplante HeterólogoRESUMEN
An activatable nanoprobe for imaging breast cancer metastases through near infrared-I (NIR-I)/NIR-II fluorescence imaging and multispectral optoacoustic tomography (MSOT) imaging was designed. With a dihydroxanthene moiety serving as the electron donor, quinolinium as the electron acceptor and nitrobenzyloxydiphenylamino as the recognition element, the probe can specifically respond to nitroreductase and transform into an activated D-π-A structure with a NIR emission band extending beyond 900â nm. The activated nanoprobe exhibits NIR emission enhanced by aggregation-induced emission (AIE) and produces strong optoacoustic signal. The nanoprobe was used to detect and image metastases from the orthotopic breast tumors to lymph nodes and then to lung in two breast cancer mouse models. Moreover, the nanoprobe can monitor the treatment efficacy during chemotherapeutic course through fluorescence and MSOT imaging.
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Neoplasias de la Mama/diagnóstico , Imagen Óptica/métodos , Técnicas Fotoacústicas/métodos , Animales , Colorantes Fluorescentes , Humanos , Rayos Infrarrojos , Ratones , Nanoestructuras , Metástasis de la Neoplasia/diagnóstico , Tomografía/métodosRESUMEN
The palladium-catalyzed decarbonylative Suzuki-Miyaura coupling of amides via selective amide C-N bond cleavage was reported, which afforded mild access to substitute biaryl products in the presence of low catalyst loading with NaHCO3 as the base in good yields within 4 h (29 examples).
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Dietary fibres are main substances in the pig's feed. Because of the recalcitrance, they could enter swine wastewater and become a serious obstruction factor for the anaerobic digestion process. In this work, three dietary fibres abundant in pig feedstocks: Wheat Bran Fibre (WBF), Alfalfa Fibre (AF) and Rice Chaff Fibre (RCF) were chosen and their anaerobic degradability was determined. The results showed that the biochemical methane potential in 10 days (BMP10) of WBF, AF and RCF was 258, 176 and 86 mL/g-VS, respectively. The size, purity, crystallinity, and lignin coating in particular, were found having influences on the anaerobic biodegradability of dietary fibres. To surprise, a negative rather than positive effect was observed for the direct addition of extraneous cellulase into the anaerobic digestion systems, leading to a longer lag time and a smaller BMP10. The enhancement was achieved for the addition of extraneous bacteria in the form of anaerobic granular sludge (AnGS), shortening the lag time of WBF and AF by 36% and 13%, respectively. By high-throughput sequencing analysis, abundant protein and amino acids degraders found in anaerobic activated sludge (AnAS) could degrade the exogenous enzymes. Abundant members affiliated to the family Anaerolineaceae, and Syntrophobacteraceae in AnGS, related to the cellulolytic and syntrophic activity respectively, probably contribute to the acceleration effect of AnGS.
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Reactores Biológicos , Aguas Residuales , Anaerobiosis , Animales , Biodegradación Ambiental , Fibras de la Dieta , Metano , Aguas del Alcantarillado , PorcinosRESUMEN
In recent years, it has been demonstrated that amide carbon-nitrogen bonds can be activated and selectively cleaved using transition metal catalysts. However, these methodologies have been restricted to specific amides; a one-to-one relationship exists between the catalytic system and the amides and also uses large amounts of transition-metal catalysts and ligands. Hence, we now report a general strategy for esterification of common amides using fluoride as a catalyst. This method shows high functional group tolerance, and notably it requires only a slight excess of the alcohol nucleophile, which is a rare case in transition-metal-free amide transformations. Moreover, this approach may provide a new understanding for further studies on esterification of amides and is expected to stimulate the development of alternative methods for direct functionalization of amides.
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A rhodium-catalyzed C-H functionalization with activated amides by decarbonylation has been developed. Notably, this is the first C-H arylation employing N-acylsaccharins as coupling partners to give biaryls in good to excellent yields. The highlight of the work is the high tolerance of functional groups such as formyl, ester, and vinyl and the use of a removable directing group.
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Amidas/química , Rodio/química , Sacarina/síntesis química , Catálisis , Cristalografía por Rayos X , Modelos Moleculares , Estructura Molecular , Sacarina/químicaRESUMEN
A palladium-catalyzed one-pot procedure for the synthesis of aryl ketones has been developed. Triazine esters when coupled with aryl boronic acids provided aryl ketones in moderate to excellent yields (up to 95%) in the presence of 1 mol % Pd(PPh3)2Cl2 for 30 min.
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Carbon capture, utilization, and storage (CCUS) technology is widely recognized as a key solution for mitigating global climate change. Consequently, it has received significant attention from countries worldwide. However, carbon dioxide corrosion poses a significant challenge to CCUS and represents a bottleneck to the large-scale development and application of this technology. To mitigate this issue, this review starts with a discussion of corrosion problems in CCUS. Later, the fundamentals of the carbon dioxide corrosion mechanism are introduced. Then, the influences of various factors that affect the corrosion are highlighted, such as water content, pH, flow rate, etc. Afterward, we summarize the commonly used methods for corrosion protection, with a particular focus on inhibitor, given their eco-friendly and effective nature. Lastly, challenges and prospects are discussed to motivate future studies on developing novel, high-performance green inhibitor and studying the corresponding protection mechanisms, hoping to make some contributions to carbon emission reduction.
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Histone H2B is a member of the core histones, which together with other histones form the nucleosome, the basic structural unit of chromosomes. As scientists delve deeper into histones, researchers gradually realize that histone H2B is not only an important part of nucleosomes, but also plays a momentous role in regulating gene transcription, acting as a receptor and antimicrobial action outside the nucleus. There are a variety of epigenetically modified sites in the H2B tail rich in arginine and lysine, which can occur in ubiquitination, phosphorylation, methylation, acetylation, etc. When stimulated by foreign factors such as bacteria, viruses or parasites, histone H2B can act as a receptor for the recognition of these pathogens, and induce an intrinsic immune response to enhance host defense. In addition, the extrachromosomal histone H2B is also an important anti-microorganism agent, which may be the key to the development of antibiotics in the future. This review aims to summarize the interaction between histone H2B and etiological agents and explore the role of H2B in epigenetic modifications, receptors and antimicrobial activity.
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Epigénesis Genética , Histonas , Histonas/metabolismo , Humanos , Animales , Bacterias/metabolismo , Bacterias/genéticaRESUMEN
Graph domain adaptation (GDA) aims to address the challenge of limited label data in the target graph domain. Existing methods such as UDAGCN, GRADE, DEAL, and COCO for different-level (node-level, graph-level) adaptation tasks exhibit variations in domain feature extraction, and most of them solely rely on representation alignment to transfer label information from a labeled source domain to an unlabeled target domain. However, this approach can be influenced by irrelevant information and usually ignores the conditional shift of the downstream predictor. To effectively address this issue, we introduce a target-oriented unsupervised graph domain adaptive framework for graph adaptation called TO-UGDA. Particularly, domain-invariant feature representations are extracted using graph information bottleneck. The discrepancy between two domains is minimized using an adversarial alignment strategy to obtain a unified feature distribution. Additionally, the meta pseudo-label is introduced to enhance downstream adaptation and improve the model's generalizability. Through extensive experimentation on real-world graph datasets, it is proved that the proposed framework achieves excellent performance across various node-level and graph-level adaptation tasks.