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Understanding the molecular-level mechanisms involved in transmembrane ion selectivity is essential for optimizing membrane separation performance. In this study, we reveal our observations regarding the transmembrane behavior of Li+ and Mg2+ ions as a response to the changing pore solvation abilities of the covalent-organic-framework (COF) membranes. These abilities were manipulated by adjusting the lengths of the oligoether segments attached to the pore channels. Through comparative experiments, we were able to unravel the relationships between pore solvation ability and various ion transport properties, such as partitioning, conduction, and selectivity. We also emphasize the significance of the competition between Li+ and Mg2+ with the solvating segments in modulating selectivity. We found that increasing the length of the oligoether chain facilitated ion transport; however, it was the COF membrane with oligoether chains containing two ethylene oxide units that exhibited the most pronounced discrepancy in transmembrane energy barrier between Li+ and Mg2+, resulting in the highest separation factor among all the evaluated membranes. Remarkably, under electro-driven binary-salt conditions, this specific COF membrane achieved an exceptional Li+/Mg2+ selectivity of up to 1352, making it one of the most effective membranes available for Li+/Mg2+ separation. The insights gained from this study significantly contribute to advancing our understanding of selective ion transport within confined nanospaces and provide valuable design principles for developing highly selective COF membranes.
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Loss of hepatocyte nuclear factor 4α (HNF4α) expression is frequently observed in end-stage liver disease and associated with loss of vital liver functions, thus increasing mortality. Loss of HNF4α expression is mediated by inflammatory cytokines, such as transforming growth factor (TGF)-ß. However, details of how HNF4α is suppressed are largely unknown to date. Herein, TGF-ß did not directly inhibit HNF4α but contributed to its transcriptional regulation by SMAD2/3 recruiting acetyltransferase CREB-binding protein/p300 to the HNF4α promoter. The recruitment of CREB-binding protein/p300 is indispensable for CCAAT/enhancer-binding protein α (C/EBPα) binding, another essential requirement for constitutive HNF4α expression in hepatocytes. Consistent with the in vitro observation, 67 of 98 patients with hepatic HNF4α expressed both phospho-SMAD2 and C/EBPα, whereas 22 patients without HNF4α expression lacked either phospho-SMAD2 or C/EBPα. In contrast to the observed induction of HNF4α, SMAD2/3 inhibited C/EBPα transcription. Long-term TGF-ß incubation resulted in C/EBPα depletion, which abrogated HNF4α expression. Intriguingly, SMAD2/3 inhibitory binding to the C/EBPα promoter was abolished by insulin. Two-thirds of patients without C/EBPα lacked membrane glucose transporter type 2 expression in hepatocytes, indicating insulin resistance. Taken together, these data indicate that hepatic insulin sensitivity is essential for hepatic HNF4α expression in the condition of inflammation.
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Proteína de Unión a CREB , Insulina , Humanos , Proteína alfa Potenciadora de Unión a CCAAT/metabolismo , Proteína de Unión a CREB/metabolismo , Factor Nuclear 4 del Hepatocito/genética , Factor Nuclear 4 del Hepatocito/metabolismo , Hepatocitos/metabolismo , Hígado/metabolismo , Factor de Crecimiento Transformador beta/farmacología , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
ConspectusMembranes are pivotal in a myriad of energy production processes and modern separation techniques. They are essential in devices for energy generation, facilities for extracting energy elements, and plants for wastewater treatment, each of which hinges on effective ion separation. While biological ion channels show exceptional permeability and selectivity, designing synthetic membranes with defined pore architecture and chemistry on the (sub)nanometer scale has been challenging. Consequently, a typical trade-off emerges: highly permeable membranes often sacrifice selectivity and vice versa. To tackle this dilemma, a comprehensive understanding and modeling of synthetic membranes across various scales is imperative. This lays the foundation for establishing design criteria for advanced membrane materials. Key attributes for such materials encompass appropriately sized pores, a narrow pore size distribution, and finely tuned interactions between desired permeants and the membrane. The advent of covalent-organic-framework (COF) membranes offers promising solutions to the challenges faced by conventional membranes in selective ion separation within the water-energy nexus. COFs are molecular Legos, facilitating the precise integration of small organic structs into extended, porous, crystalline architectures through covalent linkage. This unique molecular architecture allows for precise control over pore sizes, shapes, and distributions within the membrane. Additionally, COFs offer the flexibility to modify their pore spaces with distinct functionalities. This adaptability not only enhances their permeability but also facilitates tailored interactions with specific ions. As a result, COF membranes are positioned as prime candidates to achieve both superior permeability and selectivity in ion separation processes.In this Account, we delineate our endeavors aimed at leveraging the distinctive attributes of COFs to augment ion separation processes, tackling fundamental inquiries while identifying avenues for further exploration. Our strategies for fabricating COF membranes with enhanced ion selectivity encompass the following: (1) crafting (sub)nanoscale ion channels to enhance permselectivity, thereby amplifying energy production; (2) implementing a multivariate (MTV) synthesis method to control charge density within nanochannels, optimizing ion transport efficiency; (3) modifying the pore environment within confined mass transfer channels to establish distinct pathways for ion transport. For each strategy, we expound on its chemical foundations and offer illustrative examples that underscore fundamental principles. Our efforts have culminated in the creation of groundbreaking membrane materials that surpass traditional counterparts, propelling advancements in sustainable energy conversion, waste heat utilization, energy element extraction, and pollutant removal. These innovations are poised to redefine energy systems and industrial wastewater management practices. In conclusion, we outline future research directions and highlight key challenges that need addressing to enhance the ion/molecular recognition capabilities and practical applications of COF membranes. Looking forward, we anticipate ongoing advancements in functionalization and fabrication techniques, leading to enhanced selectivity and permeability, ultimately rivaling the capabilities of biological membranes.
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Premature abscission of flowers and fruits triggered by low light stress can severely reduce crop yields. However, the underlying molecular mechanism of this organ abscission is not fully understood. Here, we show that a gene (SlCLV3) encoding CLAVATA3 (CLV3), a peptide hormone that regulates stem cell fate in meristems, is highly expressed in the pedicel abscission zone (AZ) in response to low light in tomato (Solanum lycopersicum). SlCLV3 knockdown and knockout lines exhibit delayed low light-induced flower drop. The receptor kinases SlCLV1 and BARELY ANY MERISTEM1 function in the SlCLV3 peptide-induced low light response in the AZ to decrease expression of the transcription factor gene WUSCHEL (SlWUS). DNA affinity purification sequencing identified the transcription factor genes KNOX-LIKE HOMEDOMAIN PROTEIN1 (SlKD1) and FRUITFULL2 (SlFUL2) as SlWUS target genes. Our data reveal that low light reduces SlWUS expression, resulting in higher SlKD1 and SlFUL2 expression in the AZ, thereby perturbing the auxin response gradient and causing increased ethylene production, eventually leading to the initiation of abscission. These results demonstrate that the SlCLV3-SlWUS signaling pathway plays a central role in low light-induced abscission by affecting auxin and ethylene homeostasis.
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Etilenos , Flores , Ácidos Indolacéticos , Proteínas de Plantas , Solanum lycopersicum , Etilenos/metabolismo , Flores/genética , Flores/crecimiento & desarrollo , Regulación de la Expresión Génica de las Plantas/genética , Homeostasis , Ácidos Indolacéticos/metabolismo , Solanum lycopersicum/genética , Solanum lycopersicum/crecimiento & desarrollo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
All mutations in exon 9 of the Cullin3 gene associated with pseudohypoaldosteronism type II (PHA II) contribute to exon skipping to different degrees, but the specific molecular mechanism of this aberrant splicing is still unclear. The aims of this study were to investigate the regulatory mechanism underlying two synonymous splicing events, c.1221A > G (p. Glu407Glu) and c.1236G > A (p. Leu412Leu), and to discover a therapeutic strategy for correcting this aberrant splicing by targeting potential regulatory sites. Through a series of RNA pulldown, silver staining, western blotting, small interfering RNA knockdown, in vitro overexpression and single or double site-directed mutagenesis experiments, we first explored the pathogenesis of exon 9 skipping caused by mutations in the CUL3 gene and verified that the main splicing regulators associated with the synonymous c.1221A > G and c.1236G > A mutations were heterogeneous nuclear ribonucleoproteins. In addition, we verified that introducing another synonymous mutation, c.1224A > G (A18G), significantly rescued the abnormal splicing caused by c.1221A > G and c.1236G > A, highlighting the therapeutic potential for the treatment of PHA II.
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Ribonucleoproteínas Nucleares Heterogéneas , Mutación Silenciosa , Ribonucleoproteínas Nucleares Heterogéneas/genética , Exones/genética , Empalme del ARN/genética , Mutación , Empalme AlternativoRESUMEN
Here, the poly (l-lactic acid) (PLLA) membrane with multi-structured networks (MSN) is successfully prepared by electrospinning technology for the first time. It is composed of micron-sized ribbon-structured fibers and ultrafine nanofibers with a diameter of tens of nanometers, and they are connected to form the new network structure. Thanks to the special fiber morphology and structure, the interception and electrostatic adsorption ability for against atmospheric particulate matter (PM) are significantly enhanced, and the resistance to airflow is reduced due to the "slip effect" caused by ultrafine nanofibers. The PLLA MSN membrane shows excellent filtration performance with ultra-high filtration efficiency (>99.9% for PM2.5 and >99.5% for PM0.3) and ultra-low pressure drop (≈20 Pa). It has demonstrated filtration performance that even exceeds current non-biodegradable polymer materials, laying the foundation for future applications of biodegradable PLLA in the field of air filtration. In addition, this new structure also provides a new idea for optimizing the performance of other polymer materials.
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The evolution of porous membranes has revitalized their potential application in sustainable osmotic-energy conversion. However, the performance of multiporous membranes deviates significantly from the linear extrapolation of single-pore membranes, primarily due to the occurrence of ion-concentration polarization (ICP). This study proposes a robust strategy to overcome this challenge by incorporating photoelectric responsiveness into permselective membranes. By introducing light-induced electric fields within the membrane, the transport of ions is accelerated, leading to a reduction in the diffusion boundary layer and effectively mitigating the detrimental effects of ICP. The developed photoelectric-responsive covalent-organic-framework membranes exhibit an impressive output power density of 69.6 W m-2 under illumination, surpassing the commercial viability threshold by ≈14-fold. This research uncovers a previously unexplored benefit of integrating optical electric conversion with reverse electrodialysis, thereby enhancing energy conversion efficiency.
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The commitment to replicate the RNA genome of flaviviruses without a primer involves RNA-protein interactions that have been shown to include the recognition of the stem-loop A (SLA) in the 5' untranslated region (UTR) by the nonstructural protein NS5. We show that DENV2 NS5 arginine 888, located within the carboxy-terminal 18 residues, is completely conserved in all flaviviruses and interacts specifically with the top-loop of 3'SL in the 3'UTR which contains the pentanucleotide 5'-CACAG-3' previously shown to be critical for flavivirus RNA replication. We present virological and biochemical data showing the importance of this Arg 888 in virus viability and de novo initiation of RNA polymerase activity in vitro. Based on our binding studies, we hypothesize that ternary complex formation of NS5 with 3'SL, followed by dimerization, leads to the formation of the de novo initiation complex that could be regulated by the reversible zipping and unzipping of cis-acting RNA elements.
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Virus del Dengue/fisiología , ARN/genética , Proteínas no Estructurales Virales/metabolismo , Replicación Viral , Regiones no Traducidas 3' , Animales , Arginina/química , Línea Celular , Secuencia Conservada , Cricetinae , Cricetulus , ARN Polimerasas Dirigidas por ADN/metabolismo , Virus del Dengue/genética , Proteínas no Estructurales Virales/química , Proteínas no Estructurales Virales/genéticaRESUMEN
An aerobic methanotroph was isolated from a secondary sedimentation tank of a wastewater treatment plant and designated strain OY6T. Cells of OY6T were Gram-stain-negative, pink-pigmented, motile rods and contained an intracytoplasmic membrane structure typical of type I methanotrophs. OY6T could grow at a pH range of 4.5-7.5 (optimum pH 6.5) and at temperatures ranging from 20â°C to 37â°C (optimum 30â°C). The major cellular fatty acids were C14â:â0, C16â:â1ω7c/C16â:â1ω6c and C16â:â1ω5c; the predominant respiratory quinone was MQ-8. The genome size was 5.41 Mbp with a DNA G+C content of 51.7 mol%. OY6T represents a member of the family Methylococcaceae of the class Gammaproteobacteria and displayed 95.74-99.64â% 16S rRNA gene sequence similarity to the type strains of species of the genus Methylomonas. Whole-genome comparisons based on average nucleotide identity (ANI) and digital DNA-DNA hybridisation (dDDH) confirmed that OY6T should be classified as representing a novel species. The most closely related type strain was Methylomonas fluvii EbBT, with 16S rRNA gene sequence similarity, ANI by blast (ANIb), ANI by MUMmer (ANIm) and dDDH values of 99.64, 90.46, 91.92 and 44.5â%, respectively. OY6T possessed genes encoding both the particulate methane monooxygenase enzyme and the soluble methane monooxygenase enzyme. It grew only on methane or methanol as carbon sources. On the basis of phenotypic, genetic and phylogenetic data, strain OY6T represents a novel species within the genus Methylomonas for which the name Methylomonas defluvii sp. nov. is proposed, with strain OY6T (=GDMCC 1.4114T=KCTC 8159T=LMG 33371T) as the type strain.
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Methylococcaceae , Methylomonas , Metano , Filogenia , ARN Ribosómico 16S/genética , Composición de Base , Ácidos Grasos/química , Análisis de Secuencia de ADN , ADN Bacteriano/genética , Técnicas de Tipificación Bacteriana , Bacterias , Methylococcaceae/genética , Oxidación-ReducciónRESUMEN
The development of a solid-state electrolyte (SSE) is crucial for overcoming the side reactions of metal potassium anodes and advancing the progress of K-ion batteries (KIBs). Exploring the diffusion mechanism of the K ion in SSE is important for deepening our understanding and promoting its development. In this study, we conducted static calculations and utilized deep potential molecular dynamics (DeepMD) to investigate the behavior of cubic K3SbS4. The original K3SbS4 exhibited poor ionic conductivity, but we discovered that introducing heterovalent tungsten doping created vacancies, which significantly reduced the activation energy to 0.12 eV and enhanced the ionic conductivity to 1.80 × 10-2 S/cm. The diffusion of K-ions in K3SbS4 primarily occurs through the exchange of positions with K vacancies. This research provides insights into the design of SSE with high ionic conductivity. Furthermore, it highlights the effectiveness of DeepMD as a powerful tool for studying the SSE.
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OBJECTIVE: Accurate prediction of survival prognosis is helpful to guide clinical decision-making. The aim of this study was to develop a model using machine learning techniques to predict the occurrence of composite thromboembolic events (CTEs) in elderly patients with atrial fibrillation(AF). These events encompass newly diagnosed cerebral ischemia events, cardiovascular events, pulmonary embolism, and lower extremity arterial embolism. METHODS: This retrospective study included 6,079 elderly hospitalized patients (≥ 75 years old) with AF admitted to the People's Liberation Army General Hospital in China from January 2010 to June 2022. Random forest imputation was used for handling missing data. In the descriptive statistics section, patients were divided into two groups based on the occurrence of CTEs, and differences between the two groups were analyzed using chi-square tests for categorical variables and rank-sum tests for continuous variables. In the machine learning section, the patients were randomly divided into a training dataset (n = 4,225) and a validation dataset (n = 1,824) in a 7:3 ratio. Four machine learning models (logistic regression, decision tree, random forest, XGBoost) were trained on the training dataset and validated on the validation dataset. RESULTS: The incidence of composite thromboembolic events was 19.53%. The Least Absolute Shrinkage and Selection Operator (LASSO) method, using 5-fold cross-validation, was applied to the training dataset and identified a total of 18 features that exhibited a significant association with the occurrence of CTEs. The random forest model outperformed other models in terms of area under the curve (ACC: 0.9144, SEN: 0.7725, SPE: 0.9489, AUC: 0.927, 95% CI: 0.9105-0.9443). The random forest model also showed good clinical validity based on the clinical decision curve. The Shapley Additive exPlanations (SHAP) showed that the top five features associated with the model were history of ischemic stroke, high triglyceride (TG), high total cholesterol (TC), high plasma D-dimer, age. CONCLUSIONS: This study proposes an accurate model to stratify patients with a high risk of CTEs. The random forest model has good performance. History of ischemic stroke, age, high TG, high TC and high plasma D-Dimer may be correlated with CTEs.
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Fibrilación Atrial , Técnicas de Apoyo para la Decisión , Aprendizaje Automático , Valor Predictivo de las Pruebas , Tromboembolia , Humanos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Femenino , Masculino , Anciano , Estudios Retrospectivos , Medición de Riesgo , China/epidemiología , Tromboembolia/epidemiología , Tromboembolia/diagnóstico , Tromboembolia/etiología , Factores de Riesgo , Anciano de 80 o más Años , Incidencia , Pronóstico , Factores de Edad , Reproducibilidad de los Resultados , Pueblos del Este de AsiaRESUMEN
Robotic Mobile Fulfillment Systems (RMFSs) face challenges in handling large-scale orders and navigating complex environments, frequently encountering a series of intricate decision-making problems, such as order allocation, shelf selection, and robot scheduling. To address these challenges, this paper integrates Deep Reinforcement Learning (DRL) technology into an RMFS, to meet the needs of efficient order processing and system stability. This study focuses on three key stages of RMFSs: order allocation and sorting, shelf selection, and coordinated robot scheduling. For each stage, mathematical models are established and the corresponding solutions are proposed. Unlike traditional methods, DRL technology is introduced to solve these problems, utilizing a Genetic Algorithm and Ant Colony Optimization to handle decision making related to large-scale orders. Through simulation experiments, performance indicators-such as shelf access frequency and the total processing time of the RMFS-are evaluated. The experimental results demonstrate that, compared to traditional methods, our algorithms excel in handling large-scale orders, showcasing exceptional superiority, capable of completing approximately 110 tasks within an hour. Future research should focus on integrated decision-making modeling for each stage of RMFSs and designing efficient heuristic algorithms for large-scale problems, to further enhance system performance and efficiency.
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Two-dimensional (2D) nanomaterials have been widely applied as building blocks of nanoporous materials for high-precision separations. However, most existing 2D nanomaterials suffer from poor continuity and a lack of interior linking, resulting in deteriorated performance when assembled into macroscopic bulk structures. Here, a unique superspreading-based phase inversion technique is proposed to directly construct 2D nanofibrous networks (NFNs) from a polymer solution. By tailoring capillary behavior, polymer solution droplets evolve into ultrathin liquid films through superspreading; manipulating phase instability, subsequently, enables the liquid film to phase invert into continuous nanostructured networks. The assembled single-layered NFNs possess integrated structural superiorities of 1D nanoscale fiber diameter (â¼40 nm) and 2D lateral infinity, exhibiting a weblike nanoarchitecture with extremely small through-pores (â¼100 nm). Our NFNs show remarkable performances in air filtration (PM0.3 removal) and water purification (microfiltration level). This creation of such attractive 2D fibrous nanomaterials can pave the way for versatile high-performance separation applications.
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The copper-cobalt metal oxide composite magnesium oxide catalyst loaded with Ru has achieved the aerobic oxidation of 5-hydroxymethylfurfural (HMF) to the bio-based polyester monomer 2,5-furandicarboxylic acid (FDCA) under base-free conditions. Several Ru/Cu-Co-O·MgO catalysts were prepared, with Cu-Co-O being a combination of CuO and Co3O4. The catalyst's activity was boosted by the synergistic interaction between copper and cobalt, as well as an optimal copper-to-cobalt molar ratio. Optimal catalytic activity was observed in the Ru4/Cu1-Co1-O·MgO catalyst, loaded with 4 wt% Ru when copper-to-cobalt molar ratio of 1:1 and magnesium oxide compounding amount of 6 mmol were employed. The inclusion of MgO and the load of Ru not only expanded the specific surface area of the catalyst but also heightened its basicity. Additionally, the presence of loaded Ru improved the catalyst's reducibility at low temperatures. In aqueous solution under oxygen pressure, the conversion rate of HMF achieved 100%, and the yield of FDCA was 86.1%. After five reaction cycles, examining the catalyst and solution revealed that Ru nanoparticles resisted leaching or oxidation, and MgO exhibited only slight dissolution. The green separation of the product was achieved using semi-preparative liquid chromatography, selectively collecting the FDCA-containing solution by exploiting variations in interactions between solutes and the stationary/mobile phases. The subsequent steps involved rotary evaporation and drying, resulting in FDCA powder with a purity exceeding 99%. Notably, this approach eliminated the need to introduce concentrated hydrochloric acid into the system for FDCA separation, providing a novel method for synthesising powdered FDCA.
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Auxin regulates flower and fruit abscission, but how developmental signals mediate auxin transport in abscission remains unclear. Here, we reveal the role of the transcription factor BEL1-LIKE HOMEODOMAIN11 (SlBEL11) in regulating auxin transport during abscission in tomato (Solanum lycopersicum). SlBEL11 is highly expressed in the fruit abscission zone, and its expression increases during fruit development. Knockdown of SlBEL11 expression by RNA interference (RNAi) caused premature fruit drop at the breaker (Br) and 3 d post-breaker (Br+3) stages of fruit development. Transcriptome and metabolome analysis of SlBEL11-RNAi lines revealed impaired flavonoid biosynthesis and decreased levels of most flavonoids, especially quercetin, which functions as an auxin transport inhibitor. This suggested that SlBEL11 prevents premature fruit abscission by modulating auxin efflux from fruits, which is crucial for the formation of an auxin response gradient. Indeed, quercetin treatment suppressed premature fruit drop in SlBEL11-RNAi plants. DNA affinity purification sequencing (DAP-seq) analysis indicated that SlBEL11 induced expression of the transcription factor gene SlMYB111 by directly binding to its promoter. Chromatin immunoprecipitation-quantitative polymerase chain reaction and electrophoretic mobility shift assay showed that S. lycopersicum MYELOBLASTOSIS VIRAL ONCOGENE HOMOLOG111 (SlMYB111) induces the expression of the core flavonoid biosynthesis genes SlCHS1, SlCHI, SlF3H, and SlFLS by directly binding to their promoters. Our findings suggest that the SlBEL11-SlMYB111 module modulates flavonoid biosynthesis to fine-tune auxin efflux from fruits and thus maintain an auxin response gradient in the pedicel, thereby preventing premature fruit drop.
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Solanum lycopersicum , Solanum lycopersicum/genética , Frutas/metabolismo , Quercetina/farmacología , Quercetina/metabolismo , Ácidos Indolacéticos/metabolismo , Factores de Transcripción/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/metabolismoRESUMEN
OBJECTIVE: Multidrug resistance protein 2 (MRP2) is a bottleneck in bilirubin excretion. Its loss is sufficient to induce hyperbilirubinaemia, a prevailing characteristic of acute liver failure (ALF) that is closely associated with clinical outcome. This study scrutinises the transcriptional regulation of MRP2 under different pathophysiological conditions. DESIGN: Hepatic MRP2, farnesoid X receptor (FXR) and Forkhead box A2 (FOXA2) expression and clinicopathologic associations were examined by immunohistochemistry in 14 patients with cirrhosis and 22 patients with ALF. MRP2 regulatory mechanisms were investigated in primary hepatocytes, Fxr -/- mice and lipopolysaccharide (LPS)-treated mice. RESULTS: Physiologically, homeostatic MRP2 transcription is mediated by the nuclear receptor FXR/retinoid X receptor complex. Fxr-/- mice lack apical MRP2 expression and rapidly progress into hyperbilirubinaemia. In patients with ALF, hepatic FXR expression is undetectable, however, patients without infection maintain apical MRP2 expression and do not suffer from hyperbilirubinaemia. These patients express FOXA2 in hepatocytes. FOXA2 upregulates MRP2 transcription through binding to its promoter. Physiologically, nuclear FOXA2 translocation is inhibited by insulin. In ALF, high levels of glucagon and tumour necrosis factor α induce FOXA2 expression and nuclear translocation in hepatocytes. Impressively, ALF patients with sepsis express low levels of FOXA2, lose MRP2 expression and develop severe hyperbilirubinaemia. In this case, LPS inhibits FXR expression, induces FOXA2 nuclear exclusion and thus abrogates the compensatory MRP2 upregulation. In both Fxr -/- and LPS-treated mice, ectopic FOXA2 expression restored apical MRP2 expression and normalised serum bilirubin levels. CONCLUSION: FOXA2 replaces FXR to maintain MRP2 expression in ALF without sepsis. Ectopic FOXA2 expression to maintain MRP2 represents a potential strategy to prevent hyperbilirubinaemia in septic ALF.
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Factor Nuclear 3-beta del Hepatocito , Fallo Hepático Agudo , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Animales , Ratones , Bilirrubina , Factor Nuclear 3-beta del Hepatocito/metabolismo , Hepatocitos/metabolismo , Hiperbilirrubinemia/metabolismo , Hiperbilirrubinemia/patología , Lipopolisacáridos/metabolismo , Hígado/metabolismo , Fallo Hepático Agudo/metabolismo , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos/metabolismo , Miembro 4 de la Subfamilia B de Casete de Unión a ATPRESUMEN
Extremely low temperature has posed huge burden on the public safety concerns and global economics, thereby calling for high-performance warmth retention materials to resist harsh environment. However, most present fibrous warmth retention materials are limited by their large fiber diameter and simple stacking structure, leading to heavy weight, weak mechanical property, and limited thermal insulation performance. Herein, an ultralight and mechanically robust polystyrene/polyurethane fibrous aerogel by direct electrospinning for warmth retention is reported. Manipulation of charge density and phase separation of charged jet allows for the direct assembly of fibrous aerogels consisting of interweaved curly wrinkled micro/nanofibers. The resultant curly wrinkled micro/nanofibrous aerogel possesses low density of 6.8 mg cm-3 and nearly full recovery from 1500-cycle deformations, exhibiting both ultralight feature and superelastic property. The aerogel also shows low thermal conductivity of 24.5 mW m-1 K-1 , making synthetic warmth retention materials superior to down feather possible. This work may shed light on developing versatile 3D micro/nanofibrous materials for environmental, biological, and energy applications.
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The development of catalytic systems that can activate aryl chlorides for palladium-catalyzed cross-coupling reactions is at the forefront of ongoing efforts to synthesize fine chemicals. In this study, a facile ligand-template approach is adopted to achieve active-site encapsulation by forming supramolecular assemblies; this bestowed the pristine inert counterparts with reactivity, which is further increased upon the construction of a porous framework. Experimental results indicated that the isolation of ligands by the surrounding template units is key to the formation of catalytically active monoligated palladium complexes. Additionally, the construction of porous frameworks using the resulting supramolecular assemblies prevented the decomposition of the Pd complexes into nanoparticles, which drastically increased the catalyst lifetime. These findings, along with the simplicity and generality of the synthesis scheme, suggest that the strategy can be leveraged to achieve unique reactivity and potentially enable fine-chemical synthesis.
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Pathogens integrate multiple environmental signals to navigate the host and control the expression of virulence genes. In this process, small regulatory noncoding RNAs (sRNAs) may function in gene expression as post-transcriptional regulators. In this study, the sRNA Xonc3711 functioned in the response of the rice pathogen, Xanthomonas oryzae pv. oryzicola (Xoc), to oxidative stress. Xonc3711 repressed production of the DNA-binding protein Xoc_3982 by binding to the xoc_3982 mRNA within the coding region. Mutational analysis showed that regulation required an antisense interaction between Xonc3711 and xoc_3982 mRNA, and RNase E was needed for degradation of the xoc_3982 transcript. Deletion of Xonc3711 resulted in a lower tolerance to oxidative stress due to the repression of flagella-associated genes and reduced biofilm formation. Furthermore, ChIP-seq and electrophoretic mobility shift assays showed that Xoc_3982 repressed the transcription of effector xopC2, which contributes to virulence in Xoc BLS256. This study describes how sRNA Xonc3711 modulates multiple traits in Xoc via signals perceived from the external environment.
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Estrés Oxidativo/fisiología , ARN sin Sentido/metabolismo , Xanthomonas/patogenicidad , Oryza/parasitología , Enfermedades de las Plantas/genética , ARN Pequeño no Traducido , Virulencia/genética , Xanthomonas/genética , Xanthomonas/metabolismoRESUMEN
BACKGROUND AND AIMS: It remains unknown how patients with liver failure maintain essential albumin levels. Here, we delineate a hierarchical transcription regulatory network that ensures albumin expression under different disease conditions. APPROACH AND RESULTS: We examined albumin levels in liver tissues and serum in 157 patients, including 84 with HCC, 38 decompensated cirrhosis, and 35 acute liver failure. Even in patients with liver failure, the average serum albumin concentrations were 30.55 g/L. In healthy subjects and patients with chronic liver diseases, albumin was expressed in hepatocytes. In patients with massive hepatocyte loss, albumin was expressed in liver progenitor cells (LPCs). The albumin gene (ALB) core promoter possesses a TATA box and nucleosome-free area, which allows constitutive RNA polymerase II binding and transcription initiation. Chromatin immunoprecipitation assays revealed that hepatocyte nuclear factor 4 alpha (HNF4α), CCAAT/enhancer-binding protein alpha (C/EBPα), and forkhead box A2 (FOXA2) bound to the ALB enhancer. Knockdown of either of these factors reduced albumin expression in hepatocytes. FOXA2 acts as a pioneer factor to support HNF4α and C/EBPα. In hepatocytes lacking HNF4α and C/EBPα expression, FOXA2 synergized with retinoic acid receptor (RAR) to maintain albumin transcription. RAR nuclear translocation was induced by retinoic acids released by activated HSCs. In patients with massive hepatocyte loss, LPCs expressed HNF4α and FOXA2. RNA sequencing and quantitative PCR analyses revealed that lack of HNF4α and C/EBPα in hepatocytes increased hedgehog ligand biosynthesis. Hedgehog up-regulates FOXA2 expression through glioblastoma family zinc finger 2 binding to the FOXA2 promoter in both hepatocytes and LPCs. CONCLUSIONS: A hierarchical regulatory network formed by master and pioneer transcription factors ensures essential albumin expression in various pathophysiological conditions.