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1.
Proc Natl Acad Sci U S A ; 121(8): e2316716121, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38349874

RESUMO

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.

2.
Am J Pathol ; 194(1): 52-70, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37820926

RESUMO

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.


Assuntos
Proteína de Ligação a CREB , Insulina , Humanos , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Proteína de Ligação a CREB/metabolismo , Fator 4 Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Fator de Crescimento Transformador beta/metabolismo
3.
Acc Chem Res ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950424

RESUMO

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.

4.
Plant Cell ; 34(11): 4388-4408, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-35972422

RESUMO

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.


Assuntos
Etilenos , Flores , Ácidos Indolacéticos , Proteínas de Plantas , Solanum lycopersicum , Etilenos/metabolismo , Flores/genética , Flores/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas/genética , Homeostase , Ácidos Indolacéticos/metabolismo , Solanum lycopersicum/genética , Solanum lycopersicum/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
5.
Hum Mol Genet ; 31(23): 4006-4018, 2022 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-35796549

RESUMO

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.


Assuntos
Ribonucleoproteínas Nucleares Heterogêneas , Mutação Silenciosa , Ribonucleoproteínas Nucleares Heterogêneas/genética , Éxons/genética , Splicing de RNA/genética , Mutação , Processamento Alternativo
6.
Small ; 20(25): e2310791, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38214692

RESUMO

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.

7.
RNA ; 28(2): 177-193, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34759006

RESUMO

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.


Assuntos
Vírus da Dengue/fisiologia , RNA/genética , Proteínas não Estruturais Virais/metabolismo , Replicação Viral , Regiões 3' não Traduzidas , Animais , Arginina/química , Linhagem Celular , Sequência Conservada , Cricetinae , Cricetulus , RNA Polimerases Dirigidas por DNA/metabolismo , Vírus da Dengue/genética , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/genética
8.
Artigo em Inglês | MEDLINE | ID: mdl-38607367

RESUMO

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 20 °C to 37 °C (optimum 30 °C). The major cellular fatty acids were C14 : 0, C16 : 1ω7c/C16 : 1ω6c and C16 : 1ω5c; 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 95.74-99.64 % 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 44.5 %, 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.


Assuntos
Methylococcaceae , Methylomonas , Metano , Filogenia , RNA Ribossômico 16S/genética , Composição de Bases , Ácidos Graxos/química , Análise de Sequência de DNA , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Bactérias , Methylococcaceae/genética , Oxirredução
9.
Inorg Chem ; 63(15): 6743-6751, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38573011

RESUMO

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.

10.
Nano Lett ; 23(22): 10579-10586, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37934045

RESUMO

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 (∼40 nm) and 2D lateral infinity, exhibiting a weblike nanoarchitecture with extremely small through-pores (∼100 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.

11.
J Integr Plant Biol ; 66(4): 749-770, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38420861

RESUMO

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.


Assuntos
Solanum lycopersicum , Solanum lycopersicum/genética , Frutas/metabolismo , Quercetina/farmacologia , Quercetina/metabolismo , Ácidos Indolacéticos/metabolismo , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo
12.
Gut ; 72(3): 549-559, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35444014

RESUMO

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.


Assuntos
Fator 3-beta Nuclear de Hepatócito , Falência Hepática Aguda , Proteína 2 Associada à Farmacorresistência Múltipla , Animais , Camundongos , Bilirrubina , Fator 3-beta Nuclear de Hepatócito/metabolismo , Hepatócitos/metabolismo , Hiperbilirrubinemia/metabolismo , Hiperbilirrubinemia/patologia , Lipopolissacarídeos/metabolismo , Fígado/metabolismo , Falência Hepática Aguda/metabolismo , Proteína 2 Associada à Farmacorresistência Múltipla/metabolismo , Membro 4 da Subfamília B de Transportadores de Cassetes de Ligação de ATP
13.
Small ; 19(41): e2302835, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37312622

RESUMO

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.

14.
Small ; 19(36): e2301875, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37116082

RESUMO

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.

15.
PLoS Pathog ; 17(7): e1009762, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34297775

RESUMO

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.


Assuntos
Estresse Oxidativo/fisiologia , RNA Antissenso/metabolismo , Xanthomonas/patogenicidade , Oryza/parasitologia , Doenças das Plantas/genética , Pequeno RNA não Traduzido , Virulência/genética , Xanthomonas/genética , Xanthomonas/metabolismo
16.
Hepatology ; 76(6): 1673-1689, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35257388

RESUMO

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.


Assuntos
Carcinoma Hepatocelular , Falência Hepática , Neoplasias Hepáticas , Humanos , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Ouriços/metabolismo , Neoplasias Hepáticas/metabolismo , Fator 4 Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Albuminas , Falência Hepática/metabolismo
17.
Hepatology ; 75(2): 322-337, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34435364

RESUMO

BACKGROUND AND AIMS: In patients with acute liver failure (ALF) who suffer from massive hepatocyte loss, liver progenitor cells (LPCs) take over key hepatocyte functions, which ultimately determines survival. This study investigated how the expression of hepatocyte nuclear factor 4α (HNF4α), its regulators, and targets in LPCs determines clinical outcome of patients with ALF. APPROACH AND RESULTS: Clinicopathological associations were scrutinized in 19 patients with ALF (9 recovered and 10 receiving liver transplantation). Regulatory mechanisms between follistatin, activin, HNF4α, and coagulation factor expression in LPC were investigated in vitro and in metronidazole-treated zebrafish. A prospective clinical study followed up 186 patients with cirrhosis for 80 months to observe the relevance of follistatin levels in prevalence and mortality of acute-on-chronic liver failure. Recovered patients with ALF robustly express HNF4α in either LPCs or remaining hepatocytes. As in hepatocytes, HNF4α controls the expression of coagulation factors by binding to their promoters in LPC. HNF4α expression in LPCs requires the forkhead box protein H1-Sma and Mad homolog 2/3/4 transcription factor complex, which is promoted by the TGF-ß superfamily member activin. Activin signaling in LPCs is negatively regulated by follistatin, a hepatocyte-derived hormone controlled by insulin and glucagon. In contrast to patients requiring liver transplantation, recovered patients demonstrate a normal activin/follistatin ratio, robust abundance of the activin effectors phosphorylated Sma and Mad homolog 2 and HNF4α in LPCs, leading to significantly improved coagulation function. A follow-up study indicated that serum follistatin levels could predict the incidence and mortality of acute-on-chronic liver failure. CONCLUSIONS: These results highlight a crucial role of the follistatin-controlled activin-HNF4α-coagulation axis in determining the clinical outcome of massive hepatocyte loss-induced ALF. The effects of insulin and glucagon on follistatin suggest a key role of the systemic metabolic state in ALF.


Assuntos
Ativinas/genética , Folistatina/metabolismo , Fator 4 Nuclear de Hepatócito/metabolismo , Falência Hepática Aguda/metabolismo , Ativinas/metabolismo , Insuficiência Hepática Crônica Agudizada/sangue , Adulto , Idoso , Animais , Coagulação Sanguínea , Linhagem Celular , Fator V/genética , Feminino , Folistatina/sangue , Seguimentos , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Expressão Gênica , Fator 4 Nuclear de Hepatócito/genética , Hepatócitos/metabolismo , Humanos , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/patologia , Falência Hepática Aguda/cirurgia , Regeneração Hepática , Transplante de Fígado , Masculino , Metronidazol , Camundongos , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras Genéticas , Estudos Prospectivos , Protrombina/genética , Transdução de Sinais , Proteína Smad2/genética , Proteína Smad2/metabolismo , Proteína Smad3/genética , Proteína Smad3/metabolismo , Proteína Smad4/genética , Células-Tronco/metabolismo , Fator de Crescimento Transformador beta1/genética , Peixe-Zebra
18.
Chemistry ; 29(63): e202302460, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37605607

RESUMO

Insufficient access to clean water and resources has emerged as one of the most pressing issues affecting people globally. Membrane-based ion separation has become a focal point of research for the generation of fresh water and the extraction of energy elements. This Review encapsulates recent advancements in the selective ion transport of covalent organic framework (COF) membranes, accomplished by strategically pairing diverse monomers to create membranes with various pore sizes and environments for specific purposes. We first discuss the merits of using COF materials as a basis for fabricating membranes for ion separation. We then explore the development of COF membranes in areas such as desalination, acid recovery, and energy element extraction, with a particular emphasis on the fundamental principles of membrane design. Lastly, we address both theoretical and practical challenges, as well as potential opportunities in the targeted design of ion-selective membranes. The goal of this Review is to stimulate future investigative efforts in this field, which is of significant scientific and strategic importance.

19.
Phys Chem Chem Phys ; 25(13): 9492-9499, 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-36938804

RESUMO

The development of eco-friendly anti-counterfeiting materials with high optical transparency and bright luminescence in the aggregate state is tremendously challenging. Herein, waterborne polyurethane/tetraphenylethylene-cellulose nanocrystal (WPU/TPE-CNC) nanocomposite aqueous solutions and films were prepared via direct blending aggregation-induced emission (AIE) active fluorescent CNCs (TPE-CNCs) with WPU and then applied in the anti-counterfeiting field. TPE-CNCs are compatible with WPU and dispersed homogeneously in the nanocomposite aqueous solutions and films. The thermal stability and mechanical properties of these films significantly improved with the increase in the content of TPE-CNCs. WPU/TPE-CNC nanocomposite films display high transparency (above 80%), excellent fluorescence properties, high mechanical strength, and good flexibility and then successfully applied to anti-counterfeit marking. Moreover, the dispersions of the aqueous WPU/TPE-CNC nanocomposite were nearly colorless and demonstrated promise as fluorescent anti-counterfeiting inks. This novel eco-friendly nanocomposite exhibited the potential for applications in anti-counterfeiting, fluorescent transparent paper and coating, fluorescent 3D printing, and optical/sensing devices.

20.
BMC Anesthesiol ; 23(1): 357, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37919658

RESUMO

BACKGROUND: Tracheobronchomegaly (TBM) is a rare disorder mainly characterized by dilatation and malacia of the trachea and major bronchi with diverticularization. This will be a great challenge for airway management, especially in thoracic surgery requiring one-lung ventilation. Using a laryngeal mask airway and a modified double-lumen Foley catheter (DFC) as a "blocker" may achieve one-lung ventilation. This is the first report introducing this method in a patient with TBM. CASE PRESENTATION: We present a 64-year-old man with TBM receiving left lower lobectomy. Preoperative chest computed tomography demonstrated a prominent tracheobronchial dilation and deformation with multiple diverticularization. The most commonly used double-lumen tube or bronchial blocker could not match the distorted airways. After general anesthesia induction, a 4# laryngeal mask was inserted, through which the modified DFC was positioned in the left main bronchus with the guidance of a fiberoptic bronchoscope. The DFC balloon was inflated with 10 ml air and lung isolation was achieved without any significant air leak during one-lung or two-lung ventilation. However, the collapse of the non-dependent lung was delayed and finally achieved by low-pressure artificial pneumothorax. The surgery was successful and the patient was extubated soon after the surgery. CONCLUSIONS: Using a laryngeal mask airway with a modified double-lumen Foley catheter acted as a bronchial blocker could be an alternative method to achieve lung isolation.


Assuntos
Ventilação Monopulmonar , Traqueobroncomegalia , Masculino , Humanos , Pessoa de Meia-Idade , Intubação Intratraqueal/métodos , Manuseio das Vias Aéreas , Traqueia , Ventilação Monopulmonar/métodos
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