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1.
Cell ; 181(3): 621-636.e22, 2020 04 30.
Artículo en Inglés | MEDLINE | ID: mdl-32259487

RESUMEN

Long noncoding RNAs (lncRNAs) evolve more rapidly than mRNAs. Whether conserved lncRNAs undergo conserved processing, localization, and function remains unexplored. We report differing subcellular localization of lncRNAs in human and mouse embryonic stem cells (ESCs). A significantly higher fraction of lncRNAs is localized in the cytoplasm of hESCs than in mESCs. This turns out to be important for hESC pluripotency. FAST is a positionally conserved lncRNA but is not conserved in its processing and localization. In hESCs, cytoplasm-localized hFAST binds to the WD40 domain of the E3 ubiquitin ligase ß-TrCP and blocks its interaction with phosphorylated ß-catenin to prevent degradation, leading to activated WNT signaling, required for pluripotency. In contrast, mFast is nuclear retained in mESCs, and its processing is suppressed by the splicing factor PPIE, which is highly expressed in mESCs but not hESCs. These findings reveal that lncRNA processing and localization are previously under-appreciated contributors to the rapid evolution of function.


Asunto(s)
Espacio Intracelular/genética , ARN Largo no Codificante/metabolismo , Células Madre/metabolismo , Animales , Diferenciación Celular/genética , Línea Celular , Células Cultivadas , Células Madre Embrionarias/metabolismo , Células Madre Embrionarias Humanas/metabolismo , Humanos , Ratones , Células Madre Embrionarias de Ratones/metabolismo , Empalme del ARN/genética , ARN Largo no Codificante/genética , ARN Mensajero/metabolismo , Transducción de Señal/genética , Células Madre/patología
2.
Mol Cell ; 84(12): 2304-2319.e8, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38838666

RESUMEN

Circular RNAs (circRNAs) are upregulated during neurogenesis. Where and how circRNAs are localized and what roles they play during this process have remained elusive. Comparing the nuclear and cytoplasmic circRNAs between H9 cells and H9-derived forebrain (FB) neurons, we identify that a subset of adenosine (A)-rich circRNAs are restricted in H9 nuclei but exported to cytosols upon differentiation. Such a subcellular relocation of circRNAs is modulated by the poly(A)-binding protein PABPC1. In the H9 nucleus, newly produced (A)-rich circRNAs are bound by PABPC1 and trapped by the nuclear basket protein TPR to prevent their export. Modulating (A)-rich motifs in circRNAs alters their subcellular localization, and introducing (A)-rich circRNAs in H9 cytosols results in mRNA translation suppression. Moreover, decreased nuclear PABPC1 upon neuronal differentiation enables the export of (A)-rich circRNAs, including circRTN4(2,3), which is required for neurite outgrowth. These findings uncover subcellular localization features of circRNAs, linking their processing and function during neurogenesis.


Asunto(s)
Transporte Activo de Núcleo Celular , Adenosina , Núcleo Celular , Neurogénesis , Neuronas , Proteína I de Unión a Poli(A) , ARN Circular , ARN , ARN Circular/metabolismo , ARN Circular/genética , Neuronas/metabolismo , Adenosina/metabolismo , Núcleo Celular/metabolismo , Humanos , Proteína I de Unión a Poli(A)/metabolismo , Proteína I de Unión a Poli(A)/genética , Animales , ARN/metabolismo , ARN/genética , Línea Celular , Diferenciación Celular , Citoplasma/metabolismo , Prosencéfalo/metabolismo
3.
Mol Cell ; 82(2): 420-434.e6, 2022 01 20.
Artículo en Inglés | MEDLINE | ID: mdl-34951963

RESUMEN

Exon back-splicing-generated circular RNAs, as a group, can suppress double-stranded RNA (dsRNA)-activated protein kinase R (PKR) in cells. We have sought to synthesize immunogenicity-free, short dsRNA-containing RNA circles as PKR inhibitors. Here, we report that RNA circles synthesized by permuted self-splicing thymidylate synthase (td) introns from T4 bacteriophage or by Anabaena pre-tRNA group I intron could induce an immune response. Autocatalytic splicing introduces ∼74 nt td or ∼186 nt Anabaena extraneous fragments that can distort the folding status of original circular RNAs or form structures themselves to provoke innate immune responses. In contrast, synthesized RNA circles produced by T4 RNA ligase without extraneous fragments exhibit minimized immunogenicity. Importantly, directly ligated circular RNAs that form short dsRNA regions efficiently suppress PKR activation 103- to 106-fold higher than reported chemical compounds C16 and 2-AP, highlighting the future use of circular RNAs as potent inhibitors for diseases related to PKR overreaction.


Asunto(s)
Inhibidores de Proteínas Quinasas/farmacología , ARN Circular/farmacología , eIF-2 Quinasa/antagonistas & inhibidores , Células A549 , Bacteriófago T4/enzimología , Bacteriófago T4/genética , Células HEK293 , Células HeLa , Humanos , Inmunidad Innata/efectos de los fármacos , Intrones , Conformación de Ácido Nucleico , Inhibidores de Proteínas Quinasas/inmunología , ARN Ligasa (ATP)/genética , ARN Ligasa (ATP)/metabolismo , Precursores del ARN/genética , Precursores del ARN/metabolismo , ARN Circular/genética , ARN Circular/inmunología , Timidilato Sintasa/genética , Timidilato Sintasa/metabolismo , Proteínas Virales/genética , Proteínas Virales/metabolismo , eIF-2 Quinasa/metabolismo
4.
Nature ; 602(7897): 431-436, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35173341

RESUMEN

Marked evolution of properties with minute changes in the doping level is a hallmark of the complex chemistry that governs copper oxide superconductivity as manifested in the celebrated superconducting domes and quantum criticality taking place at precise compositions1-4. The strange-metal state, in which the resistivity varies linearly with temperature, has emerged as a central feature in the normal state of copper oxide superconductors5-9. The ubiquity of this behaviour signals an intimate link between the scattering mechanism and superconductivity10-12. However, a clear quantitative picture of the correlation has been lacking. Here we report the observation of precise quantitative scaling laws among the superconducting transition temperature (Tc), the linear-in-T scattering coefficient (A1) and the doping level (x) in electron-doped copper oxide La2-xCexCuO4 (LCCO). High-resolution characterization of epitaxial composition-spread films, which encompass the entire overdoped range of LCCO, has enabled us to systematically map its structural and transport properties with unprecedented accuracy and with increments of Δx = 0.0015. We have uncovered the relations Tc ~ (xc - x)0.5 ~ (A1□)0.5, where xc is the critical doping in which superconductivity disappears and A1□ is the coefficient of the linear resistivity per CuO2 plane. The striking similarity of the Tc versus A1□ relation among copper oxides, iron-based and organic superconductors may be an indication of a common mechanism of the strange-metal behaviour and unconventional superconductivity in these systems.

5.
Dev Biol ; 512: 57-69, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38750688

RESUMEN

Understanding the developmental processes and signaling pathways involved in larval myogenesis and metamorphosis is crucial for comprehending the life history and adaptive strategies of marine organisms. In this study, we investigated the temporal and spatial patterns of myogenesis in the mussel Mytilus coruscus (Mc), focusing on the emergence and transformation of major muscle groups during different larval stages. We also explored the role of the Hedgehog (Hh) signaling pathway in regulating myogenesis and larval metamorphosis. The results revealed distinct developmental stages characterized by the emergence of specific muscular components, such as velum retractor muscles and anterior adductor muscles, in D-veliger and umbo larvae, which are responsible for the planktonic stage. In the pediveliger stage, posterior ventral, posterior adductor, and foot muscles appeared. After larval metamorphosis, the velum structure and its corresponding retractor muscles degenerate, indicating the transition from planktonic to benthic life. We observed a conserved pattern of larval musculature development and revealed a high degree of conservation across bivalve species, with comparable emergence times during myogenesis. Furthermore, exposure to the Hh signaling inhibitor cyclopamine impaired larval muscle development, reduced larval swimming activity, and inhibited larval metamorphosis in M. coruscus. Cyclopamine-mediated inhibition of Hh signaling led to reduced expression of four key genes within the Hh signaling pathway (McHh, McPtc, McSmo, and McGli) and the striated myosin heavy chain gene (McMHC). It is hypothesised that the abnormal larval muscle development in cyclopamine-treated groups may be an indirect effect due to disrupted McMHC expression. We provide evidence for the first time that cyclopamine treatment inhibited larval metamorphosis in bivalves, highlighting the potential involvement of Hh signaling in mediating larval muscle development and metamorphosis in M. coruscus. The present study provides insights into the dynamic nature of myogenesis and the regulatory role of the Hh signaling pathway during larval development and metamorphosis in M. coruscus. The results obtained in this study contribute to a better understanding of the evolutionary significance of Hh signaling in bivalves and shed light on the mechanisms underlying larval muscle development and metamorphosis in marine invertebrates.


Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Proteínas Hedgehog , Larva , Metamorfosis Biológica , Desarrollo de Músculos , Mytilus , Transducción de Señal , Animales , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/genética , Larva/crecimiento & desarrollo , Larva/metabolismo , Mytilus/crecimiento & desarrollo , Mytilus/metabolismo , Alcaloides de Veratrum/farmacología , Músculos/metabolismo
6.
FASEB J ; 38(7): e23562, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38578557

RESUMEN

Our recent investigation has indicated that the global deletion of MBD2 can mitigate the progression of AKI induced by VAN. Nevertheless, the role and regulatory mechanisms of proximal tubular MBD2 in this pathophysiological process have yet to be elucidated. Our preceding investigation revealed that autophagy played a crucial role in advancing AKI induced by VAN. Consequently, we postulated that MBD2 present in the proximal tubule could upregulate the autophagic process to expedite the onset of AKI. In the present study, we found for the first time that MBD2 mediated the autophagy production induced by VAN. Through the utilization of miRNA chip analysis, we have mechanistically demonstrated that MBD2 initiates the activation of miR-597-5p through promoter demethylation. This process leads to the suppression of S1PR1, which results in the induction of autophagy and apoptosis in renal tubular cells. Besides, PT-MBD2-KO reduced autophagy to attenuate VAN-induced AKI via regulation of the miR-597-5p/S1PR1 axis, which was reversed by rapamycin. Finally, the overexpression of MBD2 aggravated the diminished VAN-induced AKI in autophagy-deficient mice (PT-Atg7-KO). These data demonstrate that proximal tubular MBD2 facilitated the process of autophagy via the miR-597-5p/S1PR1 axis and subsequently instigated VAN-induced AKI through the induction of apoptosis. The potentiality of MBD2 being a target for AKI was established.


Asunto(s)
Lesión Renal Aguda , MicroARNs , Animales , Ratones , Vancomicina , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/genética , Riñón , MicroARNs/genética , Apoptosis/fisiología , Autofagia
7.
Mol Cell ; 65(1): 52-65, 2017 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-27916661

RESUMEN

Tetrameric assembly of channel subunits in the endoplasmic reticulum (ER) is essential for surface expression and function of K+ channels, but the molecular mechanism underlying this process remains unclear. In this study, we found through genetic screening that ER-located J-domain-containing chaperone proteins (J-proteins) are critical for the biogenesis and physiological function of ether-a-go-go-related gene (ERG) K+ channels in both Caenorhabditis elegans and human cells. Human J-proteins DNAJB12 and DNAJB14 promoted tetrameric assembly of ERG (and Kv4.2) K+ channel subunits through a heat shock protein (HSP) 70-independent mechanism, whereas a mutated DNAJB12 that did not undergo oligomerization itself failed to assemble ERG channel subunits into tetramers in vitro and in C. elegans. Overexpressing DNAJB14 significantly rescued the defective function of human ether-a-go-go-related gene (hERG) mutant channels associated with long QT syndrome (LQTS), a condition that predisposes to life-threatening arrhythmia, by stabilizing the mutated proteins. Thus, chaperone proteins are required for subunit stability and assembly of K+ channels.


Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Canal de Potasio ERG1/metabolismo , Retículo Endoplásmico/metabolismo , Proteínas del Choque Térmico HSP40/metabolismo , Proteínas del Choque Térmico HSP47/metabolismo , Canales de Potasio/metabolismo , Animales , Animales Modificados Genéticamente , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/química , Proteínas de Caenorhabditis elegans/genética , Línea Celular Tumoral , Canal de Potasio ERG1/química , Canal de Potasio ERG1/genética , Células HEK293 , Proteínas del Choque Térmico HSP40/química , Proteínas del Choque Térmico HSP40/genética , Proteínas del Choque Térmico HSP47/química , Proteínas del Choque Térmico HSP47/genética , Proteínas HSP70 de Choque Térmico/metabolismo , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Síndrome de QT Prolongado/genética , Síndrome de QT Prolongado/metabolismo , Potenciales de la Membrana , Chaperonas Moleculares , Mutación , Miocitos Cardíacos/metabolismo , Canales de Potasio/química , Canales de Potasio/genética , Multimerización de Proteína , Estabilidad Proteica , Estructura Cuaternaria de Proteína , Interferencia de ARN , Canales de Potasio Shal/genética , Canales de Potasio Shal/metabolismo , Factores de Tiempo , Transfección
8.
Proc Natl Acad Sci U S A ; 119(26): e2122805119, 2022 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-35733260

RESUMEN

During viral infection, sensing of viral RNA by retinoic acid-inducible gene-I-like receptors (RLRs) initiates an antiviral innate immune response, which is mediated by the mitochondrial adaptor protein VISA (virus-induced signal adaptor; also known as mitochondrial antiviral signaling protein [MAVS]). VISA is regulated by various posttranslational modifications (PTMs), such as polyubiquitination, phosphorylation, O-linked ß-d-N-acetylglucosaminylation (O-GlcNAcylation), and monomethylation. However, whether other forms of PTMs regulate VISA-mediated innate immune signaling remains elusive. Here, we report that Poly(ADP-ribosyl)ation (PARylation) is a PTM of VISA, which attenuates innate immune response to RNA viruses. Using a biochemical purification approach, we identified tankyrase 1 (TNKS1) as a VISA-associated protein. Viral infection led to the induction of TNKS1 and its homolog TNKS2, which translocated from cytosol to mitochondria and interacted with VISA. TNKS1 and TNKS2 catalyze the PARylation of VISA at Glu137 residue, thereby priming it for K48-linked polyubiquitination by the E3 ligase Ring figure protein 146 (RNF146) and subsequent degradation. Consistently, TNKS1, TNKS2, or RNF146 deficiency increased the RNA virus-triggered induction of downstream effector genes and impaired the replication of the virus. Moreover, TNKS1- or TNKS2-deficient mice produced higher levels of type I interferons (IFNs) and proinflammatory cytokines after virus infection and markedly reduced virus loads in the brains and lungs. Together, our findings uncover an essential role of PARylation of VISA in virus-triggered innate immune signaling, which represents a mechanism to avoid excessive harmful immune response.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Inmunidad Innata , Infecciones por Virus ARN , Virus ARN , Tanquirasas , Ubiquitina-Proteína Ligasas , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Células HEK293 , Humanos , Inmunidad Innata/genética , Ratones , Infecciones por Virus ARN/inmunología , Virus ARN/inmunología , Tanquirasas/genética , Tanquirasas/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación
9.
Nano Lett ; 24(14): 4241-4247, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38546270

RESUMEN

Electrochemistry that empowers innovative nanoscopic analysis has long been pursued. Here, the concept of aggregation-enabled electrochemistry (AEE) in a confined nanopore is proposed and devised by reactive oxygen species (ROS)-responsive aggregation of CdS quantum dots (QDs) within a functional nanopipette. Complementary Faradaic and non-Faradaic operations of the CdS QDs aggregate could be conducted to simultaneously induce the signal-on of the photocurrents and the signal-off of the ionic signals. Such a rationale permits the cross-checking of the mutually corroborated signals and thus delivers more reliable results for single-cell ROS analysis. Combined with the rich biomatter-light interplay, the concept of AEE can be extended to other stimuli-responsive aggregations for electrochemical innovations.

10.
J Am Chem Soc ; 146(2): 1305-1317, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38169369

RESUMEN

Aprotic lithium-oxygen (Li-O2) batteries are considered to be a promising alternative option to lithium-ion batteries for high gravimetric energy storage devices. However, the sluggish electrochemical kinetics, the passivation, and the structural damage to the cathode caused by the solid discharge products have greatly hindered the practical application of Li-O2 batteries. Herein, the nonsolid-state discharge products of the off-stoichiometric Li1-xO2 in the electrolyte solutions are achieved by iridium (Ir) single-atom-based porous organic polymers (termed as Ir/AP-POP) as a homogeneous, soluble electrocatalyst for Li-O2 batteries. In particular, the numerous atomic active sites act as the main nucleation sites of O2-related discharge reactions, which are favorable to interacting with O2-/LiO2 intermediates in the electrolyte solutions, owing to the highly similar lattice-matching effect between the in situ-formed Ir3Li and LiO2, achieving a nonsolid LiO2 as the final discharge product in the electrolyte solutions for Li-O2 batteries. Consequently, the Li-O2 battery with a soluble Ir/AP-POP electrocatalyst exhibits an ultrahigh discharge capacity of 12.8 mAh, an ultralow overpotential of 0.03 V, and a long cyclic life of 700 h with the carbon cloth cathode. The manipulation of nonsolid discharge products in aprotic Li-O2 batteries breaks the traditional growth mode of Li2O2, bringing Li-O2 batteries closer to being a viable technology.

11.
Mass Spectrom Rev ; 42(6): 2273-2323, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35652168

RESUMEN

Food adulteration, mislabeling, and fraud, are rising global issues. Therefore, a number of precise and reliable analytical instruments and approaches have been proposed to ensure the authenticity and accurate labeling of food and food products by confirming that the constituents of foodstuffs are of the kind and quality claimed by the seller and manufacturer. Traditional techniques (e.g., genomics-based methods) are still in use; however, emerging approaches like mass spectrometry (MS)-based technologies are being actively developed to supplement or supersede current methods for authentication of a variety of food commodities and products. This review provides a critical assessment of recent advances in food authentication, including MS-based metabolomics, proteomics and other approaches.

12.
Acc Chem Res ; 56(2): 169-186, 2023 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-36571794

RESUMEN

ConspectusThe past decades have witnessed tremendous progress on radical reactions. However, in comparison with carbon, nitrogen, oxygen, and other main group element centered radicals, the synthetic chemistry of boron centered radicals was less studied, mainly due to the high electron-deficiency and instability of such 3-center-5-electron species. In the 1980s, Roberts and co-workers found that the coordination of a Lewis base (amines or phosphines) with the boron center could form 4-center-7-electron boryl radicals (Lewis base-boryl radicals, LBRs) that are found to be more stable. However, only limited synthetic applications were developed. In 2008, Curran and co-workers achieved a breakthrough with the discovery of N-heterocyclic carbene (NHC) boryl radicals, which could enable a range of radical reduction and polymerization reactions. Despite these exciting findings, more powerful and valuable synthetic applications of LBRs would be expected, given that the structures and reactivities of LBRs could be easily modulated, which would provide ample opportunities to discover new reactions. In this Account, a summary of our key contributions in LBR-enabled radical borylation reactions and selective activation of inert carbon-heteroatom bonds will be presented.Organoboron compounds have shown versatile applications in chemical society, and their syntheses rely principally on ionic borylation reactions. The development of mechanistically different radical borylation reactions allows synthesizing products that are inaccessible by traditional methods. For this purpose, we progressively developed a series of NHC-boryl radical mediated chemo-, regio-, and stereoselective radical borylation reactions of alkenes and alkynes, by which a wide variety of structurally diverse organoboron molecules were successfully prepared. The synthetic utility of these borylated products was also demonstrated. Furthermore, we disclosed a photoredox protocol for oxidative generation of NHC-boryl radicals, which enabled useful defluoroborylation and arylboration reactions.Selective bond activation is an ideal way to convert simple starting materials to value-added products, while the cleavage of inert chemical bonds, in particular the chemoselectivity control when multiple identical bonds are present in similar chemical environments, remains a long-standing challenge. We envisaged that finely tuning the properties of LBRs might provide a new solution to address this challenge. Recently, we disclosed a 4-dimethylaminopyridine (DMAP)-boryl radical promoted sequential C-F bond functionalization of trifluoroacetic acid derivatives, in which the α-C-F bonds were selectively snipped via a spin-center shift mechanism. This strategy enables facile conversion of abundantly available trifluoroacetic acid to highly valuable mono- and difluorinated molecules. Encouraged by this finding, we further developed a boryl radical enabled three-step sequence to construct all-carbon quaternary centers from a range of trichloromethyl groups, where the three C-Cl bonds were selectively cleaved by the rational choice of suitable boryl radical precursors in each step. Furthermore, a boryl radical promoted dehydroxylative alkylation of α-hydroxy carboxylic acid derivatives was achieved, allowing for the efficient conversion of some biomass platform molecules to high value products.

13.
J Anat ; 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38922713

RESUMEN

Current studies on facial growth and development have been largely based on European populations. Less studied are African populations, who because of their distinct genetic makeup and environmental conditions, provide deeper insights into patterns of facial development. Patterns of facial shape development in African populations remain largely uncharacterised. Our study aimed to establish facial growth and development trajectories based on a cohort of 2874 Bantu Africans from Tanzania aged 6-18 years, with particular focus on identifying morphogenetic processes that lead to observed developmental shape changes. Procrustes ANCOVA suggested sexually dimorphic patterns of facial shape development (p = 0.0036). The forehead was relatively contracted during development in both sexes. The glabella region was more anteriorly displaced in females due to expansion in the region laterosuperior to the eyes. Nasal protrusion increased with development, which was found to arise from local expansion in the nasal alae and columella. Local expansion in the upper and lower labial regions resulted in forward displaced lips in both sexes, with the effect more pronounced in males. The mentum was displaced more anteriorly in females due to comparatively more expanded mental regions with development. The lateral facial region corresponding to the underlying body of the mandible were developmentally expanded but were posteriorly positioned due to protrusive growth of surrounding structures. Generalised additive modelling of Procrustes variance suggested that facial variation decreased non-linearly with age (p < 0.05). Relative principal component analysis suggested that variations in facial outline shape were developmentally constrained, whereas nasolabial and mental regions, where developmental changes were significant, became morphologically diversified with development. In contrast to simple descriptive illustration of facial shape development, we gained transformative insights into patterns of facial shape development by analysing morphogenetic processes and variational properties. Our analytical framework is broadly applicable to morphometric studies on ontogenetic shape changes.

14.
Langmuir ; 40(8): 4186-4197, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38358822

RESUMEN

The dissolution of minerals within rock fractures is fundamental to many geological processes. Previous research on fracture dissolution has highlighted the significant role of buoyancy-driven convection leading to dissolution instability. Yet, the pore-scale mechanisms underlying this instability are poorly understood primarily due to the challenges in experimentally determining flow velocity and concentration fields. Here, we integrate pore-scale simulations with theoretical analysis to delve into the dissolution instability prompted by buoyancy-driven convection in a radial horizontal geometry. Initially, we develop a pore-scale modeling approach incorporating gravitational effects, subsequently validating it through experiments. We then employ pore-scale numerical simulations to elucidate the 3D intricacies of flow-dissolution dynamics. Our findings reveal that a simple criterion can delineate the condition for the onset of buoyancy-driven dissolution instability. If the characteristic length falls below a critical threshold, dissolution remains stable. Conversely, exceeding this threshold leads to two distinct regimes: the unstable regime of the confined domain affected by the initial aperture and the unstable regime of the semi-infinite domain independent of the initial aperture where the instability is no longer influenced by the lower boundary. We demonstrate that the pore-scale mechanism for this instability is due to the concentration boundary layer attaining a gravitationally unstable critical thickness. Through theoretical analysis of this layer and the time scales of diffusion and advection, we establish a theoretical model to predict where the dissolution instability occurs. This model aligns closely with our numerical simulations and experimental data across diverse conditions. Our work improves the understanding of buoyancy-driven dissolution instability in radial horizontal geometry. It is also of practical significance in understanding cavity formation in karst hydrology and preventing leaks in geological CO2 storage.

15.
Langmuir ; 40(20): 10759-10768, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38712734

RESUMEN

Bouncing dynamics of a trailing drop off-center impacting a leading drop with varying time intervals and Weber numbers are investigated experimentally. Whether the trailing drop impacts during the spreading or receding process of the leading drop is determined by the time interval. For a short time interval of 0.15 ≤ Δt* ≤ 0.66, the trailing drop impacts during the spreading of the leading drop, and the drops completely coalesce and rebound; for a large time interval of 0.66 < Δt* ≤ 2.21, the trailing drop impacts during the receding process, and the drops partially coalesce and rebound. Whether the trailing drop directly impacts the surface or the liquid film of the leading drop is determined by the Weber number. The trailing drop impacts the surface directly at moderate Weber numbers of 16.22 ≤ We ≤ 45.42, while it impacts the liquid film at large Weber numbers of 45.42 < We ≤ 64.88. Intriguingly, when the trailing drop impacts the surface directly or the receding liquid film, the contact time increases linearly with the time interval but independent of the Weber number; when the trailing drop impacts the spreading liquid film, the contact time suddenly increases, showing that the force of the liquid film of the leading drop inhibits the receding of the trailing drop. Finally, a theoretical model of the contact time for the drops is established, which is suitable for different impact scenarios of the successive off-center impact. This study provides a quantitative relationship to calculate the contact time of drops successively impacting a superhydrophobic surface, facilitating the design of anti-icing surfaces.

16.
J Org Chem ; 89(2): 1083-1090, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38173188

RESUMEN

A metal-free and thiol-free organophosphorus-catalyzed method for forming thioethers was disclosed, driven by PIII/PV═O redox cycling. In this work, one-step dehydroxylative thioetherification of alcohols was fulfilled with various hypervalent organosulfur compounds. This established strategy features an excellent functional group tolerance and broad substrate scope, especially inactivated alcohols. The scale-up reaction and further transformation of the product were also successful. Additionally, this method offers a protecting-group-free and step-efficient approach for synthesizing peroxisome proliferator-activated receptor agonists which exhibited promising potential for treating osteoporosis in mammals.

17.
J Org Chem ; 89(2): 928-938, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38181049

RESUMEN

Chiral diarylmethylamides are a privileged skeleton in many bioactive molecules. However, the enantioselective synthesis of such molecules remains a long-standing challenge in organic synthesis. Herein, we report a chiral bifunctional squaramide catalyzed asymmetric aza-Michael addition of amides to in situ generated ortho-quinomethanes, affording enantioenriched diarylmethylamides in good yields with excellent enantioselectivities. This work not only provides a new strategy for the construction of the diarylmethylamides but also represents the practicability of amides as nitrogen-nucleophiles in asymmetric organocatalysis.

18.
J Org Chem ; 89(2): 975-985, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38181067

RESUMEN

Enantioselective synthesis of eight-membered N-heterocycles represents a long-standing challenge in organic synthesis. Here, by combining the squaramide and DBU catalysis, a sequential asymmetric conjugate addition/cyclization reaction between benzofuran-derived azadienes and ynones has been well-developed, providing straightforward access to chiral eight-membered N-heterocycles in high yields with stereoselectivities. This protocol features the use of a bifunctional squaramide catalyst for controlling the enantioselectivity of products, while the DBU is utilized to achieve intramolecular cyclization and improve the diastereoselectivity of products.

19.
J Org Chem ; 89(11): 7741-7746, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38741558

RESUMEN

A novel three-component cyclization carbonylation reaction of iodoarene-tethered propargyl ethers with amine and CO is reported. This palladium-catalyzed cascade reaction undergoes a sequence of oxidative addition, unsaturated bond migration, carbonyl insertion, and nucleophilic attack to deliver the benzofuran skeleton. Both aromatic amines and aliphatic amines could proceed smoothly in this transformation under one atm of CO.

20.
BMC Neurol ; 24(1): 59, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38336624

RESUMEN

OBJECTIVES: Computed tomographic perfusion (CTP) can play an auxiliary role in the selection of patients with acute ischemic stroke for endovascular treatment. However, data on CTP in non-stroke patients with intracranial arterial stenosis are scarce. We aimed to investigate images in patients with asymptomatic intracranial arterial stenosis to determine the detection accuracy and interpretation time of large/medium-artery stenosis or occlusion when combining computed tomographic angiography (CTA) and CTP images. METHODS: We retrospectively reviewed 39 patients with asymptomatic intracranial arterial stenosis from our hospital database from January 2021 to August 2023 who underwent head CTP, head CTA, and digital subtraction angiography (DSA). Head CTA images were generated from the CTP data, and the diagnostic performance for each artery was assessed. Two readers independently interpreted the CTA images before and after CTP, and the results were analyzed. RESULTS: After adding CTP maps, the accuracy (area under the curve) of diagnosing internal carotid artery (R1: 0.847 vs. 0.907, R2: 0.776 vs. 0.887), middle cerebral artery (R1: 0.934 vs. 0.933, R2: 0.927 vs. 0.981), anterior cerebral artery (R1: 0.625 vs. 0.750, R2: 0.609 vs. 0.750), vertebral artery (R1: 0.743 vs. 0.764, R2: 0.748 vs. 0.846), and posterior cerebral artery (R1: 0.390 vs. 0.575, R2: 0.390 vs. 0.585) occlusions increased for both readers (p < 0.05). Mean interpretation time (R1: 72.4 ± 6.1 s vs. 67.7 ± 6.4 s, R2: 77.7 ± 3.8 s vs. 72.6 ± 4.7 s) decreased when using a combination of both images both readers (p < 0.001). CONCLUSIONS: The addition of CTP images improved the accuracy of interpreting CTA images and reduced the interpretation time in asymptomatic intracranial arterial stenosis. These findings support the use of CTP imaging in patients with asymptomatic intracranial arterial stenosis.


Asunto(s)
Accidente Cerebrovascular Isquémico , Humanos , Estudios Retrospectivos , Constricción Patológica/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Angiografía por Tomografía Computarizada/métodos , Perfusión , Angiografía Cerebral/métodos
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