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1.
Immunity ; 57(6): 1306-1323.e8, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38815582

RESUMO

Group 3 innate lymphoid cells (ILC3s) regulate inflammation and tissue repair at mucosal sites, but whether these functions pertain to other tissues-like the kidneys-remains unclear. Here, we observed that renal fibrosis in humans was associated with increased ILC3s in the kidneys and blood. In mice, we showed that CXCR6+ ILC3s rapidly migrated from the intestinal mucosa and accumulated in the kidney via CXCL16 released from the injured tubules. Within the fibrotic kidney, ILC3s increased the expression of programmed cell death-1 (PD-1) and subsequent IL-17A production to directly activate myofibroblasts and fibrotic niche formation. ILC3 expression of PD-1 inhibited IL-23R endocytosis and consequently amplified the JAK2/STAT3/RORγt/IL-17A pathway that was essential for the pro-fibrogenic effect of ILC3s. Thus, we reveal a hitherto unrecognized migration pathway of ILC3s from the intestine to the kidney and the PD-1-dependent function of ILC3s in promoting renal fibrosis.


Assuntos
Movimento Celular , Fibrose , Rim , Linfócitos , Receptor de Morte Celular Programada 1 , Receptores CXCR6 , Receptores de Interleucina , Transdução de Sinais , Animais , Fibrose/imunologia , Camundongos , Receptores CXCR6/metabolismo , Receptores CXCR6/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Transdução de Sinais/imunologia , Movimento Celular/imunologia , Humanos , Rim/patologia , Rim/imunologia , Rim/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Receptores de Interleucina/metabolismo , Receptores de Interleucina/imunologia , Camundongos Endogâmicos C57BL , Nefropatias/imunologia , Nefropatias/metabolismo , Nefropatias/patologia , Imunidade Inata/imunologia , Camundongos Knockout , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Intestinos/imunologia , Intestinos/patologia
2.
Immunity ; 56(9): 1991-2005.e9, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37659413

RESUMO

In mammals, the enzyme cGAS senses the presence of cytosolic DNA and synthesizes the cyclic dinucleotide (CDN) 2'3'-cGAMP, which triggers STING-dependent immunity. In Drosophila melanogaster, two cGAS-like receptors (cGLRs) produce 3'2'-cGAMP and 2'3'-cGAMP to activate STING. We explored CDN-mediated immunity in 14 Drosophila species covering 50 million years of evolution and found that 2'3'-cGAMP and 3'2'-cGAMP failed to control infection by Drosophila C virus in D. serrata and two other species. We discovered diverse CDNs produced in a cGLR-dependent manner in response to viral infection in D. melanogaster, including 2'3'-c-di-GMP. This CDN was a more potent STING agonist than cGAMP in D. melanogaster and it also activated a strong antiviral transcriptional response in D. serrata. Our results shed light on the evolution of cGLRs in flies and provide a basis for understanding the function and regulation of this emerging family of pattern recognition receptors in animal innate immunity.


Assuntos
Antivirais , Drosophila , Animais , Drosophila melanogaster , GMP Cíclico , Mamíferos
3.
EMBO J ; 42(7): e111148, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-36843552

RESUMO

Osteoclasts are bone-resorbing polykaryons responsible for skeletal remodeling during health and disease. Coincident with their differentiation from myeloid precursors, osteoclasts undergo extensive transcriptional and metabolic reprogramming in order to acquire the cellular machinery necessary to demineralize bone and digest its interwoven extracellular matrix. While attempting to identify new regulatory molecules critical to bone resorption, we discovered that murine and human osteoclast differentiation is accompanied by the expression of Zeb1, a zinc-finger transcriptional repressor whose role in normal development is most frequently linked to the control of epithelial-mesenchymal programs. However, following targeting, we find that Zeb1 serves as an unexpected regulator of osteoclast energy metabolism. In vivo, Zeb1-null osteoclasts assume a hyperactivated state, markedly decreasing bone density due to excessive resorptive activity. Mechanistically, Zeb1 acts in a rheostat-like fashion to modulate murine and human osteoclast activity by transcriptionally repressing an ATP-buffering enzyme, mitochondrial creatine kinase 1 (MtCK1), thereby controlling the phosphocreatine energy shuttle and mitochondrial respiration. Together, these studies identify a novel Zeb1/MtCK1 axis that exerts metabolic control over bone resorption in vitro and in vivo.


Assuntos
Reabsorção Óssea , Osteoclastos , Camundongos , Animais , Humanos , Osteoclastos/metabolismo , Creatina Quinase Mitocondrial/metabolismo , Reabsorção Óssea/genética , Reabsorção Óssea/metabolismo , Osso e Ossos , Diferenciação Celular , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo
4.
Nature ; 594(7861): 57-61, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34079133

RESUMO

If a bulk material can withstand a high load without any irreversible damage (such as plastic deformation), it is usually brittle and can fail catastrophically1,2. This trade-off between strength and fracture toughness also extends into two-dimensional materials space3-5. For example, graphene has ultrahigh intrinsic strength (about 130 gigapascals) and elastic modulus (approximately 1.0 terapascal) but is brittle, with low fracture toughness (about 4 megapascals per square-root metre)3,6. Hexagonal boron nitride (h-BN) is a dielectric two-dimensional material7 with high strength (about 100 gigapascals) and elastic modulus (approximately 0.8 terapascals), which are similar to those of graphene8. Its fracture behaviour has long been assumed to be similarly brittle, subject to Griffith's law9-14. Contrary to expectation, here we report high fracture toughness of single-crystal monolayer h-BN, with an effective energy release rate up to one order of magnitude higher than both its Griffith energy release rate and that reported for graphene. We observe stable crack propagation in monolayer h-BN, and obtain the corresponding crack resistance curve. Crack deflection and branching occur repeatedly owing to asymmetric edge elastic properties at the crack tip and edge swapping during crack propagation, which intrinsically toughens the material and enables stable crack propagation. Our in situ experimental observations, supported by theoretical analysis, suggest added practical benefits and potential new technological opportunities for monolayer h-BN, such as adding mechanical protection to two-dimensional devices.

5.
PLoS Pathog ; 20(9): e1012508, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39303003

RESUMO

Influenza and coronavirus disease 2019 (COVID-19) represent two respiratory diseases that have significantly impacted global health, resulting in substantial disease burden and mortality. An optimal solution would be a combined vaccine capable of addressing both diseases, thereby obviating the need for multiple vaccinations. Previously, we conceived a chimeric protein subunit vaccine targeting both influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), utilizing the receptor binding domain of spike protein (S-RBD) and the stalk region of hemagglutinin protein (HA-stalk) components. By integrating the S-RBD from the SARS-CoV-2 Delta variant with the headless hemagglutinin (HA) from H1N1 influenza virus, we constructed stable trimeric structures that remain accessible to neutralizing antibodies. This vaccine has demonstrated its potential by conferring protection against a spectrum of strains in mouse models. In this study, we designed an mRNA vaccine candidate encoding the chimeric antigen. The resultant humoral and cellular immune responses were meticulously evaluated in mouse models. Furthermore, the protective efficacy of the vaccine was rigorously examined through challenges with either homologous or heterologous influenza viruses or SARS-CoV-2 strains. Our findings reveal that the mRNA vaccine exhibited robust immunogenicity, engendering high and sustained levels of neutralizing antibodies accompanied by robust and persistent cellular immunity. Notably, this vaccine effectively afforded complete protection to mice against H1N1 or heterosubtypic H5N8 subtypes, as well as the SARS-CoV-2 Delta and Omicron BA.2 variants. Additionally, our mRNA vaccine design can be easily adapted from Delta RBD to Omicron RBD antigens, providing protection against emerging variants. The development of two-in-one vaccine targeting both influenza and COVID-19, incorporating the mRNA platform, may provide a versatile approach to combating future pandemics.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Glicoproteínas de Hemaglutininação de Vírus da Influenza , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Vacinas de mRNA , Animais , Camundongos , SARS-CoV-2/imunologia , COVID-19/prevenção & controle , COVID-19/imunologia , Vacinas de mRNA/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Humanos , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vacinas contra COVID-19/imunologia , Vacinas contra Influenza/imunologia , Anticorpos Antivirais/imunologia , Camundongos Endogâmicos BALB C , Feminino , Vírus da Influenza A Subtipo H1N1/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/imunologia , Vacinas Sintéticas/imunologia , Influenza Humana/prevenção & controle , Influenza Humana/imunologia , Anticorpos Neutralizantes/imunologia
6.
Nature ; 578(7794): 251-255, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32015545

RESUMO

Solid-state lithium metal batteries require accommodation of electrochemically generated mechanical stress inside the lithium: this stress can be1,2 up to 1 gigapascal for an overpotential of 135 millivolts. Maintaining the mechanical and electrochemical stability of the solid structure despite physical contact with moving corrosive lithium metal is a demanding requirement. Using in situ transmission electron microscopy, we investigated the deposition and stripping of metallic lithium or sodium held within a large number of parallel hollow tubules made of a mixed ionic-electronic conductor (MIEC). Here we show that these alkali metals-as single crystals-can grow out of and retract inside the tubules via mainly diffusional Coble creep along the MIEC/metal phase boundary. Unlike solid electrolytes, many MIECs are electrochemically stable in contact with lithium (that is, there is a direct tie-line to metallic lithium on the equilibrium phase diagram), so this Coble creep mechanism can effectively relieve stress, maintain electronic and ionic contacts, eliminate solid-electrolyte interphase debris, and allow the reversible deposition/stripping of lithium across a distance of 10 micrometres for 100 cycles. A centimetre-wide full cell-consisting of approximately 1010 MIEC cylinders/solid electrolyte/LiFePO4-shows a high capacity of about 164 milliampere hours per gram of LiFePO4, and almost no degradation for over 50 cycles, starting with a 1× excess of Li. Modelling shows that the design is insensitive to MIEC material choice with channels about 100 nanometres wide and 10-100 micrometres deep. The behaviour of lithium metal within the MIEC channels suggests that the chemical and mechanical stability issues with the metal-electrolyte interface in solid-state lithium metal batteries can be overcome using this architecture.

7.
Proc Natl Acad Sci U S A ; 120(39): e2305883120, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37725637

RESUMO

Inspired by the development of single-atom catalysts (SACs), the fabrication of multimetallic SACs can be a promising technical approach for the in situ electro-Fenton (EF) process. Herein, dual-functional atomically dispersed Mo-Fe sites embedded in carbon nitride (C3N5) (i.e., MoFe/C3N5) were synthesized via a facile SiO2 template method. The atomically isolated bimetallic configuration in MoFe/C3N5 was identified by combining the microscopic and spectroscopic techniques. The MoFe/C3N5 catalyst on the cathode exhibited a remarkable catalytic activity toward the three electron-dominated oxygen reduction reaction in sodium sulfate, leading to a highly effective EF reaction with a low overpotential for the removal of organic contaminants from wastewater. The new catalyst showed a superior performance over its conventional counterparts, owing to the dual functions of the dual-metal active sites. Density functional theory (DFT) analysis revealed that the dual-functional 50-MoFe/C3N5 catalyst enabled a synergistic action of the Mo-Fe dual single atomic centers, which can alter the adsorption/dissociation behavior and decrease the overall reaction barriers for effective organic oxidation during the EF process. This study not only sheds light on the controlled synthesis of atomically isolated catalyst materials but also provides deeper understanding of the structure-performance relationship of the nanocatalysts with dual active sites for the catalytic EF process. Additionally, the findings will promote the advanced catalysis for the treatment of emerging organic contaminants in water and wastewater.

8.
Proc Natl Acad Sci U S A ; 120(8): e2210385120, 2023 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-36787350

RESUMO

Immunotherapy holds great promise for the treatment of aggressive and metastatic cancers; however, currently available immunotherapeutics, such as immune checkpoint blockade, benefit only a small subset of patients. A photoactivatable toll-like receptor 7/8 (TLR7/8) nanoagonist (PNA) system that imparts near-infrared (NIR) light-induced immunogenic cell death (ICD) in dying tumor cells in synchrony with the spontaneous release of a potent immunoadjuvant is developed here. The PNA consists of polymer-derived proimmunoadjuvants ligated via a reactive oxygen species (ROS)-cleavable linker and polymer-derived photosensitizers, which are further encapsulated in amphiphilic matrices for systemic injection. In particular, conjugation of the TLR7/8 agonist resiquimod to biodegradable macromolecular moieties with different molecular weights enabled pharmacokinetic tuning of small-molecule agonists and optimized delivery efficiency in mice. Upon NIR photoirradiation, PNA effectively generated ROS not only to ablate tumors and induce the ICD cascade but also to trigger the on-demand release of TLR agonists. In several preclinical cancer models, intravenous PNA administration followed by NIR tumor irradiation resulted in remarkable tumor regression and suppressed postsurgical tumor recurrence and metastasis. Furthermore, this treatment profoundly shifted the tumor immune landscape to a tumoricidal one, eliciting robust tumor-specific T cell priming in vivo. This work highlights a simple and cost-effective approach to generate in situ cancer vaccines for synergistic photodynamic immunotherapy of metastatic cancers.


Assuntos
Neoplasias , Receptor 7 Toll-Like , Animais , Camundongos , Receptor 7 Toll-Like/agonistas , Espécies Reativas de Oxigênio , Imunoterapia/métodos , Neoplasias/terapia , Adjuvantes Imunológicos , Polímeros/química , Vacinação , Linhagem Celular Tumoral
9.
Proc Natl Acad Sci U S A ; 120(52): e2307477120, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38134195

RESUMO

Potassium-ion batteries (PIBs) have attracted ever-increasing interest due to the abundant potassium resources and low cost, which are considered a sustainable energy storage technology. However, the graphite anodes employed in PIBs suffer from low capacity and sluggish reaction kinetics caused by the large radius of potassium ions. Herein, we report nitrogen-doped, defect-rich hollow carbon nanospheres with contact curved interfaces (CCIs) on carbon nanotubes (CNTs), namely CCI-CNS/CNT, to boost both electron transfer and potassium-ion adsorption. Density functional theory calculations validate that engineering CCIs significantly augments the electronic state near the Fermi level, thus promoting electron transfer. In addition, the CCIs exhibit a pronounced affinity for potassium ions, promoting their adsorption and subsequently benefiting potassium storage. As a result, the rationally designed CCI-CNS/CNT anode shows remarkable cyclic stability and rate capability. This work provides a strategy for enhancing the potassium storage performance of carbonaceous materials through CCI engineering, which can be further extended to other battery systems.

10.
Mol Biol Evol ; 41(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38377349

RESUMO

Viruses represent a major threat to all animals, which defend themselves through induction of a large set of virus-stimulated genes that collectively control the infection. In vertebrates, these genes include interferons that play a critical role in the amplification of the response to infection. Virus- and interferon-stimulated genes include restriction factors targeting the different steps of the viral replication cycle, in addition to molecules associated with inflammation and adaptive immunity. Predictably, antiviral genes evolve dynamically in response to viral pressure. As a result, each animal has a unique arsenal of antiviral genes. Here, we exploit the capacity to experimentally activate the evolutionarily conserved stimulator of IFN genes (STING) signaling pathway by injection of the cyclic dinucleotide 2'3'-cyclic guanosine monophosphate-adenosine monophosphate into flies to define the repertoire of STING-regulated genes in 10 Drosophila species, spanning 40 million years of evolution. Our data reveal a set of conserved STING-regulated factors, including STING itself, a cGAS-like-receptor, the restriction factor pastel, and the antiviral protein Vago, but also 2 key components of the antiviral RNA interference pathway, Dicer-2, and Argonaute2. In addition, we identify unknown species- or lineage-specific genes that have not been previously associated with resistance to viruses. Our data provide insight into the core antiviral response in Drosophila flies and pave the way for the characterization of previously unknown antiviral effectors.


Assuntos
Drosophila , Imunidade Inata , Animais , Nucleotídeos Cíclicos , Antivirais/farmacologia
11.
Int Immunol ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38899915

RESUMO

Interferons (IFNs) are cytokines produced and secreted by immune cells when viruses, tumor cells, and so forth, invade the body. Their biological effects are diverse, including antiviral, cell growth-inhibiting, and antitumor effects. The main subclasses of interferons include type-I (e.g., IFN-α and IFN-ß) and type-II (IFN-γ), which activate intracellular signals by binding to type-I and type-II IFN receptors, respectively. We have previously shown that when macrophages are treated with supersulfide donors, which have polysulfide structures in which three or more sulfur atoms are linked within the molecules, IFN-ß-induced cellular responses, including signal transducer and activator of transcription 1 (STAT1) phosphorylation and inducible nitric oxide synthase (iNOS) expression, were strongly suppressed. However, the subfamily specificity of the suppression of IFN signals by supersulfides and the mechanism of this suppression are unknown. This study demonstrated that supersulfide donor N-acetyl-L-cysteine tetrasulfide (NAC-S2) can inhibit IFN signaling in macrophages stimulated not only with IFN-α/ß but also with IFN-γ. Our data suggest that NAC-S2 blocks phosphorylation of Janus kinases (JAKs), thereby contributes to the inhibition of phosphorylation of STAT1. Under the current experimental conditions, hydrogen sulfide (H2S) donor NaHS failed to inhibit IFN signaling. Similar to NAC-S2, carbohydrate-based supersulfide donor thioglucose tetrasulfide (TGS4) was capable of strongly inhibiting tumor necrosis factor-αproduction, iNOS expression, and nitric oxide production from macrophages stimulated with lipopolysaccharide. Further understanding of molecular mechanisms how supersulfide donors exhibit their inhibitory actions towards JAK/STAT signaling is necessary basis for development of supersulfide-based therapeutic strategy against autoimmune disorders with dysregulated IFN signaling.

12.
J Immunol ; 210(6): 820-831, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36881904

RESUMO

High CXCL16 levels during acute cardiovascular events increase long-term mortality. However, the mechanistic role of CXCL16 in myocardial infarction (MI) is unknown. Here we investigated the role of CXCL16 in mice with MI injury. CXCL16 deficiency increased the survival of mice after MI injury, and inactivation of CXCL16 resulted in improved cardiac function and decreased infarct size. Hearts from CXCL16 inactive mice exhibited decreased infiltration of Ly6Chigh monocytes. In addition, CXCL16 promoted the macrophage expression of CCL4 and CCL5. Both CCL4 and CCL5 stimulated Ly6Chigh monocyte migration, and CXCL16 inactive mice had a reduced expression of CCL4 and CCL5 in the heart after MI. Mechanistically, CXCL16 promoted CCL4 and CCL5 expression by activating the NF-κB and p38 MAPK signaling pathways. Anti-CXCL16 neutralizing Ab administration inhibited Ly6Chigh monocyte infiltration and improved cardiac function after MI. Additionally, anti-CCL4 and anti-CCL5 neutralizing Ab administration inhibited Ly6Chigh monocyte infiltration and improved cardiac function after MI. Thus, CXCL16 aggravated cardiac injury in MI mice by facilitating Ly6Chigh monocyte infiltration.


Assuntos
Monócitos , Infarto do Miocárdio , Animais , Camundongos , Macrófagos , Sistema de Sinalização das MAP Quinases , NF-kappa B , Quimiocina CXCL16
13.
Proc Natl Acad Sci U S A ; 119(4)2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-35046038

RESUMO

An optical antenna can convert a propagative optical radiation into a localized excitation and the reciprocal. Although optical antennas can be readily created using resonant nanoparticles (metallic or dielectric) as elementary building blocks, the realization of antennas sustaining multiple resonances over a broad range of frequencies remains a challenging task. Here, we use aluminum self-similar, fractal-like structures as broadband optical antennas. Using electron energy loss spectroscopy, we experimentally evidence that a single aluminum Cayley tree, a simple self-similar structure, sustains multiple plasmonic resonances. The spectral position of these resonances is scalable over a broad spectral range spanning two decades, from ultraviolet to midinfrared. Such multiresonant structures are highly desirable for applications ranging from nonlinear optics to light harvesting and photodetection, as well as surface-enhanced infrared absorption spectroscopy.

14.
Proc Natl Acad Sci U S A ; 119(34): e2119536119, 2022 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-35969756

RESUMO

Recent developments in mechanical metamaterials exemplify a new paradigm shift called mechanomaterials, in which mechanical forces and designed geometries are proactively deployed to program material properties at multiple scales. Here, we designed shell-based micro-/nanolattices with I-WP (Schoen's I-graph-wrapped package) and Neovius minimal surface topologies. Following the designed topologies, polymeric microlattices were fabricated via projection microstereolithography or two-photon lithography, and pyrolytic carbon nanolattices were created through two-photon lithography and subsequent pyrolysis. The shell thickness of created lattice metamaterials varies over three orders of magnitude from a few hundred nanometers to a few hundred micrometers, covering a wider range of relative densities than most plate-based micro-/nanolattices. In situ compression tests showed that the measured modulus and strength of our shell-based micro-/nanolattices with I-WP topology are superior to those of the optimized plate-based lattices with cubic and octet plate unit cells and truss-based lattices. More strikingly, when the density is larger than 0.53 g cm-3, the strength of shell-based pyrolytic carbon nanolattices with I-WP topology was found to achieve its theoretical limit. In addition, our shell-based carbon nanolattices exhibited an ultrahigh strength of 3.52 GPa, an ultralarge fracture strain of 23%, and an ultrahigh specific strength of 4.42 GPa g-1 cm3, surpassing all previous micro-/nanolattices at comparable densities. These unprecedented properties can be attributed to the designed topologies inducing relatively uniform strain energy distributions and avoiding stress concentrations as well as the nanoscale feature size. Our study demonstrates a mechanomaterial route to design and synthesize micro-/nanoarchitected materials.


Assuntos
Carbono , Fenômenos Mecânicos , Nanoestruturas , Carbono/química , Nanoestruturas/química , Polímeros/química
15.
Nano Lett ; 24(6): 2094-2101, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38315573

RESUMO

Prelithiation plays a crucial role in advancing the development of high-energy-density batteries, and ultrathin lithium (UTL) has been proven to be a promising anode prelithiation reagent. However, there remains a need to explore an adjustable, efficient, and cost-effective method for manufacturing UTL. In this study, we introduce a method for producing UTL with adjustable thicknesses ranging from 1.5 to 10 µm through blade coating of molten lithium on poly(vinylidene fluoride)-modified copper current collectors. By employing the transfer-printing method, prelithiated graphite and Si-C composite electrodes are prepared, which exhibit significantly improved initial Coulombic efficiencies of 99.60% and 99.32% in half-cells, respectively. Moreover, the energy densities of Li(NiCoMn)1/3O2 and LiFePO4 full cells assembled with the prelithiated graphite electrodes increase by 13.1% and 23.6%, respectively.

16.
Plant J ; 116(1): 173-186, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37366219

RESUMO

Plants employ various molecular mechanisms to maintain primary root elongation upon salt stress. Identification of key functional genes, therein, is important for improving crop salt tolerance. Through analyzing natural variation of the primary root length of Arabidopsis natural population under salt stress, we identified NIGT1.4, encoding an MYB transcription factor, as a novel contributor to maintained root growth under salt stress. Using both T-DNA knockout and functional complementation, NIGT1.4 was confirmed to have a role in promoting primary root growth in response to salt stress. The expression of NIGT1.4 in the root was shown induced by NaCl treatments in an ABA-dependent manner. SnRK2.2 and 2.3 were shown to interact with and phosphorylate NIGT1.4 individually. The growth of the primary root of snrk2.2/2.3/2.6 triple mutant was shown sensitive to salt stress, which was similar to nigt1.4 plants. Using DNA affinity purification sequencing, ERF1, a known positive regulator for primary root elongation and salt tolerance, was identified as a target gene for NIGT1.4. The transcriptional induction of ERF1 by salt stress was shown absent in nigt1.4 background. NIGT1.4 was also confirmed to bind to the promoter region of ERF1 by yeast one-hybrid experiment and to induce the expression of ERF1 by dual-luciferase analysis. All data support the notion that salt- and ABA-elicited NIGT1.4 induces the expression of ERF1 to regulate downstream functional genes that contribute to maintained primary root elongation. NIGT1.4-ERF1, therefore, acts as a signaling node linking regulators for stress resilience and root growth, providing new insights for breeding salt-tolerant crops.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Melhoramento Vegetal , Plantas Geneticamente Modificadas/genética , Tolerância ao Sal/genética , Estresse Fisiológico/genética
17.
J Am Chem Soc ; 146(20): 14267-14277, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38717595

RESUMO

Converting CO2 to synthetic hydrocarbon fuels is of increasing interest. In light of progress in electrified CO2 to ethylene, we explored routes to dimerize to 1-butene, an olefin that can serve as a building block to ethylene longer-chain alkanes. With goal of selective and active dimerization, we investigate a series of metal-organic frameworks having bimetallic catalytic sites. We find that the tunable pore structure enables optimization of selectivity and that periodic pore channels enhance activity. In a tandem system for the conversion of CO2 to 1-C4H8, wherein the outlet cathodic gas from a CO2-to-C2H4 electrolyzer is fed directly (via a dehumidification stage) into the C2H4 dimerizer, we study the highest-performing MOF found herein: M' = Ru and M″ = Ni in the bimetallic two-dimensional M'2(OAc)4M″(CN)4 MOF. We report a 1-C4H8 production rate of 1.3 mol gcat-1 h-1 and a C2H4 conversion of 97%. From these experimental data, we project an estimated cradle-to-gate carbon intensity of -2.1 kg-CO2e/kg-1-C4H8 when CO2 is supplied from direct air capture and when the required energy is supplied by electricity having the carbon intensity of wind.

18.
J Am Chem Soc ; 146(12): 8641-8649, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38470826

RESUMO

Renewable-energy-powered electrosynthesis has the potential to contribute to decarbonizing the production of propylene glycol, a chemical that is used currently in the manufacture of polyesters and antifreeze and has a high carbon intensity. Unfortunately, to date, the electrooxidation of propylene under ambient conditions has suffered from a wide product distribution, leading to a low faradic efficiency toward the desired propylene glycol. We undertook mechanistic investigations and found that the reconstruction of Pd to PdO occurs, followed by hydroxide formation under anodic bias. The formation of this metastable hydroxide layer arrests the progressive dissolution of Pd in a locally acidic environment, increases the activity, and steers the reaction pathway toward propylene glycol. Rh-doped Pd further improves propylene glycol selectivity. Density functional theory (DFT) suggests that the Rh dopant lowers the energy associated with the production of the final intermediate in propylene glycol formation and renders the desorption step spontaneous, a concept consistent with experimental studies. We report a 75% faradic efficiency toward propylene glycol maintained over 100 h of operation.

19.
Anal Chem ; 96(5): 2059-2067, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38258754

RESUMO

Human respiratory adenovirus (ADV) is a highly infectious respiratory virus with potential for pandemics. There are currently no specific drugs to treat ADV worldwide, so early rapid detection of ADV infection is essential. In this study, we developed an innovative magnetic-optical triple-mode lateral flow immunoassay (LFIA) using magnetic quantum dots as immunomarkers. This novel approach addresses the need for rapid and accurate ADV detection, allowing for multimodal quantitative/semiquantitative analysis of magnetic, fluorescent, and visible signals within a mere 15 min. The lower limit of detection (LOD) for magnetic, fluorescent, and visual signals was determined to be 5.6 × 103, 1.2 × 103, and 1.95 × 104 copies/mL, respectively. The detection range for ADV using this approach was 1.2 × 103-5 × 107 copies/mL. Additionally, semiquantitative analysis, which is user-friendly and does not necessitate specialized equipment, was successfully implemented. Notably, seven respiratory viruses showed no cross-reactivity with the generated LFIA test strips. The intrabatch repeatability exhibited a coefficient of variation (CV) of less than 5%, while the interbatch repeatability had a CV of less than 15%. Furthermore, recovery values ranged from 95% to 106.8% for samples analyzed concurrently with dual signals at the same spiking concentration. The assay developed in this study boasts a wide detection range and exceptional sensitivity and specificity. This technique is exceptionally well-suited for on-site rapid detection, with the potential for personal self-testing and early ADV infection diagnosis. Its versatility extends to a broad array of application scenarios.


Assuntos
Adenoviridae , Fenômenos Magnéticos , Humanos , Imunoensaio/métodos , Sensibilidade e Especificidade , Limite de Detecção
20.
J Comput Chem ; 45(6): 331-340, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-37846101

RESUMO

Main-group metallomimetics provide a new way to replace transition metal complexes to activate inert small molecules under mild conditions. In this work, the activation mechanisms of CO2 , iPrNCO, and iPrNCNiPr by (µ-Hydrido) diborane anion ([1H]- ) have been investigated by density functional theory (DFT) calculations. Two different activation sites, BB versus BH bond of [1H]- , are investigated and compared. The results show that these inert molecules can be activated by [1H]- through cycloadditions under mild conditions. The reactions with iPrNCO and iPrNCNiPr are dynamic and thermodynamic controlling, the obtained products are related not only to the energy barrier but also to the stability of the products. Moreover, the competition for BB/BH bond site activation is directly related to the steric effect of small molecules. CO2 , which is without steric hindrance, can only be activated by the BB bond, whereas iPrNCNiPr can only be activated by the BH bond due to the large steric effect. The medium iPrNCO can be activated not only by the BB bond but also by the BH bond. Our study provides theoretical explanations for the reaction activity and chemoselectivity controlling of the title reaction, and displays the potential applications for compounds containing boron-boron bonds and inert small molecule activation.

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