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1.
Nat Immunol ; 25(1): 117-128, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38012417

RESUMEN

In cancer and infections, self-renewing stem-like CD8+ T cells mediate the response of immunotherapies and replenish terminally exhausted T cells and effector-like T cells. However, the programs governing the lineage choice in chimeric antigen receptor (CAR) T cells are unclear. Here, by simultaneously profiling single-cell chromatin accessibility and transcriptome in the same CAR T cells, we identified heterogeneous chromatin states within CD8+ T cell subsets that foreshadowed transcriptional changes and were primed for regulation by distinct transcription factors. Transcription factors that controlled each CD8+ T cell subset were regulated by high numbers of enhancers and positioned as hubs of gene networks. FOXP1, a hub in the stem-like network, promoted expansion and stemness of CAR T cells and limited excessive effector differentiation. In the effector network, KLF2 enhanced effector CD8+ T cell differentiation and prevented terminal exhaustion. Thus, we identified gene networks and hub transcription factors that controlled the differentiation of stem-like CD8+ CAR T cells into effector or exhausted CD8+ CAR T cells.


Asunto(s)
Linfocitos T CD8-positivos , Factores de Transcripción , Factores de Transcripción/genética , Subgrupos de Linfocitos T , Diferenciación Celular , Cromatina
2.
Immunity ; 54(4): 632-647.e9, 2021 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-33667382

RESUMEN

Aging is associated with DNA accumulation and increased homeostatic proliferation of circulating T cells. Although these attributes are associated with aging-related autoimmunity, their direct contributions remain unclear. Conventionally, KU complex, the regulatory subunit of DNA-dependent protein kinase (DNA-PK), together with the catalytic subunit of DNA-PK (DNA-PKcs), mediates DNA damage repair in the nucleus. Here, we found KU complex abundantly expressed in the cytoplasm, where it recognized accumulated cytoplasmic DNA in aged human and mouse CD4+ T cells. This process enhanced T cell activation and pathology of experimental autoimmune encephalomyelitis (EAE) in aged mice. Mechanistically, KU-mediated DNA sensing facilitated DNA-PKcs recruitment and phosphorylation of the kinase ZAK. This activated AKT and mTOR pathways, promoting CD4+ T cell proliferation and activation. We developed a specific ZAK inhibitor, which dampened EAE pathology in aged mice. Overall, these findings demonstrate a KU-mediated cytoplasmic DNA-sensing pathway in CD4+ T cells that potentiates aging-related autoimmunity.


Asunto(s)
Envejecimiento/inmunología , Enfermedades Autoinmunes/inmunología , Linfocitos T CD4-Positivos/inmunología , Citoplasma/inmunología , Proteína Quinasa Activada por ADN/inmunología , ADN/inmunología , Inflamación/inmunología , Animales , Línea Celular , Línea Celular Tumoral , Núcleo Celular/inmunología , Proliferación Celular/fisiología , Reparación del ADN/inmunología , Células HEK293 , Humanos , Células Jurkat , Activación de Linfocitos/inmunología , Ratones , Ratones Endogámicos C57BL , Células U937
3.
EMBO Rep ; 24(4): e56932, 2023 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-36862324

RESUMEN

Obesity is associated with metabolic disorders and chronic inflammation. However, the obesity-associated metabolic contribution to inflammatory induction remains elusive. Here, we show that, compared with lean mice, CD4+ T cells from obese mice exhibit elevated basal levels of fatty acid ß-oxidation (FAO), which promote T cell glycolysis and thus hyperactivation, leading to enhanced induction of inflammation. Mechanistically, the FAO rate-limiting enzyme carnitine palmitoyltransferase 1a (Cpt1a) stabilizes the mitochondrial E3 ubiquitin ligase Goliath, which mediates deubiquitination of calcineurin and thus enhances activation of NF-AT signaling, thereby promoting glycolysis and hyperactivation of CD4+ T cells in obesity. We also report the specific GOLIATH inhibitor DC-Gonib32, which blocks this FAO-glycolysis metabolic axis in CD4+ T cells of obese mice and reduces the induction of inflammation. Overall, these findings establish a role of a Goliath-bridged FAO-glycolysis axis in mediating CD4+ T cell hyperactivation and thus inflammation in obese mice.


Asunto(s)
Ácidos Grasos , Inflamación , Animales , Ratones , Ratones Obesos , Ácidos Grasos/metabolismo , Inflamación/metabolismo , Obesidad/metabolismo , Glucólisis , Ubiquitina-Proteína Ligasas/metabolismo , Oxidación-Reducción
4.
Proc Natl Acad Sci U S A ; 118(40)2021 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-34588309

RESUMEN

The ability to create highly efficient and stable bifunctional electrocatalysts, capable of oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) in the same electrolyte, represents an important endeavor toward high-performance zinc-air batteries (ZABs). Herein, we report a facile strategy for crafting wrinkled MoS2/N-doped carbon core/shell nanospheres interfaced with single Fe atoms (denoted MoS2@Fe-N-C) as superior ORR/OER bifunctional electrocatalysts for robust wearable ZABs with a high capacity and outstanding cycling stability. Specifically, the highly crumpled MoS2 nanosphere core is wrapped with a layer of single-Fe-atom-impregnated, N-doped carbon shell (i.e., Fe-N-C shell with well-dispersed FeN4 sites). Intriguingly, MoS2@Fe-N-C nanospheres manifest an ORR half-wave potential of 0.84 V and an OER overpotential of 360 mV at 10 mA⋅cm-2 More importantly, density functional theory calculations reveal the lowered energy barriers for both ORR and OER, accounting for marked enhanced catalytic performance of MoS2@Fe-N-C nanospheres. Remarkably, wearable ZABs assembled by capitalizing on MoS2@Fe-N-C nanospheres as an air electrode with an ultralow area loading (i.e., 0.25 mg⋅cm-2) display excellent stability against deformation, high special capacity (i.e., 442 mAh⋅g-1Zn), excellent power density (i.e., 78 mW⋅cm-2) and attractive cycling stability (e.g., 50 cycles at current density of 5 mA⋅cm-2). This study provides a platform to rationally design single-atom-interfaced core/shell bifunctional electrocatalysts for efficient metal-air batteries.

5.
Angew Chem Int Ed Engl ; 62(13): e202218229, 2023 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-36714922

RESUMEN

The application of solid polymer electrolytes (SPEs) in all-solid-state(ASS) batteries is hindered by lower Li+ -conductivity and narrower electrochemical window. Here, three families of ester-based F-modified SPEs of poly-carbonate (PCE), poly-oxalate (POE) and poly-malonate (PME) were investigated. The Li+ -conductivity of these SPEs prepared from pentanediol are all higher than the counterparts made of butanediol, owing to the enhanced asymmetry and flexibility. Because of stronger chelating coordination with Li+ , the Li+ -conductivity of PME and POE is around 10 and 5 times of PCE. The trifluoroacetyl-units are observed more effective than -O-CH2 -CF2 -CF2 -CH2 -O- during the in situ passivation of Li-metal. Using trifluoroacetyl terminated POE and PCE as SPE, the interfaces with Li-metal and high-voltage-cathode are stabilized simultaneously, endowing stable cycling of ASS Li/LiNi0.6 Co0.2 Mn0.2 O2 (NCM622) cells. Owing to an enol isomerization of malonate, the cycling stability of Li/PME/NCM622 is deteriorated, which is recovered with the introduce of dimethyl-group in malonate and the suppression of enol isomerization. The coordinating capability with Li+ , molecular asymmetry and existing modes of elemental F, are all critical for the molecular design of SPEs.

6.
Angew Chem Int Ed Engl ; 62(38): e202309613, 2023 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-37555781

RESUMEN

In situ polymerization of liquid electrolytes is currently the most feasible way for constructing solid-state batteries, which, however, is affected by various interfering factors of reactions and so the electrochemical performance of cells. To disclose the effects from polymerization conditions, two types of generally used in situ polymerizing reactions of ring-opening polymerization (ROP) and double bond radical polymerization (DBRP) were investigated on the aspects of monomer conversion and electrochemical properties (Li+ -conductivity and interfacial stability). The ROP generated poly-ester and poly-carbonate show a high monomer conversion of ≈90 %, but suffer a poor Li+ -conductivity of lower than 2×10-5  S cm-1 at room temperature (RT). Additionally, the terminal alkoxy anion derived from the ROP is not resistant to high-voltage cathodes. While, the DBRP produced poly-VEC(vinyl ethylene carbonate) and poly-VC(vinylene carbonate) show lower monomer conversions of 50-80 %, delivering relatively higher Li+ -conductivities of 2×10-4  S cm-1 at RT. Compared two polymerizing reactions and four monomers, the VEC-based F-containing copolymer possesses advantages in Li+ -conductivity and antioxidant capacity, which also shows simultaneous stability towards Li-metal with the help of LiF-based passivating layer, allowing a long-term stable cycling of high-voltage quasi solid-state cells.

7.
Nano Lett ; 21(18): 7435-7447, 2021 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-34515493

RESUMEN

The past decades have witnessed rapid development of lithium-based batteries. Significant research efforts have been progressively diverted from electrodes to electrolytes, particularly polymer electrolytes (PEs), to tackle the safety concern and promote the energy storage capability of batteries. To further increase the ionic conductivity of PEs, various branched polymers (BPs) have been rationally designed and synthesized. Compared with linear polymers, branched architectures effectively increase polymer segmental mobility, restrain crystallization, and reduce chain entanglement, thereby rendering BPs with greatly enhanced lithium transport. In this Mini Review, a diversity of BPs for PEs is summarized by scrutinizing their unique topologies and properties. Subsequently, the design principles for enhancing the physical properties, mechanical properties, and electrochemical performance of BP-based PEs (BP-PEs) are provided in which the ionic conduction is particularly examined in light of the Li+ transport mechanism. Finally, the challenges and future prospects of BP-PEs in this rapidly evolving field are outlined.

8.
Angew Chem Int Ed Engl ; 61(38): e202209169, 2022 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-35900253

RESUMEN

Solid polymer electrolytes (SPEs) with LiTFSI (lithium bis(trifluoromethane sulfonimide)) are promising candidates for solid-state batteries, owing to their good interfacial contact with solid electrodes. Here, three copolymerized polyethers were prepared as SPEs, using the catalysts of SnF2 or SnF2 -LiPF6 . The thermal depolymerization of these polyethers was observed at elevated temperatures, which limits their operating temperature ranges. Once the catalyst is removed, the thermal degradation temperatures of these SPEs are raised by 30-55 °C, together with improved thermal performance in cells. For SPEs, the high price of LiTFSI is an obstacle for their large-scale application, and it's recycling is hindered by the strong interaction with polymers. By the thermal depolymerization of polyethers, LiTFSI can be easier reclaimed from above mentioned SPEs and even the commercial PEO(poly(ethylene-oxide)) based SPE in rates of 70-80 %, providing a low-cost strategy for the recycling of LiTFSI.

9.
Chemistry ; 24(65): 17339-17344, 2018 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-30226279

RESUMEN

Although the electrochemical catalytic conversion process is effective in increasing the reversible capacity of lithium-ion batteries, the low contact efficiency between metal catalyst and substrate and pulverization of the solid electrolyte interface (SEI) film without protection are not beneficial for the electrochemical reactions. Herein, Fe7 S8 nanoparticles are confined by both reduced graphene oxide (RGO) and in-situ-formed amorphous carbon (C) to form dual-carbon-confined Fe7 S8 as a lithium-ion anode. The dual-carbon-confined structure provides a confined space to prevent pulverization of the SEI film and increases the local concentration of intermediate phases, which could be electrocatalytically decomposed by Fe nanoparticles formed in situ to increase the reversibility of the electrochemical reactions and gain high reversible capacity. In addition, the dual-carbon-confined structure ensures fast transfer of electrons and boosts transport of lithium ions due to the highly conductive dual-carbon shell. Thus, the Fe7 S8 /C/RGO anode delivers an excellent rate performance and long cycling stability. At current densities of 2000 and 5000 mA g-1 , the reversible capacities are 520 mA h g-1 over 1500 cycles and 294 mA h g-1 over 2000 cycles, respectively.

10.
Chemistry ; 22(10): 3397-3404, 2016 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-26836983

RESUMEN

Ion diffusion efficiency at the solid-liquid interface is an important factor for energy storage and adsorption from aqueous solution. Although K2 Mn4 O8 (KMO) exhibits efficient ion diffusion and ion-exchange capacities, due to its high interlayer space of 0.70 nm, how to enhance its mass transfer performance is still an issue. Herein, novel layered KMO/reduced graphene oxide (RGO) nanocomposites are fabricated through the anchoring of KMO nanoplates on RGO with a mild solution process. The face-to-face structure facilitates fast transfer of lithium and lead ions; thus leading to excellent lithium storage and lead ion adsorption. The anchoring of KMO on RGO not only increases electrical conductivity of the layered nanocomposites, but also effectively prevents aggregation of KMO nanoplates. The KMO/RGO nanocomposite with an optimal RGO content exhibits a first cycle charge capacity of 739 mA h g-1 , which is much higher than that of KMO (326 mA h g-1 ). After 100 charge-discharge cycles, it still retains a charge capacity of 664 mA h g-1 . For the adsorption of lead ions, the KMO/RGO nanocomposite exhibits a capacity of 341 mg g-1 , which is higher than those of KMO (305 mg g-1 ) and RGO (63 mg g-1 ) alone.

11.
Adv Sci (Weinh) ; 9(2): e2103798, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34741443

RESUMEN

Lithium-sulfur batteries (LSBs) hold great promise as one of the next-generation power supplies for portable electronics and electric vehicles due to their ultrahigh energy density, cost effectiveness, and environmental benignity. However, their practical application has been impeded owing to the electronic insulation of sulfur and its intermediates, serious shuttle effect, large volume variation, and uncontrollable formation of lithium dendrites. Over the past decades, many pioneering strategies have been developed to address these issues via improving electrodes, electrolytes, separators and binders. Remarkably, polymers can be readily applied to all these aspects due to their structural designability, functional versatility, superior chemical stability and processability. Moreover, their lightweight and rich resource characteristics enable the production of LSBs with high-volume energy density at low cost. Surprisingly, there have been few reviews on development of polymers in LSBs. Herein, breakthroughs and future perspectives of emerging polymers in LSBs are scrutinized. Significant attention is centered on recent implementation of polymers in each component of LSBs with an emphasis on intrinsic mechanisms underlying their specific functions. The review offers a comprehensive overview of state-of-the-art polymers for LSBs, provides in-depth insights into addressing key challenges, and affords important resources for researchers working on electrochemical energy systems.

12.
Adv Mater ; 33(16): e2004577, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33686697

RESUMEN

The increasing demand for higher-energy-density batteries driven by advancements in electric vehicles, hybrid electric vehicles, and portable electronic devices necessitates the development of alternative anode materials with a specific capacity beyond that of traditional graphite anodes. Here, the state-of-the-art developments made in the rational design of Si-based electrodes and their progression toward practical application are presented. First, a comprehensive overview of fundamental electrochemistry and selected critical challenges is given, including their large volume expansion, unstable solid electrolyte interface (SEI) growth, low initial Coulombic efficiency, low areal capacity, and safety issues. Second, the principles of potential solutions including nanoarchitectured construction, surface/interface engineering, novel binder and electrolyte design, and designing the whole electrode for stability are discussed in detail. Third, applications for Si-based anodes beyond LIBs are highlighted, specifically noting their promise in configurations of Li-S batteries and all-solid-state batteries. Fourth, the electrochemical reaction process, structural evolution, and degradation mechanisms are systematically investigated by advanced in situ and operando characterizations. Finally, the future trends and perspectives with an emphasis on commercialization of Si-based electrodes are provided. Si-based anode materials will be key in helping keep up with the demands for higher energy density in the coming decades.

13.
Cell Mol Immunol ; 18(4): 969-978, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33707688

RESUMEN

T follicular helper (Tfh) cells are crucial for regulating autoimmune inflammation and protective immunity against viral infection. However, the molecular mechanism controlling Tfh cell differentiation is poorly understood. Here, through two mixed bone marrow chimeric experiments, we identified Peli1, a T cell-enriched E3 ubiquitin ligase, as an intrinsic regulator that inhibits Tfh cell differentiation. Peli1 deficiency significantly promoted c-Rel-mediated inducible T-cell costimulator (ICOS) expression, and PELI1 mRNA expression was negatively associated with ICOS expression on human CD4+ T cells. Mechanistically, increased ICOS expression on Peli1-KO CD4+ T cells enhanced the activation of PI3K-AKT signaling and thus suppressed the expression of Klf2, a transcription factor that inhibits Tfh differentiation. Therefore, reconstitution of Klf2 abolished the differences in Tfh differentiation and germinal center reaction between WT and Peli1-KO cells. As a consequence, Peli1-deficient CD4+ T cells promoted lupus-like autoimmunity but protected against H1N1 influenza virus infection in mouse models. Collectively, our findings established Peli1 as a critical negative regulator of Tfh differentiation and indicated that targeting Peli1 may have beneficial therapeutic effects in Tfh-related autoimmunity or infectious diseases.


Asunto(s)
Autoinmunidad , Proteína Coestimuladora de Linfocitos T Inducibles/metabolismo , Lupus Eritematoso Sistémico/patología , Activación de Linfocitos/inmunología , Proteínas Nucleares/fisiología , Infecciones por Orthomyxoviridae/prevención & control , Células T Auxiliares Foliculares/inmunología , Ubiquitina-Proteína Ligasas/fisiología , Animales , Diferenciación Celular , Femenino , Regulación de la Expresión Génica , Humanos , Proteína Coestimuladora de Linfocitos T Inducibles/genética , Subtipo H1N1 del Virus de la Influenza A/inmunología , Lupus Eritematoso Sistémico/etiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Infecciones por Orthomyxoviridae/inmunología
14.
J Exp Med ; 218(7)2021 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-33914044

RESUMEN

TGFß is essential for the generation of anti-tumor Th9 cells; on the other hand, it causes resistance against anti-tumor immunity. Despite recent progress, the underlying mechanism reconciling the double-edged effect of TGFß signaling in Th9-mediated cancer immunotherapy remains elusive. Here, we find that TGFß-induced down-regulation of bifunctional apoptosis regulator (BFAR) represents the key mechanism preventing the sustained activation of TGFß signaling and thus impairing Th9 inducibility. Mechanistically, BFAR mediates K63-linked ubiquitination of TGFßR1 at K268, which is critical to activate TGFß signaling. Thus, BFAR deficiency or K268R knock-in mutation suppresses TGFßR1 ubiquitination and Th9 differentiation, thereby inhibiting Th9-mediated cancer immunotherapy. More interestingly, BFAR-overexpressed Th9 cells exhibit promising therapeutic efficacy to curtail tumor growth and metastasis and promote the sensitivity of anti-PD-1-mediated checkpoint immunotherapy. Thus, our findings establish BFAR as a key TGFß-regulated gene to fine-tune TGFß signaling that causes Th9 induction insensitivity, and they highlight the translational potential of BFAR in promoting Th9-mediated cancer immunotherapy.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/inmunología , Proteínas Reguladoras de la Apoptosis/inmunología , Proteínas de la Membrana/inmunología , Neoplasias/inmunología , Neoplasias/terapia , Transducción de Señal/inmunología , Factor de Crecimiento Transformador beta/inmunología , Animales , Diferenciación Celular/inmunología , Regulación hacia Abajo/inmunología , Humanos , Inmunoterapia/métodos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Linfocitos T Colaboradores-Inductores/inmunología
15.
J Phys Chem Lett ; 11(17): 7407-7416, 2020 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-32794709

RESUMEN

The intrinsic internal electric field in a ferroelectric photocatalyst is beneficial for improving the photocatalytic properties because of its positive effect on the separation and migration of photogenerated carriers. However, this kind of internal electric field is static and easily saturated by inner and outer shielding effects, seriously restricting its potential in photocatalysis. To overcome this problem, a sustainable internal electric field was introduced into photocatalysis based on piezoelectric and pyroelectric effect, which exhibits good capability in consistently boosting photocatalytic activity, thus becoming a hot research topic. In this Perspective we summarize the recent significant progress in the construction of sustainable internal electric fields for facilitating photocatalysis from material design to energy utilization. Moreover, the fascinating influence of sustainable internal electric fields on carrier behavior is also discussed. Finally, a summary and outlook for building a sustainable internal electric field to further enhance photocatalytic performance are provided.

16.
J Colloid Interface Sci ; 561: 396-407, 2020 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-31732146

RESUMEN

Efficient separation of photogenerated electron-hole pairs is always one of the key factors boosting visible light photodegradation efficiency. Till now, there are few reports on the synergistic competitive consumption of photogenerated active species and the synergistic adsorption of organic contaminants to promote the performance of a designed heterojunction. Herein, we design and construct a novel BiOBr/Ag6Si2O7 heterojunction with the dual synergistic effects towards methylene blue (MB) and methyl orange (MO). The dual synergistic effects could avoid the combination of photogenerated h+/e- pairs, improve the adsorption efficiency, and even regulate the photodegradation efficiency. Thus, for an aqueous mixture of MB and MO, the BiOBr/Ag6Si2O7 photocatalyst exhibits largely improved adsorption capacities of the dyes by a multi-layer adsorption mode. Moreover, the photocatalyst could further promote the photodegradation rate of MO while slow that of MB due to the competitive consumption of photogenerated active species, showing a sequential selectivity phenomenon. Thanks to the dual synergistic effects, the adsorption capacity of MO increases 1379% higher than that of neat MO solution, and the photodegradation time decrease from 30 to 12 min with a rate constant of 0.22 min-1, 38% higher than that of neat MO solution.

17.
Nanomicro Lett ; 12(1): 56, 2020 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-34138296

RESUMEN

Mn-based rechargeable aqueous zinc-ion batteries (ZIBs) are highly promising because of their high operating voltages, attractive energy densities, and eco-friendliness. However, the electrochemical performances of Mn-based cathodes usually suffer from their serious structure transformation upon charge/discharge cycling. Herein, we report a layered sodium-ion/crystal water co-intercalated Birnessite cathode with the formula of Na0.55Mn2O4·0.57H2O (NMOH) for high-performance aqueous ZIBs. A displacement/intercalation electrochemical mechanism was confirmed in the Mn-based cathode for the first time. Na+ and crystal water enlarge the interlayer distance to enhance the insertion of Zn2+, and some sodium ions are replaced with Zn2+ in the first cycle to further stabilize the layered structure for subsequent reversible Zn2+/H+ insertion/extraction, resulting in exceptional specific capacities and satisfactory structural stabilities. Additionally, a pseudo-capacitance derived from the surface-adsorbed Na+ also contributes to the electrochemical performances. The NMOH cathode not only delivers high reversible capacities of 389.8 and 87.1 mA h g-1 at current densities of 200 and 1500 mA g-1, respectively, but also maintains a good long-cycling performance of 201.6 mA h g-1 at a high current density of 500 mA g-1 after 400 cycles, which makes the NMOH cathode competitive for practical applications.

18.
J Exp Med ; 217(7)2020 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-32324863

RESUMEN

Ubiquitination is an essential mechanism in the control of antiviral immunity upon virus infection. Here, we identify a series of ubiquitination-modulating enzymes that are modulated by vesicular stomatitis virus (VSV). Notably, TRIM24 is down-regulated through direct transcriptional suppression induced by VSV-activated IRF3. Reducing or ablating TRIM24 compromises type I IFN (IFN-I) induction upon RNA virus infection and thus renders mice more sensitive to VSV infection. Mechanistically, VSV infection induces abundant TRIM24 translocation to mitochondria, where TRIM24 binds with TRAF3 and directly mediates K63-linked TRAF3 ubiquitination at K429/K436. This modification of TRAF3 enables its association with MAVS and TBK1, which consequently activates downstream antiviral signaling. Together, these findings establish TRIM24 as a critical positive regulator in controlling the activation of antiviral signaling and describe a previously unknown mechanism of TRIM24 function.


Asunto(s)
Antivirales/metabolismo , Inmunidad , Lisina/metabolismo , Proteínas Nucleares/metabolismo , Factor 3 Asociado a Receptor de TNF/metabolismo , Factores de Transcripción/metabolismo , Ubiquitinación , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Núcleo Celular/metabolismo , Regulación hacia Abajo , Células HEK293 , Humanos , Inflamación/genética , Interferón Tipo I/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Mitocondrias/metabolismo , Modelos Biológicos , Proteínas Nucleares/química , Proteínas Nucleares/deficiencia , Proteínas Nucleares/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Transporte de Proteínas , Dominios RING Finger , Transducción de Señal , Factor 3 Asociado a Receptor de TNF/química , Factor 3 Asociado a Receptor de TNF/genética , Factores de Transcripción/química , Factores de Transcripción/deficiencia , Factores de Transcripción/genética , Transcripción Genética , Virus de la Estomatitis Vesicular Indiana/fisiología
19.
J Colloid Interface Sci ; 545: 128-137, 2019 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-30877996

RESUMEN

Self-sacrificial biomass-derived silica is a rising and promising approach to fabricate large metal silicates, which are practical water treatment agents ascribed for easy sedimentation and separation. However, the original biomass architecture is difficult to be maintained and utilized. Furthermore, sufficient ion diffusion pathways need to be created to satisfy massive mass transport in large bulk materials. Herein, a series of metal silicates, including cobalt silicate (CoSiOx), copper silicate, nickel silicate, iron silicate, and magnesium silicate, are synthesized from Indocalamus tessellatus leaf as the biomass-derived silica source and investigated as catalysts in sulfate-radical-based advanced oxidization processes (SR-AOPs) for the first time. Among them, CoSiOx presents an analogical sandwich structure as a leaf-derived template of micron-level size. More importantly, the interior hollow nanotubes assembled by small nanosheets provide numerous pathways for ion diffusion and remarkably promote the mass transport in such large bulk materials. Owing to the combination of the unique structure with the high reactivity of Co (II) toward peroxymonosulfate, CoSiOx exhibits excellent catalytic performance with 0.242 and 0.153 min-1 rate constants for the removal of methylene blue and phenol, respectively, which outperforms/is comparable to that of the reported nanomaterials toward organic contaminants in SR-AOPs.

20.
ACS Appl Mater Interfaces ; 11(37): 34222-34231, 2019 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-31425650

RESUMEN

Macroscopic three-dimensional catalytic materials could overcome the poor operability and avoid secondary pollution of common powdery counterparts, especially in flow-type setups. However, conventional isotropic graphene-based aerogels and foams have randomly distributed graphene sheets, which may cause stream erosion and reduce the flux seriously. Herein, for the first time, we design and fabricate a novel anisotropic CoFe2O4@graphene hybrid aerogel (CFO@GA-A) with a hydrothermal synthesis followed by directional-freezing and freeze-drying for a tube-like flow-type setup analogous to a wastewater discharge pipeline. The long and vertically aligned pores inside the aerogel provide an exceptional flux of 1100 L m-2 h-1, 450% higher than that of the rough and zigzag paths in the isotropic CoFe2O4@graphene hybrid aerogel (CFO@GA-I), and the leaching of metal ions is obviously inhibited by relieving the erosion of CoFe2O4. Besides, the CFO@GA-A could sustain the scour of high-speed flowing wastewater and maintain its structural stability. Therefore, organic contaminants of indigo carmine, methyl orange, orange II, malachite green, phenol, and norfloxacin could readily flow over the nanocatalysts and be degraded rapidly within 7.5-12.5 min at varied flow rates from 60 to 120 mL h-1. The CFO@GA-A also exhibits a much better long-term stability with removal efficiencies toward indigo carmine at 100%, 91%, and 85% for at least 30 h (60 mL h-1), 25 h (90 mL h-1), and 21 h (120 mL h-1), respectively. On the contrary, the CFO@GA-I exhibits unsatisfactory removal efficiencies of <40%. Interestingly, CFO@GA-A could also serve as building blocks to stack on each other for degrading intense flowing wastewater, exhibiting an outstanding composability. The high-flux and long-term stability make the CFO@GA-A promising as an ideal catalytic material for wastewater treatments.

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