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1.
Luminescence ; 39(6): e4809, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38890149

RESUMEN

Utilizing the structure characteristic of KCaY (PO4)2 crystal, the site distribution of Eu2+ in KCaY (PO4)2:Eu phosphor coactivated with Eu2+ and Eu3+ ions is tuned. Upon 393-nm excitation, the as-prepared phosphor exhibits a broadband emission of Eu2+ peaked at ~ 475 nm and a typical red emission of Eu3+ with a strong 5D0-7F1 emission at ~ 591 nm. The luminescence color of the phosphor can be adjusted from blue to green, white, yellow, and red. The increasing concentration of Sr2+ and Eu2+ results in a blue shifting of Eu2+ emission. The increasing concentration of Eu3+ results in a red shifting of Eu2+ emission and an enhanced red emission of Eu3+. The luminescence behaviors of the phosphors are analyzed in terms of the site distribution of Eu2+ and Eu3+. A single-phase white light emitting was achieved in KCaY (PO4)2:Eu phosphor upon UV and NUV light excitation, indicating that the phosphor has potential application in white lighting.


Asunto(s)
Europio , Luminiscencia , Sustancias Luminiscentes , Europio/química , Sustancias Luminiscentes/química , Mediciones Luminiscentes , Fosfatos/química
2.
Biosensors (Basel) ; 14(5)2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38785719

RESUMEN

Since SARS-CoV-2 is a highly transmissible virus, alternative reliable, fast, and cost-effective methods are still needed to prevent virus spread that can be applied in the laboratory and for point-of-care testing. Reverse transcription real-time fluorescence quantitative PCR (RT-qPCR) is currently the gold criteria for detecting RNA viruses, which requires reverse transcriptase to reverse transcribe viral RNA into cDNA, and fluorescence quantitative PCR detection was subsequently performed. The frequently used reverse transcriptase is thermolabile; the detection process is composed of two steps: the reverse transcription reaction at a relatively low temperature, and the qPCR performed at a relatively high temperature, moreover, the RNA to be detected needs to pretreated if they had advanced structure. Here, we develop a fast and sensitive one-tube SARS-CoV-2 detection platform based on Ultra-fast RTX-PCR and Pyrococcus furiosus Argonaute-mediated Nucleic acid Detection (PAND) technology (URPAND). URPAND was achieved ultra-fast RTX-PCR process based on a thermostable RTX (exo-) with both reverse transcriptase and DNA polymerase activity. The URPAND can be completed RT-PCR and PAND to detect nucleic acid in one tube within 30 min. This method can specifically detect SARS-CoV-2 with a low detection limit of 100 copies/mL. The diagnostic results of clinical samples with one-tube URPAND displayed 100% consistence with RT-qPCR test. Moreover, URPAND was also applied to identify SARS-CoV-2 D614G mutant due to its single-nucleotide specificity. The URPAND platform is rapid, accurate, tube closed, one-tube, easy-to-operate and free of large instruments, which provides a new strategy to the detection of SARS-CoV-2 and other RNA viruses.


Asunto(s)
Proteínas Argonautas , COVID-19 , Pyrococcus furiosus , ARN Viral , SARS-CoV-2 , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , ARN Viral/análisis , COVID-19/diagnóstico , COVID-19/virología , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Técnicas Biosensibles/métodos , Prueba de Ácido Nucleico para COVID-19/métodos
3.
Biosens Bioelectron ; 259: 116400, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38776799

RESUMEN

CRISPR based nucleic acid detection technology provides a deployable approach to point of care testing. While, there remain challenges limiting its practical applications, such as the need for pre-amplification and the long turnaround time. Here, we present a self-cascade signal amplification method with LwaCas13a and an artificially designed "U" rich RNA of stem-loop structure (URH) for pre-amplification-free ultra-fast and ultra-sensitive point-of-care testing (PASSPORT). The PASSPORT system contains: URH, crRNA targeted the URH, crRNA targeted the interesting RNA, fluorescent RNA reporter and LwaCas13a. The assay realized the detection of 100 copies/mL, within 5 min. The PASSPORT platform was further adopted for the detection of marker gene from SASR-CoV-2 and Severe fever with thrombocytopenia syndrome virus (SFTSV), respectively, and 100% accuracy for the analysis of clinical specimens (100 SASR-CoV-2 specimens and 16 SFTSV specimens) was obtained. Integrated with a lateral flow assay device, this assay could provide an alternative platform for the development of point of care testing (POCT) biosensors. PASSPORT has the potential to enable sensitive, specific, user-friendly, rapid, affordable, equipment-free and point-of-care testing for the purpose of large-scale screening and in case of epidemic outbreak.


Asunto(s)
Técnicas Biosensibles , COVID-19 , Sistemas CRISPR-Cas , Pruebas en el Punto de Atención , SARS-CoV-2 , Técnicas Biosensibles/métodos , Humanos , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/genética , COVID-19/virología , COVID-19/diagnóstico , ARN Viral/genética , ARN Viral/análisis , ARN Viral/aislamiento & purificación , Técnicas de Amplificación de Ácido Nucleico/métodos , Sistemas de Atención de Punto , Límite de Detección
4.
Antioxidants (Basel) ; 13(3)2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38539904

RESUMEN

Hericium erinaceus, a consumable mushroom, has shown a potential to enhance the production of neuroprotective bioactive metabolites. Traumatic brain injury (TBI) often leads to cognitive, physical, and psychosocial impairments, resulting in neuroinflammation and the loss of cortical neurons. In this research, the effects of H. erinaceus mycelium, its derivative erinacine C, along with the underlying mechanisms, were examined in terms of oxidative stress modulation and neurological improvement in a rat model of mild traumatic brain injury (mTBI). Male Sprague-Dawley rats were administered diets containing H. erinaceus mycelium and erinacine C following experimental brain injury; these supplements were continued throughout the recovery phase. The binding activity of NF-E2-related factor 2 (Nrf2) near antioxidant genes in mixed glial cells was measured by chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR). The motor beam walking test revealed that dietary supplementation of H. erinaceus mycelium resulted in modest improvements in spatial memory while inhibiting neuron cell death and microglial activation according to brain histological examination. These findings were further corroborated by the upregulation of several antioxidant enzymes (catalase, glutathione reductase, thioredoxin reductase, and superoxide dismutase) and phospho-CAMP-response element-binding (p-CREB) levels in the mTBI model treated with H. erinaceus mycelium. Erinacine C treatment led to significantly reduced brain inflammation and normalization of mTBI-induced deficits through the modulation of the Nrf2 activation pathway and upregulated expression of numerous Nrf2-binding antioxidant genes such as catalase, thioredoxin reductase, superoxide dismutase, and brain-derived neurotrophic factor. This study demonstrates the potential of H. erinaceus mycelium and erinacine C in facilitating recovery following mTBI, including the prevention of neuronal injury and inactivation of microglia through the Nrf2-mediated antioxidant pathway in vivo.

5.
Biomed Pharmacother ; 173: 116297, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38394854

RESUMEN

Hericium erinaceus mycelium extract (HEM), containing erinacine A (HeA) and erinacine S (HeS), has shown promise in promoting the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs), crucial for myelin production in the central nervous system (CNS). The main aim of this study was to characterize the protective effects of HEM and its components on OLs and myelin in demyelinating rodents by exposure to cuprizone (CPZ), a copper chelating agent commonly used to induce demyelination in the corpus callosum of the brain. Rats were fed by CPZ-containing diet and simultaneously orally administered HEM, HeA, or HeS on a daily basis for three weeks. We found that HEM and HeS preserved myelin and OLs in the corpus callosum of CPZ-fed rats, along with reduced microglia and astrocyte activation, and downregulated IL-1ß expression. Furthermore, post-treatment with HeS, in mouse models with acute (6 weeks) or chronic (12 weeks) CPZ-induced demyelination demonstrated oral administration during the final 4 weeks (HeS4/6 or HeS4/12) effectively preserved myelin in the corpus callosum. Additionally, HeS4/6 and HeS4/12 inhibited anxious and depressive-like behaviors in CPZ-fed mice. In summary, simultaneous administration of HEM and HeS in rats during short-term CPZ intoxication preserved OLs and myelin. Furthermore, post-administration of HeS not only inhibited demyelination and gliosis but also alleviated anxiety and depression in both acute and chronic CPZ-fed mice. This study presents compelling evidence supporting the potential of HeS as a promising small active compound for protecting OLs and preserving myelin in demyelinating diseases associated with emotional disorders.


Asunto(s)
Cuprizona , Enfermedades Desmielinizantes , Hericium , Ratas , Ratones , Animales , Cuprizona/toxicidad , Enfermedades Desmielinizantes/inducido químicamente , Enfermedades Desmielinizantes/tratamiento farmacológico , Enfermedades Desmielinizantes/prevención & control , Roedores , Oligodendroglía , Vaina de Mielina/metabolismo , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad
6.
Microbiol Spectr ; 12(2): e0371723, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38179919

RESUMEN

All life forms have evolved to respond appropriately to various environmental and internal cues. In the animal kingdom, the prototypical regulator class of such cellular responses is the Rel homology domain proteins including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Fungi, the close relatives of animals, have also evolved with their own NF-κB-like regulators called velvet family proteins to govern cellular and chemical development. Here, we conducted a detailed investigation of the taxonomic broad presence of velvet proteins. We observed that velvet proteins are widely distributed in the fungal kingdom. Moreover, we have identified and characterized 21 major velvet clades in fungi. We have further revealed that the highly conserved velvet domain is composed of three distinct motifs and acts as an evolutionarily independent domain, which can be shuffled with various functional domains. Such rearrangements of the velvet domain have resulted in the functional and type diversity of the present velvet regulators. Importantly, our in-deep analyses of the primary and 3D structures of the various velvet domains showed that the fungal velvet domains can be divided into two major clans: the VelB and the VosA clans. The 3D structure comparisons revealed a close similarity of the velvet domain with many other eukaryotic DNA-binding proteins, including those of the Rel, Runt, and signal transducer and activator of transcription families, sharing a common ß-sandwich fold. Altogether, this study improves our understanding of velvet regulators in the fungal kingdom.IMPORTANCEFungi are the relatives of animals in Opisthokonta and closely associated with human life by interactive ways such as pathogenicity, food, and secondary metabolites including beneficial ones like penicillin and harmful ones like the carcinogenic aflatoxins. Similar to animals, fungi have also evolved with NF-κB-like velvet family regulators. The velvet proteins constitute a large protein family of fungal transcription factors sharing a common velvet domain and play a key role in coordinating fungal secondary metabolism, developmental and differentiation processes. Our current understanding on velvet regulators is mostly from Ascomycota fungi; however, they remain largely unknown outside Ascomycota. Therefore, this study performed a taxonomic broad investigation of velvet proteins across the fungal kingdom and conducted a detailed analysis on velvet distribution, structure, diversity, and evolution. The results provide a holistic view of velvet regulatory system in the fungal kingdom.


Asunto(s)
Proteínas Fúngicas , FN-kappa B , Humanos , FN-kappa B/metabolismo , Proteínas Fúngicas/genética , Filogenia , Factores de Transcripción/metabolismo , Proteínas de Unión al ADN/metabolismo , Regulación Fúngica de la Expresión Génica , Esporas Fúngicas/metabolismo
7.
Mol Cell ; 84(4): 675-686.e4, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38295801

RESUMEN

The Argonaute nuclease from the thermophilic archaeon Pyrococcus furiosus (PfAgo) contributes to host defense and represents a promising biotechnology tool. Here, we report the structure of a PfAgo-guide DNA-target DNA ternary complex at the cleavage-compatible state. The ternary complex is predominantly dimerized, and the dimerization is solely mediated by PfAgo at PIWI-MID, PIWI-PIWI, and PAZ-N interfaces. Additionally, PfAgo accommodates a short 14-bp guide-target DNA duplex with a wedge-type N domain and specifically recognizes 5'-phosphorylated guide DNA. In contrast, the PfAgo-guide DNA binary complex is monomeric, and the engagement of target DNA with 14-bp complementarity induces sufficient dimerization and activation of PfAgo, accompanied by movement of PAZ and N domains. A closely related Argonaute from Thermococcus thioreducens adopts a similar dimerization configuration with an additional zinc finger formed at the dimerization interface. Dimerization of both Argonautes stabilizes the catalytic loops, highlighting the important role of Argonaute dimerization in the activation and target cleavage.


Asunto(s)
Pyrococcus furiosus , Pyrococcus furiosus/genética , Dimerización , ADN/genética , Proteínas Argonautas/metabolismo , Dominios Proteicos
8.
Chemosphere ; 349: 140916, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38081522

RESUMEN

Peroxyl radicals (RO2) are important components of atmospheric radical cycling and generation, but their formation, distribution and evolution mechanisms in the atmospheric environment have not been investigated. In this paper, we propose a novel atmospheric RO2 radical trapping membrane that can trap low carbon number (Rc ≤ 5) RO2 radicals and identify their R-group structures by fluorescence spectroscopy and chromatography. We also analyzed the composition and evolution mechanism of RO2 species under different meteorological conditions in the atmospheric environment of Lanzhou, China, to provide scientific support for the treatment and research of atmospheric chemical pollution.


Asunto(s)
Atmósfera , Colorantes Fluorescentes , Radicales Libres/química , China
9.
Front Bioeng Biotechnol ; 11: 1167534, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37635997

RESUMEN

Molecular cloning is used in a wide variety of biological and medical research. Here, we developed a rapid and efficient DNA-assembling method for routine laboratory work. We discovered that the cleavage speed of T5 exonuclease is approximately 3 nt/min at 0°C and hence developed a T5 exonuclease-mediated low-temperature sequence- and ligation-independent cloning method (TLTC). Two homologous regions of 15 bp-25 bp compatible with the ends of the vector backbones were introduced into the inserts through PCR. Approximately 120 fmol of inserts and linear vectors was mixed at a molar ratio of approximately 3:1 and treated with 0.5 U of T5 exonuclease at 0°C for 5 min. Then, the mixture was transformed into Escherichia coli to generate recombinant plasmids. Single segment and multi-segments can be assembled efficiently using TLTC. For single segment, the overall cloning efficiency is above 95%. Moreover, extra nucleotides in the vectors can be removed during TLTC. In conclusion, an extremely simple and fast DNA cloning/assembling method was established in the present study. This method facilitates routine DNA cloning and synthesis of DNA fragments.

10.
Sci Rep ; 13(1): 13014, 2023 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-37563169

RESUMEN

The influence of a single water molecule on the BrO + HO2 hydrogen extraction reaction has been explored by taking advantage of CCSD(T)/aug-cc-pVTZ//B3LYP/6-311 + + G(d,p) method. The reaction in the absence of water have two distinct kinds of H-extraction channels to generate HOBr + O2 (1Δg) and HBr + O3, and the channel of generation of HOBr + O2 (1Δg) dominated the BrO + HO2 reaction. The rate coefficient of the most feasible channel for the BrO + HO2 reaction in the absence of water is estimated to be 1.44 × 10-11 cm3 molecule-1 s-1 at 298.15 K, which is consistent with the experiment. The introduction of water made the reaction more complex, but the products are unchanged. Four distinct channels, beginning with HO2…H2O with BrO, H2O…HO2 with BrO, BrO…H2O with HO2, H2O…BrO with HO2 are researched. The most feasible channels, stemming from H2O…HO2 with BrO, and BrO…H2O with HO2, are much slower than the reaction of BrO + HO2 without water, respectively. Thus, the existence of water molecule takes a negative catalytic role for BrO + HO2 reaction.

11.
Acta Biochim Biophys Sin (Shanghai) ; 55(8): 1204-1212, 2023 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-37431184

RESUMEN

Argonaute (Ago) proteins are conserved programmable nucleases present in eukaryotes and prokaryotes and provide defense against mobile genetic elements. Almost all characterized pAgos prefer to cleave DNA targets. Here, we describe a novel pAgo from Verrucomicrobia bacterium (VbAgo) that can specifically cleave RNA targets rather than DNA targets at 37°C and function as a multiple-turnover enzyme showing prominent catalytic capacity. VbAgo utilizes DNA guides (gDNAs) to cleave RNA targets at the canonical cleavage site. Meanwhile, the cleavage activity is remarkably strengthened at low concentrations of NaCl. In addition, VbAgo presents a weak tolerance for mismatches between gDNAs and RNA targets, and single-nucleotide mismatches at positions 11‒12 and dinucleotide mismatches at positions 3‒15 dramatically reduce target cleavage. Moreover, VbAgo can efficiently cleave highly structured RNA targets at 37°C. These properties of VbAgo broaden our understanding of Ago proteins and expand the pAgo-based RNA manipulation toolbox.


Asunto(s)
Bacterias , ADN , Bacterias/genética , ADN/metabolismo , ARN/metabolismo , Endonucleasas/metabolismo , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo
12.
ACS Appl Mater Interfaces ; 15(28): 33744-33750, 2023 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-37431755

RESUMEN

X-ray detectors based on conventional semiconductors with large atomic numbers are suffering from the poor stability under a high dose rate of ionizing irradiation. In this work, we demonstrate that a wide band gap ceramic-boron nitride with small atomic numbers could be used for sensitive X-ray detection. Boron nitride samples showed excellent resistance to ionizing radiation, which have been systematically studied with the neutron- and electron-aging experiments. Then, we fully analyzed the influence of these aging effects on the fundamental properties of boron nitride. Interestingly, we found that the boron nitride samples could maintain relatively good charge transport properties even after large dose of neutron irradiation. The fabricated X-ray detectors showed decent performance metrics, and the neutron-aged boron nitride even showed improved operational stability under continuous X-ray irradiation, suggesting the great potential for real applications.

13.
Angew Chem Int Ed Engl ; 62(33): e202305988, 2023 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-37339945

RESUMEN

Ether solvents with superior reductive stability promise excellent interphasial stability with high-capacity anodes while the limited oxidative resistance hinders their high-voltage operation. Extending the intrinsic electrochemical stability of ether-based electrolytes to construct stable-cycling high-energy-density lithium-ion batteries is challenging but rewarding. Herein, the anion-solvent interactions were concerned as the key point to optimize the anodic stability of the ether-based electrolytes and an optimized interphase was realized on both pure-SiOx anodes and LiNi0.8 Mn0.1 Co0.1 O2 cathodes. Specifically, the small-anion-size LiNO3 and tetrahydrofuran with high dipole moment to dielectric constant ratio realized strengthened anion-solvent interactions, which enhance the oxidative stability of the electrolyte. The designed ether-based electrolyte enabled a stable cycling performance over 500 cycles in pure-SiOx ||LiNi0.8 Mn0.1 Co0.1 O2 full cell, demonstrating its superior practical prospects. This work provides new insight into the design of new electrolytes for emerging high-energy density lithium-ion batteries through the regulation of interactions between species in electrolytes.

14.
ACS Appl Mater Interfaces ; 15(21): 26215-26224, 2023 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-37212392

RESUMEN

Increasing the thickness of a superconducting layer and simultaneously reducing the thickness effect in iron-based superconducting coated conductors are particularly essential for improving the critical current Ic. Here, for the first time, we have deposited high-performance FeSe0.5Te0.5 (FST) superconducting films up to 2 µm on LaMnO3-buffered metal tapes by pulsed laser deposition. An interface engineering strategy, alternating growth of a 10 nm-thick nonsuperconducting FST seed layer and a 400 nm-thick FST superconducting layer, was employed to guarantee the crystalline quality of the films with thicknesses of the order of micrometers, resulting in a highly biaxial texture with grain boundary misorientation angle less than the critical value θc ∼ 9°. Moreover, the thickness effect, that the critical current density (Jc) shows a clear dependence on thickness as in cuprates, is reduced by the interface engineering. Also, the maximum Jc was found for a 400 nm-thick film with 1.3 MA/cm2 in self-field at 4.2 K and 0.71 MA/cm2 (H∥ab) and 0.50 MA/cm2 (H∥c) at 9 T. Anisotropic Ginzburg-Landau scaling indicates that the major pinning centers vary from correlated to uncorrelated as the film thickness increases, while the thickness effect is most likely related to the weakening of flux pinning by the fluctuation of charge-carrier mean free path (δl) and strengthening of flux pinning caused by the variation of superconducting transition temperature (δTc) due to off-stoichiometry with thickness.

15.
J Mol Graph Model ; 122: 108489, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37084667

RESUMEN

The mechanism and dynamics of CHF2CF2OCHF2 initiated by OH radical evaluated through the density functional theory and variflex code. The solvation pattern of PCM was utilized to analyze the influence of water on the CHF2CF2OCHF2 + OH reaction. The most feasible reaction channel is resulting in the product CF2CF2OCHF2 with H2O by hydrogen abstraction. The computed rate coefficient is consistent with the experimental data. The results turned out that aqueous water act as a disincentive to the title reaction. In the atmosphere, the computation results testified that OH, H2O, NH3 and HCOOH could not accelerate the degradation of the CHF2CF2OCHF2 through OH-initiated in view of the Gibbs free barriers. The research of the follow-up oxidation procedure of the products CHF2CF2OCF2 and CF2CF2OCHF2 with O2/NO reactions indicated that CF2O and CHF2 were the most feasible products. The atmospheric lifetimes of CHF2CF2OCHF2 were in the scope of 71.10-4.74 years in altitude of 0-12 km and at 200-300 K. This research supplies discernment into the conversion of CHF2CF2OCHF2 in a complex environment.


Asunto(s)
Atmósfera , Agua , Cinética , Oxidación-Reducción , Radical Hidroxilo
16.
Molecules ; 28(4)2023 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-36838747

RESUMEN

Composite ceramics of metal oxides and noble metals have received much attention for sensing reducing gases at room temperature. Presently, composite ceramics of SnO2 and noble metals have been prepared and investigated for sensing oxidizing NO2 at room temperature. While dramatic increases in resistance were observed for both 1 wt% Pt-SnO2 and 5 wt% Au-SnO2 composite nanoceramics after being exposed to NO2 at room temperature, the largest increase in resistance was observed for 1 wt% Pt-5 wt% -Au-SnO2 composite nanoceramics among the three composites. The response to 0.5 ppm NO2--20% O2-N2 was as high as 875 at room temperature, with a response time of 2566 s and a recovery time of 450 s in the air of 50% relative humidity (RH). Further investigation revealed that water molecules in the air are essential for recovering the resistance of Pt-Au-SnO2 composite nanoceramics. A room temperature NO2-sensing mechanism has been established, in which NO2 molecules are catalyzed by Pt-Au to be chemisorbed on SnO2 at room temperature, and desorbed from SnO2 by the attraction of water molecules in the air. These results suggest that composite ceramics of metal oxides and noble metals should be promising for room temperature sensing, not only reducing gases, but also oxidizing gases.


Asunto(s)
Cerámica , Dióxido de Nitrógeno , Temperatura , Gases , Óxidos
17.
Int J Mol Sci ; 24(4)2023 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-36835573

RESUMEN

Cytochrome P450 monooxygenases (CYPs/P450s) and their redox partners, ferredoxins, are ubiquitous in organisms. P450s have been studied in biology for over six decades owing to their distinct catalytic activities, including their role in drug metabolism. Ferredoxins are ancient proteins involved in oxidation-reduction reactions, such as transferring electrons to P450s. The evolution and diversification of P450s in various organisms have received little attention and no information is available for archaea. This study is aimed at addressing this research gap. Genome-wide analysis revealed 1204 P450s belonging to 34 P450 families and 112 P450 subfamilies, where some families and subfamilies are expanded in archaea. We also identified 353 ferredoxins belonging to the four types 2Fe-2S, 3Fe-4S, 7Fe-4S and 2[4Fe-4S] in 40 archaeal species. We found that bacteria and archaea shared the CYP109, CYP147 and CYP197 families, as well as several ferredoxin subtypes, and that these genes are co-present on archaeal plasmids and chromosomes, implying the plasmid-mediated lateral transfer of these genes from bacteria to archaea. The absence of ferredoxins and ferredoxin reductases in the P450 operons suggests that the lateral transfer of these genes is independent. We present different scenarios for the evolution and diversification of P450s and ferredoxins in archaea. Based on the phylogenetic analysis and high affinity to diverged P450s, we propose that archaeal P450s could have diverged from CYP109, CYP147 and CYP197. Based on this study's results, we propose that all archaeal P450s are bacterial in origin and that the original archaea had no P450s.


Asunto(s)
Archaea , Ferredoxinas , Humanos , Ferredoxinas/metabolismo , Archaea/metabolismo , Filogenia , Oxidación-Reducción , Sistema Enzimático del Citocromo P-450/metabolismo , Bacterias/metabolismo
18.
Int J Mol Sci ; 24(2)2023 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-36675019

RESUMEN

Erinacine A (EA), a natural neuroprotectant, is isolated from a Chinese herbal medicine, Hericium erinaceus. The aim of this study was to investigate the neuroprotective effects of EA in a rat model of traumatic optic neuropathy. The optic nerves (ONs) of adult male Wistar rats were crushed using a standardized method and divided into three experimental groups: phosphate-buffered saline (PBS control)-treated group, standard EA dose-treated group (2.64 mg/kg in 0.5 mL of PBS), and double EA dose-treated group (5.28 mg/kg in 0.5 mL of PBS). After ON crush, each group was fed orally every day for 14 days before being euthanized. The visual function, retinal ganglion cell (RGC) density, and RGC apoptosis were determined using flash visual-evoked potentials (fVEP) analysis, retrograde Fluoro-Gold labelling, and TdT-dUTP nick end-labelling (TUNEL) assay, respectively. Macrophage infiltration of ON was detected by immunostaining (immunohistochemistry) for ED1. The protein levels of phosphor-receptor-interacting serine/threonine-protein kinase1 (pRIP1), caspase 8 (Cas8), cleaved caspase 3 (cCas3), tumour necrosis factor (TNF)-α, tumour necrosis factor receptor1 (TNFR1), interleukin (IL)-1ß, inducible nitric oxide synthase (iNOS), nuclear factor erythroid 2-related factor 2 (Nrf2), haem oxygenase-1 (HO-1), and superoxide dismutase 1 (SOD1) were evaluated by Western blotting. When comparing the standard EA dose-treated group and the double EA dose-treated group with the PBS-treated group, fVEP analysis showed that the amplitudes of P1−N2 in the standard EA dose group and the double EA dose-treated group were 1.8 and 2.4-fold, respectively, higher than that in the PBS-treated group (p < 0.05). The density of RGC in the standard EA dose-treated group and the double EA dose-treated group were 2.3 and 3.7-fold, respectively, higher than that in the PBS-treated group (p < 0.05). The TUNEL assay showed that the standard EA dose-treated group and the double EA dose-treated group had significantly reduced numbers of apoptotic RGC by 10.0 and 15.6-fold, respectively, compared with the PBS-treated group (p < 0.05). The numbers of macrophages on ON were reduced by 1.8 and 2.2-fold in the standard EA dose-treated group and the double EA dose-treated group, respectively (p < 0.01). On the retinal samples, the levels of pRIP, Cas8, cCas3, TNF-α, TNFR1, IL-1ß, and iNOS were decreased, whereas those of Nrf2, HO-1, and SOD1 were increased in both EA-treated groups compared to those in the PBS-treated group (p < 0.05). EA treatment has neuroprotective effects on an experimental model of traumatic optic neuropathy by suppressing apoptosis, neuroinflammation, and oxidative stress to protect the RGCs from death as well as preserving the visual function.


Asunto(s)
Fármacos Neuroprotectores , Traumatismos del Nervio Óptico , Ratas , Masculino , Animales , Traumatismos del Nervio Óptico/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Ratas Wistar , Factor 2 Relacionado con NF-E2 , Receptores Tipo I de Factores de Necrosis Tumoral , Superóxido Dismutasa-1 , Apoptosis , Factor de Necrosis Tumoral alfa/farmacología , Modelos Teóricos , Modelos Animales de Enfermedad
19.
Elife ; 122023 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-36655976

RESUMEN

A defining feature of successful vaccination is the ability to induce long-lived antigen-specific memory cells. T follicular helper (Tfh) cells specialize in providing help to B cells in mounting protective humoral immunity in infection and after vaccination. Memory Tfh cells that retain the CXCR5 expression can confer protection through enhancing humoral response upon antigen re-exposure but how they are maintained is poorly understood. CXCR5+ memory Tfh cells in human blood are divided into Tfh1, Tfh2, and Tfh17 cells by the expression of chemokine receptors CXCR3 and CCR6 associated with Th1 and Th17, respectively. Here, we developed a new method to induce Tfh1, Tfh2, and Tfh17-like (iTfh1, iTfh2, and iTfh17) mouse cells in vitro. Although all three iTfh subsets efficiently support antibody responses in recipient mice with immediate immunization, iTfh17 cells are superior to iTfh1 and iTfh2 cells in supporting antibody response to a later immunization after extended resting in vivo to mimic memory maintenance. Notably, the counterpart human Tfh17 cells are selectively enriched in CCR7+ central memory Tfh cells with survival and proliferative advantages. Furthermore, the analysis of multiple human cohorts that received different vaccines for HBV, influenza virus, tetanus toxin or measles revealed that vaccine-specific Tfh17 cells outcompete Tfh1 or Tfh2 cells for the persistence in memory phase. Therefore, the complementary mouse and human results showing the advantage of Tfh17 cells in maintenance and memory function supports the notion that Tfh17-induced immunization might be preferable in vaccine development to confer long-term protection.


Asunto(s)
Memoria Inmunológica , Células T Auxiliares Foliculares , Humanos , Animales , Ratones , Células Th17/metabolismo , Linfocitos B , Linfocitos T Colaboradores-Inductores
20.
Angew Chem Int Ed Engl ; 62(4): e202216354, 2023 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-36440597

RESUMEN

The interfacial stability is highly responsible for the longevity and safety of sodium ion batteries (SIBs). However, the continuous solid-electrolyte interphase(SEI) growth would deteriorate its stability. Essentially, the SEI growth is associated with the electron leakage behavior, yet few efforts have tried to suppress the SEI growth, from the perspective of mitigating electron leakage. Herein, we built two kinds of SEI layers with distinct growth behaviors, via the additive strategy. The SEI physicochemical features (morphology and componential information) and SEI electronic properties (LUMO level, band gap, electron work function) were investigated elaborately. Experimental and calculational analyses showed that, the SEI layer with suppressed growth delivers both the low electron driving force and the high electron insulation ability. Thus, the electron leakage is mitigated, which restrains the continuous SEI growth, and favors the interface stability with enhanced electrochemical performance.

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