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1.
EMBO J ; 39(22): e104748, 2020 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-33058207

RESUMEN

Programmable A > I RNA editing is a valuable tool for basic research and medicine. A variety of editors have been created, but a genetically encoded editor that is both precise and efficient has not been described to date. The trade-off between precision and efficiency is exemplified in the state of the art editor REPAIR, which comprises the ADAR2 deaminase domain fused to dCas13b. REPAIR is highly efficient, but also causes significant off-target effects. Mutations that weaken the deaminase domain can minimize the undesirable effects, but this comes at the expense of on-target editing efficiency. We have now overcome this dilemma by using a multipronged approach: We have chosen an alternative Cas protein (CasRx), inserted the deaminase domain into the middle of CasRx, and redirected the editor to the nucleus. The new editor created, dubbed REPAIRx, is precise yet highly efficient, outperforming various previous versions on both mRNA and nuclear RNA targets. Thus, REPAIRx markedly expands the RNA editing toolkit and illustrates a novel strategy for base editor optimization.


Asunto(s)
Edición Génica/métodos , Edición de ARN , ARN/metabolismo , Adenosina Desaminasa/genética , Células HEK293 , Humanos , Mutación , Proteínas de Unión al ARN/genética , Transcriptoma
2.
EMBO J ; 39(22): e104741, 2020 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-33058229

RESUMEN

Programmable RNA cytidine deamination has recently been achieved using a bifunctional editor (RESCUE-S) capable of deaminating both adenine and cysteine. Here, we report the development of "CURE", the first cytidine-specific C-to-U RNA Editor. CURE comprises the cytidine deaminase enzyme APOBEC3A fused to dCas13 and acts in conjunction with unconventional guide RNAs (gRNAs) designed to induce loops at the target sites. Importantly, CURE does not deaminate adenosine, enabling the high-specificity versions of CURE to create fewer missense mutations than RESCUE-S at the off-targets transcriptome-wide. The two editing approaches exhibit overlapping editing motif preferences, with CURE and RESCUE-S being uniquely able to edit UCC and AC motifs, respectively, while they outperform each other at different subsets of the UC targets. Finally, a nuclear-localized version of CURE, but not that of RESCUE-S, can efficiently edit nuclear RNAs. Thus, CURE and RESCUE are distinct in design and complementary in utility.


Asunto(s)
Citidina Desaminasa/genética , Proteínas/genética , Edición de ARN , Núcleo Celular/metabolismo , Células HEK293 , Humanos , ARN/química , ARN/metabolismo , ARN Guía de Kinetoplastida , Transcriptoma
4.
Mol Ther Nucleic Acids ; 35(2): 102190, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38721279

RESUMEN

RNA base editors should ideally be free of immunogenicity, compact, efficient, and specific, which has not been achieved for C > U editing. Here we first describe a compact C > U editor entirely of human origin, created by fusing the human C > U editing enzyme RESCUE-S to Cas inspired RNA targeting system (CIRTS), a tiny, human-originated programmable RNA-binding domain. This editor, CIRTS-RESCUEv1 (V1), was inefficient. Remarkably, a short histidine-rich domain (HRD), which is derived from the internal disordered region (IDR) in the human CYCT1, a protein capable of liquid-liquid phase separation (LLPS), enhanced V1 editing at on-targets as well as off-targets, the latter effect being minor. The V1-HRD fusion protein formed puncta characteristic of LLPS, and various other IDRs (but not an LLPS-impaired mutant) could replace HRD to effectively induce puncta and potentiate V1, suggesting that the diverse domains acted via a common, LLPS-based mechanism. Importantly, the HRD fusion strategy was applicable to various other types of C > U RNA editors. Our study expands the RNA editing toolbox and showcases a general method for stimulating C > U RNA base editors.

5.
Vet Res Commun ; 47(4): 2357-2362, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37458877

RESUMEN

Blastocystis is a common enteric protist infecting humans, domestic animals, and wildlife worldwide. However, data on the prevalence and subtype diversity of Blastocystis in free-living wild birds in urban districts are rare. In this study, a total of 138 fresh fecal samples from free-living wild birds were collected from three universities and three communities in Xinxiang, China, to explore the infection rate, Blastocystis subtypes present and zoonotic potential of this protist. Blastocystis presence was determined with nested-PCR amplification based on the partial small ribosomal subunit (SSU rRNA) gene. Presence was detected from one community (Wupu) at an overall rate of 1.5% (2/136). Further DNA sequencing and phylogenetic analyses identified two ruminant-associated subtypes, ST10 (n = 1) and ST24 (n = 1), implying a cross-species transmission of Blastocystis from ruminants. This is the first report on the infection of ST10 and ST24 in free-living wild birds in an urban area in China. As potentially zoonotic subtypes, the occurrence of ST10 and ST24 suggests that these free-living birds could play a role in spreading Blastocystis to humans in Xinxiang.


Asunto(s)
Infecciones por Blastocystis , Blastocystis , Humanos , Animales , Blastocystis/genética , Infecciones por Blastocystis/epidemiología , Infecciones por Blastocystis/veterinaria , Animales Salvajes , Filogenia , China/epidemiología , Prevalencia , Aves , Heces , Variación Genética
6.
ACS Nano ; 16(10): 15586-15626, 2022 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-36226846

RESUMEN

Benefiting from the inherent properties of ultralight weight, ultrahigh porosity, ultrahigh specific surface area, adjustable thermal/electrical conductivities, and mechanical flexibility, aerogels are considered ideal supporting alternatives to efficiently encapsulate phase change materials (PCMs) and rationalize phase transformation behaviors. The marriage of versatile aerogels and PCMs is a milestone in pioneering advanced multifunctional composite PCMs. Emerging aerogel-based composite PCMs with high energy storage density are accepted as a cutting-edge thermal energy storage (TES) concept, enabling advanced functionality of PCMs. Considering the lack of a timely and comprehensive review on aerogel-based composite PCMs, herein, we systematically retrospect the state-of-the-art advances of versatile aerogels for high-performance and multifunctional composite PCMs, with particular emphasis on advanced multiple functions, such as acoustic-thermal and solar-thermal-electricity energy conversion strategies, mechanical flexibility, flame retardancy, shape memory, intelligent grippers, and thermal infrared stealth. Emphasis is also given to the versatile roles of different aerogels in composite PCMs and the relationships between their architectures and thermophysical properties. This review also showcases the discovery of an interdisciplinary research field combining aerogels and 3D printing technology, which will contribute to pioneering cutting-edge PCMs. This review aims to arouse wider research interests among interdisciplinary fields and provide insightful guidance for the rational design of advanced multifunctional aerogel-based composite PCMs, thus facilitating the significant breakthroughs in both fundamental research and commercial applications.

7.
J Colloid Interface Sci ; 628(Pt B): 350-358, 2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-35998460

RESUMEN

Transition metal nitrides (TMNs) have been regarded as an excellent class of electrocatalysts for hydrogen evolution reaction (HER), but there is still huge room for improvement. In this work, cobalt nitride (CoNx) coupled with N-doped carbon (NC) and supported by nickel foam (NF) is designed as an efficient HER electrocatalyst (NF/CoNx@NC). The introduction of NC can not only optimize the electronic structure of CoNx to boost the intrinsic activity, but also enhance the electronic conductivity and stability of the catalyst. As a result, NF/CoNx@NC exhibits excellent HER performance. On the one hand, it only needs an overpotential of 69 mV to deliver a current density of 20 mA cm-2 in 1.0 mol/L KOH, far better than that of CoNx (182 mV). On the other hand, the electronic conductivity and stability of the catalyst can be significantly enhanced after the introduction of NC. This work has done successful material design with the goal of enhancing the intrinsic activity, electronic conductivity, and stability, which has certain reference and guiding significance for the design of novel transition metal-based electrocatalysts.

8.
iScience ; 23(10): 101606, 2020 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-33205018

RESUMEN

Efficient thermal energy harvesting using phase change materials (PCMs) has great potential for thermal energy storage and thermal management applications. Benefiting from these merits of pore structure diversity, convenient controllability, and excellent thermophysical stability, SiO2-based composite PCMs have comparatively shown more promising prospect. In this regard, the microstructure-thermal property correlation of SiO2-based composite PCMs is still unclear despite the significant achievements in structural design. To enrich the fundamental understanding on the correlations between the microstructure and the thermal properties, we systematically summarize the state-of-the-art advances in SiO2-based composite PCMs for tuning thermal energy storage from the perspective of tailoring chemistry strategies. In this review, the tailoring chemistry influences of surface functional groups, pore sizes, dopants, single shell, and hybrid shells on the thermal properties of SiO2-based composite PCMs are systematically summarized and discussed. This review aims to provide in-depth insights into the correlation between structural designs and thermal properties, thus showing better guides on the tailor-made construction of high-performance SiO2-based composite PCMs. Finally, the current challenges and future recommendations for the tailoring chemistry are also highlighted.

9.
ACS Appl Mater Interfaces ; 12(43): 48495-48510, 2020 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-33050703

RESUMEN

The development of highly efficient and low-cost bifunctional noble metal-free electrocatalysts for both the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) is an effective strategy for improving efficiency. Herein, novel three-dimensional (3D) bimetallic metal-organic frameworks containing Ni and V with adjustable stoichiometry were synthesized on nickel foam successfully. Notably, Ni2V-MOFs@NF only require rather low overpotentials of 244 and 89 mV for the OER and HER, respectively, and expedites overall water splitting with 1.55 V at 10 mA cm-2 with robust durability during the 80 h test. The high efficiency of the novel obtained electrocatalysts should be attributed to the particular morphological design of the two-dimensional (2D) ultrathin nanosheets self-assembling into a 3D nanoflower and the electronic structure regulation resulting from the synergetic interaction between nickel and vanadium. Subsequent theoretical calculations reveal the following conclusions: (I) the exceptional electronic conductivity of Ni2V-MOFs shows enhanced optimization as a result of electronic structure reconstruction, (II) the energy barrier reduction of the rate-limiting step is responsible for the enhanced dynamics of Ni2V-MOFs for the OER, and (III) the facilitation of the adsorption of H+ and H2O plays a key role in progressing the HER catalytic activity of Ni2V-MOFs.

10.
Rev Sci Instrum ; 84(4): 045101, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23635226

RESUMEN

In order to reduce the volume of exploding initiator system, a metal foil spark gap switch was designed and fabricated using magnetron sputter deposition and standard microelectronic technology. The switch constitutes of two main electrodes and a trigger electrode, and stylus profiler was employed to ascertain dimension of the switch. We discussed the discharge characterization of the metal foil spark gap switch under nitrogen atmosphere and at pressure of 0.5 bars, 0.75 bars, 1.0 bar, 1.25 bars, 1.5 bars, and 1.75 bars, respectively. The relationship between self-breakdown voltage of the switch and pressure times distance corresponds to linearity. The switch had short delay time and low time jitter when the operating voltage was between 70% and 90% of its self-breakdown voltage. Compared with a commercial stereo spark gap switch, when it was fired by a conventional capacitive discharge unit, the firing circuit had lower inductance and higher resistance.

11.
Rev Sci Instrum ; 84(6): 066105, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23822392

RESUMEN

The main influence factors of exploding bridge foil were studied in order to improve energy utilization of the explosion foil initiator. "Square" and "curving" shaped bridge foils were fabricated using magnetron sputtering and chemical etching techniques, and the key dimension of the bridge foil was measured using surface profiler. Commercial software MATLAB was employed to calculate the burst current, burst voltage, and energy deposition. Simulation results were in good agreement with experiment data. In this study, the energy deposition ratio of "square" shaped bridge is between 45%-50%, while the value of "curving" shaped bridge is between 55%-75%.

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