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1.
Cell ; 187(15): 3936-3952.e19, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38936359

RESUMO

Duplication is a foundation of molecular evolution and a driver of genomic and complex diseases. Here, we develop a genome editing tool named Amplification Editing (AE) that enables programmable DNA duplication with precision at chromosomal scale. AE can duplicate human genomes ranging from 20 bp to 100 Mb, a size comparable to human chromosomes. AE exhibits activity across various cell types, encompassing diploid, haploid, and primary cells. AE exhibited up to 73.0% efficiency for 1 Mb and 3.4% for 100 Mb duplications, respectively. Whole-genome sequencing and deep sequencing of the junctions of edited sequences confirm the precision of duplication. AE can create chromosomal microduplications within disease-relevant regions in embryonic stem cells, indicating its potential for generating cellular and animal models. AE is a precise and efficient tool for chromosomal engineering and DNA duplication, broadening the landscape of precision genome editing from an individual genetic locus to the chromosomal scale.


Assuntos
Duplicação Gênica , Edição de Genes , Genoma Humano , Humanos , Edição de Genes/métodos , Sistemas CRISPR-Cas/genética , DNA/genética , Animais , Células-Tronco Embrionárias/metabolismo , Cromossomos Humanos/genética
2.
Mol Cell ; 82(21): 4160-4175.e6, 2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36272409

RESUMO

CRISPR-Cas9-mediated genome editing depends on PAM recognition to initiate DNA unwinding. PAM mutations can abolish Cas9 binding and prohibit editing. Here, we identified a Cas9 from the thermophile Alicyclobacillus tengchongensis for which the PAM interaction can be robustly regulated by DNA topology. AtCas9 has a relaxed PAM of N4CNNN and N4RNNA (R = A/G) and is able to bind but not cleave targets with mutated PAMs. When PAM-mutated DNA was in underwound topology, AtCas9 exhibited enhanced binding affinity and high cleavage activity. Mechanistically, AtCas9 has a unique loop motif, which docked into the DNA major groove, and this interaction can be regulated by DNA topology. More importantly, AtCas9 showed near-PAMless editing of supercoiled plasmid in E. coli. In mammalian cells, AtCas9 exhibited broad PAM preference to edit plasmid with up to 72% efficiency and effective base editing at four endogenous loci, representing a potentially powerful tool for near-PAMless editing.


Assuntos
Sistemas CRISPR-Cas , Escherichia coli , Animais , Escherichia coli/genética , Escherichia coli/metabolismo , Edição de Genes , DNA/genética , Plasmídeos , Mamíferos/metabolismo
3.
Small ; 20(37): e2401565, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38745539

RESUMO

Stretchable strain sensors play a crucial role in intelligent wearable systems, serving as the interface between humans and environment by translating mechanical strains into electrical signals. Traditional fiber strain sensors with intrinsic uniform axial strain distribution face challenges in achieving high sensitivity and anisotropy. Moreover, existing micro/nano-structure designs often compromise stretchability and durability. To address these challenges, a novel approach of using 3D printing to fabricate MXene-based flexible sensors with tunable micro and macrostructures.  Poly(tetrafluoroethylene) (PTFE) as a pore-inducing agent is added into 3D printable inks to achieve controllable microstructural modifications. In addition to microstructure tuning, 3D printing is employed for macrostructural design modifications, guided by finite element modeling (FEM) simulations. As a result, the 3D printed sensors exhibit heightened sensitivity and anisotropy, making them suitable for tracking static and dynamic displacement changes. The proposed approach presents an efficient and economically viable solution for standardized large-scale production of advanced wire strain sensors.

4.
Small ; 20(15): e2307736, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38009506

RESUMO

Herein, a drug-loading nanosystem that can in situ form drug depository for persistent antitumor chemotherapy and immune regulation is designed and built. The system (DOX@MIL-LOX@AL) is fabricated by packaging alginate on the surface of Doxorubicin (DOX) and lactate oxidase (LOX) loaded MIL-101(Fe)-NH2 nanoparticle, which can easily aggregate in the tumor microenvironment through the cross-linking with intratumoral Ca2+. Benefiting from the tumor retention ability, the fast-formed drug depository will continuously release DOX and Fe ions through the ATP-triggered slow degradation, thus realizing persistent antitumor chemotherapy and immune regulation. Meanwhile, LOX in the non-aggregated nanoparticles is able to convert the lactic acid to H2O2, which will be subsequently decomposed into ·OH by Fe ions to further enhance the DOX-induced immunogenic death effect of tumor cells. Together, with the effective consumption of immunosuppressive lactic acid, long-term chemotherapy, and oxidation therapy, DOX@MIL-LOX@AL can execute high-performance antitumor chemotherapy and immune activation with only one subcutaneous administration.


Assuntos
Nanopartículas , Microambiente Tumoral , Peróxido de Hidrogênio , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Portadores de Fármacos/farmacologia , Ácido Láctico , Linhagem Celular Tumoral
5.
Small ; 20(35): e2301074, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38659180

RESUMO

The coating of filter media with silver is typically achieved by chemical deposition and aerosol processes. Whilst useful, such approaches struggle to provide uniform coating and are prone to blockage. To address these issues, an in situ method for coating glass fibers is presented via the dopamine-mediated electroless metallization method, yielding filters with low air resistance and excellent antibacterial performance. It is found that the filtration efficiency of the filters is between 94 and 97% and much higher than that of silver-coated filters produced using conventional dipping methods (85%). Additionally, measured pressure drops ranged between 100 and 150 Pa, which are lower than those associated with dipped filters (171.1 Pa). Survival rates of Escherichia coli and Bacillus subtilis bacteria exposed to the filters decreased to 0 and 15.7%±1.49, respectively after 2 h, with no bacteria surviving after 6 h. In contrast, survival rates of E. coli and B. subtilis bacteria on the uncoated filters are 92.5% and 89.5% after 6 h. Taken together, these results confirm that the in situ deposition of silver onto fiber surfaces effectively reduces pore clogging, yielding low air resistance filters that can be applied for microbial filtration and inhibition in a range of environments.


Assuntos
Antibacterianos , Bacillus subtilis , Dopamina , Escherichia coli , Vidro , Prata , Prata/química , Prata/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Vidro/química , Dopamina/química , Dopamina/farmacologia , Escherichia coli/efeitos dos fármacos , Bacillus subtilis/efeitos dos fármacos , Filtração/métodos
6.
Inorg Chem ; 63(19): 8977-8987, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38690714

RESUMO

Integration of hydrogen evolution with the oxidation of organic substances in one electrochemical system is highly desirable. However, achieving selective oxidation of organic substances in the integrated system is still highly challenging. In this study, a phosphorylated NiMoO4 nanoneedle-like array was designed as the catalytic active electrode for the integration of highly selective electrochemical dehydrogenation of tetrahydroisoquinolines (THIQs) with hydrogen production. The leaching of anions, including MoO42- and PO43-, facilitates the reconstruction of the catalyst. As a result, nickel oxyhydroxides with the doping of PO43- and richness of defects are in situ formed. In situ Raman and density functional theory calculations have shown that the high catalytic activity is attributed to the in situ formed PO43- involved NiOOH substance. In the dehydrogenation process, the involved C-H bond but not the N-H bond is first destroyed. A two-electrode system was then fabricated with the optimized electrode that shows a benchmark current density of 10 mA cm-2 at 1.783 V, providing a yield of 70% for dihydroisoquinolines. A robust stability was also shown for this integrated electrochemical system. The understanding of the reconstruction behavior and the achievement of selective dehydrogenation will provide some hints for electrochemical synthesis.

7.
Angew Chem Int Ed Engl ; 63(18): e202401903, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38380841

RESUMO

In this study, we introduce a novel approach for synthesizing two-dimensional (2D) MXene heterostructures featuring a sandwiched and cross-linked network structure. This method addresses the common issue of activity degradation in 2D nanomaterials caused by inevitable aggregation. By utilizing the distinct surface characteristics of MXene, we successfully induced the growth of various 2D nanomaterials on MXene substrates. This strategy effectively mitigates self-stacking defects and augments the exposure of surface areas. In particular, the obtained 2D-2D MXene@NiCo-layered double hydroxide (MH-NiCo) heterostructures exhibit enhanced structural stability, improved chemical reversibility, and heightened charge transfer efficiency, outperforming pure NiCo LDH. The aqueous MH-Ni4Co1//Zn@carbon cloth (MH-Ni4Co1//Zn@CC) battery demonstrates exceptional performance with a remarkable specific capacity of 0.61 mAh cm-2, maintaining 96.6 % capacitance after 2300 cycles. Additionally, it achieves an energy density of 1.047 mWh cm-2 and a power density of 32.899 mW cm-2. This research not only paves the way for new design paradigms in energy-related nanomaterials but also offers invaluable insights for the application and optimization of 2D-2D heterostructures in advanced electrochemical devices.

8.
Angew Chem Int Ed Engl ; : e202414650, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39206502

RESUMO

Investigating the formation and transformation mechanisms of spiral-concave crystals holds significant potential for advancing innovative material design and comprehension. We examined the kinetics-controlled nucleation and growth mechanisms of Prussian Blue crystals with spiral concave structures, and constructed a detailed crystal growth phase diagram. The spiral-concave hexacyanoferrate (SC-HCF) crystals, characterized by high-density surface steps and a low stress-strain architecture, exhibit enhanced activity due to their facile interaction with reactants. Notably, the coordination environment of SC-HCF can be precisely modulated by the introduction of diverse metals. Utilizing X-ray absorption fine structure spectroscopy and in situ ultraviolet-visible spectroscopy, we elucidated the formation mechanism of SC-HCF to Co-HCF facilitated by oriented adsorption-ion exchange (OA-IE) process. Both experimental data, and density functional theory confirm that Co-HCF possesses an optimized energy band structure, capable of adjusting the local electronic environment and enhancing the performance of the oxygen evolution reaction. This work not only elucidates the formation mechanism and coordination regulation for rich steps HCF, but also offers a novel perspective for constructing nanocrystals with intricate spiral-concave structures.

9.
Neurobiol Learn Mem ; 203: 107791, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37380098

RESUMO

Learning and memory impairment is commonly noted in Alzheimer's disease (AD), which is regarded as a progressive synaptic failure disease. Exercise is a nonpharmacological strategy that may help prevent cognitive decline and reduce the risk of AD, which is usually thought to be related to synaptic damage in the hippocampus. However, the effects of exercise intensity on hippocampal memory and synaptic function in AD remain unclear. In this study, senescence-accelerated mouse prone-8 (SAMP8) mice were randomly assigned to the control group (Con), low-intensity exercise group (Low), and moderate-intensity exercise group (Mid). Here, we showed that eight weeks of treadmill exercise beginning in four-month-old mice improved spatial memory and recognition memory in six-month-old SAMP8 mice, while the Con group exhibited impaired spatial memory and recognition memory. Treadmill exercise also improved hippocampal neuron morphology in SAMP8 mice. Furthermore, dendritic spine density and the levels of postsynaptic density protein-95 (PSD95) and Synaptophysin (SYN) increased significantly in the Low and Mid groups as compared with the Con group. We further showed that moderate-intensity exercise (60 % of maximum speed) was more efficacious in increasing dendritic spine density、PSD95 and SYN, than low-intensity exercise (40 % of maximum speed). In conclusion, the positive effect of treadmill exercise is closely related to exercise intensity, with moderate-intensity exercise showing the most optimal effects.


Assuntos
Doença de Alzheimer , Memória Espacial , Camundongos , Animais , Envelhecimento/psicologia , Hipocampo , Transtornos da Memória , Proteína 4 Homóloga a Disks-Large , Modelos Animais de Doenças
10.
Cancer Cell Int ; 23(1): 189, 2023 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-37660019

RESUMO

The tumor vasculature was different from the normal vasculature in both function and morphology, which caused hypoxia in the tumor microenvironment (TME). Previous anti-angiogenesis therapy had led to a modest improvement in cancer immunotherapy. However, antiangiogenic therapy only benefitted a few patients and caused many side effects. Therefore, there was still a need to develop a new approach to affect tumor vasculature formation. The CD93 receptor expressed on the surface of vascular endothelial cells (ECs) and its natural ligands, MMRN2 and IGFBP7, were now considered potential targets in the antiangiogenic treatment because recent studies had reported that anti-CD93 could normalize the tumor vasculature without impacting normal blood vessels. Here, we reviewed recent studies on the role of CD93, IGFBP7, and MMRN2 in angiogenesis. We focused on revealing the interaction between IGFBP7-CD93 and MMRN2-CD93 and the signaling cascaded impacted by CD93, IGFBP7, and MMRN2 during the angiogenesis process. We also reviewed retrospective studies on CD93, IGFBP7, and MMRN2 expression and their relationship with clinical factors. In conclusion, CD93 was a promising target for normalizing the tumor vasculature.

11.
Inorg Chem ; 62(42): 17433-17443, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37817640

RESUMO

Oxygen evolution in electrochemical water splitting needs a high overpotential that significantly reduces the energy efficiency. To explore an alternative anodic reaction to promote the production of hydrogen at the other end of water splitting and at the same time to get high-value-added chemicals is highly desirable. Herein, we demonstrate a novel branched porous Ni3N catalyst that is prepared for dehydrogenation of tetrahydroisoquinoline, which acts as an anodic oxidation reaction to promote H2 formation on the other end. Interestingly, the Ni3N catalytic electrode can induce effective semidehydrogenation with the selective formation of dihydroisoquinoline, which is difficult to be obtained by the usual direct synthesis route. The catalytic electrode exhibits a low potential of 1.55 V (vs RHE) for a catalytic current density of 61 mA cm-2 with dehydrogenation of tetrahydroisoquinoline and hydrogen production. In situ Raman spectra studies suggest that NiOOH is formed on the electrode surface, which mediates the oxidation semidehydrogenation process. This work also provides a strategy to fabricate nitride materials for applications beyond selective semidehydrogenation of tetrahydroisoquinoline.

12.
Nanotechnology ; 34(50)2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37812619

RESUMO

Temporal information processing is critical for a wide spectrum of applications, such as finance, biomedicine, and engineering. Reservoir computing (RC) can efficiently process temporal information with low training costs. Various memristors have been explored to demonstrate RC systems leveraging the short-term memory and nonlinear dynamic behaviours. However, the short-term memory is fixed after the device fabrication, limiting the applications to diverse temporal analysis tasks. In this work, we propose the approaches to modulating the short-term memory of Pt/SiOx:Ag/Pt memristor for the performance improvement of the RC systems. By controlling the read voltage, pulse amplitude and pulse width applied to the devices, the obtainable range of the characteristic time reaches three orders of magnitude from microseconds to around milliseconds. Based on the fabricated memristor, the classification of 4-bit pulse streams is demonstrated. Memristor-based RC systems with adjustable short-term memory are constructed for time-series prediction and pattern recognition tasks with different requirements for the characteristic times. The simulation results show that low normalized root mean square error of 0.003 (0.27) in Hénon map (Mackey-Glass time series) and excellent classification accuracy of 99.6% (91.7%) in spoken-digit recognition (MNIST image recognition) are achieved, which outperforms most memristor-based RC systems recently reported. Furthermore, the RC networks with diverse short-term memories are constructed to address more complicated tasks with low prediction errors. This work proves the high controllability of memristor-based RC systems to handle multiple temporal processing tasks.

13.
BMC Surg ; 23(1): 131, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37194000

RESUMO

BACKGROUND: To explore the clinical prognostic utility of the preoperative cholesterol-to-lymphocyte ratio (CLR) in outcomes for colorectal cancer liver metastasis (CRLM) patients receiving simultaneous resection of the primary lesion and liver metastases. METHODS: A total of 444 CRLM patients receiving simultaneous resections were enrolled. The optimal cut-off value for CLR was determined using the highest Youden's index. Patients were divided into the CLR < 3.06 group and the CLR≥3.06 group. Propensity score matching analysis (PSM) and the inverse probability of treatment weighting (IPTW) method were conducted to eliminate bias between the two groups. The outcomes included short-term outcomes and long-term outcomes. Kaplan-Meier curves and log-rank tests were used to analyse progression-free survival (PFS) and overall survival (OS). RESULTS: In the short-term outcome analysis, after 1:1 PSM, 137 patients were distributed to the CLR < 3.06 group and CLR≥3.06 group. No significant difference was noted between the two groups (P > 0.1). Compared with patients with CLR < 3.06, patients with CLR≥3.06 had comparable operation times (320.0 [272.5-421.0] vs. 360.0 [292.5-434.5], P = 0.088), blood loss (200.0 [100.0-400.0] vs. 200.0 [150.0-450.0], P = 0.831), postoperative complication rates (50.4% vs. 46.7%, P = 0.546) and postoperative ICU rates (5.8% vs. 11.7%, P = 0.087). In the long-term outcome analysis, Kaplan-Meier analysis showed that compared with patients with CLR < 3.06, patients with CLR≥3.06 had worse PFS (P = 0.005, median: 10.2 months vs. 13.0 months) and OS (P = 0.002, median: 41.0 months vs. 70.9 months). IPTW-adjusted Kaplan-Meier analysis showed that the CLR≥3.06 group had worse PFS (P = 0.027) and OS (P = 0.010) than the CLR < 3.06 group. In the IPTW-adjusted Cox proportional hazards regression analysis, CLR≥3.06 was an independent factor for PFS (HR = 1.376, 95% CI 1.097-1.726, P = 0.006) and OS (HR = 1.723, 95% CI 1.218-2.439, P = 0.002). IPTW-adjusted Cox proportional hazards regression analysis including postoperative complications, operation time, intraoperative blood loss, intraoperative blood transfusion and postoperative chemotherapy revealed that CLR≥3.06 was an independent factor for PFS (HR = 1.617, 95% CI 1.252-2.090, P < 0.001) and OS (HR = 1.823, 95% CI 1.258-2.643, P = 0.002). CONCLUSIONS: The preoperative CLR level predicts unfavourable outcomes in CRLM patients receiving simultaneous resection of the primary lesion and liver metastases and should be taken into consideration when developing treatment and monitoring strategies.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Estudos Retrospectivos , Neoplasias Colorretais/patologia , Hepatectomia/métodos , Prognóstico , Linfócitos/patologia , Complicações Pós-Operatórias/etiologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/secundário
14.
Chem Soc Rev ; 51(8): 2972-2990, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35225307

RESUMO

2D carbides and nitrides of transition metals, also known as MXenes, are an emerging class of 2D nanomaterials that have shown excellent performances and broad application prospects in the fields of energy storage, catalysis, sensing, electromagnetic shielding, electronics and photonics, and life sciences. This unusual diversity of applications is due to their superior hydrophilicity and conductivity, high carrier concentration, ultra-high volumetric capacitance, rich surface chemistry, and large specific surface area. However, it is difficult to make MXenes with the desired surface functional groups that deliver high reactivity and high stability, because most MXenes are extracted from ceramics (MAX phase) by an etching process, where a large number of metal atoms are inevitably exposed on the surface, with other anions and cations embedded uncontrollably. The exposed metal atoms and implanted ions are thermodynamically unstable and readily react with trace oxygen or oxygen-containing groups to form the corresponding metal oxides or degrade chemically, resulting in a sharp decline in activity and loss of excellent physicochemical properties. The addition of certain synergistic additives during the intercalation and chemical modification of surface functional groups under non-hazardous conditions can result in stable and efficient MXene-based materials with exceptional optical, electrical, and magnetic properties. This review discusses several such methods, mainly additive-mediated intercalation and chemical modification of the surface functional groups of MXene-based materials, followed by their potential applications. Finally, perspectives are given to discuss the future challenges and promising opportunities of this exciting field.

15.
Chem Soc Rev ; 51(8): 3314, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35293418

RESUMO

Correction for 'Additive-mediated intercalation and surface modification of MXenes' by Jing Zou et al., Chem. Soc. Rev., 2022, DOI: 10.1039/d0cs01487g.

16.
Angew Chem Int Ed Engl ; 62(5): e202216089, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36409041

RESUMO

Vanadium-based oxides with high theoretical specific capacities and open crystal structures are promising cathodes for aqueous zinc-ion batteries (AZIBs). In this work, the confined synthesis can insert metal ions into the interlayer spacing of layered vanadium oxide nanobelts without changing the original morphology. Furthermore, we obtain a series of nanomaterials based on metal-confined nanobelts, and describe the effect of interlayer spacing on the electrochemical performance. The electrochemical properties of the obtained Al2.65 V6 O13 ⋅ 2.07H2 O as cathodes for AZIBs are remarkably improved with a high initial capacity of 571.7 mAh ⋅ g-1 at 1.0 A g-1 . Even at a high current density of 5.0 A g-1 , the initial capacity can still reach 205.7 mAh g-1 , with a high capacity retention of 89.2 % after 2000 cycles. This study demonstrates that nanobelts confined with metal ions can significantly improve energy storage applications, revealing new avenues for enhancing the electrochemical performance of AZIBs.

17.
Small ; 18(47): e2204888, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36228091

RESUMO

Aqueous ammonium-ion storage has been considered a promising energy storage competitor to meet the requirements of safety, affordability, and sustainability. However, ammonium-ion storage is still in its infancy in the absence of reliable electrode materials. Here, defective VO2 (d-VO) is employed as an anode material for ammonium-ion batteries with a moderate transport pathway and high reversible capacity of ≈200 mAh g-1 . Notably, an anisotropic or anisotropic behavior of structural change of d-VO between c-axis and ab planes depends on the state of charge (SOC). Compared with potassium-ion storage, ammonium-ion storage delivers a higher diffusion coefficient and better electrochemical performance. A full cell is further fabricated by d-VO anode and MnO2 cathode, which delivers a high energy density of 96 Wh kg-1 (based on the mass of VO2 ), and a peak energy density of 3254 W kg-1 . In addition, capacity retention of 70% can be obtained after 10 000 cycles at a current density of 1 A g-1 . What's more, the resultant quasi-solid-state MnO2 //d-VO full cell based on hydrogel electrolyte also delivers high safety and decent electrochemical performance. This work will broaden the potential applications of the ammonium-ion battery for sustainable energy storage.

18.
Mol Cell ; 53(1): 127-39, 2014 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-24332809

RESUMO

The endoplasmic reticulum (ER) stress transducer BBF2H7/CREB3L2 is an ER-resident transmembrane transcription factor. In response to physiological ER stress, it is processed at the transmembrane region to generate a cytoplasmic N terminus, which contains a basic leucine zipper (bZIP) domain, and luminal C terminus. The BBF2H7 N terminus functions as a transcription factor to promote the expression of ER-Golgi trafficking-related genes and plays crucial roles in chondrocyte differentiation. Here, we found that the BBF2H7 C terminus is secreted into the extracellular space as a signaling molecule for cell-to-cell communication. The secreted BBF2H7 C terminus directly binds to both Indian hedgehog and its receptor Patched-1, followed by activation of Hedgehog signaling, resulting in promoting the proliferation of neighboring chondrocytes. The dual N- and C-terminal functions of BBF2H7 triggered by physiological ER stress may allow chondrocytes to simultaneously regulate distinct cellular events for differentiation and proliferation in developing cartilage.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Cartilagem/metabolismo , Proliferação de Células , Condrócitos/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Retículo Endoplasmático/metabolismo , Animais , Fatores de Transcrição de Zíper de Leucina Básica/genética , Cartilagem/citologia , Células Cultivadas , Condrócitos/citologia , Retículo Endoplasmático/genética , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Camundongos , Camundongos Knockout , Estrutura Terciária de Proteína
19.
FASEB J ; 34(11): 15047-15061, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32954540

RESUMO

Tristetraprolin (TTP), an RNA-binding protein encoded by the ZFP36 gene, is vital for neural differentiation; however, its involvement in neurodegenerative diseases such as Parkinson's disease (PD) remains unclear. To explore the role of TTP in PD, an in vitro 1-methyl-4-phenylpyridinium (MPP+ ) cell model and an in vivo 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) of PD were used. Transfection of small interfering (si)-TTP RNA upregulated pro-oxidative NOX2 expression and ROS formation, downregulated anti-oxidative GSH and SOD activity;si-TTP upregulated pro-apoptotic cleaved-caspase-3 expression, and downregulated antiapoptotic Bcl-2 expression; while overexpression (OE)-TTP lentivirus caused opposite effects. Through database prediction, luciferase experiment, RNA immunoprecipitation (RIP), and mRNA stability analysis, we evaluated the potential binding sites of TTP to 3'-untranslated regions (3'-UTR) of NOX2 mRNA. TTP affected the NOX2 luciferase activity by binding to two sites in the NOX2 3'-UTR. RIP-qPCR confirmed TTP binding to both sites, with a higher affinity for site-2. In addition, TTP reduced the NOX2 mRNA stability. si-NOX2 and antioxidant N-acetyl cysteine (NAC) reversed si-TTP-induced cell apoptosis. In MPTP-treated mice, TTP expression increased and was co-located with dopaminergic neurons. TTP also inhibited NOX2 and decreased the oxidative stress in vivo. In conclusion, TTP protects against dopaminergic oxidative injury by promoting NOX2 mRNA degradation in the MPP+ /MPTP model of PD, suggesting that TTP could be a potential therapeutic target for regulating the oxidative stress in PD.


Assuntos
Neurônios Dopaminérgicos/efeitos dos fármacos , NADPH Oxidase 2/química , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , RNA Mensageiro/química , Tristetraprolina/farmacologia , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/efeitos adversos , Animais , Apoptose , Neurônios Dopaminérgicos/enzimologia , Neurônios Dopaminérgicos/patologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/enzimologia , Mitocôndrias/patologia , NADPH Oxidase 2/genética , NADPH Oxidase 2/metabolismo , Neuroblastoma/tratamento farmacológico , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Neurotoxinas/toxicidade , Doença de Parkinson/enzimologia , Doença de Parkinson/etiologia , Doença de Parkinson/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
20.
Chem Soc Rev ; 49(20): 7229-7251, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-32936169

RESUMO

Hydrogels have recently garnered tremendous interest due to their potential application in soft electronics, human-machine interfaces, sensors, actuators, and flexible energy storage. Benefiting from their impressive combination of hydrophilicity, metallic conductivity, high aspect ratio morphology, and widely tuneable properties, when two-dimensional (2D) transition metal carbides/nitrides (MXenes) are incorporated into hydrogel systems, they offer exciting and versatile platforms for the design of MXene-based soft materials with tunable application-specific properties. The intriguing and, in some cases, unique properties of MXene hydrogels are governed by complex gel structures and gelation mechanisms, which require in-depth investigation and engineering at the nanoscale. On the other hand, the formulation of MXenes into hydrogels can significantly increase the stability of MXenes, which is often the limiting factor for many MXene-based applications. Moreover, through simple treatments, derivatives of MXene hydrogels, such as aerogels, can be obtained, further expanding their versatility. This tutorial review intends to show the enormous potential of MXene hydrogels in expanding the application range of both hydrogels and MXenes, as well as increasing the performance of MXene-based devices. We elucidate the existing structures of various MXene-containing hydrogel systems along with their gelation mechanisms and the interconnecting driving forces. We then discuss their distinctive properties stemming from the integration of MXenes into hydrogels, which have revealed an enhanced performance, compared to either MXenes or hydrogels alone, in many applications (energy storage/harvesting, biomedicine, catalysis, electromagnetic interference shielding, and sensing).

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