Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
Mais filtros








Base de dados
Intervalo de ano de publicação
1.
Small ; : e2310547, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712578

RESUMO

The interfacial instability between PEO-based solid electrolyte (SPE) and high-voltage cathode materials inhibits the longevity of high-energy-density all-solid-state polymer lithium metal batteries (ASSPLBs). Herein, for the first time it is demonstrated, that contact loss caused by gas generation from interfacial side reactions between the high-voltage cathode and solid polymer electrolyte (SPE) can also arise in ASSPLBs. To alleviate the interfacial side reactions, a LiNb0.6Ti0.5O3 (LNTO) layer is well coated on LiNi0.83Co0.07Mn0.1O2 (NCM83), denoted as (CNCM83). The LNTO layer with low electronic conductivity reduces the decomposition drive force of SPE. Furthermore, Ti and Nb in the LNTO layer spontaneously migrate inside the NCM83 surface to form a strong Ti/Nb─O bond, stalling oxygen evolution in high-voltage cathodes. The interfacial degradation phenomena, including SPE decomposition, detrimental phase transition and intragranular cracks of NCM83, and void formation between cathode and SPE, are effectively mitigated by the LNTO layer. Therefore, the growth rate of interfacial resistance (RCEI) decreases from 37.6 Ω h-0.5 for bare NCM83 to 2.4 Ω h-0.5 for CNCM83 at 4.2 V. Moreover, 4.2 V PEO-based ASSPLBs achieve impressive cyclability with high capacity retention of 135 mAh g-1 (75%) even after 300 cycles at 0.5 C.

2.
Nanoscale ; 16(19): 9476-9487, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38647227

RESUMO

Two-dimensional transition metal dichalcogenide-based memtransistors provide simulation, sensing, and storage capabilities for applications in a remotely operated aerospace environment. Swift heavy ion (SHI) irradiation technology is a common method to simulate the influences of radiation ions on electronic devices in space environments. Here, SHI irradiation technology under different conditions was utilized to produce complex defects in WSe2-based memtransistors. Low-resistance state to low-resistance state (LRS-LRS) switching behaviors under light illumination were achieved and photocurrent responses with different spike trains were observed in SHI-irradiated memtransistors, which facilitated the design of devices with enriched analog functions. Reduction of the Schottky barrier height due to the introduced defects at the metal/WSe2 interface was confirmed to be the major factor responsible for the observed behaviors. 1T phase and concentric circle-type vacancies were also created in the SHI-irradiated 2H-WSe2 channel besides the amorphous structure; these complex defects could seriously affect the transport properties of the devices. We believe that this work serves as a foundation for aerospace radiation applications of all-in-one devices. It also opens a new application field of heavy ion irradiation technology for the development of multiterminal memtransistor-based optoelectronic artificial synapses for neuromorphic computing.

3.
J Orthop Surg Res ; 18(1): 358, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37183257

RESUMO

OBJECTIVE: To explore the efficacy and safety of the posterior paramedian approach combined with a novel inverted V-shaped surgical access for the treatment of intraspinal schwannomas. METHODS: This study retrospectively reviewed consecutive patients who underwent surgical resection of the intraspinal schwannomas via the inverted V-shaped approach at our center between January 2016 and May 2021. Changes between the preoperative and postoperative visual analog scale (VAS) scores and neurological function Japan Orthopaedic Association (JOA) scores were assessed. Secondary outcomes such as success rate of tumor resection, operation time, blood loss, spinal stability, and disruption degree of intervertebral joints. Postoperative complications were also investigated. RESULTS: Of these 36 consecutive patients, there were 6 cases in the cervical spine, 2 cases at the cervical-thoracic junction, 11 cases in the thoracic spine, 4 cases at the thoracic-lumbar junction and 13 cases in the lumbar spine. The average operation time was 99 min, and the average blood loss was 95.4 mL. The tumor removal rate was 100%. Postoperative CT re-examination showed that the spinous processes were intact in all cases, the facet joint surfaces were intact in 32 cases. At the time of last follow-up, the median JOA score was 25 (9-27), which was significantly improved compared to the preoperative median JOA score of 15 (10-22) (P < 0.01). The overall excellent and good rate were 88.9 %. The median VAS score at post-surgery was 0 (0-2), which was significantly improved compared to the preoperative median VAS score of 4 (2-8) (P < 0.01). As for complications, there were no cases of cerebrospinal fluid leakage or spinal instability. Three patients who had a postoperative fever finally recovered after lumbar cistern drainage. CONCLUSION: The inverted V-shaped surgical access via the posterior paramedian approach is an effective and safe method for the treatment of intraspinal schwannomas.


Assuntos
Neurilemoma , Fusão Vertebral , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Neurilemoma/diagnóstico por imagem , Neurilemoma/cirurgia
4.
Nano Lett ; 23(10): 4502-4509, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37171532

RESUMO

Extending the fabrication methodology of solid-state nanopores in a wide range of materials is significant in the fields of single molecule detection, nanofluidic devices, and nanofiltration membranes. Here, we demonstrate a new method to directly fabricate size- and density-controllable sub-10 nm nanopores in WO3 nanosheets using single swift heavy ions (SHIs) without any chemical etching process. By selecting ions of different electronic energy losses (Se), nanopores with sizes from 1.8 to 7.4 nm can be created in WO3 nanosheets. The creation efficiency of nanopores achieves ∼100% for Se > 20 keV/nm, and there exists a critical thickness below which nanopores can be created. Combined with molecular dynamics simulations, we propose that the viscosity and surface tension of the transient molten phase caused by SHIs are the key factors for the formation of nanopores. This method paves a way to fabricate solid-state nanopores in materials with a low viscosity and surface tension.

5.
Front Microbiol ; 13: 1062282, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36532451

RESUMO

Drug-resistant fungal infections are emerging as an important clinical problem. In general, antifungal resistance results from increased target expression or mutations within the target protein sequence. However, the molecular mechanisms of non-drug target mutations of antifungal resistance in fungal pathogens remain to be explored. Previous studies indicated that the metal chaperone protein Mtm1 is required for mitochondrial Sod2 activation and responses to oxidative stress in yeast and in the fungal pathogen Aspergillus fumigatus, but there is no report of MtmA-related antifungal resistance. In this study, we found that repressed expression of MtmA (only 10% expression) using a conditional promoter resulted in significantly enhanced itraconazole resistance, which was not the result of highly expressed drug targets Erg11A and Erg11B. Furthermore, we demonstrated that repressed expression of MtmA results in upregulation of a series of multidrug resistance-associated transport genes, which may cause multidrug resistance. Further mechanistic studies revealed that inhibition of MtmA expression led to abnormal activation of the calcium signaling system and prompted persistent nucleation of the calcium signaling transcription factor CrzA. Our findings suggest that the metal chaperone protein MtmA is able to negatively regulate fungal resistance via affecting calcium signaling pathway.

6.
Microorganisms ; 10(12)2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36557722

RESUMO

Aspergillus fumigatus is an opportunistic airborne fungus that causes severe invasive aspergillosis in immunocompromised patients. Zinc is an essential micronutrient for the growth of A. fumigatus and even for all microorganisms. An increasing number of studies have reported that fungal zinc acquisition ability plays a key role in fungal survival in hosts with an extremely zinc-limited microenvironment. The ability to fight scarcity and excess of zinc are tightly related to fungal virulence and may be used as new potential targets. Because the regulation of zinc homeostasis is important, a thorough understanding of the functional genes involved in the regulatory network for zinc homeostasis is required for fungal pathogens. The current mini-review summarized potential zinc homeostasis regulators in A. fumigatus and classified these regulators according to localization and function, which were identified or predicted based on A. fumigatus or deduced from homologs in model yeasts. Future perspectives for zinc homeostasis regulators as potential antifungal targets to treat invasive aspergillosis are also discussed.

7.
Nanoscale Adv ; 4(22): 4809-4818, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36381509

RESUMO

A free-standing nano-sulfur-based carbon nanotube/graphene (S/CNT/G) film with a conductive interlinked three-dimensional (3D) nanoarchitecture is fabricated via a facile solution-based method. This 3D multidimensional carbon-sulfur network combines three different nanoarchitectures, as follows: zero-dimensional sulfur nanoparticles, one-dimensional carbon nanotubes, and two-dimensional graphene. The CNTs with a one-dimensional structure act as a conductive matrix, and graphene with two-dimensional sheets is intercalated into the CNT scaffold to build a 3D structure, extending in an additional dimension to provide improved restriction for sulfur/polysulfides. Zero-dimensional sulfur nanoparticles are anchored uniformly on the interpenetrative 3D carbon framework to form a free-standing cathode. Moreover, this well-designed S/CNT/G film is flexible, highly conductive, binder free and current collector free. When directly used as a flexible cathode electrode, the synthesized S/CNT/G film delivers both excellent long-term cycling and high-rate performances. A high initial capacity of 948 mA h g-1 is obtained, and subsequently, a reversible discharge capacity of 593 mA h g-1 over 200 cycles is achieved at 0.5C. Even at a high rate of 3C, the S/CNT/G film with a 50 wt% sulfur content still exhibits a discharge capacity of 598 mA h g-1. These results demonstrate the great potential of the S/CNT/G nanocomposite as a flexible and binder-free cathode for high performance Li-S batteries.

8.
Front Immunol ; 13: 975695, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36148235

RESUMO

Background: Central nervous system tumor (CNST) is one of the most complicated and lethal forms of human tumors with very limited treatment options. In recent years, growing evidence indicates that oncolytic virotherapy (OVT) has emerged as a promising therapeutic strategy for CNSTs. And a considerable amount of literature on OVT-CNSTs has been published. However, there are still no studies summarizing the global research trends and hotspots of this field through a bibliometric approach. To fulfill this knowledge gap, bibliometric analysis was conducted based on all publications relating to OVT-CNSTs since 2000s. Methods: We searched the Web of Science Core Collection for all relevant studies published between 2000 and 2022. Four different tools (online analysis platform, R-bibliometrix, CiteSpace and VOSviewer) were used to perform bibliometric analysis and network visualization, including annual publication output, active journals, contribution of countries, institutions, and authors, references, as well as keywords. Results: A total of 473 articles and reviews were included. The annual number of publications on OVT-CNSTs showed a significant increasing trend. Molecular Therapy and Cancer Research were the most active and co-cited journals, respectively. In terms of contributions, there is no doubt that the United States occupied a leading position with the most publications (n=307, 64.9%) and the highest H-index (57). The institution and author that contributed the largest number of publications were Ohio State University and Chiocca EA, respectively. As can be seen from citation analysis, the current studies mainly focused on preclinical and phase I/II clinical results of various oncolytic virus for CNSTs treatment. Keywords co-occurrence and burst analysis revealed that the following research topics including immunotherapy, T-cells, tumor microenvironment, vaccine, blood-brain-barrier, checkpoint inhibitors, macrophage, stem cell, and recurrent glioblastoma have been research frontiers of this field and also have great potential to continue to be research hotspots in the future. Conclusion: There has been increasing attention on oncolytic viruses for use as CNSTs therapeutics. Oncolytic immunotherapy is a topic of great concern in this field. This bibliometric study provides a comprehensive analysis of the knowledge base, research hotspots, development perspective in the field of OVT-CNSTs, which could become an essential reference for scholars in this area.


Assuntos
Pesquisa Biomédica , Neoplasias do Sistema Nervoso Central , Terapia Viral Oncolítica , Vírus Oncolíticos , Bibliometria , Neoplasias do Sistema Nervoso Central/terapia , Humanos , Recidiva Local de Neoplasia , Vírus Oncolíticos/genética , Microambiente Tumoral , Estados Unidos
9.
Fungal Genet Biol ; 163: 103731, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36087858

RESUMO

SreA has been identified as a GATA-type transcription factor that represses iron uptake to avoid iron excess during iron sufficiency. However, knowledge about whether SreA also affects the homeostasis of other divalent metal ions is limited. In this study, by screening Aspergillus fumigatus transcription factor deletion mutant libraries, we demonstrate that the sreA deletion mutant shows the greatest tolerance to MnCl2 among the tested divalent metal ions. Fe and Mn stimuli are able to enhance the expression of SreA with the different time-dependent manner, while the expression of SreA contributes to Mn2+ tolerance. Lack of SreA results in abnormally increased expression of a series of siderophore biosynthesis genes and iron transport-related genes, especially under MnCl2 treatment. Further mechanistic exploration indicated that lack of SreA exacerbates abnormal iron uptake, and iron excess inhibits cellular Mn content; thus, deletion of sreA results in Mn tolerance. Thus, findings in this study have demonstrated a new unexplored function for the transcription factor SreA in regulation of the Mn2+ tolerance.


Assuntos
Fatores de Transcrição GATA , Ferro , Fatores de Transcrição GATA/genética , Ferro/metabolismo , Manganês/metabolismo , Regulação Fúngica da Expressão Gênica/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Íons/metabolismo
10.
Appl Environ Microbiol ; 88(9): e0018222, 2022 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-35435716

RESUMO

The detoxification system of reactive oxygen species (ROS) plays critical roles in the survival and virulence of fungal pathogens in infected hosts, while superoxide dismutase (SOD) is the primary ROS scavenger. In the model yeast Saccharomyces cerevisiae, the metal chaperone protein Mtm1 is required for mitochondrial Sod2 activation and responses to oxidative stress. However, the function of the S. cerevisiae Mtm1 homolog in the human fungal pathogen Aspergillus fumigatus has not yet been clarified. In this study, we found that mitochondria-localized MtmA in A. fumigatus, a putative homolog of yeast Mtm1, not only has a similar function to Mtm1 in responding to oxidative stress resistance by affecting SodB (MnSOD) activity but is also essential for hyphal growth such that repressed expression of MtmA results in severe growth defects in A. fumigatus. In addition, the chelation of Zn2+ can obviously rescue growth defects caused by repression of MtmA, suggesting that MtmA may be involved in hyphal growth by affecting cellular Zn2+ detoxification. Moreover, MtmA contains four Mito-carr domains, whereas only the first Mito-carr domain is required for the function of MtmA. Therefore, the findings in this study suggest that MtmA in A. fumigatus has an important and unique function that is different from that in yeast. IMPORTANCE Knowledge of the key factors required for the viability of pathogenic fungi can help to explore new antifungal drugs. Here, we demonstrate that MtmA is involved in responding to oxidative stress by activating mitochondrial SodB activity. MtmA, especially for the first Mito-carr domain, is essential for colony growth by regulating cellular Zn2+ equilibrium and responses to oxidative stress in A. fumigatus. This is the first report of the vital and unique role of the MtmA protein in pathogenic fungi, indicating that it might be a potential antifungal drug target.


Assuntos
Aspergillus fumigatus , Saccharomyces cerevisiae , Antifúngicos/metabolismo , Antifúngicos/farmacologia , Aspergillus fumigatus/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Humanos , Chaperonas Moleculares/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo
11.
Sci Total Environ ; 821: 153427, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35090906

RESUMO

Ammonia (NH3) volatilization is a major pathway of soil nitrogen loss in tropical farmland, causing many environmental issues. Biochar can improve soil quality and affect soil NH3 volatilization. However, little is known about the effects of tropical crop residue biochar on soil NH3 volatilization in tropical farmland. Therefore, a laboratory incubation study was conducted using four kinds of tropical crop residue biochar (pineapple straw (stem and leaves), banana straw, cassava straw and sugarcane bagasse pyrolyzed at 500 °C) with five addition rates (0.5%, 1%, 2%, 4%, and 6%) to evaluate their impact on NH3 volatilization from tropical latosols. The results showed that NH3 volatilization peaked twice under biochar application, once at 1-5 days and again at 12-16 days. The cumulative NH3 volatilization (0.14-0.47 mg kg-1) of the 20 biochar treatments was higher than that of the control (0.12 mg kg-1). With the increase in the biochar addition rate, the soil pH, soil organic matter (SOM), urease activity, nitrate nitrogen content (NO3--N), nitrification rate and cumulative NH3 volatilization increased gradually, and the 6% biochar treatment resulted in the highest NH3 volatilization loss (0.19-0.47 mg kg-1). The type of biochar is also a main factor affecting soil NH3 volatilization. The cumulative NH3 volatilization was the highest under pineapple straw biochar, as it was 19-43% higher than when the other three biochars were applied. However, sugarcane bagasse biochar had the lowest cumulative NH3 volatilization due to its low quartz, sylvite and calcite contents, lack of -OH hydroxyl groups and high adsorbability. NH3 volatilization was positively correlated with the soil pH, SOM, urease activity, NO3--N and nitrification rate. In conclusion, four tropical crop residue biochars can increase NH3 volatilization in tropical latosols, so reducing NH3 volatilization needs to be further considered in tropical crop residue biochar applications.


Assuntos
Ananas , Manihot , Musa , Oryza , Saccharum , Amônia/análise , Celulose , Carvão Vegetal , Fazendas , Fertilizantes/análise , Nitrogênio/análise , Solo/química , Volatilização
12.
Appl Environ Microbiol ; 87(22): e0112021, 2021 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-34524893

RESUMO

An efficient reactive oxygen species (ROS) detoxification system is vital for the survival of the pathogenic fungus Aspergillus fumigatus within the host high-ROS environment of the host. Therefore, identifying and targeting factors essential for oxidative stress response is one approach to developing novel treatments for fungal infections. The oxidation resistance 1 (Oxr1) protein is essential for protection against oxidative stress in mammals, but its functions in pathogenic fungi remain unknown. The present study aimed to characterize the role of an Oxr1 homolog in A. fumigatus. The results indicated that the OxrA protein plays an important role in oxidative stress resistance by regulating the catalase function in A. fumigatus, and overexpression of catalase can rescue the phenotype associated with OxrA deficiency. Importantly, the deficiency of oxrA decreased the virulence of A. fumigatus and altered the host immune response. Using the Aspergillus-induced lung infection model, we demonstrated that the ΔoxrA mutant strain induced less tissue damage along with decreased levels of lactate dehydrogenase (LDH) and albumin release. Additionally, the ΔoxrA mutant caused inflammation at a lower degree, along with a markedly reduced influx of neutrophils to the lungs and a decreased secretion of cytokine usually associated with recruitment of neutrophils in mice. These results characterize the role of OxrA in A. fumigatus as a core regulator of oxidative stress resistance and fungal pathogenesis. IMPORTANCE Knowledge of ROS detoxification in fungal pathogens is useful in the design of new antifungal drugs and could aid in the study of oxidative stress resistance mechanisms. In this study, we demonstrate that OxrA protein localizes to the mitochondria and functions to protect against oxidative damage. We demonstrate that OxrA contributes to oxidative stress resistance by regulating catalase function, and overexpression of catalase (CatA or CatB) can rescue the phenotype that is associated with OxrA deficiency. Remarkably, a loss of OxrA attenuated the fungal virulence in a mouse model of invasive pulmonary aspergillosis and altered the host immune response. Therefore, our finding indicates that inhibition of OxrA might be an effective approach for alleviating A. fumigatus infection. The present study is, to the best of our knowledge, a pioneer in reporting the vital role of Oxr1 protein in pathogenic fungi.


Assuntos
Aspergilose , Aspergillus fumigatus , Proteínas Fúngicas/metabolismo , Estresse Oxidativo , Animais , Aspergillus fumigatus/enzimologia , Aspergillus fumigatus/patogenicidade , Catalase , Camundongos , Espécies Reativas de Oxigênio , Virulência
13.
Appl Environ Microbiol ; 87(17): e0101321, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34160279

RESUMO

Superoxide dismutases (SODs) are important metalloenzymes that protect fungal pathogens against the toxic effects of reactive oxygen species (ROS) generated by host defense mechanisms during the infection process. The activation of Cu/Zn-SOD1 is found to be dependent on copper chaperone for SOD1 (Ccs1). However, the role of the Ccs1 ortholog in the human pathogen Aspergillus fumigatus and how these SODs coordinate to mediate oxidative stress response remain elusive. Here, we demonstrated that A. fumigatus CcsA, a Saccharomyces cerevisiae Ccs1 ortholog, is required for cells in response to oxidative response and the activation of Sod1. Deletion of ccsA resulted in increased ROS accumulation and enhanced sensitivity to oxidative stress due to the loss of SodA activity. Molecular characterization of CcsA revealed that the conserved CXC motif is required not only for the physical interaction with SodA but also for the oxidative stress adaption. Notably, addition of Mn2+ or overexpression of cytoplasmic Mn-SodC could rescue the defects of the ccsA or sodA deletion mutant, indicating the important role of Mn2+ and Mn-SodC in ROS detoxification; however, deletion of the CcsA-SodA complex could not affect A. fumigatus virulence. Collectively, our findings demonstrate that CcsA functions as a Cu/Zn-Sod1 chaperone that participates in the adaptation to oxidative stress in A. fumigatus and provide a better understanding of the CcsA-SodA complex-mediated oxidative stress response in filamentous fungi. IMPORTANCE Reactive oxygen species (ROS) produced by phagocytes have been reported to participate in the killing of fungal pathogens. Superoxide dismutases (SODs) are considered to be the first line of defense against superoxide anions. Characterizing the regulatory mechanisms of SOD activation is important for understanding how fungi adapt to oxidative stress in hosts. Our findings demonstrated that CcsA functions as a SodA chaperone in A. fumigatus and that the conserved CXC motif within CcsA is required for its interaction with SodA and the CcsA-SodA-mediated oxidative response. These data may provide new insights into how fungal pathogens adapt to oxidative stress via the CcsA-SodA complex.


Assuntos
Aspergilose/microbiologia , Aspergillus fumigatus/metabolismo , Cobre/metabolismo , Proteínas Fúngicas/metabolismo , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Aspergilose/metabolismo , Aspergillus fumigatus/enzimologia , Aspergillus fumigatus/genética , Aspergillus fumigatus/crescimento & desenvolvimento , Citoplasma/genética , Citoplasma/metabolismo , Proteínas Fúngicas/genética , Humanos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/genética , Virulência
14.
Artigo em Inglês | MEDLINE | ID: mdl-33431412

RESUMO

The emergence of azole-resistant fungal pathogens has posed a great threat to public health worldwide. Although the molecular mechanism of azole resistance has been extensively investigated, the potential regulators of azole resistance remain largely unexplored. In this study, we identified a new function of the fungal specific C2H2 zinc finger transcription factor SltA (involved in the salt tolerance pathway) in the regulation of azole resistance of the human fungal pathogen Aspergillus fumigatus A lack of SltA results in an itraconazole hypersusceptibility phenotype. Transcriptional profiling combined with LacZ reporter analysis and electrophoretic mobility shift assays (EMSA) demonstrated that SltA is involved in its own transcriptional regulation and also regulates the expression of genes related to ergosterol biosynthesis (erg11A, erg13A, and erg24A) and drug efflux pumps (mdr1, mfsC, and abcE) by directly binding to the conserved 5'-AGGCA-3' motif in their promoter regions, and this binding is dependent on the conserved cysteine and histidine within the C2H2 DNA binding domain of SltA. Moreover, overexpression of erg11A or mdr1 rescues sltA deletion defects under itraconazole conditions, suggesting that erg11A and mdr1 are related to sltA-mediated itraconazole resistance. Most importantly, deletion of SltA in laboratory-derived and clinical azole-resistant isolates significantly attenuates drug resistance. Collectively, we have identified a new function of the transcription factor SltA in regulating azole resistance by coordinately mediating the key azole target Erg11A and the drug efflux pump Mdr1, and targeting SltA may provide a potential strategy for intervention of clinical azole-resistant isolates to improve the efficiency of currently approved antifungal drugs.


Assuntos
Aspergillus fumigatus , Antifúngicos/farmacologia , Aspergillus fumigatus/genética , Azóis/farmacologia , Farmacorresistência Fúngica/genética , Proteínas Fúngicas/genética , Humanos , Testes de Sensibilidade Microbiana , Fatores de Transcrição/genética
15.
RSC Adv ; 11(27): 16388-16395, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35479174

RESUMO

(H2dabco)[NH4(ClO4)3] (DAP, dabco = 1,4-diazabicyclo[2.2.2]octane) is a recently synthesized ammonium perchlorate-based molecular perovskite energetic material. The high-symmetry perovskite configuration assembles the oxidant ClO4 - and fuel H2dabco2+ into a compact cubic crystal, realizing a high energy-releasing efficiency. In this study, the thermal decomposition of DAP has been investigated by thermogravimetric analysis (TG) and differential scanning calorimetry (DSC) coupled with Fourier transform infrared (FTIR) spectroscopy and mass spectroscopy (MS). The TG-DSC profiles show that DAP has an intense one-stage heat release process with a weight loss of 94.7%. The evolved gas products are identified as H2O, CO2, CO, HCl, HCN, NH3, HNCO by FTIR spectrum, in which the infrared characteristic peak at 2283 and 2250 cm-1 is clarified not from N2O and assigned to HNCO. The principal products are H2O and CO2 together with significant amounts of HCl, HCN, NH3 in MS, while few nitrogen oxides and O2 are detected. The experimental results show that organic components have been the prominent media for the degradation of ClO4 -. To refine the mechanism observed in experiment, ab initio molecular dynamics simulations are carried out to reveal the atomistic reaction mechanisms. The decomposition of DAP starts with proton transfer from NH4 + and H2dabco2+ to ClO4 -. The deprotonated carbon skeleton is preferable to NH3 in capturing O atoms, realizing a faster consumption of O atoms. Amounts of H atoms enter the environment being active free radicals, realizing an efficient autocatalytic chain propagation of degradation of ClO4 -. The atomistic thermal decomposition reaction mechanism of DAP uncovers the role of organic components in promoting the degradation of ClO4 -, which will help improve the synthesis strategy of molecular perovskite energetic materials with improved performance.

16.
ACS Appl Mater Interfaces ; 11(42): 38654-38662, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31566358

RESUMO

In virtue of their distinctive superiorities, lithium-sulfur (Li-S) batteries were deemed as novel and potential energy storage equipment. However, the low actual energy density and rapid capacity fading are still hindering their practical applications. Herein, MXene-based Co, N-codoped porous carbon nanosheets (MCoNPCNSs) are first developed as sulfur hosts by in situ self-assembly of the bimetallic zeolite imidazole framework on Ti3C2Tx MXene nanosheets followed by calcining and etching treatments. Co, N codoping on the one hand highly enhances the adsorptivity to polysulfides and on the other hand significantly promotes the kinetics of sulfur cathodes. Therefore, the MCoNPCNSs/S-M-PP electrode achieves a high capacity of 1340.2 mA h g-1 in the first-cycle discharge process at 0.2 C and an exceptional capacity retention of 914.7 mA h g-1 after 1000 cycles at 1 C. Moreover, the integrated structure of the cathode and separator imparts the MCoNPCNSs/S-M-PP electrode a significantly elevated gravimetric energy density of 1211.8 W h kg-1. Therefore, the integrated MCoNPCNSs/S-M-PP electrode provides a delighted direction for constructing the potentially practical Li-S batteries.

17.
Cell Microbiol ; 21(12): e13092, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31376233

RESUMO

Previous studies identified that the budding yeast Saccharomyces cerevisiae have two sphingolipid synthesis-related proteins, Orm1p and Orm2p, that negatively regulate the activities of SPT, which is a key rate-limiting enzyme in sphingolipid synthesis. However, little is known about whether sphingolipids in the cell membrane, which are closely related to ergosterols, could affect the efficacy of azole drugs, which target to the ergosterol biosynthesis. In this study, through genome-wide homologue search analysis, we found that the Aspergillus fumigatus genome only contains one Orm homologue, referred to as OrmA for which the protein expression could be induced by azole antifungals in a dose-dependent manner. Deletion of ormA caused hypersensitivity to azoles, and adding the sphingolipid synthesis inhibitor myriocin rescued the azole susceptibility induced by lack of ormA. In contrast, overexpression of OrmA resulted in azole resistance, indicating that OrmA is a positive azole-response regulator. Further mechanism analysis verified that OrmA is related to drug susceptibility by affecting endoplasmic reticulum stress responses in an unfolded protein response pathway-HacA-dependent manner. Lack of ormA led to an abnormal profile of sphingolipid ceramide components accompanied by hypersensitivity to low temperatures. Furthermore, deletion of OrmA significantly reduced virulence in an immunosuppressed mouse model. The findings in this study collectively suggest that the sphingolipid metabolism pathway in A. fumigatus plays a critical role in azole susceptibility and fungal virulence.


Assuntos
Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/metabolismo , Azóis/farmacologia , Proteínas Fúngicas/metabolismo , Esfingolipídeos/metabolismo , Virulência/efeitos dos fármacos , Animais , Antifúngicos/farmacologia , Farmacorresistência Fúngica/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo , Resposta a Proteínas não Dobradas/efeitos dos fármacos
18.
RSC Adv ; 9(34): 19390-19396, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-35519389

RESUMO

An energetic ionic salt (EIS)-based cocrystal formation, cyclotetramethylene tetra-nitramine (HMX)/hydrazine 5,5'-bitetrazole-1,1'-diolate (HA·BTO), is predicted based on molecular dynamics simulations. HA·BTO is a newly-synthesized environmentally friendly energetic ionic salt with good detonation performance and low sensitivity. Calculated powder X-ray diffraction patterns and intermolecular interactions deduce the formation of the new cocrystal structure. Radial distribution function analysis suggests that hydrogen bonds and van der Waals (vdW) forces exist between the H⋯O pairs of HMX and HA·BTO, while the hydrogen bonds between the H of HA·BTO and the O of HMX play a prominent role. The cohesive energy density and mechanical properties are also analyzed. The cohesive energy density of the HMX/HA·BTO cocrystal is larger than that of the composite of HMX and HA·BTO, indicating an improvement in crystal stability by cocrystalization. Compared to both HMX and HA·BTO, HMX/HA·BTO has smaller Young modulus, bulk modulus and shear modulus values, but larger K/G values and a positive Cauchy pressure, suggesting decreased stiffness and improved ductibility. Moreover, the calculated formation energy is -405.79 kJ mol-1 at 298 K, which implies that the proposed cocrystal structure is likely to be synthesized at ambient temperature. In summary, we have predicted an EIS-based cocrystal formation in which the safety and mechanical properties of HMX have been improved via cocrystalization with HA·BTO, and this provides deep insight into the formation mechanism of the EIS-based cocrystal.

19.
Nanoscale ; 10(48): 22954-22962, 2018 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-30500035

RESUMO

Lithium-sulfur (Li-S) batteries, with high theoretical energy density, cost-effective preparation and environmental benignancy, have been deemed as new encouraging energy storage solutions. However, their development and applications are limited by their low practical energy density and rapid capacity fading. Herein, self-supporting Ti3C2Tx foam, as a novel sulfur host, was synthesized via direct stacking of Ti3C2Tx flakes into film followed by hydrazine-induced foaming. This Ti3C2Tx foam exhibits a well-defined porous structure, increased surface area, enlarged pore volume, and enhanced exposure of Lewis acidic sites, thus effectively strengthening the capability of physical and chemical co-adsorption for polysulfides under a high sulfur loading of 5.1 mg cm-2. Combined with a favorable electrolyte wettability and extraordinary structural stability, the resultant self-supporting Ti3C2Tx foam/S cathodes demonstrated excellent performances: a high initial discharge capacity (1226.4 mA h g-1 at 0.2C), exceptional rate performance (711.0 mA h g-1 at 5C), and extraordinary long-term cycling stability (689.7 mA h g-1 at 1C after 1000 cycles with ultralow capacity decay of ≈0.025% per cycle). Remarkably, the self-supporting structure confers a significantly elevated gravimetric energy density (1297.8 W h kg-1). Therefore, this elaborately designed Ti3C2Tx foam/S cathode opens new delightful opportunities for constructing practical high-energy-density Li-S batteries.

20.
Nanomaterials (Basel) ; 7(5)2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28505116

RESUMO

Gold nanowires with diameters ranging from 20 to 90 nm were fabricated by the electrochemical deposition technique in etched ion track polycarbonate templates and were then irradiated by Xe and Kr ions with the energy in MeV range. The surface modification of nanowires was studied by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) characterizations. Different craters with and without protrusion on the gold nanowires were analyzed, and the two corresponding formation mechanisms, i.e., plastic flow and micro-explosion, were investigated. In addition, the sputtered gold nanoparticles caused by ion irradiation were studied and it was confirmed that the surface damage produced in gold nanowires was increased as the diameter of the nanowires decreased. It was also found that heavy ion irradiation can also create stacking fault tetrahedrons (SFTs) in gold nanowires and three different SFTs were confirmed in irradiated nanowires. A statistical analysis of the size distribution of SFTs in gold nanowires proved that the average size distribution of SFT was positively related to the nuclear stopping power of incident ions, i.e., the higher nuclear stopping power of incident ions could generate SFT with a larger average size in gold nanowires.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA