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1.
Int J Nanomedicine ; 19: 4977-4994, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828204

RESUMO

Purpose: Exosomes are membrane vesicles secreted by various cells and play a crucial role in intercellular communication. They can be excellent delivery vehicles for oligonucleotide drugs, such as microRNAs, due to their high biocompatibility. MicroRNAs have been shown to be more stable when incorporated into exosomes; however, the lack of targeting and immune evasion is still the obstacle to the use of these microRNA-containing nanocarriers in clinical settings. Our goal was to produce functional exosomes loaded with target ligands, immune evasion ligand, and oligonucleotide drug through genetic engineering in order to achieve more precise medical effects. Methods: To address the problem, we designed engineered exosomes with exogenous cholecystokinin (CCK) or somatostatin (SST) as the targeting ligand to direct the exosomes to the brain, as well as transduced CD47 proteins to reduce the elimination or phagocytosis of the targeted exosomes. MicroRNA-29b-2 was the tested oligonucleotide drug for delivery because our previous research showed that this type of microRNA was capable of reducing presenilin 1 (PSEN1) gene expression and decreasing the ß-amyloid accumulation for Alzheimer's disease (AD) in vitro and in vivo. Results: The engineered exosomes, containing miR29b-2 and expressing SST and CD47, were produced by gene-modified dendritic cells and used in the subsequent experiments. In comparison with CD47-CCK exosomes, CD47-SST exosomes showed a more significant increase in delivery efficiency. In addition, CD47-SST exosomes led to a higher delivery level of exosomes to the brains of nude mice when administered intravenously. Moreover, it was found that the miR29b-2-loaded CD47-SST exosomes could effectively reduce PSEN1 in translational levels, which resulted in an inhibition of beta-amyloid oligomers production both in the cell model and in the 3xTg-AD animal model. Conclusion: Our results demonstrated the feasibility of the designed engineered exosomes. The application of this exosomal nanocarrier platform can be extended to the delivery of other oligonucleotide drugs to specific tissues for the treatment of diseases while evading the immune system.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Encéfalo , Antígeno CD47 , Exossomos , MicroRNAs , Presenilina-1 , Receptores de Somatostatina , Animais , Exossomos/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/genética , MicroRNAs/genética , MicroRNAs/administração & dosagem , Presenilina-1/genética , Encéfalo/metabolismo , Receptores de Somatostatina/genética , Receptores de Somatostatina/metabolismo , Peptídeos beta-Amiloides/metabolismo , Camundongos , Antígeno CD47/genética , Antígeno CD47/metabolismo , Somatostatina , Humanos , Modelos Animais de Doenças
2.
JCI Insight ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842948

RESUMO

Sleep disturbance usually accompanies anxiety disorders and exacerbates their incidence rates. The precise circuit mechanisms remain poorly understood. Here, we found that glutamatergic neurons in the posteroventral medial amygdala (MePVGlu) are involved in arousal and anxiety-like behaviors. Excitation of MePVGlu neurons not only promoted wakefulness but also increased anxiety-like behaviors. Different projections of MePVGlu neurons played various roles in regulating anxiety-like behaviors and sleep-wakefulness. MePVGlu neurons promoted wakefulness through the MePVGlu-posteromedial cortical amygdaloid area (PMCo) pathway and the MePVGlu-bed nucleus of the stria terminals (BNST) pathway. In contrast, MePVGlu neurons increased anxiety-like behaviors through the MePVGlu-ventromedial hypothalamus (VMH) pathway. Chronic sleep disturbance increased anxiety levels and reduced reparative sleep, accompanied by the enhanced excitability of MePVGlu-PMCo and MePVGlu-VMH circuits but suppressed responses of glutamatergic neurons in the BNST. Inhibition of the MePVGlu neurons could rescue chronic sleep deprivation-induced phenotypes. Our findings provide important circuit mechanisms for chronic sleep disturbance-induced hyperarousal response and obsessive anxiety-like behavior, and are expected to provide a promising strategy for treating sleep-related psychiatric disorders and insomnia.

3.
Front Oncol ; 14: 1275769, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38746682

RESUMO

Background: Whole Slide Image (WSI) analysis, driven by deep learning algorithms, has the potential to revolutionize tumor detection, classification, and treatment response prediction. However, challenges persist, such as limited model generalizability across various cancer types, the labor-intensive nature of patch-level annotation, and the necessity of integrating multi-magnification information to attain a comprehensive understanding of pathological patterns. Methods: In response to these challenges, we introduce MAMILNet, an innovative multi-scale attentional multi-instance learning framework for WSI analysis. The incorporation of attention mechanisms into MAMILNet contributes to its exceptional generalizability across diverse cancer types and prediction tasks. This model considers whole slides as "bags" and individual patches as "instances." By adopting this approach, MAMILNet effectively eliminates the requirement for intricate patch-level labeling, significantly reducing the manual workload for pathologists. To enhance prediction accuracy, the model employs a multi-scale "consultation" strategy, facilitating the aggregation of test outcomes from various magnifications. Results: Our assessment of MAMILNet encompasses 1171 cases encompassing a wide range of cancer types, showcasing its effectiveness in predicting complex tasks. Remarkably, MAMILNet achieved impressive results in distinct domains: for breast cancer tumor detection, the Area Under the Curve (AUC) was 0.8872, with an Accuracy of 0.8760. In the realm of lung cancer typing diagnosis, it achieved an AUC of 0.9551 and an Accuracy of 0.9095. Furthermore, in predicting drug therapy responses for ovarian cancer, MAMILNet achieved an AUC of 0.7358 and an Accuracy of 0.7341. Conclusion: The outcomes of this study underscore the potential of MAMILNet in driving the advancement of precision medicine and individualized treatment planning within the field of oncology. By effectively addressing challenges related to model generalization, annotation workload, and multi-magnification integration, MAMILNet shows promise in enhancing healthcare outcomes for cancer patients. The framework's success in accurately detecting breast tumors, diagnosing lung cancer types, and predicting ovarian cancer therapy responses highlights its significant contribution to the field and paves the way for improved patient care.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38634834

RESUMO

A novel mesophilic, hydrogenotrophic methanogen, strain CWC-04T, was obtained from a sediment sample extracted from a gravity core retrieved at station 22 within the KP-9 area off the southwestern coast of Taiwan during the ORIII-1368 cruise in 2009. Cells of strain CWC-04T were rod-shaped, 1.4-2.9 µm long by 0.5-0.6 µm wide, and occurred singly. Strain CWC-04Tutilized formate, H2/CO2, 2-propanol/CO2 or 2-butanol/CO2 as catabolic substrates. The optimal growth conditions were 42 °C, 0.17 M NaCl and pH 5.35. The genomic DNA G+C content calculated from the genome sequence of strain CWC-04T was 46.19 mol%. Phylogenetic analysis of 16S rRNA gene revealed that strain CWC-04T is affiliated with the genus Methanocella. The 16S rRNA gene sequences similarities within strains Methanocella arvoryzae MRE50T, Methanocella paludicola SANAET and Methanocella conradii HZ254T were 93.7, 93.0 and 91.3 %, respectively. In addition, the optical density of CWC-04T culture dropped abruptly upon entering the late-log growth phase, with virus-like particles (150 nm in diameter) being observed on and around the cells. This observation suggests that strain CWC-04T harbours a lytic virus. Based on these phenotypic, phylogenetic and genomic results, we propose that strain CWC-04T represents a novel species of a novel genus in the family Methanocellaceae, for which the name Methanooceanicella nereidis gen. nov., sp. nov. is proposed. The type strain is CWC-04T (=BCRC AR10050T=NBRC 113165T).


Assuntos
Dióxido de Carbono , Euryarchaeota , Composição de Bases , Filogenia , RNA Ribossômico 16S/genética , Taiwan , Análise de Sequência de DNA , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Ácidos Graxos/química , Metano
5.
Int J Biol Macromol ; 260(Pt 1): 129424, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38219929

RESUMO

Calcins are a group of scorpion toxin peptides specifically binding to ryanodine receptors (RyRs) with high affinity, and have the ability to activate and stabilize RyR in a long-lasting subconductance state. Five newly calcins synthesized compounds exhibit typical structural characteristics of a specific family through chemical synthesis and virtual analysis. As the calcins from the same species, Petersiicalcin1 and Petersiicalcin2, Jendekicalcin2 and Jendekicalcin3, have only one residue difference. Both Petersiicalcin1 and Petersiicalcin2 exhibited different affinities in stimulating [3H]ryanodine binding, but the residue mutation resulted in a 2.7 folds difference. Other calcins also exhibited a stimulatory effect on [3H]ryanodine binding to RyR1, however, their affinities were significantly lower than that of Petersiiicalcin1 and Petersiiicalcin2. The channel domain of RyR1 was found to be capable of binding with the basic residues of these calcins, which also exhibited interactions with the S6 helices on RyR1. Dynamic simulations were conducted for Petersiicalcin1 and Petersiicalcin2, which demonstrated their ability to form a highly stable conformation and resulting in an asymmetric tetramer structure of RyR1. The discovery of five newly calcins further enriches the diversity of the natural calcin family, which provides more native peptides for the structure-function analysis between calcin and RyRs.


Assuntos
Peptídeos , Canal de Liberação de Cálcio do Receptor de Rianodina , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/química , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Sequência de Aminoácidos , Rianodina/metabolismo , Rianodina/farmacologia , Peptídeos/química , Estrutura Secundária de Proteína , Cálcio/metabolismo , Músculo Esquelético
7.
Acad Radiol ; 30(4): 668-679, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35778306

RESUMO

RATIONALE AND OBJECTIVES: To establish a radiomics nomogram for detecting deep myometrial invasion (DMI) in early stage endometrioid adenocarcinoma (EAC). MATERIALS AND METHODS: A total of 266 patients with stage I EAC were divided into training (n = 185) and test groups (n = 81). Logistic regression were used to identify clinical predictors. Radiomics features were extracted and selected from multiparameter MR images. The important clinical factors and radiomics features were integrated into a nomogram. A receiver operating characteristic curve was used to evaluate the nomogram. Two radiologists evaluated MR images with or without the help of the nomogram to detect DMI. The clinical benefit of using the nomogram was evaluated by decision curve analysis (DCA) and by calculating net reclassification index (NRI) and integrated discrimination index (IDI). RESULTS: Age and CA125 were independent clinical predictors. The area under the curves of the clinical parameters, radiomics signature and nomogram in evaluating DMI were 0.744, 0.869 and 0.883, respectively. The accuracies of the two radiologists increased from 79.0% and 80.2% to 90.1% and 92.5% when they used the nomogram. The NRI of the two radiologists were 0.262 and 0.318, and the IDI were 0.322 and 0.405. According to DCA, the nomogram showed a higher net benefit than the radiomics signature or unaided radiologists. Cross-validation showed the outcome of radiomics analysis may not be influenced by changes in field strength. CONCLUSION: The radiomics nomogram based on radiomics features and clinical factors can help radiologists evaluate DMI and improve their accuracy in predicting DMI in early stage EAC.


Assuntos
Adenocarcinoma , Nomogramas , Humanos , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Curva ROC , Adenocarcinoma/diagnóstico por imagem
8.
J Oral Microbiol ; 15(1): 2278937, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38415078

RESUMO

Candida albicans is a normal resident of the human oral cavity. It is also the most common fungal pathogen, causing various oral diseases, particularly in immunocompromised individuals. Chlorhexidine digluconate (CHG) is a broad-spectrum antimicrobial agent widely used in dental practice and has been recommended to treat oral candidiasis. However, its action mechanism against the fungal pathogen C. albicans remains poorly understood. The aim of the present study was to investigate the effect of CHG at sub-lethal concentrations against C. albicans. CHG inhibited the growth of C. albicans in a dose- and time-dependent manner. Cells treated with CHG exhibited altered membrane permeability, reduced metabolic activity, and enhanced metal ion and reactive oxygen species (ROS) accumulation. Copper-sensing transcription factor Mac1, iron-sensing transcription factors Sfu1 and Sef2, and copper transporter Ctr1 regulated intracellular metal ion and ROS homeostasis in response to CHG. Deletion of MAC1, SFU1, or SEF2 increased intracellular ROS production and cell susceptibility to CHG. This study revealed a novel mechanism by which CHG induced apoptosis of C. albicans cells through the disruption of metal ion and ROS homeostasis, which may help to identify new targets for fungal infections.

9.
Front Oncol ; 12: 939930, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992858

RESUMO

Purpose: The aim of this study was to evaluate the value of different multiparametric MRI-based radiomics models in differentiating stage IA endometrial cancer (EC) from benign endometrial lesions. Methods: The data of patients with endometrial lesions from two centers were collected. The radiomics features were extracted from T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) map, and late contrast-enhanced T1-weighted imaging (LCE-T1WI). After data dimension reduction and feature selection, nine machine learning algorithms were conducted to determine which was the optimal radiomics model for differential diagnosis. The univariate analyses and logistic regression (LR) were performed to reduce valueless clinical parameters and to develop the clinical model. A nomogram using the radscores combined with clinical parameters was developed. Two integrated models were obtained respectively by the ensemble strategy and stacking algorithm based on the clinical model and optimal radiomics model. The area under the curve (AUC), clinical decisive curve (CDC), net reclassification index (NRI), and integrated discrimination index (IDI) were used to evaluate the performance and clinical benefits of the models. Results: A total of 371 patients were incorporated. The LR model was the optimal radiomics model with the highest average AUC (0.854) and accuracy (0.802) in the internal and external validation groups (AUC = 0.910 and 0.798, respectively), and outperformed the clinical model (AUC = 0.739 and 0.592, respectively) or the radiologist (AUC = 0.768 and 0.628, respectively). The nomogram (AUC = 0.917 and 0.802, respectively) achieved better discrimination performance than the optimal radiomics model in two validation groups. The stacking model (AUC = 0.915) and ensemble model (AUC = 0.918) had a similar performance compared with the nomogram in the internal validation group, whereas the AUCs of the stacking model (AUC = 0.792) and ensemble model (AUC = 0.794) were lower than those of the nomogram and radiomics model in the external validation group. According to the CDC, NRI, and IDI, the optimal radiomics model, nomogram, stacking model, and ensemble model achieved good net benefits. Conclusions: Multiparametric MRI-based radiomics models can non-invasively differentiate stage IA EC from benign endometrial lesions, and LR is the best machine learning algorithm. The nomogram presents excellent and stable diagnostic efficiency.

10.
Sci Total Environ ; 839: 156160, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35609692

RESUMO

High-efficiency desulfurization is key to the recovery and use of landfill gases. In this study, a nano­iron oxide desulfurization agent modified from iron pentacarbonyl was prepared in n-decane (DE) and hexadecane (HE) by ultrasonic disruption without any supporting materials and its hydrogen sulfide removal ability and desulfurization mechanism were studied. The yield of the desulfurization agent was higher when HE was used as the solvent; however, the products generated by both solvents had the same crystal type and similar properties. The efficiency of the desulfurization agent was significantly improved at 150-200 °C, exceeding 90% at 150 °C with single sulfur production. The maximum sulfur adsorption capacity of the desulfurization agent produced after 3 h of DE ultrasonic treatment at 200 °C (DE3) was 492 mg/g (desulfurization efficiency = 97.33%), while that of the agent produced after 3 h of HE ultrasonic treatment at 250 °C (HE3) was 522 mg/g (desulfurization efficiency = 99.30%). The desulfurization reaction involved both chemical adsorption and catalytic decomposition and the catalytic decomposition reaction rate was lower than that of chemical adsorption. Therefore, the more FexSy produced in the chemical adsorption process, the better catalytic performance was.


Assuntos
Sulfeto de Hidrogênio , Adsorção , Gases/química , Compostos de Ferro , Enxofre/química , Instalações de Eliminação de Resíduos
11.
J Struct Biol ; 214(1): 107837, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35104612

RESUMO

Scanning transmission electron microscopy (STEM) is a powerful imaging technique and has been widely used in current material science research. The attempts of applying STEM (annual dark field (ADF)-STEM or annular bright field (ABF)-STEM) into biological research have been going on for decades while applications have still been limited because of the existing bottlenecks in dose efficiency and non-linearity in contrast. Recently, integrated differential phase contrast (iDPC) STEM technique emerged and achieved a linear phase contrast imaging condition, while resolving signals of light elements next to heavy ones even at low electron dose. This enables successful investigation of beam sensitive materials. Here, we investigate iDPC-STEM advantages in biology, in particular, chemically fixed and resin embedded biological tissues. By comparing results to the conventional TEM, we have found that iDPC-STEM not only shows better contrast but also resolves more structural details at molecular level, including conditions of extremely low dose and minimal heavy-atom staining. We also compare iDPC-STEM with ABF-STEM and found that contrast of iDPC-STEM is even further improved, moderately in lower frequency domains while highly with preserving high frequency biological structural details. For thick sample sections, iDPC-STEM is particularly advantageous. It avoids contrast inversion canceling effects, and by adjusting the depth of focus, fully preserves the contrast of structural details along with the sample. In addition, using depth-sectioning, iDPC-STEM enables resolving in-depth structural variation. Our results suggest that iDPC-STEM have the place and advantages within the future biological research.


Assuntos
Elétrons , Microscopia Eletrônica de Transmissão e Varredura/métodos , Microscopia de Contraste de Fase
12.
Int J Mol Sci ; 23(3)2022 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-35163312

RESUMO

Spinocerebellar ataxia type 3 (SCA3) is characterized by the over-repetitive CAG codon in the ataxin-3 gene (ATXN3), which encodes the mutant ATXN3 protein. The pathological defects of SCA3 such as the impaired aggresomes, autophagy, and the proteasome have been reported previously. To date, no effective treatment is available for SCA3 disease. This study aimed to study anti-excitotoxic effects of n-butylidenephthalide by chemically insulted Purkinje progenitor cells derived from SCA3 iPSCs. We successfully generated Purkinje progenitor cells (PPs) from SCA3 patient-derived iPSCs. The PPs, expressing both neural and Purkinje progenitor's markers, were acquired after 35 days of differentiation. In comparison with the PPs derived from control iPSCs, SCA3 iPSCs-derived PPs were more sensitive to the excitotoxicity induced by quinolinic acid (QA). The observations of QA-treated SCA3 PPs showing neural degeneration including neurite shrinkage and cell number decrease could be used to quickly and efficiently identify drug candidates. Given that the QA-induced neural cell death of SCA3 PPs was established, the activity of calpain in SCA3 PPs was revealed. Furthermore, the expression of cleaved poly (ADP-ribose) polymerase 1 (PARP1), a marker of apoptotic pathway, and the accumulation of ATXN3 proteolytic fragments were observed. When SCA3 PPs were treated with n-butylidenephthalide (n-BP), upregulated expression of calpain 2 and concurrent decreased level of calpastatin could be reversed, and the overall calpain activity was accordingly suppressed. Such findings reveal that n-BP could not only inhibit the cleavage of ATXN3 but also protect the QA-induced excitotoxicity from the Purkinje progenitor loss.


Assuntos
Ataxina-3/metabolismo , Anidridos Ftálicos/farmacologia , Células de Purkinje/efeitos dos fármacos , Proteínas Repressoras/metabolismo , Animais , Autofagia/efeitos dos fármacos , Calpaína/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Doença de Machado-Joseph/metabolismo , Masculino , Complexo de Endopeptidases do Proteassoma/metabolismo , Células de Purkinje/metabolismo
13.
Natl Sci Rev ; 9(1): nwab026, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35111329

RESUMO

Synthesis of atomically dispersed catalysts with high metal loading and thermal stability is challenging but particularly valuable for industrial application in heterogeneous catalysis. Here, we report a facile synthesis of a thermally stable atomically dispersed Ir/α-MoC catalyst with metal loading as high as 4 wt%, an unusually high value for carbide supported metal catalysts. The strong interaction between Ir and the α-MoC substrate enables high dispersion of Ir on the α-MoC surface, and modulates the electronic structure of the supported Ir species. Using quinoline hydrogenation as a model reaction, we demonstrate that this atomically dispersed Ir/α-MoC catalyst exhibits remarkable reactivity, selectivity and stability, for which the presence of high-density isolated Ir atoms is the key to achieving high metal-normalized activity and mass-specific activity. We also show that the water-promoted quinoline hydrogenation mechanism is preferred over the Ir/α-MoC, and contributes to high selectivity towards 1,2,3,4-tetrahydroquinoline. The present work demonstrates a new strategy in constructing a high-loading atomically dispersed catalyst for the hydrogenation reaction.

14.
J Am Chem Soc ; 144(8): 3535-3542, 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35107999

RESUMO

Identification of catalytic active sites is pivotal in the design of highly effective heterogeneous metal catalysts, especially for structure-sensitive reactions. Downsizing the dimension of the metal species on the catalyst increases the dispersion, which is maximized when the metal exists as single atoms, namely, single-atom catalysts (SACs). SACs have been reported to be efficient for various catalytic reactions. We show here that the Pt SACs, although with the highest metal atom utilization efficiency, are totally inactive in the cyclohexane (C6H12) dehydrogenation reaction, an important reaction that could enable efficient hydrogen transportation. Instead, catalysts enriched with fully exposed few-atom Pt ensembles, with a Pt-Pt coordination number of around 2, achieve the optimal catalytic performance. The superior performance of a fully exposed few-atom ensemble catalyst is attributed to its high d-band center, multiple neighboring metal sites, and weak binding of the product.

15.
Microbiol Spectr ; 9(3): e0077921, 2021 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-34878301

RESUMO

Phenotypic plasticity is a common strategy adopted by fungal pathogens to adapt to diverse host environments. Candida haemulonii is an emerging multidrug-resistant human pathogen that is closely related to Candida auris. Until recently, it was assumed that C. haemulonii is incapable of phenotypic switching or filamentous growth. In this study, we report the identification of three distinct phenotypes in C. haemulonii: white, pink, and filament. The white and pink phenotypes differ in cellular size, colony morphology, and coloration on phloxine B- or CuSO4-containing agar. Switching between the white and pink cell types is heritable and reversible and is referred to as "the primary switching system." The additional switch phenotype, filament, has been identified and exhibits obviously filamentous morphology when grown on glycerol-containing medium. Several unique characteristics of the filamentous phenotype suggest that switching from or to this phenotype poses as a second yeast-filament switching system. The yeast-filament switch is nonheritable and temperature-dependent. Low temperatures favor the filamentous phenotype, whereas high temperatures promote filament-yeast transition. We further demonstrated that numerous aspects of the distinct cell types differ in numerous biological aspects, including their high temperature response, specific gene expression, CuSO4 tolerance, secreted aspartyl protease (SAP) activity, and virulence. Therefore, transition among the three phenotypes could enable C. haemulonii to rapidly adapt to, survive, and thrive in certain host niches, thereby contributing to its virulence. IMPORTANCE The capacity to switch between distinct cell types, known as phenotypic switching, is a common strategy adopted by Candida species to adapt to diverse environments. Despite considerable studies on phenotypic plasticity of various Candida species, Candida haemulonii is considered to be incapable of phenotypic switching or filamentous growth. Here, we report and describe filamentation and three distinct phenotypes (white, pink, and filament) in C. haemulonii. The three cell types differ in cellular and colony appearance, gene expression profiles, CuSO4 tolerance, and virulence. C. haemulonii cells switch heritably and reversibly between white and pink cell types, which is referred to as the "primary switching system." Switching between pink and filamentous phenotypes is nonheritable and temperature-dependent, representing a second switching system. As in other Candida species, switching among distinct morphological types may provide C. haemulonii with phenotypic plasticity for rapid responses to the changing host environment, and may contribute to its virulence.


Assuntos
Adaptação Fisiológica/fisiologia , Variação Biológica da População/fisiologia , Candida/classificação , Candida/fisiologia , Fenótipo , Ácido Aspártico Proteases/metabolismo , Candida/genética , Candidíase/microbiologia , Sulfato de Cobre/farmacologia , Regulação Fúngica da Expressão Gênica/genética , Temperatura Alta , Humanos
16.
Materials (Basel) ; 14(21)2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34771842

RESUMO

Dense SiC ceramics were fabricated by high-temperature physical vapor transport (HTPVT) growth process using SiC nanoarrays as the crystal seeds, which was obtained by vacuum heat treatment of amorphous SiC films prepared by plasma-enhanced chemical vapor deposition (PECVD) with a porous anodic aluminum oxide (AAO) template. In the HTPVT process, two-step holding was adopted, and the temperature at the first step was controlled at 2100 and 2150 °C to avoid SiC nanoarrays evaporation, and the grain size of SiC crystal increased with the increase in temperature and decrease in the pressure of Ar. The temperature of the second step was 2300 °C, and rapid SiC grain growth and gradual densification were achieved. The prepared SiC ceramics exhibited a relative density of more than 99%, an average grain size of about 100 µm, a preferred orientation along the (0 0 0 6) plane, a Vickers hardness of about 29 GPa, a flexural strength of about 360 MPa, and thermal conductivity at room temperature of more than 200 W·m-1·K-1.

17.
Front Microbiol ; 12: 744502, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690991

RESUMO

Wickerhamomyces anomalus is an emerging pathogen, which has been associated with clonal outbreaks and poor clinical outcomes. Despite being an important emerging yeasts species, our understanding concerning the microbiological and clinical characteristics of infections due to this species is limited. Herein, we are reporting a retrospective analysis of fungemia patients with W. anomalus from a 2,100-bed hospital in Shanghai during 2014-2016. Moreover, we conducted an extensive literature review to gain a deeper clinical and microbiological insights. Detailed clinical data were recorded. Antifungal susceptibility testing (AFST) followed CLSI M27-A3, and isolates were identified using MALDI-TOF MS. In total, 13 patients were identified with a mortality rate of 38.5% (5/13). Central venous catheter (CVC), broad-spectrum antibiotic therapy, total parenteral nutrition (TPN), surgery, and mechanical ventilation were the most frequently observed risk factors. Eight patients (61.5%) experienced mixed bacterial/Candida bloodstream infections, and four patients developed mixed candidemia (MC). W. anomalus isolates showed high minimum inhibitory concentrations (MICs) against all azoles tested and flucytosine, while AMB showed the highest in vitro activity. Azoles were used for 84.6% (11/13) of the cases, while 36.4% (4/11) of them died. When combining with the AFST data and the literature review, our study highlights the poor efficacy of azoles and optimal efficacy of AMB and LAMB against infections caused by W. anomalus. In conclusion, our study highlights the emerging threat of W. anomalus affecting both neonates and adults. Furthermore, our results advocate the use of AMB formulations rather than azoles among patients infected with W. anomalus. Future studies are warranted to reach a definitive consensus regarding the utility of echinocandins among such patients.

19.
Nat Commun ; 12(1): 2664, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976155

RESUMO

Metal nanoparticle (NP), cluster and isolated metal atom (or single atom, SA) exhibit different catalytic performance in heterogeneous catalysis originating from their distinct nanostructures. To maximize atom efficiency and boost activity for catalysis, the construction of structure-performance relationship provides an effective way at the atomic level. Here, we successfully fabricate fully exposed Pt3 clusters on the defective nanodiamond@graphene (ND@G) by the assistance of atomically dispersed Sn promoters, and correlated the n-butane direct dehydrogenation (DDH) activity with the average coordination number (CN) of Pt-Pt bond in Pt NP, Pt3 cluster and Pt SA for fundamentally understanding structure (especially the sub-nano structure) effects on n-butane DDH reaction at the atomic level. The as-prepared fully exposed Pt3 cluster catalyst shows higher conversion (35.4%) and remarkable alkene selectivity (99.0%) for n-butane direct DDH reaction at 450 °C, compared to typical Pt NP and Pt SA catalysts supported on ND@G. Density functional theory calculation (DFT) reveal that the fully exposed Pt3 clusters possess favorable dehydrogenation activation barrier of n-butane and reasonable desorption barrier of butene in the DDH reaction.

20.
ACS Appl Mater Interfaces ; 13(12): 14407-14416, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33750095

RESUMO

Developing room-temperature phosphorescence (RTP) materials with color-tunability performance in an aqueous environment is crucial for application in optoelectronic areas to a higher stage, such as multicolor display, visual detection of external stimulus, and high-level information anticounterfeiting, but still faces a formidable challenge. Herein, we propose an efficient design strategy to develop excitation wavelength-responsive RTP supramolecular co-assembly systems of a simple benzoic acid derivative and Laponite (Lap) clay nanoplates in aqueous solution, displaying an ultralong lifetime (0.632 s) and a high phosphorescence quantum efficiency (18.04%) simultaneously. Experimental and theoretical research studies suggest that this distinctive feature is due to the generation of more and efficient intersystem crossing pathways benefiting from the coexistence of isolated and J-aggregation states via controlling the doping of the benzoic acid derivative and the inhibition of phosphorescence quenching by water because of the synergistic effects of robust hydrogen-bonding interactions between Lap and the benzoic acid derivative, J-aggregations of the benzoic acid derivative, and good oxygen tolerance of the Lap clay. By virtue of their excellent RTP performances in aqueous solution, the visual colorimetric detection of Ag+ in a water environment was achieved for the first time, and visible and high-level information encryption was accomplished as well.

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