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1.
Scand J Gastroenterol ; : 1-7, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38742832

RESUMO

BACKGROUND AND AIM: To explore the feasibility of a standardized training and assessment system for magnetically controlled capsule gastroscopy (MCCG). METHODS: The results of 90 trainees who underwent the standardized training and assessment system of the MCCG at the First Affiliated Hospital of Xi'an Jiaotong University from May 2020 to November 2023 was retrospectively analyzed. The trainees were divided into three groups according to their medical backgrounds: doctor, nurse, and non-medical groups. The training and assessment system adopted the '7 + 2' mode, seven days of training plus two days of theoretical and operational assessment. The passing rates of theoretical, operational, and total assessment were the primary outcomes. Satisfaction and mastery of the MCCG was checked. RESULTS: Ninety trainees were assessed; theoretical assessment's passing rates in the three groups were 100%. The operational and total assessment passing rates were 100% (25/25), 97.92% (47/48), and 94.12% (16/17), for the doctor, nurse, and non-doctor groups respectively, with no significant difference (χ2 = 1.741, p = 0.419). No bleeding or perforation occurred during the procedure. Approximately, 96.00% (24/25), 95.83% (46/48), and 94.12% (16/17) of the doctor, nurse and non-medical groups anonymously expressed great satisfaction, respectively, without statistically significant difference (χ2 = 0.565, p = 1.000). The average follow-up time was 4-36 months, and 87 trainees (96.67%) had mastered the operation of the MCCG in daily work. CONCLUSIONS: Standardized training and assessment of magnetically controlled capsule endoscopists is effective and feasible. Additionally, a strict assessment system and long-term communication and learning can improve teaching effects.

2.
Exp Cell Res ; 438(2): 114054, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38657723

RESUMO

Recent studies have suggested exosomes (EXO) as potential therapeutic tools for cardiovascular diseases, including atherosclerosis (AS). This study investigates the function of bone marrow stem cell (BMSC)-derived exosomes (EXO) on macrophage pyroptosis in AS and explores the associated mechanism. BMSC-EXO were isolated from healthy mice and identified. RAW264.7 cells (mouse macrophages) were exposed to oxLDL to simulate an AS condition. BMSC-EXO treatment enhanced viability and reduced lactate dehydrogenase release of macrophages. An animal model of AS was established using ApoE-/- mice. BMSC-EXO treatment suppressed plaque formation as well as macrophage and lipid infiltration in mouse aortic tissues. Moreover, BMSC-EXO decreased concentrations of pyroptosis-related markers interleukin (IL)-1ß, IL-18, cleaved-caspase-1 and gasdermin D in vitro and in vivo. Long non-coding RNA AU020206 was carried by the BMSC-EXO, and it bound to CCAAT enhancer binding protein beta (CEBPB) to block CEBPB-mediated transcriptional activation of NLR family pyrin domain containing 3 (NLRP3). Functional assays revealed that silencing of AU020206 aggravated macrophage pyroptosis and exacerbated AS symptoms in mice. These exacerbations were blocked upon CEBPB silencing but then restored after NLRP3 overexpression. In conclusion, this study demonstrates that AU020206 delivered by BMSC-EXO alleviates macrophage pyroptosis in AS by blocking CEBPB-mediated transcriptional activation of NLRP3.


Assuntos
Aterosclerose , Proteína beta Intensificadora de Ligação a CCAAT , Exossomos , Macrófagos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , RNA Longo não Codificante , Animais , Piroptose/efeitos dos fármacos , Piroptose/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Camundongos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Aterosclerose/metabolismo , Aterosclerose/genética , Aterosclerose/patologia , RNA Longo não Codificante/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/genética , Exossomos/metabolismo , Células RAW 264.7 , Camundongos Endogâmicos C57BL , Masculino
3.
iScience ; 27(4): 109381, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38500822

RESUMO

Sleep disturbance led by BMAL1-deficiency has been recognized both in rodent and non-human primate models. Yet it remained unclear how their diurnal brain oscillations were affected upon BMAL1 ablation and what caused the discrepancy in the quantity of sleep between the two species. Here, we investigated diurnal electroencephalographs of BMAL1-deficient mice and cynomolgus monkeys at young adult age and uncovered a shared defect of dysregulated high-frequency oscillations by Kullback-Leibler divergence analysis. We found beta and gamma oscillations were significantly disturbed in a day versus night manner in BMAL1-deficient monkeys, while in mice the beta band difference was less evident. Notably, the dysregulation of beta oscillations was particularly associated with psychiatric behaviors in BMAL1-deficient monkeys, including the occurrence of self-injuring and delusion-like actions. As such psychiatric phenotypes were challenging to uncover in rodent models, our results offered a unique method to study the correlation between circadian clock dysregulation and psychiatric disorders.

4.
BMJ ; 384: e078581, 2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443074

RESUMO

OBJECTIVE: To evaluate the diagnostic accuracy and safety of using magnetically guided capsule endoscopy with a detachable string (ds-MCE) for detecting and grading oesophagogastric varices in adults with cirrhosis. DESIGN: Prospective multicentre diagnostic accuracy study. SETTING: 14 medical centres in China. PARTICIPANTS: 607 adults (>18 years) with cirrhosis recruited between 7 January 2021 and 25 August 2022. Participants underwent ds-MCE (index test), followed by oesophagogastroduodenoscopy (OGD, reference test) within 48 hours. The participants were divided into development and validation cohorts in a ratio of 2:1. MAIN OUTCOME MEASURES: The primary outcomes were the sensitivity and specificity of ds-MCE in detecting oesophagogastric varices compared with OGD. Secondary outcomes included the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices and the diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices. RESULTS: ds-MCE and OGD examinations were completed in 582 (95.9%) of the 607 participants. Using OGD as the reference standard, ds-MCE had a sensitivity of 97.5% (95% confidence interval 95.5% to 98.7%) and specificity of 97.8% (94.4% to 99.1%) for detecting oesophagogastric varices (both P<0.001 compared with a prespecified 85% threshold). When using the optimal 18% threshold for luminal circumference of the oesophagus derived from the development cohort (n=393), the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices in the validation cohort (n=189) were 95.8% (89.7% to 98.4%) and 94.7% (88.2% to 97.7%), respectively. The diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices was 96.3% (92.6% to 98.2%), 96.9% (95.2% to 98.0%), and 96.7% (95.0% to 97.9%), respectively. Two serious adverse events occurred with OGD but none with ds-MCE. CONCLUSION: The findings of this study suggest that ds-MCE is a highly accurate and safe diagnostic tool for detecting and grading oesophagogastric varices and is a promising alternative to OGD for screening and surveillance of oesophagogastric varices in patients with cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03748563.


Assuntos
Endoscopia por Cápsula , Varizes Esofágicas e Gástricas , Varizes , Adulto , Humanos , Varizes Esofágicas e Gástricas/diagnóstico , Varizes Esofágicas e Gástricas/etiologia , Cirrose Hepática/complicações , Estudos Prospectivos
5.
Small ; : e2311125, 2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38342583

RESUMO

Research on 2D materials originally focused on the highly symmetrical materials like graphene, h-BN. Recently, 2D materials with low-symmetry lattice such as PdSe2 have drawn extensive attention, due to the interesting layer-dependent bandgap, promising mechanical properties and excellent thermoelectric performance, etc. In this work, the phonon thermal transport is studied in PdSe2 with a pentagonal fold structure. The thermal conductivity of PdSe2 flakes with different thicknesses ranging from few nanometers to several tens of nanometers is measured through the thermal bridge method, where the thermal conductivity increases from 5.04 W mk-1 for 60 nm PdSe2 to 34.51 W mk-1 for the few-layer one. The atomistic modelings uncover that with the thickness thinning down, the lattice of PdSe2 becomes contracted and the phonon group velocity is enhanced, leading to the abnormal increase in the thermal conductivity. And the upshift of the optical phonon modes contributes to the increase of the thermal conductivity as well by creating less acoustic phonon scattering as the thickness reduces. This study probes the interesting abnormal thickness-dependent thermal transport in 2D materials, which promotes the potential thermal management at nanoscale.

6.
Environ Toxicol ; 39(1): 341-356, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37713600

RESUMO

The Warburg effect is the preference of cancer cells to use glycolysis rather than oxidative phosphorylation to generate energy. Accumulating evidence suggests that aerobic glycolysis is widespread in hepatocellular carcinoma (HCC) and closely related to tumorigenesis. The purpose of this study was to investigate the role and mechanism of forkhead box P2 (FOXP2) in aerobic glycolysis and tumorigenesis in HCC. Here, we found that FOXP2 was lower expressed in HCC tissues and cells than in nontumor tissues and normal hepatocytes. Overexpression of FOXP2 suppressed cell proliferation and invasion of HCC cells and promoted cell apoptosis in vitro, and hindered the growth of mouse xenograft tumors in vivo. Further researches showed that FOXP2 inhibited the Warburg effect in HCC cells. Moreover, we demonstrated that FOXP2 up-regulated the expression of fructose-1, 6-diphosphatase (FBP1), and the inhibitory effect of FOXP2 on glycolysis was dependent on FBP1. Mechanistically, as a transcription factor, FOXP2 negatively regulated the transcription of lysine-specific demethylase 5A (KDM5A), and then blocked KDM5A-induced H3K4me3 demethylation in FBP1 promoter region, thereby promoting the expression of FBP1. Consistently, overexpressing KDM5A or silencing FBP1 effectively reversed the inhibitory effect of FOXP2 on HCC progression. Together, our findings revealed the mechanistic role of the FOXP2/KDM5A/FBP1 axis in glycolysis and malignant progression of HCC cells, providing a potential molecular target for the therapy of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Linhagem Celular Tumoral , Glicólise , Transformação Celular Neoplásica/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Proteína 2 de Ligação ao Retinoblastoma/metabolismo , Fatores de Transcrição Forkhead/metabolismo
7.
Langmuir ; 40(1): 380-388, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38153039

RESUMO

Surface-enhanced Raman spectroscopy (SERS) has emerged as a highly sensitive trace detection technique in recent decades, yet its exceptional performance remains elusive in semiconductor materials due to the intricate and ambiguous nature of the SERS mechanism. Herein, we have synthesized MoS2 nanoflowers (NFs) decorated with Au nanoparticles (NPs) by hydrothermal and redox methods to explore the size-dependence SERS effect. This strategy enhances the interactions between the substrate and molecules, resulting in exceptional uniformity and reproducibility. Compared to the unadorned Au nanoparticles (NPs), the decoration of Au NPs induces an n-type effect on MoS2, resulting in a significant enhancement of the SERS effect. This augmentation empowers MoS2 to achieve a low limit of detection concentration of 2.1 × 10-9 M for crystal violet (CV) molecules and the enhancement factor (EF) is about 8.52 × 106. The time-stability for a duration of 20 days was carried out, revealing that the Raman intensity of CV on the MoS2/Au-6 substrate only exhibited a reduction of 24.36% after undergoing aging for 20 days. The proposed mechanism for SERS primarily stems from the synergistic interplay among the resonance of CV molecules, local surface plasma resonance (LSPR) of Au NPs, and the dual-step charge transfer enhancement. This research offers comprehensive insights into SERS enhancement and provides guidance for the molecular design of highly sensitive SERS systems.

8.
Anal Chem ; 95(42): 15736-15744, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37816003

RESUMO

Immobilization-free sensors (IFSs), with no requirement of fixing the recognition element to the electrode surface, have received increasing attention due to their unique advantages of reusable electrodes, not being limited by the load of the recognition element, and not being easily changed to the structure of the probe. In the present work, an effective visible light-driven immobilization-free photoelectric aptasensor for ultrasensitive detection of atrazine (ATZ) was proposed based on a reusable BiOBr/Ag NP substrate electrode with ultrafast charge transfer. Controllable thiols were used as conditioning agents for the photoelectric signal. The ingeniously designed bifunctional graphene can act as not only a molecular "bridge" for the ATZ aptamer through a strong π-π stacking effect, obtaining a graphene-aptamer complex, serving as a homogeneous recognition element, but also a switch for signal modulation for quantitative detection of target substances. Benefiting from the synergistic effect of the above-mentioned factors, the proposed sensor is capable of ultrasensitive and highly selective detection of ATZ in real water samples with a low detection limit of 1.2 pM and a wide linear range from 5.0 pM to 10.0 nM. Furthermore, it shows high stability, good selectivity, and strong anti-interference ability. Thus, this work has provided a fresh perspective for designing advanced immobilization-free photoelectric sensors and convenient detection of environmental pollutants.

9.
Horm Metab Res ; 55(10): 701-710, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37813099

RESUMO

Circular RNAs (circRNAs) are implicated in regulating the pathogenesis of papillary thyroid carcinoma (PTC). Herein, we aimed to investigate how circRNA phosphatidylinositol 4-kinase IIIα (circPI4KA, hsa_circ_0062389) functioned as an oncogene in PTC. CircPI4KA, microRNA-1287-5p (miR-1287-5p) and Neuropilin-2 (NRP2) level detection were completed by reverse transcription-quantitative polymerase chain reaction assay. Cell proliferation was assessed through Cell Counting Kit-8 assay, colony formation assay, and EdU assay. Transwell assay was used for detecting migration and invasion abilities. Cell migration was also determined by wound healing assay. Cell apoptosis was assessed using flow cytometry assay. The protein examination was performed using western blot. Glycolysis was evaluated via commercial kits. Dual-luciferase reporter assay and RNA immunoprecipitation assay were conducted for target analysis. The role of circPI4KA in vivo was explored and analyzed via tumor xenograft assay. CircPI4KA was significantly upregulated in PTC tissues and cells. Knockdown of circPI4KA suppressed proliferation, migration, invasion, glycolysis, and induced apoptosis of PTC cells. CircPI4KA interacted with miR-1287-5p in PTC cells. The antitumor function of circPI4KA downregulation was reversed by inhibition of miR-1287-5p. The miR-1287-5p directly targeted NRP2, and circPI4KA elevated the NRP2 expression by sponging miR-1287-5p. PTC progression was impeded by miR-1287-5p via targeting NRP2. Silencing circPI4KA inhibited tumor growth in vivo through the miR-1287-5p/NRP2 axis. The collective results revealed that circPI4KA induced the upregulation of NRP2 via sponging miR-1287-5p, thus acting as a carcinogenic factor in PTC.


Assuntos
MicroRNAs , Neuropilina-2 , RNA Circular , Neoplasias da Glândula Tireoide , Humanos , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Glicólise/genética , MicroRNAs/genética , Neuropilina-2/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , RNA Circular/genética
10.
Res Sq ; 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37674728

RESUMO

There is limited research investigating the relationship between self-reported diabetes mellitus and subjective sleep patterns. Our study aims to explore this association by analyzing trends in a cohort study conducted in China using data from the China Health and Nutrition Survey longitudinal research (CHNS). We used multilevel logistic regression models to analyze the relationship. Our findings indicate that the prevalence of self- reported diabetes in China increased from 1.10% in 2004 to 3.36% in 2015, with an increase in the prevalence of short-term sleep from 7.03-10.24%. The prevalence of self-reported diabetes increased with increasing BMI levels (Normal and below: 0.67-2.16%, Overweight: 1.58-4.35%, Obesity: 2.68-6.57%, p < 0.01). The short-term sleep subgroup had the highest prevalence (2.14-5.64%). Additionally, we found significant associations between age, education level, ethnicity, coffee, smoking, drinking and the self-reported diabetes. Interestingly, the risk ratios for self-reported diabetes differed between sleep durations. With 6-8hours as the reference group, the risk ratios for self-reported diabetes in the short-term, and long-term sleep subgroups were 1.80 (95% CI: 1.23-2.63), and 1.41 (95%CI: 1.01-1.96), respectively. Raising awareness about the impact of irregular sleep duration on diabetes risk is essential, and these initiatives may serve as effective policies for diabetes control.

11.
Brain Sci ; 13(8)2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37626573

RESUMO

BACKGROUND: Stroke-associated pneumonia (SAP) is a common stroke complication, and the changes in the gut microbiota composition may play a role. Our study aimed to evaluate the predictive ability of gut microbiota for SAP. METHODS: Acute ischemic stroke patients were prospectively enrolled and divided into two groups based on the presence or absence of SAP. The composition of gut microbiota was characterized by the 16S RNA Miseq sequencing. The gut microbiota that differed significantly between groups were incorporated into the conventional risk scores, the Acute Ischemic Stroke-Associated Pneumonia Score (AIS-APS), and the Age, Atrial fibrillation, Dysphagia, Sex, Stroke Severity Score (A2DS2). The predictive performances were assessed in terms of the area under the curve (AUC), the Net Reclassification Improvement (NRI), and the Integrated Discrimination Improvement (IDI) indices. RESULTS: A total of 135 patients were enrolled, of whom 43 had SAP (31%). The short-chain fatty acids (SCFAs)-producing bacteria, such as Bacteroides, Fusicatenibacter, and Butyricicoccus, were decreased in the SAP group. The integrated models showed better predictive ability for SAP (AUC = 0.813, NRI = 0.333, p = 0.052, IDI = 0.038, p = 0.018, for AIS-APS; AUC = 0.816, NRI = 0.575, p < 0.001, IDI = 0.043, p = 0.007, for A2DS2) in comparison to the differential genera (AUC = 0.699) and each predictive score (AUCAISAPS = 0.777; AUCA2DS2 = 0.777). CONCLUSIONS: The lower abundance of SCFAs-producing gut microbiota after acute ischemic stroke was associated with SAP and may play a role in SAP prediction.

12.
Biomed Pharmacother ; 162: 114593, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37001184

RESUMO

Multiple sclerosis (MS) is an autoimmune, inflammatory demyelinating disorder of the central nervous system. Accumulating evidence has underscored the therapeutic potential of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (BMSC-Exos) containing bioactive compounds in MS. Herein, the current study sought to characterize the mechanism of BMSC-Exos harboring miR-367-3p both in BV2 microglia by Erastin-induced ferroptosis and in experimental autoimmune encephalomyelitis (EAE), a typical animal model of MS. Exosomes were firstly isolated from BMSCs and identified for further use. BV2 microglia were co-cultured with miR-367-3p-containing BMSC-Exos, followed by an assessment of cell ferroptosis. Mechanistic exploration was furthered by the interaction of miR-367-3p and its downstream regulators. Lastly, BMSC-Exos harboring miR-367-3p were injected into EAE mice for in vivo validation. BMSC-Exos carrying miR-367-3p restrained microglial ferroptosis in vitro. Mechanistically, miR-367-3p could bind to Enhancer of zeste homolog 2 (EZH2) and restrain EZH2 expression, leading to the over-expression of solute carrier family 7 member 11 (SLC7A11). Meanwhile, over-expression of SLC7A11 resulted in Glutathione Peroxidase 4 (GPX4) activation and ferroptosis suppression. Ectopic expression of EZH2 in vitro negated the protective effects of BMSC-Exos. Furthermore, BMSC-Exos containing miR-367-3p relieved the severity of EAE by suppressing ferroptosis and restraining EZH2 expression in vivo. Collectively, our findings suggest that BMSC-Exos carrying miR-367-3p brings about a significant decline in microglia ferroptosis by repressing EZH2 and alleviating the severity of EAE in vivo, suggesting a possible role of miR-367-3p overexpression in the treatment strategy of EAE. AVAILABILITY OF DATA AND MATERIALS: The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.


Assuntos
Encefalomielite Autoimune Experimental , Proteína Potenciadora do Homólogo 2 de Zeste , Ferroptose , Células-Tronco Mesenquimais , MicroRNAs , Animais , Camundongos , Encefalomielite Autoimune Experimental/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Células-Tronco Mesenquimais/metabolismo , Microglia/metabolismo , MicroRNAs/metabolismo
13.
Int J Nanomedicine ; 18: 1145-1158, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36915699

RESUMO

Background: Drug-resistant microbes pose a global health concern, requiring the urgent development of effective antibacterial agents and strategies in clinical practice. Therefore, there is an urgent need to explore novel antibacterial materials to effectively eliminate bacteria. The synthesis of quaternary phosphonium salt in haloargentate systems, wherein the phosphorus atom is represented in a cationic form, is a possible strategy for the development of antibacterial materials. Methods: Using (triphenyl)phosphonium-based quaternary phosphorus salts with different spacer lengths (n=2, 4, 6) as a template, we designed three kinds of quaternary phosphorus salts as effective antibacterial agents against drug-resistant bacteria. Results: The synthesized quaternary phosphorus salt of (1,4-DBTPP)Br2 effectively prevented the formation of the bacterial biofilms, and degraded bacterial membranes and cell walls by promoting the production of reactive oxygen species, which exhibited effective therapeutic effects in a rat model of a superficial wound infected with methicillin-resistant Staphylococcus aureus. Conclusion: The quaternary phosphorus salt (1,4-DBTPP)Br2 demonstrated hemocompatibility and low toxicity, revealing its potential in the treatment of clinical infections.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Ratos , Animais , Fósforo , Sais/farmacologia , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Cloreto de Sódio/farmacologia , Cicatrização
14.
Nature ; 616(7955): 190-198, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36949198

RESUMO

The membrane-integrated synthase FKS is involved in the biosynthesis of ß-1,3-glucan, the core component of the fungal cell wall1,2. FKS is the target of widely prescribed antifungal drugs, including echinocandin and ibrexafungerp3,4. Unfortunately, the mechanism of action of FKS remains enigmatic and this has hampered development of more effective medicines targeting the enzyme. Here we present the cryo-electron microscopy structures of Saccharomyces cerevisiae FKS1 and the echinocandin-resistant mutant FKS1(S643P). These structures reveal the active site of the enzyme at the membrane-cytoplasm interface and a glucan translocation path spanning the membrane bilayer. Multiple bound lipids and notable membrane distortions are observed in the FKS1 structures, suggesting active FKS1-membrane interactions. Echinocandin-resistant mutations are clustered at a region near TM5-6 and TM8 of FKS1. The structure of FKS1(S643P) reveals altered lipid arrangements in this region, suggesting a drug-resistant mechanism of the mutant enzyme. The structures, the catalytic mechanism and the molecular insights into drug-resistant mutations of FKS1 revealed in this study advance the mechanistic understanding of fungal ß-1,3-glucan biosynthesis and establish a foundation for developing new antifungal drugs by targeting FKS.


Assuntos
Microscopia Crioeletrônica , Glucosiltransferases , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Antifúngicos/farmacologia , beta-Glucanas/metabolismo , Domínio Catalítico , Membrana Celular/química , Membrana Celular/metabolismo , Farmacorresistência Fúngica/efeitos dos fármacos , Farmacorresistência Fúngica/genética , Equinocandinas/farmacologia , Glucosiltransferases/antagonistas & inibidores , Glucosiltransferases/química , Glucosiltransferases/genética , Glucosiltransferases/metabolismo , Glucosiltransferases/ultraestrutura , Testes de Sensibilidade Microbiana , Mutação , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/enzimologia , Proteínas de Saccharomyces cerevisiae/antagonistas & inibidores , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/ultraestrutura
15.
Exp Neurol ; 363: 114374, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36907352

RESUMO

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system and is marked by inflammation and damage to the myelin sheath surrounding nerve fibers. Recent studies have highlighted the therapeutic value of exosomes (Exos) obtained from bone marrow mesenchymal stem cells (BMSCs) in MS treatment. These BMSC-Exos contain biologically active molecules that show promising results in preclinical evaluations. The aim of this study was to investigate the mechanism of BMSC-Exos containing miR-23b-3p in both LPS-stimulated BV2 microglia and in experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Exos were isolated from BMSCs, and their effects were evaluated in vitro by co-culturing with BV2 microglia. The interaction between miR-23b-3p and its downstream targets was also explored. The efficacy of BMSC-Exos was further verified in vivo by injecting the Exos into EAE mice. The results showed that BMSC-Exos containing miR-23b-3p reduced microglial pyroptosis in vivo by specifically binding to and suppressing the expression of NEK7. In vivo, BMSC-Exos containing miR-23b-3p alleviated the severity of EAE by decreasing microglial inflammation and pyroptosis via the repression of NEK7. These findings provide new insights into the therapeutic potential of BMSC-Exos containing miR-23b-3p for MS.


Assuntos
Encefalomielite Autoimune Experimental , Células-Tronco Mesenquimais , MicroRNAs , Esclerose Múltipla , Camundongos , Animais , Microglia/metabolismo , Encefalomielite Autoimune Experimental/terapia , Encefalomielite Autoimune Experimental/metabolismo , Piroptose , Células-Tronco Mesenquimais/metabolismo , Inflamação/metabolismo , Esclerose Múltipla/terapia , MicroRNAs/genética , MicroRNAs/metabolismo
16.
Nano Lett ; 23(5): 1726-1734, 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36794942

RESUMO

Zn metal has received immense interest as a promising anode of rechargeable aqueous batteries for grid-scale energy storage. Nevertheless, the uncontrollable dendrite growth and surface parasitic reactions greatly retard its practical implementation. Herein, we demonstrate a seamless and multifunctional metal-organic framework (MOF) interphase for building corrosion-free and dendrite-free Zn anodes. The on-site coordinated MOF interphase with 3D open framework structure could function as a highly zincophilic mediator and ion sifter that synergistically induces fast and uniform Zn nucleation/deposition. In addition, the surface corrosion and hydrogen evolution are significantly suppressed by the interface shielding of the seamless interphase. An ultrastable Zn plating/stripping is achieved with elevated Coulombic efficiency of 99.2% over 1000 cycles and prolonged lifetime of 1100 h at 10 mA cm-2 with a high cumulative plated capacity of 5.5 Ah cm-2. Moreover, the modified Zn anode assures the MnO2-based full cells with superior rate and cycling performance.

17.
J Clin Med ; 12(3)2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36769839

RESUMO

BACKGROUND: Postoperative nausea and vomiting (PONV) is one of the most common complications after general anesthesia. The traditional comprehensive management of PONV usually uses one or two drugs, but this regimen fails to meet the requirements of the latest version of PONV guidelines. The purpose of this study was to evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on high-risk PONV patients who are undergoing laparoscopic gynecological surgery. METHODS: In total, 162 high-risk PONV patients were randomly divided into an experimental group (n = 81) and a control group (n = 81). Both groups were injected with 4 mg of dexamethasone and 0.25 mg of palonosetron. In the experimental group, Nei-guan (PC6) and He-gu (LI4) were stimulated by a transcutaneous acupoint electrical stimulation instrument (HANS200E) 30 min before the surgery. The control group also received electrodes but no stimulation. Variance analysis and rank sum test were used to compare the differences between the two groups. RESULTS: The results of the incidence of postoperative nausea, vomiting, NRS score, degree of abdominal distension, and time to first flatus in the experimental group were lower than those in the control group. Nursing satisfaction of the experimental group was higher than that of the control group. CONCLUSIONS: The study demonstrates that TEAS combined with dexamethasone and palonosetron can effectively prevent PONV, reduce postoperative abdominal distension and postoperative pain, and shorten the first postoperative flatus time in high-risk patients with PONV. At the same time, it can improve nursing satisfaction.

18.
J Thorac Dis ; 15(1): 135-145, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36794127

RESUMO

Background: Stanford type B aortic dissection (TBAD) is a rare cardiovascular emergency with rapid onset and great harm. Currently, no relevant studies have analyzed the difference in clinical benefits of endovascular repair in patients with TBAD in acute and non-acute stages. To investigate the clinical characteristics and prognosis of endovascular repair in patients with TBAD at different surgical timing. Methods: The medical records of 110 patients with TBAD from June 2014 to June 2022 were retrospectively selected as the study subjects. The patients were divided into an acute group (onset time ≤14 days) and a non-acute group (onset time >14 days) according to the time to surgery, and the two groups were compared in terms of surgery and hospitalization, aortic remodeling, and follow-up results. Univariate and multivariate logistic regression were used to analyze the factors affecting the prognosis of TBAD treated with endoluminal repair. Results: The proportion of pleural effusion, heart rate, the rate of complete thrombosis of the false lumen and the difference in the maximum diameter of the false lumen in the acute group were higher than those in the non-acute group (P=0.015, <0.001, 0.029, <0.001). The length of hospital stay and the maximum postoperative diameter of the false lumen was lower than in the non-acute group (P=0.001, 0.004). There was no statistically significant difference between the two groups in the technical success rate, overlapping stent length, overlapping stent diameter, immediate postoperative contrast type I endoleak, incidence of renal failure, ischemic disease, endoleaks, aortic dilatation, retrograde type A aortic coarctation, and death (P=0.386, 0.551, 0.093, 0.176, 0.223, 0.739, 0.085, 0.098, 0.395, 0.386); coronary artery disease [odds ratio (OR) =6.630, P=0.012], pleural effusion (OR =5.026, P=0.009), non-acute surgery (OR =2.899, P=0.037), and involvement of the abdominal aorta (OR =11.362, P=0.001) were all independent risk factors affecting the prognosis of TBAD treated with endoluminal repair. Conclusions: Acute phase endoluminal repair of TBAD may contribute to aortic remodeling, and the prognosis of TBAD patients can be assessed clinically in combination with coronary artery disease, pleural effusion, and involvement of the abdominal aorta for early intervention to reduce the associated mortality.

19.
J Colloid Interface Sci ; 633: 24-31, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36434932

RESUMO

Corrosion engineering is an efficient strategy to achieve durable oxygen evolution reaction (OER) catalysts at high current densities beyond 500 mA cm-2. However, the spontaneous electrochemical corrosion has a slow reaction rate, and most of them need to add large amounts of salts (such as NaCl) to accelerate the corrosion process. In this report, a novel and effective phytic acid (PA)-assisted in situ electrochemical corrosion strategy is demonstrated to accelerate the the corrosion process and form bimetallic active catalysts to show excellent OER performance at large current densities. In situ rapid electrochemical corrosion of nickel foam substrate and PA ligands etching realize localized high concentrations of Ni and Fe ions. High concentrations of metal ions will combine with hydroxyl to effectively form defects-enriched NiFe layered double hydroxides porous nanosheets tightly anchoring on the underneath substrate. Remarkably, the activated electrode exhibits excellent OER catalytic activities with ultralow overpotentials of 289 and 315 mV to reach high current densities of 500 and 1000 mA cm-2, respectively. When coupled with Ni-Mo-N hydrogen evolution reaction catalysts, the two-electrode cell merely requires 1.87 V to deliver 1000 mA cm-2. The ligands-assisted rapid electrochemical corrosion strategy provides a fresh perspective for facile, cost-effective, and scale-up production of superior OER catalysts at large current densities.

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