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1.
Small ; : e2407615, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39388503

RESUMO

O3-type layered oxide cathode exhibits great application potential for practical sodium-ion batteries, due to its cost-effectiveness, abundant sodium and manganese resources, and high theoretical capacity. However, the irreversible phase transition, coupled with rapid capacity decay, which is primarily attributed to the Jahn-Teller effect of Mn3+, remains a significant bottleneck for commercial application. Additionally, the sluggish kinetics during the (de)sodiation process require urgent improvement. Herein, an electronic structure regulation strategy is proposed by low-valence Li/Cu co-substitution to address these issues. The roles of Li/Cu on the electronic structure, structural evolution, and electrochemical properties in the Na0.96Ni0.22Fe0.2Mn0.5Li0.04Cu0.04O2 (NFMLC) cathode are comprehensively explored through systematic in situ/ex situ characterization techniques and theoretical calculations. The results reveal that this strategy effectively activates more Ni2+/3+ and Fe3+/4+ redox reactions above 2.5 V, while suppressing Mn3+/4+ redox activity below 2.5 V, thereby achieving highly structural reversibility. Therefore, the NFMLC electrode displays excellent long-term cycling stability (81.5% capacity retention after 2000 cycles at 5 C), and significantly enhanced rate performance (from 45.5% to 80.4% under a ratio of 5 C to 0.5 C). This work provides a valuable perspective on the design of low-cost, long-life, and high-performance layered oxide cathodes for practical sodium-ion batteries.

2.
Bioorg Med Chem ; 104: 117698, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38552597

RESUMO

Serotonin reuptake inhibition combined with the action targeting 5-hydroxytryptamine receptor subtypes can serve as a potential target for the development of antidepressant drugs. Herein a series of new aralkyl piperazines and piperidines were designed and synthesized by the structural modifications of the previously discovered aralkyl piperidine compound 1, targeting SSRI/5-HT1A/5-HT7. The results exhibited that compound 5a showed strong binding to 5-HT1A and 5-HT7 (Ki of 0.46 nM, 2.7 nM, respectively) and a high level of serotonin reuptake inhibition (IC50 of 1.9 nM), all of which were significantly elevated compared to 1. In particular, compound 5a showed weaker inhibitory activity against hERG than 1, and demonstrated good stability in liver microsomes in vitro. The preliminary screening using FST indicated that orally administered 5a, at a high dose, could reduce immobility time in mice markedly, indicating potential antidepressant activity.


Assuntos
Inibidores Seletivos de Recaptação de Serotonina , Serotonina , Camundongos , Animais , Piperazina/farmacologia , Serotonina/metabolismo , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Piperidinas/farmacologia , Piperazinas/química , Receptor 5-HT1A de Serotonina
3.
Chirality ; 36(3): e23658, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38414199

RESUMO

Diabrotica balteata LeConte is one of the most important polyphagous agricultural pests. The sex pheromone of this pest was synthesized using Evans asymmetric alkylation, ring-opening reaction of (R)-2-methyloxirane, SN 2 alkylation of secondary tosylate, and coupling of chiral tosylate with Grignard reagent as central strategies. The sex pheromone prepared herein would be useful to control D. balteata.


Assuntos
Besouros , Atrativos Sexuais , Animais , Estereoisomerismo , Alquilação
4.
Appl Opt ; 63(1): 85-92, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38175012

RESUMO

Optical probes are the preferred choice for high-precision surface metrology, necessitating improved flexibility and a broader range of motion to adapt to the increasing complexity of surfaces. This study introduces an interferometric probe designed for measuring aspheric surfaces, utilizing a wave-plate-array detection component. By integrating splitter elements into the detector, the probe improves integration and dynamic scanning performance, while maintaining high-precision measurement capability. The system design and working principle are explored, and comprehensive nonlinear models based on the Jones matrix theory are established. These models focus on the nonlinear errors arising from alignment errors in various cases. Moreover, rigorous numerical simulations and optical experiments are conducted to validate the proposed models. When the alignment error reaches 10°, it results in a maximum nonlinear error of 3.02 nm. The experimental results demonstrate the effectiveness of the models in capturing nonlinear errors induced by alignment errors, providing a theoretical foundation for error reduction and compensation.

5.
Altern Ther Health Med ; 30(7): 84-89, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38814613

RESUMO

Objective: To explore how miRNA-28-3p targets BIN1 and affects the biological behavior of nasopharyngeal carcinoma cells, and to evaluate its potential as a predictive biomarker for NPC. Methods: We studied 100 nasopharyngeal carcinoma patients who underwent surgery between January 2021 and January 2022. Tissues from tumors and adjacent normal areas were analyzed. Participants were categorized into two groups: one with nasopharyngeal carcinoma and another with adjacent normal tissue. Additionally, the nasopharyngeal carcinoma cell line CNE-2 was divided into three groups: an untreated control, a negative control with NC plasmid, and a test group treated with a miRNA-28-3p inhibitor. Key techniques included PCR, Western blotting, CCK-8, flow cytometry, focusing on the interactions between miRNA-28-3p and BIN1 and their predictive significance for NPC. Results: miRNA-28-3p levels were significantly higher in nasopharyngeal carcinoma tissues compared to adjacent normal tissues (P < .05). The predictive performance of miRNA-28-3p for NPC featured an AUC > 0.75 with sensitivity and specificity both exceeding 70% (P < .001). In nasopharyngeal carcinoma cells, miRNA-28-3p levels were significantly elevated compared to normal cells (P < .05). Transfection with the miRNA-28-3p inhibitor increased apoptosis and BIN1 protein levels while reducing cell proliferation, invasion, and migration significantly (P < .05). Conclusion: miRNA-28-3p is overexpressed in nasopharyngeal carcinoma and inhibits tumor cell proliferation, migration, and invasion, while promoting apoptosis by targeting BIN1. The level of miRNA-28-3p expression serves as a sensitive indicator for predicting nasopharyngeal carcinoma, affirming its potential as a diagnostic biomarker and underscoring the significance of these findings in enhancing understanding and clinical management of NPC.


Assuntos
MicroRNAs , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Apoptose/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/diagnóstico
6.
Mikrochim Acta ; 191(5): 289, 2024 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-38683210

RESUMO

As a common chlorinated nicotinic pesticide with high insecticidal activity, acetamiprid has been widely used for pest control. However, the irrational use of acetamiprid will pollute the environment and thus affect human health. Therefore, it is crucial to develop a simple, highly sensitive, and rapid method for acetamiprid residue detection. In this study, the capture probe (Fe3O4@Pt-Aptamer) was connected with the signal probe (Au@DTNB@Ag CS-cDNA) to form an assembly with multiple SERS-enhanced effects. Combined with magnetic separation technology, a SERS sensor with high sensitivity and stability was constructed to detect acetamiprid residue. Based on the optimal conditions, the SERS intensity measured at 1333 cm-1 is in relation to the concentration of acetamiprid in the range 2.25 × 10-9-2.25 × 10-5 M, and the calculated limit of detection (LOD) was 2.87 × 10-10 M. There was no cross-reactivity with thiacloprid, clothianidin, nitenpyram, imidacloprid, and chlorpyrifos, indicating that this method has good sensitivity and specificity. Finally, the method was applied to the detection of acetamiprid in cucumber samples, and the average recoveries were 94.19-103.58%, with RSD < 2.32%. The sensor can be used to analyse real samples with fast detection speed, high sensitivity, and high selectivity.


Assuntos
Aptâmeros de Nucleotídeos , Ouro , Limite de Detecção , Nanopartículas Metálicas , Neonicotinoides , Prata , Análise Espectral Raman , Neonicotinoides/análise , Aptâmeros de Nucleotídeos/química , Ouro/química , Prata/química , Nanopartículas Metálicas/química , Análise Espectral Raman/métodos , Platina/química , Inseticidas/análise , Cucumis sativus/química
7.
Ren Fail ; 46(1): 2349136, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38770992

RESUMO

BACKGROUND: Research has showcased a correlation between disruptions in gut microbiota and primary membranous nephropathy (pMN), giving rise to the concept of the 'gut-kidney axis'. However, the precise relationship between gut microbiota and pMN remains elusive. Hence, this study endeavors to investigate whether a causal relationship exists between gut microbiota and pMN utilizing Mendelian randomization (MR) analysis. METHODS: The primary method employed for MR analysis is the inverse variance weighting method, supplemented by MR-Egger and the weighted median method, to infer causality. This approach was validated within the pMN cohort across two distinct populations. RESULTS: At the species level, the abundance of Bifidobacterium bifidum and Alistipes indistinctus was negatively correlated with the risk of pMN. Conversely, pMN was positively associated with Bacilli abundance at the class level, Lachnospiraceae abundance at the family level, and Dialister abundance at the genus level. Specifically, at the species level, pMN was positively correlated with the abundance of Ruminococcus lactaris, Dialister invisus, and Coprococcus_sp_ART55_1. CONCLUSION: These findings lay the groundwork for future research exploring the interplay between pMN and the gut microbiota, with substantial implications for the prevention and treatment of pMN and its associated complications.


Assuntos
Microbioma Gastrointestinal , Glomerulonefrite Membranosa , Análise da Randomização Mendeliana , Humanos , Glomerulonefrite Membranosa/microbiologia , Glomerulonefrite Membranosa/genética , Masculino , Feminino , Pessoa de Meia-Idade , Bifidobacterium bifidum , Adulto
8.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732112

RESUMO

The paulownia bagworm, Clania variegata Snell, is an economically important pest of agriculture and forests. The sex pheromone of this pest and its stereoisomers were synthesized, and two of the stereoisomers were prepared for the first time. Our strategy was efficient and mainly included the ring-opening reaction of (S)-2-methyloxirane, the coupling of chiral sulfonate, the oxidative cleavage of olefin, and Yamaguchi esterification. Moreover, the overall yields of our synthesis were 23-29%, with eight steps in the longest route.


Assuntos
Atrativos Sexuais , Atrativos Sexuais/síntese química , Atrativos Sexuais/química , Estereoisomerismo , Animais
9.
Geriatr Nurs ; 58: 282-289, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38848609

RESUMO

OBJECTIVE: To compare perspectives of family and professional caregivers regarding an online self-learning platform. METHODS: Family and professional caregivers were interviewed separately. A thematic analysis was conducted with 12 family caregivers and 13 professional caregivers of people living with dementia in Macao using six semi-structured focus group interviews. RESULTS: Family and professional caregivers had different perspectives regarding the application of online learning program Four main themes emerged from the focus groups, including similarities and differences, namely 1) Need for services; 2) Accessibility to services; 3) Barriers to online learning; 4) Adjustments to the platform. CONCLUSIONS: The psychological assurance offered by an online learning program is imperative to the well-being of family caregivers. By identifying the gap between the needs and abilities of family caregivers and those imagined by professional caregivers, it allows for the development of support programs and interventions tailored to meet the specific needs of family caregivers.


Assuntos
Cuidadores , Demência , Grupos Focais , Humanos , Cuidadores/psicologia , Cuidadores/educação , Demência/enfermagem , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Família/psicologia , Pesquisa Qualitativa , Adulto , Internet
10.
Sensors (Basel) ; 23(5)2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36905071

RESUMO

OBJECTIVE: To accurately achieve distal contact force, a novel temperature-compensated sensor is developed and integrated into an atrial fibrillation (AF) ablation catheter. METHODS: A dual elastomer-based dual FBGs structure is used to differentiate the strain on the two FBGs to achieve temperature compensation, and the design is optimized and validated by finite element simulation. RESULTS: The designed sensor has a sensitivity of 90.5 pm/N, resolution of 0.01 N, and root-mean-square error (RMSE) of 0.02 N and 0.04 N for dynamic force loading and temperature compensation, respectively, and can stably measure distal contact forces with temperature disturbances. CONCLUSION: Due to the advantages, i.e., simple structure, easy assembly, low cost, and good robustness, the proposed sensor is suitable for industrial mass production.

11.
J Stroke Cerebrovasc Dis ; 32(12): 107443, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38771722

RESUMO

BACKGROUND AND AIMS: We aimed to investigate the relationship between the cumulative exposure to different lipid parameters and carotid intima-media thickness(CIMT), which is considered a marker for the early stage of atherosclerosis. This is due to the shift in research focus from assessing individual lipoproteins to considering their cumulative exposure. METHODS AND RESULTS: The study included 2,348 participants who had their lipid parameters measured biennially since 2006.To calculate the cumulative lipid burden, the weighted sum of the difference between the measured value and the cutoff value of each parameter, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), and non-HDLC, was added. Carotid ultrasound was used to detect CIMT. The association between cumulative lipid burden and CIMT was evaluated using linear and logistic analyses. TC and LDLC burden were significantly associated with thickening CIMT (p<0.05). A 2.65-fold, 1.67-fold increased risk of abnormal CIMT was documented in the highest quartile of these two lipid burdens. Notably, a dose-dependent relationship was observed in the overall population when taking non-HDLC burden as a continuous variable (fully-adjusted ß coefficient=0.0013, 95%CI 0.0004-0.0022). CONCLUSIONS: Out of the five lipid parameters, TC and LDLC burden showed independent associations with abnormal CIMT. it is crucial to attain optimal lipid levels for the prevention and treatment of subclinical atherosclerosis.


Assuntos
Doenças Assintomáticas , Biomarcadores , Doenças das Artérias Carótidas , Espessura Intima-Media Carotídea , Lipídeos , Valor Preditivo dos Testes , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/epidemiologia , Biomarcadores/sangue , Fatores de Risco , Lipídeos/sangue , Adulto , Medição de Risco , Dislipidemias/sangue , Dislipidemias/epidemiologia , Dislipidemias/diagnóstico , Triglicerídeos/sangue , Idoso , LDL-Colesterol/sangue , HDL-Colesterol/sangue , Fatores de Tempo
12.
Opt Express ; 30(4): 5618-5633, 2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-35209520

RESUMO

In this paper, the Karhunen-Loeve transform (KLT) and wavelength domain interferometric spectral singular value decomposition (SVD) are used for the first time to demodulate the pressure of an optical fiber Fabry-Perot (F-P) micro-pressure sensor, and the feasibility of the proposed method is demonstrated experimentally. The eigenvalue decomposition of the dominant frequency part of the beam-domain interferometric spectrum after the fast Fourier transform (FFT) is performed using KLT, and the singular value decomposition of the wavelength domain interferometric spectrum is additionally performed using SVD. Both methods use high-order eigenvalues as a new metric and then derive the relation between the new metric and the reference pressure. The two demodulation methods are experimentally compared, and we used an optical fiber F-P pressure sensor with unknown structure and material for pressure measurements. Even though the interferometric spectral signal is acquired using a coarse spectrometer (2.5 nm wavelength resolution), one can still achieve high demodulation accuracy with both algorithms. However, the SVD demodulation accuracy decreases significantly after reducing the spectral data points in the wavelength domain from 1566 to 783. KLT still has high demodulation accuracy and linearity after spectral data points are reduced from 1024 to 256 in the wavenumber domain. The satisfactory linearity of the measured pressure versus reference pressure and low reading errors validate the feasibility of the proposed demodulation algorithm.

13.
Microb Pathog ; 168: 105597, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35605739

RESUMO

Many insects are capable of developing enhanced resistance in response to repeated infection with the same pathogen, which is defined "immune priming". However, little is known in housefly, an ideal insect model for studying immunity. Here, Candida albicans (C. albicans) was used as the pathogen to explore whether housefly larvae are capable of eliciting immune priming. Firstly, we found that 2nd-instar larvae pre-exposure to heat-killed C. albicans could confer protection upon re-infection with C. albicans, as evidenced by the survival rate was higher in C. albicans primed larvae. Moreover, the hemocyte density was increased by priming, but phenoloxidase (PO) activity was not affected. For this reason, RNA sequencing (RNA-seq) was performed and found that 145 genes were differentially expressed after priming, in which 22 genes were related to immune response. Then, KEGG enrichment showed that Toll signaling pathway and Phagosome signaling pathway, as well as many other signaling pathways were enriched. Finally, qPCR was performed and found that the expression of 2 pattern recognition receptor (PRR) genes (PGRP-SD-like precursor and lectin subunit alpha-like) and 6 immune effector genes (phormicin, cecropin-A2-like, defensin-1, attacin-A-like, sarcotoxin-1C and lysozyme 1-like) in C. albicans primed larvae was significantly up-regulated after challenge. Taken together, our findings suggested that housefly larvae are capable of eliciting immune priming against C. albicans, and cellular immunity as well as the gene expression, especially genes involved in Toll signaling pathway were induced by immune priming with C. albicans.


Assuntos
Moscas Domésticas , Animais , Candida albicans/genética , Expressão Gênica , Moscas Domésticas/genética , Imunidade Celular , Larva/genética
14.
Bioorg Med Chem Lett ; 76: 129006, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36202190

RESUMO

A series of novel 1-(1-benzoylpiperidin-4-yl) methanamine derivatives were synthesized and evaluated for the serotonin reuptake inhibitory abilities and binding affinities to the 5-HT1A receptor. The metabolic stabilities of these compounds were measured in vitro using human or mouse liver microsomes and the antidepressant activities were explored In vivo using the forced swimming test (FST) and tail suspension test (TST) in mice. The results indicated that the compound 12a exhibited strongest serotonin reuptake inhibition (IC50 = 8.2 nM) and marked 5-HT1A receptor affinity (Ki = 0.069 nM), which were significantly superior to lead compounds Ⅰ and Ⅱ. Meanwhile, compound 12a showed good metabolic stability in vitro and exhibited potential antidepressant-like effects in the FST and TST in mice.


Assuntos
Inibidores Seletivos de Recaptação de Serotonina , Serotonina , Humanos , Camundongos , Animais , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Receptor 5-HT1A de Serotonina , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Natação
15.
Nutr Metab Cardiovasc Dis ; 32(11): 2561-2567, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36163218

RESUMO

BACKGROUND AND AIMS: This study aimed to investigate the association between the steatosis severity of nonalcoholic fatty liver disease (NAFLD) and future intracerebral hemorrhage (ICH) risk. METHODS AND RESULTS: We used data from the Kailuan study. Participants without a history of stroke, myocardial infarction, cancer, other liver diseases or alcohol abuse were enrolled. NAFLD and the severity of liver steatosis were assessed by abdominal ultrasonography. We stratified the participants into different groups according to the severity changes in liver steatosis status across the first 4-year follow-up period. The outcome was the first occurrence of ICH during the next 6-year follow-up period. Hazard ratios (HRs) and 95% CI of ICH were estimated using Cox models adjusted for potential risk factors. A total of 49,906 participants were enrolled in this study. During a median of 6.79 years of follow-up, 193 incident ICH cases were identified. Compared with persistent nonfatty liver participants, the hazard ratios (HRs) for participants with persistent mild steatosis, persistent moderate steatosis, persistent severe steatosis, alleviating steatosis, and aggravating steatosis were 1.28 (95% CI, 0.75-2.18), 2.33 (95% CI, 1.24-4.38), 1.63 (95% CI, 0.22-12.11), 1.41 (95% CI, 0.91-2.18), and 1.37 (95% CI, 0.94-2.00), respectively, in the fully adjusted model. CONCLUSIONS: NAFLD with persistent moderate steatosis was significantly related to an increased risk of future ICH, independent of other conventional risk factors.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/epidemiologia , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Modelos de Riscos Proporcionais , Fatores de Risco , Ultrassonografia
16.
Neurol Sci ; 43(5): 3121-3129, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34806117

RESUMO

BACKGROUND AND PURPOSE: The relationship between lipid levels and the prognosis of acute intracerebral hemorrhage (ICH) remains controversial. Thus, we aimed to investigate whether lower low-density lipoprotein cholesterol (LDL-C) levels increased the risk of adverse outcomes, as well as the current situation of statin treatment in acute ICH patients with premorbid lipid-lowering therapy. METHODS: From August 1, 2015, to July 31, 2019, a total of 73,098 ICH patients were included in our study from the Chinese Stroke Center Alliance program. Patients were grouped by LDL-C levels of < 1.4 mmol/L, 1.4-1.8 mmol/L, 1.8-2.6 mmol/L, and > 2.6 mmol/L. Logistic regression was used to assess the association between LDL-C levels and the composite risk of hematoma expansion (HE) or in-hospital death. Moreover, statin treatment in ICH patients with cardio-cerebrovascular diseases was analyzed. RESULTS: In total, 6368 (8.7%) patients were identified as a composite of HE or in-hospital death with a mean LDL-C level of 2.9 ± 1.7 mmol/L. In the univariate analysis, patients who achieved lower LDL-C concentrations under 1.4 mmol/L had a 36% higher risk of adverse outcomes compared with the ≥ 2.6 mmol/L group (OR 1.36, 95%CI 1.23-1.51). Similar results were obtained in multivariate analyses, especially for patients with GCS scores of 9-15. For acute ICH patients with concomitant atherosclerotic disease, statin treatment was discontinued in the majority of Chinese population. CONCLUSIONS: Lower LDL-C levels (< 1.4 mmol/L) are associated with an increased risk of HE and ensuing mortality in acute ICH patients. Maintaining an optimal LDL-C range may have therapeutic potential against HE which merits further investigation.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Hemorragia Cerebral/complicações , LDL-Colesterol , Hematoma/complicações , Mortalidade Hospitalar , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico
17.
Int Microbiol ; 24(2): 233-242, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33452940

RESUMO

Invasive candidiasis is a major threat to human health, and Candida albicans is the most common pathogenic species responsible for this condition. The incidence of drug-resistant strains of C. albicans is rising, necessitating the development of new antifungal drugs. Antimicrobial peptides (AMPs) have recently attracted attention due to their unique ability to evade the drug resistance of microorganisms. However, the mechanism of their activity has not yet been identified. The current study analyzed the mode of action of MAF-1A by confocal microscopy, scanning electron microscopy, fluorescent staining, flow cytometry, and qRT-PCR. The results indicate that MAF-1A disrupts the cell membrane of C. albicans and enters the cell where it binds and interacts with nucleic acids. qRT-PCR demonstrated that the expression of several sterol biosynthesis-related genes in C. albicans was increased after MAF-1A treatment. Together, these findings suggest that MAF-1A exerts antifungal action by affecting both the cell membrane and intracellular components. The antifungal mechanism of MAF-1A is unique, and its identification has great research and clinical significance.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Peptídeos/farmacologia , Candida albicans/genética , Candida albicans/metabolismo , Candidíase/microbiologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/genética , Membrana Celular/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Humanos
18.
Bioorg Med Chem Lett ; 31: 127681, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33189775

RESUMO

In this study, a series of trans-4-(2-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)ethyl)cyclohexan-1-amine derivatives as potential antipsychotics were synthesized and biologically evaluated to discover potential antipsychotics with good drug target selectivity. The preliminary structure-activity relationship was discussed, and optimal compound 12a showed both nanomolar affinity for D2/D3/5-HT1A/5-HT2A receptors and weak α1 and H1 receptor binding affinity. In addition, 12a was metabolically stable in vitro, displayed micromolar affinity for the hERG channel, and exhibited antipsychotic efficacy in the animal model of locomotor-stimulating effects of phencyclidine.


Assuntos
Aminas/farmacologia , Antipsicóticos/farmacologia , Azepinas/farmacologia , Cicloexanos/farmacologia , Receptores Dopaminérgicos/metabolismo , Receptores de Serotonina/metabolismo , Aminas/síntese química , Aminas/química , Animais , Antipsicóticos/síntese química , Antipsicóticos/química , Azepinas/síntese química , Azepinas/química , Cicloexanos/síntese química , Cicloexanos/química , Relação Dose-Resposta a Droga , Humanos , Locomoção/efeitos dos fármacos , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade
19.
J Antimicrob Chemother ; 75(11): 3391-3394, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32785699

RESUMO

BACKGROUND: We aimed to study the prevalence of secondary antibiotic resistance of Helicobacter pylori in southern China and its risk factors, particularly geographical and socio-economic factors. METHODS: This was a municipality-wide, multicentre, prospective cohort study involving five major hospitals. Patients aged ≥18 years who failed first-line bismuth-based quadruple anti-H. pylori therapy between September 2016 and February 2018 were recruited. Participants underwent upper gastrointestinal endoscopy with biopsy from the antrum and body for H. pylori culture and antimicrobial susceptibility testing for six antibiotics (clarithromycin, levofloxacin, metronidazole, amoxicillin, tetracycline and furazolidone). Patients with failure of H. pylori culture were excluded. Participants completed a questionnaire profiling 22 potential risk factors of H. pylori infection and antibiotic resistance, including medical, social, household and birthplace factors. RESULTS: A total of 1113 patients failed first-line therapy, with successful H. pylori culture in 791 (71.1%) [male = 433 (54.7%); median age = 43 years]. Secondary resistance rates of dual antibiotics (clarithromycin + metronidazole and levofloxacin + metronidazole) and triple antibiotics (clarithromycin + levofloxacin + metronidazole) were 34.0%, 38.7% and 17.8%, respectively. Risk factors for clarithromycin + metronidazole resistance were history of ≥2 courses of H. pylori therapies [adjusted OR (aOR) = 1.71; 95% CI = 1.17-2.54], ≥3 household members (aOR = 2.00; 95% CI = 1.07-3.90) and family history of gastric cancer (aOR = 1.85; 95% CI = 1.18-2.85). Risk factors for levofloxacin + metronidazole resistance were age ≥40 years (aOR = 1.94; 95% CI = 1.37-2.75), lower gross domestic product per capita (aOR = 0.29; 95% CI = 0.10-0.80) and higher number of doctors/10 000 population (aOR = 1.59; 95% CI = 1.07-2.39). A higher human development index was of borderline significance (aOR = 2.79; 95% CI = 0.97-8.70). CONCLUSIONS: The rates of secondary resistance of H. pylori to multiple antibiotics were high in southern China. Certain population-level risk factors were associated with levofloxacin + metronidazole resistance.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Adolescente , Adulto , Amoxicilina/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , China/epidemiologia , Claritromicina/farmacologia , Farmacorresistência Bacteriana , Feminino , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Humanos , Masculino , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Prevalência , Estudos Prospectivos , Fatores de Risco
20.
J Insect Sci ; 20(6)2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33347588

RESUMO

Peritrophic matrix/membrane (PM) critically prevents the midgut of insects from external invasion by microbes. The proteins in the peritrophic membrane are its major structural components. Additionally, they determine the formation and function of this membrane. However, the role of PM proteins in immune regulation is unclear. Herein, we isolated a novel PM protein (MdPM-17) from Musca domestica larvae. Further, the function of MdPM-17 in regulating host innate immunity was identified. Results showed that the cDNA of MdPM-17 full is 635 bp in length. Moreover, it consists of a 477-bp open reading frame encoding 158 amino acid residues. These amino acid residues are composed of two Chitin-binding type-2 domain (ChtBD2) and 19 amino acids as a signal peptide. Moreover, tissue distribution analysis indicates that MdPM-17 was enriched expressed in midgut, and moderate levels in the fat body, foregut, and malpighian tubule. Notably, MdPM-17 recombinant protein showed high chitin-binding capacity, thus belongs to the Class III PM protein group. MdPM-17 protein silencing via RNA interference resulted in the expression of antimicrobial peptide (defensin, cecropins, and diptericin) genes, and this occurred after oral inoculation with exogenous microbes Escherichia coli (Enterobacteriales:Enterobacteriaceae), Staphylococcus aureus (Bacillales:Staphylococcaceae), and Candida albicans (Endomycetales:Saccharomycetaceae)). Therefore, all the antimicrobial peptide (AMP) gene expression levels are high in MdPM-17-depleted larvae during microbial infection compared to controls. Consequently, these findings indicate that MdPM-17 protein is associated with the antibacterial response from the housefly.


Assuntos
Moscas Domésticas/imunologia , Proteínas de Insetos/isolamento & purificação , Intestinos/imunologia , Animais , Peptídeos Catiônicos Antimicrobianos/metabolismo , Perfilação da Expressão Gênica , Genes de Insetos , Moscas Domésticas/genética , Moscas Domésticas/metabolismo , Imunidade Inata/fisiologia , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Larva/imunologia , Larva/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Interferência de RNA
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