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1.
Cereb Cortex ; 34(5)2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38725292

RESUMEN

The local field potential (LFP) is an extracellular electrical signal associated with neural ensemble input and dendritic signaling. Previous studies have linked gamma band oscillations of the LFP in cortical circuits to sensory stimuli encoding, attention, memory, and perception. Inconsistent results regarding gamma tuning for visual features were reported, but it remains unclear whether these discrepancies are due to variations in electrode properties. Specifically, the surface area and impedance of the electrode are important characteristics in LFP recording. To comprehensively address these issues, we conducted an electrophysiological study in the V1 region of lightly anesthetized mice using two types of electrodes: one with higher impedance (1 MΩ) and a sharp tip (10 µm), while the other had lower impedance (100 KΩ) but a thicker tip (200 µm). Our findings demonstrate that gamma oscillations acquired by sharp-tip electrodes were significantly stronger than those obtained from thick-tip electrodes. Regarding size tuning, most gamma power exhibited surround suppression at larger gratings when recorded from sharp-tip electrodes. However, the majority showed enhanced gamma power at larger gratings when recorded from thick-tip electrodes. Therefore, our study suggests that microelectrode parameters play a significant role in accurately recording gamma oscillations and responsive tuning to sensory stimuli.


Asunto(s)
Ritmo Gamma , Ratones Endogámicos C57BL , Estimulación Luminosa , Corteza Visual Primaria , Animales , Ritmo Gamma/fisiología , Ratones , Estimulación Luminosa/métodos , Corteza Visual Primaria/fisiología , Masculino , Microelectrodos , Corteza Visual/fisiología , Electrodos
2.
Drug Metab Dispos ; 52(8): 754-764, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38302428

RESUMEN

The mammalian gut microbiota plays diverse and essential roles in modulating host physiology. Key mediators determining the outcome of the microbiota-host interactions are the small molecule metabolites produced by the gut microbiota. The liver is a major organ exposed to gut microbial metabolites, and it serves as the nexus for maintaining healthy interactions between the gut microbiota and the host. At the same time, the liver is the primary target of potentially harmful gut microbial metabolites. In this review, we provide an up-to-date list of gut microbial metabolites that have been identified to either increase or decrease host susceptibility to acetaminophen (APAP)-induced liver injury. The signaling pathways and molecular factors involved in the progression of APAP-induced hepatotoxicity are well-established, and we propose that the mouse model of APAP-induced hepatotoxicity serves as a model system for uncovering gut microbial metabolites with previously unknown functions. Furthermore, we envision that gut microbial metabolites identified to alter APAP-induced hepatotoxicity likely have broader implications in other liver diseases. SIGNIFICANCE STATEMENT: This review provides an overview of the role of the gut microbiota in modulating the host susceptibility to acetaminophen (APAP)-induced liver injury. It focuses on the roles of gut bacterial small molecule metabolites as mediators of the interaction between the gut microbiota and the liver. It also illustrates the utility of APAP-induced liver injury as a model to identify gut microbial metabolites with biological function.


Asunto(s)
Acetaminofén , Enfermedad Hepática Inducida por Sustancias y Drogas , Microbioma Gastrointestinal , Acetaminofén/metabolismo , Acetaminofén/toxicidad , Acetaminofén/efectos adversos , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/fisiología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Animales , Humanos , Hígado/metabolismo , Hígado/efectos de los fármacos , Ratones , Susceptibilidad a Enfermedades , Analgésicos no Narcóticos/toxicidad , Analgésicos no Narcóticos/metabolismo , Analgésicos no Narcóticos/efectos adversos
3.
Langmuir ; 40(21): 11307-11316, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38739878

RESUMEN

Metallenes have received sustained attention owing to their unique microstructure characteristics and compelling catalytic applications, but the synthesis of multielement crystalline-amorphous metallenes remains a formidable challenge. Herein, we report a one-step wet chemical reduction method to synthesize composition-tunable crystalline-amorphous heterophase PdMoCrW tetrametallene. As-synthesized PdMoCrW tetrametallene is composed of approximately six to seven atomic layers and has flexible crimpiness, a crystalline-amorphous heterophase structure, and high-valence metal species. Time-dependent experiments show that PdMoCrW tetrametallene follows a three-step growth mechanism that includes nucleation, lateral growth, and atom diffusion, respectively. The novel ultrathin structure, optimized Pd electronic structure, and hydrophilic surface together greatly promote the activity and stability of PdMoCrW tetrametallene in the alkaline oxygen reduction reaction. Pd75.9Mo9.4Cr8.9W5.8/C exhibits excellent mass and specific activities of 2.81 A mgPd-1 and 4.05 mA cm-2, which are 20.07/14.46 and 23.42/16.20 times higher than those of commercial Pt/C and Pd/C, respectively. Furthermore, a Zn-air battery assembled using Pd75.9Mo9.4Cr8.9W5.8/C as a cathode catalyst achieves a peak power density of 156 mW cm-2 and an ultralong durability of 329 h. This study reports an effective strategy for constructing crystalline-amorphous quaternary metallenes to advance non-Pt electrocatalysts toward oxygen reduction reaction (ORR) performance and for a Zn-air battery.

4.
Ecotoxicol Environ Saf ; 277: 116371, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38663196

RESUMEN

Nicotine, a naturally occurring alkaloid found in tobacco, is a potent neurotoxin extensively used to control Nilaparvata lugens (Stål), a destructive insect pest of rice crops. The insect gut harbors a wide array of resident microorganisms that profoundly influence several biological processes, including host immunity. Maintaining an optimal gut microbiota and immune homeostasis requires a complex network of reciprocal regulatory interactions. However, the underlying molecular mechanisms driving these symbiotic exchanges, particularly between specific gut microbe and immunity, remain largely unknown in insects. Our previous investigations identified and isolated a nicotine-degrading Burkholderia cepacia strain (BsNLG8) with antifungal properties. Building on those findings, we found that nicotine intake significantly increased the abundance of a symbiotic bacteria BsNLG8, induced a stronger bacteriostatic effect in hemolymph, and enhanced the nicotine tolerance of N. lugens. Additionally, nicotine-induced antimicrobial peptides (AMPs) exhibited significant antibacterial effects against Staphylococcus aureus. We adopted RNA-seq to explore the underlying immunological mechanisms in nicotine-stressed N. lugens. Bioinformatic analyses identified numerous differentially expressed immune genes, including recognition/immune activation (GRPs and Toll) and AMPs (i.e., Defensin, Lugensin, lysozyme). Temporal expression profiling (12, 24, and 48 hours) of immune genes revealed pattern recognition proteins and immune effectors as primary responders to nicotine-induced stress. Defensin A, a broad-spectrum immunomodulatory cationic peptide, exhibited significantly high expression. RNA interference-mediated silencing of Defensin A reduced the survival, enhanced nicotine sensitivity of N. lugens to nicotine, and decreased the abundance of BsNLG8. The reintroduction of BsNLG8 improved the expression of immune genes, aiding nicotine resistance of N. lugens. Our findings indicate a potential reciprocal immunomodulatory interaction between Defensin A and BsNLG8 under nicotine stress. Moreover, this study offers novel and valuable insights for future research into enhancing nicotine-based pest management programs and developing alternative biocontrol methods involving the implication of insect symbionts.


Asunto(s)
Burkholderia cepacia , Microbioma Gastrointestinal , Hemípteros , Nicotina , Animales , Nicotina/toxicidad , Nicotina/farmacología , Hemípteros/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Burkholderia cepacia/efectos de los fármacos , Defensinas/genética , Estrés Fisiológico/efectos de los fármacos , Simbiosis
5.
J Craniofac Surg ; 35(1): e102-e103, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37983056

RESUMEN

It is rare that cavernous sinus complications are caused by maxillary sinus lesions because the locations of these lesions are some distant from each other. The authors describe an unusual presentation that the primary lesion was located in the maxillary sinus and triggered cavernous sinus syndrome and optic nerve symptoms. The most likely possibility was that the infection traveled retrograde along the vascular plexus. Removal of maxillary sinus lesions and establishment ventilation may achieve source control.


Asunto(s)
Síndromes del Seno Cavernoso , Seno Cavernoso , Sinusitis Maxilar , Micosis , Sinusitis , Humanos , Sinusitis Maxilar/diagnóstico por imagen , Sinusitis Maxilar/cirugía , Sinusitis/complicaciones , Sinusitis/diagnóstico por imagen , Sinusitis/terapia , Micosis/complicaciones , Seno Cavernoso/diagnóstico por imagen , Seno Cavernoso/patología , Seno Maxilar/diagnóstico por imagen , Seno Maxilar/cirugía
6.
Nano Lett ; 23(8): 3467-3475, 2023 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-37036504

RESUMEN

Finding a high-performance low-Pt bipolar electrocatalyst in actual direct alcohol fuel cells (DAFCs) remains challenging and desirable. Here, we developed a crystalline PdPtCu@amorphous subnanometer Pd-Pt "dual site" layer core-shell structure for the oxygen reduction reaction (ORR) and alcohol (methanol, ethylene glycol, glycerol, and their mixtures) oxidation reaction (AOR) in an alkaline electrolyte (denoted D-PdPtCu). The prepared D-PdPtCu/C achieved a direct 4-electron ORR pathway, a full oxidation pathway for AOR, and high CO tolerance. The ORR mass activity (MA) of D-PdPtCu/C delivered a 52.8- or 59.3-fold increase over commercial Pt/C or Pd/C, respectively, and no activity loss after 20000 cycles. The D-PdPtCu/C also exhibited much higher AOR MA and stability than Pt/C or Pd/C. Density functional theory revealed the intrinsic nature of a subnanometer Pd-Pt "dual site" surface for ORR and AOR activity enhancement. The D-PdPtCu/C as an effective bipolar electrocatalyst yielded higher peak power densities than commercial Pt/C in actual DAFCs.

7.
Fa Yi Xue Za Zhi ; 40(2): 154-163, 2024 Apr 25.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-38847030

RESUMEN

OBJECTIVES: To develop a deep learning model for automated age estimation based on 3D CT reconstructed images of Han population in western China, and evaluate its feasibility and reliability. METHODS: The retrospective pelvic CT imaging data of 1 200 samples (600 males and 600 females) aged 20.0 to 80.0 years in western China were collected and reconstructed into 3D virtual bone models. The images of the ischial tuberosity feature region were extracted to create sex-specific and left/right site-specific sample libraries. Using the ResNet34 model, 500 samples of different sexes were randomly selected as training and verification set, the remaining samples were used as testing set. Initialization and transfer learning were used to train images that distinguish sex and left/right site. Mean absolute error (MAE) and root mean square error (RMSE) were used as primary indicators to evaluate the model. RESULTS: Prediction results varied between sexes, with bilateral models outperformed left/right unilateral ones, and transfer learning models showed superior performance over initial models. In the prediction results of bilateral transfer learning models, the male MAE was 7.74 years and RMSE was 9.73 years, the female MAE was 6.27 years and RMSE was 7.82 years, and the mixed sexes MAE was 6.64 years and RMSE was 8.43 years. CONCLUSIONS: The skeletal age estimation model, utilizing ischial tuberosity images of Han population in western China and employing the ResNet34 combined with transfer learning, can effectively estimate adult ischium age.


Asunto(s)
Determinación de la Edad por el Esqueleto , Aprendizaje Profundo , Imagenología Tridimensional , Isquion , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Isquion/diagnóstico por imagen , Adulto , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodos , Imagenología Tridimensional/métodos , China , Estudios Retrospectivos , Determinación de la Edad por el Esqueleto/métodos , Anciano , Adulto Joven , Anciano de 80 o más Años , Reproducibilidad de los Resultados
8.
Small ; 19(23): e2300594, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36755191

RESUMEN

A primary concern about photodynamic therapy (PDT) is its inability to regulate the generation levels of reactive oxidative species (ROS) based on the complex microenvironment, resulting in the impairment toward normal tissues and immunosuppression. Besides, tumor metastasis also compromises PDT's efficacy and drives mortality. However, it is very challenging to achieve such two goals within one nanosystem. Here, the nanoassembly (CPR) with self-regulated photodynamic and antimetastasis properties comprises three parts: chlorin e6-conjugated ß-cyclodextrin (CD-Ce6) acts as the main PDT agent and ferrocene (Fc)-terminated phenylboronic acid-containing conjugates entering into the cavity of CD-Ce6, as well as rosmarinic acid (RA)-boronic acid crosslinked shell. Compared with non-crosslinked counterpart, CPR displays better stability and enhanced tumor accumulation. Under laser irradiation, CPR generates plenty of ROS to damage tumor cells and induce immunogenic cell death. Mildly acidic TME partly cleaves the crosslinkers to dissociate antioxidant RAs from micelles, which together with Fc in CPR scavenge PDT-induced ROS in the TME. By contrast, under acidic lysosomal conditions, Fc catalyzes abundant H2 O2 in tumor cells to produce highly cytotoxic •OH, while RA continuously reduces ferroptosis-generated Fc+ into Fc, both to augment the PDT efficacy in tumor cells. CPR also remarkably hinders the epithelial-mesenchymal transition to prevent the lung metastasis.


Asunto(s)
Nanopartículas , Fotoquimioterapia , Porfirinas , Fotoquimioterapia/métodos , Especies Reactivas de Oxígeno/metabolismo , Fototerapia , Cinamatos/farmacología , Porfirinas/farmacología , Línea Celular Tumoral , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Ácido Rosmarínico
9.
Bioorg Chem ; 137: 106617, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37267793

RESUMEN

Artemyrianolide H (AH) is a germacrene-type sesquiterpenolid isolated from Artemisia myriantha, and showed potent cytotoxicity against three human hepatocellular carcinoma cell lines HepG2, Huh7, and SK-Hep-1 with IC50 values of 10.9, 7.2, and 11.9 µM, respectively. To reveal structure-activity relationship, 51 artemyrianolide H derivatives including 19 dimeric analogs were designed, synthesized, and assayed for their cytotoxicity against three human hepatoma cell lines. Among them, 34 compounds were more active than artemyrianolide H and sorafenib on the three cell lines. Especially, compound 25 exhibited the most promising activity with IC50 values of 0.7 (HepG2), 0.6 (Huh7), and 1.3 µM (SK-Hep-1), which were 15.5, 12.0, and 9.2-fold higher than that of AH and 16.4, 16.3 and 17.5-fold higher than that of sorafenib. Cytotoxicity evaluation on normal human liver cell lines (THLE-2) demonstrated good safety profile of compound 25 with SI of 1.9 (HepG2), 2.2 (Huh 7) and 1.0 (SK-Hep1). Further studies revealed that compound 25 dose-dependently arrested cells at G2/M phase which was correlated with the up-regulation of both cyclin B1 and p-CDK1, and induced apoptosis through the activation of mitochondrial pathways in HepG2 cells. In addition, the migratory and invasive abilities in HepG2 cells after treatment with 1.5 µM of compound 25 were decreased by 89% and 86% with the increase of E-cadherin expression accompanied by the decrease of N-cadherin, vimentin expression. Bioinformatics analysis based on machine learning predicted that PDGFRA and MAP2K2 might be acting targets of compound 25, and SPR assays demonstrated compound 25 were bound with PDGFRA and MAP2K2 with KD value of 0.168 nM, and 8.49 µM, respectively. This investigation proposed that compound 25 might be considered as a promising lead compound for the development of antihepatoma candidate.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Sorafenib/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/patología , Relación Estructura-Actividad , Células Hep G2 , Proliferación Celular , Apoptosis , Ensayos de Selección de Medicamentos Antitumorales , Línea Celular Tumoral
10.
Artículo en Inglés | MEDLINE | ID: mdl-37029805

RESUMEN

Patients with autoimmune encephalitis (AE) often developed psychiatric features during the disease course. Many studies focused on the psychiatric characteristic in anti-NMDAR encephalitis (NMDAR-E), but anti-LGI1 encephalitis (LGI1-E) had received less attention regarding the analysis of psychiatric features, and no study compared psychiatric characteristic between these two groups. The clinical data of AE patients (62 NMDAR-E and 20 LGI1-E) who developed psychiatric symptoms were analyzed in this study. In NMDAR-E, the most common higher-level feature was "behavior changes" (60/62, 96.8%) and the lower-level feature "incoherent speech" was observed in 33 patients (33/62, 53.2%), followed by "agitation" (29/62, 46.8%) and "incongruent laughter/crying" (20/62, 32.3%). Similar to NMDAR-E, "behavior changes" was most common in LGI1-E (17/20, 85.0%), but the features of suicidality, eating, and obsessive-compulsive were not reported. The top three lower-level features were visual hallucinations (9/20, 45.0%), incoherent speech (8/20, 40.0%), and mood instability (7/20, 35.0%). The comparative study found that "incongruent laughter/crying", in lower-level features, was more frequently observed in NMDAR-E (32.3% vs. 0%, p = 0.002). Moreover, the Bush Francis Catatonia Rating Scale (BFCRS) assessing the catatonic symptoms in NMDAR-E were higher than LGI1-E, but the 18 item-Brief Psychiatric Rating Scale (BPRS-18) showed no difference in the two groups. In summary, both NMDAR-E and LGI1-E often developed psychiatric symptoms. In contrast with LGI1-E, the psychiatric feature "incongruent laughter/crying" was more frequently associated with NMDAR-E, and catatonic symptoms were more severe in NMDAR-E.

11.
Nutr Neurosci ; 26(8): 727-742, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35694842

RESUMEN

Objectives: Alzheimer's disease (AD) is a serious neurodegenerative disease. Although many therapeutic strategies have been studied, their clinical applications are immature. Moreover, these methods can only alleviate symptoms rather than cure it, posing a challenge to brain health in older adults worldwide. Curcumin (CUR) is a very promising natural compound for nerve protection and treatment. It can prevent and treat AD, and on the other hand, its fluorescence properties can be used in the diagnosis of AD. However, CUR is characterized by very low water solubility, fluid instability, rapid metabolism, low bioavailability and difficulty in penetrating the biological barriers, which limit its application. Nanocarriers are a potential material to improve the biocompatibility of CUR and its ability to cross biological barriers. Therefore, delivering CUR by nanocarriers is an effective method to achieve better efficacy. Methods: In this review, the preventive, therapeutic and diagnostic effects of CUR nanoformulations on AD, as well as various patents, clinical trials and experimental research progress in this field are discussed. The aim is to provide detailed reference and practical suggestions for future research. Results: CUR has a variety of pharmacological activities in the prevention and treatment of AD, and its nanoformulation can effectively improve solubility, bioavailability and the ability to penetrate the blood-brain barrier. Significant benefits have been observed in the current study. Discussion: CUR formulations have a good prospect in the prevention, diagnosis and treatment of AD, but the safety and principle of its administration need more detailed study in the future.


Asunto(s)
Enfermedad de Alzheimer , Curcumina , Enfermedades Neurodegenerativas , Humanos , Anciano , Curcumina/uso terapéutico , Curcumina/farmacología , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/prevención & control , Disponibilidad Biológica
12.
Molecules ; 28(10)2023 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-37241867

RESUMEN

Rice, which is a major part of the daily diet, is becoming more and more contaminated by cadmium (Cd). This study combined low-intensity ultrasonic waves with the Lactobacillus plantarum fermentation method and optimized this technique by a single-factor and response surface experiment, aiming to solve the practical problems that the current Cd removal methods for rice cannot address, due to the fact that they require a long time (nearly 24 h), which prevents meeting the rice production demands. The described technique required a short time (10 h), and the highest Cd removal reached 67.05 ± 1.38%. Further analysis revealed that the maximum adsorption capacity of Lactobacillus plantarum for Cd increased by nearly 75%, and the equilibrium adsorption capacity increased by almost 30% after the ultrasonic intervention. Additionally, a sensory evaluation and other experiments proved that the properties of the rice noodles prepared from Cd-reduced rice obtained by ultrasound-assisted fermentation were comparable to those of traditional rice noodles, indicating that this method can be used in actual rice production.


Asunto(s)
Lactobacillus plantarum , Oryza , Contaminantes del Suelo , Cadmio/análisis , Fermentación , Manipulación de Alimentos/métodos , Contaminantes del Suelo/análisis , Suelo
13.
Fa Yi Xue Za Zhi ; 39(1): 27-33, 2023 Feb 25.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-37038852

RESUMEN

OBJECTIVES: To examine the reliability and accuracy of Walker's model for estimating the sex of Han adults in western China by using cranium three-dimensional (3D) CT reconstruction, and to study the suitable cranial sex estimation model for Han people in western China. METHODS: A total of 576 cranial CT 3D reconstructed images from Hanzhong Hospital in Shaanxi Province from 2017 to 2021 were collected. These images were divided into the experimental group with 486 samples and the validation group with 90 samples. Walker's model was used by observer 1 to estimate the sex of experimental group samples. The logistic function applicable to Han people in western China was corrected by observer 1. The 90 samples in the validation group were scored and substituted into the modified logistic function to complete the back substitution test by observer 1, 2 and 3. RESULTS: The accuracy of sex estimation of Han adults in western China was 63.2%-77.2% by applying Walker's model. The accuracy of modified logistic function was 82.9%. The accuracy of sex estimation through back substitution test by 3 observers was 75.6%-91.1%, with a Kappa value of 0.689 (P<0.05) for inter-observer consistency and 0.874 (P<0.05) for intra-observer consistency. CONCLUSIONS: There are great differences in bone characteristics among people from different regions. The modified logistic function can achieve higher accuracy in Han adults in western China.


Asunto(s)
Determinación del Sexo por el Esqueleto , Humanos , Adulto , Reproducibilidad de los Resultados , Determinación del Sexo por el Esqueleto/métodos , Antropología Forense , Cráneo/diagnóstico por imagen , Cráneo/anatomía & histología , Imagenología Tridimensional , China , Tomografía Computarizada por Rayos X
14.
Biochem Biophys Res Commun ; 615: 9-16, 2022 07 30.
Artículo en Inglés | MEDLINE | ID: mdl-35679751

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy driven by genetic mutations and/or epigenetic dysregulation. Gemcitabine chemotherapy is the first-line regimen for pancreatic cancer but has limited efficacy. Our previous study revealed the role of SETD2-H3K36me3 loss in the initiation and metastasis of PDAC, but little is known about its role in tumor metabolism. Here, we found that SETD2-deficient PDAC enhanced glycolysis addiction via upregulation of glucose transporter 1 (GLUT1) to meet its large demand for glucose in progression. Moreover, SETD2 deficiency impaired nucleoside synthesis by directly downregulating the transcriptional level of transketolase (TKT) in the pentose phosphate pathway. The metabolic changes confer SETD2-deficient PDAC cells with increased sensitivity to gemcitabine under glycolysis restriction conditions. Collectively, our study provides mechanistic insights into how SETD2 deficiency reprograms glycolytic metabolism to compensate for insufficient nucleoside synthesis, suggesting that glycolysis restriction combined with gemcitabine might be a potential therapeutic strategy for PDAC patients with SETD2 deficiency.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Glucólisis , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Vía de Pentosa Fosfato , Gemcitabina , Neoplasias Pancreáticas
15.
Small ; 18(30): e2203182, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35771092

RESUMEN

Alzheimer's disease (AD), as a progressive and irreversible brain disorder, remains the most universal neurodegenerative disease. No effective therapeutic methods are established yet due to the hindrance of the blood-brain barrier (BBB) and the complex pathological condition of AD.  Therefore, a multifunctional nanocarrier (Rapa@DAK/siRNA) for AD treatment is constructed to achieve small interfering RNA of ß-site precursor protein (APP) cleaving enzyme-1 (BACE1 siRNA) and rapamycin co-delivery into the brain, based on Aleuria aurantia lectin (AAL) and ß-amyploid (Aß)-binding peptides (KLVFF) modified PEGylated dendrigraft poly-l-lysines (DGLs) via intranasal administration. Nasal administration provides an effective way to deliver drugs directly into the brain through the nose-to-brain pathway. AAL, specifically binding to L-fucose located in the olfactory epithelium, endows Rapa@DAK/siRNA with high brain entry efficiency through intranasal administration. KLVFF peptide as an Aß targeting ligand and aggregation inhibitor enables nanoparticles to bind with Aß, inhibit Aß aggregation, and reduce toxicity. Meanwhile, the release of BACE1 siRNA and rapamycin is confirmed to reduce BACE1 expression, promote autophagy, and reduce Aß deposition. Rapa@DAK/siRNA is verified to improve the cognition of transgenic AD mice after intranasal administration. Collectively, the multifunctional nanocarrier provides an effective and potential intranasal avenue for combination therapy of AD.


Asunto(s)
Enfermedad de Alzheimer , Nanopartículas , Enfermedades Neurodegenerativas , Administración Intranasal , Enfermedad de Alzheimer/tratamiento farmacológico , Secretasas de la Proteína Precursora del Amiloide/genética , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Secretasas de la Proteína Precursora del Amiloide/farmacología , Péptidos beta-Amiloides/metabolismo , Animales , Ácido Aspártico Endopeptidasas/genética , Ácido Aspártico Endopeptidasas/metabolismo , Ácido Aspártico Endopeptidasas/farmacología , Encéfalo/metabolismo , Ratones , Ratones Transgénicos , ARN Interferente Pequeño , Sirolimus/farmacología
16.
Opt Express ; 30(4): 6341-6354, 2022 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-35209574

RESUMEN

An in-line Mach-Zehnder interferometer based on a multimode-fiber-assisted tapered open-cavity (TOC) is proposed. Light field distributions of the TOC were investigated using beam propagation method with different offsets and diameters of the taper waist. Bias and uniform taper (BT and UT)-based structures were fabricated and compared using one- and two-step arc-discharge methods, and comprehensive tests were then conducted considering axial-strain. The experimental results show that the UT structure has more than -45 pm/µÉ› linear wavelength shift with the applied axial-strain. Owing to its compact size and low cost, the proposed sensor is promising for axial-strain-related high-precision engineering applications.

17.
Cardiovasc Drugs Ther ; 36(6): 1109-1119, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34491473

RESUMEN

PURPOSE: Abdominal aortic aneurysm (AAA) rupture is one of the most common causes of mortality in cardiovascular diseases, but currently there is no approved drug for AAA treatment or prevention in the clinic. Naringenin (NGN) has been reported to have anti-AAA effects. However, water solubility and in vivo absorption of NGN are not satisfactory, which leads to its low bioavailability, thus affecting its pharmacological effects. In this project, the improving effects of isonicotinamide (INT) co-crystal and hydroxy propyl methyl cellulose (HPMC) or polyvinyl pyrrolidone (PVP) on the solubility, in vivo absorption, and anti-AAA effects of NGN were evaluated. METHODS: In the current study, co-crystals of naringenin-isonicotinamide (NGN-INT) were prepared, and effects of PVP or HPMC on precipitation rate, supersaturation, and bioavailability of NGN were explored. In addition, with or without HPMC supply, the effects of NGN-INT co-crystal on anti-AAA efficacy of NGN were investigated on an elastase-induced AAA mouse model, and the results were compared with the efficacy of the NGN crude drug. RESULTS: Our results demonstrate that NGN-INT formulation, compared to the NGN crude drug, enhanced the dissolution rate of NGN and significantly increased Cmax and AUC(0-∞) of NGN by 18 times and 1.97 times, respectively. Addition of PVP or HPMC in NGN-INT co-crystal further increased bioavailability of NGN in NGN-INT. The in vivo pharmacodynamic study showed that NGN-INT with HPMC significantly improved the inhibitory effects of NGN against AAA. CONCLUSION: NGN-INT significantly improved the absorption and aortic protective effects of NGN. The supersaturation-prolonging effect of HPMC further enhanced bioavailability and anti-AAA effects of NGN-INT.


Asunto(s)
Aneurisma de la Aorta Abdominal , Ratones , Animales , Aneurisma de la Aorta Abdominal/tratamiento farmacológico , Aneurisma de la Aorta Abdominal/prevención & control , Derivados de la Hipromelosa/química , Solubilidad , Povidona/química
18.
J Dairy Sci ; 105(7): 5573-5586, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35570036

RESUMEN

Amyloid fibrils have many excellent functional properties that facilitate their applications in the food industry. There are 2 pathways for whey protein concentrate (WPC) to form amyloid fibril aggregates: spontaneous pathway and nuclear induction pathway. Low ionic strength is a necessary condition for the spontaneous pathway to proceed successfully. In this paper, the effect of salt ions on 2 WPC fibrillation pathways was investigated by adding CaCl2. The results demonstrated WPC fibrils were unable to form normally through spontaneous pathway as adding CaCl2; but still could form through nuclear induction pathway with 20 to 30 mM CaCl2, the nuclei accelerated the fibrillation process led to the resistance to the disordered aggregation brought by CaCl2. Moreover, divalent cations (Ca2+, Mg2+) had much stronger effects than monovalent cations (Na+) on fibril formation, and the results of X-ray photoelectron spectrum together with Fourier-transform infrared spectroscopy suggested that Ca2+ had a greater effect on the fibril formation than Cl-.


Asunto(s)
Amiloide , Calor , Animales , Cloruro de Calcio , Espectroscopía Infrarroja por Transformada de Fourier/veterinaria , Proteína de Suero de Leche/química
19.
J Dairy Sci ; 105(7): 5600-5609, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35570048

RESUMEN

The addition of homogeneous nuclei (HN) or secondary nuclei (SN) could lead to different kinetics and thermodynamics as the nucleation energy barrier decreases and the lag time is shortened to different degrees compared with spontaneous fibrillation. To explain these differences, we monitored the formation and depletion of HN during fibril formation and found that both SN-induced fibrils and HN-induced fibrils follow the same nucleated growth pathway as spontaneously formed WPC fibrils. Moreover, there were also other paths, which were confirmed by X-ray diffraction, transmission electron microscopy, and atomic force microscopy. The surfaces of the SN could recruit monomers and resulted in stronger intersheet stacking and a larger fibril height and periodicity. The HN incorporation led to a propensity for hydrogen-bonding interactions and a longer fibril. Fibrillation by the addition HN and SN followed both common and distinct pathways, as spontaneous fibrillation and led to different capacities to induce fibrillation.


Asunto(s)
Amiloide , Animales , Concentración de Iones de Hidrógeno , Cinética , Microscopía de Fuerza Atómica/veterinaria , Proteína de Suero de Leche
20.
Sensors (Basel) ; 22(22)2022 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-36433352

RESUMEN

Deep learning-based fault diagnosis usually requires a rich supply of data, but fault samples are scarce in practice, posing a considerable challenge for existing diagnosis approaches to achieve highly accurate fault detection in real applications. This paper proposes an imbalanced fault diagnosis of rotatory machinery that combines time-frequency feature oversampling (TFFO) with a convolutional neural network (CNN). First, the sliding segmentation sampling method is employed to primarily increase the number of fault samples in the form of one-dimensional signals. Immediately after, the signals are converted into two-dimensional time-frequency feature maps by continuous wavelet transform (CWT). Subsequently, the minority samples are expanded again using the synthetic minority oversampling technique (SMOTE) to realize TFFO. After such two-fold data expansion, a balanced data set is obtained and imported to an improved 2dCNN based on the LeNet-5 to implement fault diagnosis. In order to verify the proposed method, two experiments involving single and compound faults are conducted on locomotive wheel-set bearings and a gearbox, resulting in several datasets with different imbalanced degrees and various signal-to-noise ratios. The results demonstrate the advantages of the proposed method in terms of classification accuracy and stability as well as noise robustness in imbalanced fault diagnosis, and the fault classification accuracy is over 97%.

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