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1.
Nano Lett ; 24(17): 5260-5269, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38639406

RESUMEN

High-temperature affordable flexible polymer-based pressure sensors integrated with repeatable early fire warning service are strongly desired for harsh environmental applications, yet their creation remains challenging. This work proposed an approach for preparing such advanced integrated sensors based on silver nanoparticles and an ammonium polyphosphate (APP)-modified laminar-structured bulk wood sponge (APP/Ag@WS). Such integrated sensors demonstrated excellent fire warning performance, including a short response time (minimum of 0.44 s), a long-lasting alarm time (>750 s), and reliable repeatability. Moreover, it achieved high-temperature affordable flexible pressure sensing that exhibited an almost unimpaired working range of 0-7.5 kPa and a higher sensitivity (in the low-pressure range, maximum to 226.03 kPa-1) after fire. The high stability was attributed to reliable structural elasticity, and the wood-derived amorphous carbon is capable of repeatable fire warnings. Finally, a Ag@APP/WS-based wireless fire alarm system that realized reliable house fire accident detection was demonstrated, showing great promise for smart firefighting application.

2.
Eur J Pharmacol ; 970: 176493, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38484925

RESUMEN

Excessive activation of FGF19/fibroblast growth factor receptor 4 (FGFR4) signaling is associated with poor survival of patients with hepatocellular carcinoma (HCC). FGFR4 inhibitors show promise for HCC treatment. F30, an indazole derivative designed through computer-aided drug design targeting FGFR4, demonstrated anti-HCC activity as described in our previous studies. However, the precise molecular mechanisms underlying F30's anticancer effects remain largely unexplored. We report here that F30 could effectively induce ferroptosis in HCC cells. The concentrations of cellular ferrous iron, the peroxidation of cell membranes and the homeostasis of reduced glutathione (GSH)/oxidized glutathione disulfide (GSSG) were dysregulated by F30, thereby affecting cellular redox status. Induction of ferroptosis in HCC by F30 was inhibited by specific ferroptosis inhibitor ferrostatin-1. F30 upregulates various ferroptosis-related genes, including the heme oxygenase enzymes 1 (HMOX1), a key mediator of redox regulation. Surprisingly, F30-induced ferroptosis in HCC is dependent on HMOX1. The dysregulation of cellular ferrous iron concentrations and cell membrane peroxidation was rescued when knocking down HMOX1 with specific small interfering RNA. These findings shed light on the molecular mechanisms underlying FGFR4-targeting F30's anti-HCC effects and suggest that FGFR4 inactivation could be beneficial for HCC treatment involving ferroptosis.


Asunto(s)
Carcinoma Hepatocelular , Ferroptosis , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/metabolismo , Línea Celular Tumoral , Proliferación Celular , Hierro , Hemo-Oxigenasa 1
3.
J Biochem Mol Toxicol ; 38(4): e23686, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38549433

RESUMEN

Part of human long noncoding RNAs (lncRNAs) has been elucidated to play an essential role in the carcinogenesis and progression of hepatocellular carcinoma (HCC), a type of malignant tumor with poor outcomes. Tumor-derived exosomes harboring lncRNAs have also been implicated as crucial mediators to orchestrate biological functions among neighbor tumor cells. The recruitment of tumor-associated macrophages (TAMs) exerting M2-like phenotype usually indicates the poor prognosis. Yet, the precise involvement of tumor-derived lncRNAs in cross-talk with environmental macrophages has not been fully identified. In this study, we reported the aberrantly overexpressed HCC upregulated EZH2-associated lncRNA (HEIH) in tumor tissues and cell lines was positively correlated with poor prognosis, as well as enriched exosomal HEIH levels in blood plasma and cell supernatants. Besides, HCC cell-derived exosomes transported HEIH into macrophages for triggering macrophage M2 polarization, thereby in turn promoting the proliferation, migration, and invasion of HCC cells. Mechanistically, HEIH acted as a miRNA sponge for miR-98-5p to up-regulate STAT3, which was then further verified in the tumor xenograft models. Collectively, our study provides the evidence for recognizing tumor-derived exosomal lncRNA HEIH as a novel regulatory function through targeting miR-98-5p/STAT3 axis in environmental macrophages, which may shed light on the complicated tumor microenvironment among tumor and immune cells for HCC treatment.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , ARN Largo no Codificante , Humanos , Carcinoma Hepatocelular/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias Hepáticas/metabolismo , Línea Celular Tumoral , Macrófagos/metabolismo , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Microambiente Tumoral , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo
4.
J Cell Biol ; 223(3)2024 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-38349334

RESUMEN

The cell cycle is a highly regulated process in which proteins involved in cell cycle progression exhibit periodic expression patterns, controlled by specific mechanisms such as transcription, translation, and degradation. However, the precise mechanisms underlying the oscillations of mRNA levels in cell cycle regulators are not fully understood. In this study, we observed that the stability of cyclin D1 (CCND1) mRNA fluctuates during the cell cycle, with increased stability during interphase and decreased stability during the M phase. Additionally, we identified a key RNA binding protein, positive coactivator 4 (PC4), which plays a crucial role in stabilizing CCND1 mRNA and regulating its periodic expression. Moreover, the binding affinity of PC4 to CCND1 mRNA is modulated by two cell cycle-specific posttranslational modifications: ubiquitination of K68 enhances binding and stabilizes the CCND1 transcript during interphase, while phosphorylation of S17 inhibits binding during the M phase, leading to degradation of CCND1 mRNA. Remarkably, PC4 promotes the transition from G1 to S phase in the cell cycle, and depletion of PC4 enhances the efficacy of CDK4/6 inhibitors in hepatocellular carcinoma, suggesting that PC4 could serve as a potential therapeutic target. These findings provide valuable insights into the intricate regulation of cell cycle dynamics.


Asunto(s)
Ciclo Celular , Ciclina D1 , Estabilidad del ARN , Proteínas de Unión al ARN , Ciclo Celular/genética , División Celular , Ciclina D1/genética , Proteínas Inhibidoras de las Quinasas Dependientes de la Ciclina , Estabilidad del ARN/genética , ARN Mensajero/genética , Masculino , Animales , Ratones , Ratones Endogámicos BALB C , Humanos , Línea Celular Tumoral , Proteínas de Unión al ARN/genética , Fosforilación , Ubiquitinación
5.
Nanoscale Adv ; 6(2): 559-569, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38235083

RESUMEN

Optoelectronic synaptic transistors are attractive for applications in next-generation brain-like computation systems, especially for their visible-light operation and in-sensor computing capabilities. However, from a material perspective, it is difficult to build a device that meets expectations in terms of both its functions and power consumption, prompting the call for greater innovation in materials and device construction. In this study, we innovatively combined a novel perovskite carrier supply layer with an Al/MoO3 interface carrier regulatory layer to fabricate optoelectronic synaptic devices, namely Al/MoO3/CsFAMA/ITO transistors. The device could mimic a variety of biological synaptic functions and required ultralow-power consumption during operation with an ultrafast speed of >0.1 µs under an optical stimulus of about 3 fJ, which is equivalent to biological synapses. Moreover, Pavlovian conditioning and visual perception tasks could be implemented using the spike-number-dependent plasticity (SNDP) and spike-rate-dependent plasticity (SRDP). This study suggests that the proposed CsFAMA synapse with an Al/MoO3 interface has the potential for ultralow-power neuromorphic information processing.

6.
Int Wound J ; 21(1): e14384, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37697692

RESUMEN

Pathological scarring resulting from traumas and wounds, such as hypertrophic scars and keloids, pose significant aesthetic, functional and psychological challenges. This study provides a comprehensive transcriptomic analysis of these conditions, aiming to illuminate underlying molecular mechanisms and potential therapeutic targets. We employed a co-expression and module analysis tool to identify significant gene clusters associated with distinct pathophysiological processes and mechanisms, notably lipid metabolism, sebum production, cellular energy metabolism and skin barrier function. This examination yielded critical insights into several skin conditions including folliculitis, skin fibrosis, fibrosarcoma and congenital ichthyosis. Particular attention was paid to Module Cluster (MCluster) 3, encompassing genes like BLK, TRPV1 and GABRD, all displaying high expression and potential implications in immune modulation. Preliminary immunohistochemistry validation supported these findings, showing elevated expression of these genes in non-fibrotic samples rich in immune activity. The complex interplay of different cell types in scar formation, such as fibroblasts, myofibroblasts, keratinocytes and mast cells, was also explored, revealing promising therapeutic strategies. This study underscores the promise of targeted gene therapy for pathological scars, paving the way for more personalised therapeutic approaches. The results necessitate further research to fully ascertain the roles of these identified genes and pathways in skin disease pathogenesis and potential therapeutics. Nonetheless, our work forms a strong foundation for a new era of personalised medicine for patients suffering from pathological scarring.


Asunto(s)
Cicatriz Hipertrófica , Queloide , Humanos , Cicatriz Hipertrófica/genética , Cicatriz Hipertrófica/terapia , Cicatriz Hipertrófica/metabolismo , Queloide/genética , Queloide/terapia , Queratinocitos/metabolismo , Fibroblastos/metabolismo , Miofibroblastos/metabolismo
7.
Biosens Bioelectron ; 248: 115941, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38160634

RESUMEN

Environmental pollution caused by tetracycline antibiotics is a major concern of global public health. Here, a novel and portable molecularly imprinted electrochemiluminescence (MIECL) sensor based on smartphones for highly sensitive detection of chlortetracycline (CTC) has been successfully established. The high-performance ECL emitter of biomass carbon (BC) encapsulated CdZnTeS (CdZnTeS@BC) was successfully synthesized by hydrothermal. The enhanced ECL performance was ascribed to the introduction of the BC and increased the overall electrical conductivity of the nanoemitter, as well as increased the number of sulfur vacancies and doping on the surface of the emitter based on density functional theory calculations. An aniline-CTC molecular imprinted polymer was synthesized on the surface of the CdZnTeS@BC modified electrode by in-situ electropolymerization. The decrease in MIECL signal was attributed to the increase in impedance effect. The MIECL nanoplatform enabled a wide linear relationship in the range of 0.05-100 µmol/L with a detection limit of 0.029 µmol/L for spectrometer sensors. Interestingly, the light emitted during the MIECL reaction can be captured by a smartphone. Thus, machine learning was used to screen the photos that were taken, and color analysis was carried out on the screened photos by self-developed software, thus achieving a portable, convenient, and intelligent sensing mode. Finally, the sensor obtains satisfactory results in the detection of actual samples, with no significant differences from those of liquid chromatography.


Asunto(s)
Técnicas Biosensibles , Cadmio , Clortetraciclina , Impresión Molecular , Telurio , Zinc , Carbono/química , Mediciones Luminiscentes/métodos , Impresión Molecular/métodos , Inteligencia Artificial , Biomasa , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , Límite de Detección
8.
J Chem Neuroanat ; 133: 102338, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37708947

RESUMEN

BACKGROUND: Mesenchymal stem cells (MSCs) and Salvianolic acid B (SAB) are known to exert potent anti-inflammatory and anti-oxidative properties. But the effect of SAB and MSCs combination treatment on the cerebral ischemia/reperfusion injury (CI/RI) is not clear. METHODS: After the CI/RI animal model established, rats were administered with MSCs and SAB individually or combination treatment. To evaluate the therapeutic potential, behavioral tests, TTC staining, Hematoxylin-eosin (HE) staining, and immunofluorescence assays were performed to evaluate the neuroprotection and endogenous neurogenesis. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and enzyme linked immunosorbent assay (ELISA) were performed to evaluate the anti-apoptosis and anti-inflammatory effect. Meanwhile, the expression of the TLR4/NF-ĸB/MYD88 signal pathway-related proteins was evaluated by Western blot. RESULTS: MSCs and SAB individually or combination treatment have protective effect in CI/RI rats. More importantly, the rats with the combination treatment showed a better behavioral recovery, neurogenesis and smaller infarct size compared with the rats administered with MSCs or SAB individually. Further research showed that the combination treatment decreased CI/RI induced inflammatory cytokines and oxidative stress, including inhibiting the production of IL-1ß, IL-6, TNF-α, decreasing the levels of malondialdehyde (MDA), and increased the activity of superoxide dismutase (SOD). In addition, the neuroprotection effect of SAB and MSCs combination was achieved through the regulation of TLR4/NF-κB/MyD88 signaling pathway related proteins, including inhibition the protein levels of TLR4, MYD88, p-NF-κB p65, TRAF6-and action of SIRT1 in brain tissues. CONCLUSION: The present study indicated that the MSCs and SAB combination treatment had better protective effect against rat ischemic brain injury. The combination of SAB and MSCs may provide a potent and promising strategy for the treatment of ischemic stroke and is worthy for further development.


Asunto(s)
Lesiones Encefálicas , Isquemia Encefálica , Células Madre Mesenquimatosas , Daño por Reperfusión , Ratas , Animales , FN-kappa B/metabolismo , Ratas Sprague-Dawley , Receptor Toll-Like 4/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Antiinflamatorios/uso terapéutico , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/prevención & control , Células Madre Mesenquimatosas/metabolismo
9.
Altern Ther Health Med ; 29(8): 674-679, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37678875

RESUMEN

Background: Patients with prior cancer are generally exempt from cancer experiments. This research aims to describe the prevalence, clinical features, and effects of past malignancy among patients with chondrosarcoma. Methods: Chondrosarcoma patients diagnosed between 2010 to 2015 were collected from the SEER database. The propensity score matching method was used to reconcile the disparity in baseline attributes. Kaplan-Meier analysis was employed to explore the outcomes of prior cancer on overall survival. The proportional hazards assumption was used to certain whether the covariate matched the Cox regression model. The potential outliers were estimated by deviance residuals type. Results: A total of 1,721 unique individuals were collected, of those 284 (16.50%) patients had a history of cancer, with prostate cancer being commonly documented (n = 49, 17.25%). Approximately half of the previous tumors are diagnosed within 5 years before the diagnosis of chondrosarcoma. Chondrosarcoma patients with prior cancers have a lower survival rate than those without prior malignancy (P < .001). A multivariable Cox analysis reveals that past cancer is a distinct risk factor for lifespan (hazard ratio = 2.489, P < .001). Conclusion: This study initially discovered that chondrosarcoma patients with past cancer have a bad prognosis. Different types of past cancer have varying effects on survival. We urgently propose that cancer trial exclusion criteria be set specifically by cancer classification, rather than accepting the unchangeable criterion for default.


Asunto(s)
Neoplasias Óseas , Condrosarcoma , Masculino , Humanos , Neoplasias Óseas/epidemiología , Neoplasias Óseas/patología , Programa de VERF , Pronóstico , Condrosarcoma/epidemiología , Condrosarcoma/patología , Factores de Riesgo
10.
Electrophoresis ; 44(17-18): 1342-1352, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37309725

RESUMEN

Meat adulteration detection is a common concern of consumers. Here, we proposed a multiplex digital polymerase chain reaction method and a low-cost device for meat adulteration detection. Using a polydimethylsiloxane microfluidic device, polymerase chain reaction reagents could be pump-free loaded into microchambers (40 × 40 chambers) automatically. Due to the independence of multiplex fluorescence channels, deoxyribonucleic acid templates extracted from different animal species could be distinguished by one test. In this paper, we designed primers and probes for four types of meat (beef, chicken, pork, and duck) and labeled each of the four fluorescent markers (hexachlorocyclohexane [HEX], 6-carboxyfluorescein [FAM], X-rhodamine [ROX], and cyanine dyes 5 [CY5]) on the probes. Specific detection and mixed detection experiments were performed on four types of meat, realizing a limit of detection of 3 copies/µL. A mixture of four different species can be detected by four independent fluorescence channels. The quantitative capability of this method is found to meet the requirements of meat adulteration detections. This method has great potential for point-of-care testing together with portable microscopy equipment.


Asunto(s)
Contaminación de Alimentos , Carne , Animales , Bovinos , Contaminación de Alimentos/análisis , Carne/análisis , Reacción en Cadena de la Polimerasa Multiplex/métodos , Cartilla de ADN/análisis , Patos
11.
Food Chem ; 423: 136339, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37192558

RESUMEN

A smartphone-based sensitive, rapid, label-free and high-throughput detection platform for Escherichia coli O157:H7 was established. The specific recognition capability of this platform was dependent of the aptamer modified on the silica photonic microsphere (SPM), whose structural colour was utilized for the quantification of the target bacterium. Gold nanoparticles and silver staining technique were employed to improve the sensitivity of the detection platform. Such smartphone-based detection platform gave a wide linear detection range of 102 âˆ¼ 108 CFU/mL with a low limit of detection (LOD) of 68 CFU/mL and high specificity for Escherichia coli O157:H7. Moreover, the recovery rates of the detection method were measured in the range of 99 âˆ¼ 108% in the milk, pork and purified water samples. Furthermore, the developed detection platform did not require complex sample pretreatment and could be easily manipulated, displaying great application potential in the fields of food safety, environmental monitoring and disease diagnosis.


Asunto(s)
Escherichia coli O157 , Sistemas de Atención de Punto , Teléfono Inteligente , Escherichia coli O157/aislamiento & purificación , Color , Microesferas , Calibración , Nanopartículas del Metal , Oro/química
12.
Food Chem ; 424: 136433, 2023 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-37244192

RESUMEN

The aim of this research was to develop a simple, rapid, sensitive, high-throughput detection method for foodborne Escherichia coli (E. coli) O157:H7 based on the aptamer-modified gold nanoparticles@macroporous magnetic silica photonic microsphere (Au@MMSPM). Such Au@MMSPM array system for E. coli O157:H7 not only integrated sample pretreatment with rapid detection, but also showed highly enhanced effect to develop a highly sensitive SERS assay. The established SERS assay platform gave a wide linear detection range (10-106 CFU/mL) and low limit of detection (2.20 CFU/mL) for E. coli O157:H7. The whole analysis time including sample pretreatment and detection was 110 min. This SERS-based assay platform provided a new high-throughput, highly sensitive and fast detection technology for monitoring E. coli O157:H7 in real samples from the fields of food industry, medicine and environment.


Asunto(s)
Técnicas Biosensibles , Escherichia coli O157 , Nanopartículas del Metal , Dióxido de Silicio , Oro , Microesferas , Oligonucleótidos , Fenómenos Magnéticos , Microbiología de Alimentos
13.
Injury ; 2023 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-37028952

RESUMEN

Adipose-derived stem cells (ADSCs) have been widely proven to facilitate wound healing. Our study aimed to estimate the influence of combined ADSCs and platelet-derived growth factor-BB (PDGF-BB) on wound healing. We utilized 4 healthy SD rats to isolate ADSCs. Platelet-rich plasma (PRP) was acquired utilizing a two-step centrifugation technology. The role of PRP, PDGF-BB, and PDGF-BB combined with a PI3k inhibitor LY294002 on the viability, migration, and PTEN/AKT pathway in ADSCs were examined utilizing CCK-8, Transwell, and western blot assays. Then, we constructed an open trauma model in SD rats. Effects of ADSCs treated with PDGF-BB on pathological changes, CD31, and PTEN/AKT pathway of wound closure were assessed by hematoxylin & eosin (H&E) staining, Masson staining, immunohistochemical, and western blot assays, respectively. PRP and PDGF-BB intensified the viability and migration of ADSCs by modulating the PTEN/AKT pathway. Interestingly, LY294002 reversed the role of PDGF-BB on ADSCs. In vivo experiments, combined intervention with ADSCs plus PDGF-BB/PRP facilitated wound closure and ameliorated histological injury. Moreover, combined intervention with ADSCs and PDGF-BB attenuated the PTEN level and elevated the CD31 level as well as the ratio of p-AKT/AKT in the skin tissues. A combination of ADSCs and PDGF-BB facilitated wound healing might associate with the regulation of the PTEN/AKT pathway.

14.
J Agric Food Chem ; 71(6): 3050-3059, 2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36734836

RESUMEN

Rapid identification and quantitative simultaneous analysis for multiple pesticide in real samples based on surface-enhanced Raman spectroscopy (SERS) is still a challenge because of sample complexity, reproducibility, and stability of SERS substrate. With use of colloidal silver nanoparticles loaded three-dimensional (3D) silica photonic microspheres (SPMs) array as the analytical platform, a SERS-based array assay for multiple pesticides was developed in this work. The silver nanoparticles were fixed into the gaps formed by the self-assembled nanospheres of the 3D SPMs to produce "hot spots", on which the Raman enhanced effect was up to 9.86 × 107 and the maximum electric field enhancement effect reached to 9.75 times, ensuring the target pesticides on the surface of the SERS-substrate integrated SPM can be detected sensitively. Using 2,4-dichlorophenoxyacetic acid (2,4-D), glyphosate, and imidacloprid as the testing pesticides, the label-free and high-throughput SERS assay for simultaneous detection of the pesticides was established, giving good linear detection ranges (0.1-204.8 µg/mL for 2,4-D, 0.3-247.9 µg/mL for glyphosate, and 0.2-204.8 µg/mL for imidacloprid) and low detection limits (3.03 ng/mL for 2,4-D, 3.14 ng/mL for glyphosate, and 8.82 ng/mL for imidacloprid). The spiked recovery rates in the real samples were measured in the range of 82-112%, which was consistent with that of the classical standard methods. The label-free 3D SERS array analytical platform provides a powerful tool for high-throughput and low-cost screening of multiple pesticide residues in real samples.


Asunto(s)
Nanopartículas del Metal , Plaguicidas , Plaguicidas/análisis , Nanopartículas del Metal/química , Dióxido de Silicio , Microesferas , Reproducibilidad de los Resultados , Plata/química , Espectrometría Raman/métodos , Ácido 2,4-Diclorofenoxiacético
15.
J Orthop Surg Res ; 18(1): 86, 2023 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-36737821

RESUMEN

BACKGROUND: Osteoporotic fracture (OPF) is one of the most common skeletal diseases in an aging society. The Chinese medicine formula Buzhong Yiqi Decoction (BZYQD) is commonly used for treating OPF. However, the essential bioactive compounds and the underlying molecular mechanisms that promote fracture repair remain unclear. METHODS: We used network pharmacology and experimental animal validation to address this issue. First, 147 bioactive BZYQD compounds and 32 target genes for treating OPF were screened and assessed. A BZYQD-bioactive compound-target gene-disease network was constructed using the Cytoscape software. Functional enrichment showed that the candidate target genes were enriched in oxidative stress- and inflammation-related biological processes and multiple pathways, including nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) signaling pathways. Furthermore, an OPF rat model was established and treated with BZYQD. RESULTS: The results revealed that BZYQD ameliorated OPF characteristics, including femoral microarchitecture, biomechanical properties, and histopathological changes, in a dose-dependent manner. Results of enzyme-linked immunosorbent assay showed that BZYQD reduced the serum's pro-inflammatory cytokines [Tumor necrosis factor-alpha (TNF-α), Interleukin (IL)-1ß, and IL-6] and improved oxidative stress-related factors [glutathione (GSH) and superoxide dismutase (SOD)]. BZYQD significantly decreased the protein expression of NF-κB in OPF rat femurs, suppressed NF-κB activation, and activated the nuclear factor-erythroid factor 2-related factor (Nrf2)/heme oxygenase 1 (HO-1) and p38 MAPK as well ERK pathways. CONCLUSIONS: Our results suggest that BZYQD could improve inflammation and oxidative stress during fracture repair by suppressing NF-κB and activating Nrf2/MAPK signaling pathways.


Asunto(s)
FN-kappa B , Fracturas Osteoporóticas , Animales , Ratas , Inflamación/patología , Farmacología en Red , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/uso terapéutico , FN-kappa B/metabolismo , Fracturas Osteoporóticas/tratamiento farmacológico
16.
Drug Resist Updat ; 67: 100929, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36739809

RESUMEN

Currently, renal cell carcinoma (RCC) is the most prevalent type of kidney cancer. Targeted therapy has replaced radiation therapy and chemotherapy as the main treatment option for RCC due to the lack of significant efficacy with these conventional therapeutic regimens. Sunitinib, a drug used to treat gastrointestinal tumors and renal cell carcinoma, inhibits the tyrosine kinase activity of a number of receptor tyrosine kinases, including vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), c-Kit, rearranged during transfection (RET) and fms-related receptor tyrosine kinase 3 (Flt3). Although sunitinib has been shown to be efficacious in the treatment of patients with advanced RCC, a significant number of patients have primary resistance to sunitinib or acquired drug resistance within the 6-15 months of therapy. Thus, in order to develop more efficacious and long-lasting treatment strategies for patients with advanced RCC, it will be crucial to ascertain how to overcome sunitinib resistance that is produced by various drug resistance mechanisms. In this review, we discuss: 1) molecular mechanisms of sunitinib resistance; 2) strategies to overcome sunitinib resistance and 3) potential predictive biomarkers of sunitinib resistance.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Biomarcadores , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Indoles/farmacología , Indoles/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Pirroles/farmacología , Pirroles/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Sunitinib/farmacología , Sunitinib/uso terapéutico , Factor A de Crecimiento Endotelial Vascular , Resistencia a Antineoplásicos
17.
Biosens Bioelectron ; 222: 114996, 2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36521203

RESUMEN

Here, a novel and portable machine learning-assisted smartphone-based visual molecularly imprinted ratiometric electrochemiluminescence (MIRECL) sensing platform was constructed for highly selective sensitive detection of 2,4-Dichlorophenoxyacetic acid (2,4-D) for the first time. Te doped CdS-coated Mn3O4 (Te-CdS@Mn3O4) with catalase-like activity served as cathode-emitter, while luminol as anode luminophore accompanied H2O2 as co-reactant, and Te-CdS@Mn3O4 decorated molecularly imprinted polymers (MIPs) as recognition unit, respectively. Molecular models were constructed and MIP band and binding energies were calculated to elucidate the luminescence mechanism and select the best functional monomers. The peroxidase activity and the large specific surface area of Mn3O4 and the electrochemical effect can significantly improve the ECL intensity and analytical sensitivity of Te-CdS@Mn3O4. 2,4-D-MIPs were fabricated by in-situ electrochemical polymerization, and the rebinding of 2,4-D inhibits the binding of H2O2 to the anode emitter, and with the increase of the cathode impedance, the ECL response of Te-CdS@Mn3O4 decreases significantly. However, the blocked reaction of luminol on the anode surface also reduces the ECL response. Thus, a double-reduced MIRECL sensing system was designed and exhibited remarkable performance in sensitivity and selectivity due to the specific recognition of MIPs and the inherent ratio correction effect. Wider linear range in the range of 1 nM-100 µM with a detection limit of 0.63 nM for 2,4-D detection. Interestingly, a portable and visual smartphone-based MIRECL analysis system was established based on the capture of luminescence images by smartphones, classification and recognition by convolutional neural networks, and color analysis by self-developed software. Therefore, the developed MIRECL sensor is suitable for integration with portable devices for intelligent, convenient, and fast detection of 2,4-D in real samples.


Asunto(s)
Técnicas Biosensibles , Impresión Molecular , Impresión Molecular/métodos , Teléfono Inteligente , Luminol/química , Peróxido de Hidrógeno , Mediciones Luminiscentes/métodos , Técnicas Biosensibles/métodos , Límite de Detección , Polímeros Impresos Molecularmente , Ácido 2,4-Diclorofenoxiacético , Técnicas Electroquímicas/métodos
18.
IEEE Trans Cybern ; 53(7): 4204-4217, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35316202

RESUMEN

This article proposes a novel barrier-based adaptive line-of-sight (ALOS) three-dimensional (3-D) path-following system for an underactuated multijoint robotic fish. The framework of the developed path-following system is established based on a detailed dynamic model, including a barrier-based ALOS guidance strategy, three integrated inner-loop controllers, and a nonlinear disturbance observer (NDOB)-based sideslip angle compensation, which is employed to preserve a reliable tracking under a frequently varying sideslip angle of the robotic fish. First, a barrier-based convergence strategy is proposed to deal with probable along-track error disruption and suppress the error within a manageable range. Meanwhile, an improved adaptive guidance scheme is adopted with an appropriate look-ahead distance. Afterward, a novel NDOB-based sideslip angle compensation is put forward to identify the varying sideslip angle independent of speed estimation. Subsequently, inner-loop controllers are intended for regulation about the controlled references, including a super-twisting sliding-mode control (STSMC)-based speed controller, a global fast terminal sliding-mode control (GFTSMC)-based heading controller, and a GFTSMC-based depth controller. Finally, simulations and experiments with quantitative comparison in 3-D linear and helical path following are presented to verify the effectiveness and robustness of the proposed system. This path-following system provides a solid foundation for future marine autonomous cruising of the underwater multijoint robot.


Asunto(s)
Procedimientos Quirúrgicos Robotizados , Robótica , Animales
19.
Food Res Int ; 162(Pt B): 112098, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36461404

RESUMEN

Yellow pigments in the water-extract of safflower (Carthamus tinctorius L.) belong to quinochalcone flavonoid family and are widely used as food colourants. The aim of the study was to characterize the main quinochalcone compounds in safflower water-extract during blooming period when floret changed colour. Mass-spectrometry results showed that hydroxysafflor yellow A (HSYA) and anhydrosafflor yellow B (AHSYB) were the most abundant. Based on 370 florets samples collected from 144 cultivars, the contents of HSYA and AHSYB were determined, which showed that only AHSYB content had relatively strong positive association with colour indexes. The ratio of HSYA/AHSYB and visual colour exhibited certain patterns: yellow = 2, orange = 3-4, red = more dispersed, mostly falling 5-6. Most of the florets had HSYA increased first and decreased, while AHSYB decreased all the time when floret changed colour as yellow â†’ orange â†’ red. Regardless of the composition of HSYA/AHSYB in florets, the antioxidant capacities of safflower petal water-extracts were the same.


Asunto(s)
Carthamus tinctorius , Antioxidantes , Color , Extractos Vegetales , Agua
20.
Anal Chem ; 94(51): 17939-17946, 2022 12 27.
Artículo en Inglés | MEDLINE | ID: mdl-36519631

RESUMEN

We have demonstrated the proof-of-concept of a label-free fluorescence quantitative detection platform based on gold nanoparticle (AuNP) enhancement intrinsic fluorescence of protein on the silica photonic crystal microsphere (SPCM) array. The label-free one-step competitive fluorescence immunoassay protocol has been proposed on the surface of the SPCM. Aflatoxin B1 (AFB1) as a model molecule was detected by the newly established method. AFB1-bovine serum albumin and monoclonal antibodies (Abs) of anti-AFB1 have been immobilized on the surfaces of SPCMs and AuNPs, respectively. AuNPs remarkably enhanced the intrinsic fluorescence of artificial antigens on the surface of the SPCM at near UV excitation. The simulation of electric field distribution showed that the maximum value of the near-field enhancement |E/E0| of the SPCM with AuNPs could reach 20. The label-free fluorescence enhancement effect comes from the synergistic effects of photonic crystal effect and AuNP plasmon effect. Such a label-free fluorescence detection method can provide a linear detection range from 0.1 to 10 ng/mL with a limit of detection of 0.025 ng/mL and good specificity for AFB1. The recovery rates in the spiked cereal samples were measured in the range of 84.07 ± 5.71%-101.02 ± 5.13%, which were consistent with that of the traditional enzyme linked immunosorbent assay method. The label-free detection platform displays great application potential in biology, medicine, agriculture, food industry, chemical industry, energy source, and environmental protection.


Asunto(s)
Técnicas Biosensibles , Nanopartículas del Metal , Microesferas , Oro/química , Dióxido de Silicio/química , Nanopartículas del Metal/química , Ensayo de Inmunoadsorción Enzimática , Aflatoxina B1/análisis , Límite de Detección
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