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An innovative acidic hydrolysate fingerprinting workflow was proposed for the characterization of Lyophyllum Decastes polysaccharide (LDP) by ultra performance liquid chromatography-mass spectrometry (UPLC-MS). The crude polysaccharides were firstly separated and purified by using DE-52 column and the BRT GPC purification system, respectively. The molecular weight and monosaccharide content of homogeneous polysaccharides were ascertained by utilizing HPGPC and ion chromatography separately. Secondly, the linkage of LDP was identified by methylation analysis and 1D/2D NMR spectra. The UPLC-MS/MS was used to scan and identify the acidic hydrolysate products of LDP using the PGC column. The oligosaccharides were collected by chromatography and identified by mass spectrometry. Thirdly, the expression of IL-1ß, IL-6, iNOS, TNF-α and IFNAR-I was measured in order to assess the immunological activity of LDP. Besides, the targeted receptors identification of polysaccharides was performed by screening the expression of TLRs family protein. The results showed that oligosaccharide fragments with different molecular weights can be obtained by partial hydrolysis, which further verified that the structures of LDP polysaccharides was a 1-6-linked ß-glucan. Moreover, the LDP polysaccharide can up-regulate the content of IL-1ß, IL-6, iNOS, TNF-α and IFNAR-I and plays an important immunoregulation role through TLRs family.
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PURPOSE: This study aims to explore the correlation between PET and CMR in integrated [68Ga]Ga-FAPI-04 PET/CMR multimodal imaging and its value in the diagnosis and risk assessment of hypertrophic cardiomyopathy (HCM). METHODS: This study included 20 HCM patients and 11 age- and gender-matched controls. PET analysis evaluated left ventricular (LV) [68Ga]Ga-FAPI-04 uptake, including SUVmax, TBR, cardiac fibroblast activity (CFA) and volume (CFV), and total SUV of the 16 segments. CMR tissue characterization parameters included cardiac function, myocardial thickness, late gadolinium enhancement (LGE), relaxation time, extracellular volume (ECV), and peak strain parameters. The 5-year sudden cardiac death (SCD) risk score and the 2-year and 5-year atrial fibrillation (AF) risk scores were calculated for each patient. The study analyzed differences between HCM patients and controls, the correlation between [68Ga]Ga-FAPI-04 PET and concurrent CMR imaging results, and the predictive value of PET/CMR. RESULT: The FAPI uptake, myocardial mass, myocardial thickness, and T1/T2 mapping values were significantly higher in HCM patients compared to controls. Twenty HCM patients and their 320 myocardial segments were discussed. Increased [68Ga]Ga-FAPI-04 uptake in the left ventricular wall was observed in 95% (19/20) of the patients, covering 48.8% (156/320) of the segments. On concurrent CMR, 80% (16/20) of the patients showed LGE, including 95 (29.7%) segments. The FAPI(+)LGE(+) segments exhibited the highest myocardial PET uptake, greatest thickness, longest T1/T2 native values, largest ECV value and the greatest loss of myocardial strain capacity (P < 0.05). There was a significant correlation between FAPI uptake and CMR parameters (P < 0.05). Higher [68Ga]Ga-FAPI-04 uptake showed a positive correlation with SCD and AF risk scores (P < 0.05). The number of LGE(+) segments, mapping parameters, and ECV values in CMR also had prognostic significance. Combining PET with CMR aided in further risk stratification of HCM. CONCLUSION: [68Ga]Ga-FAPI-04 PET/CMR multimodal imaging has potential value in the detection of damaged myocardial lesions and risk assessment of HCM patients. [68Ga]Ga-FAPI-04 PET can detect more affected myocardium compared to CMR, and segments with abnormalities in both PET and CMR show more severe myocardial damage.
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The implementation of energy-saving policies has stimulated intensive interest in exploring self-powered optoelectronic devices. The 2D p-n homojunction exhibits effective generation and separation of carriers excited by light, realizing lower power consumption and higher performance photodetectors. Here, a self-powered photodetector with high performance is fabricated based on an F4-TCNQ localized molecular-doped lateral InSe homojunction. Compared with the intrinsic InSe photodetector, the switching light ratio (Ilight/Idark) of the p-n homojunction device can be enhanced by 2.2 × 104, and the temporal response is also dramatically improved to 24/30 µs. Benefiting from the built-in electric field, due to the formation of an InSe p-n homojunction after partial doping of F4-TCNQ on InSe, the device possesses a high responsivity (R) of 93.21 mA/W, with a specific detectivity (D*) of 1.14 × 1011 Jones. These results suggest a promising approach to get a lateral InSe p-n homojunction and reveal the potential application of the device for next generation low-consumption photodetectors.
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The mature processes of metal oxide semiconductors (MOS) have attracted considerable interest. However, the low sensitivity of metal oxide semiconductor gas sensors is still challenging, and constrains its practical applications. Bimetallic nanoparticles are of interest owing to their excellent catalytic properties. This excellent feature of bimetallic nanoparticles can solve the problems existing in MOS gas sensors, such as the low response, high operating temperature and slow response time. To enhance acetone sensing performance, we successfully synthesized Au-Pd/ZnO nanorods. In this work, we discovered that Au-Pd nanoparticles modified on ZnO nanorods can remarkably enhance sensor response. The Au-Pd/ZnO gas sensor has long-term stability and an excellent response/recovery process. This excellent sensing performance is attributed to the synergistic catalytic effect of bimetallic AuPd nanoparticles. Moreover, the electronic and chemical sensitization of noble metals also makes a great contribution. This work presents a simple method for preparing Au-Pd/ZnO nanorods and provides a new solution for the detection of acetone based on metal oxide semiconductor.
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Background: The role of cardiopulmonary exercise testing (CPET) parameters in evaluating the functional severity of coronary disease remains unclear. The aim of this study was to quantify the O2-pulse morphology and investigate its relevance in predicting the functional severity of coronary stenosis, using Murray law-based quantitative flow ratio (µQFR) as the reference. Methods: CPET and µQFR were analyzed in 138 patients with stable coronary artery disease (CAD). The O2-pulse morphology was quantified through calculating the O2-pulse slope ratio. The presence of O2-pulse plateau was defined according to the best cutoff value of O2-pulse slope ratio for predicting µQFR ≤ 0.8. Results: The optimal cutoff value of O2-pulse slope ratio for predicting µQFR ≤ 0.8 was 0.4, with area under the curve (AUC) of 0.632 (95 % CI: 0.505-0.759, p = 0.032). The total discordance rate between O2-pulse slope ratio and µQFR was 27.5 %, with 13 patients (9.4 %) being classified as mismatch (O2-pulse slope ratio > 0.4 and µQFR ≤ 0.8) and 25 patients being classified as reverse-mismatch (O2-pulse slope ratio ≤ 0.4 and µQFR > 0.8). Angiography-derived microvascular resistance was independently associated with mismatch (OR 0.07; 95 % CI: 0.01-0.38, p = 0.002) and reverse-mismatch (OR 9.76; 95 % CI: 1.47-64.82, p = 0.018). Conclusion: Our findings demonstrate the potential of the CPET-derived O2-pulse slope ratio for assessing myocardial ischemia in stable CAD patients.
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Efficient sensors for toluene detecting are urgently needed to meet people's growing demands for both environment and personal health. Metal oxide semiconductor (MOS)-based sensors have become brilliant candidates for the detection of toluene because of their superior performance over gas sensing. However, gas sensors based on pure MOS have certain limitations in selectivity, operating temperature, and long-term stability, which hinders their further practical applications. Noble metals (including Ag, Au, Pt, Pd, etc.) have the ability to enhance the performance of MOS-based sensors via surface functionalization. Herein, ZnO nanoflowers (ZNFs) modified with bimetallic AuPt are prepared for toluene detection through hydrothermal method. The response of a AuPt@ZNF-based gas sensor can reach 69.7 at 175 °C, which is 30 times, 9 times, and 10 times higher than that of the original ZNFs, Au@ZNFs, and Pt@ZNFs, respectively. Furthermore, the sensor also has a lower optimal operating temperature (175 °C), good stability (94% of previous response after one month), and high selectivity towards toluene, which is the result of the combined influence of the electronic and chemical sensitization of noble metals, as well as the unique synergistic effect of the AuPt alloy. In summary, AuPt@ZNF-based sensors can be further applied in toluene detection in practical applications.
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Hypoxia-induced cardiomyocyte apoptosis is one major pathological change of acute myocardial infarction (AMI), but the underlying mechanism remains unexplored. CDC-like kinase 3 (CLK3) plays crucial roles in cell proliferation, migration and invasion, and nucleotide metabolism, however, the role of CLK3 in AMI, especially hypoxia-induced apoptosis, is largely unknown. The expression of CLK3 was elevated in mouse myocardial infarction (MI) models and neonatal rat ventricular myocytes (NRVMs) under hypoxia. Furthermore, CLK3 knockdown significantly promoted apoptosis and inhibited NRVM survival, while CLK3 overexpression promoted NRVM survival and inhibited apoptosis under hypoxic conditions. Mechanistically, CLK3 regulated the phosphorylation status of AKT, a key player in the regulation of apoptosis. Furthermore, overexpression of AKT rescued hypoxia-induced apoptosis in NRVMs caused by CLK3 deficiency. Taken together, CLK3 deficiency promotes hypoxia-induced cardiomyocyte apoptosis through AKT signaling pathway.
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Apoptosis , Hipoxia de la Célula , Miocitos Cardíacos , Proteínas Serina-Treonina Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Animales , Masculino , Ratones , Ratas , Ratones Endogámicos C57BL , Infarto del Miocardio/patología , Infarto del Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Fosforilación , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/deficiencia , Proteínas Tirosina Quinasas/metabolismo , Proteínas Tirosina Quinasas/genética , Proteínas Tirosina Quinasas/deficiencia , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Sprague-DawleyRESUMEN
Bemisia tabaci (Gennadius) is an important invasive pest transmitting plant viruses that are maintained through a plant-insect-plant cycle. Tomato yellow leaf curl virus (TYLCV) can be transmitted in a persistent manner by B. tabaci, which causes great losses to global agricultural production. From an environmentally friendly, sustainable, and efficient point of view, in this study, we explored the function of d-limonene in reducing the acquisition and transmission of TYLCV by B. tabaci as a repellent volatile. D-limonene increased the duration of non-feeding waves and reduced the duration of phloem feeding in non-viruliferous and viruliferous whiteflies by the Electrical Penetration Graph technique (EPG). Additionally, after treatment with d-limonene, the acquisition and transmission rate of TYLCV was reduced. Furthermore, BtabOBP3 was determined as the molecular target for recognizing d-limonene by real-time quantitative PCR (RT-qPCR), fluorescence competitive binding assays, and molecular docking. These results confirmed that d-limonene is an important functional volatile which showed a potential contribution against viral infections with potential implications for developing effective TYLCV control strategies.
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Begomovirus , Hemípteros , Solanum lycopersicum , Animales , Limoneno , Simulación del Acoplamiento Molecular , Insectos Vectores , Enfermedades de las Plantas/prevención & control , Conducta AlimentariaRESUMEN
A novel photoelectrochemical (PEC) cytosensor for the ultrasensitive detection of circulating tumor cells (CTCs) was developed. The bio-inspired reduced graphene oxide (rGO) honeycomb film photoelectrode was fabricated via a "breath figure" method, followed by the self-assembly of a Bi2S3-MoS2 heterojunction. The resulting Bi2S3-MoS2 heterojunction-modified rGO honeycomb film was employed as a sensing matrix for the first time. Compared to the smooth rGO film, the significant enhanced photocurrent of the photoelectrode under visible light was attributed to its improved visible light absorption, increased surface area and enhanced separation efficiency of photo-generated electron-hole pairs, which met the requirements of the PEC sensor for detecting larger targets. By virtue of the photocurrent decrease due to the steric hindrance of MCF-7 cells, which were captured by an aptamer immobilized on the surface of the photoelectrode, a cytosensor for detecting CTCs was achieved, showing a wide linear range of 10-1 × 105 cells per mL and a low detection limit of 2 cells per mL. Furthermore, MCF-7 cells in human serum were determined by this PEC biosensor, exhibiting great potential in the clinical detection of CTCs.
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Técnicas Biosensibles , Grafito , Células Neoplásicas Circulantes , Humanos , Óxidos , Molibdeno , Límite de Detección , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodosRESUMEN
The inflammatory response is one of the general symptoms that accompany tumorigenesis, the pro-inflammatory factors cyclooxygenase-2 (COX-2) and COX-2-derived prostaglandin-2 (PGE-2) in the inflammatory environment surrounding tumors possess promoting tumor development, metastasis and angiogenesis effects. In addition, the hypoxic environment of tumors severely limits the effectiveness of photodynamic therapy (PDT). In this study, a universal extracellular-intracellular 'on-demand' release nanomedicine DOX@PDA-ICG@MnO2@GN-CEL was developed for the combined fight against malignant tumors using a spatiotemporal controlled gelatin coated polydopamine (PDA@GN) as the carrier and loaded with the chemotherapeutic drug doxorubicin (DOX), the photosensitizer indocyanine green (ICG), the PDT enhancer MnO2and the anti-inflammatory drug celecoxib (CEL) individually. Our results showed that DOX@PDA-ICG@MnO2@GN-CEL could release CEL extracellularly by matrix metalloproteinase-2 response and inhibit the COX-2/PGE-2 pathway, reduce chemotherapy resistance and attenuate the concurrent inflammation. After entering the tumor cells, the remaining DOX@PDA-ICG@MnO2released DOX, ICG and MnO2intracellularly through PDA acid response. MnO2promoted the degradation of endogenous H2O2to generate oxygen under acidic conditions to alleviate the tumor hypoxic environment, enhance PDT triggered by ICG. PDA and ICG exhibited photothermal therapy synergistically, and DOX exerted chemotherapy with reduced chemotherapy resistance. The dual responsive drug release switch enabled the chemotherapeutic, photothermal, photodynamic and anti-inflammatory drugs precisely acted on different sites of tumor tissues and realized a promising multimodal combination therapy.
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Hipertermia Inducida , Nanopartículas , Neoplasias , Humanos , Metaloproteinasa 2 de la Matriz , Liberación de Fármacos , Microambiente Tumoral , Ciclooxigenasa 2 , Compuestos de Manganeso , Hipertermia Inducida/métodos , Óxidos , Doxorrubicina/farmacología , Verde de Indocianina/farmacología , Antiinflamatorios , Línea Celular TumoralRESUMEN
OBJECTIVE: Opioid-induced nausea and vomiting are frequently observed as an adverse effect in the treatment of cancer-related pain. The factors that affect OINV in cancer patients remain unclear. In this study, we developed a nomogram for predicting the occurrence of OINV in this population using retrospective clinical data. METHODS: We collected data from 416 cancer pain patients, 70% of whom used the training set to analyze demographic and clinical variables. We used multivariate logistic regression to identify significant factors associated with OINV. Then, we construct a prediction nomogram. The validation set comprises the remaining 30%. The reliability of the nomogram is evaluated by bootstrap resampling. RESULTS: Using multivariate logistic regression, we identified five significant factors associated with OINV. The C-index was 0.835 (95% confidence interval [CI], 0.828-0.842) for the training set and 0.810 (95% CI, 0.793-0.826) for the validation set. The calibrated curves show a good agreement between the predicted and actual occurrence of OINV. CONCLUSION: In a retrospective study based on five saliency-found variables, we developed and proved a reliable nomogram model to predict OINV in cancer pain patients. Future prospective studies should assess the model's reliability and usefulness in clinical practice.
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Antieméticos , Dolor en Cáncer , Neoplasias , Humanos , Analgésicos Opioides/efectos adversos , Dolor en Cáncer/tratamiento farmacológico , Dolor en Cáncer/inducido químicamente , Estudios Retrospectivos , Antieméticos/uso terapéutico , Nomogramas , Estudios Prospectivos , Reproducibilidad de los Resultados , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológico , Náusea/inducido químicamente , Náusea/tratamiento farmacológico , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológicoRESUMEN
Exosomal microRNA (miRNA) exerts potential roles in non-small-cell lung cancer (NSCLC). The current study elucidated the role of miR-30b-5p shuttled by bone marrow mesenchymal stem cells (BMSCs)-derived exosomes in treating NSCLC. Bioinformatics analysis was performed with NSCLC-related miRNA microarray GSE169587 and mRNA data GSE74706 obtained for collection of the differentially expressed miRNAs and mRNAs. The relationship between miR-30b-5p and EZH2 was predicted and confirmed. Exosomes were isolated from BMSCs and identified. BMSCs-derived exosomes overexpressing miR-30b-5p were used to establish subcutaneous tumorigenesis models to study the effects of miR-30b-5p, EZH2 and PI3K/AKT signalling pathway on tumour growth. A total of 86 BMSC-exo-miRNAs were differentially expressed in NSCLC. Bioinfomatics analysis found that BMSC-exo-miR-30b-5p could regulate NSCLC progression by targeting EZH2, which was verified by in vitro cell experiments. Besides, the target genes of miR-30b-5p were enriched in PI3K/AKT signalling pathway. Animal experiments validated that BMSC-exo-miR-30b-5p promoted NSCLC cell apoptosis and prevented tumorigenesis in nude mice via EZH2/PI3K/AKT axis. Collectively, the inhibitory role of BMSC-derived exosomes-loaded miR-30b-5p in NSCLC was achieved through blocking the EZH2/PI3K/AKT axis.
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Carcinoma de Pulmón de Células no Pequeñas , Exosomas , Neoplasias Pulmonares , Células Madre Mesenquimatosas , MicroARNs , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Exosomas/metabolismo , Ratones Desnudos , Neoplasias Pulmonares/patología , MicroARNs/metabolismo , Células Madre Mesenquimatosas/metabolismo , Carcinogénesis/patologíaRESUMEN
Objective: Acute kidney injury (AKI) is a common adverse reaction observed with the clinical use of cefoperazone-sulbactam sodium and mezlocillin-sulbactam sodium. Based upon real-world data, we will herein determine the risk factors associated with AKI in inpatients after receipt of these antimicrobial drugs, and we will develop predictive models to assess the risk of AKI. Methods: Data from all adult inpatients who used cefoperazone-sulbactam sodium and mezlocillin-sulbactam sodium at the First Affiliated Hospital of Shandong First Medical University between January 2018 and December 2020 were analyzed retrospectively. The data were collected through the inpatient electronic medical record (EMR) system and included general information, clinical diagnosis, and underlying diseases, and logistic regression was exploited to develop predictive models for the risk of AKI. The training of the model strictly adopted 10-fold cross-validation to validate its accuracy, and model performance was evaluated employing receiver operating characteristic (ROC) curves and the areas under the curve (AUCs). Results: This retrospective study comprised a total of 8767 patients using cefoperazone-sulbactam sodium, of whom 1116 developed AKI after using the drug, for an incidence of 12.73%. A total of 2887 individuals used mezlocillin-sulbactam sodium, of whom 265 developed AKI after receiving the drug, for an incidence of 9.18%. In the cohort administered cefoperazone-sulbactam sodium, 20 predictive factors (p < 0.05) were applied in constructing our logistic predictive model, and the AUC of the predictive model was 0.83 (95% CI, 0.82-0.84). In the cohort comprising mezlocillin-sulbactam sodium use, nine predictive factors were determined by multivariate analysis (p < 0.05), and the AUC of the predictive model was 0.74 (95% CI, 0.71-0.77). Conclusion: The incidence of AKI induced by cefoperazone-sulbactam sodium and mezlocillin-sulbactam sodium in hospitalized patients may be related to the combined treatment of multiple nephrotoxic drugs and a past history of chronic kidney disease. The AKI-predictive model based on logistic regression showed favorable performance in predicting the AKI of adult in patients who received cefoperazone-sulbactam sodium or mezlocillin-sulbactam sodium.
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Unpredicted human organ level toxicity remains one of the major reasons for drug clinical failure. There is a critical need for cost-efficient strategies in the early stages of drug development for human toxicity assessment. At present, artificial intelligence methods are popularly regarded as a promising solution in chemical toxicology. Thus, we provided comprehensive in silico prediction models for eight significant human organ level toxicity end points using machine learning, deep learning, and transfer learning algorithms. In this work, our results showed that the graph-based deep learning approach was generally better than the conventional machine learning models, and good performances were observed for most of the human organ level toxicity end points in this study. In addition, we found that the transfer learning algorithm could improve model performance for skin sensitization end point using source domain of in vivo acute toxicity data and in vitro data of the Tox21 project. It can be concluded that our models can provide useful guidance for the rapid identification of the compounds with human organ level toxicity for drug discovery.
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Algoritmos , Inteligencia Artificial , Humanos , Aprendizaje Automático , Simulación por Computador , Descubrimiento de Drogas/métodosRESUMEN
Objective:To analyze the diagnosis, treatment and prognosis of patients with rare malignant tumors of the temporal bone. Methods:Four cases of rare temporal bone malignant tumors in our hospital between March 2014 and December 2020 were reviewed, including two cases of chondrosarcoma, one case of fibrosarcoma and one case of endolymphatic cystic papillary adenocarcinoma. There were three males and one female, ages between 28 and 56 years at the time of surgery. Common symptoms included hearing loss, facioplegia, tinnitus, and headache. All patients underwent imaging examinations to evaluate the extent of the lesions. Tumors were removed by subtotal temporal bone resection or infratemporal fossa approach, and postoperative adjuvant radiotherapy was applied if necessary. Results:One of the two chondrosarcoma patients was cured by complete resection of the tumor for 75 months, the other one recurred after the first excision of the tumor and underwent infratemporal fossa approach resection of skull base mass again with no recurrence found yet for 112 months. One patient with fibrosarcoma survived for 28 months after surgery with a positive margin and post-operative radiotherapy. One patient with endolymphatic cystic papillary adenocarcinoma recurred 12 months after subtotal lithotomy, and underwent subtotal temporal bone resection again, combined with radiotherapy. No recurrence was found for 63 months. Conclusion:The incidence of rare temporal bone malignant tumors is extremely low, the location is hidden, and the symptoms are atypical. Attention should be paid for early detection and early treatment. Surgical resection is the main treatment, and radiotherapy can be supplemented in the advanced stage or with a positive margin.
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Condrosarcoma , Fibrosarcoma , Neoplasias de la Base del Cráneo , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Condrosarcoma/diagnóstico , Condrosarcoma/cirugía , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Base del Cráneo/cirugía , Neoplasias de la Base del Cráneo/cirugía , Hueso Temporal/patología , Resultado del TratamientoRESUMEN
BACKGROUND: A woven coronary artery is a rare feature on coronary angiography. Distinguishing woven-like change and recanalization of an occluded artery is difficult. CASE PRESENTATION: A 59-year-old man was admitted to the hospital for chest tightness. Coronary angiography showed a woven coronary artery at the middle segment of the left anterior descending branch (LAD). The middle segment of the right coronary artery (RCA) exhibited 99% occlusion. A 3.5 × 26-mm drug-eluting stent was implanted in the middle segment of the RCA. One week later, we examined the LAD using optical coherence tomography (OCT). Considering the patient's medical history and the results of OCT, a 2.7 × 38-mm drug-eluting stent was inserted into the LAD. Re-examination by OCT indicated that the stent was well attached to the wall, with no dissection at the edge of the stent. Antiplatelet therapy and statin-based plaque stabilization were continued. No obvious abnormality was found during follow-up one year later. CONCLUSIONS: OCT can help distinguish woven-like change and recanalization of an occluded coronary artery. The evaluation and formulation of treatment strategies for a woven coronary artery are important.
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Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Masculino , Humanos , Persona de Mediana Edad , Vasos Coronarios/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Resultado del Tratamiento , Angiografía Coronaria/métodosRESUMEN
In a previous study, we demonstrated that the hydro extract of Mao Jian Green Tea (MJGT) promotes gastrointestinal motility. In this study, the effect of MJGT ethanol extract (MJGT_EE) in treating irritable bowel syndrome with constipation (IBS-C) in a rat model constructed via maternal separation combined with an ice water stimulation was investigated. First, a successful model construction was confirmed through the determination of the fecal water content (FWC) and the smallest colorectal distension (CRD) volume. Then, the overall regulatory effects of MJGT_EE on the gastrointestinal tract were preliminarily evaluated through gastric emptying and small intestinal propulsion tests. Our findings indicated that MJGT_EE significantly increased FWC (p < 0.01) and the smallest CRD volume (p < 0.05) and promoted gastric emptying and small intestinal propulsion (p < 0.01). Furthermore, mechanistically, MJGT_EE reduced intestinal sensitivity by regulating the expression of proteins related to the serotonin (5-hydroxytryptamine; 5-HT) pathway. More specifically, it decreased tryptophan hydroxylase (TPH) expression (p < 0.05) and increased serotonin transporter (SERT) expression (p < 0.05), thereby decreasing 5-HT secretion (p < 0.01), activating the calmodulin (CaM)/myosin light chain kinase (MLCK) pathway, and increasing 5-HT4 receptor (5-HT4R) expression (p < 0.05). Moreover, MJGT_EE enhanced the diversity of gut microbiota, increased the proportion of beneficial bacteria, and regulated the number of 5-HT-related bacteria. Flavonoids may play the role of being active ingredients in MJGT_EE. These findings suggest that MJGT_EE could serve as a potential therapeutic pathway for IBS-C.
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Three-dimensional NAND flash memory is widely used in sensor systems as an advanced storage medium that ensures system stability through fast data access. However, in flash memory, as the number of cell bits increases and the process pitch keeps scaling, the data disturbance becomes more serious, especially for neighbor wordline interference (NWI), which leads to a deterioration of data storage reliability. Thus, a physical device model was constructed to investigate the NWI mechanism and evaluate critical device factors for this long-standing and intractable problem. As simulated by TCAD, the change in channel potential under read bias conditions presents good consistency with the actual NWI performance. Using this model, NWI generation can be accurately described through the combination of potential superposition and a local drain-induced barrier lowering (DIBL) effect. This suggests that a higher bitline voltage (Vbl) transmitted by the channel potential can restore the local DIBL effect, which is ever weakened by NWI. Furthermore, an adaptive Vbl countermeasure is proposed for 3D NAND memory arrays, which can significantly minimize the NWI of triple-level cells (TLC) in all state combinations. The device model and the adaptive Vbl scheme were successfully verified by TCAD and 3D NAND chip tests. This study introduces a new physical model for NWI-related problems in 3D NAND flash, while providing a feasible and promising voltage scheme as a countermeasure to optimize data reliability.
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BACKGROUND: Hepatic fibrosis, a common pathological feature of chronic liver injuries, is a serious public health problem and lacks effective therapy. Glycyrrhizic acid (GA) is a bioactive ingredient in the root of traditional Chinese medicine licorice, and exhibits remarkable anti-viral, anti-inflammatory and hepatoprotective actions. PURPOSE: Here we aimed to investigated whether GA provided a therapeutic efficacy in hepatic fibrosis and uncover its molecular mechanisms. STUDY DESIGN AND METHODS: We investigated the anti-fibrosis effects of GA using CCl4-induced mouse mode of liver fibrosis as well as TGF-ß1-activated human LX-2 cells and primary hepatic stellate cells (HSCs). CUGBP1-mediated IFN-γ/STAT1/Smad7 signaling was examined with immunofluorescence staining and western blot analysis. We designed and studied the binding of GA to CUGBP1 using in silico docking, and validated by microscale thermophoresis (MST) assay. RESULTS: GA obviously attenuated CCl4-induced liver histological damage, and reduced serum ALT and AST levels. Meanwhile, GA decreased liver fibrogenesis markers such as α-SMA, collagen α1, HA, COL-III, and LN in the hepatic tissues. Mechanistically, GA remarkably elevated the levels of IFN-γ, p-STAT1, Smad7, and decreased CUGBP1 in vivo and in vitro. Over-expression of CUGBP1 completely abolished the anti-fibrotic effect of GA and regulation on IFN-γ/STAT1/Smad7 pathway in LX-2 cells and primary HSCs, confirming CUGBP1 played a pivotal role in the protection by GA from liver fibrosis. Further molecular docking and MST assay indicated that GA had a good binding affinity with the CUGBP1 protein. The dissociation constant (Kd) of GA and CUGBP1 was 0.293 µM. CONCLUSION: Our study demonstrated for the first time that GA attenuated liver fibrosis and hepatic stellate cell activation by promoting CUGBP1-mediated IFN-γ/STAT1/Smad7 signalling pathways. GA may be a potential candidate compound for preventing or reliving liver fibrosis.
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Ácido Glicirrínico , Transducción de Señal , Animales , Humanos , Ratones , Ácido Glicirrínico/farmacología , Células Estrelladas Hepáticas , Interferón gamma/metabolismo , Hígado , Cirrosis Hepática/metabolismo , Simulación del Acoplamiento Molecular , Proteína smad7/metabolismo , Factor de Transcripción STAT1/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Proteínas CELF1/metabolismoRESUMEN
Detecting and analyzing circulating tumor cells(CTCs) is significant for early diagnosis, management, and personalized treatment of tumors. Herein, a smart magnetic aptamer modified Fe3O4@ZIF-8 core/shell structured nanoparticle (NPs) was successfully constructed using for capture and simultaneous pH- and NIR-irradiation responsive release of CTCs. Taking MCF-7 as model CTCs, it could be captured ca. 60 % in low-concentration artificial blood by aptamer (SYL3C) on the surface of Fe3O4@ZIF-8 NPs. After magnetic separation, the ZIF-8 shell in aptamer-modified Fe3O4@ZIF-8 NPs carrying captured CTCs would disintegrate within 20 min under the synergistic effect of an acidic environment (pH=6.0) and NIR irradiation leading to the release of CTCs with high cell viability, which was benefited for the subsequent culture and analysis. This magnetic and core/shell structured device integrated high-efficiency capture, quick isolation and perfect release into one system, which showed great potentials for the detection of CTCs in the clinic.