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1.
Rapid Commun Mass Spectrom ; 38(15): e9769, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38782757

RESUMEN

RATIONALE: Succinic acid and lactic acid have been associated with diarrhea in weaned piglets. The level of succinic acid and lactic acid in serum, meat, and intestinal contents is important to elucidate the mechanism of diarrhea in weaned piglets. METHODS: A facile method was developed for the quantification of succinic acid and lactic acid in pigs' serum, intestinal contents, and meat using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC/MS/MS). The serum samples underwent protein precipitation with methanol. The meat and intestinal contents were freeze-dried and homogenized using a tissue grinding apparatus. Methanol-water mixture (80:20, v/v) was used for homogenizing the meat, while water was used for homogenizing the intestinal contents. An additional step of protein precipitation with acetonitrile was required for the intestinal contents. The resulting solution was diluted with water before being analyzed by UHPLC/MS/MS. Separation of succinic acid and lactic acid could be achieved within 3 min using a Kinetic XB-C18 column. RESULTS: The coefficients of variation for peak areas of succinic acid and lactic acid were less than 5.0%. The established method demonstrated good linearity as indicated by correlation coefficients exceeding 0.996. Additionally, satisfactory recoveries ranging from 88.58% to 108.8% were obtained. The detection limits (RS/N = 3) for succinic acid and lactic acid were determined to be 0.75 ng/mL and 0.02 µg/mL, respectively. CONCLUSION: This method exhibited high sensitivity, simplicity in operation, and small sample weight, making it suitable for quantitative determination of succinic acid and lactic acid in pigs' serum, intestinal contents, and meat. The method developed will provide valuable technical support in studying the metabolic mechanisms of succinic acid and lactic acid in pigs.


Asunto(s)
Ácido Láctico , Ácido Succínico , Espectrometría de Masas en Tándem , Animales , Espectrometría de Masas en Tándem/métodos , Ácido Láctico/sangre , Ácido Láctico/análisis , Cromatografía Líquida de Alta Presión/métodos , Porcinos , Ácido Succínico/sangre , Ácido Succínico/análisis , Ácido Succínico/química , Carne/análisis , Reproducibilidad de los Resultados , Límite de Detección , Modelos Lineales
2.
Anal Chem ; 95(5): 3108-3118, 2023 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-36693709

RESUMEN

Here, the transcriptomics and metabolomics on a model of exposure to a cocktail of neonicotinoids (Neo) containing seven commercial compounds and a synergist piperonyl butoxide (PBO) were established. The results showed that Neo and PBO disrupted mRNA and metabolite levels in a dose-dependent manner. Neo caused tryptophan pathway-related neurotoxicity, reduced lipolysis, and promoted fat mass accumulation in the liver, while PBO induced an increase in inflammatory factors and damage to intercellular membranes. Co-exposure enhanced Neo-induced liver steatosis, focal necrosis, and oxidative stress by inhibiting oxidative phosphorylation (OXPHOS). Furthermore, diglycerides and metabolic biomarkers demonstrated that the activation of insulin signaling is associated with restricted OXPHOS, which commonly leads to a high risk of non-alcoholic fatty liver disease (NAFLD) and Alzheimer's disease (AD) as the result of over-synthesis of lipids, low energy supply, and high thermogenesis. The study demonstrates that chronic disease can be induced by Neo and the synergist PBO at the molecular level.


Asunto(s)
Sinergistas de Plaguicidas , Butóxido de Piperonilo , Butóxido de Piperonilo/farmacología , Sinergistas de Plaguicidas/toxicidad , Neonicotinoides , Transcriptoma , Hígado
3.
Entropy (Basel) ; 25(5)2023 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-37238513

RESUMEN

The Space-Air-Ground Integrated Network (SAGIN) expands cyberspace greatly. Dynamic network architecture, complex communication links, limited resources, and diverse environments make SAGIN's authentication and key distribution much more difficult. Public key cryptography is a better choice for terminals to access SAGIN dynamically, but it is time-consuming. The semiconductor superlattice (SSL) is a strong Physical Unclonable Function (PUF) to be the hardware root of security, and the matched SSL pairs can achieve full entropy key distribution through an insecure public channel. Thus, an access authentication and key distribution scheme is proposed. The inherent security of SSL makes the authentication and key distribution spontaneously achieved without a key management burden and solves the assumption that excellent performance is based on pre-shared symmetric keys. The proposed scheme achieves the intended authentication, confidentiality, integrity, and forward security, which can defend against masquerade attacks, replay attacks, and man-in-the-middle attacks. The formal security analysis substantiates the security goal. The performance evaluation results confirm that the proposed protocols have an obvious advantage over the elliptic curve or bilinear pairings-based protocols. Compared with the protocols based on the pre-distributed symmetric key, our scheme shows unconditional security and dynamic key management with the same level performance.

4.
Entropy (Basel) ; 25(5)2023 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-37238566

RESUMEN

Blockchain technology affords data integrity protection and building trust mechanisms in transactions for distributed networks, and, therefore, is seen as a promising revolutionary information technology. At the same time, the ongoing breakthrough in quantum computation technology contributes toward large-scale quantum computers, which might attack classic cryptography, seriously threatening the classic cryptography security currently employed in the blockchain. As a better alternative, a quantum blockchain has high expectations of being immune to quantum computing attacks perpetrated by quantum adversaries. Although several works have been presented, the problems of impracticality and inefficiency in quantum blockchain systems remain prominent and need to be addressed. First, this paper develops a quantum-secure blockchain (QSB) scheme by introducing a consensus mechanism-quantum proof of authority (QPoA) and an identity-based quantum signature (IQS)-wherein QPoA is used for new block generation and IQS is used for transaction signing and verification. Second, QPoA is developed by adopting a quantum voting protocol to achieve secure and efficient decentralization for the blockchain system, and a quantum random number generator (QRNG) is deployed for randomized leader node election to protect the blockchain system from centralized attacks like distributed denial of service (DDoS). Compared to previous work, our scheme is more practical and efficient without sacrificing security, greatly contributing to better addressing the challenges in the quantum era. Extensive security analysis demonstrates that our scheme provides better protection against quantum computing attacks than classic blockchains. Overall, our scheme presents a feasible solution for blockchain systems against quantum computing attacks through a quantum strategy, contributing toward quantum-secured blockchain in the quantum era.

5.
Environ Sci Technol ; 56(3): 1841-1853, 2022 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-35041393

RESUMEN

Pesticides are used in agricultural production worldwide, resulting in widespread environmental pollution. Many diseases are closely related to exposure to pesticide residues. In this study, the association between exposure to the pesticide flupyradifurone (FPF), a substitute for neonicotinoids, and sex-dependent thyroid dysfunction was explored for the first time. Exposure using rat models revealed that the FPF metabolism is sex-dependent, with males preferring N-dealkylation and hydrolytic metabolism and females preferring hydroxylation. In particular, novel chloropyridine-site hydroxylation I and II metabolic pathways of FPF were discovered. More importantly, differential metabolic pathways of FPF induced sex-based dysregulation of the hypothalamic-pituitary-thyroid axis, in which females exhibited subclinical hyperthyroidism, while males displayed abnormal hypothyroidism. This may be attributed to the potential agonistic or antagonistic effect of FPF sex-dependent metabolites on liver thyroid hormone receptors. Furthermore, FPF exposure further mediated sex-specific dysregulation of cellular lipid homeostasis, with abnormal fatty acid ß-oxidation and excessive energy expenditure in females and the risk of excessive accumulation of triglycerides in males. These results illustrate the potential risk of sex-related thyroid metabolic diseases caused by FPF and provide an important basis and support for further studies of FPF on human health and as an environmental pollutant.


Asunto(s)
Insecticidas , Plaguicidas , 4-Butirolactona/análogos & derivados , Animales , Salud Ambiental , Femenino , Masculino , Neonicotinoides , Piridinas , Ratas , Medición de Riesgo
6.
Molecules ; 27(3)2022 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-35164010

RESUMEN

In this paper, antimony trisulfide (Sb2S3) was successfully prepared with the liquid phase exfoliation method and embedded into polyvinyl alcohol (PVA) as a saturable absorber (SA) in a passively mode-locked Er-doped fiber laser for the first time. Based on Sb2S3-PVA SA with a modulation depth of 4.0% and a saturable intensity of 1.545 GW/cm2, a maximum average output power of 3.04 mW and maximum peak power of 325.6 W for the stable mode-locked pulses was achieved with slope a efficiency of 0.87% and maximum single pulse energy of 0.81 nJ at a repetition rate of 3.47 MHz under a pump power of 369 mW. A minimum pulse width value of 2.4 ps with a variation range less than 0.1 ps, and a maximum signal to noise ratio (SNR) of 54.3 dB indicated reliable stability of mode-locking, revealing promising potentials of Sb2S3 as a saturable absorber in ultrafast all-fiber lasers.

7.
Entropy (Basel) ; 24(8)2022 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-36010789

RESUMEN

Parameter calibration is critical for self-localization based on dead reckoning in the control of intelligent vehicles such as autonomous driving. Most traditional calibration methods for robotics control based on dead reckoning rely on data collection with specially designed paths. For the calibration of parameters in the control of intelligent vehicles, the design of such paths is considered impossible due to the complexity of road conditions. To solve this problem, an optimization-based dead reckoning calibration scheme is introduced in this research using the differential global positioning system to obtain the actual positions of the intelligent vehicle. In this scheme, the difference between the positions obtained through dead reckoning and the positions obtained through the differential global positioning system is selected as the optimization objective function to be minimized. An adaptive quantum-inspired evolutionary algorithm is developed to improve the quality and efficiency of optimization. Experiments with an intelligent vehicle were also conducted to demonstrate the effectiveness of the developed calibration scheme. In addition, the newly introduced adaptive quantum-inspired evolutionary algorithm is compared with the classic genetic algorithm and the classic quantum-inspired evolutionary algorithm using eight benchmark test functions considering computation quality and efficiency.

8.
Carcinogenesis ; 42(8): 1056-1067, 2021 08 19.
Artículo en Inglés | MEDLINE | ID: mdl-34128973

RESUMEN

This study tried to explore the molecular mechanism underlying progression of lung adenocarcinoma (LUAD) and discuss the extracellular communication between cancer cells and vascular endothelial cells. Roughly, differential analysis was carried out to note that miR-30a-5p was lowly expressed in LUAD, whereas CCNE2 was highly expressed. Cell functional experiments demonstrated that overexpressed miR-30a-5p led to suppressed cell abilities in proliferation, migration and invasion. Dual-luciferase reporter gene assay and RNA immunoprecipitation verified the binding of miR-30a-5p and CCNE2, as well as decreased mRNA and protein expression of CCNE2 with miR-30a-5p overexpression. Simultaneous up-regulation of miR-30a-5p and CCNE2 reversed the promotion of CCNE2 on malignant behaviors of LUAD cells. In vivo mice experiments exhibited that high miR-30a-5p expression hindered tumor growth. Additionally, miR-30a-5p was localized on the Extracellular Vesicles microRNA (EVmiRNA) database. MiR-30a-5p was abundant in exosomes derived from vascular endothelial cells. To validate that miR-30a-5p could be delivered to LUAD cells via exosomes and then make an effect, exosomes from vascular endothelial cells were first extracted and identified by transmission electron microscopy and detection of exosomal marker proteins (Alix, CD63, TSG101). Sequentially, the extracted exosomes were labeled with DIO to note that exosomes could be internalized by cancer cells. Further experiments indicated that miR-30a-5p was increased in cancer cells co-cultured with exosomes, which in turn suppressed cell malignant behaviors and made cell cycle arrest. In all, our findings clarified that exosomes derived from vascular endothelial cells delivered miR-30a-5p to LUAD cells to affect tumor malignant progression via the miR-30a-5p/CCNE2 axis.


Asunto(s)
Adenocarcinoma del Pulmón/patología , Ciclinas/metabolismo , Endotelio Vascular/metabolismo , Exosomas/metabolismo , Neoplasias Pulmonares/patología , Adenocarcinoma del Pulmón/metabolismo , Animales , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Progresión de la Enfermedad , Endotelio Vascular/patología , Humanos , Neoplasias Pulmonares/metabolismo , Ratones , MicroARNs/metabolismo
9.
Carcinogenesis ; 42(1): 31-37, 2021 02 11.
Artículo en Inglés | MEDLINE | ID: mdl-32772072

RESUMEN

Epidemiological cohort studies investigating the association between vasectomy and prostate cancer risk have yielded inconsistent results. The aim of the present meta-analysis is to update the evidence on the association between vasectomy and prostate cancer. A comprehensively literature search of relevant studies was performed in December 2019 using PubMed. A DerSimonian and Laird random-effects model was used to calculate the summary relative risk (RR) and its 95% confidence interval (CI). A total of 15 eligible cohort studies (16 data sets) with more than four million of participants were eventually included in this meta-analysis. There was a statistically significant higher risk of prostate cancer among men who underwent vasectomy (RR: 1.09, 95% CI: 1.04-1.13) with obvious heterogeneity among included studies (P < 0.001, I2 = 64.2%). Vasectomy was also associated with the risk of advanced prostate cancer (RR: 1.07, 95% CI: 1.02-1.13), which is less likely to be affected from detection bias. In conclusion, findings from this meta-analysis of prospective studies indicate that vasectomy may be positively associated with the risk of prostate cancer. Further large prospective studies with long follow-up are warranted to verify the findings from this meta-analysis. In addition, the potential underlying molecular mechanism needed further exploration with in vitro and animal studies.


Asunto(s)
Neoplasias de la Próstata/epidemiología , Vasectomía/efectos adversos , Humanos , Masculino , Estadificación de Neoplasias , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo , Vasectomía/estadística & datos numéricos
10.
Environ Sci Technol ; 55(11): 7541-7550, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-33983014

RESUMEN

The extensive use of neonicotinoid pesticides has led to their widespread presence in the environment, resulting in considerable safety risks to the ecosystem and human health. In this study, we investigated the biotransformation behavior of a cocktail of multiple neonicotinoids and piperonyl butoxide (PBO) synergist in vivo and their potential environmental health risk. It was found that neonicotinoids with a cyano group, such as acetamiprid and thiacloprid, tended to accumulate in liver and spleen tissues, while others with nitro groups (imidacloprid, thiamethoxam, clothianidin, dinotefuran, and nitenpyram) were mostly excreted in urine. In the presence of the synergist PBO, the metabolism of neonicotinoids in vivo changed, mainly through the nitro reduction pathway, while a low abundance of related metabolites was observed in the conventional hydroxylation and demethylation metabolic pathways, due to inhibition of CYP450 enzymes by the synergist. Furthermore, DNA methylation damage in vivo was exacerbated by the induction of hydroxylamine metabolites formed in the intermediate process of neonicotinoid metabolism with the synergistic effect of PBO, which resulted in a higher level of the O6-methyldeoxyguanosine (O6-medG) biomarker in the liver. Therefore, during the comprehensive evaluation of pesticide environmental risks, attention should be paid not only to the co-exposure mode under real environmental conditions but also to the potential risks of intermediate metabolism and related intermediate metabolites. This study provides a referential strategy and theoretical support for the health risk assessment of co-exposure of chemicals.


Asunto(s)
Ecosistema , Insecticidas , Salud Ambiental , Humanos , Insecticidas/análisis , Insecticidas/toxicidad , Neonicotinoides , Nitrocompuestos , Medición de Riesgo
11.
J Cell Mol Med ; 24(2): 1245-1255, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31782902

RESUMEN

Nowadays, gene expression profiling has been widely used in screening out prognostic biomarkers in numerous kinds of carcinoma. Our studies attempt to construct a clinical nomogram which combines risk gene signature and clinical features for individual recurrent risk assessment and offer personalized managements for clear cell renal cell carcinoma. A total of 580 differentially expressed genes (DEGs) were identified via microarray. Functional analysis revealed that DEGs are of fundamental importance in ccRCC progression and metastasis. In our study, 338 ccRCC patients were retrospectively analysed and a risk gene signature which composed of 5 genes was obtained from a LASSO Cox regression model. Further analysis revealed that identified risk gene signature could usefully distinguish the patients with poor prognosis in training cohort (hazard ratio [HR] = 3.554, 95% confidence interval [CI] 2.261-7.472, P < .0001, n = 107). Moreover, the prognostic value of this gene-signature was independent of clinical features (P = .002). The efficacy of risk gene signature was verified in both internal and external cohorts. The area under receiver operating characteristic curve of this signature was 0.770, 0.765 and 0.774 in the training, testing and external validation cohorts, respectively. Finally, a nomogram was developed for clinicians and did well in the calibration plots. This nomogram based on risk gene signature and clinical features might provide a practical way for recurrence prediction and facilitating personalized managements of ccRCC patients after surgery.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma de Células Renales/mortalidad , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Nomogramas , Transcriptoma , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Renales/genética , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
12.
Bioorg Chem ; 96: 103596, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32004895

RESUMEN

The natural calcitonin (CT) receptor and its peptide agonists are considered validated targets for drug discovery. A small molecule agonist, SUN-B8155, has previously been shown to efficiently activate cellular CTR. Herein, we report the synthesis of a series of compounds (S8155 1-9) derived from SUN-B8155, and investigate the structural-functional relationship, bias properties and their cellular activity profile. We discover that the N-hydroxyl group from the pyridone ring is required for G protein activity and its affinity to the CT receptor. Among the compounds studied, S8155-7 exhibits improved G protein activity while S8155-4 displays a significant ß-arrestin-2 signaling bias. Finally, we show that both S8155-4 and S8155-7 inhibit tumour cell invasion through CTR activation. These two compounds are anticipated to find extensive applications in chemical biology research as well drug development efforts targeting CT receptor.


Asunto(s)
Receptores de Calcitonina/agonistas , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Células HEK293 , Humanos , Células MCF-7 , Piridonas/química , Piridonas/farmacología , Receptores de Calcitonina/metabolismo , Transducción de Señal/efectos de los fármacos , beta-Arrestinas/metabolismo
13.
Angew Chem Int Ed Engl ; 59(37): 16218-16224, 2020 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-32484601

RESUMEN

In the present study, we investigated the biotransformation of the neonicotinoid pesticide sulfoxaflor and the metabolic responses in Sprague-Dawley rats. Sulfoxaflor transformation was catalyzed by cytochrome P450 while five phase I and four phase II metabolites were identified for the first time in vivo. The experimental results demonstrated that sulfoxaflor brought about the metabolic profiling disturbances in liver and bile. Exposure to sulfoxaflor caused dysregulation of bile acid synthesis and reabsorption by the expression of farnesoid X receptor (FXR). Our data provided insights into biotransformation of chemicals while enabling the implementation of a new toolbox for the design of sulfoximine compounds.


Asunto(s)
Plaguicidas/farmacocinética , Piridinas/farmacocinética , Compuestos de Azufre/farmacocinética , Animales , Bilis/metabolismo , Biocatálisis , Biotransformación , Relación Dosis-Respuesta a Droga , Hígado/metabolismo , Metabolómica , Piridinas/administración & dosificación , Ratas , Ratas Sprague-Dawley , Compuestos de Azufre/administración & dosificación
14.
Mol Cancer ; 18(1): 151, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31672157

RESUMEN

BACKGROUND: Circular RNA (circRNA) is a type of circular endogenous RNA produced by special selective splicing and participates in progression of diverse diseases. However, the role of circRNA in clear cell renal cell carcinoma (ccRCC) is still rarely reported. METHODS: We detected lower circ-AKT3 expression in ccRCC using the circular RNA microarray. Then, qPCR array was applied to verify the expression of circ-AKT3 in between 60 ccRCC tissues and adjacent normal tissues, as well as ccRCC cell lines and human normal kidney cell (HK-2). We investigated the function of circ-AKT3 in ccRCC in vitro and in vivo and detected underlying mechanisms by Western blotting, bioinformatic analysis, RNA pull-down assay and luciferase reporter assay. RESULTS: Circ-AKT3 was verified significantly downregulated in ccRCC. Knockdown of circ-AKT3 promoted ccRCC migration and invasion, while overexpression of circ-AKT3 suppressed ccRCC metastasis. Further, circ-AKT3/miR-296-3p/E-cadherin axis was shown responsible for circ-AKT3 inhibiting ccRCC metastasis. CONCLUSION: Circ-AKT3 suppresses ccRCC metastasis by enforcing E-cadherin expression through competitively binding miR-296-3p. Circ-AKT3 may therefore serve as a novel therapeutic to better suppress ccRCC metastasis.


Asunto(s)
Cadherinas/metabolismo , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , MicroARNs/genética , Proteínas Proto-Oncogénicas c-akt/genética , ARN Circular , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Movimiento Celular/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Renales/patología , Modelos Biológicos , Clasificación del Tumor , Interferencia de ARN , Transducción de Señal
15.
Cancer Sci ; 109(2): 384-394, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29197138

RESUMEN

Seminoma is the most common testicular germ cell tumor worldwide and mainly occurs in 15-35-year-old young men. Early studies have indicated that testicular nuclear receptor 4 (TR4) first cloned from testis is involved in the invasion and metastasis of several human tumors; however, little attention is paid to the function of TR4 in seminoma. Our immunohistochemical (IHC) staining results showed that patients with advanced stage tumors tended to have higher expression of TR4. Importantly, there was a significant association between elevated TR4 expression and reduced overall survival in seminoma patients. In vitro MTS, western blot and transwell assays, after manipulating TR4 expression in Tcam-2 cells, revealed that TR4 induced epithelial-to-mesenchymal transition (EMT) and promoted Tcam-2 cell proliferation and invasion. Mechanism dissection demonstrated that AKT3, a critical component in the signaling pathway, played a crucial role in mediating TR4-promoted Tcam-2 cell proliferation and invasion. We further revealed that TR4 modulated AKT3 at the transcriptional level via chromatin immunoprecipitation and luciferase assays. Meanwhile, addition of the AKT3 siRNA blocked the function of TR4. Overall, these findings first elucidate that TR4 is a novel prognostic marker and plays a critical role in the metastatic capacity of Tcam-2 cells by EMT regulation and, consequently, targeting TR4-AKT3 pathway may serve as a potential therapeutic approach for seminoma.


Asunto(s)
Proteínas Proto-Oncogénicas c-akt/genética , Receptores de Esteroides/metabolismo , Receptores de Hormona Tiroidea/metabolismo , Seminoma/patología , Neoplasias Testiculares/patología , Adulto , Anciano , Anciano de 80 o más Años , Animales , Células COS , Línea Celular Tumoral , Proliferación Celular , Chlorocebus aethiops , Progresión de la Enfermedad , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Células HEK293 , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Seminoma/genética , Seminoma/metabolismo , Transducción de Señal , Neoplasias Testiculares/genética , Neoplasias Testiculares/metabolismo , Regulación hacia Arriba , Adulto Joven
16.
Appl Opt ; 57(24): 6898-6905, 2018 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-30129575

RESUMEN

In the system of tracking and detection based on the four-quadrant detector (4-QD), the energy distribution of the incident spot and the blind area of the photosensitive surface will affect the location accuracy. The current model of the spot is based on the ideal circular Gauss spot, which makes the error caused by the spot shape easily ignored. In this paper, the model of the spot energy distribution is improved, which can adapt to the elliptical Gauss distribution. The width of the blind area is also added to the response models of the detector so that the output of each quadrant and the error of the localization algorithm can be calculated more accurately. The simulation results show that the measurement accuracy of 4-QD decreases with the increase of the blind area, the shape, and the inclination of the light spot. In the experiment, we first verify the correctness and practicability of the improved model of the spot energy distribution, and then the improved model is proved to be able to make the response and error calculation more accurate.

17.
J Obstet Gynaecol Res ; 43(9): 1472-1480, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28613020

RESUMEN

AIM: This study explored the possible mechanisms of the transcriptional regulatory activities of C-terminal binding protein (CtBP) and the role of CtBP in the pathogenesis of breast cancer. METHODS: Microarray data of GSE36529, including three CtBP-knockdown breast cancer MCF-7 cell samples, three control knockdown samples and data of CtBP binding profile in MCF-7 cells, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened between CtBP-knockdown MCF-7 cell samples and controls. Newly developed chromatin immunoprecipitation followed by sequencing technology was used to identify the CtBP binding regions. The direct target genes of CtBP were identified using ChIP-Array software and a regulatory network was constructed, followed by gene ontology (GO) enrichment analysis of all identified DEGs and DEGs targeted by CtBP. RESULTS: In total, 404 DEGs were identified in CtBP-knockdown MCF-7 cell samples. These DEGs were enriched in different GO terms, such as cellular response to stress and cell cycle, endoplasmic reticulum and nucleotide binding. Additionally, 143 DEGs were identified as potential direct targets of CtBP in the regulatory network. CtBP target genes such as hypoxia up-regulated 1, BTG family member 2 and endothelin 1 were mainly related to response to hypoxia and regulation of cell proliferation. CONCLUSIONS: Hypoxia up-regulated 1, BTG family member 2 and endothelin 1 may be associated with the progression of breast cancer through interaction with CtBP in different biological processes. CtBP may be a therapeutic target for the treatment of breast cancer.


Asunto(s)
Oxidorreductasas de Alcohol/genética , Neoplasias de la Mama/genética , Proteínas de Unión al ADN/genética , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica/genética , Ontología de Genes , Femenino , Humanos , Células MCF-7
18.
Biochem Biophys Res Commun ; 464(1): 154-60, 2015 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-26093299

RESUMEN

The hepatocyte growth factor and its receptor c-Met are correlated with castration-resistance in prostate cancer. Although HGF has been considered as an attractive target for therapeutic antibodies, the lack of cross-reactivity of monoclonal antibodies with human/mouse HGFs is a major obstacle in preclinical developments. We generated a panel of anti-HGF RabMAbs either blocking HGF/c-Met interaction or inhibiting c-Met phosphorylation. We selected one RabMAb with mouse cross-reactivity and demonstrated that it blocked HGF-stimulated downstream activation in PC-3 and DU145 cells. Anti-HGF RabMAb inhibited not only the growth of PC-3 cells but also HGF-dependent proliferation in HUVECs. We further demonstrated the efficacy and potency of the anti-HGF RabMAb in tumor xenograft mice models. Through these in vitro and in vivo experiments, we explored a novel therapeutic antibody for advanced prostate cancer.


Asunto(s)
Anticuerpos Monoclonales/farmacología , Anticuerpos Neutralizantes/farmacología , Regulación Neoplásica de la Expresión Génica , Factor de Crecimiento de Hepatocito/antagonistas & inhibidores , Neoplasias de la Próstata/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-met/antagonistas & inhibidores , Animales , Anticuerpos Monoclonales/biosíntesis , Anticuerpos Monoclonales/aislamiento & purificación , Anticuerpos Neutralizantes/biosíntesis , Anticuerpos Neutralizantes/aislamiento & purificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Factor de Crecimiento de Hepatocito/genética , Factor de Crecimiento de Hepatocito/metabolismo , Células Endoteliales de la Vena Umbilical Humana/citología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Masculino , Ratones , Ratones Desnudos , Fosforilación/efectos de los fármacos , Próstata/efectos de los fármacos , Próstata/metabolismo , Próstata/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Unión Proteica/efectos de los fármacos , Proteínas Proto-Oncogénicas c-met/genética , Proteínas Proto-Oncogénicas c-met/metabolismo , Conejos , Transducción de Señal , Relación Estructura-Actividad , Ensayos Antitumor por Modelo de Xenoinjerto
19.
BMC Genomics ; 15: 835, 2014 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-25273267

RESUMEN

BACKGROUND: Independent transcriptome profile analyses of miRNAs or mRNAs under conditions of cadmium (Cd) stress have been widely reported in plants. However, a combined analysis of sRNA sequencing expression data with miRNA target expression data to infer the relative activities of miRNAs that regulate gene expression changes resulting from Cd stress has not been reported in rice. To elucidate the roles played by miRNAs in the regulation of changes in gene expression in response to Cd stress in rice (Oryza sativa L.), we simultaneously characterized changes in the miRNA and mRNA profiles following treatment with Cd. RESULTS: A total of 163 miRNAs and 2,574 mRNAs were identified to be differentially expressed under Cd stress, and the changes in the gene expression profile in the shoot were distinct from those in the root. At the miRNA level, 141 known miRNAs belonging to 48 families, and 39 known miRNAs in 23 families were identified to be differentially expressed in the root and shoot, respectively. In addition, we identified eight new miRNA candidates from the root and five from the shoot that were differentially expressed in response to Cd treatment. For the mRNAs, we identified 1,044 genes in the root and 448 genes in the shoot that were up-regulated, while 572 and 645 genes were down-regulated in the root and shoot, respectively. GO and KEGG enrichment analyses showed that genes encoding secondary, metabolite synthases, signaling molecules, and ABC transporters were significantly enriched in the root, while only ribosomal protein and carotenoid biosynthesis genes were significantly enriched in the shoot. Then 10 known miRNA-mRNA interaction pairs and six new candidate ones, that showed the opposite expression patterns, were identified by aligning our two datasets against online databases and by using the UEA sRNA toolkit respectively. CONCLUSIONS: This study is the first to use high throughput DNA sequencing to simultaneously detect changes in miRNA and mRNA expression patterns in the root and shoot in response to Cd treatment. These integrated high-throughput expression data provide a valuable resource to examine global genome expression changes in response to Cd treatment and how these are regulated by miRNAs.


Asunto(s)
Cadmio/toxicidad , MicroARNs/genética , Oryza/efectos de los fármacos , Oryza/genética , Plantones/efectos de los fármacos , Plantones/genética , Transcriptoma/efectos de los fármacos , Contaminantes Ambientales/toxicidad , Secuenciación de Nucleótidos de Alto Rendimiento , Oryza/metabolismo , Oryza/fisiología , ARN Mensajero/genética , Estrés Fisiológico/efectos de los fármacos , Estrés Fisiológico/genética
20.
Materials (Basel) ; 17(12)2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38930209

RESUMEN

In this study, we synthesized Fe3O4 nanoparticles (Fe3O4 NPs) of varying sizes and morphologies using the solvothermal method and incorporated them as additives into carbonyl iron magnetorheological fluids (CI-MRFs). We tested the shear stress, yield stress, viscosity and storage modulus of the MRFs using a magnetorheometer to investigate how the size and morphology of Fe3O4 NPs influence the performance of MRFs. Our results indicate that the size of the additive nanoparticles significantly enhances the MR properties of MRFs more than their morphological attributes. This enhancement results from optimizing and stabilizing the CI magnetic chain structure of the nanoparticles in the presence of a magnetic field. Specifically, MRFs with Fe3O4 NPs averaging 250 nm in size exhibit higher yield stress and storage modulus and show increased resistance to shear strains. Although the nanoparticle morphology has a modest effect on the rheological properties of MRFs, hexahedral and octahedral particles can enhance rheological properties through increased internal friction compared to spherical particles. Additionally, Fe3O4 NPs of different sizes and morphologies improve the sedimentation stability of MRFs, with those around 250 nm being particularly effective at slowing down sedimentation. Both hexahedral and octahedral Fe3O4 NPs slow down sedimentation more effectively than spherical Fe3O4 NPs. This paper investigates the rheological properties of CI-MRFs by controlling the additive particle size and morphological features, providing a research foundation for the design and optimization of MRFs.

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