RESUMO
Sleep quality is heavily influenced by sleep posture, with research indicating that a supine posture can worsen obstructive sleep apnea (OSA) while lateral postures promote better sleep. For patients confined to beds, regular changes in posture are crucial to prevent the development of ulcers and bedsores. This study presents a novel sparse sensor-based spatiotemporal convolutional neural network (S3CNN) for detecting sleep posture. This S3CNN holistically incorporates a pair of spatial convolution neural networks to capture cardiorespiratory activity maps and a pair of temporal convolution neural networks to capture the heart rate and respiratory rate. Sleep data were collected in actual sleep conditions from 22 subjects using a sparse sensor array. The S3CNN was then trained to capture the spatial pressure distribution from the cardiorespiratory activity and temporal cardiopulmonary variability from the heart and respiratory data. Its performance was evaluated using three rounds of 10 fold cross-validation on the 8583 data samples collected from the subjects. The results yielded 91.96% recall, 92.65% precision, and 93.02% accuracy, which are comparable to the state-of-the-art methods that use significantly more sensors for marginally enhanced accuracy. Hence, the proposed S3CNN shows promise for sleep posture monitoring using sparse sensors, demonstrating potential for a more cost-effective approach.
Assuntos
Frequência Cardíaca , Redes Neurais de Computação , Postura , Sono , Humanos , Postura/fisiologia , Sono/fisiologia , Frequência Cardíaca/fisiologia , Monitorização Fisiológica/métodos , Monitorização Fisiológica/instrumentação , Masculino , Feminino , Adulto , Taxa Respiratória/fisiologia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/fisiopatologia , Polissonografia/métodos , Polissonografia/instrumentaçãoRESUMO
BACKGROUND: Immune thrombocytopenia (ITP), which is a well-known hemorrhagic disorder characterized by low platelet counts, has been shown to be associated with the risk of thrombosis. Thrombopoietic agents (TAs) are extensively used as second-line treatments for ITP, effectively reducing the risk of hemorrhage. However, thrombosis, a potential adverse effect of TAs, raises clinical challenges. METHODS: The MEDLINE(PubMed), Embase, and the Cochrane Library databases were systematically searched for relevant studies, including both single-arm trials and randomized controlled trials (RCTs), without language restrictions. RESULTS: A total of 17 RCTs comprising 2,105 patients and 29 single-arm trials comprising 3,227 patients were included. In the single-arm meta-analysis, the pooled rate of overall thrombotic events in ITP patients receiving TAs was 2.2% (95% CI 1.0% - 3.7%). In RCTs, a higher incidence of thrombosis (33/1425 vs. 4/680) and higher risk ratios (RR) of overall, arterial, and venous thrombotic events (1.73, 95% CI [0.88, 3.39], P = 0.113; RR 1.98, 95% CI [0.80, 4.92], P = 0.141; RR 1.06, 95% CI [0.46, 2.41], P = 0.895, respectively) were observed in the TAs group than in the control group, although the differences were not significant. Subgroup analysis demonstrated that hetrombopag was the only TA with no increased thrombotic risk (rate 0.3% 95% CI [0.0 - 1.5%]; RR 0.76, 95% CI [0.03, 18.41], P = 0.864) compared to eltrombopag, avatrombopag, romiplostim, and rhTPO. Subgroup analyses also revealed that ITP patients with advanced age (3.7% vs. 1.3%, P = 0.132) or with a thrombotic history (3.0% vs. 1.4%, P = 0.257), and patients who received TAs therapy for a long duration (4.7% vs. 0.1%, P < 0.001) had an increased risk of thrombosis. CONCLUSION: Our findings suggest ITP patients treated with TAs have a nonsignificantly higher risk of overall, arterial, and venous thrombotic events. Furthermore, hetrombopag is the recommended TA to avoid thrombophilia. Patients receiving long-term TAs, as well as elderly ITP patients or those with a history of thrombosis, face an increased thrombotic risk. In general, clinicians should consider potential thrombotic risks, address underlying risk factors, and ensure ongoing monitoring and follow-up when treating ITP patients with TAs.
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According to the chemiluminescence characteristics of the luminol-hydrogen peroxide (H2O2) system, this work designed a novel and effective electrochemiluminescence (ECL) aptasensor to detect atrazine (ATZ) rapidly. Silver nanoparticles (AgNPs) could effectively catalyze the decomposition of H2O2 and enhance the ECL intensity of the luminol-H2O2 system. Once ATZ was modified on the aptasensor, the ECL intensity was significantly weakened because of the specific combination between ATZ and its aptamer. Therefore, the changes in ECL intensity could be used to detect the concentration of ATZ. Under optimal detecting conditions, the aptasensor had a wide linear range from 1 × 10-3 ng/mL to 1 × 103 ng/mL and a low limit of detection (3.3 × 10-4 ng/mL). The designed aptasensor had the advantages of good stability, reproducibility, and specificity. The aptasensor could be used to detect the ATZ content of tap water, soil, and cabbage and had satisfactory results. This work effectively constructs a novel, effective, and rapid ECL aptasensor for detecting ATZ in actual samples.
Assuntos
Aptâmeros de Nucleotídeos , Atrazina , Técnicas Biossensoriais , Nanopartículas Metálicas , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Peróxido de Hidrogênio/química , Limite de Detecção , Medições Luminescentes/métodos , Luminol/química , Nanopartículas Metálicas/química , Reprodutibilidade dos Testes , Prata/químicaRESUMO
In this work, we reported a rapid and sensitive fluorescence assay in homogenous solution for detecting organophosphorus pesticides by using tetramethylrhodamine (TAMRA)-labeled aptamer and its complementary DNA (cDNA) with extended guanine (G) bases. The hybridization of cDNA and aptamer drew TAMRA close to repeated G bases, then the fluorescence of TAMRA was quenched by G bases due to the photoinduced electron transfer (PET). Upon introducing the pesticide target, the aptamer bound to pesticide instead of cDNA because of the competition between pesticide and cDNA. Thus, the TAMRA departed from G bases, resulting in fluorescence recovery of TAMRA. Under optimal conditions, the limits of detection for phorate, profenofos, isocarbophos, and omethoate were 0.333, 0.167, 0.267, and 0.333 µg/L, respectively. The method was also used in the analysis of profenofos in vegetables. Our fluorescence design was simple, rapid, and highly sensitive, which provided a means for monitoring the safety of agricultural products.
Assuntos
Aptâmeros de Nucleotídeos , Praguicidas , Aptâmeros de Nucleotídeos/genética , DNA Complementar , Fluorescência , Compostos Organofosforados/análise , Praguicidas/análiseRESUMO
This paper presents a straightforward method to develop a nanoporous graphene oxide (NGO)-functionalized quartz crystal microbalance (QCM) gas sensor for the detection of trimethylamine (TMA), aiming to form a reliable monitoring mechanism strategy for low-concentration TMA that can still cause serious odor nuisance. The synthesized NGO material was characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy to verify its structure and morphology. Compared with the bare and GO-based QCM sensors, the NGO-based QCM sensor exhibited ultra-high sensitivity (65.23 Hz/µL), excellent linearity (R2 = 0.98), high response/recovery capability (3 s/20 s) and excellent repeatability (RSD = 0.02, n = 3) toward TMA with frequency shift and resistance. Furthermore, the selectivity of the proposed NGO-based sensor to TMA was verified by analysis of the dual-signal responses. It is also proved that increasing the conductivity did not improve the resistance signal. This work confirms that the proposed NGO-based sensor with dual signals provides a new avenue for TMA sensing, and the sensor is expected to become a potential candidate for gas detection.
Assuntos
Grafite , Nanoporos , Técnicas de Microbalança de Cristal de Quartzo , Grafite/química , QuartzoRESUMO
Enterocytozoon hepatopenaei (EHP) is the pathogen of hepatopancreatic microsporidiosis (HPM) in shrimp. The diseased shrimp Litopenaeus vannamei exhibits a slow growth syndrome, which causes severe economic losses. Herein, 4D label-free quantitative proteomics was employed to analyze the hepatopancreas of L. vannamei with a light (EHPptp2 < 103 copies/50 ng hpDNA, L group) and heavy (EHPptp2 > 104 copies/50 ng hpDNA, H group) load of EHP to better understand the pathogenesis of HPM. Exactly 786 (L group) and 1056 (H group) differentially expressed proteins (DEPs) versus the EHP-free (C group) control were mainly clustered to lipid metabolism, amino acid metabolism, and energy production processing. Compared with the L group, the H group exhibited down-regulation significantly in lipid metabolism, especially in the elongation and degradation of fatty acid, biosynthesis of unsaturated fatty acid, metabolism of α-linolenic acid, sphingolipid, and glycerolipid, as well as juvenile hormone (JH) degradation. Expression pattern analysis showed that the degree of infection was positively correlated with metabolic change. About 479 EHP proteins were detected in infected shrimps, including 95 predicted transporters. These findings suggest that EHP infection induced the consumption of storage lipids and the entire down-regulation of lipid metabolism and the coupling energy production, in addition to the hormone metabolism disorder. These were ultimately responsible for the stunted growth.
Assuntos
Hepatopâncreas , Penaeidae , Aminoácidos , Animais , Regulação para Baixo , Enterocytozoon , Hormônios , Hormônios Juvenis , Metabolismo dos Lipídeos , Proteômica , Esfingolipídeos , Ácido alfa-LinolênicoRESUMO
As a pleiotropic signal molecule, melatonin is ubiquitous throughout the animal and plant kingdoms and plays important roles in the regulation of plant growth, development, and responses to environmental stresses. In this study, we quantified the endogenous melatonin levels in upland cotton (Gossypium hirsutum L.), using high-performance liquid chromatography-tandem mass spectrometry. The melatonin concentrations in root, stem, and leaf were 150.60, 37.92, and 40.58 ng g fresh weight- 1, respectively. The effects of exogenous melatonin (1 µM) on plant growth, photosynthesis, antioxidant enzyme activity, and ion homeostasis in upland cotton seedlings exposed to 100 mM NaCl treatment were determined. Pretreatment (prior to exposure to salt stress) of seedlings with exogenous melatonin significantly alleviated plant growth inhibition by salt stress and maintained an improved photosynthetic capacity. The application of melatonin also significantly reduced the salt-induced oxidative damage, possibly through the accumulation of osmotic regulatory substances and the activation of antioxidant enzymes. We also showed that exogenous melatonin regulated the expression of stress-responsive and ion-channel genes under salinity, which could contribute to improved salt tolerance in cotton. Taken together, our study provides evidence that cotton contains endogenous melatonin, and it may have unraveled crucial evidence of the role of melatonin in cotton against salt stress.
Assuntos
Gossypium , Melatonina , Regulação da Expressão Gênica de Plantas , Melatonina/farmacologia , Estresse Salino , Tolerância ao Sal , Plântula , Estresse FisiológicoRESUMO
BACKGROUND: Plant NADPH oxidase (NOX), also known as respiratory burst oxidase homolog (rboh), encoded by the rboh gene, is a key enzyme in the reactive oxygen species (ROS) metabolic network. It catalyzes the formation of the superoxide anion (O2â¢-), a type of ROS. In recent years, various studies had shown that members of the plant rboh gene family were involved in plant growth and developmental processes as well as in biotic and abiotic stress responses, but little is known about its functional role in upland cotton. RESULTS: In the present study, 26 putative Ghrboh genes were identified and characterized. They were phylogenetically classified into six subfamilies and distributed at different densities across 18 of the 26 chromosomes or scaffolds. Their exon-intron structures, conserved domains, synteny and collinearity, gene family evolution, regulation mediated by cis-acting elements and microRNAs (miRNAs) were predicted and analyzed. Additionally, expression profiles of Ghrboh gene family were analyzed in different tissues/organs and at different developmental stages and under different abiotic stresses, using RNA-Seq data and real-time PCR. These profiling studies indicated that the Ghrboh genes exhibited temporal and spatial specificity with respect to expression, and might play important roles in cotton development and in stress tolerance through modulating NOX-dependent ROS induction and other signaling pathways. CONCLUSIONS: This comprehensive analysis of the characteristics of the Ghrboh gene family determined features such as sequence, synteny and collinearity, phylogenetic and evolutionary relationship, expression patterns, and cis-element- and miRNA-mediated regulation of gene expression. Our results will provide valuable information to help with further gene cloning, evolutionary analysis, and biological function analysis of cotton rbohs.
Assuntos
Genoma de Planta , Genômica , Gossypium/genética , Família Multigênica , NADPH Oxidases/genética , Biologia Computacional/métodos , Evolução Molecular , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Genômica/métodos , Gossypium/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Anotação de Sequência Molecular , Filogenia , Regiões Promotoras Genéticas , Espécies Reativas de Oxigênio/metabolismo , Sequências Reguladoras de Ácido Nucleico , Estresse Fisiológico , SinteniaRESUMO
Elucidating the regulation mechanism of integrin αIIbß3 is key to understand platelet biology and thrombotic diseases. Previous in vitro studies have implicated a role of migfilin in the support of platelet αIIbß3 activation, however, contribution of migfilin to thrombosis and hemostasis in vivo and a detailed mechanism of migfilin in platelets are not known. In this study, with migfilin deletion (migfilin-/-) mice, we report that migfilin is a pivotal positive regulator of hemostasis and thrombosis. Migfilin-/- mice showed a nearly doubled tail-bleeding time and a prolonged occlusion time in Fecl3-induced mesenteric arteriolar thrombosis. Migfilin deficiency impedes platelet thrombi formation on collagen surface and impairs platelet aggregation and dense-granule secretion. Supported by characteristic functional readings and phosphorylation status of distinctive signaling molecules in the bidirectional signaling processes of αIIbß3, the functional defects of migfilin-/- platelets appear to be mechanistically associated with a compromised outside-in signaling, rather than inside-out signaling. A synthesized cell-permeable migfilin peptide harboring filamin A binding sequence rescued the defective function and phosphorylation of signaling molecules of migfilin-/- platelets. Finally, migfilin does not influence the binding of filamin A and ß3 subunit of αIIbß3 in resting platelets, but hampers the re-association of filamin A and ß3 during the conduct of outside-in signaling, suggesting that migfilin functions through regulating the interaction dynamics of αIIbß3 and filamin A in platelets. Our study enhances the current understanding of platelet integrin αIIbß3-mediated outside-in signaling and proves that migfilin is an important regulator for platelet activation, hemostasis and thrombosis.
Assuntos
Complexo Glicoproteico GPIIb-IIIa de Plaquetas , Trombose , Animais , Plaquetas , Hemostasia , Camundongos , Ativação Plaquetária , Agregação Plaquetária , Trombose/genéticaRESUMO
BACKGROUND: Long non-coding (lnc) RNAs are a class of functional RNA molecules greater than 200 nucleotides in length, and lncRNAs play important roles in various biological regulatory processes and response to the biotic and abiotic stresses. LncRNAs associated with salt stress in cotton have been identified through RNA sequencing, but the function of lncRNAs has not been reported. We previously identified salt stress-related lncRNAs in cotton (Gossypium spp.), and discovered the salt-related lncRNA-lncRNA973. RESULTS: In this study, we identified the expression level, localization, function, and preliminary mechanism of action of lncRNA973. LncRNA973, which was localized in the nucleus, was expressed at a low level under nonstress conditions but can be significantly increased by salt treatments. Here lncRNA973 was transformed into Arabidopsis and overexpressed. Along with the increased expression compared with wild type under salt stress conditions in transgenic plants, the seed germination rate, fresh weights and root lengths of the transgenic plants increased. We also knocked down the expression of lncRNA973 using virus-induced gene silencing technology. The lncRNA973 knockdown plants wilted, and the leaves became yellowed and dropped under salt-stress conditions, indicating that the tolerance to salt stress had decreased compared with wild type. LncRNA973 may be involved in the regulation of reactive oxygen species-scavenging genes, transcription factors and genes involved in salt stress-related processes in response to cotton salt stress. CONCLUSIONS: LncRNA973 was localized in the nucleus and its expression was increased by salt treatment. The lncRNA973-overexpression lines had increased salt tolerance compared with the wild type, while the lncRNA973 knockdown plants had reduced salt tolerance. LncRNA973 regulated cotton responses to salt stress by modulating the expression of a series of salt stress-related genes. The data provides a basis for further studies on the mechanisms of lncRNA973-associated responses to salt stress in cotton.
Assuntos
Regulação da Expressão Gênica de Plantas , Gossypium/fisiologia , Folhas de Planta/fisiologia , RNA Longo não Codificante/genética , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Arabidopsis/fisiologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Gossypium/efeitos dos fármacos , Gossypium/genética , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Plantas Geneticamente Modificadas/efeitos dos fármacos , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/fisiologia , RNA Longo não Codificante/metabolismo , Tolerância ao Sal/genéticaRESUMO
Salinity stress is a major abiotic stress affecting the productivity and fiber quality of cotton. Although reactive oxygen species (ROS) play critical roles in plant stress responses, their complex molecular regulatory mechanism under salinity stress is largely unknown in cotton, especially microRNA (miRNA)-mediated regulation of superoxide dismutase gene expression. Here, we report that a cotton iron superoxide dismutase gene GhFSD1 and the cotton miRNA ghr-miR414c work together in response to salinity stress. The miRNA ghr-miR414c targets the coding sequence region of GhFSD1, inhibiting expression of transcripts of this antioxidase gene, which represents the first line of defense against stress-induced ROS. Expression of GhFSD1 was induced by salinity stress. Under salinity stress, ghr-miR414c showed expression patterns opposite to those of GhFSD1. Ectopic expression of GhFSD1 in Arabidopsis conferred salinity stress tolerance by improving primary root growth and biomass, whereas Arabidopsis constitutively expressing ghr-miR414c showed hypersensitivity to salinity stress. Silencing GhFSD1 in cotton caused an excessive hypersensitive phenotype to salinity stress, whereas overexpressing miR414c decreased the expression of GhFSD1 and increased sensitivity to salinity stress, yielding a phenotype similar to that of GhFSD1-silenced cotton. Taken together, our results demonstrated that ghr-miR414c was involved in regulation of plant response to salinity stress by targeting GhFSD1 transcripts. This study provides a new strategy and method for plant breeding in order to improve plant salinity tolerance.
Assuntos
Gossypium/genética , Gossypium/metabolismo , MicroRNAs/genética , Espécies Reativas de Oxigênio/metabolismo , Salinidade , Estresse Salino , Tolerância ao Sal/genética , Sequência de Aminoácidos , Biomarcadores , Clonagem Molecular , MicroRNAs/química , Fenótipo , Filogenia , Análise de Sequência de DNARESUMO
OBJECTIVE: To investigate the biochemical and enzymatic properties of chlorogenic acid hydrolase (ChlH) from Aspergillus niger SD14.721 and its applicability in sunflower seed protein processing. RESULTS: The ChlH with two identical subunits (97 kDa) was highly stable. Its optimal temperature and pH were determined as 60 °C and pH 7.0. The Km towards chlorogenic acid (CGA) was 1.85 µM. Based on its N-terminal sequence (AVDSVDAIFA), the purified ChlH appeared to be a new chlorogenic acid hydrolase. When applied in sunflower seed protein extraction, ChlH removed 99.13% of CGA in sunflower seed pastes, thus the colour of sunflower seed protein (SSP) changed from green to grey and its visual acceptance improved. Meanwhile, the solubility, water absorption capacity, and emulsification stability of SSP were increased 48.39%, 59.32% and 22.92%, respectively. CONCLUSIONS: A new ChlH was obtained and its feasibility as a CGA-removal tool to obtain high quality SSP was demonstrated.
Assuntos
Aspergillus niger/enzimologia , Ácido Clorogênico/metabolismo , Helianthus/química , Hidrolases/metabolismo , Proteínas de Plantas/metabolismo , Processamento de Proteína Pós-Traducional , Sementes/química , Biotecnologia/métodos , Estabilidade Enzimática , Concentração de Íons de Hidrogênio , Hidrolases/química , Cinética , Peso Molecular , Proteínas de Plantas/química , Multimerização Proteica , Solubilidade , TemperaturaRESUMO
Quercetin is a bioactive compound that is widely used in botanical medicine and traditional Chinese medicine due to its potent antioxidant activity. In recent years, antioxidant activities of quercetin have been studied extensively, including its effects on glutathione (GSH), enzymatic activity, signal transduction pathways, and reactive oxygen species (ROS) caused by environmental and toxicological factors. Chemical studies on quercetin have mainly focused on the antioxidant activity of its metal ion complexes and complex ions. In this review, we highlight the recent advances in the antioxidant activities, chemical research, and medicinal application of quercetin.
Assuntos
Antioxidantes/farmacologia , Quercetina/farmacologia , Antioxidantes/química , Catalase/metabolismo , Glutationa/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Quercetina/química , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Relação Estrutura-Atividade , Superóxido Dismutase/metabolismoRESUMO
The sterile-20 kinase misshapen/Nck-interacting kinase (NIK)-related kinase 1 (MINK1) is involved in many important cellular processes such as growth, cytoskeletal rearrangement, and motility. Here, with MINK1-deficient (MINK1(-/-)) mice, we showed that MINK1 plays an important role in hemostasis and thrombosis via the regulation of platelet functions. In the tail-bleeding assay, MINK1(-/-) mice exhibited a longer bleeding time than wild-type (WT) mice (575.2 ± 59.7 seconds vs 419.6 ± 66.9 seconds). In a model of ferric chloride-induced mesenteric arteriolar thrombosis, vessel occlusion times were twice as long in MINK1(-/-) mice as in WT mice. In an in vitro microfluidic whole-blood perfusion assay, thrombus formation on a collagen matrix under arterial shear conditions was significantly reduced in MINK1(-/-) platelets. Moreover, MINK1(-/-) platelets demonstrated impaired aggregation and secretion in response to low doses of thrombin and collagen. Furthermore, platelet spreading on fibrinogen was largely hampered in MINK1(-/-) platelets. The functional differences of MINK1(-/-) platelets could be attributed to impaired adenosine 5'-diphosphate secretion. Signaling events associated with MINK1 appeared to involve extracellular signal-regulated kinase, p38, and Akt. Hence, MINK1 may be an important signaling molecule that mediates mitogen-activated protein kinase signaling and participates in platelet activation and thrombus formation.
Assuntos
Plaquetas/enzimologia , Sistema de Sinalização das MAP Quinases , Ativação Plaquetária , Proteínas Serina-Treonina Quinases/metabolismo , Trombose/enzimologia , Difosfato de Adenosina/genética , Difosfato de Adenosina/metabolismo , Animais , Plaquetas/patologia , Cloretos/toxicidade , Compostos Férricos/toxicidade , Camundongos , Camundongos Knockout , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Trombose/induzido quimicamente , Trombose/genética , Trombose/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
OBJECTIVE: Class III phosphoinositide 3-kinase, also known as VPS34 (vacuolar protein sorting 34), is a highly conserved enzyme regulating important cellular functions such as NADPH oxidase (NOX) assembly, membrane trafficking, and autophagy. Although VPS34 is expressed in platelets, its involvement in platelet activation remains unclear. Herein, we investigated the role of VPS34 in platelet activation and thrombus formation using VPS34 knockout mice. APPROACH AND RESULTS: Platelet-specific VPS34-deficient mice were generated and characterized. VPS34 deficiency in platelets did not influence tail bleeding time. In a ferric chloride-induced mesenteric arteriolar thrombosis model, VPS34-/- mice exhibited a prolonged vessel occlusion time compared with wild-type mice (42.05±4.09 versus 18.30±2.47 minutes). In an in vitro microfluidic whole-blood perfusion assay, thrombus formation on collagen under arterial shear was significantly reduced for VPS34-/- platelets. VPS34-/- platelets displayed an impaired aggregation and dense granule secretion in response to low doses of collagen or thrombin. VPS34 deficiency delayed clot retraction but did not influence platelet spreading on fibrinogen. We also demonstrated that VPS34 deficiency altered the basal level of autophagy in resting platelets and hampered NOX assembly and mTOR (mammalian target of rapamycin) signaling during platelet activation. Importantly, we identified the NOX-dependent reactive oxygen species generation as the major downstream effector of VPS34, which in turn can mediate platelet activation. In addition, by using a specific inhibitor 3-methyladenine, VPS34 was found to operate through a similar NOX-dependent mechanism to promote human platelet activation. CONCLUSIONS: Platelet VPS34 is critical for thrombosis but dispensable for hemostasis. VPS34 regulates platelet activation by influencing NOX assembly.
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Coagulação Sanguínea , Plaquetas/enzimologia , Classe III de Fosfatidilinositol 3-Quinases/sangue , NADPH Oxidases/sangue , Fosfatos de Fosfatidilinositol/sangue , Ativação Plaquetária , Trombose/enzimologia , Adulto , Animais , Autofagia , Cloretos , Classe III de Fosfatidilinositol 3-Quinases/deficiência , Classe III de Fosfatidilinositol 3-Quinases/genética , Colágeno/sangue , Modelos Animais de Doenças , Feminino , Compostos Férricos , Genótipo , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenótipo , Agregação Plaquetária , Espécies Reativas de Oxigênio/sangue , Transdução de Sinais , Serina-Treonina Quinases TOR/sangue , Trombina/metabolismo , Trombose/sangue , Trombose/induzido quimicamente , Trombose/genética , Fatores de Tempo , Adulto JovemRESUMO
Osteoarthritis (OA) is the most common age-related degenerative joint disease and platelet-rich plasma (PRP) has been shown to be beneficial in OA. Therefore, in this study, we aimed to investigate the effects of platelets on chondrocytes and the underlying mechanisms. Anabolic and catabolic activity and the proliferation rate of chondrocytes were evaluated after co-culture with platelets. Chondrocyte gene expression was measured by real-time PCR. Chondrocyte protein expression and phosphorylation were measured by western blot. Chondrocytes treated with or without platelets were transplanted into a rat model of OA induced by intra-articular injection of monosodium iodoacetate and the repair of articular cartilage was evaluated macroscopically and histologically. Platelets significantly promoted the proliferation of chondrocytes, while mildly influencing anabolic and catabolic activity. Chondrocytes co-cultured with platelets showed significantly increased production of bone morphogenetic protein 7 (BMP7). The autocrine/paracrine effect of BMP7 was responsible for the increased proliferation of chondrocytes, via the ERK/CDK1/cyclin B1 signaling pathway. Transplantation of platelet-treated chondrocytes showed better cartilage repair in the OA model. Platelet-derived ADP was identified as the major mediator to promote the production of BMP7 and the proliferation of chondrocytes, through the ADP receptor P2Y1. Finally, direct injection of α,ß-methyleneadenosine-5'-diphosphate into OA joints also enhanced cartilage repair. This study has identified that platelet-derived ADP, but not ATP, is the key mediator for platelet-promoted chondrocyte proliferation and cartilage repair in osteoarthritis. This finding may provide a key explanation for the therapeutic effect of platelets in OA and help shaping a strategy to improve OA therapy.
Assuntos
Difosfato de Adenosina/metabolismo , Plaquetas/metabolismo , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Osteoartrite/metabolismo , Animais , Biocatálise , Proteína Morfogenética Óssea 7/metabolismo , Cartilagem Articular/patologia , Proliferação de Células , Células Cultivadas , Condrócitos/transplante , Análise por Conglomerados , Técnicas de Cocultura , Ciclina B1/metabolismo , Quinases Ciclina-Dependentes/metabolismo , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Masculino , Osteoartrite/genética , Osteoartrite/patologia , Plasma Rico em Plaquetas/metabolismo , Ratos , Transdução de Sinais , CicatrizaçãoRESUMO
A novel dual-mode aptasensor was constructed for aminoglycoside antibiotics (AAs) detection by using a broad-spectrum aptamer as a biorecognition element, and Au-Pd@Fc functionalized by signal DNA as nanoprobes. In electrochemical mode, the target-induced cyclic amplification reaction run under the action of exonuclease-III, which increased the number of nanoprobes on the electrode surface. AAs could be quantitatively detected with LOD of 0.0355 ± 0.00613 nM. In colorimetric mode, the Au-Pd@Fc nanozyme catalyzed the color reaction of 3,3',5,5'-tetramethylbenzidine. The blue-shifted absorbance will be observed with the change of AAs concentration, and the LOD was 0.0458 ± 0.00572 nM. Furthermore, a magnetic molecular-imprinted material capable of specific adsorption of AAs was prepared on milk sample pretreatment. The aptasensor was used to detect 10 kinds of AAs in milk and the recoveries were 97.19 ± 4.41% â¼ 98.70 ± 4.45% and 96.38 ± 3.53%-97.54 ± 4.13% in electrochemical and colorimetric methods. This work provided a theoretical basis for the application of aptamers in simultaneous detection of antibiotics.
Assuntos
Aminoglicosídeos , Antibacterianos , Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Exodesoxirribonucleases , Contaminação de Alimentos , Ouro , Leite , Paládio , Animais , Aminoglicosídeos/química , Aminoglicosídeos/análise , Aminoglicosídeos/isolamento & purificação , Antibacterianos/análise , Antibacterianos/química , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/instrumentação , Colorimetria , Técnicas Eletroquímicas/instrumentação , Exodesoxirribonucleases/química , Exodesoxirribonucleases/metabolismo , Contaminação de Alimentos/análise , Ouro/química , Limite de Detecção , Leite/química , Paládio/químicaRESUMO
Ovarian cancer, an aggressive malignancy of the female reproductive tract, is frequently linked to an elevated risk of thrombotic events. This association is manifested by a pronounced rise in platelet counts and activation levels. Current research firmly supports the pivotal role of platelets in the oncogenic processes of ovarian cancer, influencing tumor cell proliferation and metastasis. Platelets influence these processes through direct interactions with tumor cells or by secreting cytokines and growth factors that enhance tumor growth, angiogenesis, and metastasis. This review aims to thoroughly dissect the interactions between platelets and ovarian cancer cells, emphasizing their combined role in tumor progression and associated thrombotic events. Additionally, it summarizes therapeutic strategies targeting platelet-cancer interface which show significant promise. Such approaches could not only be effective in managing the primary ovarian tumor but also play a pivotal role in preventing metastasis and attenuating thrombotic complications associated with ovarian cancer.
Assuntos
Plaquetas , Neoplasias Ovarianas , Humanos , Neoplasias Ovarianas/patologia , Feminino , Plaquetas/patologia , Plaquetas/metabolismo , Trombose/etiologia , Neovascularização Patológica/patologiaRESUMO
Food safety is an important cornerstone of protecting human health and life. Therefore, it is of great significance to detect possible pollutants in food sensitively and efficiently. Molecularly imprinted polymers (MIPs) and metal-organic frameworks (MOFs) have been widely used in the adsorption and detection of food pollutants. However, traditional MIPs have problems such as uneven loading of the imprinted cavity and slow mass transfer efficiency. While the adsorption of MOFs has low specificity and cannot accurately identify target molecules. Therefore, some researchers have taken advantage of the high specific recognition abilities of MIPs and the large specific surface areas, high porosity and easy functionalization of MOFs to combine MOFs with MIPs, and have achieved a series of important results in the field of food safety detection. This paper reviews the research progress of the application of MOFs-MIPs in the field of food safety detection from 2019 to 2024. It furnishes researchers interested in this domain with a rapid and comprehensive grasp of the latest research status, it also offers them a chance to anticipate future development trends, thereby supporting the continuous advances of MOFs-MIPs in food safety detection.
Assuntos
Contaminação de Alimentos , Inocuidade dos Alimentos , Estruturas Metalorgânicas , Polímeros Molecularmente Impressos , Estruturas Metalorgânicas/química , Polímeros Molecularmente Impressos/química , Contaminação de Alimentos/análise , Adsorção , Impressão Molecular , Humanos , Polímeros/químicaRESUMO
In light of the significant risks that mycotoxins posed to public health and environmental safety, this research developed an adsorbent MIPs/Apt/AuNPs@ZIF-67 (MA-AZ) utilizing a dual-recognition approach combining molecularly imprinted polymers (MIPs) and aptamer (Apt). This innovative method enabled the effective and highly selective recognition and enrichment of ochratoxin A (OTA). ZIF-67 was utilized as a carrier with a substantial specific surface area, and gold nanoparticles (AuNPs) were loaded on its surface to fix the thiol-modified Apt on the surface of the carrier. Then, an initiator was used to initiate a polymerization reaction, and the generated MIPs coated Apt/AuNPs@ZIF-67, thereby synthesizing the MA-AZ with a "synergistic recognition" effect. The Apt significantly increased the number of recognition sites within the imprinted cavities, and MIPs played roles in identifying targets, fixing and protecting Apt. The combination of the both produced the effect of "1+1>2". The study on the adsorption performance of MA-AZ found that the adsorption capacity of MA-AZ could reach 65.1 mg/g, and the imprinted factor was 5.48. In addition, MA-AZ exhibited excellent stability, specificity, reusability and recovery rate. Thus, this study offers valuable insights for the recognition and enrichment of hazardous substances, and helps to promote the rapid development of safety detection.