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1.
Nature ; 620(7976): 1047-1053, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37459895

RESUMO

Zygotic genome activation (ZGA) activates the quiescent genome to enable the maternal-to-zygotic transition1,2. However, the identity of transcription factors that underlie mammalian ZGA in vivo remains elusive. Here we show that OBOX, a PRD-like homeobox domain transcription factor family (OBOX1-OBOX8)3-5, are key regulators of mouse ZGA. Mice deficient for maternally transcribed Obox1/2/5/7 and zygotically expressed Obox3/4 had a two-cell to four-cell arrest, accompanied by impaired ZGA. The Obox knockout defects could be rescued by restoring either maternal and zygotic OBOX, which suggests that maternal and zygotic OBOX redundantly support embryonic development. Chromatin-binding analysis showed that Obox knockout preferentially affected OBOX-binding targets. Mechanistically, OBOX facilitated the 'preconfiguration' of RNA polymerase II, as the polymerase relocated from the initial one-cell binding targets to ZGA gene promoters and distal enhancers. Impaired polymerase II preconfiguration in Obox mutants was accompanied by defective ZGA and chromatin accessibility transition, as well as aberrant activation of one-cell polymerase II targets. Finally, ectopic expression of OBOX activated ZGA genes and MERVL repeats in mouse embryonic stem cells. These data thus demonstrate that OBOX regulates mouse ZGA and early embryogenesis.


Assuntos
Desenvolvimento Embrionário , Regulação da Expressão Gênica no Desenvolvimento , Genoma , Proteínas de Homeodomínio , Fatores de Transcrição , Zigoto , Animais , Camundongos , Cromatina/genética , Cromatina/metabolismo , Desenvolvimento Embrionário/genética , Elementos Facilitadores Genéticos/genética , Genoma/genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Células-Tronco Embrionárias Murinas/metabolismo , Mutação , Regiões Promotoras Genéticas/genética , RNA Polimerase II/metabolismo , Fatores de Transcrição/deficiência , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Zigoto/metabolismo
2.
Nature ; 587(7832): 139-144, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33116310

RESUMO

Zygotic genome activation (ZGA) is the first transcription event in life1. However, it is unclear how RNA polymerase is engaged in initiating ZGA in mammals. Here, by developing small-scale Tn5-assisted chromatin cleavage with sequencing (Stacc-seq), we investigated the landscapes of RNA polymerase II (Pol II) binding in mouse embryos. We found that Pol II undergoes 'loading', 'pre-configuration', and 'production' during the transition from minor ZGA to major ZGA. After fertilization, Pol II is preferentially loaded to CG-rich promoters and accessible distal regions in one-cell embryos (loading), in part shaped by the inherited parental epigenome. Pol II then initiates relocation to future gene targets before genome activation (pre-configuration), where it later engages in full transcription elongation upon major ZGA (production). Pol II also maintains low poising at inactive promoters after major ZGA until the blastocyst stage, coinciding with the loss of promoter epigenetic silencing factors. Notably, inhibition of minor ZGA impairs the Pol II pre-configuration and embryonic development, accompanied by aberrant retention of Pol II and ectopic expression of one-cell targets upon major ZGA. Hence, stepwise transition of Pol II occurs when mammalian life begins, and minor ZGA has a key role in the pre-configuration of transcription machinery and chromatin for genome activation.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento/genética , Genoma/genética , RNA Polimerase II/metabolismo , Zigoto/metabolismo , Alelos , Animais , Cromatina/genética , Cromatina/metabolismo , Embrião de Mamíferos/citologia , Embrião de Mamíferos/enzimologia , Embrião de Mamíferos/metabolismo , Epigenoma/genética , Feminino , Masculino , Herança Materna/genética , Camundongos , Camundongos Endogâmicos C57BL , Oócitos/enzimologia , Oócitos/metabolismo , Regiões Promotoras Genéticas/genética , RNA Polimerase II/genética , Zigoto/citologia , Zigoto/enzimologia
3.
PLoS Pathog ; 19(3): e1011218, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36947557

RESUMO

In plants, age-related resistance (ARR) refers to a gain of disease resistance during shoot or organ maturation. ARR associated with vegetative phase change, a transition from juvenile to adult stage, is a widespread agronomic trait affecting resistance against multiple pathogens. How innate immunity in a plant is differentially regulated during successive stages of shoot maturation is unclear. In this work, we found that Arabidopsis thaliana showed ARR against its bacterial pathogen Pseudomonas syringae pv. tomato DC3000 during vegetative phase change. The timing of the ARR activation was associated with a temporal drop of miR156 level. The microRNA miR156 maintains juvenile phase by inhibiting the accumulation and translation of SPL transcripts. A systematic inspection of the loss- and gain-of-function mutants of 11 SPL genes revealed that a subset of SPL genes, notably SPL2, SPL10, and SPL11, activated ARR in adult stage. The immune function of SPL10 was independent of its role in morphogenesis. Furthermore, the SPL10 mediated an age-dependent augmentation of the salicylic acid (SA) pathway partially by direct activation of PAD4. Disrupting SA biosynthesis or signaling abolished the ARR against Pto DC3000. Our work demonstrated that the miR156-SPL10 module in Arabidopsis is deployed to operate immune outputs over developmental timing.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , MicroRNAs , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Resistência à Doença/genética , Regulação da Expressão Gênica de Plantas , MicroRNAs/genética , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Pseudomonas syringae/metabolismo , Ácido Salicílico/metabolismo
4.
Lancet Oncol ; 25(6): e270-e280, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38821101

RESUMO

Although radiotherapy continues to evolve as a mainstay of the oncological armamentarium, research and innovation in radiotherapy in low-income and middle-income countries (LMICs) faces challenges. This third Series paper examines the current state of LMIC radiotherapy research and provides new data from a 2022 survey undertaken by the International Atomic Energy Agency and new data on funding. In the context of LMIC-related challenges and impediments, we explore several developments and advances-such as deep phenotyping, real-time targeting, and artificial intelligence-to flag specific opportunities with applicability and relevance for resource-constrained settings. Given the pressing nature of cancer in LMICs, we also highlight some best practices and address the broader need to develop the research workforce of the future. This Series paper thereby serves as a resource for radiation professionals.


Assuntos
Países em Desenvolvimento , Neoplasias , Radioterapia (Especialidade) , Humanos , Países em Desenvolvimento/economia , Neoplasias/radioterapia , Radioterapia (Especialidade)/economia , Pesquisa Biomédica/economia , Radioterapia/economia , Pobreza
5.
Int J Cancer ; 154(7): 1143-1157, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38059788

RESUMO

Radiotherapy has unique immunostimulatory and immunosuppressive effects. Although high-dose radiotherapy has been found to have systemic antitumor effects, clinically significant abscopal effects were uncommon on the basis of irradiating single lesion. Low-dose radiation therapy (LDRT) emerges as a novel approach to enhance the antitumor immune response due to its role as a leverage to reshape the tumor immune microenvironment (TIME). In this article, from bench to bedside, we reviewed the possible immunomodulatory role of LDRT on TIME and systemic tumor immune environment, and outlined preclinical evidence and clinical application. We also discussed the current challenges when LDRT is used as a combination therapy, including the optimal dose, fraction, frequency, and combination of drugs. The advantage of low toxicity makes LDRT potential to be applied in multiple lesions to amplify antitumor immune response in polymetastatic disease, and its intersection with other disciplines might also make it a direction for radiotherapy-combined modalities.


Assuntos
Neoplasias , Humanos , Neoplasias/radioterapia , Previsões , Imunidade , Terapia Combinada , Imunomodulação , Imunoterapia , Microambiente Tumoral
6.
Exp Brain Res ; 242(5): 1061-1069, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38472448

RESUMO

Emotional intelligence (EI) is one's ability to monitor one's own and other's emotions and the use of emotional information to enhance thought and action. Previous behavioral studies have shown that EI is separable into trait EI and ability EI, which are known to have distinct characteristics at the behavioral level. A relevant and unanswered question is whether both forms of EI have a dissociable neural basis. Previous studies have individually explored the neural underpinnings of trait EI and ability EI, but there has been no direct comparison of the neural mechanisms underlying these two types of emotional intelligence. The present study addresses this question by using resting-state fMRI to examine the correlational pattern between the regional amplitude of low-frequency fluctuations (ALFF) of the brain and individuals' trait EI and ability EI scores. We found that trait EI scores were positively correlated with the ALFF in the bilateral superior temporal gyrus, and negatively correlated with the ALFF in the ventral medial prefrontal cortex. In contrast, ability EI scores were positively correlated with the ALFF in the insula. Taken together, these results provide preliminary evidence of dissociable neural substrates between trait EI and ability EI.


Assuntos
Mapeamento Encefálico , Encéfalo , Inteligência Emocional , Imageamento por Ressonância Magnética , Descanso , Humanos , Masculino , Feminino , Adulto Jovem , Inteligência Emocional/fisiologia , Descanso/fisiologia , Adulto , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Emoções/fisiologia , Adolescente
7.
Psychol Res ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38632161

RESUMO

Reward has been known to render the reward-associated stimulus more salient to block effective attentional orienting in space. However, whether and how reward influences goal-directed attention in time remains unclear. Here, we used a modified attentional cueing paradigm to explore the effect of reward on temporal attention, in which the valid targets were given a low monetary reward and invalid targets were given a high monetary reward. The results showed that the temporal cue validity effect was significantly smaller when the competitive reward structure was employed (Experiment 1), and we ruled out the possibility that the results were due to the practice effect (Experiment 2a) or a reward-promoting effect (Experiment 2b). When further strengthening the intensity of the reward from 1:10 to 1:100 (Experiment 3), we found a similar pattern of results to those in Experiment 1. These results suggest that reward information which was based on relative instead of absolute values can weaken, but not reverse, the orienting attention in time.

8.
Sensors (Basel) ; 24(4)2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38400335

RESUMO

Electrical energy is often wasted through human negligence when people do not switch off electrical appliances such as lighting after leaving a place. Such a scenario often happens in a classroom when the last person leaves the class and forgets to switch off the electrical appliances. Such wastage may not be able to be afforded by schools that are limited financially. Therefore, this research proposed a simple and cost-effective system that can analyze whether there is or is not a human presence in the classroom by applying a counter to count the total number of people entering and leaving the classroom based on the sensing signals of a set of dual PIR sensors only and then correlating this to automatically turn on or off the electrical appliances mentioned. The total number of people identified in the classroom is also displayed on an LCD screen. A TRIZ approach is used to support the ideation of the system. The system can switch on several electrical output loads simultaneously when the presence of people is detected and switch them off when there are no people in the classroom. The proposed system can be expanded to be used in homes, offices, and buildings to prevent the high cost of electricity consumption caused by the negligence of people. This enables smarter control of electricity consumption.


Assuntos
Iluminação , Instituições Acadêmicas , Humanos , Eletricidade
9.
Int J Psychol ; 59(1): 111-120, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38016937

RESUMO

Colour is a ubiquitous perceptual stimulus, and theoretical models of colour and psychological functioning posit that colour plays a key role in influencing the behaviour and mental function of a person. One investigation and two experiments investigated the colour metaphor representation of happiness concepts and the mapping mode of the colour metaphor of happiness concepts. A questionnaire was conducted to explore the relationship between colour preference and happiness. Study 2 shows that the identification of happiness words was facilitated more when words were viewed on an orange background than when viewed on a blue background. Study 3 further verifies the links of the connection between colour and happiness at the sentence level, and the orange-happiness facilitation effect was replicated. These results document a novel influence of colour on emotion recognition processes, where an orange background may facilitate the processing of the concept of happiness and provide support for conceptual metaphor theory and colour-in-context theory.


Assuntos
Felicidade , Metáfora , Humanos , Cor , Reconhecimento Psicológico , Idioma
10.
Worldviews Evid Based Nurs ; 21(2): 120-127, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38374516

RESUMO

BACKGROUND: Nurse job satisfaction is a critical area of study with far-reaching implications for healthcare organizations, patient care, and the retention of nursing staff. AIMS: This study aimed to investigate the association of gratitude with job satisfaction among Chinese nurses and examine the potential mediating roles of resilience and stress in this relationship. METHODS: Two separate studies were conducted to examine our research hypotheses. In Study 1, a total of 460 nurses completed the questionnaire related to gratitude, resilience, stress, and job satisfaction. A validation study was conducted in Study 2, which consisted of 709 nurses who also completed the same measures of gratitude, resilience, and stress to ensure the repeatability of the Study 1 results. Furthermore, a different scale was used to measure nurses' job satisfaction. RESULTS: The two studies consistently found that both resilience and stress mediated gratitude-job satisfaction independently among Chinese nurses. Furthermore, resilience was found to be a significantly stronger mediator than stress in the association of gratitude with job satisfaction. Finally, we found that gratitude predicted nurses' job satisfaction via the serial mediating effects of resilience and stress. CONCLUSION: These findings highlight the complex interplay between gratitude, resilience, stress, and job satisfaction by demonstrating that resilience and stress act as parallel and sequential mediators between nurses' gratitude and job satisfaction. The healthcare sector can improve nurses' job satisfaction by increasing gratitude, building resilience, and reducing feelings of stress. LINKING EVIDENCE TO ACTION: Nurse managers have the potential to enhance job satisfaction among nurses by implementing measures that increase gratitude, build resilience, and reduce stress levels.


Assuntos
Enfermeiros Administradores , Enfermeiras e Enfermeiros , Recursos Humanos de Enfermagem Hospitalar , Resiliência Psicológica , Humanos , Satisfação no Emprego , Inquéritos e Questionários
11.
Artigo em Inglês | MEDLINE | ID: mdl-38831543

RESUMO

BACKGROUND: A common psychological problem among nurses is depression, potentially affecting their well-being and job performance. It is vital to explore how to alleviate nurses' depressive symptoms. AIM: The current research explored the mediating impact of basic psychological needs satisfaction on the link of gratitude with depressive symptoms. METHODS: The nurses in this study were from mainland China. A total of 724 subjects completed an online questionnaire, which included measures of depressive symptoms, basic psychological needs satisfaction and gratitude. RESULTS: Our research found that gratitude was negatively linked to depressive symptoms. Furthermore, basic psychological needs satisfaction had a partial mediation effect on the link of gratitude with depressive symptoms after controlling for five demographic variables. These results suggest that gratitude may influence depressive symptoms via basic psychological needs satisfaction. LINKING EVIDENCE TO ACTION: Our study found that basic psychological need satisfaction partially mediates the gratitude-depression relationship in nurses. The result means that hospital administrators and nurse leaders should design gratitude interventions to alleviate nurses' depressive symptoms. They also help nurses decrease depressive symptoms by creating an environment that meets their basic psychological needs.

12.
Curr Psychol ; : 1-16, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36713621

RESUMO

The present work investigated fundamental mediating mechanisms (i.e., flow experience, organizational identification, and trust), underlining the impact of authentic leadership on employee resilience during the turbulent COVID-19 pandemic. A total of 901 frontline employees working in a construction engineering company in China participated in this study. They were asked to respond to a battery of questionnaires comprising Trust Scale (affective-based, cognitive-based, and competence-based), Flow Proneness Questionnaire (FPQ), Organizational Identification Scale, Authentic Leadership Questionnaire, and Employee Resilience Scale. Results of structural equation modeling indicated that: (1) Authentic leadership positively predicted employee resilience in the COVID-19 pandemic, directly and indirectly. (2) As for the indirect relationship, two parallel mediation effects and one chain mediation were detected: employees' flow at work and organizational identification respectively and dependently mediated the relationship between authentic leadership and employee resilience; trust and organizational identification played as a chain mediation role within authentic leadership-employee resilience association. The study provides empirical evidence for organizations' resilience-building and leadership training programs. Findings also contribute to the literature by facilitating flow intervention, promoting organizational identification and trust to enhance the effect of authentic leadership in promoting positive psychological functioning of employee resilience. Limitations with respect to future research directions were also outlined.

13.
Reprod Fertil Dev ; 34(15): 991-1001, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36064201

RESUMO

CONTEXT: With aging, various problems in the reproductive system emerge, especially in females. However, our understanding of reproductive aging in livestock and humans is limited. AIMS: We aimed to investigate reproductive changes between young and aged mice. METHODS: Eight- to ten-week-old female mice were used as the young group, and 10-month-old mice were studied as the aged group. Reproductive changes were investigated from physiological, histological, cytological, and epigenetic perspectives. KEY RESULTS: The estrus cycle was shortened (P <0.0001), and the estradiol (E2) concentration was lower in aged mice (P <0.01), whereas the progesterone (P4) concentration did not differ between young and aged mice (P >0.05). The histological results revealed a lower number of antral follicles in the ovary and disordered epithelial tissue structures in the oviducts in aged mice. During oogenesis, the surrounded nucleolus (SN)-type oocytes in aged mice exhibited increased mitochondrial agglutination (P <0.05) and cellular apoptosis (P <0.01) as well as decreased H3K36 triple-methylation (P <0.001). Although many defects existed, the oocytes from aged mice could normally support cellular reprogramming after somatic cell nuclear transfer. CONCLUSIONS: Our results indicate that the reduced levels of reproductive hormones in aged females lead to shorter estrus cycles and reduced follicular development, leading to abnormal oogenesis, particularly in SN-type immature oocytes. IMPLICATIONS: These results provide new insight that enhance our understanding and improve the reproductive ability of aged females.


Assuntos
Oogênese , Progesterona , Idoso , Animais , Estradiol/metabolismo , Estrogênios/metabolismo , Feminino , Humanos , Lactente , Camundongos , Oócitos/metabolismo , Oogênese/fisiologia , Progesterona/metabolismo
14.
Int J Mol Sci ; 23(13)2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35806295

RESUMO

Salt is one of the most common abiotic stresses, causing ionic and osmotic pressure changes that affect plant growth and development. In this work, we present molecular and genetic evidence that Arabidopsis Toxicos en Levadura 12 (ATL12) is involved in both salt stress and in the abscisic acid response to this stress. We demonstrate that ATL12 is highly induced in response to salt stress and that atl12 mutants have a lower germination rate, decreased root length, and lower survival rate compared to the Col-0 wild-type in response to salt stress. Overexpression of ATL12 increases expression of the salt stress-associated genes SOS1/2, and ABA-responsive gene RD29B. Additionally, higher levels of reactive oxygen species are detected when ATL12 is overexpressed, and qRT-PCR showed that ATL12 is involved in the AtRBOHD/F-mediated signaling. ATL12 expression is also highly induced by ABA treatment. Mutants of atl12 are hypersensitive to ABA and have a shorter root length. A decrease in water loss and reduced stomatal aperture were also observed in atl12 mutants in response to ABA. ABA-responsive genes RD29B and RAB18 were downregulated in atl12 mutants but were upregulated in the overexpression line of ATL12 in response to ABA. Taken together our results suggest that ATL12 modulates the response to salt stress and is involved in the ABA signaling pathway in Arabidopsis thaliana.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacologia , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Germinação/genética , Plantas Geneticamente Modificadas/genética , Estresse Salino/genética , Estresse Fisiológico
15.
J Nurs Manag ; 29(6): 1660-1667, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33792987

RESUMO

AIMS: This study aimed to reveal the role of satisfying basic psychological needs in the relationship between strength use and depressive symptoms in nurses. BACKGROUND: There is a high prevalence of depressive symptoms among nurses. Previous studies on different groups have reported that strength use is beneficial for alleviating individuals' depressive symptoms. METHOD: A total of 475 participating Chinese nurses completed questionnaires. Hypotheses were tested using the PROCESS macro. RESULTS: Strength use was positively correlated with basic psychological needs satisfaction overall and negatively correlated with depressive symptoms. Furthermore, autonomy and relatedness satisfaction acted as mediating mechanisms through which strength use influenced depressive symptoms. CONCLUSIONS: Autonomy and relatedness satisfaction can mediate the influence of strength use on depressive symptoms in nurses. IMPLICATIONS FOR NURSING MANAGEMENT: Focus should be placed on improving nurses' strength use level to reduce their depressive symptoms. Hospital managers should create an organisational environment conducive to meeting nurses' basic psychological needs and thereby reduce their depressive symptoms.


Assuntos
Enfermeiras e Enfermeiros , Recursos Humanos de Enfermagem Hospitalar , Estudos Transversais , Depressão/etiologia , Humanos , Satisfação no Emprego , Satisfação Pessoal , Inquéritos e Questionários
16.
J Transl Med ; 18(1): 184, 2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32366311

RESUMO

BACKGROUND: Primary glomerulonephritis (GN) is the leading cause of chronic kidney disease (CKD) and frequently progresses into end stage renal diseases (ESRDs). Shorter leukocyte telomere length (LTL) has been implicated in the CKD susceptibility and diminished kidney function, however, it is unclear whether the variants in telomerase genes contribute to risk to GN/CKD/ESRD. Here we address this issue by determining their association with the genetic variants of rs12696304 at the telomerase RNA component (TERC) and rs2736100 at the telomerase reverse transcriptase (TERT) loci. METHODS: The study includes 769 patients (243 primary GN-derived CKD and 526 ESRD cases) and sex-/age-matched healthy controls. Genomic DNA was extracted from peripheral blood of both controls and patients. Genotyping of rs12696304 and rs2736100 variants was carried out using PCR-based assays. Leukocyte telomere length (LTL) was determined using quantitative PCR (qPCR). RESULTS: A significantly higher frequency of TERC rs12696304 G allele was observed in patients and associated with increased disease risk (C vs G: OR = 1.334, 95% CI 1.112-1.586, P = 0.001; CC + GC vs GG: OR = 1.334, 95% CI 1.122-1.586, P = 0.001). Further analyses showed that such significant differences were only present between female controls and patients (C vs G: OR = 1.483, 95% CI 1.140-1.929, P = 0.003; CC + GC vs CC: OR = 1.692, 95% CI 1.202-2.383, P = 0.003), but not males. There were no differences in rs2736100 variants between controls and patients, but female ESRD patients carried significantly higher C allele frequencies than did female controls (A vs C: OR = 1.306, 95% CI 1.005-1.698, P = 0.046; AA vs CC: OR = 1.781, 95% CI 1.033-3.070, P = 0.037). There was no difference in LTL between controls and patients. CONCLUSIONS: Our results reveal that the TERC rs12696304 and TERT rs2736100 polymorphisms, but not LTL per se, contribute to GN/CDK/ESRD risk.


Assuntos
Glomerulonefrite , Falência Renal Crônica , Telomerase , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Glomerulonefrite/genética , Humanos , Falência Renal Crônica/genética , Leucócitos , Polimorfismo de Nucleotídeo Único/genética , Telomerase/genética , Telômero/genética
17.
J Vis ; 20(9): 17, 2020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32976595

RESUMO

Previous studies have confirmed that both non-reward objects (such as rectangles) and reward objects (such as banknotes) can guide the allocation of our attention; however, it is unclear whether the allocation mode of attention for reward objects is the same as for non-reward objects. This study aims to evaluate different modes of object-based attentional selection elicited by two types of objects: reward objects and non-reward objects. In our analysis, we used a two-rectangle paradigm in which two objects were presented visually. In a series of four experiments, we found a constant object-based effect with non-reward objects, such as rectangles and umbrellas, as stimuli in all of the stimulus onset asynchrony (SOA) conditions (Experiments 1 and 4), but the object-based effect disappeared only at longer SOA with reward objects such as monetary and food objects as stimuli (Experiments 2 and 3). Moreover, we found that monetary and food objects induced similar object-based effects. These results suggest that the temporal dynamics of object-based attentional allocation are different with respect to reward and non-reward objects, and different types of reward objects can guide attentional allocation in a similar way.


Assuntos
Atenção , Recompensa , Adulto , Feminino , Humanos , Masculino , Percepção Visual
18.
Ren Fail ; 42(1): 89-97, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31900008

RESUMO

Background: Embryonic metanephros is the mammalian renal anlagen, which is considered as a potential source for the regeneration of functional whole kidneys. Some studies reported that metanephros implanted into unilateral nephrectomized animals can develop into kidney tissue. However, kidneys are nephrotoxic in renal failure patients, and whether metanephros can grow in nephrotoxic has not been reported. This study aims to investigate the growth of metanephros in acute nephrotoxic environment and analyze the therapeutic effect of metanephros microenvironment on acute kidney injury (AKI).Methods: AKI was induced in 200 g Wistar rats by giving intramuscular injections of 50% glycerol (10 mL/kg) in their hind limbs. 45 rats were divided randomly into three groups (control, glycerin, and metanephros). Metanephros group was transplanted two metanephroi (embryonic day 15) into the renal capsule of AKI rats. Glycerin group was AKI rats without transplantation. Control group was untreated.Results: Mature glomeruli and tubules were detected in the grafts in metanephros group, which means that metanephroi can grow into tissues with mature kidney structure under acute nephrotoxic. Then, we assessed the renal function of host rats and found that there were fewer tubular necrosis in metanephros group than glycerin group, and the serum creatinine and urea nitrogen were significantly lower in metanephros group than glycerin group.Conclusion: These results suggested that embryonic metanephroi can grow into tissues with mature kidney structure under acute nephrotoxic, and the graft microenvironment was effective in inhibiting the progression of AKI, which provides a new approach for the treatment of acute renal injury.


Assuntos
Injúria Renal Aguda/terapia , Aloenxertos/crescimento & desenvolvimento , Transplante de Rim/métodos , Rim/embriologia , Regeneração , Injúria Renal Aguda/sangue , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/patologia , Animais , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Modelos Animais de Doenças , Progressão da Doença , Glicerol/toxicidade , Humanos , Rim/fisiologia , Masculino , Nefrectomia , Ratos , Ratos Wistar
19.
Eur J Nucl Med Mol Imaging ; 46(4): 940-947, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30187104

RESUMO

PURPOSE: To explore the relationship between metabolic uptake of the 18F-ALF-NOTA-PRGD2 (18F-RGD) tracer on positron emission tomography/computerized tomography (PET/CT) and the antiangiogenic effect of apatinib in patients with solid malignancies. MATERIALS AND PATIENTS: Patients with measurable lesions scheduled for second- or third-line single-agent therapy with apatinib were eligible for this prospective clinical trial. All patients underwent 18F-RGD PET/CT examination before the start of treatment. Standardized uptake values (SUVs) of contoured tumor lesions were computed and compared using independent sample t-tests or the Mann-Whitney U test. Receiver-operating characteristic (ROC) curve analysis was used to determine accuracy in predicting response. Survival curves were compared using the Kaplan-Meier method. RESULTS: Of 38 patients who consented to study participation, 25 patients with 42 measurable lesions met the criteria for inclusion in this response assessment analysis. The median follow-up time was 3 months (range, 1-10 months), and the median progression-free survival (PFS) was 3 months (95% confidence interval, 1.04-4.96). The SUVpeak and SUVmean were significantly higher in responding tumors than in non-responding tumors (4.98 ± 2.34 vs 3.59 ± 1.44, p = 0.048; 3.71 ± 1.15 vs 2.95 ± 0.49, P = 0.036). SUVmax did not differ between responding tumors and non-responding tumors (6.58 ± 3.33 vs 4.74 ± 1.83, P = 0.078). An exploratory ROC curve analysis indicated that SUVmean [area under the ROC curve (AUC) = 0.700] was a better parameter than SUVpeak (AUC = 0.689) for predicting response. Using a threshold value of 3.82, high SUVmean at baseline was associated with improved PFS (5.0 vs. 3.4 months, log-rank P = 0.036). CONCLUSION: 18F-RGD uptake on PET/CT imaging pretreatment may predict the response to antiangiogenic therapy, with higher 18F-RGD uptake in tumors predicting a better response to apatinib therapy.


Assuntos
Radioisótopos de Flúor , Neovascularização Patológica/diagnóstico por imagem , Neovascularização Patológica/tratamento farmacológico , Oligopeptídeos/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Transporte Biológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/metabolismo , Piridinas/farmacologia , Piridinas/uso terapêutico , Curva ROC , Traçadores Radioativos , Resultado do Tratamento
20.
Acta Pharmacol Sin ; 40(5): 689-698, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30171201

RESUMO

Acquired docetaxel-resistance of prostate cancer (PCa) remains a clinical obstacle due to the lack of effective therapies. Acetyl-11-keto-ß-boswellic acid (AKBA) is a pentacyclic triterpenic acid isolated from the fragrant gum resin of the Boswellia serrata tree, which has shown intriguing antitumor activity against human cell lines established from PCa, colon cancer, malignant glioma, and leukemia. In this study, we examined the effects of AKBA against docetaxel-resistant PCa in vitro and in vivo as well as its anticancer mechanisms. We showed that AKBA dose-dependently inhibited cell proliferation and induced cell apoptosis in docetaxel-resistant PC3/Doc cells; its IC50 value in anti-proliferation was ∼17 µM. Furthermore, AKBA dose-dependently suppressed the chemoresistant stem cell-like properties of PC3/Doc cells, evidenced by significant decrease in the ability of mammosphere formation and down-regulated expression of a number of stemness-associated genes. The activation of Akt and Stat3 signaling pathways was remarkably enhanced in PC3/Doc cells, which contributed to their chemoresistant stem-like phenotype. AKBA (10-30 µM) dose-dependently suppressed the activation of Akt and Stat3 signaling pathways in PC3/Doc cells. In contrast, overexpression of Akt and Stat3 significantly attenuated the inhibition of AKBA on PC3/Doc cell proliferation. In docetaxel-resistant PCa homograft mice, treatment with AKBA significantly suppresses the growth of homograft RM-1/Doc, equivalent to its human PC3/Doc, but did not decrease their body weight. In summary, we demonstrate that AKBA inhibits the growth inhibition of docetaxel-resistant PCa cells in vitro and in vivo via blocking Akt and Stat3 signaling, thus suppressing their cancer stem cell-like properties.


Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Triterpenos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Docetaxel/farmacologia , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos Endogâmicos C57BL , Células-Tronco Neoplásicas/efeitos dos fármacos , Triterpenos/farmacologia
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