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BACKGROUND: Limited evidence exists for the association between dietary patterns and later obesity phenotypes among Chinese adults. This longitudinal study aimed to evaluate associations of dietary patterns with general and central obesity in Chinese adults. METHODS: Based on the China Health and Nutrition Survey (CHNS) waves 2004 and 2015, the study was conducted on 4207 adult men and women (age range: 18-65 years). Dietary intakes were assessed by three consecutive 24-h dietary recalls, and dietary patterns were identified using exploratory factor analysis. Longitudinal associations of dietary patterns with general and central obesity were evaluated using logistic regression analyses. RESULTS: The prevalence rates of general and central obesity were 14.2% and 42.1%, respectively. Factor analysis extracted three major dietary patterns: "traditional southern," "modern," and "traditional northern." After adjustment for potential confounders, adults in the highest quartile of the traditional southern dietary group were less likely to develop over 10 years general (odds ratio [OR] = 0.50, 95% confidence interval [95%CI]: 0.39, 0.65) and central (OR = 0.52, 95%CI: 0.43, 0.63) obesity compared to those in the lowest quartile group. The modern dietary pattern was not significantly associated with general and central obesity. Adherence to the traditional northern dietary pattern increased the chance of both general and central obesity (OR = 1.61, 95%CI: 1.23, 2.10; OR = 1.64, 95%CI: 1.36, 1.98) after 10 years. CONCLUSIONS: Our study provides longitudinal evidence for associations between dietary patterns and later obesity phenotypes among Chinese adults. Our findings may guide the development of evidence-based preventive nutrition interventions to control the obesity epidemic.
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Dieta , População do Leste Asiático , Obesidade Abdominal , Feminino , Humanos , Masculino , Estudos Longitudinais , Obesidade Abdominal/epidemiologia , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , IdosoRESUMO
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in Wuhan, China has dispersed rapidly worldwide. Although most patients present with mild fever, cough with varying pulmonary shadows, a significant portion still develops severe respiratory dysfunction. And these severe cases are often associated with manifestations outside the respiratory tract. Currently, it is not difficult to find inflammatory cytokines upregulated in the blood of infected patients. However, some complications in addition to respiratory system with the coronavirus disease 2019 (COVID-19) are impossible to explain or cannot be attributed to virus itself. Thus excessive cytokines and their potentially fatal adverse effects are probably the answer to the multiple organ dysfunctions and growing mortality. This review provides a comprehensive overview of the mechanisms underlying cytokine storm, summarizes its pathophysiology and improves understanding of cytokine storm associated with coronavirus infections by comparing SARS-CoV-2 with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV).
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COVID-19/complicações , Síndrome da Liberação de Citocina/etiologia , SARS-CoV-2 , Infecções por Coronavirus/virologia , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , Síndrome Respiratória Aguda Grave/virologiaRESUMO
OBJECTIVE: To provide information on clinical, virological, and molecular epidemiological characteristics for early identification, diagnosis, and treatment of acute HIV infection (AHI). METHODS: A retrospective study was conducted with patients with AHI from 2012 to 2017 in West China Hospital. RESULTS: A total of 47 patients with AHI were found using a fourth-generation kit. Thirteen (27.66%) of these patients were negative if tested by third-generation tests. Median age of patients with AHI was 26 and 91.49% of them were males. Homosexual contact was responsible for 46.81% of AHI transmission. Among the individuals with AHI, 80.85% were outpatients. Common symptoms/signs were fever, headache, rash, cough and sputum, and sore throat. The syphilis coinfection rate was 17.24%. Most of the AHI was distributed in Fiebig stages IV (61.70%) and II (27.66%) with different clinical and virological characteristics. The increasing trend of cut-off index values was obvious in the course of AHI, helpful for auxiliary diagnosis. The main genetic forms of AHI were CRF07_BC and CRF01_AE, and a rare subtype CRF55_01B in Sichuan province was found. The drug resistance mutation rate was relatively high (17.65%) and five different mutations were identified. CONCLUSIONS: Fourth-generation assays are strongly recommended for screening AHI compared to third-generation ones. Different clinical and virological characteristics in different Fiebig stages were found. Young individuals and outpatients were the majority of patients with AHI and this deserves special attention. Attention should also be paid to the rare CRF55_01B in Sichuan province and surveillance of HIV resistance ought to be strengthened.
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OBJECTIVE: To analyze the results of different cut-off index (COI) values of Elecsys® HIV combi PT assay and to assess the role of COI in reducing the frequency of false-positive results. METHODS: We conducted a retrospective study of samples analyzed by Elecsys® HIV combi PT assay, a 4th-generation ECLIA, between 2016 and 2017. A total amount of 379 122 samples were collected for HIV (Human Immunodeficiency Virus) screening. RESULTS: A total of 379 122 samples were analyzed. 2528 (0.67%) were positive by Elecsys® HIV combi PT. Of these, 468 were false-positive results, and most of them (94.87%) were in samples with 1 < COI <â¯15. The false-positive rate was 0.12%. Patients with false-positive samples were more distributed in elder (P < .001) and female (P < .001) than true-positive specimens. The median COI in true-positive specimens was (385.20), which is significantly higher than false-positive specimens (2.08). The consistency between Elecsys® HIV combi PT assay and 3rd-generation and positive predictive value (PPV) increased with higher COI values. Cancer, infection, and neurological diseases were considered the potential confounding factors of HIV false-positive results (19.44%, 11.11%, and 6.62%, respectively). CONCLUSION: Samples with low COI values, especially those contain confounding factors, need to be further scrutinized to determine whether the confounding factors may cause false-positive problem. In addition, the hypothesis that low COI values may predict false-positive results is valid.
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Infecções por HIV/diagnóstico , Imunoensaio , Algoritmos , Reações Falso-Positivas , Feminino , Anticorpos Anti-HIV/sangue , Antígenos HIV/sangue , Humanos , Imunoensaio/métodos , Imunoensaio/normas , Masculino , Valores de Referência , Estudos RetrospectivosRESUMO
This paper investigates the ultimately bounded filtering problem for a kind of time-delay nonlinear stochastic systems with random access protocol (RAP) and uniform quantization effects (UQEs). In order to reduce the occurrence of data conflicts, the RAP is employed to regulate the information transmissions over the shared communication channel. The scheduling behavior of the RAP is characterized by a Markov chain with known transition probabilities. On the other hand, the measurement outputs are quantized by the uniform quantizer before being transmitted via the communication channel. The objective of this paper is to devise a nonlinear filter such that, in the simultaneous presence of RAP and UQEs, the filtering error dynamics is exponentially ultimately bounded in mean square (EUBMS). By resorting to the stochastic analysis technique and the Lyapunov stability theory, sufficient conditions are obtained under which the desired nonlinear filter exists, and then the filter design algorithm is presented. At last, two simulation examples are given to validate the proposed filtering strategy.
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BACKGROUND: Polymorphisms near the interferon lambda 3 (IFNL3, also known as IL28B) have been proposed to be associated with interferon (IFN)-induced hepatitis C virus (HCV) clearance, but the impact of IFNL3 variations on the result of IFN-based therapy in chronic hepatitis B (CHB) infection is still poor understood. METHODS: The purpose of this study was to evaluate the relationship between the IFNL3 polymorphisms and the effectiveness of IFN therapy in patients infected with CHB by means of meta-analysis. PubMed and Embase were utilized to identify relevant studies. Odds ratio (OR) and 95% confidence interval (CI) were analysed together to assess the strength of the association. Subgroup analysis was mainly performed according to HBeAg. RESULTS: Twelve studies of 1645 CHB patients met the inclusion criteria and were selected in our meta-analysis. One polymorphism, rs12979860, near to the IFNL3 gene had significant association with the response of CHB patients to IFN-based therapy (ORâ¯=â¯2.35, 95% CI: 1.61-3.42 in allelic model). Another polymorphism, rs8099917, had a similar result (ORâ¯=â¯1.57, 95% CI: 1.03-2.40 in dominant model; and ORâ¯=â¯1.88, 95% CI: 1.21-2.90 in allelic model). When stratified by HBeAg, the antiviral outcome was markedly influenced by both two SNPs in HBeAg positive group (for rs12979860, ORâ¯=â¯1.90, 95% CI: 1.31-2.76 and ORâ¯=â¯2.07, 95% CI: 1.26-3.41 in dominant and allelic models respectively; for rs8099917, ORâ¯=â¯1.67, 95% CI: 1.04-2.67 in dominant model and ORâ¯=â¯1.77, 95% CI: 1.10-2.85 in allelic model). CONCLUSION: We concluded that two polymorphisms (rs12979860 and rs8099917) of IFNL3 may play a crucial role in the IFN-based treatment of CHB, especially in HBeAg positive group.
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Antivirais/uso terapêutico , Genótipo , Hepatite B Crônica/tratamento farmacológico , Interferons/genética , Interferons/uso terapêutico , Alelos , Estudos de Casos e Controles , Bases de Dados Factuais , Hepacivirus , Antígenos E da Hepatite B , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/imunologia , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The phenomenon of delayed flowering after the application of nitrogen (N) fertilizer has long been known in agriculture, but the detailed molecular basis for this phenomenon is largely unclear. Here we used a modified method of suppression-subtractive hybridization to identify two key factors involved in N-regulated flowering time control in Arabidopsis thaliana, namely ferredoxin-NADP(+)-oxidoreductase and the blue-light receptor cryptochrome 1 (CRY1). The expression of both genes is induced by low N levels, and their loss-of-function mutants are insensitive to altered N concentration. Low-N conditions increase both NADPH/NADP(+) and ATP/AMP ratios, which in turn affect adenosine monophosphate-activated protein kinase (AMPK) activity. Moreover, our results show that the AMPK activity and nuclear localization are rhythmic and inversely correlated with nuclear CRY1 protein abundance. Low-N conditions increase but high-N conditions decrease the expression of several key components of the central oscillator (e.g., CCA1, LHY, and TOC1) and the flowering output genes (e.g., GI and CO). Taken together, our results suggest that N signaling functions as a modulator of nuclear CRY1 protein abundance, as well as the input signal for the central circadian clock to interfere with the normal flowering process.
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Proteínas de Arabidopsis/fisiologia , Arabidopsis/fisiologia , Criptocromos/fisiologia , Ferredoxina-NADP Redutase/metabolismo , Flores/fisiologia , Nitrogênio/fisiologia , Proteínas Quinases Ativadas por AMP/metabolismo , Trifosfato de Adenosina/metabolismo , Relógios Circadianos , Mutação , NADP/metabolismo , Técnicas de Hibridização SubtrativaRESUMO
As the subunits of the SWI/SNF (mating-type switching (SWI) and sucrose nonfermenting (SNF)) chromatin-remodeling complexes (CRCs), Swi3-like proteins are crucial to chromatin remodeling in yeast and human. Growing evidence indicate that AtSWI3s are also essential for development and response to hormones in Arabidopsis. Nevertheless, the biological functions of Swi3-like proteins in tomato (Solanum lycopersicum) have not been investigated. Here we identified four Swi3-like proteins from tomato, namely SlSWI3A, SlSWI3B, SlSWI3C, and SlSWI3D. Subcellular localization analysis revealed that all SlSWI3s are localized in the nucleus. The expression patterns showed that all SlSWI3s are ubiquitously expressed in all tissues and organs, and SlSWI3A and SlSWI3B can be induced by cold treatment. In addition, we found that SlSWI3B can form homodimers with itself and heterodimers with SlSWI3A and SlSWI3C. SlSWI3B can also interact with SlRIN and SlCHR8, two proteins involved in tomato reproductive development. Overexpression of SlSWI3C increased the leaf size in transgenic Arabidopsis with increased expression of GROWTH REGULATING FACTORs, such as GRF3, GRF5, and GRF6. Taken together, our results indicate that SlSWI3s may play important roles in tomato growth and development.
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Arabidopsis/genética , Expressão Gênica , Fenótipo , Folhas de Planta/anatomia & histologia , Folhas de Planta/genética , Proteínas de Plantas/genética , Solanum lycopersicum/genética , Arabidopsis/metabolismo , Estudos de Associação Genética , Humanos , Solanum lycopersicum/classificação , Filogenia , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Transporte ProteicoRESUMO
BACKGROUND: Associations of dietary patterns in Chinese adolescents and children with later obesity have not previously been investigated. The purpose of the present study was to evaluate the associations between dietary patterns and the risk of obesity in Chinese adolescents and children by using a longitudinal design. METHODS: Data from the China Health and Nutrition Survey (CHNS), a nationally representative survey, were used for our analysis. 489 participants 6-14 years of age were followed from 2006 to 2011. Factor analysis was used to identify the dietary patterns in Chinese adolescents and children. Ordered logistic regression models were used to examine the association between dietary patterns and later obesity. RESULTS: Two dietary patterns were revealed by factor analysis, the traditional Chinese dietary pattern (with high intake of rice, vegetables, poultry, pork and fish and the modern dietary pattern (with high intake of wheat, processed meat and fast food). Children in the highest quartile and the second-highest quartile of the traditional Chinese dietary pattern was inversely associated with later obesity compared with children in the lowest quartile over 5 years (OR = 0.19, 95%CI: 0.09, 0.40 for Q4; OR = 0.47, 95%CI: 0.33, 0.67 for Q3); Children in the highest quartile of the modern dietary pattern was positively associated with later obesity compared with children in the lowest quartile over 5 years (OR = 2.02, 95%CI: 1.17, 3.48). CONCLUSIONS: Dietary patterns in Chinese adolescents and children are associated with later obesity. These findings further confirm the importance of children's dietary patterns in later obesity and lay groundwork for dietary culture-specific interventions targeted at reducing rates of obesity in children and adolescents.
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Dieta , Inquéritos Nutricionais , Obesidade Infantil/epidemiologia , Adolescente , Fenômenos Fisiológicos da Nutrição do Adolescente , Criança , Fenômenos Fisiológicos da Nutrição Infantil , China/epidemiologia , Cultura , Ingestão de Energia , Análise Fatorial , Fast Foods , Humanos , Estudos Longitudinais , Carne , Produtos da Carne , Oryza , Obesidade Infantil/prevenção & controle , Fatores de Risco , Triticum , VerdurasRESUMO
OBJECTIVE: To investigate caregiver type as a potential moderating effect in the relationship between feeding style and weight status among Chinese pre-school children. DESIGN: Cross-sectional data collected with the Caregiver's Feeding Style Questionnaire (CFSQ), anthropometric data, childcare and sociodemographic information. SETTING: Shenyang, China. SUBJECTS: Caregiver-child dyads (n 857). RESULTS: After controlling for confounders, authoritarian feeding style was associated with a 0·30 lower BMI Z-score. Fathers as primary caregivers were related to lower BMI Z-score (ß=-0·66), while grandparents as main caregivers were associated with higher BMI Z-score (ß=0·66) after adjusting for covariates. Mothers buffered the relationship between authoritarian (ß=0·50, 95 % CI 0·04, 0·95) or indulgent (ß=-0·60, 95 % CI -1·06, -0·14) feeding styles and BMI Z-score. Grandparents strengthened the trend that indulgent feeding style was related to higher BMI Z-score (ß=0·54, 95 % CI 0·01, 1·08). CONCLUSIONS: The results of independent and interactive effects of specific feeding styles and caregiver types had different influences on child BMI Z-scores. Longitudinal investigations are needed to evaluate the effect of fathers' and grandparents' feeding on their children's nutrition and weight status.
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Cuidadores/estatística & dados numéricos , Dieta/estatística & dados numéricos , Comportamento Alimentar/fisiologia , Pré-Escolar , China/epidemiologia , Estudos Transversais , Humanos , Modelos Estatísticos , Sobrepeso/epidemiologia , Magreza/epidemiologiaRESUMO
OBJECTIVE: The aim of study was to construct a nomogram to effectively predict the overall survival (OS) and cancer-specific survival (CSS) for patients with vulvar squamous cell carcinoma (VSCC). METHODS: The training cohort consisted of 5405 patients with VSCC, extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. Eighty-four patients with VSCC were selected from the disease database of the Shengjing Hospital of China Medical University from 2014 to 2020, and enrolled as the external validation cohort. Significant independent prognostic factors were identified using Cox regression analysis and used to develop nomograms to predict 1-, 3-, and 5-year OS and CSS in patients with VSCC. RESULTS: The nomogram predicting OS was developed based on tumor size, histological grade, International Federation of Gynecology and Obstetrics (FIGO) stage, regional lymph node involvement, distant metastases, surgery, chemotherapy, age, and race. The nomogram for CSS was constructed using the similar factors, excluding race but including marital status. The nomogram for 1-, 3-, and 5-year OS demonstrated robust performance with receiver operating characteristic curves (AUCs) exceeding 80% (0.86, 0.84, and 0.82), outperforming the FIGO staging alone (0.77, 0.75, and 0.72). Similarly, for CSS, our nomograms achieved larger AUCs of 0.89, 0.88, and 0.86 compared with FIGO staging alone (0.81, 0.79, and 0.78). CONCLUSION: The nomograms more accurately predict prognosis than simple FIGO staging. Moreover, the nomograms developed in this study provide a convenient, operable, and reliable tool for individual assessment and clinical decision-making for patients with VSCC.
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Carcinoma de Células Escamosas , Nomogramas , Programa de SEER , Neoplasias Vulvares , Humanos , Feminino , Neoplasias Vulvares/mortalidade , Neoplasias Vulvares/patologia , Neoplasias Vulvares/terapia , Pessoa de Meia-Idade , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , China/epidemiologia , Idoso , Adulto , Estadiamento de Neoplasias , Prognóstico , Estudos de Coortes , Curva ROC , População do Leste AsiáticoRESUMO
Solid-oxide electrolysis cells are a clean energy conversion device with the ability to directly electrolyze the conversion of CO2 to CO efficiently. However, their practical applications are limited due to insufficient CO2 adsorption performance of the cathode materials. To overcome this issue, the A-site cation deficiency strategy has been applied in a layered perovskite PrBaFe1.6Ni0.4O6-δ (PBFN) cathode for direct CO2 electrolysis. The introduction of 5% deficiency at the Pr/Ba site leads to a significant increase in the concentration of oxygen vacancies (nonstoichiometric number δ of oxygen vacancies increased from 0.093 to 0.132), which greatly accelerates the CO2 adsorption performance as well as the O2- transport capacity toward the CO2 reduction reaction (CO2RR). CO2 temperature-programmed desorption indicates that A-site cation-deficient (PrBa)0.95Fe1.6Ni0.4O6-δ (PB95FN) shows a larger desorption peak area and a higher desorption temperature. PB95FN also exhibits a greater presence of carbonate in Fourier transform infrared (FT-IR) spectroscopy. The electrical conductivity relaxation test shows that the introduction of the 5% A-site deficiency effectively improves the surface oxygen exchange and diffusion kinetics of PB95FN. The current density of the electrolysis cell with the (PrBa)0.95Fe1.6Ni0.4O6-δ (PB95FN) cathode reaches 0.876 A·cm-2 under 1.5 V at 800 °C, which is 41% higher than that of PB100FN. Moreover, the PB95FN cathode demonstrates excellent long-term stability over 100 h and better short-term stability than PB100FN under high voltages, which can be ascribed to the enhanced CO2 adsorption performance. The PB95FN cathode maintains a porous structure and tightly binds to the electrolyte after stability testing. This study highlights the potential of regulating oxygen defects in layered perovskite PrBaFe1.6Ni0.4O6-δ cathode materials via incorporation of cation deficiency toward high-temperature CO2 electrolysis.
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Genetic and physiological studies have revealed evidences for multiple signaling pathways by which the plastid exerts retrograde control over photosynthesis-associated-nuclear-genes. In this study we have examined the mechanisms of control of transcription by plastid signals, focusing on transcription factors. We have also further addressed the physical nature of plastid signals and the physiological role, in stress acclimation of this regulatory pathway. ABI4, a master Apetala 2 (AP2)-type transcription factor (TF), is targeted by multiple signalling pathways in plant cells, such as abscisic acid (ABA) signals, sugar signals and plastid signals derived from reactive oxygen species (ROS) and chlorophyll intermediates. ABI4 binds the promoter of target genes to prevent their transcription by competing with other competitive TFs. However, we found that once ABI4 bound the element (CCACGT), it may not be bound by other TFs, therefore making the signalling long-lasting. Downstream of ABI4, CBFA (CCAAT binding factor A) is a subunit of the HAP2/HAP3/HAP5 (Heme activator protein) trimeric transcription complex. CBFA however is a redundant HAP3 subunit. When emergency occurs (such as herbicide treatments or environmental stresses followed by ABA and ROS accumulation), the master transcription factor ABI4 down-regulates some TFs, like CBFA, and then some other TF subunits enter the transcription complex and transcriptional efficiency of stress-responsive genes (including the transcription co-factor CBP) is improved instantaneously. abi4, cbfA and cbp mutants showed weaker drought-tolerance after a herbicide norflurazon treatment, which indicated the physiological role of these key transcription factors.
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Ácido Abscísico/metabolismo , Arabidopsis/fisiologia , Regulação da Expressão Gênica de Plantas , Reguladores de Crescimento de Plantas/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Adaptação Fisiológica , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Sítios de Ligação , Fator de Ligação a CCAAT/genética , Fator de Ligação a CCAAT/metabolismo , Regulação para Baixo , Secas , Hemina/farmacologia , Herbicidas/farmacologia , Mutagênese Insercional , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Folhas de Planta/fisiologia , Plantas Geneticamente Modificadas , Plastídeos/fisiologia , Regiões Promotoras Genéticas , Piridazinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Plântula/efeitos dos fármacos , Plântula/genética , Plântula/fisiologia , Estresse Fisiológico , Transativadores , Fatores de Transcrição/genéticaRESUMO
Reversible phosphorylation of proteins is a key event in many fundamental cellular processes. Under stressful conditions, many thylakoid membrane proteins in photosynthetic apparatus of higher plants undergo rapid phosphorylation and dephosphorylation in response to environmental changes. CP29 is the most frequently phosphorylated protein among three minor antennae complexes in higher plants. CP29 phosphorylation in dicotyledons has been known for several decades and is well characterized. However, CP29 phosphorylation in monocotyledons is less studied and appears to have a different phosphorylation pattern. In this review, we discuss recent advancements in CP29 phosphorylation and dephosphorylation studies and its physiological significance under environmental stresses in higher plants, especially in the monocotyledonous crops. Physiologically, the phosphorylation of CP29 is likely to be a prerequisite for state transitions and the disassembly of photosystem II supercomplexes, but not involved in non-photochemical quenching (NPQ). CP29 is phosphorylated in monocots exposed to environmental cues, with its subsequent lateral migration from grana stacks to stroma lamellae. However, neither CP29 phosphorylation nor its lateral migration occurs in dicotyledonous plants after drought, cold, or salt stress. Since the molecular mechanisms of differential CP29 phosphorylation under stresses are not fully understood, this review provides insights for future studies regarding the physiological function of CP29 reversible phosphorylation.
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Meio Ambiente , Complexos de Proteínas Captadores de Luz/metabolismo , Complexo de Proteína do Fotossistema II/metabolismo , Plantas/metabolismo , Estresse Fisiológico , Tilacoides/metabolismo , Sequência de Aminoácidos , Complexos de Proteínas Captadores de Luz/química , Dados de Sequência Molecular , Fosforilação , Complexo de Proteína do Fotossistema II/químicaRESUMO
In this work, we have developed a tumor-specific self-accelerating prodrug activation nanosystem consisting of self-amplifying degradable polyprodrug PEG-TA-CA-DOX and encapsulated fluorescent prodrug BCyNH2, equipped with a reactive oxygen species dual-cycle amplification effect. Furthermore, activated CyNH2 is a therapeutic agent with potential to synergistically improve chemotherapy.
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Nanopartículas , Pró-Fármacos , Pró-Fármacos/farmacologia , Espécies Reativas de Oxigênio , Liberação Controlada de Fármacos , Sistemas de Liberação de Medicamentos , Doxorrubicina/farmacologia , Linhagem Celular TumoralRESUMO
In this study, we combined low pH and cathepsin B dual-stimulus-triggered delivery carriers with a bioorthogonal reaction-activated prodrug to achieve regulated activation of the prodrug. A workable method for precise tumor therapy and imaging is provided by the bioorthogonal reaction, which activates the prodrug and fluorescent probe.
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Pró-Fármacos , Pró-Fármacos/uso terapêutico , Corantes Fluorescentes , Imagem Óptica/métodosRESUMO
Tumor-associated enzyme activated prodrug is a potential strategy to overcome the limitations of chemotherapeutic agents. However, the efficiency of enzymatic prodrug activation is limited by the inability to reach adequate enzyme levels in vivo. Herein, we report an intelligent nanoplatform with cyclic amplification of intracellular reactive oxygen species (ROS) that significantly up-regulates the expression of tumor-associated enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1), to efficiently activate the prodrug of doxorubicin (DOX) for enhanced chemo-immunotherapy. The nanoplatform termed as CF@NDOX was fabricated by self-assembly of the amphiphilic cinnamaldehyde (CA) containing poly(thioacetal) conjugated with ferrocene (Fc) and poly(ethylene glycol) (PEG) (TK-CA-Fc-PEG), which further encapsulated the NQO1 responsive prodrug of DOX (NDOX). After CF@NDOX accumulates in tumors, the TK-CA-Fc-PEG with ROS responsive thioacetal group responds to endogenous ROS in tumor to release CA, Fc or NDOX. CA induces mitochondria dysfunction and elevates the intracellular hydrogen peroxide (H2O2) levels, which react with Fc to generate highly oxidative hydroxyl radical (â¢OH) through Fenton reaction. The â¢OH not only promotes ROS cyclic amplification but also increase the expression of NQO1 through Keap1-Nrf2 pathway regulation, which further boost the prodrug activation of NDOX for enhanced chemo-immunotherapy. Overall, our well-designed intelligent nanoplatform provides a tactic to enhance the antitumor efficacy of tumor-associated enzyme activated prodrug. STATEMENT OF SIGNIFICANCE: In this work, a smart nanoplatform CF@NDOX with intracellular ROS cyclic amplification for continuous upregulation of NQO1 enzyme expression was innovatively designed. It could utilize Fenton reaction of Fc to increase the level of NQO1 enzyme and CA to increase the level of intracellular H2O2, thereby facilitating the continuous Fenton reaction. This design allowed for a sustained elevation of the NQO1 enzyme, and a more complete activation of the NQO1 enzyme in response to the prodrug NDOX. This smart nanoplatform can achieve a desirable anti-tumor effect with the combined therapy of chemotherapy and ICD effects.
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Nanopartículas , Neoplasias , Pró-Fármacos , Humanos , Pró-Fármacos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Peróxido de Hidrogênio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Doxorrubicina/farmacologia , Linhagem Celular TumoralRESUMO
This article is concerned with the distributed set-membership fusion estimation problem for a class of artificial neural networks (ANNs), where the dynamic event-triggered mechanism (ETM) is utilized to schedule the signal transmission from sensors to local estimators to save resource consumption and avoid data congestion. The main purpose of this article is to design a distributed set-membership fusion estimation algorithm that ensures the global estimation error resides in a zonotope at each time instant and, meanwhile, the radius of the zonotope is ultimately bounded. By means of the zonotope properties and the linear matrix inequality (LMI) technique, the zonotope restraining the prediction error is first calculated to improve the prediction accuracy and subsequently, the zonotope enclosing the local estimation error is derived to enhance the estimation performance. By taking into account the side-effect of the order reduction technique (utilized in designing the local estimation algorithm) of the zonotope, a sufficient condition is derived to guarantee the ultimate boundedness of the radius of the zonotope that encompasses the local estimation error. Furthermore, parameters of the local estimators are obtained via solutions to certain bilinear matrix inequalities. Moreover, the zonotope-based distributed fusion estimator is obtained through minimizing certain upper bound of the radius of the zonotope (that contains the global estimation error) according to the matrix-weighted fusion rule. Finally, the effectiveness of the proposed distributed fusion estimation method is illustrated via a numerical example.
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Methamphetamine (METH) is a highly addictive psychostimulant. The adipocyte-derived hormone adiponectin has a broad spectrum of functions in the brain. However, limited research has been conducted on the effect of adiponectin signaling on METH-induced conditioned place preference (CPP) and knowledge of the underlying neural mechanisms is scarce. The METH induced adult male C57/BL6J mice model were used for testing the therapeutic activities of intraperitoneal injection of AdipoR agonist AdipoRon and peroxisome proliferator-activated receptor gamma (PPARγ)-selective agonist rosiglitazone, adiponectin receptor 1 (AdipoR1) overexpression in hippocampal dentate gyrus (DG), and chemogenetic inhibiting the neural activity of DG, and the changes of neurotrophic factors, synaptic molecules, glutamate receptors, and inflammatory cytokines were also measured. We found that adiponectin expression was significantly reduced in METH addicted patients and mice. Our findings also showed that injection of AdipoRon or rosiglitazone alleviated the METH-induced CPP behavior. Moreover, the expression of AdipoR1 in the hippocampus was also reduced, and AdipoR1 overexpression blocked the development of METH-induced CPP behavior through regulatory effects on neurotrophic factors, synaptic molecules, and glutamate receptors. The observed inhibitory neural activity of the hippocampal dentate gyrus (DG) induced via a chemogenetic approach produced a therapeutic effect on the METH-induced CPP behavior. Finally, we identified an abnormal expression of some key inflammatory cytokines through the PPARγ/Adiponectin/AdipoR1 axis. This study demonstrates that adiponectin signaling is a promising diagnostic and therapeutic target for METH addiction.
Assuntos
Estimulantes do Sistema Nervoso Central , Metanfetamina , Masculino , Camundongos , Animais , Metanfetamina/farmacologia , PPAR gama/metabolismo , Adiponectina , Rosiglitazona/farmacologia , Rosiglitazona/metabolismo , Estimulantes do Sistema Nervoso Central/farmacologia , Estimulantes do Sistema Nervoso Central/metabolismo , Hipocampo/metabolismo , Transdução de Sinais , Citocinas/metabolismoRESUMO
Surgery and drug therapy are the two principal options for cancer treatment. However, their clinical benefits are hindered by the difficulty of accurate location of the tumors and timely monitoring of the treatment efficacy of drugs, respectively. Rapid development of imaging techniques provides promising tools to address these challenges. Compared with conventional imaging techniques such as magnetic resonance imaging and computed tomography etc., fluorescence imaging exhibits high spatial resolution, real-time imaging capability, and relatively low costs devices. The advancements in fluorescent probes further accelerate the implementation of fluorescence imaging in tumor diagnosis and treatment monitoring. In particular, the emergence of site-specifically activatable fluorescent probes fits the demands of tumor delineation and real-time feedback of the treatment efficacy. A variety of small molecule probes or nanoparticle-based probes have been developed and explored for the above-mentioned applications. This review will discuss recent advances in fluorescent probes with a special focus on activatable nanoprobes and highlight the potential implementation of activatable nanoprobes in fluorescence imaging-guided surgery as well as imaging-guided drug therapy.