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1.
Cent Eur J Public Health ; 32(2): 95-100, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39069312

RESUMO

OBJECTIVES: The current study examined the links and interactions among headaches, screen-based media use, physical activity, sleep, and the family environment in Lithuanian school-aged children during the second COVID-19 lockdown. METHODS: The study comprised data of 541 children aged 7-14 years from different Lithuania regions, and without chronic health conditions or developmental disorders. Information about the child was provided by their parents or caregivers who filled questionnaire on child's screen time, sleep duration and quality, physical activity, parental distress, parent-child relationship, history of child's headaches and infectious diseases. RESULTS: During the study period, 54% of the children had headaches, and the frequency was positively associated with child's age, screen time and parental distress, as well as negatively related to physical activity (PA), sleep quality, and the parent-child relationship. Parental education was related to child's PA, screen time and sleep quality. The results of binary logistic regression analysis and path analysis revealed that sleep quality and parental distress were significant predictors of headaches in children. CONCLUSIONS: Family and child or adolescent education and lifestyle modification aiming to improve sleep hygiene and PA, and to reduce screen-based sedentary behaviour should be provided. Family centred approach for more effective coping with distress and improvement of parent-child relationship is also important in treating child and adolescent headache.


Assuntos
COVID-19 , Exercício Físico , Cefaleia , Tempo de Tela , Humanos , COVID-19/epidemiologia , Criança , Adolescente , Masculino , Feminino , Cefaleia/epidemiologia , Lituânia/epidemiologia , Relações Pais-Filho , SARS-CoV-2 , Inquéritos e Questionários , Pandemias , Quarentena/psicologia
2.
Front Psychol ; 15: 1290935, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39070585

RESUMO

Objectives: This study investigated associations between the use of electronic media and sleep in children and young adolescents, with a specific focus on the moderation of associations by sex and age. Methods: Between 2021 and 2022, 453 10- to 14-year-old children participating in the LIFE Child cohort study (Germany) reported on their use of electronic media (daily screen time, use at bedtime, device ownership) and on their sleep difficulties (Sleep Self Report). Associations between media use and sleep as well as interactions with age and sex were assessed using linear regression analyses. Results: The analyses revealed significant associations between the use of media at bedtime and bedtime problems (in girls only), sleep behavior problems (in girls only), and daytime sleepiness (in girls and boys). Daily screen time, in contrast, was associated with none of the sleep difficulties. The number of media devices owned by the child was only associated with bedtime problems in girls, and this association lost statistical significance once media use at bedtime was included as further predictor. Conclusion: The findings underline the potentially sleep-disturbing role of electronic media at bedtime. Furthermore, they suggest that this effect is more pronounced in girls than in boys.

3.
J Family Med Prim Care ; 13(7): 2761-2766, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39071030

RESUMO

Context: During the "coronavirus disease 2019 (COVID-19)" pandemic, screen time saw a notable increase, ranging from 2.5 to 7.5 hours per day. Scientific evidence has demonstrated a strong correlation between heightened digital media usage and heightened levels of stress, anxiety, and depression. Research indicates that engaging in screen time for four hours or more daily can elevate the likelihood of experiencing symptoms of depression among children and adolescents by 46-80%. Despite this, there remains a paucity of medical evidence elucidating the intricate interplay between screen time, physical inactivity, and insomnia in adults. Aim: The aim of the study was to estimate the prevalence of increased screen time, insomnia, and physical inactivity among adults and their association during the COVID-19 pandemic. Settings and Design: A cross-sectional study through an online Google Form questionnaire was conducted among the Indian population. Methods and Materials: The study was conducted between June and August 2020 and comprised 658 participants aged 18 and above. Participants were recruited using a chain sampling procedure, with the majority being female, accounting for 54% (355 individuals). Statistical Analysis: The mean and standard deviation were calculated for numerical variables, while percentages and proportions were determined for categorical variables. The Chi-square test was employed to examine associations between variables. For assessing the predictors of screen time, a multivariate logistic regression analysis was conducted. Results: The majority of participants reported screen time exceeding 2 hours per day (85%), clinical insomnia symptoms (59%), moderate to high physical activity levels (92.8%), and low levels of sedentary behavior (60.5%). Variables such as gender, age, and screen time demonstrated significant associations with insomnia and physical activity. The odds ratio for insomnia in relation to screen time was 2.84 (95% confidence interval: 1.78-4.58) with a P value of 0.001. Multivariate logistic regression analysis indicated that increasing age was significantly associated with lower levels of screen time. Conclusions: Screen time showed a significant association with insomnia. Less screen time was reported with increased age.

4.
Asian Pac J Cancer Prev ; 25(7): 2439-2444, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39068578

RESUMO

PURPOSE: To evaluate the efficacy of a prostate cancer educational program in enhancing knowledge, beliefs, and screening intentions among Saudi men. METHODS: A quasi-experimental design with a non-equivalent control group was employed. Participants (n=152) were randomly assigned to either the intervention or control group. Assessments of knowledge, beliefs, and screening intentions were conducted at baseline and one-month post-intervention. Independent samples t-tests were used for data analysis. RESULTS: Significant improvements were observed in the intervention group compared to the control group after one month. The mean score for knowledge increased by 7.72 (p = 0.001). Beliefs regarding susceptibility, severity, and benefits of prostate-specific antigen (PSA) and digital rectal examination (DRE) also improved significantly (p < 0.005). Additionally, health motivation and intention to screen increased (p < 0.005).   Conclusion: Prostate cancer educational programs can effectively enhance knowledge, address beliefs, and promote screening intentions among Saudi men. Implementing these programs holds promise for increasing awareness and reducing the burden of prostate cancer through early detection and timely intervention.


Assuntos
Detecção Precoce de Câncer , Conhecimentos, Atitudes e Prática em Saúde , Intenção , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/psicologia , Detecção Precoce de Câncer/psicologia , Pessoa de Meia-Idade , Arábia Saudita , Antígeno Prostático Específico/sangue , Educação em Saúde/métodos , Seguimentos , Prognóstico , Exame Retal Digital/psicologia , Inquéritos e Questionários , Idoso , Educação de Pacientes como Assunto/métodos , Estudos de Casos e Controles , Adulto , Programas de Rastreamento/métodos
5.
Children (Basel) ; 11(7)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-39062204

RESUMO

The role and potential impact of digital screen technology in the lives of children is heavily debated. Current evidence is limited by the weakness of measures typically used to characterise screen use, predominantly proxy- or self-reports with known inaccuracy and bias. However, robust and detailed evidence is needed to provide practical trustworthy guidance to families and professionals working with families. The purpose of this paper is to support researchers to select measurement method(s) that will provide robust and detailed evidence. The paper outlines the challenges in measuring contemporary screen use by children, using a child-technology interaction model to organise considerations. A range of different methods used to measure digital screen technology use in children and adolescents (i.e., questionnaires, diaries, electronically prompted sampling, direct observation, fixed room cameras, wearable/portable cameras, audio recorders, screen-device onboard logging, remote digital trace logging and proximity logging) are described along with examples of their use and constructs typically measured as well as a summary of the advantages and disadvantages of each method. A checklist and worked examples are provided to support researchers determining the best methods or combination of methods for a research project.

6.
Children (Basel) ; 11(7)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-39062244

RESUMO

BACKGROUND: Post-pandemic psychosomatic complaints in children and adolescents have been underreported. This study investigated psychosomatic complaints in children and adolescents in Northern Italy in 2023, with the aim of identifying changes in predictors and vulnerable subgroups. METHODS: Cross-sectional data representative of scholars from a northern Italian province were analyzed using the Health Behavior in School-aged Children (HBSC) checklist. The sum scores, count data, and dichotomized data were examined, and predictor effects were expressed using a linear regression model for the sum scores. RESULTS: Data from 4525 participants (aged 7-19 years, 50.5% girls) were analyzed. Psychosomatic symptoms remained unchanged after the pandemic. Significant gender differences were noted, especially in older age groups, with girls reporting more complaints. Factors such as children's health, digital media use, and school problems significantly influence psychosomatic outcomes. While migration background negatively affected girls' psychosomatic well-being, boys showed improvement through sports. CONCLUSION: The psychosomatic well-being of children and adolescents did not improve after the pandemic. These findings indicate the need for targeted interventions, improved health literacy, and ongoing monitoring to support the mental well-being of this vulnerable population. Reducing screen time remains a critical strategy for enhancing youth well-being.

7.
Children (Basel) ; 11(7)2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39062305

RESUMO

Children who open their eyes to a digital world begin interacting with screens in the early years of life. The interaction between screens and children starts from the very first moments of life and intensifies over time. The aim of this study is to examine the effects of screen use patterns on the life habits of preschool children. In this context, the relationships between problematic media use, eating habits, and self-care skills among preschool children are analyzed from various perspectives. Structured according to a mixed-methods research approach, this study employs both qualitative and quantitative research designs. The study group consists of 582 children continuing their education in preschool institutions across seven different regions and nine different provinces in Turkey, along with 20 of their parents. Random and non-random sampling methods were used to form the study group. Quantitative data were collected using the Problematic Media Use Measure, Children's Eating Behavior Inventory, and Preschool Children (36-72 months) Self-Care Skills Scale-Teacher Form, while qualitative data were gathered through a semi-structured parent interview form. The study results indicate that problematic media use and eating behaviors significantly vary according to the screen time of children, with an increase in problematic media use linked to a rise in negative eating behaviors. Parents are found to perceive the use of media devices during mealtime as a necessity, thus employing them, and believe that their children's social behaviors are shaped according to screen content.

8.
Children (Basel) ; 11(7)2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-39062332

RESUMO

BACKGROUND/OBJECTIVES: Childhood and adolescence are important stages of life for acquiring healthy habits. There is a high prevalence of sedentary lifestyles worldwide during these ages, which negatively impacts health. This is attributed, in part, to excessive time spent engaging in sedentary behaviors. The aim of this study was to assess the time spent on sedentary behaviors and their relationship with physical activity levels in children and adolescents in the Community of Madrid. METHODS: A total of 26,729 participants aged 10-17 from various schools and institutes took part in this study. The International Physical Activity Questionnaire Short Form (IPAQ-SF) was used, and they were asked about the time they spent on different leisure time habits (specific sedentary behaviors and organized physical activity). A generalized linear model was used to analyze the association between the time spent in sedentary activities and the time spent in physical activity. RESULTS: The results revealed that children and adolescents engage in low levels of physical activity and most of them spend considerable time in sedentary behaviors such as studying, watching television, or using social media. Completing school homework (Coef: 1.23, 95% CI: -0.51 to 2.97, p = 0.167) or using social media for more than 2 h (Coef: 1.29, 95% CI: -2.98 to 0.40, p = 0.133) compared to not dedicating time to them did not show a significant association with daily physical activity time. Watching television for more than 2 h was associated with a decrease of 2.60 min (95% CI: -4.41 to -0.78, p = 0.005). Thus, no or only irrelevant associations were found between time spent in sedentary activities and physical activity time. CONCLUSIONS: Despite the drawbacks of spending time engaging in sedentary behaviors, they seem to be compatible with physical activity levels. Therefore, it is important to continue research on physical activity adherence strategies to promote overall health and well-being.

9.
Behav Sci (Basel) ; 14(7)2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39062415

RESUMO

The intricate relationship between physical health and cognitive development has been a focal point of multidisciplinary research, suggesting that motor skill proficiency could influence academic outcomes. This study aimed to investigate the correlation between motor control, mobility, stability-measured by the Functional Movement Screen (FMS)-and academic performance among high school students. Conducted with 201 participants from a public high school in Spain, this descriptive non-experimental research divided students into high and low academic performance groups based on their average grade scores, with the median used as the criterion for distinction. The FMS was utilized to assess fundamental motor skills, and academic performance was verified across mathematics, language, science, and physical education subjects. The findings revealed a significant positive relationship between the FMS scores and academic achievement (r = 0.691; p < 0.001), indicating that students with higher motor skill proficiency had higher academic achievement. This correlation persisted across the various subjects, highlighting the potential benefits of integrating physical education and motor skill development into educational strategies. The study's results suggest that educational policies should advocate for comprehensive physical education programs to foster both physical well-being and academic improvement, thereby promoting a holistic educational model that enhances student performance across disciplines.

10.
Viruses ; 16(7)2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39066332

RESUMO

The African swine fever virus (ASFV) is an often deadly disease in swine and poses a threat to swine livestock and swine producers. With its complex genome containing more than 150 coding regions, developing effective vaccines for this virus remains a challenge due to a lack of basic knowledge about viral protein function and protein-protein interactions between viral proteins and between viral and host proteins. In this work, we identified ASFV-ASFV protein-protein interactions (PPIs) using artificial intelligence-powered protein structure prediction tools. We benchmarked our PPI identification workflow on the Vaccinia virus, a widely studied nucleocytoplasmic large DNA virus, and found that it could identify gold-standard PPIs that have been validated in vitro in a genome-wide computational screening. We applied this workflow to more than 18,000 pairwise combinations of ASFV proteins and were able to identify seventeen novel PPIs, many of which have corroborating experimental or bioinformatic evidence for their protein-protein interactions, further validating their relevance. Two protein-protein interactions, I267L and I8L, I267L__I8L, and B175L and DP79L, B175L__DP79L, are novel PPIs involving viral proteins known to modulate host immune response.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Biologia Computacional , Proteínas Virais , Vírus da Febre Suína Africana/genética , Vírus da Febre Suína Africana/metabolismo , Proteínas Virais/metabolismo , Proteínas Virais/genética , Proteínas Virais/química , Animais , Suínos , Febre Suína Africana/virologia , Febre Suína Africana/metabolismo , Biologia Computacional/métodos , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Interações Hospedeiro-Patógeno , Genoma Viral , Inteligência Artificial
11.
Elife ; 132024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39073063

RESUMO

Activating transcription factor 6 (ATF6) is one of three endoplasmic reticulum (ER) transmembrane stress sensors that mediate the unfolded protein response (UPR). Despite its crucial role in long-term ER stress adaptation, regulation of ATF6 alpha (α) signalling remains poorly understood, possibly because its activation involves ER-to-Golgi and nuclear trafficking. Here, we generated an ATF6α/Inositol-requiring kinase 1 (IRE1) dual UPR reporter CHO-K1 cell line and performed an unbiased genome-wide CRISPR/Cas9 mutagenesis screen to systematically profile genetic factors that specifically contribute to ATF6α signalling in the presence and absence of ER stress. The screen identified both anticipated and new candidate genes that regulate ATF6α activation. Among these, calreticulin (CRT), a key ER luminal chaperone, selectively repressed ATF6α signalling: Cells lacking CRT constitutively activated a BiP::sfGFP ATF6α-dependent reporter, had higher BiP levels and an increased rate of trafficking and processing of ATF6α. Purified CRT interacted with the luminal domain of ATF6α in vitro and the two proteins co-immunoprecipitated from cell lysates. CRT depletion exposed a negative feedback loop implicating ATF6α in repressing IRE1 activity basally and overexpression of CRT reversed this repression. Our findings indicate that CRT, beyond its known role as a chaperone, also serves as an ER repressor of ATF6α to selectively regulate one arm of the UPR.


Assuntos
Fator 6 Ativador da Transcrição , Sistemas CRISPR-Cas , Calreticulina , Cricetulus , Fator 6 Ativador da Transcrição/metabolismo , Fator 6 Ativador da Transcrição/genética , Calreticulina/metabolismo , Calreticulina/genética , Animais , Células CHO , Humanos , Resposta a Proteínas não Dobradas , Estresse do Retículo Endoplasmático/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais
12.
Int J Mol Sci ; 25(14)2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39062856

RESUMO

The 3 Screen ICA ELISA is a novel assay capable of simultaneously measuring autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A), making it a valuable tool for screening type 1 diabetes. Despite its advantages, it cannot specify which individual autoantibodies are positive or negative. This study aimed to estimate individual positive autoantibodies based on the 3 Screen ICA titer. Six hundred seventeen patients with type 1 diabetes, simultaneously measured for 3 Screen ICA and three individual autoantibodies, were divided into five groups based on their 3 Screen ICA titer. The sensitivities and contribution rates of the individual autoantibodies were then examined. The study had a cross-sectional design. Sixty-nine percent (424 of 617) of patients with type 1 diabetes had 3 Screen ICA titers exceeding the 99th percentile cut-off level (20 index). The prevalence of GADA ranged from 80% to 100% in patients with a 3 Screen ICA over 30 index and 97% of patients with a 3 Screen ICA ≥300 index. Furthermore, the prevalence of all individual autoantibodies being positive was 0% for ≤80 index and as high as 92% for ≥300 index. Significant associations were observed in specific titer groups: the 20-29.9 index group when all the individual autoantibodies were negative, the 30-79.9 index group when positive for GADA alone or IA-2A alone, the 30-299.9 index group when positive for ZnT8A alone, the 80-299.9 index group when positive for both IA-2A and ZnT8A, the 300-499.9 index group when positive for both GADA and ZnT8A, and the ≥300 index group when positive for all individual autoantibodies. These results suggest that the 3 Screen ICA titer may be helpful in estimating individual positive autoantibodies.


Assuntos
Autoanticorpos , Diabetes Mellitus Tipo 1 , Glutamato Descarboxilase , Transportador 8 de Zinco , Humanos , Autoanticorpos/sangue , Autoanticorpos/imunologia , Masculino , Feminino , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Adulto , Transportador 8 de Zinco/imunologia , Glutamato Descarboxilase/imunologia , Estudos Transversais , Adolescente , Pessoa de Meia-Idade , Ensaio de Imunoadsorção Enzimática/métodos , Ilhotas Pancreáticas/imunologia , Adulto Jovem , Proteínas Tirosina Fosfatases Classe 8 Semelhantes a Receptores/imunologia , Criança
13.
Artigo em Inglês | MEDLINE | ID: mdl-39063506

RESUMO

The levels of adequacy of movement behaviors after returning to in-person school activities following the COVID-19 pandemic are not yet well understood. This study aimed to assess the adherence of Brazilian minors to the recommendations of the 24-Hour Movement Guidelines (moderate to vigorous physical activity, recreational screen time, and sleep duration), as well as overall adherence to these guidelines, after the relaxation of COVID-19 social isolation measures and the resumption of in-person schooling. A cross-sectional study was conducted with parents or guardians (39 ± 7.8) of minors aged up to 18 years of age (3.8 ± 2.5). A total of 172 individuals responded to the questionnaire. Data were compared with those obtained in the Survey of the Adequacy of Brazilian Children and Adolescents to the 24-Hour Movement Guidelines before and during the COVID-19 Pandemic. There was an 18.6 percentage decrease (p-value < 0.001) in overall adherence to the 24-Hour Movement Guidelines when comparing the periods before the COVID-19 pandemic (March 2020) and after the return to in-person schooling (March 2021). The largest percentage drop in adherence between these periods was observed for moderate to vigorous physical activity (27.4%; p-value < 0.001) and the lowest for sleep (10.5%; p-value < 0.001). Adherence to the 24-Hour Movement Guidelines did not return to pre-pandemic levels with the resumption of in-person school activities.


Assuntos
COVID-19 , Exercício Físico , Humanos , Brasil , Adolescente , Estudos Transversais , Masculino , Feminino , Criança , Sono , Fidelidade a Diretrizes/estatística & dados numéricos , Retorno à Escola , Instituições Acadêmicas , SARS-CoV-2 , Inquéritos e Questionários , Tempo de Tela
14.
Artigo em Inglês | MEDLINE | ID: mdl-39063509

RESUMO

BACKGROUND: The exacerbation of psychosocial problems among children and adolescents during the coronavirus disease 2019 (COVID-19) pandemic necessitates an assessment of the long-term mental health impact of pandemic interventions. Focusing on both pandemic-related factors and demographic variables, such as gender and daily habits, an analysis was conducted to understand how these elements continue to affect young populations in the post-pandemic era. METHODS: In April 2023, a comprehensive online survey was administered to families in South Tyrol, Italy, with children aged 7-19 years, to ensure age and gender representation. The survey included parent ratings and adolescent (11-19 years) self-reports using standardized instruments to measure the symptoms of mental health problems (Strengths and Difficulties Questionnaire, SDQ), anxiety (Screen for Child Anxiety Related Emotional Disorders, SCARED), and depression (Patient Health Questionnaire-2, PHQ-2). Statistical analyses included descriptive statistics, chi-square tests, and unadjusted odds ratios (ORs). RESULTS: Of the 4525 valid responses, 1831 were self-reported by adolescents. Notable gender differences in mental health outcomes were identified, along with significant demographic predictors, such as age, single parenthood, parental mental health problems, and immigrant background. Negative effects were associated with reduced family climate and increased screen time, whereas physical activity showed beneficial effects. Proxy reports overestimated adolescents' mental health problems, whereas self-reports tended to underestimate them. CONCLUSIONS: Persistent mental health problems and gender disparities highlight the need for a public health approach. This should include accessible support services, resilience building, targeted support for vulnerable families and gender-specific interventions.


Assuntos
COVID-19 , Estilo de Vida , Saúde Mental , Pais , Humanos , Adolescente , Itália/epidemiologia , Feminino , Masculino , Criança , COVID-19/psicologia , COVID-19/epidemiologia , Estudos Transversais , Pais/psicologia , Fatores Sexuais , Adulto Jovem , Inquéritos e Questionários , Transtornos Mentais/epidemiologia , Transtornos Mentais/psicologia , SARS-CoV-2
15.
Molecules ; 29(14)2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39064905

RESUMO

The development of temperature-sensitive sensors upgraded by poly(N-isopropylacrylamide) (PNIPAM) represents a significant stride in enhancing performance and tailoring thermoresponsiveness. In this study, an array of temperature-responsive electrochemical sensors modified with different PNIPAM-based copolymer films were fabricated via a "coating and grafting" two-step film-forming technique on screen-printed platinum electrodes (SPPEs). Chemical composition, grafting density, equilibrium swelling, surface wettability, surface morphology, amperometric response, cyclic voltammograms, and other properties were evaluated for the modified SPPEs, successively. The modified SPPEs exhibited significant changes in their properties depending on the preparation concentrations, but all the resulting sensors showed excellent stability and repeatability. The modified sensors demonstrated favorable sensitivity to hydrogen peroxide and L-ascorbic acid. Furthermore, notable temperature-induced variations in electrical signals were observed as the electrodes were subjected to temperature fluctuations above and below the lower critical solution temperature (LCST). The ability to reversibly respond to temperature variations, coupled with the tunability of PNIPAM's thermoresponsive properties, opens up new possibilities for the design of sensors that can adapt to changing environments and optimize their performance accordingly.

16.
Sensors (Basel) ; 24(14)2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39065899

RESUMO

The progressive increase in nitrate's (NO3-) presence in surface and groundwater enhances environmental and human health risks. The aim of this work is the fabrication and characterization of sensitive, real-time, low-cost, and portable amperometric sensors for low NO3- concentration detection in water. Copper (Cu) micro-flowers were electrodeposited on top of carbon screen-printed electrodes (SPCEs) via cyclic voltammetry (with voltage ranging from -1.0 V to 0.0 V at a scan rate of 0.1 V s-1). The obtained sensors exhibited a high catalytic activity toward the electro-reduction in NO3-, with a sensitivity of 44.71 µA/mM. They had a limit of detection of 0.87 µM and a good dynamic linear concentration range from 0.05 to 3 mM. The results were compared to spectrophotometric analysis. In addition, the devices exhibited good stability and a maximum standard deviation (RSD) of 5% after ten measurements; reproducibility, with a maximum RSD of 4%; and repeatability after 10 measurements with the RSD at only 5.63%.

17.
Biomimetics (Basel) ; 9(7)2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39056867

RESUMO

Sensitivity in the sub-nanomolar concentration region is required to determine important protein biomarkers, e.g., ferritin. As a prerequisite for high sensitivity, in this paper, the affinity of the functional monomer to the macromolecular target ferritin in solution was compared with the value for the respective molecularly imprinted polymer (MIP)-based electrodes, and the influence of various surface modifications of the electrode was investigated. The analytical performance of ferritin sensing was investigated using three different carbon electrodes (screen-printed carbon electrodes, single-walled-carbon-nanotube-modified screen-printed carbon electrodes, and glassy carbon electrodes) covered with a scopoletin-based MIP layer. Regardless of the electrode type, the template molecule ferritin was mixed with the functional monomer scopoletin, and electropolymerization was conducted using multistep amperometry. All stages of MIP preparation were followed by evaluating the diffusional permeability of the redox marker ferricyanide/ferrocyanide through the polymer layer by differential pulse voltammetry. The best results were obtained with glassy carbon electrodes. The MIP sensor responded up to 0.5 µM linearly with a Kd of 0.30 µM. Similar results were also obtained in solution upon the interaction of scopoletin and ferritin using fluorescence spectroscopy, resulting in the quenching of the scopoletin signal, with a calculated Kd of 0.81 µM. Moreover, the binding of 1 µM ferritin led to 49.6% suppression, whereas human serum albumin caused 8.6% suppression.

18.
J Fungi (Basel) ; 10(7)2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39057376

RESUMO

Mercury (Hg) is a global pollutant and a bioaccumulative toxin that seriously affects the environment. Though increasing information has been obtained on the mechanisms involved in mercury toxicity, there is still a knowledge gap between the adverse effects and action mechanisms, especially at the molecular level. In the current study, we screened a diploid library of Saccharomyces cerevisiae single-gene deletion mutants to identify the nonessential genes associated with increased sensitivity to mercury ions. By genome-scale screening, we identified 64 yeast single-gene deletion mutants. These genes are involved in metabolism, transcription, antioxidant activity, cellular transport, transport facilitation, transport routes, and the cell cycle, as well as in protein synthesis, folding, modification, and protein destination. The concentration of mercury ions was different in the cells of yeast deletion mutants. Moreover, the disruption of antioxidant systems may play a key role in the mercurial toxic effects. The related functions of sensitive genes and signal pathways were further analyzed using bioinformatics-related technologies. Among 64 sensitive genes, 37 genes have human homologous analogs. Our results may provide a meaningful reference for understanding the action mode, cellular detoxification, and molecular regulation mechanisms of mercury toxicity.

19.
Bioorg Med Chem Lett ; 110: 129865, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38950758

RESUMO

Pyruvate kinase (PK) is an essential component of cellular metabolism, converting ADP and phosphoenolpyruvate (PEP) to pyruvate in the final step of glycolysis. Of the four unique isoforms of pyruvate kinase, R (PKR) is expressed exclusively in red blood cells and is a tetrameric enzyme that depends on fructose-1,6-bisphosphate (FBP) for activation. PKR deficiency leads to hemolysis of red blood cells resulting in anemia. Activation of PKR in both sickle cell disease and beta-thalassemia patients could lead to improved red blood cell fitness and survival. The discovery of a novel series of substituted urea PKR activators, via the serendipitous identification and diligent characterization of a minor impurity in an High Throughput Screening (HTS) hit will be discussed.


Assuntos
Ensaios de Triagem em Larga Escala , Piruvato Quinase , Piruvato Quinase/metabolismo , Piruvato Quinase/antagonistas & inibidores , Humanos , Descoberta de Drogas , Relação Estrutura-Atividade , Ureia/química , Ureia/farmacologia , Ativadores de Enzimas/farmacologia , Ativadores de Enzimas/química , Ativadores de Enzimas/síntese química , Estrutura Molecular , Animais
20.
Mol Cell ; 84(14): 2634-2647.e9, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38964321

RESUMO

DNA repair is directly performed by hundreds of core factors and indirectly regulated by thousands of others. We massively expanded a CRISPR inhibition and Cas9-editing screening system to discover factors indirectly modulating homology-directed repair (HDR) in the context of ∼18,000 individual gene knockdowns. We focused on CCAR1, a poorly understood gene that we found the depletion of reduced both HDR and interstrand crosslink repair, phenocopying the loss of the Fanconi anemia pathway. CCAR1 loss abrogated FANCA protein without substantial reduction in the level of its mRNA or that of other FA genes. We instead found that CCAR1 prevents inclusion of a poison exon in FANCA. Transcriptomic analysis revealed that the CCAR1 splicing modulatory activity is not limited to FANCA, and it instead regulates widespread changes in alternative splicing that would damage coding sequences in mouse and human cells. CCAR1 therefore has an unanticipated function as a splicing fidelity factor.


Assuntos
Processamento Alternativo , Proteína do Grupo de Complementação A da Anemia de Fanconi , Humanos , Animais , Camundongos , Proteína do Grupo de Complementação A da Anemia de Fanconi/genética , Proteína do Grupo de Complementação A da Anemia de Fanconi/metabolismo , Reparo de DNA por Recombinação , Anemia de Fanconi/genética , Anemia de Fanconi/metabolismo , Células HEK293 , Éxons , Sistemas CRISPR-Cas , Reparo do DNA , Células HeLa , Dano ao DNA
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