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1.
Chaos ; 34(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38717416

RESUMO

Mixed-mode oscillations (MMOs) are complex oscillatory behaviors of multiple-timescale dynamical systems in which there is an alternation of large-amplitude and small-amplitude oscillations. It is well known that MMOs in two-timescale systems can arise either from a canard mechanism associated with folded node singularities or a delayed Andronov-Hopf bifurcation (DHB) of the fast subsystem. While MMOs in two-timescale systems have been extensively studied, less is known regarding MMOs emerging in three-timescale systems. In this work, we examine the mechanisms of MMOs in coupled Morris-Lecar neurons with three distinct timescales. We investigate two kinds of MMOs occurring in the presence of a singularity known as canard-delayed-Hopf (CDH) and in cases where CDH is absent. In both cases, we examine how features and mechanisms of MMOs vary with respect to variations in timescales. Our analysis reveals that MMOs supported by CDH demonstrate significantly stronger robustness than those in its absence. Moreover, we show that the mere presence of CDH does not guarantee the occurrence of MMOs. This work yields important insights into conditions under which the two separate mechanisms in two-timescale context, canard and DHB, can interact in a three-timescale setting and produce more robust MMOs, particularly against timescale variations.

2.
Public Health ; 227: 250-258, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38262230

RESUMO

OBJECTIVES: Rapid internet penetration and technological advancements have facilitated accessibility to internet-enabled devices globally. Since Asia lacks comprehensive data on internet addiction among college students, this review aims to estimate its pooled prevalence. STUDY DESIGN: This was a systematic review and meta-analysis. METHODS: Searches were conducted in PubMed, Scopus, CINAHL, and MEDLINE from their inception through August 2022 using terms appropriate to internet addiction and Asian countries/territorial for publications in English peer-reviewed journals. The studies included those done on current college students and provided unambiguous indicators of the threshold of internet addiction. The pooled prevalence was calculated through a random-effects meta-analysis by RStudio software, and I2 statistic was used to assess heterogeneity. The Joanna Briggs Institute critical appraisal checklist was used for quality assessment. RESULTS: Overall, between 2007 and 2021, 39 papers comprising 45 effect sizes and totaling 58,058 participants met the inclusion criteria. The pooled prevalence of internet addiction among Asian college students was 24.3% (95% confidence interval: 19.8%-29.5%, Q = 6234, df = 44, τ2 = 0.79, I2 = 99.29%), and strikingly, this percentage increased over time. A high degree of heterogeneity was seen, and no publication bias was found. CONCLUSIONS: To our knowledge, this is the first comprehensive review report on Asian college students, which found that one-fifth suffer from internet addiction. The findings emphasize the significance of multidisciplinary prevention and management strategies to mitigate the harmful effects of internet addiction. Further research is warranted to develop a standardized diagnostic tool for a more precise estimation of internet addiction among this population.


Assuntos
Comportamento Aditivo , Transtorno de Adição à Internet , Humanos , Prevalência , Comportamento Aditivo/epidemiologia , Estudantes , Ásia , Internet
3.
Ann Ig ; 36(3): 335-352, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38085560

RESUMO

Background: Vaccination plays a central role in protecting children against severe diseases and preventing child mortality. Objectives: This study aimed to determine the rate and factors associated with complete and timely vaccination in 2-year-old children, as well as maternal knowledge on expanded vaccination in Go Cong Tay district, Tien Giang province, Vietnam. Methods: A cross-sectional descriptive study was conducted on 558 2-year-old children and their mothers residing in Go Cong Tay district, Tien Giang province, Vietnam. The study employed a systematic random sampling method from June to September 2021. Results: The rate of complete vaccination in children was 74.7%. Factors associated with the rate of complete vaccination were occupation (OR=0.3; 95%CI: 0.1-0.7; p=0.006), economic status (OR=3.8; 95%CI: 1.7-8.6; p=0.001), and maternal general knowledge on expanded vaccination (OR=1.7; 95%CI: 1.1-2.6; p=0.01). The rate of timely vaccination was 47.8%. Factors associated with the rate of timely vaccination were maternal age group (OR=3.1; 95%CI: 1.6-6.0; p=0.001; OR=3.0; 95%CI: 1.3-6.6; p=0.006) and economic status (OR=0.4; 95%CI: 0.2-0.9; p=0.04). The rate of both complete and timely vaccination was 22.6%. Factors associated with the rate of complete and timely vaccination were maternal age group (OR=3.1; 95%CI: 1.3-7.2; p=0.009; OR=3.3; 95%CI: 1.2-9.1; p=0.02) and maternal general knowledge on expanded vaccination (OR=1.5; 95%CI: 1.0-2.4; p=0.03). The rate of maternal general knowledge on expanded vaccination was 57.5%. Conclusion: The rates of complete and timely vaccination are still low, and various factors influence expanded vaccination. The-refore, it is crucial to continue health education campaigns to improve knowledge on expanded vaccination, remind mothers of vaccination schedules, strengthen confidence in vaccination programs and vaccine safety, attract customers to vaccination services, provide adequate healthcare for children, and ensure vaccination activities during disease outbreaks.

4.
Cancer Invest ; : 1-17, 2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36719061

RESUMO

The SPOT-MAS assay "Screening for the Presence Of Tumor by Methylation And Size" detects the five most common cancers in Vietnam by evaluating circulating tumor DNA in the blood. Here, we validated its performance in a prospective multi-center clinical trial, K-DETEK. Our analysis of 2795 participants from 14 sites across Vietnam demonstrates its ability to detect cancers in asymptomatic individuals with a positive predictive value of 60%, with 83.3% accuracy in detecting tumor location. We present a case report to support further using SPOT-MAS as a complementary method to achieve early cancer detection and provide the opportunity for early treatment.

5.
Lett Appl Microbiol ; 76(1)2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36688780

RESUMO

Cronobacter sakazakii is an opportunistic foodborne pathogen in powdered infant formula (PIF) associated with several foodborne outbreaks. Biofilms of C. sakazakii in the PIF manufacturing plant may be a source of contamination, but information on the treatment of these biofilms is limited. This study investigated the inactivation of C. sakazakii biofilms on three food contact surfaces (stainless steel, silicone, and PVC) using high voltage atmospheric cold plasma (HVACP) applied as a dielectric barrier discharge in a 10:90 air: helium modified atmosphere. After the 90 s  of cold plasma exposure at 40 kV, C. sakazakii was reduced by ∼3 log CFU/coupon comparing to without cold plasma treatments. HVACP treatment caused cell shrinkage, fragmentation of the cell membrane, and leakage of cytoplasm. The inactivation of the cells on the surface was confirmed by live/dead staining. These above-mentioned results indicate the antibiofilm efficacy of HVACP on C. sakazakii isolates on various food contact surfaces.


Assuntos
Cronobacter sakazakii , Cronobacter , Gases em Plasma , Humanos , Lactente , Microbiologia de Alimentos , Biofilmes , Fórmulas Infantis
6.
Sensors (Basel) ; 23(21)2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37960447

RESUMO

Artificial intelligence (AI) radar technology offers several advantages over other technologies, including low cost, privacy assurance, high accuracy, and environmental resilience. One challenge faced by AI radar technology is the high cost of equipment and the lack of radar datasets for deep-learning model training. Moreover, conventional radar signal processing methods have the obstacles of poor resolution or complex computation. Therefore, this paper discusses an innovative approach in the integration of radar technology and machine learning for effective surveillance systems that can surpass the aforementioned limitations. This approach is detailed into three steps: signal acquisition, signal processing, and feature-based classification. A hardware prototype of the signal acquisition circuitry was designed for a Continuous Wave (CW) K-24 GHz frequency band radar sensor. The collected radar motion data was categorized into non-human motion, human walking, and human walking without arm swing. Three signal processing techniques, namely short-time Fourier transform (STFT), mel spectrogram, and mel frequency cepstral coefficients (MFCCs), were employed. The latter two are typically used for audio processing, but in this study, they were proposed to obtain micro-Doppler spectrograms for all motion data. The obtained micro-Doppler spectrograms were then fed to a simplified 2D convolutional neural networks (CNNs) architecture for feature extraction and classification. Additionally, artificial neural networks (ANNs) and 1D CNN models were implemented for comparative analysis on various aspects. The experimental results demonstrated that the 2D CNN model trained on the MFCC feature outperformed the other two methods. The accuracy rate of the object classification models trained on micro-Doppler features was 97.93%, indicating the effectiveness of the proposed approach.


Assuntos
Inteligência Artificial , Radar , Humanos , Processamento de Sinais Assistido por Computador , Caminhada , Análise de Fourier
7.
Nutr Health ; 29(3): 443-452, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36285514

RESUMO

BACKGROUND: Chronic noncommunicable diseases (NCDs) associated with excess weight as a significant risk factor, but few studies have been sufficient enough to examine the magnitude of excess weight of Vietnamese adults. This review aimed to provide a generalized estimate of the prevalence of excess weight among Vietnamese adults. METHODS: PubMed, Scopus and national database were used to identify articles published up to May 2022. The Newcastle-Ottawa Quality Assessment Scale was used to rate the study quality. The data was analyzed using RStudio software, and the combined effects were estimated using random-effects meta-analysis. The Cochran's Q-test and the I2 test were employed to examine heterogeneity, and subgroups were conducted. Egger's test and visual inspection of the symmetry in funnel plots were used to determine publication bias. RESULTS: 58 studies with 432,585 participants from 1998 to 2020 were suitable for inclusion in the final model after meeting the prerequisites. Over the last three decades, the combined pooled prevalence of excess weight among adults in Vietnam was 20.3% (95% CI: 15.2-26.6). Notably, this proportion has a tendency to go up between 1998 and 2020. Moreover, rates of excess weight were found to be substantially higher in non-national studies (23.1%, 17.3-30.1) compared to national studies (8.4%, 3.6-18.3) and significantly higher when Asian and Pacific cut-offs (27.6%, 20.0-36.7) were used rather than WHO classification (11.2%, 6.7-18.0). CONCLUSION: The findings suggest healthcare professionals and policymakers should focus more on designing and implementing preventive initiatives to lower the rising prevalence of excess weight adults in Vietnam.


Assuntos
Sobrepeso , População do Sudeste Asiático , Adulto , Humanos , Prevalência , Fatores de Risco , Vietnã/epidemiologia , Sobrepeso/epidemiologia
8.
Nutr Health ; : 2601060231152278, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36706790

RESUMO

Background: Atypical eating behaviors and feeding issues are common in children with autism spectrum disorder (ASD). Aim: This study aims to evaluate the nutritional status and eating behavior of the ASD and typically developing groups. Methods: A case-control study was conducted from January to April 2019 in Nghe An, Vietnam. A total of 93 children in each group participated in the study with their main caregivers. We applied the Children's Eating Behavior Inventory (CEBI) to evaluate the eating behaviors of children. Results: Overweight and obesity in ASD children accounted for 41.9%. The CEBI score and %CEBI of the ASD group was higher than that of the control group (104.0 ± 14.2 and 91.3 ± 8.3; 24.1 ± 21.4 and 5.0 ± 11.8, respectively). Most of the adverse mealtime behaviors of ASD children focused on excessive duration (52.7%), distraction (40.9%), and food refusal (39.8%). In total 88.2% of caregivers had to comfort their ASD children at every meal, followed by threatening, scolding, or punishing children if they refused to eat (57.0%). Conclusion: Being overweight/obese and having eating behavior difficulties were prevalent among ASD children in Vietnam. Safer alternatives, such as lifestyle measures and seeking help from a nutritional therapist, can help ASD children reduce weight and modify their erroneous feeding habits.

9.
J Environ Sci (China) ; 124: 379-396, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36182147

RESUMO

Wastewater containing an azo dye Orange G (OG) causes massive environmental pollution, thus it is critical to develop a highly effective, environmental-friendly, and reusable catalyst in peroxymonosulfate (PMS) activation for OG degradation. In this work, we successfully applied a magnetic MnFe2O4/α-MnO2 hybrid fabricated by a simple hydrothermal method for OG removal in water. The characteristics of the hybrid were investigated by X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller method, vibrating sample magnetometry, electron paramagnetic resonance, thermogravimetric analysis, and X-ray photoelectron spectroscopy. The effects of operational parameters (i.e., catalytic system, catalytic dose, solution pH, and temperature) were investigated. The results exhibited that 96.8% of OG degradation was obtained with MnFe2O4/α-MnO2(1:9)/PMS system in 30 min regardless of solution pH changes. Furthermore, the possible reaction mechanism of the coupling system was proposed, and the degradation intermediates of OG were identified by mass spectroscopy. The radical quenching experiments and EPR tests demonstrated that SO4•̶, O2•̶, and 1O2 were the primary reactive oxygen species responsible for the OG degradation. The hybrid also displayed unusual stability with less than 30% loss in the OG removal after four sequential cycles. Overall, magnetic MnFe2O4/α-MnO2 hybrid could be used as a high potential activator of PMS to remove orange G and maybe other dyes from wastewater.


Assuntos
Compostos de Manganês , Águas Residuárias , Compostos Azo/química , Corantes , Fenômenos Magnéticos , Compostos de Manganês/química , Óxidos , Peróxidos/química , Espécies Reativas de Oxigênio , Água
10.
Phys Chem Chem Phys ; 24(10): 6053-6063, 2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35212351

RESUMO

A wide range of harmonics especially continuum harmonics is a prerequisite for attosecond pulse generation. One can use longer-wavelength lasers to push the cutoff to a higher order. However, this does not translate to the same amount of continuum range extension because multiple rescattering phenomena are also enhanced in the process, potentially affecting the lower end of the continuum harmonics. It is then important to understand exactly how multiple rescatterings affect the harmonic structure and their response to various laser parameters, which is the main theme of this paper. Particularly, by applying the synchrosqueezed time-frequency transform and classical electron trajectory analysis to the asymmetric molecule carbon monoxide (CO), we justify that the multiple rescatterings indeed influence the periodicity of the harmonic spectra and the stable periodicity is, in fact, bounded by the first- and third-order returns. Moreover, for the first time, we find that the high-order rescatterings are asymmetric regarding the molecular rotation of 180°, but always correlate with the first-order returns. Our last result is that by breaking the laser symmetry in an appropriate way, the contribution of multiple rescatterings is removed so that the continuum region is entirely defined by the first-order return energies.

11.
Early Child Res Q ; 60: 307-318, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35340352

RESUMO

This study utilized a nationally distributed survey to explore early childhood teachers' experience of providing remote learning to young children and their families during the early months of the U.S. response to the COVID-19 pandemic. A convergent parallel mixed-methods design was used to analyze 805 participants' responses to closed and open-ended survey questions. Results indicated that teachers provided various remote learning activities and spent more time planning instruction and communicating with families than providing instruction directly to children. Early childhood teachers reported several positive aspects of remote learning and various challenges during the initial months of the pandemic. Study findings are discussed in the context of policy and practical implications for supporting early childhood teachers to deliver high-quality and developmentally appropriate remote learning for all young children and their families.

12.
Hum Mutat ; 42(10): 1229-1238, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34233069

RESUMO

Accurate profiling of population-specific recessive diseases is essential for the design of cost-effective carrier screening programs. However, minority populations and ethnic groups, including Vietnamese, are still underrepresented in existing genetic studies. Here, we reported the first comprehensive study of recessive diseases in the Vietnamese population. Clinical exome sequencing data of 4503 disease-associated genes obtained from a cohort of 985 Vietnamese individuals was analyzed to identify pathogenic variants, associated diseases and their carrier frequencies in the population. A total of 118 recessive diseases associated with 164 pathogenic or likely pathogenic variants were identified, among which 28 diseases had carrier frequencies of at least 1% (1 in 100 individuals). Three diseases were prevalent in the Vietnamese population with carrier frequencies of 2-12 times higher than in the world populations, including beta-thalassemia (1 in 23), citrin deficiency (1 in 31), and phenylketonuria (1 in 40). Seven novel pathogenic and two likely pathogenic variants associated with nine recessive diseases were discovered. The comprehensive profile of recessive diseases identified in this study enables the design of cost-effective carrier screening programs specific to the Vietnamese population.


Assuntos
Etnicidade , Exoma , Povo Asiático , Estudos de Coortes , Exoma/genética , Humanos , Sequenciamento do Exoma
13.
Nanotechnology ; 32(16): 16LT01, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33455951

RESUMO

In this study, oxygenated graphene nanosheets (OGNs) were successfully synthesized using a simple electrochemical exfoliation approach and applied to remove methylene blue (MB) in an aqueous solution. The surface morphology and structure of the OGNs were characterized by scanning electron microscopy, transmission electron microscopy, Raman, and x-ray photoelectron spectroscopy. The adsorption performance of OGNs towards aqueous MB was tested by batch experiments. Results showed that a large number of functional groups in OGNs enhanced the removal of MB from the aqueous solution due to the electrostatic interactions between the electrochemically oxygenated groups (e.g. C-OH, C-O, and C=O) and dye molecules. Using Langmuir adsorption isotherm, the maximum MB adsorption capacity (q max) was determined as high as 476.19 mg g-1. These results suggested that the as-prepared OGNs is an effective and promising adsorbent for removing MB, which could be studied extensively for color removal in wastewater treatment.

14.
J Phys Chem A ; 125(7): 1476-1489, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33570408

RESUMO

The effects of vibrational motions on dynamic Stark-induced π-electron rotations in a low-symmetry aromatic ring molecule are theoretically studied in the adiabatic approximation. We adopt a simplified three-electronic state model with a few vibronic states. A pair of the lowest vibronic states in two electronic excited states is set degenerate by irradiation of two linearly polarized UV lasers. The resultant degenerate state is named the dynamic Stark-induced degenerate vibronic state (DSIDVS). The laser parameters (intensities and central frequencies) are determined under the conditions of DSIDVS formation. The aromatic ring molecules of interest are supposed to belong to the weak coupling case. The analytical expressions for the DSIDVS and coherent angular momentum LZ(t) are derived in the displaced harmonic oscillator (DHO) model. Two horizontal potential displacements (δα, δß) between the two electronic excited states (α and ß) and the ground state are the parameters in the DHO model. The LZ(t) calculated with δα = 뫧 is characterized by a regular sequence of the angular momentum pulses with a positive (or negative) constant. For a more general case with δα ≠ δß, the regular sequence is broken down because of the contribution of the first excited vibronic state in each electronic state to LZ(t).

15.
Telemed J E Health ; 27(4): 448-453, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32673154

RESUMO

Purpose: Viet Nam currently relies on a manual paper-based system to track and monitor 28 major infectious diseases. This inefficient system takes 2 or more months to complete. Method: We designed and pilot tested the use of text messaging to report certain infectious disease symptoms in rural areas of northern Viet Nam. The project was divided into three 6-month phases carried out in two provinces. The current analysis focuses on the implementation of a two-way feedback system between Phases II and III, which aims at (1) evaluating whether this system improves efficiency by determining the number of correctly (vs. incorrectly) formatted text messages; (2) assessing this system's influence on accuracy by comparing text messages with their respective official paper-based documented forms; and (3) determining whether the amount of information required to report through text messages influences the efficiency and accuracy of the text messages. Results: Between Phases II and III, results revealed a significant improvement in correctly formatted texts in comparison to incorrectly formatted texts. As the number of fields required to report increased, the number of correctly formatted texts (efficiency) as well as the number of matched text messages (accuracy) decreased. Conclusion: Our research demonstrates that an automated error bidirectional feedback system can significantly improve both the efficiency and accuracy of a Short Message Service-based method for disease surveillance. Also, our data may suggest that two-way communication has better engaged health care staff to follow reporting protocols as well as to maintain accuracy from their clinic's own data.


Assuntos
Envio de Mensagens de Texto , Atenção à Saúde , Retroalimentação , Humanos , Monitorização Fisiológica , Vietnã
16.
Nanotechnology ; 31(34): 345401, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32365336

RESUMO

In this work, a feasible one-pot approach to synthesize manganese oxide/graphene composites, the so-called plasma-enhanced electrochemical exfoliation process (PE3P), has been developed. Herein, a composite of graphene decorated with manganese oxide nanoparticles was prepared via PE3P from a KMnO4 solution and graphite electrode under a voltage of 70 V in an ambient environment. By controlling the initial KMnO4 concentration, we obtained distinct MnO2/graphene samples. The prepared samples were characterized by scanning electron microscopy, transmission electron microscopy, x-ray diffraction, x-ray photoelectron spectroscopy, and Raman spectroscopy. The electrochemical measurements of the MnO2/graphene composites revealed that the specific capacitance of the samples is approximately 320 F g-1 at a scan rate of 10 mV s-1, which is comparably very high for manganese oxide/carbon-based supercapacitor electrode materials. Considering the simple, low-cost, one-step and environmentally friendly preparation, our approach has the potential to be used for the fabrication of MnO2/graphene composites as the electrode materials of supercapacitors.

17.
Pediatr Blood Cancer ; 66(1): e27460, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30255556

RESUMO

BACKGROUND: Fanconi anemia is an inherited bone marrow failure disorder associated with a high incidence of leukemia and solid tumors. Currently, no interventions to prevent or delay the formation of solid tumors are available. PROCEDURE: Two of the most important hallmarks of Fanconi anemia are inflammation and oxidative stress. In this study, we administrated the antioxidant atorvastatin and the anti-inflammatory drug celecoxib to cohorts of Fancd2-/- /Trp53+/- mice, a model of Fanconi anemia. Treatment started at weaning and continued until the mice developed a palpable mass or suffered from >20% weight loss. Tumor samples and selected tissues were subjected to histopathological examination. χ2 test was performed to analyze tumor incidence, and Kaplan-Meier survival curves were evaluated with log-rank test. In addition, a small cohort of mice was monitored for the safety of the drugs. RESULTS: The combined oral administration of both drugs significantly delayed tumor onset in Fancd2-/- /Trp53+/- mice. Specifically, the treatment delayed the onset of ovarian tumors in Fancd2-/- /Trp53+/- mice and increased the mean ovarian tumor-free survival time by 17%, whereas this combinatorial drug regimen did not have a significant effect on other tumor types. In addition, no detrimental effects on hematopoiesis from the drug treatment were observed during a 12-month safety monitoring. CONCLUSIONS: The data presented here suggest that a combination of atorvastatin and celecoxib may be a good candidate for chemoprevention in Fanconi anemia.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Modelos Animais de Doenças , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/fisiologia , Anemia de Fanconi/tratamento farmacológico , Proteína Supressora de Tumor p53/fisiologia , Animais , Atorvastatina/administração & dosagem , Celecoxib/administração & dosagem , Anemia de Fanconi/patologia , Feminino , Masculino , Camundongos , Camundongos Knockout , Taxa de Sobrevida
18.
Phys Chem Chem Phys ; 21(43): 24177-24186, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31657822

RESUMO

We present a detailed theoretical study of the odd-even harmonics generated from the polar molecule CO by the method based on numerically solving the time-dependent Schrödinger equation within the single-active-electron approximation. First, we reproduce the pure even harmonic generation of CO predicted theoretically by Hu et al. using the time-dependent density functional theory [H. Hu et al., Phys. Rev. Lett., 2017, 119, 173201]. Then, based on the Floquet approach, we are able to attribute this behavior to the half-cycle mirror symmetry of the molecule-field system when the polar molecule is perpendicular to the laser polarization. By numerical simulations, we show that this symmetry is broken at orientation angles other than 90° resulting in the odd-even harmonic generation and a non-trivial even-to-odd harmonics ratio strongly dependent on the molecular orientation. Furthermore, we investigate the influence of the dynamic core-electron polarization (DCeP) on the odd-even behavior near the cutoff of the high-order harmonic spectra. We emphasize that the DCeP effect is noticeable for the odd harmonics only.

19.
Bioconjug Chem ; 29(8): 2628-2635, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-29953207

RESUMO

Intracellular drug delivery systems are often limited by their poor serum stability and delivery efficiency. Cell-penetrating peptides (CPPs), particularly those derived from basic protein subunits, have been studied extensively in this regard and used for the delivery of a variety of cargoes in vitro. Although promising, traditional cationic CPPs have some drawbacks that hinder their therapeutic application such as rapid proteolytic degradation and undesired interactions with the biological milieu. To overcome these limitations, this article details the discovery of a new class of noncharged cell-penetrating oligoTEAs (CPOTs) that undergo extensive and rapid cellular entry across different cell lines with low cytotoxicity. CPOTs outperform a widely used CPP, R9 peptide. This new class of highly efficient noncharged macromolecular transporters are distinct from their cationic counterparts and show strong promise for the intracellular delivery of hydrophilic small-molecule therapeutics.


Assuntos
Biopolímeros/administração & dosagem , Peptídeos Penetradores de Células/administração & dosagem , Sistemas de Liberação de Medicamentos , Biopolímeros/química , Peptídeos Penetradores de Células/química , Citoplasma/metabolismo , Endocitose , Corantes Fluorescentes/química , Células HeLa , Humanos , Interações Hidrofóbicas e Hidrofílicas , Proteólise
20.
Blood ; 128(24): 2774-2784, 2016 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-27756748

RESUMO

Fanconi anemia (FA) is an inherited bone marrow failure disorder associated with a high incidence of leukemia and solid tumors. Bone marrow transplantation is currently the only curative therapy for the hematopoietic complications of this disorder. However, long-term morbidity and mortality remain very high, and new therapeutics are badly needed. Here we show that the widely used diabetes drug metformin improves hematopoiesis and delays tumor formation in Fancd2-/- mice. Metformin is the first compound reported to improve both of these FA phenotypes. Importantly, the beneficial effects are specific to FA mice and are not seen in the wild-type controls. In this preclinical model of FA, metformin outperformed the current standard of care, oxymetholone, by improving peripheral blood counts in Fancd2-/- mice significantly faster. Metformin increased the size of the hematopoietic stem cell compartment and enhanced quiescence in hematopoietic stem and progenitor cells. In tumor-prone Fancd2-/-Trp53+/- mice, metformin delayed the onset of tumors and significantly extended the tumor-free survival time. In addition, we found that metformin and the structurally related compound aminoguanidine reduced DNA damage and ameliorated spontaneous chromosome breakage and radials in human FA patient-derived cells. Our results also indicate that aldehyde detoxification might be one of the mechanisms by which metformin reduces DNA damage in FA cells.


Assuntos
Carcinogênese/patologia , Anemia de Fanconi/tratamento farmacológico , Anemia de Fanconi/patologia , Hematopoese/efeitos dos fármacos , Metformina/farmacologia , Aldeídos/metabolismo , Animais , Contagem de Células Sanguíneas , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/patologia , Carcinogênese/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Quebra Cromossômica , Dano ao DNA , Dieta , Anemia de Fanconi/sangue , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/deficiência , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/metabolismo , Guanidinas/farmacologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/patologia , Humanos , Inativação Metabólica/efeitos dos fármacos , Metformina/administração & dosagem , Camundongos , Poli I-C/farmacologia
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