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1.
Sci Total Environ ; : 172732, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38663609

RESUMEN

East Asian continental outflows with PM2.5, O3, and other species may determine the baseline conditions and affect the air quality in downwind areas via long-range transport (LRT). To gain insight into the impact and spatiotemporal characteristics of airborne pollutants in East Asian continental outflows, a versatile multicopter drone sounding platform was used to simultaneously observe PM2.5, O3, CO2, and meteorological variables (temperature, specific humidity, pressure, and wind vector) above the northern tip of Taiwan, Cape Fuiguei, which often encounters continental outflows during winter monsoon periods. By coordinating hourly high-spatial-resolution profiles provided by drone soundings, WRF/CMAQ model air quality predictions, HYSPLIT-simulated backward trajectories, and MERRA-2 reanalysis data, we analyzed two prominent phenomena of airborne pollutants in continental outflows to better understand their physical/chemical characteristics. First, we found that pollutants were well mixed within a sounding height of 500 m when continental outflows passed through and completely enveloped Cape Fuiguei. Eddies induced by significant fluctuations in wind speeds coupled with minimal temperature inversion and LRT facilitated vertical mixing, possibly resulting in high homogeneity of pollutants within the outflow layer. Second, the drone soundings indicated exceptionally high O3 concentrations (70-100 ppbv) but relatively low concentrations of PM2.5 (10-20 µg/m3), CO2 (420-425 ppmv), and VOCs in some air masses. The low levels of PM2.5, CO2, and VOCs ruled out photochemistry as the cause of the formation of high-level O3. Further coordination of spatiotemporal data with air mass trajectories and O3 cross sections provided by MERRA-2 suggested that the high O3 concentrations could be attributed to stratospheric intrusion and advection via continental outflows. High-level O3 concentrations persisted in the lower troposphere, even reaching the surface, suggesting that stratospheric intrusion O3 may be involved in the rising trend in O3 concentrations in parts of East Asia in recent years in addition to surface photochemical factors.

2.
J Virol ; 98(4): e0177323, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38530012

RESUMEN

Dengue vaccine candidates have been shown to improve vaccine safety and efficacy by altering the residues or accessibility of the fusion loop on the virus envelope protein domain II (DIIFL) in an ex vivo animal study. The current study aimed to comprehensively investigate the impact of DIIFL mutations on the antigenicity, immunogenicity, and protective efficacy of Japanese encephalitis virus (JEV) virus-like particles (VLPs) in mice. We found the DIIFL G106K/L107D (KD) and W101G/G106K/L107D (GKD) mutations altered the binding activity of JEV VLP to cross-reactive monoclonal antibodies but had no effect on their ability to elicit total IgG antibodies in mice. However, JEV VLPs with KD or GKD mutations induced significantly less neutralizing antibodies against JEV. Only 46% and 31% of the KD and GKD VLPs-immunized mice survived compared to 100% of the wild-type (WT) VLP-immunized mice after a lethal JEV challenge. In passive protection experiments, naïve mice that received sera from WT VLP-immunized mice exhibited a significantly higher survival rate of 46.7% compared to those receiving sera from KD VLP- and GKD VLP-immunized mice (6.7% and 0%, respectively). This study demonstrated that JEV DIIFL is crucial for eliciting potently neutralizing antibodies and protective immunity against JEV. IMPORTANCE: Introduction of mutations into the fusion loop is one potential strategy for generating safe dengue and Zika vaccines by reducing the risk of severe dengue following subsequent infections, and for constructing live-attenuated vaccine candidates against newly emerging Japanese encephalitis virus (JEV) or Japanese encephalitis (JE) serocomplex virus. The monoclonal antibody studies indicated the fusion loop of JE serocomplex viruses primarily comprised non-neutralizing epitopes. However, the present study demonstrates that the JEV fusion loop plays a critical role in eliciting protective immunity in mice. Modifications to the fusion loop of JE serocomplex viruses might negatively affect vaccine efficacy compared to dengue and zika serocomplex viruses. Further studies are required to assess the impact of mutant fusion loop encoded by commonly used JEV vaccine strains on vaccine efficacy or safety after subsequent dengue virus infection.


Asunto(s)
Dengue , Virus de la Encefalitis Japonesa (Especie) , Encefalitis Japonesa , Vacunas contra la Encefalitis Japonesa , Infección por el Virus Zika , Virus Zika , Animales , Ratones , Virus de la Encefalitis Japonesa (Especie)/genética , Proteínas del Envoltorio Viral/genética , Epítopos , Aminoácidos , Vacunas contra la Encefalitis Japonesa/genética , Anticuerpos Antivirales , Anticuerpos Neutralizantes
3.
Environ Monit Assess ; 196(3): 246, 2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38329592

RESUMEN

An integrated, remotely sensed approach to assess land-use and land-cover change (LULCC) dynamics plays an important role in environmental monitoring, management, and policy development. In this study, we utilized the advantage of land-cover seasonality, canopy height, and spectral characteristics to develop a phenology-based classification model (PCM) for mapping the annual LULCC in our study areas. Monthly analysis of normalized difference vegetation index (NDVI) and near-infrared (NIR) values derived from SPOT images enabled the detection of temporal characteristics of each land type, serving as crucial indices for land type classification. The integration of normalized difference built-up index (NDBI) derived from Landsat images and airborne LiDAR canopy height into the PCM resulted in an overall performance of 0.85, slightly surpassing that of random forest analysis or principal component analysis. The development of PCM can reduce the time and effort required for manual classification and capture annual LULCC changes among five major land types: forests, built-up land, inland water, agriculture land, and grassland/shrubs. The gross change LULCC analysis for the Taoyuan Tableland demonstrated fluctuations in land types over the study period (2013 to 2022). A negative correlation (r = - 0.79) in area changes between grassland/shrubs and agricultural land and a positive correlation (r = 0.47) between irrigation ponds and agricultural land were found. Event-based LULCC analysis for Taipei City demonstrated a balance between urbanization and urban greening, with the number of urbanization events becoming comparable to urban greening events when the spatial extent of LULCC events exceeds 1000 m2. Besides, small-scale urban greening events are frequently discovered and distributed throughout the metropolitan area of Taipei City, emphasizing the localized nature of urban greening events.


Asunto(s)
Monitoreo del Ambiente , Tecnología de Sensores Remotos , Agricultura , Formulación de Políticas , Estanques
4.
Appl Microbiol Biotechnol ; 108(1): 242, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38416210

RESUMEN

Flavivirus virus-like particles (VLPs) exhibit a striking structural resemblance to viral particles, making them highly adaptable for various applications, including vaccines and diagnostics. Consequently, increasing VLPs production is important and can be achieved by optimizing expression plasmids and cell culture conditions. While attempting to express genotype III (GIII) Japanese encephalitis virus (JEV) VLPs containing the G104H mutation in the envelope (E) protein, we failed to generate VLPs in COS-1 cells. However, VLPs production was restored by cultivating plasmid-transfected cells at a lower temperature, specifically 28 °C. Furthermore, we observed that the enhancement in JEV VLPs production was independent of amino acid mutations in the E protein. The optimal condition for JEV VLPs production in plasmid-transfected COS-1 cells consisted of an initial culture at 37 °C for 6 h, followed by a shift to 28 °C (37/28 °C) for cultivation. Under 37/28 °C cultivation conditions, flavivirus VLPs production significantly increased in various mammalian cell lines regardless of whether its expression was transiently transfected or clonally selected cells. Remarkably, clonally selected cell lines expressing flavivirus VLPs consistently achieved yields exceeding 1 µg/ml. Binding affinity analyses using monoclonal antibodies revealed similar binding patterns for VLPs of genotype I (GI) JEV, GIII JEV, West Nile virus (WNV), and dengue virus serotype 2 (DENV-2) produced under both 37 °C or 37/28 °C cultivation conditions. In summary, our study demonstrated that the production of flavivirus VLPs can be significantly improved under 37/28 °C cultivation conditions without affecting the conformational structure of the E protein. KEYPOINTS: • Low-temperature culture (37/28 °C) enhances production of flavivirus VLPs. • Flavivirus VLPs consistently achieved yields exceeding 1 µg/ml. • 37/28 °C cultivation did not alter the structure of flavivirus VLPs.


Asunto(s)
Virus de la Encefalitis Japonesa (Especie) , Encefalitis Japonesa , Flavivirus , Chlorocebus aethiops , Animales , Flavivirus/genética , Temperatura , Virus de la Encefalitis Japonesa (Especie)/genética , Frío , Células COS , Mamíferos
5.
Small ; 20(8): e2307547, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37814367

RESUMEN

The sluggish four-electron oxygen evolving reaction is one of the key limitations of photoelectrochemical water decomposition. Optimizing the binding of active sites to oxygen in water and promoting the conversion of *O to *OOH are the key to enhancing oxygen evolution reaction. In this work, W-doped Cu2 V2 O7 (CVO) constructs corner-sharing tetrahedrally coordinated W-V dual active sites to induce the generation of electron deficiency active centers, promote the adsorption of ─OH, and accelerate the transformation of *O to *OOH for water splitting. The photocurrent obtained by the W-modified CVO photoanode is 0.97 mA cm-2 at 1.23 V versus RHE, which is much superior to that of the reported CVO. Experimental and theoretical results show that the excellent catalytic performance may be attributed to the formation of synergistic dual active sites between W and V atoms, and the introduction of W ions reduces the charge migration distance and prolongs the lifetime of photogenerated carriers. Meanwhile, the electronic structure in the center of the d-band is modulated, which leads to the redistribution of the electron density in CVO and lowers the energy barrier for the conversion of the rate-limiting step *O to *OOH.

6.
Antiviral Res ; 219: 105735, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37858764

RESUMEN

A class of 1-(4-(arylethylenylcarbonyl)phenyl)-4-carboxy-2-pyrrolidinones were designed and synthesized via Michael addition, cyclization, aldol condensation, and deprotonation to inhibit the human transmembrane protease serine 2 (TMPRSS2) and Furin, which are involved in priming the SARS-CoV-2 Spike for virus entry. The most potent inhibitor 2f (81) was found to efficiently inhibit the replication of various SARS-CoV-2 delta and omicron variants in VeroE6 and Calu-3 cells, with EC50 range of 0.001-0.026 µM by pre-incubation with the virus to avoid the virus entry. The more potent antiviral activities than the proteases inhibitory activities led to discovery that the synthesized compounds also inhibited Spike's receptor binding domain (RBD):angiotensin converting enzyme 2 (ACE2) interaction as a main target, and their antiviral activities were enhanced by inhibiting TMPRSS2 and/or Furin. To further confirm the blocking effect of 2f (81) on virus entry, SARS-CoV-2 Spike pseudovirus was used in the entry assay and the results showed that the compound inhibited the pseudovirus entry in a ACE2-dependent pathway, via mainly inhibiting RBD:ACE2 interaction and TMPRSS2 activity in Calu-3 cells. Finally, in the in vivo animal model of SARS-CoV-2 infection, the oral administration of 25 mg/kg 2f (81) in hamsters resulted in reduced bodyweight loss and 5-fold lower viral RNA levels in nasal turbinate three days post-infection. Our findings demonstrated the potential of the lead compound for further preclinical investigation as a potential treatment for SARS-CoV-2.


Asunto(s)
COVID-19 , SARS-CoV-2 , Animales , Humanos , Furina/farmacología , Enzima Convertidora de Angiotensina 2/química , Pirrolidinonas/farmacología , Antivirales/farmacología , Glicoproteína de la Espiga del Coronavirus/metabolismo , Internalización del Virus
7.
BMC Emerg Med ; 23(1): 103, 2023 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-37679682

RESUMEN

BACKGROUND: The purpose of the study was to investigate the relationship between the independent practice time of residents and the quality of care provided in the Emergency Department (ED) across three urban hospitals in Taiwan. The study focused on non-pediatric and non-obstetric complaints, aiming to provide insights into the optimal balance between resident autonomy and patient safety. METHODS: A comprehensive retrospective study was conducted using de-identified electronic health records (EHRs) from the hospital's integrated medical database (iMD) from August 2015 to July 2019. The independent practice time was defined as the duration from the first medical order by a resident to the first modifications by the attending physician. The primary outcome was revisits to the ED within 72 h following discharge. Statistical analysis was conducted using RStudio and pyGAM. RESULTS: The study identified several factors associated with shorter independent practice times (< 30 minutes), including older patient age, male sex, higher body temperature, higher heart rate, lower blood pressure, and the presence of certain comorbidities. Residents practicing independently for 30-120 minutes were associated with similar adjusted odds of patient revisits to the ED (OR 1.034, 95% CI 0.978-1.093) and no higher risk of 7-day mortality (OR 0.674, 95% CI 0.592-0.767) compared to the group with less autonomy. However, independent practice times exceeding 120 minutes were associated with higher odds of revisiting the ED within 72 h. For the group with 120-210 minutes of independent practice time, the OR was 1.113 (95% CI: 1.025-1.208, p = 0.011). For the group with > 210 minutes, the OR was 1.259 (95% CI: 1.094-1.449, p = 0.001), indicating an increased risk of adverse outcomes as the independent practice time increasing. CONCLUSIONS: The study concludes that while providing residents an independent practice time between 30 to 120 minutes may be beneficial, caution should be exercised when this time exceeds 120 minutes. The findings underscore the importance of optimal supervision in enhancing patient care quality and safety. Further research is recommended to explore the long-term effects of different levels of resident autonomy on patient outcomes and the professional development of the residents themselves.


Asunto(s)
Servicio de Urgencia en Hospital , Hospitales Urbanos , Humanos , Masculino , Taiwán/epidemiología , Estudios Retrospectivos , Presión Sanguínea
8.
Sci Rep ; 13(1): 5672, 2023 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-37024550

RESUMEN

It is debatable whether external forcing can change the state of the climate. By investigating decadal changes with and without including the 1990s stratospheric volcanic aerosols, we explored the volcanic eruptions contribution to decadal climate regime shifts occurring in boreal winter over the North Pacific. The volcanic eruptions contribution can be characterized as a series of rapid changes, including the strengthening and poleward shift of the midlatitude westerly jet stream. In addition to the short-lived radiative effects primarily induced by the 1991 Mount Pinatubo eruption, the volcanically driven decadal change can be observed in the mid-to-late 1990s, suggesting a time-lagged characteristic of the volcanic climate impact. Compared with the decadal change irrelevant to volcanic eruption, the decadal state more dramatically enters into the next phase when volcanic forcing is included. The climate oscillation-related pattern shifts that occurred across the 1990s can provide insights into volcanically induced changes in decadal atmospheric circulation.

9.
Caries Res ; 57(2): 159-166, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36806002

RESUMEN

Cathepsin K (catK) modulates the degradation of dentin collagen. This study aimed to evaluate the effects of catK inhibitors on dentin erosion. Dentin beams were eroded (4 times/d for 5 days) and immersed in deionized water (negative control), 0.1 M NaCl, 0.3 M NaCl, 0.5 M NaCl, or 1 µm odanacatib (each n = 16) for 30 min after each erosive challenge. Erosive dentin loss (EDL) and demineralized organic matrix (DOM) thickness were evaluated profilometrically. Additionally, dentin beams were demineralized, immersed in the respective solutions for 30 min each (n = 5), and then incubated in artificial saliva for 5 days. Dentin collage degradation was evaluated by quantifying the levels of the C-terminal peptide of type I collagen (CTX), C-terminal cross-linked telopeptide of type I collagen (ICTP), and hydroxyproline (HYP) in the incubation media. Significantly lower EDL and dentin collagen degradation (CTX, ICTP, and HYP) and thicker DOM layers were observed in the samples treated with 0.3 m NaCl and 1 µm odanacatib than in those treated with deionized water (all p < 0.05). The samples treated with 1 µm odanacatib showed significantly lower levels of CTX and HYP than those treated with 0.3 M NaCl (all p < 0.05). The present findings support the potential use of catK inhibitors in controlling dentin erosion.


Asunto(s)
Colágeno Tipo I , Cloruro de Sodio , Humanos , Catepsina K/metabolismo , Colágeno Tipo I/metabolismo , Cloruro de Sodio/farmacología , Colágeno , Dentina
10.
Mar Drugs ; 20(12)2022 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-36547930

RESUMEN

κ-carrageenases are members of the glycoside hydrolase family 16 (GH16) that hydrolyze sulfated galactans in red algae, known as κ-carrageenans. In this study, a novel κ-carrageenase gene from the marine bacterium Rhodopirellula sallentina SM41 (RsCgk) was discovered via the genome mining approach. There are currently no reports on κ-carrageenase from the Rhodopirellula genus, and RsCgk shares a low identity (less than 65%) with κ- carrageenase from other genera. The RsCgk was heterologously overexpressed in Escherichia coli BL21 and characterized for its enzymatic properties. RsCgk exhibited maximum activity at pH 7.0 and 40 °C, and 50% of its initial activity was retained after incubating at 30 °C for 2 h. More than 70% of its activity was maintained after incubation at pH 6.0-8.0 and 4 °C for 24 h. As a marine derived enzyme, RsCgk showed excellent salt tolerance, retaining full activity in 1.2 M NaCl, and the addition of NaCl greatly enhanced its thermal stability. Mass spectrometry analysis of the RsCgk hydrolysis products revealed that the enzyme had high degradation specificity and mainly produced κ-carrageenan disaccharide. Comparative molecular dynamics simulations revealed that the conformational changes of tunnel-forming loops under salt environments may cause the deactivation or stabilization of RsCgk. Our results demonstrated that RsCgk could be utilized as a potential tool enzyme for efficient production of κ-carrageenan oligosaccharides under high salt conditions.


Asunto(s)
Tolerancia a la Sal , Cloruro de Sodio , Carragenina/química , Bacterias/metabolismo , Glicósido Hidrolasas/metabolismo , Proteínas Bacterianas/metabolismo
11.
J Environ Manage ; 318: 115614, 2022 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-35779296

RESUMEN

Since the 24-hr PM2.5 (particle aerodynamic diameter less than 2.5 µm) concentration standard was regulated in Taiwan in 2012, the PM2.5 concentration has been decreasing year by year, but the ozone (O3) concentration remains almost the same. In particular, the daily maximum 8-hr average O3 (MDA8 O3) concentration frequently exceeds the standard. The goal of this study is to find a solution for reducing PM2.5 and O3 simultaneously by numerical modeling. After the Volatile Organic Compounds (VOCS)-limited and nitrogen oxides (NOX)-limited areas were defined in Taiwan, then, in total, 50 scenarios are simulated in this study. In terms of the average in Taiwan, the effect of VOCS emission reduction is better than that of NOX on the decrease in PM2.5 concentration, when the same reduction proportion (20%, 40%) is implemented. While the effect of further NOX emission reduction (60%) will exceed that of VOCS. The decrease in PM2.5 is proportional to the reduction in precursor emissions such as NOX, VOCS, sulfur dioxides (SO2), and ammonia (NH3). The lower reduction of NOX emission for whole Taiwan caused O3 increases on average but higher reduction can ease the increase, which suggests the implement of NOX emission reductions must be cautious. When comparing administrative jurisdictions in terms of grids, districts/towns, and cities/counties, it was found that controlling NOX and VOCS at a finer spatial resolution of control units did not benefit the decrease in PM2.5 but did benefit the decrease in O3. The enhanced O3 control strategies obviously cause a higher decrease of O3 throughout Taiwan due to NOX and VOCS emission changes when they are implemented in the right places. Finally, three sets of short-term and long-term goals of controlling PM2.5 and O3 simultaneously are drawn from the comprehensive rankings for all simulated scenarios, depending on whether PM2.5 or O3 control is more urgent. In principle, the short-term scenarios could be ordinary or enhanced version of O3 decrease with lower NOX/VOCS emissions, while the long-term scenario is enhanced version of O3 decrease plus high emission reductions for all precursors.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Ozono , Compuestos Orgánicos Volátiles , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Contaminación del Aire/prevención & control , China , Monitoreo del Ambiente , Ozono/análisis , Material Particulado/análisis , Taiwán , Compuestos Orgánicos Volátiles/análisis
12.
J Pers Med ; 12(6)2022 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-35743722

RESUMEN

The development of precision psychiatry is largely based on multi-module measurements from the molecular, cellular, and behavioral levels, which are integrated to assess neurocognitive performances and clinically observed psychopathology. Nevertheless, quantifying mental activities and functions accurately and continuously has been a major difficulty within this field. This article reviews the latest efforts that utilize mobile apps to collect human-smartphone interaction data and contribute towards digital biomarkers of mental illnesses. The fundamental principles underlying a behavioral analysis with mobile apps were introduced, such as ways to monitor smartphone use under different circumstances and construct long-term patterns and trend changes. Examples were also provided to illustrate the potential applications of mobile apps that gain further insights into traditional research topics in occupational health and sleep medicine. We suggest that, with an optimized study design and analytical approach that accounts for technical challenges and ethical considerations, mobile apps will enhance the systemic understanding of mental illnesses.

13.
J Med Internet Res ; 24(4): e36830, 2022 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-35380546

RESUMEN

BACKGROUND: Vaccination is an important intervention to prevent the incidence and spread of serious diseases. Many factors including information obtained from the internet influence individuals' decisions to vaccinate. Misinformation is a critical issue and can be hard to detect, although it can change people's minds, opinions, and decisions. The impact of misinformation on public health and vaccination hesitancy is well documented, but little research has been conducted on the relationship between the size of the population reached by misinformation and the vaccination decisions made by that population. A number of fact-checking services are available on the web, including the Islander news analysis system, a free web service that provides individuals with real-time judgment on web news. In this study, we used such services to estimate the amount of fake news available and used Google Trends levels to model the spread of fake news. We quantified this relationship using official public data on COVID-19 vaccination in Taiwan. OBJECTIVE: In this study, we aimed to quantify the impact of the magnitude of the propagation of fake news on vaccination decisions. METHODS: We collected public data about COVID-19 infections and vaccination from Taiwan's official website and estimated the popularity of searches using Google Trends. We indirectly collected news from 26 digital media sources, using the news database of the Islander system. This system crawls the internet in real time, analyzes the news, and stores it. The incitement and suspicion scores of the Islander system were used to objectively judge news, and a fake news percentage variable was produced. We used multivariable linear regression, chi-square tests, and the Johnson-Neyman procedure to analyze this relationship, using weekly data. RESULTS: A total of 791,183 news items were obtained over 43 weeks in 2021. There was a significant increase in the proportion of fake news in 11 of the 26 media sources during the public vaccination stage. The regression model revealed a positive adjusted coefficient (ß=0.98, P=.002) of vaccine availability on the following week's vaccination doses, and a negative adjusted coefficient (ß=-3.21, P=.04) of the interaction term on the fake news percentage with the Google Trends level. The Johnson-Neiman plot of the adjusted effect for the interaction term showed that the Google Trends level had a significant negative adjustment effect on vaccination doses for the following week when the proportion of fake news exceeded 39.3%. CONCLUSIONS: There was a significant relationship between the amount of fake news to which the population was exposed and the number of vaccination doses administered. Reducing the amount of fake news and increasing public immunity to misinformation will be critical to maintain public health in the internet age.


Asunto(s)
COVID-19 , Medios de Comunicación Sociales , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/uso terapéutico , Desinformación , Humanos , Internet , Prevalencia , Estudios Retrospectivos , Taiwán/epidemiología , Vacunación
14.
Bioorg Chem ; 121: 105675, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35182882

RESUMEN

Fms-like tyrosine kinase 3 (FLT3) is considered a promising therapeutic target for acute myeloid leukemia (AML) in the clinical. However, monotherapy with FLT3 inhibitor is usually accompanied by drug resistance. Dual inhibitors might be therapeutically beneficial to patients with AML due to their ability to overcome drug resistance. Mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) phosphorylate eukaryotic translation initiation factor 4E (eIF4E), which brings together the RAS/RAF/ERK and PI3K/AKT/mTOR oncogenic pathways. Therefore, dual inhibition of FLT3 and MNK2 might have an additive effect against AML. Herein, a structure-based virtual screening approach was performed to identify dual inhibitors of FLT3 and MNK2 from the ChemDiv database. Compound K783-0308 was identified as a dual inhibitor of FLT3 and MNK2 with IC50 values of 680 and 406 nM, respectively. In addition, the compound showed selectivity for both FLT3 and MNK2 in a panel of 82 kinases. The structure-activity relationship analysis and common interactions revealed interactions between K783-0308 analogs and FLT3 and MNK2. Furthermore, K783-0308 inhibited MV-4-11 and MOLM-13 AML cell growth and induced G0/G1 cell cycle arrest. Taken together, the dual inhibitor K783-0308 showed promising results and can be potentially optimized as a lead compound for AML treatment.


Asunto(s)
Leucemia Mieloide Aguda , Tirosina Quinasa 3 Similar a fms , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Humanos , Péptidos y Proteínas de Señalización Intracelular , Leucemia Mieloide Aguda/tratamiento farmacológico , Mutación , Fosfatidilinositol 3-Quinasas , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Serina-Treonina Quinasas
15.
Artículo en Inglés | MEDLINE | ID: mdl-35206134

RESUMEN

Athletes often have poor sleep quality before a competition. Sleep quality can stabilize mood and improve sports performance. The randomized controlled study explored the effects of cranial electrotherapy stimulation (CES) on the physiology, psychology, response-ability, and sleep quality of athletes who had poor sleep quality before a competition. Athletes who had poor sleep quality (Pittsburgh Sleep Quality Scale score > 5) and had a competition in less than 2 months were recruited. The athletes were grouped into the CES group, which received a 2-week CES treatment (n = 20, age = 21.55 ± 2.26 years), and a placebo group (n = 20, age = 21.05 ± 1.46 years), which received a 2-week sham CES treatment. We performed biochemical analysis, a simple reaction time test, choice reaction time tests, the Profile of Mood States, heart rate variability (HRV), and an Actigraphy activity recorder to measure outcomes before and after the interventions. Our results revealed no significant differences in blood urea nitrogen, creatine phosphate, testosterone, cortisol, and saliva pH between and within groups (p > 0.05). Significant decreases in negative mood states (i.e., anger, tension, and depression) and choice reaction time in the CES group were noted (p < 0.05), moreover, the anger, tension, and depression mood decreased from 0.36 ± 0.45 (95% CI = 0.16-0.55), 1.62 ± 0.97 (95% CI = 1.19-2.04), and 1.67 ± 1.06 (95% CI = 1.20-2.13) to 0.11 ± 0.20 (95% CI = 0.02-0.19, p = 0.03), 1.12 ± 0.74 (95% CI = 0.79-1.44, p = 0.04), and 0.81 ± 0.75 (95% CI = 0.48-1.13, p = 0.001), respectively. Additionally, choice reaction time was decreased from 420.85 ± 41.22 ms (95% CI = 402.78-438.91) to 399.90 ± 36.71 ms (95% CI = 383.81-415.98, p = 0.04) and was also noted in the CES group. For HRV, and Actigraphy activity for sleep measure, the low-frequency (LF)/high-frequency (HF) ratios changed from 1.80 ± 1.39 (95% CI = 1.19-2.40) to 1.21 ± 0.73 (95% CI = 0.89-1.53, p = 0.10), and sleep efficiency decreased from 87.94 ± 6.76% (95% CI = 84.97-90.90) to 81.75 ± 9.62% (95% CI = 77.53-85.96, p = 0.02) in the CES group. The change in LF/HF after the trial were found between CES and placebo groups (p < 0.05). Yet, the decrease in sleep efficiency in the placebo group were noted (p < 0.05). However, we found that the regression line for sleep efficiency was decreased less during the study while using CES. The CES intervention could reduce negative emotions, improve choice reaction times, enhance the parasympathetic and sympathetic nerve activity imbalances, and slow sleep efficiency deterioration. Regardless, small effect sizes of the application of CES on psychology response, response-ability, and sleep efficiency were concluded in athletes with poor sleep quality before a competition.


Asunto(s)
Terapia por Estimulación Eléctrica , Calidad del Sueño , Adulto , Atletas , Terapia por Estimulación Eléctrica/métodos , Humanos , Cráneo , Sueño/fisiología , Adulto Joven
16.
Artículo en Inglés | MEDLINE | ID: mdl-35010774

RESUMEN

There is interest in whether nicotine could enhance attention in sporting performance, but evidence on the acute effect of nicotine on physical response and sports performance in baseball players remains scant. This was an observational study to examine whether nicotine gum chewed before exercise could provide acute effects on physiological responses and sport performance. Accordingly, heart rate variability (HRV), saliva cotinine concentration and α-amylase activity, cognitive function, muscle strength, and baseball-hitting performance were measured. Thirteen healthy male non-smoker baseball players were recruited. Conducting two sequences with 7-day intervals, they chewed nicotine gum (nicotine group) or flavor-matched placebo gum (placebo group) for 30 min. HRV and saliva analyses were conducted before gum consumption (S1), after gum consumption (S2), and after test completion (S3). Cognitive, muscle strength, and baseball-hitting performance tests were performed after nicotine or placebo gum chewing. The outcomes of all assessed variables were compared within and between the groups. Significant changes in HRV, α-amylase, testosterone, and cortisol were observed in the nicotine group at S2 and S3 (p < 0.05). Compared with the placebo group, the nicotine group exhibited enhanced motor reaction times, grooved pegboard test (GPT) results on cognitive function, and baseball-hitting performance, and small effect sizes were noted (d = 0.47, 0.46 and 0.41, respectively). Nicotine could induce changes in endocrine and sympathetic nerve activity and enhance cognitive function and baseball-hitting performance. However, no increase in muscle strength was observed after nicotine intake.


Asunto(s)
Rendimiento Atlético , Béisbol , Atención , Goma de Mascar , Humanos , Masculino , Nicotina
17.
Viruses ; 14(1)2022 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-35062317

RESUMEN

Expansion of genotype I (GI) Japanese encephalitis viruses (JEV) has resulted in the replacement of the dominant genotype III (GIII) viruses, raising serious public health concerns for using GIII virus-derived vaccines to effectively control JEV epidemics. Therefore, this study used swine as the model to estimate the effectiveness of GIII live-attenuated vaccine against GI virus infection by comparing the incidence of stillbirth/abortion in gilts from vaccinated and non-vaccinated pig farms during the GI-circulation period. In total, 389 and 213 litters of gilts were recorded from four vaccinated and two non-vaccinated pig farms, respectively. All viruses detected in the aborted fetuses and mosquitoes belonged to the GI genotype during the study period. We thus estimated that the vaccine effectiveness of GIII live-attenuated vaccine against GI viruses in naive gilts based on the overall incidence of stillbirth/abortion and incidence of JEV-confirmed stillbirth/abortion was 65.5% (50.8-75.7%) and 74.7% (34.5-90.2%), respectively. In contrast to previous estimates, the GIII live-attenuated vaccine had an efficacy of 95.6% (68.3-99.4%) to prevent the incidence of stillbirth/abortion during the GIII-circulating period. These results indicate that the vaccine effectiveness of GIII live-attenuated JEV vaccine to prevent stillbirth/abortion caused by GI viruses is lower than that against GIII viruses.


Asunto(s)
Encefalitis Japonesa/virología , Genotipo , Enfermedades de los Porcinos/virología , Vacunas Virales/inmunología , Animales , Anticuerpos Neutralizantes/inmunología , Culicidae , Virus de la Encefalitis Japonesa (Especie)/genética , Femenino , Inmunización , Vacunas contra la Encefalitis Japonesa/inmunología , Filogenia , Porcinos , Taiwán , Vacunas Atenuadas/inmunología
19.
PLoS Negl Trop Dis ; 15(12): e0009977, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34860839

RESUMEN

Virologic surveillance of Japanese encephalitis virus (JEV) relies on collecting pig blood specimens and adult mosquitoes in the past. Viral RNAs extracted from pig blood specimens suffer from low detecting positivity by reverse transcription PCR (RT-PCR). The oronasal transmission of the virus has been demonstrated in experimentally infected pigs. This observation suggested oronasal specimens could be useful source in the virus surveillance. However, the role of this unusual route of transmission remains unproven in the operational pig farm. In this study, we explore the feasibility of using pig oronasal secretions collected by chewing ropes to improve the positivity of detection in commercial pig farms. The multiplex genotype-specific RT-PCR was used in this study to determine and compare the positivity of detecting JEV viral RNAs in pig's oronasal secretions and blood specimens, and the primary mosquito vector. Oronasal specimens had the overall positive rate of 6.0% (95% CI 1.3%-16.6%) (3/50) to 10.0% (95% CI 2.1%-26.5%) (3/30) for JEV during transmission period despite the negative results of all blood-derived specimens (n = 2442). Interestingly, pig oronasal secretions and female Culex tritaeniorhynchus mosquito samples collected from the same pig farm showed similar viral RNA positive rates, 10.0% (95% CI 2.1%-26.5%) (3/30) and 8.9% (95% CI 2.5%-21.2%) (4/45), respectively (p> 0.05). Pig oronasal secretion-based surveillance revealed the seasonality of viral activity and identified closely related genotype I virus derived from the mosquito isolates. This finding indicates oronasal secretion-based RT-PCR assay can be a non-invasive, alternative method of implementing JEV surveillance in the epidemic area prior to the circulation of virus-positive mosquitoes.


Asunto(s)
Secreciones Corporales/virología , Virus de la Encefalitis Japonesa (Especie)/aislamiento & purificación , Encefalitis Japonesa/veterinaria , Boca/virología , Cavidad Nasal/virología , Manejo de Especímenes/métodos , Manejo de Especímenes/normas , Animales , Bioensayo , Culex/virología , Virus de la Encefalitis Japonesa (Especie)/genética , Encefalitis Japonesa/prevención & control , Encefalitis Japonesa/transmisión , Granjas , Femenino , Genotipo , Reacción en Cadena de la Polimerasa Multiplex , ARN Viral/genética , Porcinos
20.
Front Med (Lausanne) ; 8: 713824, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34646841

RESUMEN

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were shown to have potential for immunoregulation and tissue repair. The objective of this study was to investigate the effects of hUC-MSCs on emphysema in chronic obstructive pulmonary disease (COPD). The C57BL/6JNarl mice were exposed to cigarette smoke (CS) for 4 months followed by administration of hUC-MSCs at 3 × 106 (low dose), 1 × 107 (medium dose), and 3 × 107 cells/kg body weight (high dose). The hUC-MSCs caused significant decreases in emphysema severity by measuring the mean linear intercept (MLI) and destructive index (DI). A decrease in neutrophils (%) and an increase in lymphocytes (%) in bronchoalveolar lavage fluid (BALF) were observed in emphysematous mice after hUC-MSC treatment. Lung levels of interleukin (IL)-1ß, C-X-C motif chemokine ligand 1 (CXCL1)/keratinocyte chemoattractant (KC), and matrix metalloproteinase (MMP)-12 significantly decreased after hUC-MSC administration. Significant reductions in tumor necrosis factor (TNF)-α, IL-1ß, and IL-17A in serum occurred after hUC-MSC administration. Notably, the cell viability of lung fibroblasts improved with hUC-MSCs after being treated with CS extract (CSE). Furthermore, the hUC-MSCs-conditioned medium (hUC-MSCs-CM) restored the contractile force, and increased messenger RNA expressions of elastin and fibronectin by lung fibroblasts. In conclusion, hUC-MSCs reduced inflammatory responses and emphysema severity in CS-induced emphysematous mice.

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