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1.
Nature ; 582(7813): 557-560, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32340022

RESUMEN

The ongoing outbreak of coronavirus disease 2019 (COVID-19) has spread rapidly on a global scale. Although it is clear that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted through human respiratory droplets and direct contact, the potential for aerosol transmission is poorly understood1-3. Here we investigated the aerodynamic nature of SARS-CoV-2 by measuring viral RNA in aerosols in different areas of two Wuhan hospitals during the outbreak of COVID-19 in February and March 2020. The concentration of SARS-CoV-2 RNA in aerosols that was detected in isolation wards and ventilated patient rooms was very low, but it was higher in the toilet areas used by the patients. Levels of airborne SARS-CoV-2 RNA in the most public areas was undetectable, except in two areas that were prone to crowding; this increase was possibly due to individuals infected with SARS-CoV-2 in the crowd. We found that some medical staff areas initially had high concentrations of viral RNA with aerosol size distributions that showed peaks in the submicrometre and/or supermicrometre regions; however, these levels were reduced to undetectable levels after implementation of rigorous sanitization procedures. Although we have not established the infectivity of the virus detected in these hospital areas, we propose that SARS-CoV-2 may have the potential to be transmitted through aerosols. Our results indicate that room ventilation, open space, sanitization of protective apparel, and proper use and disinfection of toilet areas can effectively limit the concentration of SARS-CoV-2 RNA in aerosols. Future work should explore the infectivity of aerosolized virus.


Asunto(s)
Aerosoles/análisis , Aerosoles/química , Aparatos Sanitarios , Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/virología , Hospitales , Neumonía Viral/virología , Lugar de Trabajo , Betacoronavirus/genética , COVID-19 , China/epidemiología , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/transmisión , Aglomeración , Desinfección , Humanos , Unidades de Cuidados Intensivos , Máscaras , Cuerpo Médico , Pandemias/prevención & control , Pacientes/estadística & datos numéricos , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , Neumonía Viral/transmisión , ARN Viral/análisis , SARS-CoV-2 , Aislamiento Social , Ventilación
2.
Entropy (Basel) ; 26(1)2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-38248209

RESUMEN

In this work, a lattice Boltzmann method (LBM) for studying microchannel gas flow is developed in the multi-flow regime. In the LBM, by comparing previous studies' results on effective viscosity in multi-flow regimes, the values of the rarefaction factor applicable to multi-flow regions were determined, and the relationship between relaxation time and Kn number with the rarefaction factor is given. The Kn number is introduced into the second-order slip boundary condition together with the combined bounce-back/specular-reflection (CBBSR) scheme to capture the gas flow in the multi-flow regime. Sensitivity analysis of the dimensionless flow rate to adjustable parameters using the Taguchi method was carried out, and the values of adjustable parameters were determined based on the results of the sensitivity analysis. The results show that the dimensionless flow rate is more sensitive to j than h. Numerical simulations of Poiseuille flow and pulsating flow in a microchannel with second-order slip boundary conditions are carried out to validate the method. The results show that the velocity profile and dimensionless flow rate simulated by the present numerical simulation method in this work are found in the multi-flow regime, and the phenomenon of annular velocity profile in the microchannel is reflected in the phases.

3.
Mol Carcinog ; 62(2): 261-276, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36345938

RESUMEN

To identify Musashi2 as an effective biomarker regulated by the TGF-ß/Smad2/3 signaling pathway for the precise diagnosis and treatment of colorectal cancer (CRC) through bioinformatic tools and experimental verification. The Cancer Genome Atlas, Timer, and Kaplan-Meier analyses were performed to clarify the expression of Musashi2 and its influence on the prognosis of CRC. Transforming growth factor beta 1 (TGF-ß1) was used to activate the TGF-ß/Smad2/3 signaling pathway to identify whether it could regulate the expression and function of Musashi2. Western blot analysis and quantitative PCR analyses were conducted to verify the expression of Musashi2. Cell counting kit-8 (CCK8), EdU, wound healing, and Transwell assays were conducted to reveal the role of Musashi2 in the proliferation, migration, and invasion of CRC. Musashi2 was upregulated in CRC and promoted proliferation and metastasis. TGF-ß1 increased the expression of Musashi2, while the antagonist inducer of type II TGF-ß receptor degradation-1 (ITD-1) decreased the expression. CCK8 and EdU assays demonstrated that inhibition of Musashi2 or use of ITD-1 lowered proliferation ability. The Transwell and wound healing assays showed that the migration and invasion abilities of CRC cells could be regulated by Musashi2. The above functions could be enhanced by TGF-ß1 by activating the TGF-ß/Smad2/3 signaling pathway and reversed by ITD-1. A positive correlation was found between Musashi2 and the TGF-ß/Smad2/3 signaling pathway. TGF-ß1 activates the TGF-ß/Smad2/3 pathway to stimulate the expression of Musashi2, which promotes the progression of CRC. Musashi2 might become a target gene for the development of new antitumor drugs.


Asunto(s)
Neoplasias Colorrectales , Factor de Crecimiento Transformador beta , Humanos , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales/patología , Transición Epitelial-Mesenquimal/genética , Receptor Tipo II de Factor de Crecimiento Transformador beta , Transducción de Señal , Proteína Smad2/genética , Proteína Smad2/metabolismo , Proteína Smad2/farmacología , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo
4.
Opt Express ; 31(16): 27006-27019, 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37710548

RESUMEN

We analyze a new type of photonic crystal fiber which consists of the core and cladding that distinct in topology by tuning the position of air holes in each hexagonal unit cell where the C6v symmetry is respected. The p-d band inversion between the core and cladding leads to topological interface modes inside the band gap, which can propagate along the fiber with a nonzero momentum in perpendicular to the corss section of a fiber. The helical topological interface modes possess the pseudospin-momentum locking effect inherited from the corresonding two-dimensional photonic crystal characterized by the Z2 topology. The wave functions for the topological interface modes are analytically studied and compared successfully to the numerical results, enlighting a novel way to use photonic crystal fiber to transfer information.

5.
Anim Cogn ; 26(4): 1161-1175, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36934374

RESUMEN

Zebra finches rely mainly on syllable phonology rather than on syllable sequence when they discriminate between two songs. However, they can also learn to discriminate two strings containing the same set of syllables by their sequence. How learning about the phonological characteristics of syllables and their sequence relate to each other and to the composition of the stimuli is still an open question. We compared whether and how the zebra finches' relative sensitivity for syllable phonology and syllable sequence depends on the differences between syllable strings. Two groups of zebra finches were trained in a Go-Left/Go-Right task to discriminate either between two strings in which each string contained a unique set of song syllables ('Different-syllables group') or two strings in which both strings contained the same set of syllables, but in a different sequential order ('Same-syllables group'). We assessed to what extent the birds in the two experimental groups attend to the spectral characteristics and the sequence of the syllables by measuring the responses to test strings consisting of spectral modifications or sequence changes. Our results showed no difference in the number of trials needed to discriminate strings consisting of either different or identical sets of syllables. Both experimental groups attended to changes in spectral features in a similar way, but the group for which both training strings consisted of the same set of syllables responded more strongly to changes in sequence than the group for which the training strings consisted of different sets of syllables. This outcome suggests the presence of an additional learning process to learn about syllable sequence when learning about syllable phonology is not sufficient to discriminate two strings. Our study thus demonstrates that the relative importance of syllable phonology and sequence depends on how these features vary among stimuli. This indicates cognitive flexibility in the acoustic features that songbirds might use in their song recognition.


Asunto(s)
Pinzones , Animales , Pinzones/fisiología , Vocalización Animal/fisiología , Aprendizaje , Percepción Auditiva/fisiología , Cognición
6.
Sensors (Basel) ; 22(16)2022 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-36015765

RESUMEN

Traffic-related air pollution (TRAP) was monitored using a mobile sensor network on 125 urban taxis in Shanghai (November 2019/December 2020), which provide real-time patterns of air pollution at high spatial resolution. Each device determined concentrations of carbon monoxide (CO), nitrogen dioxide (NO2), and PM2.5, which characterised spatial and temporal patterns of on-road pollutants. A total of 80% road coverage (motorways, trunk, primary, and secondary roads) required 80-100 taxis, but only 25 on trunk roads. Higher CO concentrations were observed in the urban centre, NO2 higher in motorway concentrations, and PM2.5 lower in the west away from the city centre. During the COVID-19 lockdown, concentrations of CO, NO2, and PM2.5 in Shanghai decreased by 32, 31 and 41%, compared with the previous period. Local contribution related to traffic emissions changed slightly before and after COVID-19 restrictions, while changing background contributions relate to seasonal variation. Mobile networks are a real-time tool for air quality monitoring, with high spatial resolution (~200 m) and robust against the loss of individual devices.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , COVID-19 , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , COVID-19/epidemiología , China , Control de Enfermedades Transmisibles , Monitoreo del Ambiente , Humanos , Dióxido de Nitrógeno/análisis , Material Particulado/análisis
7.
Molecules ; 27(13)2022 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-35807421

RESUMEN

The ß-sheet is one of the common protein secondary structures, and the aberrant aggregation of ß-sheets is implicated in various neurodegenerative diseases. Cross-strand interactions are an important determinant of ß-sheet stability. Accordingly, both diagonal and lateral cross-strand interactions have been studied. Surprisingly, diagonal cross-strand ion-pairing interactions have yet to be investigated. Herein, we present a systematic study on the effects of charged amino acid side-chain length on a diagonal ion-pairing interaction between carboxylate- and ammonium-containing residues in a ß-hairpin. To this end, 2D-NMR was used to investigate the conformation of the peptides. The fraction folded population and the folding free energy were derived from the chemical shift data. The fraction folded population for these peptides with potential diagonal ion pairs was mostly lower compared to the corresponding peptide with a potential lateral ion pair. The diagonal ion-pairing interaction energy was derived using double mutant cycle analysis. The Asp2-Dab9 (Asp: one methylene; Dab: two methylenes) interaction was the most stabilizing (-0.79 ± 0.14 kcal/mol), most likely representing an optimal balance between the entropic penalty to enable the ion-pairing interaction and the number of side-chain conformations that can accommodate the interaction. These results should be useful for designing ß-sheet containing molecular entities for various applications.


Asunto(s)
Aminoácidos , Compuestos de Amonio , Aminoácidos/química , Ácidos Carboxílicos , Modelos Moleculares , Péptidos/química , Pliegue de Proteína , Estructura Secundaria de Proteína , Proteínas , Termodinámica
8.
Sensors (Basel) ; 21(14)2021 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-34300377

RESUMEN

Sensor technology has enabled the development of portable low-cost monitoring kits that might supplement many applications in conventional monitoring stations. Despite the sensitivity of electrochemical gas sensors to environmental change, they are increasingly important in monitoring polluted microenvironments. The performance of a compact diffusion-based Personal Exposure Kit (PEK) was assessed for real-time gaseous pollutant measurement (CO, O3, and NO2) under typical environmental conditions encountered in the subtropical city of Hong Kong. A dynamic baseline tracking method and a range of calibration protocols to address system performance were explored under practical scenarios to assess the performance of the PEK in reducing the impact of rapid changes in the ambient environment in personal exposure assessment applications. The results show that the accuracy and stability of the ppb level gas measurement is enhanced even in heterogeneous environments, thus avoiding the need for data post-processing with mathematical algorithms, such as multi-linear regression. This establishes the potential for use in personal exposure monitoring, which has been difficult in the past, and for reporting more accurate and reliable data in real-time to support personal exposure assessment and portable air quality monitoring applications.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Exposición a Riesgos Ambientales , Monitoreo del Ambiente , Hong Kong , Modelos Lineales
9.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(4): 551-557, 2021 Aug.
Artículo en Zh | MEDLINE | ID: mdl-34494525

RESUMEN

Objective To explore the performance of mobile health platform for standardized management of pregnant women with gestational diabetes mellitus(GDM). Methods A randomized controlled trial was conducted,in which 295 women with GDM were randomized into two groups(traditional management group and mobile health management group)by a computer-generated sequence.The traditional management group accepted standardized GDM management,and the mobile health management group was supplemented by mobile health management based on the standardized management.The glycemic control rate and the incidences of low birth weight,macrosomia,preterm birth,premature rupture of membranes,postpartum hemorrhage after cesarean section,neonatal asphyxia,malformation,and admission to the neonatal intensive care unit were compared between the two groups. Results The glycemic control rate in mobile health management group was significantly higher than that in the traditional management group [(67.22±22.76)% vs.(60.69±21.28)%,P=0.004].The incidences of low birth weight,macrosomia,preterm birth,premature rupture of membranes,postpartum hemorrhage after cesarean section,neonatal asphyxia,malformation,and admission to the neonatal intensive care unit demonstrated no significant differences between groups(all P > 0.05). Conclusions Mobile health applied in standardized management is conducive to the glycemic control of GDM women,whereas it does not significantly improve the pregnancy outcomes.Due to the short time of intervention,the effects of mobile health on pregnancy outcomes need further study.


Asunto(s)
Diabetes Gestacional , Nacimiento Prematuro , Telemedicina , Cesárea , Diabetes Gestacional/terapia , Femenino , Macrosomía Fetal , Humanos , Recién Nacido , Embarazo , Resultado del Embarazo
10.
Environ Sci Technol ; 54(7): 3803-3813, 2020 04 07.
Artículo en Inglés | MEDLINE | ID: mdl-32150391

RESUMEN

Brown carbon (BrC), an aerosol carbonaceous matter component, impacts atmospheric radiation and global climate because of its absorption in the near-ultraviolet-visible region. Simultaneous air sampling was conducted in two megacities of Xi'an (northern) and Hong Kong (southern) in China in winter of 2016-2017. The aim of this study is to determine and characterize the BrC compounds in collected filter samples. Characteristic absorption peaks corresponding to aromatic C-C stretching bands, organo-nitrates, and C═O functional groups were seen in spectra of Xi'an samples, suggesting that the BrC was derived from freshly smoldering biomass and coal combustion as well as aqueous formation of anthropogenic secondary organic carbon. In Hong Kong, the light absorption of secondary BrC accounted for 76% of the total absorbances of BrC. The high abundance of strong C═O groups, biogenic volatile organic compounds (BVOCs) and atmospheric oxidants suggest secondary BrC was likely formed from photochemical oxidation of BVOCs in Hong Kong. Several representative BrC molecular markers were detected using Fourier transform ion cyclotron resonance mass spectrometry and their absorption properties were simulated by quantum chemistry. The results demonstrate that light absorption capacities of secondary anthropogenic BrC with nitro-functional groups were stronger than those of biogenic secondary BrC and anthropogenic primary BrC.


Asunto(s)
Contaminantes Atmosféricos , Carbono , Aerosoles , China , Ciudades , Carbón Mineral , Monitoreo del Ambiente , Hong Kong , Material Particulado
11.
Biochem Biophys Res Commun ; 519(1): 160-165, 2019 10 29.
Artículo en Inglés | MEDLINE | ID: mdl-31481233

RESUMEN

Dihydropyrimidinase (DHPase) catalyzes the reversible cyclization of dihydrouracil to N-carbamoyl-ß-alanine in the second step of the pyrimidine degradation pathway. Whether 5-fluorouracil (5-FU), the best-known fluoropyrimidine that is used to target the enzyme thymidylate synthase for anticancer therapy, can bind to DHPase remains unknown. In this study, we found that 5-FU can form a stable complex with Pseudomonas aeruginosa DHPase (PaDHPase). The crystal structure of PaDHPase complexed with 5-FU was determined at 1.76 Šresolution (PDB entry 6KLK). Various interactions between 5-FU and PaDHPase were examined. Six residues, namely, His61, Tyr155, Asp316, Cys318, Ser289 and Asn337, of PaDHPase were involved in 5-FU binding. Except for Cys318, these residues are also known as the substrate-binding sites of DHPase. 5-FU interacts with the main chains of residues Ser289 (3.0 Å) and Asn337 (3.2 Å) and the side chains of residues Tyr155 (2.8 Å) and Cys318 (2.9 Å). Mutation at either Tyr155 or Cys318 of PaDHPase caused a low 5-FU binding activity of PaDHPase. This structure and the binding mode provided molecular insights into how the dimetal center in DHPase undergoes a conformational change during 5-FU binding. Further research can directly focus on revisiting the role of DHPase in anticancer therapy.


Asunto(s)
Amidohidrolasas/química , Antineoplásicos/química , Fluorouracilo/química , Pseudomonas aeruginosa/enzimología , Amidohidrolasas/genética , Sitios de Unión , Cristalización , Cristalografía por Rayos X , Fluorouracilo/metabolismo , Modelos Moleculares , Proteínas Mutantes/metabolismo , Mutación/genética , Unión Proteica , Homología Estructural de Proteína
12.
Metab Eng ; 54: 117-126, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30959245

RESUMEN

Bacterial polyhydroxyalkanoates (PHA) are a family of intracellular polyester granules with sizes ranging from 100 to 500 nm. Due to their small sizes, it has been very difficult to separate the PHA granules from the bacterial broths. This study aims to engineer the PHA size control mechanism to obtain large PHA granular sizes beneficial for the separation. It has been reported that phasin (PhaP) is an amphiphilic protein located on the surface of PHA granules functioning to regulate sizes and numbers of PHA granules in bacterial cells, deletions on PhaPs result in reduced PHA granule number and enhanced granule sizes. Three genes phaP1, phaP2 and phaP3 encoding three PhaP proteins were deleted in various combinations in halophilic bacterium Halomonas bluephagenesis TD01. The phaP1-knockout strain generated much larger PHA granules with almost the same size as their producing cells without significantly affecting the PHA accumulation yet with a reduced PHA molecular weights. In contrast, the phaP2- and phaP3-knockout strains produced slightly larger sizes of PHA granules with increased PHA molecular weights. While PHA accumulation by phaP3-knockout strains showed a significant reduction. All of the PhaP deletion efforts could not form PHA granules larger than a normal size of H. bluephagenesis TD01. It appears that the PHA granular sizes could be limited by bacterial cell sizes. Therefore, genes minC and minD encoding proteins that block formation of cell fission rings (Z-rings) were over-expressed in various phaP deleted H. bluephagenesis TD01, resulting in large cell sizes of H. bluephagenesis TD01 containing PHA granules with sizes of up to 10 µm that has never been observed previously. It can be concluded that PHA granule sizes are limited by the cell sizes. By engineering a large cell morphology large PHA granules can be produced by PhaP deleted mutants.


Asunto(s)
Técnicas de Silenciamiento del Gen , Halomonas , Cuerpos de Inclusión , Ingeniería Metabólica , Polihidroxialcanoatos , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Halomonas/genética , Halomonas/metabolismo , Cuerpos de Inclusión/genética , Cuerpos de Inclusión/metabolismo , Polihidroxialcanoatos/biosíntesis , Polihidroxialcanoatos/genética
13.
Atmos Environ (1994) ; 214: 1-116825, 2019 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-34434068

RESUMEN

Air monitoring is desirable in many places to understand dynamic pollution trends and sources and improve knowledge of population exposure. While highly miniaturized low cost sensor technology is quickly evolving, there is also a need for the advancement of mid-tier systems that are closer to reference-grade technologies in their longevity and performance, but also feature compactness that requires less significant infrastructure. This project evaluated the performance of a prototype solar-powered air monitoring system known as a Village Green Project (VGP) system with wireless data transmission that was deployed on a school rooftop in Hong Kong and operated for over one year. The system provided highly time-resolved and long-term data utilizing mid-tier cost ozone, PM2.5 and meteorological instruments. It operated with very minimal maintenance but shading by a nearby building reduced solar radiation, thus battery run time, over the 16-months measurement period, approximately 330,000 1-min observations were recorded (data completeness of ~62%). The monitoring data were evaluated by comparison with a nearby Hong Kong Environment Protection Department (EPD) station and exhibited good performance for 1-h resolution (R 2 = 0.74 for PM2.5 and R 2 = 0.76 for ozone). Furthermore as a demonstration, a nonparametric regression (NPR) model was applied for identifying the location of pollution source, combining air pollution and meteorological measurements. In addition, based on the high time-resolution wind data, local-scale back-trajectories were calculated as an input for receptor-oriented Nonparametric Trajectory Analysis (NTA) model. The combination of the VGP air monitoring system and NTA model identified apparent local sources in urban area. The demonstration was largely successful and operational improvements are clearly suggested to insure better siting and configurations to insure adequate power and air flow.

14.
Sensors (Basel) ; 18(2)2018 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-29360749

RESUMEN

The increasing applications of low-cost air sensors promises more convenient and cost-effective systems for air monitoring in many places and under many conditions. However, the data quality from such systems has not been fully characterized and may not meet user expectations in research and regulatory uses, or for use in citizen science. In our study, electrochemical sensors (Alphasense B4 series) for carbon monoxide (CO), nitric oxide (NO), nitrogen dioxide (NO2), and oxidants (Ox) were evaluated under controlled laboratory conditions to identify the influencing factors and quantify their relation with sensor outputs. Based on the laboratory tests, we developed different correction methods to compensate for the impact of ambient conditions. Further, the sensors were assembled into a monitoring system and tested in ambient conditions in Hong Kong side-by-side with regulatory reference monitors, and data from these tests were used to evaluate the performance of the models, to refine them, and validate their applicability in variable ambient conditions in the field. The more comprehensive correction models demonstrated enhanced performance when compared with uncorrected data. One over-arching observation of this study is that the low-cost sensors may promise excellent sensitivity and performance, but it is essential for users to understand and account for several key factors that may strongly affect the nature of sensor data. In this paper, we also evaluated factors of multi-month stability, temperature, and humidity, and considered the interaction of oxidant gases NO2 and ozone on a newly introduced oxidant sensor.

15.
Cancer Sci ; 108(3): 469-477, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28004478

RESUMEN

Although inhibitors targeting tumor angiogenic pathway have provided improvement for clinical treatment in patients with various solid tumors, the still very limited anti-cancer efficacy and acquired drug resistance demand new agents that may offer better clinical benefits. In the effort to find a small molecule potentially targeting several key pathways for tumor development, we designed, discovered and evaluated a novel multi-kinase inhibitor, CS2164. CS2164 inhibited the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα and c-Kit), mitosis-related kinase Aurora B and chronic inflammation-related kinase CSF-1R in a high potency manner with the IC50 at a single-digit nanomolar range. Consequently, CS2164 displayed anti-angiogenic activities through suppression of VEGFR/PDGFR phosphorylation, inhibition of ligand-dependent cell proliferation and capillary tube formation, and prevention of vasculature formation in tumor tissues. CS2164 also showed induction of G2/M cell cycle arrest and suppression of cell proliferation in tumor tissues through the inhibition of Aurora B-mediated H3 phosphorylation. Furthermore, CS2164 demonstrated the inhibitory effect on CSF-1R phosphorylation that led to the suppression of ligand-stimulated monocyte-to-macrophage differentiation and reduced CSF-1R+ cells in tumor tissues. The in vivo animal efficacy studies revealed that CS2164 induced remarkable regression or complete inhibition of tumor growth at well-tolerated oral doses in several human tumor xenograft models. Collectively, these results indicate that CS2164 is a highly selective multi-kinase inhibitor with potent anti-tumor activities against tumor angiogenesis, mitosis and chronic inflammation, which may provide the rationale for further clinical assessment of CS2164 as a therapeutic agent in the treatment of cancer.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Inhibidores de la Angiogénesis/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Puntos de Control de la Fase M del Ciclo Celular/efectos de los fármacos , Mitosis/efectos de los fármacos , Neovascularización Patológica/tratamiento farmacológico , Fenilendiaminas/uso terapéutico , Quinolinas/uso terapéutico , Células 3T3 , Animales , Aurora Quinasa B/antagonistas & inhibidores , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Histonas/metabolismo , Humanos , Inflamación/tratamiento farmacológico , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Simulación del Acoplamiento Molecular , Naftalenos , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-kit/antagonistas & inhibidores , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/antagonistas & inhibidores , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/antagonistas & inhibidores , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Sensors (Basel) ; 17(8)2017 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-28825633

RESUMEN

Emerging low-cost gas sensor technologies have received increasing attention in recent years for air quality measurements due to their small size and convenient deployment. However, in the diverse applications these sensors face many technological challenges, including sensor drift over long-term deployment that cannot be easily addressed using mathematical correction algorithms or machine learning methods. This study aims to develop a novel approach to auto-correct the drift of commonly used electrochemical nitrogen dioxide (NO2) sensor with comprehensive evaluation of its application. The impact of environmental factors on the NO2 electrochemical sensor in low-ppb concentration level measurement was evaluated in laboratory and the temperature and relative humidity correction algorithm was evaluated. An automated zeroing protocol was developed and assessed using a chemical absorbent to remove NO2 as a means to perform zero correction in varying ambient conditions. The sensor system was operated in three different environments in which data were compared to a reference NO2 analyzer. The results showed that the zero-calibration protocol effectively corrected the observed drift of the sensor output. This technique offers the ability to enhance the performance of low-cost sensor based systems and these findings suggest extension of the approach to improve data quality from sensors measuring other gaseous pollutants in urban air.

17.
J Am Chem Soc ; 138(17): 5543-6, 2016 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-27082786

RESUMEN

The new ion-exchange oxy-sulfide material has a three-dimensional open framework comprising the pseudo-T4 supertetrahedral [In4Sn16O10S34](12-) cluster. This material has large pores and is a fast ion exchanger. It exhibits high selectivity in sequestering heavy metal ions from aqueous solutions including solutions containing heavy concentrations of sodium, calcium, ammonium, magnesium, zinc, carbonate, phosphate, and acetate ions. Moreover, the ion-exchange efficiency in competitive ion-exchange experiments involving mixtures of metal ions is significantly higher than for solutions of single metal ions.

18.
J Appl Toxicol ; 36(10): 1355-63, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27191363

RESUMEN

Titanium dioxide (TiO2 ) nanoparticles are widely used in daily human life, and were reported to elicit biological effects such as oxidative stress either generating reactive oxygen species (ROS) or causing cell necrosis without generating ROS, whose underlying molecular mechanisms are not yet known. In this study, the role of dissolved oxygen in TiO2 catalytic activity in dark environment, and long-term cytotoxic effects of TiO2 exposure were investigated. To determine the effect of dissolved oxygen, the anatase-TiO2 nanoparticle suspension was prepared both in deoxygenated and regular MilliQ water, and a ~ 9-fold higher ROS in regular MilliQ samples was observed compared to deoxygenated samples while in the dark, which suggested dissolved oxygen as the driving agent behind the TiO2 catalytic reaction. On the other hand, the differential cell viability and endogenous ROS activity was demonstrated through a sensitive macrophage-based assay, on a dose- and time-dependent manner. Both the cell number and endogenous ROS activity increased with increase in time till 48 h, followed by a reduction at 72 h exposure period. Long-term exposures to these nanoparticles even at low concentrations were found detrimental to cells, where late apoptosis until 48 h and necrosis at 72 h leading to cell death were noted. Late apoptotic events and cell membrane cytoskeletal actin rearrangement observed were hypothesized to be induced by particle-mediated cellular ROS. This in addition to radical generation ability of TiO2 in the dark will help further in better understanding of the toxicity mechanism in cells beyond ROS generation. Copyright © 2016 John Wiley & Sons, Ltd.


Asunto(s)
Ciclo Celular/efectos de los fármacos , Macrófagos/efectos de los fármacos , Nanopartículas/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Titanio/toxicidad , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Permeabilidad de la Membrana Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Macrófagos/metabolismo , Macrófagos/patología , Ratones , Microscopía Electrónica de Transmisión , Nanopartículas/química , Oxígeno/análisis , Tamaño de la Partícula , Propiedades de Superficie , Titanio/química
19.
Sensors (Basel) ; 16(2): 211, 2016 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-26861336

RESUMEN

This study presents the development and evaluation of a next generation air monitoring system with both laboratory and field tests. A multi-parameter algorithm was used to correct for the impact of environmental conditions on the electrochemical sensors for carbon monoxide (CO) and nitrogen dioxide (NO2) pollutants. The field evaluation in an urban roadside environment in comparison to designated monitors showed good agreement with measurement error within 5% of the pollutant concentrations. Multiple sets of the developed system were then deployed in the Hong Kong Marathon 2015 forming a sensor-based network along the marathon route. Real-time air pollution concentration data were wirelessly transmitted and the Air Quality Health Index (AQHI) for the Green Marathon was calculated, which were broadcast to the public on an hourly basis. The route-specific sensor network showed somewhat different pollutant patterns than routine air monitoring, indicating the immediate impact of traffic control during the marathon on the roadside air quality. The study is one of the first applications of a next generation sensor network in international sport events, and it demonstrated the usefulness of the emerging sensor-based air monitoring technology in rapid network deployment to supplement existing air monitoring.

20.
Proc Natl Acad Sci U S A ; 108(15): 6181-6, 2011 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-21444806

RESUMEN

Human evolution is characterized by the rapid expansion of brain size and drastic increase in cognitive capabilities. It has long been suggested that these changes were accompanied by modifications of brain metabolism. Indeed, human-specific changes on gene expression or amino acid sequence were reported for a number of metabolic genes, but actual metabolite measurements in humans and apes have remained scarce. Here, we investigate concentrations of more than 100 metabolites in the prefrontal and cerebellar cortex in 49 humans, 11 chimpanzees, and 45 rhesus macaques of different ages using gas chromatography-mass spectrometry (GC-MS). We show that the brain metabolome undergoes substantial changes, both ontogenetically and evolutionarily: 88% of detected metabolites show significant concentration changes with age, whereas 77% of these metabolic changes differ significantly among species. Although overall metabolic divergence reflects phylogenetic relationships among species, we found a fourfold acceleration of metabolic changes in prefrontal cortex compared with cerebellum in the human lineage. These human-specific metabolic changes are paralleled by changes in expression patterns of the corresponding enzymes, and affect pathways involved in synaptic transmission, memory, and learning.


Asunto(s)
Evolución Biológica , Metaboloma , Corteza Prefrontal/metabolismo , Proteínas/metabolismo , Humanos
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