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1.
EClinicalMedicine ; 64: 102195, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37731938

RESUMEN

Background: COVID-19 vaccines that offer broad-spectrum protection are needed. We aimed to evaluate the safety and immunogenicity of multivalent vaccines, SCTV01E and SCTV01C, and compare them with an inactivated vaccine. Methods: In the phase 3 trial (ClinicalTrials.gov: NCT05323461), adult participants previously vaccinated with Sinopharm's inactivated SARS-CoV-2 vaccine (BBBIP-CorV) were assigned to receive one booster dose of BBBIP-CorV, 20 µg SCTV01C, or 30 µg SCTV01E. The primary endpoint was to evaluate the geometric mean titers (GMT) of neutralizing antibody (nAb) against the Delta and Omicron BA.1 variants on day 28 after injection. Additional endpoints included GMTs of nAb against Delta (B.1.617.2) and Omicron BA.1 variants on day 180, GMTs against BA.5 on day 28, as well as solicited adverse events (AEs) within seven days, unsolicited AEs within 28 days, and serious AEs, AEs of special interest within 180 days after vaccination. Findings: Between May 30, 2022 and October 28, 2022, a total of 1351 participants were randomized to BBBIP-CorV, SCTV01C, or SCTV01E in a 1:1:1 ratio, with immunogenicity assessments performed on the first 300 participants. For BBBIP-CorV, SCTV01C, and SCTV01E groups, the day 28 GMTs of neutralizing antibody against Omicron BA.1 were a 2.38-, 19.37-, and 28.06-fold increase from baseline; the GMTs against Omicron BA.5 were 2.07-, 15.89- and 21.11-fold increases; the GMTs against Delta variants were 1.97-, 12.76-, and 15.88-fold increases, respectively. The day 28 geometric mean ratio (GMR) of SCTV01C/BBIBP-CorV for Omicron BA.1 was 6.49 (95% CI: 4.75, 8.88), while the GMR of SCTV01E/BBIBP-CorV was 9.56 (95% CI: 6.85, 13.33). For the Delta variant, the day 28 GMR of SCTV01C/BBIBP-CorV was 6.26 (95% CI: 4.78, 8.19), and the day 28 GMR of SCTV01E/BBIBP-CorV was 7.26 (95% CI: 5.51, 9.56). On Day 180, the GMTs against Omicron BA.1 were 2.80-, 9.51-, and 15.56-fold increase from baseline, while those against Delta were 1.58-, 5.49-, and 6.63-fold for BBBIP-CorV, SCTV01C, and SCTV01E groups, respectively. Subgroup analyses showed that SCTV01C and SCTV01E induced uniformly high GMTs against both BA.1 and BA.5, demonstrating its superiority over BBIBP-CorV, regardless of baseline GMT levels. Safety and reactogenicity were similar among the three vaccines. Most AEs were Grade 1 or 2. There were 15 ≥Grade 3 AEs: 6 in the BBIBP-CorV group, 4 in the SCTV01C group and 5 in the SCTV01E group. No SAE was reported and one grade 1 AESI (Bell's palsy) was observed in SCTV01C group. Interpretation: A booster dose of the tetravalent vaccine SCTV01E consistently induced high neutralizing antibody responses against Omicron BA.1, BA.5, and Delta variants, demonstrating superiority over inactivated vaccine. There is evidence to suggest that SCTV01E may have GMT superiority over bivalent vaccine SCTV01C against Delta, BA.1 and BA.5 variants. Funding: This study was sponsored by Sinocelltech Ltd., and funded by the Beijing Science and Technology Planning Project [Z221100007922012] and the National Key Research and Development Program of China [2022YFC0870600].

2.
Traffic Inj Prev ; 24(4): 362-370, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36976788

RESUMEN

OBJECTIVE: To effectively explore the impacts of several key factors on taxi drivers' traffic violations and provide traffic management departments with scientific decisions to reduce traffic fatalities and injuries. METHODS: 43,458 electronic enforcement data about taxi drivers' traffic violations in Nanchang City, Jiangxi Province, China, from July 1, 2020, to June 30, 2021, were utilized to explore the characteristics of traffic violations. A random forest algorithm was used to predict the severity of taxi drivers' traffic violations and 11 factors affecting traffic violations, including time, road conditions, environment, and taxi companies were analyzed using the Shapley Additionality Explanation (SHAP) framework. RESULTS: Firstly, the ensemble method Balanced Bagging Classifier (BBC) was applied to balance the dataset. The results showed that the imbalance ratio (IR) of the original imbalanced dataset reduced from 6.61% to 2.60%. Moreover, a prediction model for the severity of taxi drivers' traffic violations was established by using the Random Forest, and the results showed that accuracy, m_F1, m_G-mean, m_AUC, and m_AP obtained 0.877, 0.849, 0.599, 0.976, and 0.957, respectively. Compared with the algorithms of Decision Tree, XG Boost, Ada Boost, and Neural Network, the performance measures of the prediction model based on Random Forest were the best. Finally, the SHAP framework was used to improve the interpretability of the model and identify important factors affecting taxi drivers' traffic violations. The results showed that functional districts, location of the violation, and road grade were found to have a high impact on the probability of traffic violations; their mean SHAP values were 0.39, 0.36, and 0.26, respectively. CONCLUSIONS: Findings of this paper may help to discover the relationship between the influencing factors and the severity of traffic violations, and provide a theoretical basis for reducing the traffic violations of taxi drivers and improving the road safety management.


Asunto(s)
Conducción de Automóvil , Humanos , Accidentes de Tránsito , Bosques Aleatorios , China/epidemiología , Algoritmos
3.
EBioMedicine ; 87: 104386, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36470077

RESUMEN

BACKGROUND: Booster vaccination is an efficient way to address the waning protection of vaccines and immune escape of SARS-CoV-2 variants. We aimed to assess the safety and immunogenicity of SCTV01C, a novel bivalent protein vaccine as a booster for people who previously received two doses of mRNA vaccine. METHODS: In this randomized, phase 1/2 trial, adults fully vaccinated with mRNA vaccines 3-24 month earlier were enrolled. Participants received SCTV01C at 20 µg, 40 µg or placebo. The primary endpoints were adverse reactions within 7 days and immunogenicity on Day 28 after vaccination. This trial was registered with ClinicalTrials.gov (NCT05043311). FINDINGS: Between January 27 and April 28, 2022, 234 adults were randomly assigned to receive SCTV01C or placebo. The most common solicited adverse events (AEs) were Grade 1 injection-site pain (10.7%) and pyrexia (6.3%). There were no reports of Grade 3 or above solicited AE, serious AEs or AEs of special interests. On Day 28 post the booster, the geometric mean concentrations (GMCs) of the specific binding IgG antibodies to spike protein for placebo, 20 µg and 40 µg SCTV01C were 1649, 4153 and 5354 BAU/mL, with fold of increase from baseline of 1.0, 2.8 and 3.4-fold, respectively. GMTs of neutralizing antibodies against live Delta variant were 1280, 3542, and 4112, with fold of increase of 1.1, 3.9 and 4.1-fold, respectively; GMTs of neutralizing antibodies against live Omicron variant were 218, 640, and 1083, with fold of increase of 1.1, 4.4 and 5.1-fold, respectively. Participants with low neutralizing antibody titers at baseline (below the lower limit of quantitation) had 64.0 and 49.4-fold of increase in GMTs for Delta and Omicron, respectively. INTERPRETATION: The heterologous booster of SCTV01C was safe, and induced uniformly high cross-neutralization antibody responses against Delta and Omicron variants. FUNDING: Beijing Science and Technology Plan Project (Z221100007922012) and the National Key Research and Development Program of China (2022YFC0870600) supported this study.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Adulto , Humanos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Método Doble Ciego , Vacunas de ARNm , SARS-CoV-2 , Vacunas Combinadas , Vacunas contra la COVID-19/efectos adversos
4.
Artículo en Inglés | MEDLINE | ID: mdl-36429560

RESUMEN

As a policy that is widely used worldwide, Vision Zero is a long-term strategic goal for road safety in China. The aim of this paper is to examine the literature in the field of Vision Zero retrieved by the Web of Science (WOS) Core Collection database from 1997 to 2021 based on mapping knowledge domain (MKD) and bibliometric methods. In this paper, we analyzed the overall development level of Vision Zero at different stages using the statistical analysis of the distribution of literature years. Based on the analysis, four major research directions of Vision Zero are obtained through keywords co-occurrence analysis, including "Vision Zero in road safety", "vulnerable road users' risks", "effect of speed on severity", and "responsibility management for crashes". Furthermore, we explore the influence and development potential of each country and region of Vision Zero based on the number and citation frequency of the literature, and the distribution of time dimensions. Among the research topics, all countries and regions are clustered into four clusters, and the current status of Vision Zero for countries in the most influential clusters, which include Sweden, the United States, Australia, China, and Norway, have been presented. Finally, an analysis of road safety in China is carried out, which includes displaying the changes in the number of road accidents, fatalities, and serious injuries in China between 2009 and 2018, comparing the fatalities per 10,000 vehicles and the fatalities per 100,000 people between China and other countries, and describing China's strategic routes toward Vision Zero.


Asunto(s)
Accidentes de Tránsito , Políticas , Humanos , Estados Unidos , Seguridad , China , Bibliometría
5.
Artículo en Inglés | MEDLINE | ID: mdl-36141769

RESUMEN

The efficiency and emission levels of taxi operations are influenced by taxi drivers' empirical judgments of hotspot travel areas. In this study, we exploited vehicle specific power (VSP) approaches and taxi trajectory data in a 1000 × 1000 m grid to calculate emission and revenue efficiency-related indicators and explored their spatial and temporal characteristics. Then, the entropy weight TOPSIS method was employed to identify the grids with the top comprehensive ranking of the indicators in the period to replace the driver experience. Finally, the k-means clustering method was utilized to identify the recommended road segments in the hotspot grid. The data from Nanchang City in China showed the following. (1) The study area was divided into 7553 grids, and the main travel and emission areas were located in the West Lake, Qingyunpu and Qingshan Lake districts (less than 200 grids). However, revenue efficiency-related indicators in this region are at a moderately low level. For example, the order revenue was about 0.9-1.2 RMB/min, and the average was 1.3-1.5 RMB/min. Areas with high trip demand had low revenue efficiency. (2) Five indicators related to emissions and revenue efficiency were selected. Of these, grid boarding points (G-bp) maintained the highest weight, reaching a maximum of 0.48 from 7:00 a.m. to 9:00 a.m. The ranking of secondary indicators was time varying. Hotspot grids and road segments were identified within each period. For example, from 1:00 a.m. to 3:00 a.m., (66,65), (68,65) were identified as hotspot grids. People's Park North Gate near the road was identified as the recommended section from 1:00 a.m. to 3:00 a.m. This study can provide recommended grids and sections for idle cruising taxis.


Asunto(s)
Automóviles , Carbono , China , Ciudades , Humanos , Viaje
6.
Comput Intell Neurosci ; 2022: 3160449, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35463280

RESUMEN

The evaluation of take-over performance and take-over safety performance is critical to improving the take-over performance of conditionally automated driving, and few studies have attempted to evaluate take-over safety performance. This study applied a binary logistic model to construct a take-over safety performance evaluation model. A take-over driving simulator was established, and a take-over simulation experiment was carried out. In the experiment, data were collected from 15 participants who took over the vehicle and performed emergency evasive maneuvers while performing non-driving-related task (NDRT). Then, to calibrate the abnormal trajectory, the Kalman filter is adopted to filter the disturbed vehicle positioning data and the belief rule-based (BRB) method is proposed to warn irregular driving behavior. The results revealed that the accident rate of male participants is higher than that of female participants in the three frequency take-over experiment, and the overall driving performance of female participants is higher than that of male participants. Meanwhile, medium and high take-over frequencies have a significant effect on the prevention of vehicle collisions. In the take-over safety performance evaluation model, the minimum time to collision (TTC) of 2.3 s is taken as the boundary between the dangerous group and the safety group, and the model prediction accuracy rate is 87.7%. In sum, this study enriches existing research on the safety performance evaluation of conditionally automated driving take-over and provides important implications for the design of driving simulators and the performance and safety evaluation of human-machine take-over.


Asunto(s)
Conducción de Automóvil , Vehículos Autónomos , Accidentes de Tránsito/prevención & control , Automatización , Simulación por Computador , Femenino , Humanos , Modelos Logísticos , Masculino , Tiempo de Reacción
7.
Comput Intell Neurosci ; 2022: 5698393, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35126496

RESUMEN

"Road rage," namely, driving anger, has been becoming increasingly common in auto era. As "road rage" has serious negative impact on road safety, it has attracted great concern to relevant scholar, practitioner, and governor. This study aims to propose a model to effectively and efficiently detect driving anger states with different intensities for taking targeted intervening measures in intelligent connected vehicles. Forty-two private car drivers were enrolled to conduct naturalistic experiments on a predetermined and busy route in Wuhan, China, where drivers' anger can be induced by various incentive events like weaving/cutting in line, jaywalking, and traffic congestion. Then, a data-driven model based on double-layered belief rule base is proposed according to the accumulation of the naturalistic experiments data. The proposed model can be used to effectively detect different driving anger states as a function of driver characteristics, vehicle motion, and driving environments. The study results indicate that average accuracy of the proposed model is 82.52% for all four-intensity driving anger states (none, low, medium, and high), which is 1.15%, 1.52%, 3.53%, 5.75%, and 7.42%, higher than C4.5, BPNN, NBC, SVM, and kNN, respectively. Moreover, the runtime ratio of the proposed model is superior to that of those models except for C4.5. Hence, the proposed model can be implemented in connected intelligent vehicle for detecting driving anger states in real time.


Asunto(s)
Conducción de Automóvil , Accidentes de Tránsito , Ira , China , Humanos
8.
Comput Intell Neurosci ; 2022: 7754961, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35154305

RESUMEN

Mapping knowledge domain (MKD) is an important application in bibliometrics, which is a method of visually presenting and explaining newly developed interdisciplinary scientific fields using data mining, information analysis, scientific measurement, and graphic rendering. This study combines applied mathematics, visual analysis technology, information science, and scientometrics to systematically analyze the development status, research distribution, and future trend of the heterogeneous traffic flow by using the MKD software tools VOSviewer and CiteSpace. Based on the MKD and Bibliometrics approaches, 4709 articles have been studied, which were published by Science Citation Index Expanded (SCIE) and Social Sciences Citation Index (SSCI) from 2004 to 2021 in the field of heterogeneous traffic flows. Firstly, this paper presents the annual numbers of articles, origin countries, main research organizations, and groups as well as the source journals on heterogeneous traffic flow studies. Then, cocitation analysis is used to divide heterogeneous traffic flow into three main research directions, which include "heterogeneous traffic flow model," "traffic flow capacity analysis," and "traffic flow stability analysis." The keyword cooccurrence analysis is applied to identify five dominant clusters: "modeling and optimization methods," "traffic flow characteristics analysis," "driving behavior analysis," "simulation experiment," and "policies and barriers." Finally, burst keywords were studied according to the publication date to present more clearly the change of research focus and direction over time.


Asunto(s)
Conducción de Automóvil , Bibliometría , Minería de Datos , Conocimiento , Proyectos de Investigación
9.
Comput Intell Neurosci ; 2021: 5412016, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34899895

RESUMEN

This paper proposes a mixed decision strategy for freight and passenger transportation in metro systems during off-peak hours (MTS-OPH). The definition of the mixed decision strategy is proposed, and fixed and flexible loading modes are considered for different passenger flow volumes. A mathematical model of the MTS-OPH is proposed and solved using an improved variable neighborhood search algorithm. Case studies demonstrate the performance and applicability of the proposed model and algorithm, and the MTS-OPH is discussed for different delivery distances, passenger flows, and metro network types. The proposed strategy is suitable for long-distance delivery, and the proposed model framework can be applied to different types of metro networks with different levels of complexity. The mixed decision strategy provides a decision support tool for metro and freight companies and can propose corresponding solutions according to different passenger flows.


Asunto(s)
Modelos Teóricos , Transportes , Algoritmos
10.
Antimicrob Agents Chemother ; 65(11): e0106321, 2021 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-34491805

RESUMEN

SCTA01 is a novel monoclonal antibody with promising prophylactic and therapeutic potential for COVID-19. This study aimed to evaluate the safety, tolerability, pharmacokinetics (PK) and immunogenicity of SCTA01 in healthy adults. This was a randomized, double-blind, placebo-controlled, dose escalation phase I clinical trial. Healthy adults were randomly assigned to cohort 1 (n = 5; 3:2), cohort 2 (n = 8; 6:2), cohort 3, or cohort 4 (both n = 10; 8:2) to receive SCTA01 (5, 15, 30, and 50 mg/kg, respectively) versus placebo. All participants were followed up for clinical, laboratory, PK, and immunogenicity assessments for 84 days. The primary outcomes were the dose-limiting toxicity (DLT) and maximal tolerable dose (MTD), and the secondary outcomes included PK parameters, immunogenicity, and adverse events (AE). Of the 33 participants, 18 experienced treatment-related AEs; the frequency was 52.0% (13/25) in participants receiving SCTA01 and 62.5% (5/8) in those receiving placebo. All AEs were mild. There was no serious AE or death. No DLT was reported, and the MTD of SCTA01 was not reached. SCTA01 with a dose range of 5 to 50 mg/kg had nearly linear dose-proportional increases in Cmax and AUC parameters. An antidrug antibody response was detected in four (16.0%) participants receiving SCTA01, with low titers, between the baseline and day 28, but all became negative later. In conclusion, SCTA01 up to 50 mg/kg was safe and well-tolerated in healthy participants. Its PK parameters were nearly linear dose-proportional. (This study has been registered at ClinicalTrials.gov under identifier NCT04483375.).


Asunto(s)
COVID-19 , SARS-CoV-2 , Adulto , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Antivirales , Método Doble Ciego , Humanos
11.
J Affect Disord ; 292: 295-304, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34134028

RESUMEN

BACKGROUND: Suicidality is common in people living with HIV/AIDS. However, the prevalence estimates of the suicidality vary between studies. Here, we performed a systematic review and estimated the prevalence of suicidal behavior in this population. METHODS: Systematic search of PubMed, Embase, Web of Science, CINAHL, Scopus and PsycINFO for relevant studies published before August 29, 2020. A random-effects model was used to pool the estimates of the prevalence of suicidal ideation, attempts and plans, which were also stratified by continent or region and screening instrument from the studies included in this meta-analysis. RESULTS: Suicide prevalence data were extracted from 36 studies(n=32,818) from 15 countries. The overall pooled crude prevalence estimates of suicidal ideation, plans, and attempts were 20.9% [95% confidence interval (CI) 16.5-21.6%],8.1% (95% CI 5.4-11.3%), and 7.5% (95% CI 5.7-9.5%), respectively. For lifetime suicidal ideation and attempts prevalence, this was 22.4% (95% CI 15.9-29.8%), and 12.0% (95% CI 6.9- 18.1%), respectively. Summary prevalence estimates ranged across assessment modalities from 6.5% to 33.7%. Pooled estimates were generally higher for females, as compared with males (risk ratios in the range 1.48-1.85). The leave-one-out analysis showed that no single study significantly affected the final pooled results.


Asunto(s)
Infecciones por VIH , Ideación Suicida , Femenino , Infecciones por VIH/epidemiología , Humanos , Masculino , Oportunidad Relativa , Prevalencia , Intento de Suicidio
12.
Opt Express ; 29(6): 9624-9634, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33820386

RESUMEN

We demonstrate a highly efficient method for the generation of a high-field terahertz (THz) pulse train via optical rectification (OR) in congruent lithium niobate (LN) crystals driven by temporally shaped laser pulses. A narrowband THz pulse has been successfully achieved with sub-percent level conversion efficiency and multi MV/cm peak field at 0.26 THz. For the single-cycle THz generation, we achieved a THz pulse with 373-µJ energy in a LN crystal excited by a 100-mJ laser pulse at room temperature. The conversion efficiency is further improved to 0.77 % pumped by a 20-mJ laser pulse with a smaller pump beam size (6 mm in horizontal and 15 mm in vertical). This method holds great potential for generating mJ-level narrow-band THz pulse trains, which may have a major impact in mJ-scale applications like terahertz-based accelerators and light sources.

13.
Nature ; 590(7847): 576-579, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33627811

RESUMEN

The use of particle accelerators as photon sources has enabled advances in science and technology1. Currently the workhorses of such sources are storage-ring-based synchrotron radiation facilities2-4 and linear-accelerator-based free-electron lasers5-14. Synchrotron radiation facilities deliver photons with high repetition rates but relatively low power, owing to their temporally incoherent nature. Free-electron lasers produce radiation with high peak brightness, but their repetition rate is limited by the driving sources. The steady-state microbunching15-22 (SSMB) mechanism has been proposed to generate high-repetition, high-power radiation at wavelengths ranging from the terahertz scale to the extreme ultraviolet. This is accomplished by using microbunching-enabled multiparticle coherent enhancement of the radiation in an electron storage ring on a steady-state turn-by-turn basis. A crucial step in unveiling the potential of SSMB as a future photon source is the demonstration of its mechanism in a real machine. Here we report an experimental demonstration of the SSMB mechanism. We show that electron bunches stored in a quasi-isochronous ring can yield sub-micrometre microbunching and coherent radiation, one complete revolution after energy modulation induced by a 1,064-nanometre-wavelength laser. Our results verify that the optical phases of electrons can be correlated turn by turn at a precision of sub-laser wavelengths. On the basis of this phase correlation, we expect that SSMB will be realized by applying a phase-locked laser that interacts with the electrons turn by turn. This demonstration represents a milestone towards the implementation of an SSMB-based high-repetition, high-power photon source.

14.
Appl Opt ; 59(35): 10995-11002, 2020 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-33361924

RESUMEN

An observation of prior-damage behavior inside a high-finesse optical resonator is reported. Intra-cavity average power drops appeared with magnitude and time scale depending on the power level. Increasing further the incident laser beam power led to irreversible damage of the cavity coupling mirror surface. The origin of this phenomenon is investigated with post mortem mirror surface imaging and analysis of the signals reflected and transmitted by the enhancement cavity. Scattering losses induced by surface deformation due to a hot-spot surface contaminant is found to be most likely the dominant physics process behind this phenomenon.

15.
Chem Commun (Camb) ; 56(97): 15321-15324, 2020 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-33205785

RESUMEN

We developed a new strategy to overcome the MDR of etoposide using self-assembling nanofibers. Compared with the original etoposide, the inhibitory activity of Nap-GFFpYK-etoposide1/2 against murine Lewis lung cancer or breast cancer cells was increased 10 times, and 20 times on these cells with artificially overexpressed MDR1. Our method to synthesize and separate etoposide isomers provides a new strategy for the modification of this drug.


Asunto(s)
Antineoplásicos/síntesis química , Portadores de Fármacos/química , Etopósido/química , Nanofibras/química , Péptidos/síntesis química , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Permeabilidad de la Membrana Celular , Composición de Medicamentos , Liberación de Fármacos , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Ratones , Imagen Óptica , Péptidos/farmacología , Técnicas de Síntesis en Fase Sólida , Espectrometría de Fluorescencia
16.
Hypertension ; 76(4): 1124-1133, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32772647

RESUMEN

Pulmonary hypertension (PH) is a rare and fatal disorder involving the vascular remodeling of pulmonary arteries mediated by the enhanced proliferation of pulmonary artery smooth muscle cells (PASMCs). Long noncoding RNAs are a subclass of regulatory molecules with diverse cellular functions, but their role in PH remains largely unexplored. We aimed to identify and determine the functions of long noncoding RNAs involved in hypoxia-induced PH and PASMC proliferation. RNA sequencing in a hypoxic mouse model identified hypoxia-regulated long noncoding RNAs, including Rps4l. Rps4l expression was significantly reduced in PH-model mice and hypoxic PASMCs. The subcellular localization of Rps4l was detected by RNA fluorescence in situ hybridization and quantification of nuclear/cytoplasmic RNA. Rps4l overexpression rescued pulmonary arterial hypertension features, as demonstrated by right ventricle hypertrophy, right ventricular systolic pressure, hemodynamics, cardiac function, and vascular remodeling. At the cellular level, Rps4l overexpression weakened cell viability and proliferation and suppressed cell cycle progression. Potential Rps4l-binding proteins were identified via RNA pull-down followed by mass spectrometry, RNA immunoprecipitation, and microscale thermophoresis. These results indicated that Rps4l is associated with and affects the stabilization of ILF3 (interleukin enhancer-binding factor 3). Rps41 further regulates the levels of HIF-1α and consequently leads to hypoxia-induced PASMC proliferation and migration. Our results showed that in hypoxic PASMCs, Rps4l expression decreases due to regulation by hypoxia. This decrease affects the proliferation, migration, and cell cycle progression of PASMCs through ILF3/HIF-1α. These results provide a theoretical basis for further investigations into the pathological mechanism of hypoxic PH and may provide insight for the development of novel treatments.


Asunto(s)
Proliferación Celular/fisiología , Hipertensión Pulmonar/metabolismo , Hipoxia/metabolismo , Miocitos del Músculo Liso/metabolismo , Arteria Pulmonar/metabolismo , ARN Largo no Codificante/metabolismo , Animales , Regulación hacia Abajo , Hipertensión Pulmonar/patología , Hipoxia/genética , Hipoxia/patología , Ratones , Ratones Transgénicos , Miocitos del Músculo Liso/patología , Arteria Pulmonar/patología , ARN Largo no Codificante/genética , Remodelación Vascular/fisiología
17.
Sci Prog ; 103(1): 36850419886471, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31829790

RESUMEN

The prevention of severe injuries during crashes has become one of the leading issues in traffic management and transportation safety. Identifying the impact factors that affect traffic injury severity is critical for reducing the occurrence of severe injuries. In this study, the Fatality Analysis Reporting System data are selected as the dataset for the analysis. An algorithm named improved Markov Blanket was proposed to extract the significant and common factors that affect crash injury severity from 29 variables related to driver characteristics, vehicle characteristics, accidents types, road condition, and environment characteristics. The Pearson correlation coefficient test is applied to verify the significant correlation between the selected factors and traffic injury severity. Two widely used classification algorithms (Bayesian networks and C4.5 decision tree) were employed to evaluate the performance of the proposed feature selection algorithm. The calculation result of the correlation coefficient, accuracy of classification, and classification error rate indicated that the improved Markov Blanket not only could extract the significant impact factors but could also improve the accuracy of classification. Meanwhile, the relationship between five selected factors (atmospheric condition, time of crash, alcohol test result, crash type, and driver's distraction) and traffic injury severity was also analyzed in this study. The results indicated that crashes occurred in bad weather condition (e.g. fog or worse), in night time, in drunk driving, in crash type of single driver, and in distracted driving, which are associated with more severe injuries.


Asunto(s)
Accidentes de Tránsito , Conducción de Automóvil , Teorema de Bayes , Análisis de Datos , Modelos Logísticos
18.
Horm Behav ; 119: 104638, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31765660

RESUMEN

Social behavior plays a significant role in the formation of social structure and population regulation in both animals and humans. Oxytocin (OXT) and its receptor (OXTR) are well known for regulating social behaviors, but their upstream regulating factors are rarely investigated. We hypothesized that the phosphorylation of the signal transducer and activator of transcription 3 (p-Stat3) may regulate social and aggressive behaviors via the OXT system in the nucleus accumbens (NAc). To test this hypothesis, OXT, p-Stat3 inhibitor, OXTR antagonist, and OXT plus p-Stat3 inhibitor were infused, respectively, into the NAc in the brain of male Brandt's voles (Lasiopodomys brandtii) - a social rodent species in grassland of Inner Mongolia, China. Our data showed that blockage of p-Stat3-Tyr705 signaling pathway in the NAc not only increased aggressive behavior but also impaired social recognition of male Brandt's voles via its effects on the expression of local OXT and OXTR. These results have illustrated a novel signaling pathway of p-Stat3-Tyr705 in regulating social behaviors via the OXT system.


Asunto(s)
Arvicolinae/fisiología , Núcleo Accumbens/metabolismo , Oxitocina/fisiología , Receptores de Oxitocina/fisiología , Factor de Transcripción STAT3/metabolismo , Conducta Social , Agresión/efectos de los fármacos , Agresión/fisiología , Animales , Arvicolinae/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/fisiología , Células HeLa , Humanos , Masculino , Núcleo Accumbens/efectos de los fármacos , Oxitocina/farmacología , Fosforilación/efectos de los fármacos , Proteínas Quinasas/metabolismo , Piridinas/farmacología , Receptores de Oxitocina/metabolismo , Reconocimiento en Psicología/efectos de los fármacos , Tirfostinos/farmacología
19.
J Opt Soc Am A Opt Image Sci Vis ; 36(12): 1949-1956, 2019 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-31873364

RESUMEN

Linearly polarized Gaussian beams, under the slowly varying envelope approximation, tightly focused by a perfect parabola modeled with the integral formalism of Ignatovsky are found to be well approximated with a generalized Lax series expansion beyond the paraxial approximation. This allows obtaining simple analytic formulas of the electromagnetic field in both the direct and momentum spaces. It significantly reduces computing time, especially when dealing with the problem of simulating direct laser acceleration. The series expansion formulation depends on integration constants that are linked to boundary conditions. They are found to depend significantly on the region of space over which the integral formulation is fit. Consequently, the net acceleration of electrons initially at rest is extremely sensitive to the chosen set of initial parameters due to the extreme focusing investigated here. This suggests avoiding too tight focusing schemes in order to obtain reliable predictions when the process of interest is sensitive mainly to the field and not the intensity.

20.
BMC Plant Biol ; 19(1): 353, 2019 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-31412775

RESUMEN

BACKGROUND: The PHOSPHATE1 (PHO1) gene family plays diverse roles in inorganic phosphate (Pi) transfer and signal transduction, and plant development. However, the functions and diversification of soybean PHO1 family are poorly understood. RESULTS: Cultivated soybean (Glycine max) was domesticated from wild soybean (Glycine soja). To illuminate their roles in this evolutionary process, we comparatively investigated the G. max PHO1 genes (GmPHO1) in Suinong 14 (SN14) and G. soja PHO1 genes (GsPHO1) in ZYD00006 (ZYD6). The sequences of the orthologous Gm-GsPHO1 pairs were grouped into two Classes. The expression of Class I in both SN14 and ZYD6 was widely but relatively high in developing fruits, whereas Class II was predominantly expressed in the roots. The whole family displayed diverse response patterns to salt stresses and Pi-starvation in roots. Between SN14 and ZYD6, most PHO1 genes responded similarly to salinity stresses, and half had sharp contrasts in response to Pi-starvation, which corroborated the differential response capacities to salinity and low-Pi stress between SN14 and ZYD6. Furthermore, in transgenic Arabidopsis plants, most Class II members and GmPHO1;H9 from Class I could enhance salt tolerance, while only two Class II genes (GmPHO1;H4 and GmPHO1;H8) differently altered sensitivity to Pi-starvation. The expression of critical genes was accordingly altered in either salt or Pi signaling pathways in transgenic Arabidopsis plants. CONCLUSIONS: Our work identifies some PHO1 genes as promising genetic materials for soybean improvement, and suggests that expression variation is decisive to functional divergence of the orthologous Gm-GsPHO1 pairs, which plays an adaptive role during soybean evolution.


Asunto(s)
Glycine max/genética , Proteínas de Transporte de Fosfato/fisiología , Proteínas de Plantas/fisiología , Adaptación Fisiológica , Arabidopsis/genética , Evolución Molecular , Proteínas de Transporte de Fosfato/genética , Proteínas de Transporte de Fosfato/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Estrés Salino/genética , Transducción de Señal/genética , Glycine max/metabolismo
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