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Despite active clinical trials on the use of Oleandrin alone or in combination with other drugs for the treatment of solid tumors, the potential synergistic effect of Oleandrin with radiotherapy remains unknown. This study reveals a new mechanism by which Oleandrin targets ATM and ATR kinase-mediated radiosensitization in lung cancer. Various assays, including clonogenic, Comet, immunofluorescence staining, apoptosis and Cell cycle assays, were conducted to evaluate the impact of oleandrin on radiation-induced double-strand break repair and cell cycle distribution. Western blot analysis was utilized to investigate alterations in signal transduction pathways related to double-strand break repair. The efficacy and toxicity of the combined therapy were assessed in a preclinical xenotransplantation model. Functionally, Oleandrin weakens the DNA damage repair ability and enhances the radiation sensitivity of lung cells. Mechanistically, Oleandrin inhibits ATM and ATR kinase activities, blocking the transmission of ATM-CHK2 and ATR-CHK1 cell cycle checkpoint signaling axes. This accelerates the passage of tumor cells through the G2 phase after radiotherapy, substantially facilitating the rapid entry of large numbers of inadequately repaired cells into mitosis and ultimately triggering mitotic catastrophe. The combined treatment of Oleandrin and radiotherapy demonstrated superior inhibition of tumor proliferation compared to either treatment alone. Our findings highlight Oleandrin as a novel and effective inhibitor of ATM and ATR kinase, offering new possibilities for the development of clinical radiosensitizing adjuvants.
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Proteínas de la Ataxia Telangiectasia Mutada , Cardenólidos , Daño del ADN , Neoplasias Pulmonares , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/radioterapia , Animales , Cardenólidos/farmacología , Daño del ADN/efectos de los fármacos , Línea Celular Tumoral , Ratones , Tolerancia a Radiación/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos , Fármacos Sensibilizantes a Radiaciones/farmacología , Ratones Desnudos , Ensayos Antitumor por Modelo de Xenoinjerto , Reparación del ADN/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células A549RESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a risk factor for herpes zoster. Vaccination can prevent or attenuate herpes zoster and its related complications. However, evidence regarding vaccine uptake among patients with COPD is limited. Therefore, this cross-sectional study aimed to evaluate trends in herpes zoster vaccination and characteristics associated with vaccination among U.S. older adults with COPD. METHODS: Data from the 2008-2022 National Health Interview Survey were used. Participants aged ≥50 years were included. Joinpoint regression analysis was performed to analyze trends in herpes zoster vaccination. A multivariable logistic regression model was used to identify factors associated with herpes zoster vaccination. RESULTS: This study included 22,853 participants with COPD, representing approximately 9.8 million U.S. older adults with COPD. From 2008 to 2022, an increasing trend in herpes zoster vaccination was observed (average annual percent change=15.10, P<0.01) This increasing trend was also observed when stratified by age groups. Disparities in vaccination were found across several factors, including age, sex, race/ethnicity, region, educational level, health insurance, income, smoking status, perceived health status, and flu and pneumococcal vaccination. CONCLUSIONS: While there has been an upward trend in herpes zoster vaccination over the past 15 years among older adults with COPD, disparities across several characteristics were identified. These findings underscore the necessity for targeted policies and interventions to promote equity in vaccination.
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Electromechanical instability (EMI) restricts the performance of dielectric elastomer actuators (DEAs), leading to premature electrical breakdown at a certain voltage. However, macro-level observations using traditional carbon grease electrodes have failed to capture the detailed features of EMI. In this study, we investigated EMI at the microscopic scale by fabricating transparent and conductive single-walled carbon nanotube (SWCNT) electrodes. Our findings reveal that EMI predominantly occurs in highly localized regions with dimensions on the order of tens of micrometers. This snap-through instability is likely induced by pre-existing defects within the elastomer, such as air voids or conductive particles, which reduce the critical voltage required for EMI in the flawed areas. From the perspective of phase transition principles, these defects act as heterogeneous nucleation sites for new phase embryos, thereby lowering the energy barrier for the electromechanical phase transition (i.e., EMI) compared to homogeneous nucleation in an ideally impurity-free elastomer. This study clarifies the longstanding discrepancy between theoretically predicted deformation bursts and the experimentally observed macroscopic continuous expansion of DEAs under low pre-stretch conditions. Additionally, it underscores the critical importance of material purity in mitigating electromechanical instability.
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BACKGROUNDS: The efficacy of endoscopic submucosal dissection (ESD) to treat poorly differentiated superficial esophageal squamous cell carcinoma (SESCC) is unclear. AIMS: To exploring the efficacy and prognosis of ESD treatment poorly differentiated SESCC compared with esophagectomy. METHODS: A retrospective cohort study was conducted, the data of poorly differentiated SESCC patients who received ESD or esophagectomy from Jan 2011 to Jan 2021 were analyzed. Overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and procedure-related variables were compared between ESD and esophagectomy group. RESULTS: 95 patients underwent ESD, while 86 underwent esophagectomy. No significant differences were found between the two groups in OS (P = 0.587), DSS (P = 0.172), and RFS (P = 0.111). Oncologic outcomes were also similar between the two groups in propensity score-matched analysis. For T1a ESCC, the rates of R0 resection, LVI or nodal metastasis and additional therapy were similar between ESD and esophagectomy groups. But for T1b ESCC, the rates of positive resection margin and additional therapy were significantly higher in ESD group than those in esophagectomy group. CONCLUSIONS: ESD is a minimally invasive procedure that has comparable oncologic outcomes with esophagectomy for treatment poorly differentiated T1a ESCC. However, ESD is not suitable for poorly differentiated T1b ESCC, additional surgery or radiochemotherapy should be required.
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Ejercicio Físico , Estudiantes , Humanos , China , Adolescente , Niño , Femenino , MasculinoRESUMEN
Based on the background of urbanization in China, we used the dynamic spatial panel Durbin model to study the driving mechanism of ozone pollution empirically. We also analyzed the spatial distribution of ozone driving factors using the GTWR. The results show that: i) The average annual increase of ozone concentration in ambient air in China from 2015 to 2019 was 1.68µg/m3, and 8.39µg/m3 elevated the year 2019 compared with 2015. ii) The Moran's I value of ozone in ambient air was 0.027 in 2015 and 0.209 in 2019, showing the spatial distribution characteristics of "east heavy and west light" and "south low and north high". iii) Per capita GDP industrial structure, population density, land expansion, and urbanization rate have significant spillover effects on ozone concentration, and the regional spillover effect is greater than the local effect. R&D intensity and education level have a significant negative impact on ozone concentration. iv) There is a decreasing trend in the inhibitory effect of educational attainment and R&D intensity on ozone concentration, and an increasing trend in the promotional effect of population urbanization rate, land expansion, and economic development on ozone concentration. Empirical results suggest a twofold policy meaning: i) to explore the causes behind the distribution of ozone from the new perspective of urbanization, and to further the atmospheric environmental protection system and ii) to eliminate the adverse impacts of ozone pollution on nature and harmonious social development.
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Contaminantes Atmosféricos , Contaminación del Aire , Ozono , Urbanización , Ozono/análisis , China , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Contaminación del Aire/efectos adversos , Humanos , Análisis Espacio-Temporal , Monitoreo del AmbienteRESUMEN
BACKGROUND: Canonical biocontrol bacteria were considered to inhibit pathogenic bacteria mainly by secreting antibiotic metabolites or enzymes. Recent studies revealed that some biocontrol bacteria can inhibit pathogenic bacteria through contact-dependent killing (CDK) mediated by contact-dependent secretion systems. The CDK was independent of antibiotic metabolites and often ignored in normal biocontrol activity assay. RESULTS: In this study, we aimed to use a pathogen enrichment strategy to isolate non-canonical bacteria with CDK ability. Rhizosphere soil samples from Chinese cabbage showing soft rot symptom were collected and Pectobacterium carotovorum subsp. carotovorum (Pcc), the pathogen of cabbage soft rot, were added into these samples to enrich bacteria which attached on Pcc cells. By co-culture with Pcc, four bacteria strains (named as PcE1, PcE8, PcE12 and PcE13) showing antibacterial activity were isolated from Chinese cabbage rhizosphere. These four bacteria strains showed CDK abilities to different pathogenic bacteria of horticultural plants. Among them, PcE1 was identified as Chryseobacterium cucumeris. Genome sequencing showed that PcE1 genome encoded a type VI secretion system (T6SS) gene cluster. By heterologous expression, four predicted T6SS effectors of PcE1 showed antibacterial activity to Escherichia coli. CONCLUSION: Overall, this study isolated four bacteria strains with CDK activity to various horticultural plant pathogens, and revealed possible involvement of T6SS of Chryseobacterium cucumeris in antibacterial activity. These results provide valuable insight for potential application of CDK activity in biocontrol bacteria. © 2024 Society of Chemical Industry.
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Antibiosis , Brassica , Pectobacterium carotovorum , Brassica/microbiología , Pectobacterium carotovorum/genética , Microbiología del Suelo , Rizosfera , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Sistemas de Secreción Tipo VI/genética , Sistemas de Secreción Tipo VI/metabolismoRESUMEN
Surface-enhanced Raman scattering (SERS) technology has been widely recognized for its remarkable sensitivity in biochip development. This study presents a novel sandwich immunoassay that synergizes SERS with magnetoplasmonic nanoparticles (MPNs) to improve sensitivity. By taking advantage of the unique magnetism of these nanoparticles, we further enhance the detection sensitivity of SERS biochips through the applied magnetic field. Despite the high sensitivity, practical applications of SERS biochips are often limited by the issues of stability and reproducibility. In this study, we introduced a straightforward statistical method known as "Gaussian binning", which involves initially binning the two-dimensional Raman mapping data and subsequently applying Gaussian fitting. This approach enables a more consistent and reliable interpretation of data by reducing the variability inherent in Raman signal measurements. Based on our method, the biochip, targeting for C-reactive protein (CRP), achieves an impressive detection limit of 5.96 fg/mL, and with the application of a 3700 G magnetic field, it further enhances the detection limit by 5.7 times, reaching 1.05 fg/mL. Furthermore, this highly sensitive and magnetically tunable SERS biochip is easily designed for versatile adaptability, enabling the detection of other proteins. We believe that this innovation holds promise in enhancing the clinical applicability of SERS biochips.
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Nanopartículas , Espectrometría Raman , Espectrometría Raman/métodos , Reproducibilidad de los Resultados , Inmunoensayo/métodos , Proteína C-ReactivaRESUMEN
OBJECTIVE: To observe the diurnal difference of acute gout attacks in men, and provide reference for accurate clinical prevention and treatment. METHODS: Using a single-center, cross-sectional study design, the patients diagnosed with gout in the outpatient department of Rheumatology and Immuno-logy of PLA Joint Logistic Support Force No.980 Hospital from October 2021 to April 2022 were selected. The information about the patient's current/last acute gout attacks (less than 2 weeks from visit), date and time of attacks, joint symptoms and signs, medication use, and relevant biochemical tests on the day of visit was recorded. The diurnal time difference of acute gout attacks in male patients was analyzed, and univariate comparison and multivariate Logistic regression analyses were conducted to compare the diurnal difference of acute gout attacks with clinical characteristics and biochemical indicators. RESULTS: A total of 100 male gout patients were included, and 100 acute attacks were recorded. Diurnal distribution of acute gout attacks: morning (6:00~11:59, 18, 18%), afternoon (12:00~17:59, 11, 11%), the first half of the night (18:00~23:59, 22, 22%), the second half of the night (0:00~05:59, 49, 49%); During the day (included morning and afternoon, 29, 29%) and at night (included the first half of the night and the second half of the night, 71, 71%). The rate of acute gout attack was significantly higher at night than in the day (about 2.5 â¶1). No matter the first or recurrent gout, no matter the duration of the disease, the number of acute gout attacks had the difference of less in the day and more in the night. Serum urate (SU) level was higher in the patients with nocturnal attack than in those with daytime attack (P=0.044). Comorbidities were significantly different in the day-night ratio of the number of acute gout attack (P=0.028). Multiple Logistic regression analysis showed that SU level (OR=1.005, 95%CI: 1.001-1.009) and comorbidities (OR=3.812, 95%CI: 1.443-10.144) were the correlative factors of nocturnal acute gout attacks. CONCLUSION: No matter the first or recurrent gout, no matter the duration of the disease, it has a diurnal variation characterized by multiple attacks at night, increased SU level and comorbidities are correlative factors for nocturnal acute attack of gout.
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Artritis Gotosa , Gota , Humanos , Masculino , Estudios Transversales , Gota/tratamiento farmacológico , Supresores de la Gota/uso terapéutico , ComorbilidadRESUMEN
To understand the role of microorganisms in litter decomposition and nutrient cycling in volcanic forest ecosystem, we conducted in-situ litterbag decomposition experiment and used Illumina MiSeq high-throughput sequencing to analyze the response of bacterial community structure and diversity during the decomposition of litters from Larix gmelinii, Betula platyphylla and Populus davidiana, the dominant tree species in volcanic lava plateau of Wudalianchi. The results showed that mass remaining percentage of litters of three species after 18-month decomposition was 63.9%-68.1%. Litter of B. platyphylla decomposed the fastest, with significant difference in N, C:N, and N:P before and after decomposition. The richness of bacterial species and diversity index differed significantly among the three litters. Proteobacteria, Actinomycetes, and Bacteroidetes were the dominant bacterial groups at the phylum level, while Rhizobium, Sphingomonas, and Pseudomonas were the dominant groups at the genus level, with significant difference among the three litters. After 18 months, the dominant bacterial groups in litter tended to be consistent with those in volcanic lava platform soil. In the volcanic forest ecosystem, bacterial diversity and community structure were mainly affected by P, C:N, and N:P in the litter.
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Ecosistema , Bosques , Microbiología del Suelo , Larix/metabolismo , Betula/metabolismo , Populus/metabolismo , Hojas de la Planta/metabolismo , Bacterias/metabolismo , BiomasaRESUMEN
Due to the chaotic structure of amorphous materials, it is challenging to identify defects in metallic glasses. Here we tackle this problem from a thermodynamic point of view using atomic vibrational entropy, which represents the inhomogeneity of atomic contributions to vibrational modes. We find that the atomic vibrational entropy is correlated to the vibrational mean-square displacement and polyhedral volume of atoms, revealing the critical role of vibrational entropy in bridging dynamics, thermodynamics, and structure. On this method, the local vibrational entropy obtained by coarse-graining the atomic vibrational entropy in space can distinguish more effectively between liquid-like and solid-like atoms in metallic glasses and establish the correlation between the local vibrational entropy and the structure of metallic glasses, offering a route to predict the plastic events from local vibrational entropy. The local vibration entropy is a good indicator of thermally activated and stress-driven plastic events, and its predictive ability is better than that of the structural indicators.
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Nonexponential relaxations are universal characteristics for glassy materials. There is a well-known hypothesis that nonexponential relaxation peaks are composed of a series of exponential events, which have not been verified. In this Letter, we discover the exponential relaxation events during the recovery process using a high-precision nanocalorimetry, which are universal for metallic glasses and organic glasses. The relaxation peaks can be well fitted by the exponential Debye function with a single activation energy. The activation energy covers a broad range from α relaxation to ß relaxation and even the fast γ/ß' relaxation. We obtain the complete spectrum of the exponential relaxation peaks over a wide temperature range from 0.63Tg to 1.03Tg, which provides solid evidence that nonexponential relaxation peaks can be decomposed into exponential relaxation units. Furthermore, the contribution of different relaxation modes in the nonequilibrium enthalpy space is measured. These results open a door for developing the thermodynamics of nonequilibrium physics and for precisely modulating the properties of glasses by controlling the relaxation modes.
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Based on the panel data of 30 provinces in China from 2011 to 2019, this paper uses a two-stage DEA model to measure regional innovation efficiency, then non-parametric test is used to examine the impact of innovation network structure and government R&D investment on regional innovation efficiency. The results show that, at the provincial level, innovation efficiency of regional R&D is not necessarily in direct proportion to the innovation efficiency in the commercialization stage. Commercialization efficiency is not necessarily high in provinces with high technical R&D efficiency. At the national level, the innovation efficiency gap between our country's R&D and commercialization stage is small, indicating that the development of the national innovation efficiency is more and more balanced. Innovation network structure can promote the R&D efficiency, but has no significant effect on the commercialization efficiency. Government R&D investment helps to improve the R&D efficiency, but it is not conducive to the improvement of commercialization efficiency. The interaction between innovation network structure and government R&D investment will have compound effects on regional innovation efficiency; the region with underdeveloped innovation network structure can increase the government R&D investment to make it have a higher level of R&D. This paper provides insights into how to improve innovation efficiency in different social networks and policy environments.
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Eficiencia , Gobierno , China , Inversiones en Salud , Desarrollo EconómicoRESUMEN
Decalcified bone matrix (DBM) is a widely used alternative material for bone transplantation. In the DBM production process, an effective particle size and the highest utilization rate of raw materials can be achieved only through multiple high-speed circulating comminution. The rat posterolateral lumbar fusion model (PLF) is the most mature small animal model for the initial evaluation of the efficacy of graft materials for bone regeneration and spinal fusion. To evaluate the differences in the in vivo osteogenic effects of DBM pulverization through 1, 5, 9, and 14 high-speed cycles, sixty athymic rats were divided into six groups: single cycling crushing (CC1), 5 cycles of crushing (CC5), 9 cycles of crushing (CC9), 13 cycles of crushing (CC13), autogenous bone graft (ABG) and negative control (NC). Posterolateral lumbar fusion was performed. Six weeks after surgery, the bilateral lumbar fusion of athymic rats was evaluated through manual palpation, X-ray, micro-CT and histological sections. Rank data were tested by the rank-sum test, and nonparametric data were tested by the KruskalâWallis H test. The manual palpation and X-ray results showed that the fusion rate did not significantly differ between the CC1, CC5, CC9, CC13 and ABG groups. However, cavities appeared in CC9 and CC13 on the micro-CT image. The bone mass (BV/TV) of CC1, CC5, CC9 and CC13 was better than that of the ABG group, while almost no osteogenesis was observed in the NC group. Histologically, there was no obvious difference between the four groups except that the CC9 group and CC13 group had more fibrous tissues in the new bone. In conclusion, DMB with different cycling crushing times has no obvious difference in fusion rate of PLF, but it is slightly better than the ABG group.
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Matriz Ósea , Fusión Vertebral , Ratas , Animales , Matriz Ósea/trasplante , Ratas Desnudas , Vértebras Lumbares/cirugía , Huesos , Fusión Vertebral/métodos , Trasplante Óseo/métodosRESUMEN
Objective: To investigate the spatial patterns of the prevalence, awareness, treatment, and control rates of dyslipidemia at the provincial level in China. Methods: A national and provincial representative cross-sectional survey was conducted among 178,558 Chinese adults in 31 provinces in mainland China in 2018-2019, using a multi-stage, stratified, cluster-randomized sampling design. Subjects, as households, were selected, followed by a home visit to collect information. Both descriptive and linear regression procedures were applied in the analyses. Results: The overall prevalence of dyslipidemia was 35.6%, and wide geographic variations of prevalence, treatment, and control rates of dyslipidemia were identified among 178,558 eligible participants with a mean age of 55.1 ± 13.8 years. The highest-lowest difference regarding the provincial level prevalence rates were 19.7% vs. 2.1% for high low-density lipoprotein cholesterol, 16.7% vs. 2.5% for high total cholesterol, 35.9% vs. 5.4% for high triglycerides, and 31.4% vs. 10.5% for low high-density lipoprotein cholesterol. The treatment rate of dyslipidemia was correlated with the socio-demographic index ( P < 0.001), urbanization rate ( P = 0.01), and affordable basic technologies and essential medicines ( P < 0.001). Conclusion: Prevailing dyslipidemia among the Chinese population and its wide geographic variations in prevalence, treatment, and control suggest that China needs both integrated and localized public health strategies across provinces to improve lipid management.
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Dislipidemias , Pueblos del Este de Asia , Humanos , Adulto , Persona de Mediana Edad , Anciano , Estudios Transversales , Prevalencia , Dislipidemias/tratamiento farmacológico , Dislipidemias/epidemiología , Dislipidemias/prevención & control , China/epidemiología , HDL-Colesterol , Factores de Riesgo , TriglicéridosRESUMEN
A novel high-conductivity Agx[(Ga2Te3)34(SnTe)66]100-x tellurium-based glassy system was fabricated via melt spinning with the glass formation area in the range of x = 0-15 mol %. A bulk Ag10[(Ga2Te3)34(SnTe)66]90 glass (A10) was obtained via spark plasma sintering at 450 K using a 5 min dwell time and 400 MPa pressure. The fabricated A10 glass exhibited higher room-temperature conductivity (σ300â¯K = 46 S m-1), larger glass transition temperature (Tg = 482 K), and ultralower thermal conductivity (â¼0.19 W m-1 K-1) compared to those of previously reported Cu-Ge-Te, Cu-As-Te, Cu-Ge-As-Te, and Cu-As-Se-Te glassy systems with the approximate doping concentrations of 5-20%, demonstrating that this distinctive Ag-Ga2Te3-SnTe system is interesting materials for thermoelectric applications. The high-conductivity Ag-Ga2Te3-SnTe glassy system will extend investigations into similar glassy semiconductors and also can be used for preparing glass ceramics with potential applications in other fields.
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The origin of ß-relaxation in metallic glasses is still not fully understood, and the guidance of slow atoms for caged dynamics and ß-relaxation is rarely mentioned. Using molecular dynamics simulations, we reveal the bridging role of slow atoms on unusual caged dynamics and ß-relaxation. In the stage of unusual caged dynamics, slow atoms are bounded by neighboring atoms. It is difficult for the slow atoms to break the cage, producing more high-frequency vibration, which causes more atoms to jump out of the cage randomly in the next stage. Precisely, the movement of the slow atoms changes from individual atoms vibrating inside the cage and gradually breaking out of the cage into a string-like pattern. The string-like collective atomic jumps cause decay of the cages, inducing ß-relaxation. This situation generally exists in binary systems with the large atomic mass difference. This work offers valuable insights for understanding the role of slow atoms in unusual caged dynamics and ß-relaxation, complementing studies on the origin of ß-relaxation in metallic glasses and their glass-forming liquids.
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The fictive temperature (Tf ) is widely applied to understand the relaxation thermodynamics of a glass; however, its atomic structural origin is still unclear. Here, we report two novel AZnP3 O9 glasses obtained by melting the composition identical single crystals. These glasses exhibit structural inheritance within 5â Å from the single crystal counterparts that is quantified by δ=nglass /ncry (0≤δ≤1, n is the number of pair correlation functions). Among the available glass-formers, glass KZnP3 O9 exhibits the highest structural inheritance (δ=1, nglass =8). More insightfully, a reverse correlation between δ and the relaxation thermodynamic parameters is observed in glass AZnP3 O9 , revealing for the first time the atomic structural origin of fictive temperature.
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The main purpose of the paper is to investigate the relationship between technological innovation and income inequality for China based on the financial Kuznets curve (FKC) hypothesis. The study uses time-series data from 1985 to 2019. We employ the Johansen cointegration, ARDL model and VECM Granger causality techniques to analyze the links between the variables. We also use the DOLS, FMOLS and CCR mechanisms to estimate the long-run parameters. The paper finds that the FKC is valid for China's economy in the long run. Technological innovation positively affects the urban-rural income gap, while there is an inverted-U shaped between financial development and the urban-rural income gap. The relationship between financial development and the urban-rural income gap is bi-directional causality. Technological innovation and the urban-rural income gap cause each other. Empirical results suggest a twofold policy meaning: i) to further the financial system and ii) to eliminate the adverse impacts of technological innovations on income distribution.