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1.
BMC Bioinformatics ; 21(1): 187, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32408861

RESUMO

BACKGROUND: Cardiotoxicity, characterized by severe cardiac dysfunction, is a major problem in patients treated with different classes of anticancer drugs. Development of predictable human-based models and assays for drug screening are crucial for preventing potential drug-induced adverse effects. Current animal in vivo models and cell lines are not always adequate to represent human biology. Alternatively, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) show great potential for disease modelling and drug-induced toxicity screenings. Fully automated high-throughput screening of drug toxicity on hiPSC-CMs by fluorescence image analysis is, however, very challenging, due to clustered cell growth patterns and strong intracellular and intercellular variation in the expression of fluorescent markers. RESULTS: In this paper, we report on the development of a fully automated image analysis system for quantification of cardiotoxic phenotypes from hiPSC-CMs that are treated with various concentrations of anticancer drugs doxorubicin or crizotinib. This high-throughput system relies on single-cell segmentation by nuclear signal extraction, fuzzy C-mean clustering of cardiac α-actinin signal, and finally nuclear signal propagation. When compared to manual segmentation, it generates precision and recall scores of 0.81 and 0.93, respectively. CONCLUSIONS: Our results show that our fully automated image analysis system can reliably segment cardiomyocytes even with heterogeneous α-actinin signals.

2.
Med Sci Monit ; 26: e922624, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32430492

RESUMO

BACKGROUND Vascularized fibular grafting (VFG) has been successfully employed for treating avascular necrosis of the femoral head (ANFH). In this study, we aimed to evaluate the bone viability of the femoral head and subchondral bone following VFG by using single photon emission computerized tomography and computerized tomography (SPECT/CT). MATERIAL AND METHODS Between March 2011 and June 2014, 14 ANFH patients (17 hips) treated with VFG at Zhongshan Hospital, Fudan University, were prospectively enrolled. The patients included 9 males and 5 females with an average age of 26.6 years (range, 18-34 years). According to the ARCO (Association Research Circulation Osseous) stage criteria, 3 hips corresponded to stage IIA, 4 hips to stage IIB, 2 hips to stage IIC, 5 hips to stage IIIA, and 3 hips to stage IIIB. A novel method based on SPECT/CT was developed to quantitative characterized the bone viability of femoral head and subchondral bone prior to surgery and at 3 months after VFG. All patients were followed for an average duration of 3.8 years (ranging 2.6-5.5 years). RESULTS The bone viability of the femoral head (Vfh) and subchondral bone (Vsb) of patients' hips at ARCO stage III was 58.9±7.6 and 48.9±6.1, respectively, which were significantly lower than the preoperative Vfh (78.1±5.2) and Vsb (69.8±4.3) of hips at stage II (P<0.05). The Vfh of hips at stage II improved to 104.0±9.7 at 3 months post-intervention, and there was no significant difference compared with the Vfh (97.3±7.4) of hips at stage III (P=0.15). The Vsb of hips at stage III improved to 80.4±7.3 at 3 months after VFG; however, this value was significantly lower than that of hips at stage II (92.7±5.5) (P<0.05). CONCLUSIONS The Vfh and Vsb of our patients were associated with their ARCO stages, and could be improved after vascularized fibular grafting procedure as measured by SPECT/CT.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32272727

RESUMO

Steady meteorological conditions are important external factors affecting air pollution. In order to analyze how adverse meteorological variables affect air pollution, surface synoptic situation patterns and meteorological conditions during heavy pollution episodes are discussed. The results showed that there were 78 RPHPDs (regional PM2.5 pollution days) in Jiangsu, with a decreasing trend year by year. Winter had the most stable meteorological conditions, thus most RPHPDs appeared in winter, followed by autumn and summer, with the least days in spring. RPHPDs were classified into three patterns, respectively, as equalized pressure (EQP), advancing edge of a cold front (ACF) and inverted trough of low pressure (INT) according to the SLP (sea level pressure). RPHPDs under EQP were the most (51%), followed by ACF (37%); INT was the minimum (12%). Using statistical methods and meteorological condition data on RPHPDs from 2013 to 2017 to deduce the thresholds and 2018 as an independent dataset to validate the proposed thresholds, the threshold values of meteorological elements are summarized as follows. The probability of RPHPDs without rain was above 92% with the daily and hourly precipitation of all RPHPDs below 2.1 mm and 0.8 mm. Wind speed, RHs, inversion intensity(ITI), height difference in the temperature inversion(ITK), the lower height of temperature inversion (LHTI) and mixed-layer height (MLH) in terms of 25%-75% high probability range were respectively within 0.5-3.6 m s-1, 55%-92%, 0.7-4.0 °C 100 m -1, 42-576 m, 3-570 m, 200-1200 m. Two conditions should be considered: whether the pattern was EQP, ACF or INT and whether the eight meteorological elements are within the thresholds. If both criteria are met, PM2.5 particles tend to accumulate and air pollution diffusion conditions are poor. Unfavorable meteorological conditions are the necessary, but not sufficient condition for RPHPDs.

4.
Adv Mater ; 32(19): e1908314, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32239583

RESUMO

Materials possessing structural phase transformations exhibit a rich set of physical and chemical properties that can be used for a variety of applications. In 2D materials, structural transformations have so far been induced by strain, lasers, electron injection, electron/ion beams, thermal loss of stoichiometry, and chemical treatments or by a combination of such approaches and annealing. However, stoichiometry-preserving, purely thermal, reversible phase transitions, which are fundamental in physics and can be easily induced, have not been observed. Here, the fabrication of monolayer Cu2 Se, a new 2D material is reported, demonstrating the existence of a purely thermal structural phase transition. Scanning tunneling microscopy, scanning transmission electron microscopy, and density functional theory (DFT) identify two structural phases at 78 and 300 K. DFT calculations trace the phase-transition mechanism via the existence/absence of imaginary (unstable) phonon modes at low and high temperatures. In situ, variable-temperature low-energy electron diffraction patterns demonstrate that the phase transition occurs across the whole sample at ≈147 K. Angle-resolved photoemission spectra and DFT calculations show that a degeneracy at the Γ point of the energy bands of the high-temperature phase is lifted in the low-temperature phase. This work opens up possibilities for studying such phase transitions in 2D materials.

5.
Acupunct Med ; : 964528420912248, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32310010

RESUMO

OBJECTIVE: To investigate the regulatory mechanism of manual acupuncture (MA) on microglial polarization-mediated neuroinflammation after traumatic brain injury (TBI), focusing on the RhoA/Rho-associated coiled coil-forming protein kinase (ROCK2) pathway. METHODS: Sprague Dawley (SD) rats were used to generate a TBI model using Feeney's freefall epidural impact method. MA was performed on half of the TBI model rats, while the others remained untreated. Acupuncture was administered at GV15, GV16, GV20, GV26, and LI4. At the end of the intervention, rat brain tissue samples were collected, and the microglial M1 polarization status was observed by immunofluorescence labeling of CD86, an M1 microglia-specific protein. RhoA/ROCK2 signaling components were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. An enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of inflammatory factors. RESULTS: Compared with normal rats, the CD86 expression density in the untreated TBI model rats was high and showed an aggregated expression pattern. The genes and proteins of the RhoA/ROCK2 signaling pathway were highly expressed, and inflammatory factors were significantly increased. The CD86 expression density in TBI rats after MA was reduced compared to that in untreated TBI rats and showed a scattered distribution. The expression of RhoA/ROCK2 signaling pathway genes and proteins was also significantly reduced, and inflammatory factors were decreased. CONCLUSION: These results show that MA may inhibit M1 polarization of microglia by regulating the RhoA/ROCK2 signaling pathway, thereby reducing neuroinflammation in TBI.

6.
J Immunol ; 204(8): 2216-2231, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32169843

RESUMO

Nucleotide oligomerization domain-like receptors (NLRs) and RIG-I-like receptors (RLRs) detect diverse pathogen-associated molecular patterns to activate the innate immune response. The role of mammalian NLR NOD1 in sensing bacteria is well established. Although several studies suggest NOD1 also plays a role in sensing viruses, the mechanisms behind this are still largely unknown. In this study, we report on the synergism and antagonism between NOD1 and MDA5 isoforms in teleost. In zebrafish, the overexpression of NOD1 enhances the antiviral response and mRNA abundances of key antiviral genes involved in RLR-mediated signaling, whereas the loss of NOD1 has the opposite effect. Notably, spring viremia of carp virus-infected NOD1-/- zebrafish exhibit reduced survival compared with wild-type counterparts. Mechanistically, NOD1 targets MDA5 isoforms and TRAF3 to modulate the formation of MDA5-MAVS and TRAF3-MAVS complexes. The cumulative effects of NOD1 and MDA5a (MDA5 normal form) were observed for the binding with poly(I:C) and the formation of the MDA5a-MAVS complex, which led to increased transcription of type I IFNs and ISGs. However, the antagonism between NOD1 and MDA5b (MDA5 truncated form) was clearly observed during proteasomal degradation of NOD1 by MDA5b. In humans, the interactions between NOD1-MDA5 and NOD1-TRAF3 were confirmed. Furthermore, the roles that NOD1 plays in enhancing the binding of MDA5 to MAVS and poly(I:C) are also evolutionarily conserved across species. Taken together, our findings suggest that mutual regulation between NOD1 and MDA5 isoforms may play a crucial role in the innate immune response and that NOD1 acts as a positive regulator of MDA5/MAVS normal form-mediated immune signaling in vertebrates.

7.
Sci Rep ; 10(1): 4465, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32144354

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

8.
ACS Appl Mater Interfaces ; 12(12): 14365-14375, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32129593

RESUMO

Exploiting the solid-state drawing (SSD) process toward polymer materials for medical implant devices is of significance to simultaneously improve the mechanical property and biocompatibility. Herein, for the first time, the bionic implants with a microvalley surface of oriented long chain branching PLA (b-PLA) was fabricated by a feasible SSD process. The as-obtained b-PLAs could not only show a high tensile strength (278.1 MPa) and modulus (4.32 GPa) but also bear a superior protein adsorption as high as 622 ng/cm2. Such exceptional mechanical properties and biocompatibility could be ascribed to the SSD process-induced highly orientation degree and the morphology of parallel grooves within ridges structures, resulting in the greatly enhanced crystallinity and surface hydrophobicity as well as a biocompatible vascular endothelial microstructure for cell to adhesion and growth and thus an improved proliferation, differentiation, and activity of osteoblasts with spindle-shaped and spread morphology on surface of the b-PLAs. These findings may pave the way for designing the novel biomaterials for vascular stent or tissue engineering devices by the SSD process.

9.
Virchows Arch ; 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32086588

RESUMO

Human epidermal growth factor receptor (HER)-2 positive (HER2+) breast cancer (BC) has a poor survival rate and is more aggressive in nature. HER2-targeting agents could be beneficial for patients with HER2+ BC. In addition, targeted therapy and chemotherapy have been successfully used. However, a few patients are resistant to treatment. ErbB3 binding protein 1 (EBP1) binds to HER3 and inhibits the proliferation and invasive potential of tumor cells. However, its role in HER2+ BC has not been demonstrated. In this study, we aimed to analyze the relationship between androgen receptor (AR) and EBP1 expression in HER2+ BC. A total of 282 cases (140 cases of HER2+ invasive BC and 142 HER2-negative invasive BC) were included in this study. We performed immunohistochemistry (IHC) to analyze the expression of AR and EBP1; thereafter, we evaluated the relationship between these two biomarkers and estrogen receptor (ER), progesterone receptor (PR), HER2, p53, Ki67 expression, and other clinicopathological parameters. Of the HER2+ cases, 67 (47.9%) showed high expression of EBP1 (EBP1high) and 73 (52.1%) showed low/no expression of EBP1 (EBP1low/no). EBP1 expression was correlated with AR expression, histological grade, and lymphatic metastasis (p < 0.001, < 0.001, and 0.013, respectively). Kaplan-Meier analysis revealed that AR+ and EBP1low/no group had poorer overall survival (OS) and disease-free survival (DFS) compared with other groups (AR- and EBP1low/no, AR+ and EBP1high, and AR- and EBP1high). AR+ and EBP1low/no expression were independent prognostic factors for OS and DFS in HER2+ BC. This study showed the clinicopathological role of EBP1 and AR in HER2+ BC. Targeting EBP1 may be an effective treatment strategy for patients with AR+ HER2+ BC.

10.
Sci Total Environ ; 714: 136839, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32018980

RESUMO

Phosphate adsorption using metal-modified biochar has awakened much attention and triggered extensive research. In this study, the effect of lanthanum (La)-modified sludge using impregnation-co-precipitation was used for phosphate adsorption. Consequently, La-coated biochar at a pyrolysis temperature of 600 °C had the highest phosphate adsorption and the lowest heavy metal leaching potential. The treatment of virgin biochar with alkali before La loading was found to be beneficial for the increase of phosphate adsorption capacity. The adsorption kinetics was well depicted by the pseudo-second-order model, and indicating that intraparticle diffusion played a crucial role in the adsorption process. The good fitness between adsorption data and the Langmuir isotherm model showed a maximal adsorption capacity of 93.91 mg/g, where phosphate absorption was highly correlated to its concentration in the solution. The La-coated biochar showed high adsorption capacity when the solution pH varied from 3.0 to 6.0, and was insensitive to the coexisting chloride, nitrate, sulfate, bicarbonate and citrate. Moreover, the adsorption mechanism was further explored by using Zeta potential analysis, FTIR and XPS, indicating that the phosphate is adsorbed through electrostatic attraction in the form of the inner-sphere complexation. All the results suggested that the sludge-based biochar, as a support material for La, could serve as a promising adsorbent for phosphate in real applications.


Assuntos
Carvão Vegetal , Esgotos , Adsorção , Cinética , Lantânio , Fosfatos
11.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 37(1): 80-86, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32096380

RESUMO

This study aims to propose a multifrequency time-difference algorithm using spectral constraints. Based on the knowledge of tissue spectrum in the imaging domain, the fraction model was used in conjunction with the finite element method (FEM) to approximate a conductivity distribution. Then a frequency independent parameter (volume or area fraction change) was reconstructed which made it possible to simultaneously employ multifrequency time-difference boundary voltage data and then reduce the degrees of freedom of the reconstruction problem. Furthermore, this will alleviate the illness of the EIT inverse problem and lead to a better reconstruction result. The numerical validation results suggested that the proposed time-difference fraction reconstruction algorithm behaved better than traditional damped least squares algorithm (DLS) especially in the noise suppression capability. Moreover, under the condition of low signal-to-noise ratio, the proposed algorithm had a more obvious advantage in reconstructions of targets shape and position. This algorithm provides an efficient way to simultaneously utilize multifrequency measurement data for time-difference EIT, and leads to a more accurate reconstruction result. It may show us a new direction for the development of time-difference EIT algorithms in the case that the tissue spectrums are known.


Assuntos
Algoritmos , Impedância Elétrica , Processamento de Imagem Assistida por Computador , Tomografia , Simulação por Computador , Humanos , Imagens de Fantasmas
12.
Exp Gerontol ; 133: 110853, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31987916

RESUMO

Physical activity may reduce cancer initiation. High-intensity interval training (HIT) has been reported to be superior to moderate continuous endurance training (ET) for maximizing health outcomes in cardiovascular disease, obesity and type 2 diabetes. However, the role of HIT vs. ET in the prevention of liver cancer is poorly understood. This study aimed to determine how HIT vs. ET affects cancer initiation in mice with the hepatocellular carcinogen diethylnitrosamine (DEN). C57BL/6 mice were treated with DEN at 3-12 weeks of age and, from 8 to 26 weeks of age, treated with either of exercise modes on treadmill: HIT (85-90% VO2max with intervals) and ET (65-75% VO2max without intervals). We found that mice treated with ET had lower cancer initiation but higher fat mass compared to control DEN-injected mice. In contrast, HIT could not significantly reduce cancer initiation and tumor volumes. Metabolomic analysis in the liver indicated marked differences in cholesterol, palmitic acid, stearic acid, uracil, hydroxypyridine and maltose between HIT- and ET-treated mice, and demonstrated good and obvious separation between ET and DEN control group. Furthermore, mice treated with ET had lower expression of pro-inflammatory cytokines and pro-proliferation genes in liver compared to DEN control group. ET protocol reduced the accumulation of toxic metabolite carbamate, increased the protein level of caspase-1, and reduced JNK phosphorylation in liver. These data indicates that moderate-intensity endurance training may be superior to high-intensity interval training for reducing liver cancer initiation in mice.

13.
Physiol Meas ; 41(1): 015004, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-31918414

RESUMO

OBJECTIVE: This study investigated the feasibility of electrical impedance tomography (EIT) for monitoring the deterioration of ischemic lesion after the onset of stroke. APPROACH: Fifteen rats were randomly distributed into two groups: rats operated to establish a right middle cerebral artery occlusion (MCAO) (n = 10), and sham-operated rats (n = 5). Then, the operated rats were kept 2 h under anesthesia for EIT monitoring. Subsequently, descriptive statistical analysis was performed on whole-brain resistivity changes, and repeated-measures analysis of variance (ANOVA) on the average resistivity variation index. Additionally, pathological examinations were performed after 6 h of infarction. MAIN RESULTS: The results obtained showed that ischemic damage developed in the right corpus striatum of the rats with MCAO, whereas the brains of the sham group showed no anomalies. The descriptive statistical analysis revealed that the whole-brain resistivity changes after 30, 60, 90, and 120 min of infarction were 0.063 ± 0.038, 0.097 ± 0.046, 0.141 ± 0.062, and 0.204 ± 0.092 for the rats with MCAO and 0.029 ± 0.021, 0.002 ± 0.002, 0.017 ± 0.011, and -0.001 ± 0.011 for the sham-operated rats, respectively. The repeated-measures ANOVA revealed that the right MCAO model resulted in a significant impedance increase in the right hemisphere, which continued to increase over time after infarction. SIGNIFICANCE: The overall study results indicate that EIT facilitates monitoring of local impedance variations caused by MCAO and may be a solution for real-time monitoring of intracranial pathological changes in ischemic stroke patients.

14.
Breast ; 49: 165-170, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31812892

RESUMO

AIM: To determine whether the addition of regional nodal irradiation (RNI) to whole-breast irradiation (WBI) would improve outcomes over WBI alone in T1-2N1 breast cancer after breast-conserving surgery (BCS) and adjuvant systematic therapy. METHODS: Data were obtained from two randomized controlled trials (NCT00174655 and NCT00312208). Univariate and multivariate Cox-regression analysis were performed to investigate predictors for overall survival and disease-free survival. A 1:1 propensity score matching (PSM) analysis was applied to eliminate selection bias. RESULTS: With median follow-up 80 months (range: 3-155 months), the 5-year local regional recurrence in the WBI group was 2% vs. 5% (p = 0.28) in the WBI + supraclavicular radiotherapy, and the rate of 5-year distant metastasis in the WBI group was 7% vs. 13% in the WBI + supraclavicular radiotherapy (p = 0.0748); In addition, the 5-year local regional recurrence in the WBI group was 3% vs. 9% (p = 0.19) in the WBI + internal mammary irradiation (IMI); However, the rate of 5-year distant metastasis in the in the WBI group was significantly lower than that in the WBI + IMI (8% vs. 24%, p = 0.036). After PSM, cox-regression analysis indicated that neither RNI nor IMI in combination with WBI in T1-2N1 breast cancer was associated with an improved overall survival and disease-free survival when compared to WBI alone. CONCLUSION: The addition of RNI to WBI in T1-2N1 breast cancer after BCS and adjuvant systematic therapy did not improve outcomes in comparison with WBI alone. Further studies are still needed to identify patients who would most benefit from RNI in this patient population.

15.
J Cell Mol Med ; 24(1): 214-226, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31657123

RESUMO

Radiation-induced lung injury (RILI) is the major complication of thoracic radiation therapy, and no effective treatment is available. This study explored the role of high-mobility group box 1 (HMGB1) in acute RILI and the therapeutic effect of glycyrrhizin, an inhibitor of HMGB1, on RILI. C57BL/6 mice received a 20 Gy dose of X-ray radiation to the whole thorax with or without administration of glycyrrhizin. Severe lung inflammation was present 12 weeks after irradiation, although only a mild change was noted at 2 weeks and could be alleviated by administration of glycyrrhizin. Glycyrrhizin decreased the plasma concentrations of HMGB1 and sRAGE as well as TNF-α, IL-1ß and IL-6 levels in the bronchoalveolar lavage fluid (BALF). The expression of RAGE was decreased while that of TLR4 was significantly increased at 12 weeks, but not 2 weeks, after irradiation in mouse lung tissue. In vitro, the expression of TLR4 increased in RAW 264.7 cells after conditioning with the supernatant from the irradiated MLE-12 cells containing HMGB1 but showed no change when conditioned medium without HMGB1 was used. However, conditioned culture had no effect on RAGE expression in RAW 264.7 cells. Glycyrrhizin also inhibited the related downstream transcription factors of HMGB/TLR4, such as NF-κB, JNK and ERK1/2, in lung tissue and RAW 264.7 cells when TLR4 was activated. In conclusion, the HMGB1/TLR4 pathway mediates RILI and can be mitigated by glycyrrhizin.

16.
Toxicol Lett ; 319: 49-57, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31693926

RESUMO

Blast lung injury is associated with high morbidity and mortality. Vaporized perfluorocarbon (PFC) inhalation has been reported to attenuate acute respiratory distress syndrome in humans and animal models. However, the effect of vaporized PFC on blast lung injury is still unknown. In this study, we investigated the protective effects and potential underlying mechanisms of action of vaporized PFC on blast lung injury in a canine model. This was a prospective, controlled, animal study in adult male hybrid dogs randomized to sham, blast (B), blast plus mechanical ventilation (B + M), and blast plus PFC (B + P) groups. All groups except for the sham were exposed to blast wave. The B + P group was treated with vaporized PFC for 1.5 h followed by 5.5 h mechanical ventilation. B + M group received 7.5 h mechanical ventilation and B group was observed for 7.5 h. Blast lung injury was induced using a shock tube. Blood gas, inflammatory cytokines, and oxidative stress were measured. Expression of nuclear factor (NF)-κB activation, mitogen-activated protein kinase (MAPK) and nuclear factor, erythroid 2 like 2 (Nrf2) were measured using western blot. Lung injury observed after blast exposure was marked by increased histopathological scores, ratio of lung wet to dry weight. PFC treatment attenuated blast lung injury as indicated by histopathological scores and ratio of lung wet to dry weight. PFC treatment downregulated interleukin (IL)-6, tumor necrosis factor (TNF)-α, and malondialdehyde (MDA), and upregulated superoxide dismutase (SOD) activity. PFC also suppressed expression of MAPK/NF-κB and Nrf2 protein levels. Our results suggest that PFC attenuated blast-induced acute lung injury by inhibiting MAPK/NF-κB activation and inducing Nrf2 expression in dogs.


Assuntos
Traumatismos por Explosões/tratamento farmacológico , Fluorcarbonetos/uso terapêutico , Lesão Pulmonar/tratamento farmacológico , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , NF-kappa B/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Administração por Inalação , Animais , Traumatismos por Explosões/patologia , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Cães , Fluorcarbonetos/administração & dosagem , Pulmão/patologia , Lesão Pulmonar/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos
17.
Science ; 367(6474): 189-192, 2020 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-31831637

RESUMO

Majorana zero modes (MZMs) are spatially localized, zero-energy fractional quasiparticles with non-Abelian braiding statistics that hold promise for topological quantum computing. Owing to the particle-antiparticle equivalence, MZMs exhibit quantized conductance at low temperature. By using variable-tunnel-coupled scanning tunneling spectroscopy, we studied tunneling conductance of vortex bound states on FeTe0.55Se0.45 superconductors. We report observations of conductance plateaus as a function of tunnel coupling for zero-energy vortex bound states with values close to or even reaching the 2e 2/h quantum conductance (where e is the electron charge and h is Planck's constant). By contrast, no plateaus were observed on either finite energy vortex bound states or in the continuum of electronic states outside the superconducting gap. This behavior of the zero-mode conductance supports the existence of MZMs in FeTe0.55Se0.45.

18.
Sci Rep ; 9(1): 20084, 2019 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-31882723

RESUMO

Acute leukaemias express high levels of MYB which are required for the initiation and maintenance of the disease. Inhibition of MYB expression or activity has been shown to suppress MLL-fusion oncoprotein-induced acute myeloid leukaemias (AML), which are among the most aggressive forms of AML, and indeed MYB transcription has been reported to be regulated by the MLL-AF9 oncoprotein. This highlights the importance of understanding the mechanism of MYB transcriptional regulation in these leukaemias. Here we have demonstrated that the MLL-AF9 fusion protein regulates MYB transcription directly at the promoter region, in part by recruiting the transcriptional regulator kinase CDK9, and CDK9 inhibition effectively suppresses MYB expression as well as cell proliferation. However, MYB regulation by MLL-AF9 does not require H3K79 methylation mediated by the methyltransferase DOT1L, which has also been shown to be a key mediator of MLL-AF9 leukemogenicity. The identification of specific, essential and druggable transcriptional regulators may enable effective targeting of MYB expression, which in turn could potentially lead to new therapeutic approaches for acute myeloid leukaemia with MLL-AF9.

19.
Biomed Environ Sci ; 32(10): 730-738, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31843043

RESUMO

OBJECTIVE: To explore the interactions between pre-pregnancy body mass index (BMI) and age on offspring neuropsychological development from 1 to 24 months in China. METHODS: In this birth cohort study, a total of 2,253 mother-child pairs were enrolled in Tianjin, China, between July 2015 and May 2018. The China Developmental Scale for Children was used to assess developmental quotient (DQ) of children aged from 1 to 24 months. RESULTS: Mixed-models analysis revealed significant age × pre-pregnancy BMI interactions for total DQ and five neurobehavioral domains (gross motor, fine motor, adaptive, language, and social; P < 0.001). Age × pre-pregnancy BMI ⪖ 25 kg/m2 was associated with a negative effect on total DQ and five neurobehavioral domains, as compared to pre-pregnancy BMI < 25 kg/m2 (P < 0.01). Multiple comparisons showed pre-pregnancy BMI ⪖ 25 kg/m2 of mothers had a positive effect on child total DQ at the age of 1 month but a negative effect at 24 months (P < 0.05). CONCLUSION: This study supported the age × pre-pregnancy BMI interaction on offspring neuropsychological development. It also revealed a short-term positive impact of high pre-pregnancy BMI on neuropsychological development at 1 month of age, but a long-term negative effect (from 1 to 24 months).


Assuntos
Índice de Massa Corporal , Desenvolvimento Infantil , Adulto , China , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Adulto Jovem
20.
Artigo em Inglês | MEDLINE | ID: mdl-31781277

RESUMO

Objectives: To evaluate the efficacy and safety of compound Kushen injection (CKI) combined with chemo treatment (chemo) for non-small-cell lung cancer (NSCLC). Methods: We systematically searched the literature published in seven databases, including Embase, PubMed, central, MEDLINE, CNKI, Wanfang, and VIP, from their inception to April 2019 for all randomized controlled trials (RCTs) comparing CKI plus chemo with chemo alone in patients with NSCLC. Our main end point was clinical efficiency and the secondary outcomes were Karnofsky performance score (KPS), immune function, and adverse events. The Cochrane risk of bias tool was applied for quality assessment. Results: 10 studies involving 1019 participants were included. The clinical response rate (relative risk (RR) = 1.21, 95% confidence interval (CI): 1.06 to 1.37; P=0.003), KPS (RR = 2.18, 95% CI: 1.49 to 3.17; P < 0.0001), immune function (mean differences (MD) = 0.82, 95% CI: 0.12 to 1.52; P=0.02) and adverse effects (RR = 0.67, 95% CI: 0.60 to 0.74; P < 0.00001) in the CKI plus chemo group showed significant differences when compared with chemo alone. Conclusions: CKI combined with chemo can improve clinical efficiency, KPS, and immune function and reduce adverse reactions in patients with NSCLC when compared with chemo alone. However, more rigorously designed RCTs are needed to validate this benefit, as some of the included RCTs are of low methodological quality.

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