Propofol affects the biological behavior of ovarian cancer SKOV3 cells via ERK1/2-MMP-2/9 signaling pathway

Purpose: To investigate the effect of propofol on the biological behavior of ovarian cancer SKOV3 cells, and the mechanism of action involved. Methods: SKOV3 cells cultured in vitro were randomly divided into control group, fat emulsion group, low-dose propofol group (LDPG, 25 μmol/L), medium-dose propofol group (MDPG) (50 μmol/L) and high-dose propofol group (HDPG) (100 μmol/L). Apoptosis was determined by flow cytometry, while Transwell assay was used to measure the migration and invasion abilities of the cells. The protein levels of ERK1/2, MMP-2, MMP-9 were assayed with Western blotting. Moreover, the cells were transfected with siERK, and the regulatory effect of propofol on ERK1/2-MMP-2/9 signaling pathway was determined. Results: Apoptosis in HDPG was significantly reduced, relative to MDPG, while migration and invasion were enhanced, relative to MDPG (p < 0.05). Moreover, MMP-2, ERK1/2, and MMP-9 proteins were significantly higher in MDPG and HDPG than in control, fat emulsion and LDPGs (p < 0.05), and were upregulated in HDPGs, relative to MDPG (p < 0.05). In contrast, propofol did not up-regulate these proteins in siRNA-treated cells. Conclusion: Propofol enhances the migration, proliferation, and invasive ability SKOV3 cells, and upregulates the expressions of MMP-2, ERK1/2, and MMP-9 in these cells, via a mechanism related to the activation of ERK1/2-MMP-2/9 signaling route. These properties provide novel leads for the development of new drugs for ovarian cancer Keywords: Propofol, ERK1/2-MMP-2/9 signal route, Ovarian cancer, Biological behavio

Observation of Core Phase ScS from the M_w 9.0 Tohoku‐Oki Earthquake with High-Rate GPS

High-rate Global Positioning Systems (GPS) observations can record ground motions from moderate to strong earthquakes at distances of a few kilometers up to thousands of kilometers (Larson et al., 2003; Bock et al., 2004; Ohta et al., 2006;Wang et al., 2007; Davis and Smalley, 2009; Delouis et al., 2010; Shi et al., 2010; Yue and Lay, 2011). These observations detect strong signals such as S wave and surface waves (Kouba, 2003; Larson et al., 2003; Irwan et al., 2004; Ohta et al., 2006;Wang et al., 2007; Davis and Smalley, 2009; Shi et al., 2010), as well as relatively weaker seismic phases such as P waves (Avallone et al., 2011). Seismic phases arriving later than surface waves have been rarely reported. Although it has been confirmed that arbitrarily large seismic signals are recorded with high-rate GPS (Bock et al., 2004), we assess here the lower limit of signals from earthquakes that can be recovered from high-rate GPS records. Benefits of exploiting high-rate GPS in earthquake source studies include the ability to detect arbitrarily large dynamic ground motions that do not clip in the presence of strong ground motion and accurate recording of ground displacements without needing to doubly integrate acceleration records of strong-motion seismometers (Graizer, 2010). As a result, high-rate GPS records are now routinely used in studies of earthquake source parameters and rupture process independently of, or jointly with, seismological observations (Miyazaki et al., 2003; Ji et al., 2004; Bilich et al., 2008; Yokota et al., 2009; Avallone et al., 2011; Yue and Lay, 2011; Bock et al., 2011; Crowell et al., 2012). Though whole waveforms of high-rate GPS records have been employed in modeling earthquake source processes, it is not certain whether the wiggles following surface waves are true ground-motion signals or contamination from GPS signal propagation effects such as multipath or ionospheric distortion. Accordingly, very few phases following the arrival time of surface waves have been confirmed on high-rate GPS records, primarily because of the inherently lower signal-to-noise ratio (SNR). Identification and retrieval of the weaker secondary arrivals from high-rate GPS records would further confirm capability of GPS in recording ground motions, and thus lead to improved broadband seismograms via collated GPS and seismometers (Bock et al., 2011). Among the later arrivals, the seismic phase ScS is expected to be strong due to the complete reflection at the core–mantle boundary between the solid mantle and the liquid outer core where shear waves disappear. Moreover, ScS is far behind surface waves at close distances (less than 20°) where contamination of the surface-wave coda is weak. Here, we present a record section of seismograms retrieved from high-rate GPS from the 2011 Tohoku earthquake wherein we observe a weak but coherent seismic phase that we associate with ScS. This inference is supported by comparison of the high-rate GPS records with seismic records and synthetic seismograms

Immunotargeting of tumor vasculature: preclinical development of novel antibody-based imaging and therapy against TEM1/CD248

The success of antibody-based theranostics depends on the identification of tumor specific biomarkers and the development of corresponding antibodies with high-affinity and specificity. Tumor endothelial marker-1 (TEM1) is highly expressed in tumor vasculature of multiple cancers but not in normal organs. The expression of TEM1 was first evaluated and confirmed by immunohistochemistry from 53 cases of metastatic serous ovarian cancer at HUP. TEM1 positive tumor stroma was observed in >95% of the cases studied. Hence, developing sensitive and effective theranostic agents against TEM1 are of utmost significance in improving diagnosis and treatment of ovarian cancer. Our goals are: 1) engineer TEM1-specific antibodies; 2) evaluate these engineered antibodies in imaging and immunotherapies in preclinical models. To generate TEM1-targeting agents, we designed a panel of multivalent fusion proteins from scFv78, a previously isolated single chain variable fragment specifically recognizing the extracellular domain of TEM1. scFv78 was fused with different huIgG1 Fc region (CH2-, CH3-, or hinge). Proteins were expressed in 293F cells and purified by affinity chromatography. All scFv78 variants exhibited comparable thermo and serum stability in vitro. Among them, the scFv78-Fc fusion (78Fc) has the highest affinity to TEM1 (Kd = 0.15nM, 15X higher than scFv78). Pharmacokinetics (PK) and biodistribution of the protein panel were evaluated in naïve and TEM1+ tumor bearing animals. 78Fc has a t1/2 of 5.1hr, which is suitable for in vivo therapeutic and imaging applications. Therefore, 78Fc was further developed as imaging tool and antibody-drug conjugate (ADC) based on its favorable affinity, stability, half-life and PK profile. In pilot studies with preclinical animal models of tumor vasculature, fluorophore- and [124-I]-labeled 78Fc demonstrated specific enrichment in TEM1+ grafts, but not in control tumor or other organs, by both optical and immunoPET imaging. In addition, 78Fc-MMAE conjugate exerted specific killing of TEM1+ cells. In summary, we have developed a panel of innovative theranostics agents targeting TEM1 on the vasculature of ovarian cancer and several other solid tumors. Our long term goal is to translate such combined approach into the clinic: Using TEM1-antibody as imaging tools to select, and monitor patients for TEM1-antibody based targeted therapies

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

An Analysis of Water Use Efficiency of Staple Grain Productions in China: Based on the Crop Water Footprints at Provincial Level

This article analyzed the water use efficiency of China’s staple grain productions (maize, rice, and wheat). This research calculated the water footprints of crop production using the CROPWAT model based on reported water use in 2000 and during 2015–2019, and both green and blue water footprints were calculated. The results showed that compared to 2000 water use efficiency of crop production for maize, rice and wheat during 2015–2019 were increased by about 12.4%, 10.8%, and 2.5% respectively. The current spatial structure of the stable grain industry that makes up grain production regions are concentrated in northern China, then grains are distributed across China (North-to-South Grain Transportation). This has advantages in the increase of agricultural water productivity. This research indicated that agricultural policies should further consider an advance of regional grain production, along with the optimization of transportation channels for stable grains to increase irrigation water use efficiency. The establishment of staple grain production in designated areas not only ensures China’s food security, but also promotes the sustainable use of irrigation water resources

Large-scale vegetation history in China and its response to climate change since the Last Glacial Maximum

Large-scale palaeovegetation reconstruction plays a critical role in improving our understanding of the response of vegetation to climate change and in reducing the uncertainty in predictions of vegetation change under global warming scenarios. Here, we present quantitative vegetation reconstructions for China since the Last Glacial Maximum (LGM), using 286 selected fossil pollen records analyzed using the biomization method. The results show that from 23 to 19 ka (1 ka = 1000 cal yr BP), steppe and desert expanded southeastwards, dominating northern China, whereas forest in eastern China shrank southwards to near the middle and lower reaches of the Yangtze River; the percentage of forested sites at this time was the lowest during the studied interval. Forest then developed gradually during 18-12 ka. During the early and middle Holocene, tropical seasonal forest, broad-leaved evergreen/warm mixed forest, and temperate deciduous forest shifted northwards by 2 degrees, 4 degrees and 5 degrees in latitude, respectively, relative to today, and then declined in the late Holocene. In detail, forest flourished in the middle Holocene (9-4 ka) in semi-arid and semi-humid northern China, whereas it reached a maximum in the early and middle Holocene (11.5-6 ka) in humid southern China. Our results suggest that although forest throughout China exhibited the expected response to the evolution of the East Asian summer monsoon, precipitation exerted a more significant effect on vegetation change in northern China, whereas temperature and precipitation played a more important role in southern China. Our results are a potentially useful reference for assessing future vegetation dynamics under global warming scenarios

Quantifying regional vegetation changes in China during three contrasting temperature intervals since the last glacial maximum

The need to reduce the uncertainty of predictions of vegetation change under global warming highlights the importance of understanding the vegetation patterns and possible mechanisms of vegetation response during past warming intervals. Here, we present quantitative regional vegetation reconstructions for China during the Last Glacial Maximum (LGM, 18 +/- 2 C-14 kyr B.P.), early Holocene (EH, 8.5 +/- 0.5 C-14 kyr B.P.), and mid Holocene (MH, 6 +/- 0.5 C-14 kyr B.P.), using the biomization method and based on 249 pollen records. In addition, we used an inverse vegetation modeling approach to investigate the effect of climate change and CO2 concentration on the observed vegetation changes. The results demonstrate that during the LGM, steppe expanded southeastwards, reaching the present-day temperate deciduous forest (TEDE) zone; in contrast, the forest in eastern China underwent a substantial southward retreat and its percentage reached a minimum. The warm mixed forest (WAMF) and TEDE shifted southwards of similar to 10 degrees N relative to today, and tropical seasonal rain forest (TSFO) was almost absent. In addition, the forest-steppe boundary shifted southwards to near the middle and lower reaches of the Yangtze River. During the EH and MH, the TSFO, WAMF, and TEDE exhibited respective northward shifts of 2 degrees, 4 degrees and 5 degrees relative to today. In MH, the percentage of forest sites increased and reached a maximum, and the forest-steppe boundary had shifted northwestwards to near the present-day 300 mm isohyet. Our palaeovegetation reconstructions and model sensitivity experiments suggest that temperature was the dominant factor controlling the vegetation distribution during the LGM, while precipitation became increasingly more important during the Holocene throughout China. We further show that precipitation was the primary factor controlling palaeovegetation distribution in northern China, while temperature became increasingly more important in southern China. Our findings are potentially important for understanding the evolution of vegetation in China in response to ongoing global warming