Imiquimod (IMQ) is an immunomodulating drug that is approved for the treatment of superficial basal cell carcinoma, actinic keratosis, external genital warts and perianal warts. However, IMQ cream ...(Aldara
) has several drawbacks including poor skin permeation, local toxicity, and compromised patient compliance as a topical pharmacological option.
Our research aimed to develop and optimize nanostructured lipid carriers (NLCs) containing IMQ for the first time using a hybrid design of experiments approach. The optimized formulation was then incorporated into a matrix-type topical patch as an alternative dosage form for topical application and evaluated for IMQ deposition across different skin layers in comparison to the performance of the commercial product. Additionally, our work also attempted to highlight the possibility of implementing environment-friendly practices in our IMQ-NLCs formulation development by reviewing our analytical methods and experimental designs and reducing energy and solvent consumption where possible.
In this study, stearyl alcohol, oleic acid, Tween
80 (polysorbate 80), and Gelucire
50/13 (Stearoyl polyoxyl-32 glycerides) were selected for formulation development. The formulation was optimized using a 2
factorial design and a central composite design. The optimized formulation achieved the average particle size, polydispersity index, and zeta potential of 75.6 nm, 0.235, and - 30.9 mV, respectively. Subsequently, a matrix-type patch containing IMQ-NLCs was developed and achieved a statistically significant improvement in IMQ deposition in the deeper skin layers. The IMQ deposition from the patch into the dermis layer and receptor chamber was 3.3 ± 0.9 µg/cm
and 12.3 ± 2.2 µg/cm
, while the commercial cream only deposited 1.0 ± 0.8 µg/cm
and 1.5 ± 0.5 µg/cm
of IMQ, respectively.
In summary, IMQ-NLC-loaded patches represent great potential as a topical treatment option for skin cancer with improved patient compliance.
The aim of this prospective trial was to investigate the ability of pulse pressure variation (PPV) and corrected flow time (FTc) to predict fluid responsiveness in the prone position.
Forty-four ...patients undergoing lumbar spine surgery in the prone position on a Wilson frame were prospectively studied. PPV and FTc were measured before and after a colloid bolus (6 ml kg−1) both in the supine and in the prone positions. Fluid responsiveness was defined as an increase in the stroke volume index of ≥10% as measured by oesophageal Doppler.
In the supine position, 26 patients were responders and the areas under the curve (AUC) of the receiver-operator characteristic (ROC) curves of PPV and FTc were 0.935 95% confidence interval (CI): 0.870–0.999, P<0.001 and 0.822 (95% CI: 0.682–0.961, P<0.001), respectively. The optimal cut-off PPV and FTc values were 15% (sensitivity 73%, specificity 94%) and 358 ms (sensitivity 88%, specificity 78%), respectively. In the prone position, 34 patients were responders and the AUCs of PPV and FTc were 0.969 (95% CI: 0.912–1.000, P<0.001) and 0.846 (95% CI: 0.706–0.985, P=0.001), respectively. The optimal cut-off PPV and FTc values were 14% (sensitivity 97%, specificity 90%) and 331 ms (sensitivity 77%, specificity 90%), respectively.
While the predictability of PPV was significantly higher than that of FTc in the prone position, both variables showed high predictability and remained as useful indices for guiding fluid therapy in prone patients with minimal alterations in their optimal cut-off values to predict fluid responsiveness.
URL: http://www.clinicaltrials.gov/ct2/show/NCT01646359?term=NCT01646359&rank=1 and unique identification number NCT01646359.
Coactosin-like protein (CLP, or Cotl1), is an F-actin-binding protein, whose role in cancer is largely unknown. Here we show that CLP/Cotl1 is highly expressed in a rat epithelial breast cancer cell ...line (FE1.3) compared with its mesenchymal counterpart (FE1.2). Knockdown of CLP/Cotl1 in FE1.3 cells increased cell proliferation, whereas its overexpression in FE1.2 cells inhibited proliferation in culture and reduced tumor growth in xenograft assays in mice. Mechanistically, we identified two major pathways through which CLP/Cotl1 exerts its suppressive effects. First, CLP/Cotl1 re-expression in FE1.2 and in human MCF7 breast cancer cells induced expression of the growth-suppressor gene interleukin-24 (IL-24), which independently of p53 upregulates the tumor-suppressor genes p53 apoptosis effector related to PMP-22 (PERP) and p21
. Second, overexpression of CLP/Cotl1 potentiated the growth-suppressive effect of transforming growth factor-β1 (TGFβ1), leading to downregulation of TGFβ-responsive genes vascular growth factor A/B (VEGFA/VEGFB), hypoxia inducing factor 1α (HIF-1α) and trombospondin 1 (TSP1), which mediate various hallmarks of cancer progression including angiogenesis, invasion and metastasis. CLP/Cotl1 inhibited TGFβ signaling via a non-canonical signaling involving IL-24-instigated inhibition of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) phosphorylation and subsequent post-transcriptional downregulation of SMAD2 and SMAD4. We also showed that CLP/COTL1 expression sensitizes breast cancer cells to chemotherapeutic drugs, and this was further enhanced by addition of exogenous TGFβ1. CLP/Cotl1 expression is lost in many human malignancies including prostate, uterine and breast cancers. Thus, our results uncover a novel tumor-suppressor role for CLP/Cotl1 and identify the downstream effectors interleukin 24 (IL-24)/PERP and IL-24/MAPK/ERK/TGFβ as potential targets for precision therapy.
Long term coal mining produces pollutants such as coal gangue, coal mine gas and mine water. With the rapid urbanization, the increased environmental burden has led to the deterioration of ...environmental pollution problems, which seriously restricts the harmonious and sustainable development of the ecological economy. In order to understand the changes of the ecological environment in Shanxi Province in the past seven years, this paper selects the ground remote sensing data of Shanxi Province in the winter of 2013–2019 to obtain remote sensing ecological indicators (RSEI) that comprehensively reflect the ground ecological status, and uses spatial autocorrelation and geological detectors to explore the driving factors of the ecological environment differences in Shanxi Province, revealing the dynamic mechanism of the RSEI differences in Shanxi Province. The results show that the overall ecological environment quality in winter in Shanxi Province has a downward trend from 2013 to 2017 and an upward trend from 2018 to 2019. The spatial distribution of ecological environment quality between 2013 and 2019 is positively correlated. The clustering and outlier analysis chart of RSEI shows that in the seven years from 2013 to 2019, there are stable high value clusters in the north of Shanxi Province, while there are more low value clusters in the south. The significance test results show that the output value of the primary industry and the output value of the secondary industry dominated from 2013 to 2019.
Two kinds of ODS high-Cr ferritic steels (commercial MA956 and an Al-free 16Cr-0.1Ti ODS ferritic steel) and one conventional ferritic/martensitic steel (T122) were irradiated at about 440 degreesC ...with high-energy super(20)Ne-ions in HIRFL. Successively increasing doses from 350 to 900 appm of Ne concentration, corresponding to atomic displacement levels from 0.7 to 1.8 dpa, were approached. A nearly uniform distribution of Ne concentration and atomic displacement damage was produced through the thickness of 60 mu m of the specimens by using an energy degrader. Mechanical properties of the specimens were tested with the small-ball punch technique. The test at room temperature shows a less significant ductility loss in the ODS ferritic steel MA956 than in the T122 irradiated to the same dose of 350 appm Ne/0.7 dpa. The test at 500 degreesC shows that the Al-free 16Cr-0.1Ti ODS ferritic steel does not exhibit observable loss of ductility even to the highest dose level (900 appm Ne/1.8dpa). An investigation with transmission electron microscopy (TEM) shows that voids with a diameter up to 70 nm were formed at grain boundaries in the conventional ferritic/martensitic steel T122 while only smaller bubbles were formed at the oxides/substrate interfaces in the ODS ferritic steel MA956. Mechanisms underlying the difference of irradiation response of the steels are discussed.
Magnetography using magnetic sensitive lines is regarded traditionally as the main instrument for measuring the magnetic field of the whole Sun. Full polarized Stokes parameters (
I
,
Q
,
U
,
V
) can ...be used to deduce the magnetic field under specific theoretical models or inversion algorithms. Due to various reasons, there are often cross-talk effects among Stokes signals observed directly by magnetographs. Especially, the circularly polarized signal
V
usually seriously affects the linearly polarized
Q
and
U
signals, which is one of the main errors in the value of the transverse magnetic field (parallel to the solar surface) that is related to
Q
and
U
. The full-disk magnetograph onboard the Advanced Space based Solar Observatory (ASO-S/FMG) is designed to observe Stokes parameters and deduce the magnetic-field vector. In this article, the methods for correcting the effects of cross-talk
V
on
Q
and
U
based on the assumption of perfectly symmetric
Q
and
U
and anti-symmetric Stokes
V
profiles and a new method for reducing the crosstalk effect under observation mode of the FMG are developed. Through the test, it is found that the two methods are effective in cross-talk removal in the sunspot region and have better consistency. Additionally, the developed method can be applied to remove the cross-talk effect by using only one group of
Q
,
U
and
V
images observed at one wavelength position.
To discuss application of apparent diffusion coefficient (ADC) in diffusion weighted imaging (DWI) combined with serum alkaline phosphatase (ALP) and tumor specific growth factor (TSGF) in evaluating ...neoadjuvant chemotherapy for osteosarcoma.
A total of 78 patients with osteosarcoma who were admitted to People's Hospital of Gansu from January 2016 to August 2018 were collected as study subjects. All the patients were treated with neoadjuvant chemotherapy. Before chemotherapy, at the end of 4 courses of chemotherapy, before and after surgery, MRI examination and detection of serum ALP and TSGF were performed. According to results of pathological examination, the 78 patients were divided into effective chemotherapy group (
54) and ineffective chemotherapy group (
24). ADC values, levels of serum ALP and TSGF, change rates of ADC values and levels of serum ALP and TSGF were compared between the two groups. The value of ADC value combined with serum ALP and TSGF in evaluating curative effect of neoadjuvant chemot
LiDAR is an important data source for disaster prevention and mitigation, its advantages include speediness, penetration, initiative, high-density and high-precision, high efficiency, ...information-richness. In this paper, we address the design and implementation of a practical parallel algorithm for Delaunay triangulation that works on massive point cloud data acquired by airborne LiDAR. The algorithm is based on the divide and conquer algorithm, Bowyer-Watson algorithm and triangulation-growth and can be easily extended to multi-core or cluster environment. It first divides the point cloud data into blocks at the MapReduce’s Map phase; then the triangulation network of each block is simultaneously constructed using Bowyer-Watson algorithm on different CPU cores; at the reduction phase, the triangular network of each block is merged and optimized using triangulation-growth and Local Optimization Procedure (LOP). Experimental results show that the speed of the paralleled triangulation algorithm can be improved significantly compared to the sequential algorithm on multi-core desktop computer. The speedup depends on partition of the dataset and the number of CPU cores used, and is usually 2–3 times that of sequential algorithms.
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