Epithelial-mesenchymal transition (EMT)/mesenchymal-epithelial transition (MET) processes are proposed to be a driving force of cancer metastasis. By studying metastasis in bone marrow-derived ...mesenchymal stem cell (BM-MSC)-driven lung cancer models, microarray time-series data analysis by systems biology approaches revealed BM-MSC-induced signaling triggers early dissemination of CD133
/CD83
cancer stem cells (CSCs) from primary sites shortly after STAT3 activation but promotes proliferation towards secondary sites. The switch from migration to proliferation was regulated by BM-MSC-secreted LIF and activated LIFR/p-ERK/pS727-STAT3 signaling to promote early disseminated cancer cells MET and premetastatic niche formation. Then, tumor-tropic BM-MSCs circulated to primary sites and triggered CD151
/CD38
cells acquiring EMT-associated CSC properties through IL6R/pY705-STAT3 signaling to promote tumor initiation and were also attracted by and migrated towards the premetastatic niche. In summary, STAT3 phosphorylation at tyrosine 705 and serine 727 differentially regulates the EMT-MET switch within the distinct molecular subtypes of CSCs to complete the metastatic process.
Parkinson’s disease (PD) is a common neurodegenerative disease characterized by progressive loss of dopaminergic (DAergic) neurons in ventral brain. A disaccharide trehalose has demonstrated the ...potential to mitigate the DAergic loss in disease models for PD. However, trehalose is rapidly hydrolyzed into glucose by trehalase in the intestine, limiting its potential for clinical practice. Here we investigated the neuroprotective potentials of two trehalase-indigestible analogs, lactulose and melibiose, in sub-chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Treatment with MPTP generated significant motor deficits, inhibited dopamine levels and down-regulated dopamine transporter (DAT) in striatum. Expression levels of genes involved in anti-oxidative stress pathways, including superoxide dismutase 2 (SOD2), nuclear factor erythroid 2-related factor 2 (NRF2) and NAD(P)H dehydrogenase (NQO1) were also down-regulated, while expressions of oxidative stress marker 4-hydroxynonenal (4-HNE), microglial activation marker ionized calcium-binding adapter molecule 1 (IBA1) and astrocyte activation marker glial fibrillary acidic protein (GFAP) in ventral midbrain were up-regulated following MPTP treatment. MPTP also reduced the activity of autophagy, evaluated by autophagosomal marker microtubule-associated protein 1 light chain 3 (LC3)-II. Lactulose and melibiose significantly rescued motor deficits, increased dopamine in striatum, reduced levels of 4-HNE, IBA1 and GFAP, up-regulated SOD2, NRF2 and NQO1 levels, as well as LC3-II/LC3-I ratio in ventral midbrain with MPTP treatment. Our findings indicate the potential of lactulose and melibiose to protect DAergic neurons in PD.
Cancer progression is commonly segregated into processes of primary tumour growth and secondary metastasis. Recent evidence suggests that a subpopulation of cancer cells, cancer stem cells (CSCs), is ...responsible for tumour growth in cancer. However, the role of CSCs in cancer metastasis is unclear. In this study, we found that the C terminus of CD44 contributes to sphere formation and survival in vitro via the CD44–SRC–integrin axis. In addition, nuclear CD44/acetylated‐STAT3 is required for clonal formation in vitro and tumourigenicity in vivo. Nuclear CD44 binds to various promoters identified by chromatin immunoprecipitation‐seq, including that of c‐myc and Twist1, leading to cell fate change through transcriptional reprogramming. We propose that nuclear CD44/acetylated‐STAT3 performs an unexpected tumour‐progressing function by enhancing cell outgrowth into structures where cells with properties of CSCs can be generated from differentiated somatic cells in suspension culture, and then exhibit attributes of cells that have undergone an epithelial–mesenchymal transition, leading to tumour metastasis, and a resulting worse prognosis.
CD44 is a known marker for cancer stem cells (CSCs) and had functionally been associated with cancer metastasis. This paper highlights the functional contribution of CD44 in determining cellular features of CSCs that include the definition of underlying molecular mechanisms.
Spin optoelectronics is an indispensable key for the future development of spintronics. In conventional spin light emitting diodes (LEDs), spin‐polarized carrier pairs are injected electrically into ...the light emitting layer and create circularly polarized light (CPL). Generally, spin‐polarized carriers are accomplished using ferromagnetic contacts or applying an external magnetic field, which will produce several drawbacks, including low temperature operation, low spin‐polarized carriers injection efficiency, etc. To circumvent the existing shortcomings, here, an alternative approach is proposed and achieves spin‐polarized LEDs at room temperature based on quantum dots (QDs)/chiral metal‐organic framework heterojunction without using ferromagnetic contacts or magnetic fields. The spin‐polarized injected layer composed of self‐assembled monolayer (SAM)/Chiral‐MOF (Sr(9,10‐adc)(DMAc)2n)) film, which produces spin‐polarized holes with spin orientation, determining the polarization and strength of circularly polarized electroluminescence (CP‐EL). The spin‐QLED emits CP‐EL at a rate of 12.24% efficiency, which provides an excellent alternative to generate new functionality for conventional QLEDs. The approach is anticipated to be very useful, enabling to offer a general methodology for generating not yet realized spin optoelectronic devices.
Chiral‐metal organic framework (Chiral‐MOF) play a crucial role in the injection of a spin‐polarized hole into the adjusted layer of the CdSe/ZnS QDs‐emitting layer. The external quantum efficiency of spin‐QLED based on chiral‐MOF is 20.39%, and circularly polarized electroluminescence is 12.24% efficiency without using an external magnetic field and ferromagnetic electrodes.
Every year cervical cancer affects more than 300,000 people, and on average one woman is diagnosed with cervical cancer every minute. Early diagnosis and classification of cervical lesions greatly ...boosts up the chance of successful treatments of patients, and automated diagnosis and classification of cervical lesions from Papanicolaou (Pap) smear images have become highly demanded. To the authors' best knowledge, this is the first study of fully automated cervical lesions analysis on whole slide images (WSIs) of conventional Pap smear samples. The presented deep learning-based cervical lesions diagnosis system is demonstrated to be able to detect high grade squamous intraepithelial lesions (HSILs) or higher (squamous cell carcinoma; SQCC), which usually immediately indicate patients must be referred to colposcopy, but also to rapidly process WSIs in seconds for practical clinical usage. We evaluate this framework at scale on a dataset of 143 whole slide images, and the proposed method achieves a high precision 0.93, recall 0.90, F-measure 0.88, and Jaccard index 0.84, showing that the proposed system is capable of segmenting HSILs or higher (SQCC) with high precision and reaches sensitivity comparable to the referenced standard produced by pathologists. Based on Fisher's Least Significant Difference (LSD) test (P < 0.0001), the proposed method performs significantly better than the two state-of-the-art benchmark methods (U-Net and SegNet) in precision, F-Measure, Jaccard index. For the run time analysis, the proposed method takes only 210 seconds to process a WSI and is 20 times faster than U-Net and 19 times faster than SegNet, respectively. In summary, the proposed method is demonstrated to be able to both detect HSILs or higher (SQCC), which indicate patients for further treatments, including colposcopy and surgery to remove the lesion, and rapidly processing WSIs in seconds for practical clinical usages.
This study is aimed toward establishing a decision-making model with multiple criteria for appraisal and reimbursement to compare the attitudes of different stakeholders toward various dimensions and ...criteria and to evaluate the five targeted therapies (bevacizumab, cetuximab, panitumumab, aflibercept, and regorafenib) for metastatic colorectal cancer.
This study is a multi-criteria decision analysis (MCDA) using a model that includes three dimensions and nine criteria. Both the overall and individual scores of the respective targeted therapies in different dimensions and criteria were calculated. A sensitivity analysis was carried out in order to evaluate the robustness of the research results. An interview-based questionnaire survey was applied to obtain the performance information for the targeted therapies and the weights of the dimensions and criteria.
Overall, the clinical dimension had the highest weight, followed by the economic dimension, and finally, the social dimension. In the clinical dimension, the "comparative efficacy" criterion had the highest weight; in the economic dimension, the "cost-effectiveness" criterion" was given the greatest importance; in the social dimension, the "social concern and patient needs" criterion was given more emphasis. The overall values ranked from high to low as follows: cetuximab (overall score 3.3666), bevacizumab (3.3043), panitumumab (3.2030), aflibercept (2.8923) and regorafenib (2.8366).
A comprehensive value assessment system combining "multi-dimensional criteria," "multi-perspectives," and an "integrative assessment" is necessary to evaluate the value of medicines. The results showed not only the order of weights of different dimensions or criteria, but also the rankings of the value of the targeted therapies.
This study examines the impacts of convective parameterization and moisture convective trigger on convectively coupled equatorial waves simulated by the Seoul National University (SNU) atmospheric ...general circulation model (AGCM). Three different convection schemes are used, including the simplified Arakawa–Schubert (SAS) scheme, the Kuo (1974) scheme, and the moist convective adjustment (MCA) scheme, and a moisture convective trigger with variable strength is added to each scheme. The authors also conduct a “no convection” experiment with deep convection schemes turned off. Space–time spectral analysis is used to obtain the variance and phase speed of dominant convectively coupled equatorial waves, including the Madden–Julian oscillation (MJO), Kelvin, equatorial Rossby (ER), mixed Rossby–gravity (MRG), and eastward inertio-gravity (EIG) and westward inertio-gravity (WIG) waves.
The results show that both convective parameterization and the moisture convective trigger have significant impacts on AGCM-simulated, convectively coupled equatorial waves. The MCA scheme generally produces larger variances of convectively coupled equatorial waves including the MJO, more coherent eastward propagation of the MJO, and a more prominent MJO spectral peak than the Kuo and SAS schemes. Increasing the strength of the moisture trigger significantly enhances the variances and slows down the phase speeds of all wave modes except the MJO, and usually improves the eastward propagation of the MJO for the Kuo and SAS schemes, but the effect for the MCA scheme is small. The no convection experiment always produces one of the best signals of convectively coupled equatorial waves and the MJO.
It is cost-efficient for a tenant with a limited budget to establish a virtual MapReduce cluster by renting multiple virtual private servers (VPSs) from a VPS provider. To provide an appropriate ...scheduling scheme for this type of computing environment, we propose in this paper a hybrid job-driven scheduling scheme (JoSS for short) from a tenant's perspective. JoSS provides not only job-level scheduling, but also map-task level scheduling and reduce-task level scheduling. JoSS classifies MapReduce jobs based on job scale and job type and designs an appropriate scheduling policy to schedule each class of jobs. The goal is to improve data locality for both map tasks and reduce tasks, avoid job starvation, and improve job execution performance. Two variations of JoSS are further introduced to separately achieve a better map-data locality and a faster task assignment. We conduct extensive experiments to evaluate and compare the two variations with current scheduling algorithms supported by Hadoop. The results show that the two variations outperform the other tested algorithms in terms of map-data locality, reduce-data locality, and network overhead without incurring significant overhead. In addition, the two variations are separately suitable for different MapReduce-workload scenarios and provide the best job performance among all tested algorithms.
Traditional electrochromic devices change the color of electrochromic materials by mainly transforming the absorption band of the materials electrically, which leads to low schedulable color ...selection and color performance of such materials after electrochromism. Although the addition of an interference‐enhanced nanocavity can improve this issue, achieving full‐color controllability on a single electrochromic device is still a huge challenge. This study first demonstrates a near‐full‐color tunable chiroptical electrothermochromic device using a supramolecular chiral photonic material called ferroelectric liquid crystal (FLC)‐doped cholesteric liquid crystal (CLC) (FLC‐CLC). Experimental results show that the pitch of the CLC can be elongated significantly by doping a low concentration of FLC (≈4 wt%) such that the photonic bandgap (PBG) redshifts from blue to the shortwave near‐infrared region at near room temperature. Based on this fascinating feature, the PBG of the FLC‐CLC can be tuned electrically over the entire visible region with high color performance at near room temperature in a low‐voltage range (≤3 V) via the efficient electrothermal effect of the indium‐tin‐oxide‐coated substrate of the sample. Two potential low‐voltage tunable applications based on electrothermochromic FLC‐CLC materials, namely, a broadband tunable laser and a near‐full‐color tunable coaxial microfibric textile, are demonstrated in the study.
This study develops a near‐room‐temperature‐usable and near‐full‐color low‐voltage tunable chiroptical electrothermochromic device based on a novel material of ferroelectric liquid crystal (FLC)‐doped cholesteric liquid crystal (CLC). Two potential low‐voltage tunable applications, a broadband tunable laser and a near‐full‐color tunable coaxial microfibric textile, are also demonstrated based on the FLC‐CLC material.
Running can induce advantageous cardiovascular effects such as improved arterial stiffness and blood-supply perfusion. However, the differences between the vascular and blood-flow perfusion ...conditions under different levels of endurance-running performance remains unclear. The present study aimed to assess the vascular and blood-flow perfusion conditions among 3 groups (44 male volunteers) according to the time taken to run 3 km: Level 1, Level 2, and Level 3.
The radial blood pressure waveform (BPW), finger photoplethygraphy (PPG), and skin-surface laser-Doppler flowmetry (LDF) signals of the subjects were measured. Frequency-domain analysis was applied to BPW and PPG signals; time- and frequency-domain analyses were applied to LDF signals.
Pulse waveform and LDF indices differed significantly among the three groups. These could be used to evaluate the advantageous cardiovascular effects provided by long-term endurance-running training, such as vessel relaxation (pulse waveform indices), improvement in blood supply perfusion (LDF indices), and changes in cardiovascular regulation activities (pulse and LDF variability indices). Using the relative changes in pulse-effect indices, we achieved almost perfect discrimination between Level 3 and Level 2 (AUC = 0.878). Furthermore, the present pulse waveform analysis could also be used to discriminate between the Level-1 and Level-2 groups.
The present findings contribute to the development of a noninvasive, easy-to-use, and objective evaluation technique for the cardiovascular benefits of prolonged endurance-running training.
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