Exosomes promote pre-metastatic niche formation in ovarian cancer.

Ovarian cancer is one of the most common gynecological malignancies. Upon initial diagnosis, the majority of patients present with widespread metastatic growth within the peritoneal cavity. This metastatic growth occurs in stages, with the formation of a pre-metastatic niche occurring prior to macroscopic tumor cell invasion. Exosomes released by the primary ovarian tumor are small extracellular vesicles which prepare the distant tumor microenvironment for accelerated metastatic invasion. They regulate intercellular communication between tumor cells and normal stroma, cancer-associated fibroblasts, and local immune cells within the tumor microenvironment. In this review, we highlight the emerging roles of ovarian cancer exosomes as coordinators of pre-metastatic niche formation, biomarkers amenable to liquid biopsy, and targets of chemotherapy

Transcriptomic-metabolomic reprogramming in EGFR-mutant NSCLC early adaptive drug escape linking TGFβ2-bioenergetics-mitochondrial priming.

The impact of EGFR-mutant NSCLC precision therapy is limited by acquired resistance despite initial excellent response. Classic studies of EGFR-mutant clinical resistance to precision therapy were based on tumor rebiopsies late during clinical tumor progression on therapy. Here, we characterized a novel non-mutational early adaptive drug-escape in EGFR-mutant lung tumor cells only days after therapy initiation, that is MET-independent. The drug-escape cell states were analyzed by integrated transcriptomic and metabolomics profiling uncovering a central role for autocrine TGFβ2 in mediating cellular plasticity through profound cellular adaptive Omics reprogramming, with common mechanistic link to prosurvival mitochondrial priming. Cells undergoing early adaptive drug escape are in proliferative-metabolic quiescent, with enhanced EMT-ness and stem cell signaling, exhibiting global bioenergetics suppression including reverse Warburg, and are susceptible to glutamine deprivation and TGFβ2 inhibition. Our study further supports a preemptive therapeutic targeting of bioenergetics and mitochondrial priming to impact early drug-escape emergence using EGFR precision inhibitor combined with broad BH3-mimetic to interrupt BCL-2/BCL-xL together, but not BCL-2 alone

MrMYB6 From Chinese Bayberry (Myrica rubra) Negatively Regulates Anthocyanin and Proanthocyanidin Accumulation

Anthocyanins and proanthocyanidins (PAs) are important flavonoids in Chinese bayberry (Morella rubra), which functions in fruit color and exhibits multiple health promoting and disease-preventing effects. To investigate the regulation of their biosynthesis in Chinese bayberries, we isolated and identified a subgroup 4 MYB transcription factor (TF), MrMYB6, and found MrMYB6 shared similar repressor domains with other MYB co-repressors of anthocyanin and PA biosynthesis after sequence analysis. Gene expression results revealed the transcripts of MrMYB6 were negatively correlated with the anthocyanin and insoluble PA contents and also with the gene expressions involved in anthocyanin biosynthesis and PA specific genes such as MrLAR and MrANR during the late ripening stages of bayberries. In addition, overexpression of MrMYB6 in tobacco inhibited the transcript levels of NtCHI, NtLAR, and NtANR2, resulting into a decline in the levels of anthocyanins and PAs in tobacco flowers. We further found that MrMYB6 interacted with MrbHLH1 and MrWD40-1 to form functional complexes that acted to directly repress the promoter activities of the PA-specific gene MrLAR and MrANR and the anthocyanin-specific gene MrANS and MrUFGT. Taken together, our results suggested that MrMYB6 might negatively regulate anthocyanin and PA accumulation in Chinese bayberry

Sciences for The 2.5-meter Wide Field Survey Telescope (WFST)

The Wide Field Survey Telescope (WFST) is a dedicated photometric survey facility under construction jointly by the University of Science and Technology of China and Purple Mountain Observatory. It is equipped with a primary mirror of 2.5m in diameter, an active optical system, and a mosaic CCD camera of 0.73 Gpix on the main focus plane to achieve high-quality imaging over a field of view of 6.5 square degrees. The installation of WFST in the Lenghu observing site is planned to happen in the summer of 2023, and the operation is scheduled to commence within three months afterward. WFST will scan the northern sky in four optical bands (u, g, r, and i) at cadences from hourly/daily to semi-weekly in the deep high-cadence survey (DHS) and the wide field survey (WFS) programs, respectively. WFS reaches a depth of 22.27, 23.32, 22.84, and 22.31 in AB magnitudes in a nominal 30-second exposure in the four bands during a photometric night, respectively, enabling us to search tremendous amount of transients in the low-z universe and systematically investigate the variability of Galactic and extragalactic objects. Intranight 90s exposures as deep as 23 and 24 mag in u and g bands via DHS provide a unique opportunity to facilitate explorations of energetic transients in demand for high sensitivity, including the electromagnetic counterparts of gravitational-wave events detected by the second/third-generation GW detectors, supernovae within a few hours of their explosions, tidal disruption events and luminous fast optical transients even beyond a redshift of 1. Meanwhile, the final 6-year co-added images, anticipated to reach g about 25.5 mag in WFS or even deeper by 1.5 mag in DHS, will be of significant value to general Galactic and extragalactic sciences. The highly uniform legacy surveys of WFST will also serve as an indispensable complement to those of LSST which monitors the southern sky.Comment: 46 pages, submitted to SCMP

Renal water molecular diffusion characteristics in healthy native kidneys: assessment with diffusion tensor MR imaging.

BACKGROUND: To explore the characteristics of diffusion tensor imaging (DTI) and magnetic resonance (MR) imaging in healthy native kidneys. METHODS: Seventy-three patients without chronic kidney disease underwent DTI-MRI with spin echo-echo planar (SE-EPI) sequences accompanied by an array spatial sensitivity encoding technique (ASSET). Cortical and medullary mean, axial and radial diffusivity (MD, AD and RD), fractional anisotropy (FA) and primary, secondary and tertiary eigenvalues (λ1, λ2, λ3) were analysed in both kidneys and in different genders. RESULTS: Cortical MD, λ2, λ3, and RD values were higher than corresponding medullary values. The cortical FA value was lower than the medullary FA value. Medullary λ1 and RD values in the left kidney were lower than in the right kidney. Medullary λ2, and λ3 values in women were higher than those in men. Medullary FA values in women were lower than those in men. Medullary FA (r = 0.351, P = 0.002) and λ1 (r = 0.277, P = 0.018) positively correlated with eGFR. Medullary FA (r = -0.25, P = 0.033) negatively correlated with age. CONCLUSIONS: Renal water molecular diffusion differences exist in human kidneys and genders. Age and eGFR correlate with medullary FA and primary eigenvalue

Bioprocess. Biosyst. Eng.

One simple but efficient carbon-supplying device was designed and developed, and the correlative carbon-supplying technology was described. The absorbing characterization of this device was studied. The carbon-supplying system proved to be economical for large-scale cultivation of Spirulina sp. in an outdoor raceway pond, and the gaseous carbon dioxide absorptivity was enhanced above 78%, which could reduce the production cost greatly.One simple but efficient carbon-supplying device was designed and developed, and the correlative carbon-supplying technology was described. The absorbing characterization of this device was studied. The carbon-supplying system proved to be economical for large-scale cultivation of Spirulina sp. in an outdoor raceway pond, and the gaseous carbon dioxide absorptivity was enhanced above 78%, which could reduce the production cost greatly

Novel strategies to prevent the development of multidrug resistance (MDR) in cancer

The development of multidrug resistance (MDR) is one of the major challenges to the success of traditional chemotherapy treatment in cancer patients. Most studies to date have focused on strategies to reverse MDR following its development. However, agents utilizing this approach have proven to be of limited clinical use, failing to demonstrate an improvement in therapeutic efficacy with almost no significant survival benefits observed in cancer clinical trials. An alternative approach that has been applied is to prevent or delay MDR prior or early in its development. Recent investigations have shown that preventing the emergence of MDR at the onset of chemotherapy treatment, rather than reversing MDR once it has developed, may assist in overcoming drug resistance. In this review, we focus on a number of novel strategies used by small-molecule inhibitors to prevent the development of MDR. These agents hold great promise for prolonging the efficacy of chemotherapy treatment and improving the clinical outcomes of patients with cancers that are susceptible to MDR development

Simulation Parameter Calibration and Test of Typical Pear Varieties Based on Discrete Element Method

To improve the accuracy of discrete element simulation parameters for the mechanized picking and collection of pears, the study calibrated the simulation parameters of pears by the method of combining a physical experiment and simulation. Based on the intrinsic parameters of four kinds of pears (Snow pears, Crisp pears, Huangguan pears and Qiuyue pears), their simulation models were constructed by the Hertz-Mindlin with a bonding model. The simulation parameters between pears and the contact material (PVC, EVA foam material) were calibrated by the methods of free fall collision, inclined sliding and rolling, respectively. The experiments of pear accumulation angle were carried out. It was obtained to process the image of pears with Matrix Laboratory software. In order to determine the optimal value interval of influencing factors of the pear accumulation angle, the steepest ascent experiment was carried out. Considering the coefficient of collision recovery, the coefficient of static friction and the coefficient of rolling friction between pears, five-level simulation experiments of the pear accumulation angle were designed for each factor by the method of orthogonal rotation combination. The regression model of the error between the measured value and the simulated value of the pear accumulation angle was established, and the influence of three factors on the pear accumulation angle was analyzed. The results showed that the static friction coefficient and rolling friction coefficient between pears have significant effects on the pear accumulation angle. Therefore, the optimal model of minimum error was constructed according to constraint condition, and the coefficient of collision recovery, coefficient of static friction and coefficient of rolling friction between pears were obtained. The accumulation angle verification experiments were carried out by the method of bottomless barrel lifting. The results showed that the relative error between the simulated and measured accumulation angle of four kinds of pears were 1.42%, 1.68%, 2.19% and 1.83%, respectively, which indicated that the calibrated simulation parameters were reliable. The research can provide a basis for the design and parameters optimization of harvesting machinery of pears

Data-Driven Model Predictive Control for Wave Energy Converters Using Gaussian Process

The energy harvested by an ocean wave energy converter (WEC) can be enhanced by a well-designed wave-by-wave control strategy. One of such superior control methods is model predictive control (MPC), which is a nonlinear constrained optimization control strategy. A limitation of the classical MPC algorithm is its requirement of an accurate WEC dynamic model for real-time implementation. This article overcomes this challenge by proposing a data-driven MPC scheme for wave energy converters. The data-based WEC model is developed by a Gaussian process (encompassing mean predictions and symmetric uncertainties) for a more accurate description of nonlinear and unmodeled system dynamics. A cross-entropy solver for data-driven MPC is employed for rapid, high-performance results, which samples trajectories from Gaussian distributions based on the concept of the symmetry principle. The proposed strategy is verified numerically by simulations which demonstrate its superior performance over a classical complex-conjugate controller

Study on the destabilization mixing in the flat plate photobioreactor by means of CFD

One destabilizing structure applied in the flat plate photobioreactor was designed, and the flow field and particle trajectory in it were simulated by means of CFD (computational fluid dynamics) to optimize structural parameters of photobioreactor. The results showed that the vertical velocity along the light path was produced in the condition of destabilization, which helps to achieve homogenous mixing of medium needed for microalgae growth. The fluid micelle in the flow field waved regularly, which made the algae cell transmitted between light and dark area and enhance the efficiency of photosynthesis. This destabilizing structure had a great potential to be used in the photobioreactor design. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved