The microbial hybrid system modified by magnetic nanomaterials can enhance the interfacial electron transfer and energy conversion under the stimulation of a magnetic field. However, the ...bioelectrocatalytic performance of a hybrid system still needs to be improved, and the mechanism of magnetic field-induced bioelectrocatalytic enhancements is still unclear. In this work, γ-Fe2O3 magnetic nanoparticles were coated on a Shewanella putrefaciens CN32 cell surface and followed by placing in an electromagnetic field. The results showed that the electromagnetic field can greatly boost the extracellular electron transfer, and the oxidation peak current of CN32@γ-Fe2O3 increased to 2.24 times under an electromagnetic field. The enhancement mechanism is mainly due to the fact that the surface modified microorganism provides an elevated contact area for the high microbial catalytic activity of the outer cell membrane’s cytochrome, while the magnetic nanoparticles provide a networked interface between the cytoplasm and the outer membrane for boosting the fast multidimensional electron transport path in the magnetic field. This work sheds fresh scientific light on the rational design of magnetic-field-coupled electroactive microorganisms and the fundamentals of an optimal interfacial structure for a fast electron transfer process toward an efficient bioenergy conversion.
One of the most distinguishing features of the adult human brain is the complexity and diversity of its cortical astrocytes. Human protoplasmic astrocytes manifest a threefold larger diameter and ...have tenfold more primary processes than those of rodents. In all mammals, protoplasmic astrocytes are organized into spatially non-overlapping domains that encompass both neurons and vasculature. Yet unique to humans and primates are additional populations of layer 1 interlaminar astrocytes that extend long (millimeter) fibers, and layer 5–6 polarized astrocytes that also project distinctive long processes. We propose that human cortical evolution has been accompanied by increasing complexity in the form and function of astrocytes, which reflects an expansion of their functional roles in synaptic modulation and cortical circuitry.
Multi-layered NiO nanowires linked with a nitrogen-doped carbon backbone grown directly on flexible carbon cloth (NiO/NCBN/CC) was successfully fabricated with a facile synthetic strategy. The ...NiO/NCBN/CC was further used as a binding-free electrode for flexible energy storage devices, showing a boosted performance including a high capacitance of 1039.4 F g−1 at 1 A g−1 and an 83.4% capacitance retention ratio. More importantly, after 1500 cycles, the capacitance retention can achieve 72.5% at a current density of 20 A g−1. The excellent electrochemical properties of the as-prepared NiO/NCBN/CC are not only attributed to the multi-layered structure that can help to tender unimpeded channels and accommodate the electrolyte ions around the electrode interface during the charge–discharge process, but is also due to the link between the NiO and N-doped carbon backbone and the nitrogen doping on the carbon substrate, which results in extra defects on the surface that could boost the interfacial electron transfer rate of the electrode.
Inhibition of O-GlcNAcase (OGA) has emerged as a promising therapeutic approach to treat tau pathology in neurodegenerative diseases such as Alzheimer’s disease and progressive supranuclear palsy. ...Beginning with carbohydrate-based lead molecules, we pursued an optimization strategy of reducing polar surface area to align the desired drug-like properties of potency, selectivity, high central nervous system (CNS) exposure, metabolic stability, favorable pharmacokinetics, and robust in vivo pharmacodynamic response. Herein, we describe the medicinal chemistry and pharmacological studies that led to the identification of (3aR,5S,6S,7R,7aR)-5-(difluoromethyl)-2-(ethylamino)-3a,6,7,7a-tetrahydro-5H-pyrano3,2-dthiazole-6,7-diol 42 (MK-8719), a highly potent and selective OGA inhibitor with excellent CNS penetration that has been advanced to first-in-human phase I clinical trials.
The sluggish electron transfer at the interface of microorganisms and an electrode is a bottleneck of increasing the output power density of microbial fuel cells (MFCs). Mo-doped carbon nanofibers ...(Mo-CNFs) prepared with electrostatic spinning and high-temperature carbonization are used as an anode in MFCs here. Results clearly indicate that Mo
C nanoparticles uniformly anchored on carbon nanowire, and Mo-doped anodes could accelerate the electron transfer rate. The Mo-CNF ΙΙ anode delivered a maximal power density of 1287.38 mW m
, which was twice that of the unmodified CNFs anode. This fantastic improvement mechanism is attributed to the fact that Mo doped on a unique nanofiber surface could enhance microbial colonization, electrocatalytic activity, and large reaction surface areas, which not only enable direct electron transfer, but also promote flavin-like mediated indirect electron transfer. This work provides new insights into the application of electrospinning technology in MFCs and the preparation of anode materials on a large scale.
Purpose
FOXA1, as a pioneering transcription factor, has been shown to drive prostate cancer progression. Previous studies showed that FOXA1 expression in prostate cancer was positively associated ...with cancer angiolymphatic invasion and metastasis. However, the mechanism underlying the correlation between FOXA1 and prostate cancer angiolymphatic invasion and metastasis remains largely unclear.
Methods
Herein, we set out to investigate the role of FOXA1 in the interactions between prostate cancer cells and endothelial cells. Endothelial cells' phenotypes were assessed through CCK‐8 assay, Transwell migration assay, and tube formation assay. The angiogenic factors acting on endothelial cells mediated by FOXA1were characterized by RNA-seq, qPCR array, angiogenesis cytokines array, and ELISA assay. The impact of FOXA1 on tumor angiogenesis was examined in a xenograft model in nude mice. The effect of FOXA1 on prostate cancer angiogenesis was validated on a primary prostate cancer tissue microarray.
Results
FOXA1 expression in prostate cancer cells promoted endothelial cell proliferation, migration, and tube formation in vitro. Mechanistically, FOXA1 increased pro-angiogenic factors production, including EGF, Endothelin-1, and Endoglin. Moreover, in vivo study showed that FOXA1 facilitated tumor angiogenesis. Furthermore, clinical samples investigation indicated that FOXA1 enhanced prostate cancer angiogenesis.
Conclusion
Overall, these findings illustrated a tumor angiogenesis-promoting role of FOXA1 in prostate cancer.
Real‐time power dispatch can coordinate wind farms, automatic generation control units and non‐automatic generation control units. In real‐time power dispatch, the probable wind power forecast errors ...should be appropriately formulated to ensure system security with high probability and minimize operational cost. Previous studies and the authors' onsite tests show that Cauchy distribution effectively fits the “leptokurtic” feature of small‐timescale wind power forecast errors distributions. In this paper, a chance‐constrained real‐time dispatch model with the wind power forecast errors represented by multivariate Cauchy distribution is proposed. Since the Cauchy distribution is stable and has promising mathematical characteristics, the proposed chance‐constrained real‐time dispatch model can be analytically transformed to a convex optimization problem considering the dependence among wind farms’ outputs. Moreover, the proposed model incorporates an affine control strategy compatible with automatic generation control systems. This strategy makes the chance‐constrained real‐time dispatch adaptively take into account both the potential power ramping requirement and power variation on transmission lines caused by the generation adjustment to offset the wind power forecast errors in real‐time power dispatch stage. Numerical test results show that the proposed method is reliable and effective. Meanwhile it is very efficient and suitable for real‐time application.
Androgen deprivation therapy (ADT) is the backbone of therapy for advanced prostate cancer (PCa). Despite the good initial response, castration resistance and metastatic progression will inevitably ...occur. Cancer-associated fibroblasts (CAFs) may be implicated in promoting metastasis of PCa after ADT. Our aim is to investigate the role and mechanism of CAFs-derived exosomes involving in metastasis of PCa after ADT.
PCa cells were co-cultured with exosomes derived from 10 nM dihydrotestosterone (DHT)-treated (simulating the high androgen level of prostate cancer microenvironment) or ethanol (ETOH) -treated (simulating the castration level of prostate cancer microenvironment after ADT) CAFs, and their migration and invasion differences under castration condition were examined both in vitro and in vivo. The miRNA profiles of exosomes derived from DHT-treated CAFs and matched ETOH-treated CAFs were analysed via next generation sequencing. The transfer of exosomal miR-146a-5p from CAFs to PCa cells was identified by fluorescent microscopy. The function and direct target gene of exosomal miR-146a-5p in PCa cells were confirmed through Transwell assays, luciferase reporter, and western blot.
Compared with DHT-treated CAFs, exosomes derived from ETOH-treated CAFs dramatically increased migration and invasion of PCa cells under castration condition. MiR-146a-5p level in exosomes from ETOH-treated CAFs was significantly reduced. The loss of miR-146a-5p may strengthen the epithelial-mesenchymal transition (EMT) to accelerate cancer cells metastasis by modulating epidermal growth factor receptor (EGFR)/ERK pathway.
CAFs-derived exosomal miR-146a-5p confers metastasis in PCa cells under ADT through the EGFR/ERK pathway and it may present a new treatment for PCa.
Abstract
Aiming at the problem that the traditional route selection of ships is difficult to meet the requirements of precision and rapidness, based on the two-dimensional structure space of the grid ...sea area, a route planning model of ships passing through waterways is established, and a method to realize the optimal route based on the dynamic programming algorithm is presented. The simulation results show that the algorithm is an optimization algorithm for the local route planning of ships.
Objectives
Previously, we found that long intergenic non‐coding RNA‐p21 (lincRNA‐p21) inhibited the development of human prostate cancer. However, the underlying molecular mechanisms are poorly ...understood. Here, we attempted to investigate the downstream targets of lincRNA‐p21 in prostate cancer.
Materials and methods
Expression of lincRNA‐p21 and PKM2 was determined by qRT‐PCR and Western blot. Lentivirus expressing shPKM2 or shCtrl was used to explore the role of PKM2 on the enhanced cell proliferation and glycolysis of lincRNA‐p21‐silenced prostate cancer cells. A xenograft mouse model was performed to investigate the effect of PKM2 suppression, glycolytic or mammalian target of rapamycin (mTOR) inhibitor on the tumorigenic capacity of lincRNA‐p21‐silenced prostate cancer cells.
Results
We revealed that lincRNA‐p21 silencing in DU145 and LNCaP cells induced up‐regulation of PKM2 and activation of glycolysis, which could be reversed by PKM2 knockdown or rapamycin treatment. We also found that the proliferation and tumorigenesis of lincRNA‐p21‐silenced prostate cancer cells were significantly inhibited after knocking down PKM2. 3‐bromopyruvate (3‐Brpa) or rapamycin treatment largely decreased the tumour burden. Importantly, PKM2 expression was inversely correlated with the lincRNA‐p21 level and the survival of prostate cancer patients.
Conclusions
We demonstrated that lincRNA‐p21 blunted the prostate cancer cell proliferation and tumorigenic capacity through down‐regulation of PKM2. Therefore, targeting PKM2 or glycolysis might be a therapeutic strategy in prostate cancer patients with lowly expressed lincRNA‐p21.
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