The potential of aryl hydrocarbon receptor as receptors for metabolic changes in tumors

Cancer cells can alter their metabolism to meet energy and molecular requirements due to unfavorable environments with oxygen and nutritional deficiencies. Therefore, metabolic reprogramming is common in a tumor microenvironment (TME). Aryl hydrocarbon receptor (AhR) is a ligand-activated nuclear transcription factor, which can be activated by many exogenous and endogenous ligands. Multiple AhR ligands can be produced by both TME and tumor cells. By attaching to various ligands, AhR regulates cancer metabolic reprogramming by dysregulating various metabolic pathways, including glycolysis, lipid metabolism, and nucleotide metabolism. These regulated pathways greatly contribute to cancer cell growth, metastasis, and evading cancer therapies; however, the underlying mechanisms remain unclear. Herein, we review the relationship between TME and metabolism and describe the important role of AhR in cancer regulation. We also focus on recent findings to discuss the idea that AhR acts as a receptor for metabolic changes in tumors, which may provide new perspectives on the direction of AhR research in tumor metabolic reprogramming and future therapeutic interventions

Joint Optimization of Radar and Jammer Space-time Cooperative Beamforming for a Multitasking Dynamic Scene

The modern radar confrontation situation is complex and changeable, and inter-system combat has become a basic feature. The overall system performance affects the initiative on the battlefield and even the final victory or defeat. By optimizing the beam resources of radar and jammers in a system, the overall performance can be improved, and the effective low-intercept detection effect can be obtained in the spatial and temporal domains. However, joint optimization of cooperative beamforming in the spatial and temporal domains is a nonconvex problem with complex multiparameter coupling. In this paper, an optimization model is established for a multitasking dynamic scene in the spatial and temporal domains. Radar detection performance is the optimization goal, while the interference performance and energy limitation of jammers are the constraints. To solve the model, a joint design method of space-time cooperative beamforming based on iterative optimization was proposed; that is, iterative optimization of radar transmitting, receiving, and multiple jammers transmitting beamforming vectors was alternately optimized. To solve the Quadratically Constrained Quadratic Programs (QCQP) problem with indefinite matrices for multijammer collaborative optimization, this paper is based on the Feasible Point Pursuit Successive Convex Approximation (FPP-SCA) algorithm. In other words, on the basis of the SCA algorithm, algorithm feasibility is ensured through reasonable relaxation by introducing relaxation variables and a penalty term, which solves the difficulty of obtaining a feasible solution when a problem contains indefinite matrices. Simulation results show that under the constraint of certain jammer energy, the proposed method achieves the effect of multiple jammers interfering with each enemy platform in the spatial and temporal domains to cover our radar detection. This effect is achieved while ensuring high-performance radar detection of the target without interference. Compared with traditional algorithms, the collaborative interference based on the FPP-SCA algorithm exhibits a better performance in the dynamic scene

Microvascular Endothelial Cells-Derived Microvesicles Imply in Ischemic Stroke by Modulating Astrocyte and Blood Brain Barrier Function and Cerebral Blood Flow

Background Endothelial cell (EC) released microvesicles (EMVs) can affect various target cells by transferring carried genetic information. Astrocytes are the main components of the blood brain barrier (BBB) structure in the brain and participate in regulating BBB integrity and blood flow. The interactions between ECs and astrocytes are essential for BBB integrity in homeostasis and pathological conditions. Here, we studied the effects of human brain microvascular ECs released EMVs on astrocyte functions. Additionally, we investigated the effects of EMVs treated astrocytes on regulating BBB function and cerebral ischemic damage. Results EMVs prepared from ECs cultured in normal condition (n-EMVs) or oxygen and glucose deprivation (OGD-EMVs) condition had diverse effects on astrocytes. The n-EMVs promoted, while the OGD-EMVs inhibited the proliferation of astrocytes via regulating PI3K/Akt pathway. Glial fibrillary acidic protein (GFAP) expression (marker of astrocyte activation) was up-regulated by n-EMVs, while down-regulated by OGD-EMVs. Meanwhile, n-EMVs inhibited but OGD-EMVs promoted the apoptosis of astrocytes accompanied by up/down-regulating the expression of Caspase-9 and Bcl-2. In the BBB model of ECs-astrocytes co-culture, the n-EMVs, conversely to OGD-EMVs, decreased the permeability of BBB accompanied with up-regulation of zonula occudens-1(ZO-1) and Claudin-5. In a transient cerebral ischemia mouse model, n-EMVs ameliorated, while OGD-EMVs aggravated, BBB disruption, local cerebral blood flow (CBF) reduction, infarct volume and neurological deficit score. Conclusions Our data suggest that EMVs diversely modulate astrocyte functions, BBB integrity and CBF, and could serve as a novel therapeutic target for ischemic stroke

Urotensin II promotes the proliferation and secretion of vascular endothelial growth factor in rat dermal papilla cells by activating the Wnt-β-catenin signaling pathway

Introduction. Urotensin II (U II) is a kind of active peptide with a variety of biological effects, such as promoting cell proliferation and endocrine effects. The aim of this study is to investigate the effect of urotensin II on the proliferation and secretion of vascular endothelial growth factor (VEGF) in cultured rat dermal papilla cells (DPCs), and to explore its molecular mechanism. Materials and Methods. We used the DPCs isolated from the thoracic aortas of Wistar-Kyoto rats to run the CCK8 and ELISA assay, RC-PCR and Western blotting techniques to identify the effect of Urotensin II on the proliferation and secretion of VEGF in DPCs, data were analyzed by one-way ANOVA or t-test. Results. U II can increase the mRNA expression of proliferation markers Ki67 and PCNA. In addition, the Wnt/β-catenin pathway was activated by U II, but Wnt inhibitor DKK1 reversed the effect of U II. Conclusions. U II promoted the proliferation and secretion of VEGF in rat DPCs through activation of the Wnt-β-catenin signaling pathway

Case report: Compound heterozygous mutations in the KDSR gene cause progressive keratodermia and thrombocytopenia

KDSR (3-ketodihydrosphingosine reductase) is a short-chain dehydrogenase located in the endoplasmic reticulum. Mutations in KDSR cause defects in ceramides, which play a key role in the biological processes of the skin and other tissues. Herein, we report a case of compound heterozygous mutations in KDSR that caused progressive keratodermia and thrombocytopenia in a 2-year-old male patient

A novel class of microRNA-recognition elements that function only within open reading frames.

MicroRNAs (miRNAs) are well known to target 3' untranslated regions (3' UTRs) in mRNAs, thereby silencing gene expression at the post-transcriptional level. Multiple reports have also indicated the ability of miRNAs to target protein-coding sequences (CDS); however, miRNAs have been generally believed to function through similar mechanisms regardless of the locations of their sites of action. Here, we report a class of miRNA-recognition elements (MREs) that function exclusively in CDS regions. Through functional and mechanistic characterization of these 'unusual' MREs, we demonstrate that CDS-targeted miRNAs require extensive base-pairing at the 3' side rather than the 5' seed; cause gene silencing in an Argonaute-dependent but GW182-independent manner; and repress translation by inducing transient ribosome stalling instead of mRNA destabilization. These findings reveal distinct mechanisms and functional consequences of miRNAs that target CDS versus the 3' UTR and suggest that CDS-targeted miRNAs may use a translational quality-control-related mechanism to regulate translation in mammalian cells

Credit Decision Problems of MSMEs (Medium, Small and Micro-sized Enterprises)

Micro, small and medium enterprises (MSMEs) have become an important force in driving the country’s market economy in the 21st century. However, because of the following drawbacks: i.e. single enterprise capital chain, unstable economy, high risk, etc., banks will take many risks if they lend to MSMEs. Therefore, it is necessary to build a sound bank credit decision system to promote the development of MSMEs. The analytic hierarchy process (AHP) is employed to classify the importance level such as credit rating and enterprise strength are used as first-grade indexes, and six indicators in terms of total sales and total profits are used as the second-grade indexes. Then, the eigenvalue method is used to obtain the importance weights of each level of indicators, and the weights of each influencing factor at each level are then calculated to achieve a quantitative analysis of credit risk and rating of each enterprise’s credit risk. This paper combines the existing loan pricing and loan interest rates to give preferential interest rates and higher loan amounts to enterprises with excellent credit risk ratings, and to give certain risky interest rates and lower loan amounts to enterprises with medium credit risk ratings.Based on the model, a quantitative analysis of the credit risk of 302 non-credit record enterprises is carried out and the bank’ credit strategy is provided when the total annual credit is 100 million yuan. Finally, this paper comprehensively considers the impact of credit risk and unexpected factors (e.g., the COVID-19) on enterprises, and provides the bank’s credit adjustment strategy when the total annual credit is 100 million yuan

Soil physical and hydraulic properties under different land uses in the black soil region of Northeast China

Black soil is inherently productive and fertile but is subject to soil erosion. Understanding the distribution of soil physical and hydraulic properties of the soil profile under various land uses would help reveal the mechanism behind the degradation of black soil. In this study, we investigated the variation in soil physical and hydraulic properties with land uses and soil depths in the black soil area of Northeast China. Disturbed samples and undisturbed soil cores were collected from 0–100 cm soil depths under agricultural land (AL), forestland (FL), and shrub land (SL). Our results showed that the land use and soil depth significantly affected the soil bulk density (BD), field capacity (FC), capillary moisture capacity (CMC), saturated hydraulic conductivity (Ks), and soil water retention curve (θs and α). Small macroaggregates accounted for most of the soil mass and were significantly higher in FL but lower in AL for the 0–50 cm of the soil samples. The FC, CMC, and Ks decreased, but the BD increased with the soil depth across the three land-use types. In addition, the soil in AL had a higher BD but lower CMC and Ks than the soil in FL and SL for most soil depths. These results indicated that land use can influence the variation in soil physical and hydraulic properties within the 0–100 cm soil depth, and agricultural use is a major reason for soil degradation in this black soil region.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author