Cellular Communication Networks Research Articles

Dual roles of cellular communication network factor 6 (CCN6) in the invasion and metastasis of oral cancer cells to bone via binding to BMP2 and RANKL.

The acquisition of motility via epithelial-mesenchymal transition (EMT) and osteoclast induction are essential for the invasion and metastasis of oral squamous cell carcinoma (OSCC) to bone. However, the molecule suppressing both EMT and osteoclastogenesis is still unknown. In this study, we found that cellular communication network factor 6 (CCN6) was less produced in a human OSCC cell line, HSC-3 with mesenchymal phenotype, than in HSC-2 cells without it. Notably, CCN6 interacted with bone morphogenetic protein 2 (BMP2) and suppressed the cell migration of HSC-3 cells stimulated by BMP2. Moreover, knockdown of CCN6 in HSC-2 cells led to the promotion of EMT and enhanced the effect of transforming growth factor-β (TGF-β) on the promotion of EMT. Furthermore, CCN6 combined with BMP2 suppressed EMT. These results suggest that CCN6 strongly suppresses EMT in cooperation with BMP2 and TGF-β. Interestingly, CCN6 combined with BMP2 increased the gene expression of receptor activator of nuclear factor-κB ligand (RANKL) in HSC-2 and HSC-3 cells. Additionally, CCN6 interacted with RANKL, and CCN6 combined with RANKL suppressed RANKL-induced osteoclast formation. In metastatic lesions, increasing BMP2 due to the bone destruction led to interference with binding of CCN6 to RANKL, which results in the promotion of bone metastasis of OSCC cells due to continuous osteoclastogenesis. These findings suggest that CCN6 plays dual roles in the suppression of EMT and in the promotion of bone destruction of OSCC in primary and metastatic lesions, respectively, through cooperation with BMP2 and interference with RANKL.

Analyzation of the Peripheral Blood Mononuclear Cells Atlas and Cell Communication of Rheumatoid Arthritis Patients Based on Single-Cell RNA-Seq.

Rheumatoid arthritis (RA) is a common chronic inflammatory autoimmune disease with a multifactorial etiology. Peripheral blood is the main channel of the immune system, and peripheral blood mononuclear cells (PBMCs) are the immune cells that initiate the autoimmune inflammatory process. However, there are few reports on the mechanisms of peripheral blood immunity in RA. ScRNA-seq was performed on four RA samples and integrated with single-cell transcriptome data from four healthy control samples downloaded from publicly available databases for analysis. A total of 52,073 cells were used for descending clustering analysis to map RA peripheral blood immune cells at single-cell resolution. Redimensional clustering analysis of four major immune cells (T cells, monocytes, B cells, and natural killer cells) revealed that double-negative T (DNT) cells were significantly altered in abundance and function. And a number of genes (including SOCS3, cAMP-responsive element modulator (CREM), B2M, MTFP1, RSRP1, and YWHAB) were specifically downregulated in DNT cells. RA T cells, especially DNT cells, exhibit significant metabolic defects and dysfunction, mainly in the form of inhibition of oxidative phosphorylation, ATP synthesis, and major histocompatibility complex (MHC)-I-mediated antigen presentation. In addition, cellular communication networks were established, and it was evident that RA is significantly attenuated in the number and intensity of cellular communication. Monocytes and T cells play key roles in the process of the immune inflammatory response through CCL and MHC-related pathways. This study describes the landscape of the peripheral blood immune system and cell communication in RA, characterizes the abundance of PBMCs, gene expression profiles, and changes in signaling pathways in RA patients, and identifies several key cell subpopulations (DNT and classic monocytes) and specific genes (SOCS3, CREM, B2M, MTFP1, RSRP1, and YWHAB). Meanwhile, we propose that classic monocytes in peripheral blood may migrate to sites of inflammation in synovial tissue under the chemotaxis of the chemokines CCL3 and CCL3L1, differentiate into macrophages, secrete proinflammatory cytokines, and thus participate in the inflammatory response. These findings provide new insights for the future elucidation of the peripheral blood immune mechanisms of RA and the search for new clinical therapeutic targets.

A bioinformatics analysis of potential cellular communication networks in non-alcoholic steatohepatitis and colorectal adenoma using scRNA-seq and bulk-seq.

Non-alcoholic fatty liver disease (NAFLD) is the global most common chronic liver disease. Non-alcoholic steatohepatitis (NASH), an inflammatory subtype of NAFLD, has been shown to significantly increase the risk of colorectal adenoma (CRA). Therefore, from the perspective of bioinformatics analysis, the potential mechanisms of NASH/NAFLD-CRA can be explored. In this study, we screened the differentially expressed genes (DEGs) and core effect pathways between NASH and CRA by analyzing the single-cell data of CRA patients and the high-throughput sequencing data (GSE37364 and GSE89632) in the online database. We screened therapeutic targets and biomarkers through gene function classification, pathway enrichment analysis, and protein-protein interaction network analysis. In terms of single cell data, we screened the core effect pathway and specific signal pathway of cell communication through cell annotation and cell communication analyses. The purpose of the study was to find potential biomarkers, therapeutic targets, and related effect pathways of NASH-CRA. NASH-CRA comorbidities were concentrated in inflammatory regulation-related pathways, and the core genes of disease progression included IL1B, FOSL1, EGR1, MYC, PTGS2, and FOS. The results suggested the key pathway of NASH-CRA might be the WNT pathway. The main cell signal communication pathways included WNT2B - (FZD6 + LRP5) and WNT2B - (FZD6 + LRP6). The send-receive process occurred in embryonic stem cells. The core genes of NASH-CRA (FOS, EGR1, MYC, PTGS2, FOSL1, and IL1B) may participate in inflammation and immune responses through up-regulation in the process of disease occurrence, interfering with the pathophysiological process of CRA and NASH. NASH-CRA produces cell signal communication in the WNT pathway sent by WNT2B and received by FZD6, LRP5, and LRP6 in embryonic stem cells. These findings may help formulate early diagnosis and treatment strategies for CRA in NAFLD/NASH patients, and further explore corresponding prognostic markers and potential approaches. The significance of scRNA-seq in exploring tumor heterogeneity lies in promoting our understanding of the expression program of tumor related genes in tumor development patterns. However, the biggest challenge is that this analysis may miss out on some biologically significant gene expression programs.

Investigation of the performance of multi-input multi-output detectors based on deep learning in non-Gaussian environments

<span lang="EN-US">The next generation of wireless cellular communication networks must be energy efficient, extremely reliable, and have low latency, leading to the necessity of using algorithms based on deep neural networks (DNN) which have better bit error rate (BER) or symbol error rate (SER) performance than traditional complex multi-antenna or multi-input multi-output (MIMO) detectors. This paper examines deep neural networks and deep iterative detectors such as OAMP-Net based on information theory criteria such as maximum correntropy criterion (MCC) for the implementation of MIMO detectors in non-Gaussian environments, and the results illustrate that the proposed method has better BER or SER performance.</span>

Genome-wide association study identifies significant SNP and related genes associated with body size in Yorkshire pigs using latent variable modelling

AbstractThis study aimed to quantify a latent variable for body size (BS) in pigs by using five linear body measurements including body length (BL), body height (BH), chest width (CW), chest girth (CG) and tube girth (TG), and also to identify the most associated single nucleotide polymorphisms (SNP) and related genes with BS by using the genomic best linear unbiased prediction (GBLUP) based genome-wide association study (GWAS) or GBLUP-GWAS methodology. To perform a GWAS on the BS latent trait, we used a mixed linear model and identified a total of 53 significant SNPs. Additionally, we found that nine genes, including Rho GTPase activating protein 12 (ARHGAP12), transmembrane protein 108 (TMEM108), T-cell lymphoma invasion and metastasis inducing factor 1 (TIAM1), ras homologue gene family member B (RHOB), POU class 4 homeobox 1 (POU4F1), follistatin-related protein 4 (FSTL4), cellular communication network factor 2 (CCN2), beaded filament structural protein 2 (BFSP2) and attractin-like protein 1 (ATRNL1) were associated with the BS trait in pigs. These genes are involved in several biological processes, including the regulation of anatomical structure, morphogenesis, the regulation of cell size and growth. The results suggest that the identified SNP and related genes may play important roles in regulating the growth and development of pigs. The results imply that these genes could be promising candidates for further exploration of the underlying mechanisms of body size variation. Furthermore, the findings have significant practical implications for enhancing the efficiency and profitability of pig farming through genetic selection.

Overview of Device-To-Device Communication In Cellular Networks: A Review

Abstract: An elaboration of cellular networks has led due to the contact increase in demand for networks because of the growing demand for subscribers. The explosive growth of cellular data demand has led to the preface of Device-to-device (D2D) dispatches. We accept a huge swell of nearly billions of connected biases in the near future. Due to the increase in subscribers and data operation, there's a vital needful for an increase in innovative ways in order to boost data experience. Mobile network drivers (MNOs) must use their limited diapason coffers flexibly in order to meet the added demand. Device-to-device (D2D) communication, which offers extremely low quiescence for stoner communication, is anticipated to play a large part in arising cellular networks. This new model may operate in a certified or unlicensed diapason. In this paper would further bandy about the bracket of D2D communication including its operation, overview, integrated ways, etc.

CCN2 Activates RIPK3, NLRP3 Inflammasome, and NRF2/Oxidative Pathways Linked to Kidney Inflammation.

Inflammation is a key characteristic of both acute and chronic kidney diseases. Preclinical data suggest the involvement of the NLRP3/Inflammasome, receptor-interacting protein kinase-3 (RIPK3), and NRF2/oxidative pathways in the regulation of kidney inflammation. Cellular communication network factor 2 (CCN2, also called CTGF in the past) is an established fibrotic biomarker and a well-known mediator of kidney damage. CCN2 was shown to be involved in kidney damage through the regulation of proinflammatory and profibrotic responses. However, to date, the potential role of the NLRP3/RIPK3/NRF2 pathways in CCN2 actions has not been evaluated. In experimental acute kidney injury induced with folic acid in mice, CCN2 deficiency diminished renal inflammatory cell infiltration (monocytes/macrophages and T lymphocytes) as well as the upregulation of proinflammatory genes and the activation of NLRP3/Inflammasome-related components and specific cytokine products, such as IL-1β. Moreover, the NRF2/oxidative pathway was deregulated. Systemic administration of CCN2 to C57BL/6 mice induced kidney immune cell infiltration and activated the NLRP3 pathway. RIPK3 deficiency diminished the CCN2-induced renal upregulation of proinflammatory mediators and prevented NLRP3 modulation. These data suggest that CCN2 plays a fundamental role in sterile inflammation and acute kidney injury by modulating the RIKP3/NLRP3/NRF2 inflammatory pathways.

A Review of Single-Cell RNA-Seq Annotation, Integration, and Cell-Cell Communication.

Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool for investigating cellular biology at an unprecedented resolution, enabling the characterization of cellular heterogeneity, identification of rare but significant cell types, and exploration of cell-cell communications and interactions. Its broad applications span both basic and clinical research domains. In this comprehensive review, we survey the current landscape of scRNA-seq analysis methods and tools, focusing on count modeling, cell-type annotation, data integration, including spatial transcriptomics, and the inference of cell-cell communication. We review the challenges encountered in scRNA-seq analysis, including issues of sparsity or low expression, reliability of cell annotation, and assumptions in data integration, and discuss the potential impact of suboptimal clustering and differential expression analysis tools on downstream analyses, particularly in identifying cell subpopulations. Finally, we discuss recent advancements and future directions for enhancing scRNA-seq analysis. Specifically, we highlight the development of novel tools for annotating single-cell data, integrating and interpreting multimodal datasets covering transcriptomics, epigenomics, and proteomics, and inferring cellular communication networks. By elucidating the latest progress and innovation, we provide a comprehensive overview of the rapidly advancing field of scRNA-seq analysis.

Performance analysis for MU-MIMO enabled LTE-U networks coexisting with D2D and WiFi network

LTE-Unlicensed (LTE-U) network is a type of cellular communication network operating the unlicensed spectrum. Offloading cellular traffic to WiFi or Device-to-Device (D2D) network can lead to interference among them. Applying Multiple-Input Multiple-Output (MIMO) technology in Cellular Base Station (CBS) and WiFi Access Point (WAP) can effectively reduce interference among D2D, WiFi and cellular networks. To our best knowledge, there is still no literature to explicitly study the characteristics of the traffic offloading in the Multiple-User MIMO (MU-MIMO) enabled network coexisting with D2D and WiFi networks. In this article, we thoroughly investigate the impact of D2D communication and MU-MIMO enabled WAP and CBS on the performance of the LTE-U network. More specifically, we derive the expressions of the downlink rates for cellular users, D2D users, and WiFi users with incomplete Channel State Information (CSI) feedback, and we validate our analysis through Monte-Carlo simulation. Numerous results illustrate the following conclusions. (i) Increasing the number of WiFi users, the length of CSI feedback, and the quantity of D2D pairs that reuse the channel with a single cellular user can increase the total throughput of the heterogeneous network. (ii) The total throughput decreases when more than two users are offloaded to D2D pairs, and increases as the number of offloaded users increases when less than six users are offloaded to WiFi network. (iii) Simultaneously offloading traffic to D2D pairs and WiFi network can obtain higher total throughput than offloading traffic to only one of them.

Flight Test Analysis of UTM Conflict Detection Based on a Network Remote ID Using a Random Forest Algorithm

In an area where unmanned aerial system (UAS) traffic is high, a conflict detection system is one of the important components for the safety of UAS operations. A novel UAS traffic management (UTM) monitoring application was developed, including a conflict detection system using the inverted teardrop area detection based on real-time flight data transmitted from the network remote identification (Remote ID) modules. This research aimed to analyze the performance of the UTM-monitoring application based on flight test data using statistical and machine learning approaches. The flight tests were conducted using several types of small fixed-wing unmanned aerial vehicles (UAVs) controlled by a human pilot using a Taiwan cellular communication network in suburban and rural areas. Two types of scenarios that involved a stationary, on-the-ground intruder and a flying intruder were used to simulate a conflict event. Besides the statistical method calculating the mean and standard deviation, the random forest algorithm, including regressor and classifier modules, was used to analyze the flight parameters and timing parameters of the flight tests. The result indicates that the processing time of the UTM application was the most significant parameter to the conflict warning parameter, besides the relative distance and height between UAVs. In addition, the latency time was higher for the flight in the rural area than the suburban area and also higher for data transmitted from the flying position than the ground position. The findings of our study can be used as a reference for aviation authorities and other stakeholders in the development of future UTM systems.

Epithelial-mesenchymal plasticity in kidney fibrosis.

Epithelial-mesenchymal transition (EMT) is an important biological process contributing to kidney fibrosis and chronic kidney disease. This process is characterized by decreased epithelial phenotypes/markers and increased mesenchymal phenotypes/markers. Tubular epithelial cells (TECs) are commonly susceptible to EMT by various stimuli, for example, transforming growth factor-β (TGF-β), cellular communication network factor 2, angiotensin-II, fibroblast growth factor-2, oncostatin M, matrix metalloproteinase-2, tissue plasminogen activator (t-PA), plasmin, interleukin-1β, and reactive oxygen species. Similarly, glomerular podocytes can undergo EMT via these stimuli and by high glucose condition in diabetic kidney disease. EMT of TECs and podocytes leads to tubulointerstitial fibrosis and glomerulosclerosis, respectively. Signaling pathways involved in EMT-mediated kidney fibrosis are diverse and complex. TGF-β1/Smad and Wnt/β-catenin pathways are the major venues triggering EMT in TECs and podocytes. These two pathways thus serve as the major therapeutic targets against EMT-mediated kidney fibrosis. To date, a number of EMT inhibitors have been identified and characterized. As expected, the majority of these EMT inhibitors affect TGF-β1/Smad and Wnt/β-catenin pathways. In addition to kidney fibrosis, these EMT-targeted antifibrotic inhibitors are expected to be effective for treatment against fibrosis in other organs/tissues.

Capacity Enhancement in D2D 5G Emerging Networks: A Survey

Several efforts are being made to improve the capacity of 5G networks using emerging technologies of interest. One of the indispensable technologies to fulfill the need is device-to-device (D2D) communication with its untapped associated benefits. Interference is introduced at the base station due to massive traffic congestion. The purpose of this research is to expand the knowledge of interference mitigation in D2D using stochastic geometrical tools which will result in capacity enhancement. This study uses a literature review method based on 5G and other already existing literature on D2D communication. More than one hundred and twenty papers on D2D communications in cellular networks exist but no precise survey paper on interference management to enhance capacity using stochastic geometrical tools exists. The contribution of this survey to theory is that apart from already existing capacity enhancement methods, interference mitigation using stochastic geometrical tools is another technique that can also be used for capacity enhancement in D2D communications.

1519-P: Role of Cyr61 in Palmitic Acid-Induced Insulin Resistance and Inflammation in Hepatocyte

Objective: Cysteine-rich protein 61 (Cyr61, also known as Cellular Communication Network Factor 1, CCN1) is involved in a variety of diseases, such as carcinoma, inflammation, and fibrosis. It was recently reported that Cyr61 was associated with nonalcoholic fatty liver disease. Here, we evaluated the effects of Cyr61 on hepatic inflammation and insulin resistance in HepG2 cells and examined the molecular mechanisms involved. Methods: We treated HepG2 cells with palmitic acid (PA) and then evaluated insulin signaling pathway using immunoblotting. After treatment with PA, the pro-inflammatory cytokines, including IL-6, TNF-α, and IL-1β, and Cyr61 were assessed by RT-PCR and ELISA. To investigate the effects of Cyr61 on insulin resistance and inflammation, we used Cyr61 small interfering (si) RNA and anti-Cyr61 neutralizing antibodies. The Cyr61 siRNA were transiently transfected into HepG2 cells using Lipofectamine 2000. Results: Compared to the control, PA reduced IR phosphorylation, IRS-1 (Tyr612) phosphorylation, AKT phosphorylation, and GSK-3α/β phosphorylation after insulin stimulation. PA stimulated NF-κB and JNK activation in a dose-dependent manner. PA significantly increased the expression and secretion of Cyr61 and pro-inflammatory cytokines. Interestingly, neutralization of Cyr61 reduced NF-κB and JNK signaling, which was increased by PA, and recovered insulin signaling. In addition, Cyr61-si RNA treatment reduced the mRNA expression of PA-induced IL-6, TNF-α and IL-1β, and decreased NF-κB and JNK signaling. Conclusion: Inhibition of Cyr61 recovered insulin signaling and reduced inflammation in HepG2 cells. Cyr61 may play a role in PA-induced insulin resistance and inflammation in HepG2 cells. Disclosure Y.Heo: None. D.Kim: None. H.Kim: None. N.Lee: None. K.Lee: None. S.E.Y.Choi: None. Y.Y.Kang: None. S.Han: None. J.Jeon: None. Funding National Research Foundation of Korea (2020R1F1A1074019, 2021M3H1A104892211)

CCN3/NOV Regulates Proliferation and Neuronal Differentiation in Mouse Hippocampal Neural Stem Cells via the Activation of the Notch/PTEN/AKT Pathway.

Neural stem cells (NSCs) persist in the subgranular zone (SGZ) throughout the lifespan and hold immense potential for the repair and regeneration of the central nervous system, including hippocampal-related diseases. Several studies have demonstrated that cellular communication network protein 3 (CCN3) regulates multiple types of stem cells. However, the role of CCN3 in NSCs remains unknown. In this study, we identified CCN3 expression in mouse hippocampal NSCs and observed that supplementing CCN3 improved cell viability in a concentration-dependent manner. Additionally, in vivo results showed that the injection of CCN3 in the dentate gyrus (DG) increased Ki-67- and SOX2-positive cells while decreasing neuron-specific class III beta-tubulin (Tuj1) and doublecortin (DCX)-positive cells. Consistently with the in vivo results, supplementing CCN3 in the medium increased the number of BrdU and Ki-67 cells and the proliferation index but decreased the number of Tuj1 and DCX cells. Conversely, both the in vivo and in vitro knockdown of the Ccn3 gene in NSCs had opposite effects. Further investigations revealed that CCN3 promoted cleaved Notch1 (NICD) expression, leading to the suppression of PTEN expression and eventual promotion of AKT activation. In contrast, Ccn3 knockdown inhibited the activation of the Notch/PTEN/AKT pathway. Finally, the effects of changes in CCN3 protein expression on NSC proliferation and differentiation were eliminated by FLI-06 (a Notch inhibitor) and VO-OH (a PTEN inhibitor). Our findings imply that while promoting proliferation, CCN3 inhibits the neuronal differentiation of mouse hippocampal NSCs and that the Notch/PTEN/AKT pathway may be a potential intracellular target of CCN3. Our findings may help develop strategies to enhance the intrinsic potential for brain regeneration after injuries, particularly stem cell treatment for hippocampal-related diseases.

Tripterygium wilfordii derivative celastrol, a YAP inhibitor, has antifibrotic effects in systemic sclerosis

ObjectivesSystemic sclerosis (SSc) is characterised by extensive tissue fibrosis maintained by mechanotranductive/proadhesive signalling. Drugs targeting this pathway are therefore of likely therapeutic benefit. The mechanosensitive transcriptional co-activator, yes activated protein-1...

#4851 MOLECULAR FEATURES OF CIRCULATORY B CELLS AND RENAL CELLS AT THE SINGLE-CELL LEVEL IN AUTOANTIBODY-NEGATIVE PRIMARY MEMBRANOUS NEPHROPATHY PATIENTS

Abstract Background and Aims Primary membranous nephropathy (PMN) is an organ-specific autoimmune disease that is the most common cause of idiopathic nephrotic syndrome in adults. Furthermore, the incidence of PMN is increasing, especially in young adults and children. The landmark discovery of nephritogenic autoantibodies against podocyte antigens such as M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing protein 7A (THSD7A) has provided a paradigm shift in diagnosis and treatment of PMN. However, there are still few patients with negative serum and renal tissue autoantibodies. This study aims to explore the molecular features of antibody-negative PMN. Method We sorted CD19+ cells from the peripheral blood of a pediatric patient with seven nephritogenic autoantibodies-negative PMN (NEG) by flow cytometry and performed single-cell transcriptome sequencing (scRNA-seq) and single-cell B cell receptor sequencing (scBCR-seq). Meanwhile, scRNA-seq was performed on renal biopsy tissues from the same patient. In addition, we included the scRNA-seq data of renal from anti-PLA2R antibody positive patients (POS) and healthy controls (CTRL), and the scBCR-seq data of B cell from CTRL for integrative analysis. Results The NEG patient showed typical nephrotic syndrome and was diagnosed as stage Ⅲ membranous nephropathy by renal biopsy. There was no evidence of anti-PLA2R or anti-THSD7A antibodies in peripheral blood and seven nephritogenic autoantibodies such as anti-PLA2R antibodies in renal tissue. After excluding secondary factors, the patient was diagnosed with PMN. Through scRNA-seq of CD19+ cells, we found that the number, characteristic gene, function and clonotype of naÏve B cells and memory B cells in NEG were significantly changed. Expanded CD38+ naÏve B cells in NEG had the molecular characteristics of CD19+CD24+CD27-CD38+, defined as transitional B cells. This group of cells had distinct function features of cell activation, and its up-regulated genes were involved in multiple aspects of the BCR signaling pathway. Pseudotime trajectory analysis suggested CD38+ naÏve B cells were highly enriched in the beginning of B cell differentiation. There was a preference in the use of VJ gene segments of B cells between NEG and CTRL, especially an increase of the IGHV3-23 and IGLV2-14 in NEG. The stronger pairing frequencies, IGLV2-14/IGLJ3 and IGKV2D-29/IGKJ2, were indicated in NEG. We identified 14 distinct kidney cell types by marker genes. Through re-clustering of glomerular parietal epithelial cells (PECs), the patients were clearly distinct from their control counterparts, indicating a major shift in gene expression for this cell type. PECs in NEG showed significant up-regulation of cellular communication network factor-related genes (CCN1, CCN2), phospholipase A and acyltransferase-related genes (PLAAT4, PLAAT3), and septin protein-related genes (SEPTIN2, SEPTIN7), accompanied by significant down-regulation of podocyte-related genes. In addition, there are clearly distinct cellular functions and pseudotime trajectory in PECs from NEG and POS, and genes such as CCN2, PLAAT4, SEPTIN2 might drive the special trajectory of PECs in NEG. For the podocytes, the genes related with extracellular matrix and cell adhesion were significantly enhanced in NEG, which consistented with the functional enrichment analysis of the differentially expressed genes and gene set-based scores. We calculated the gene set-based scores including genes encoding lumen-to-blood sodium transporters. Results indicated the enhanced expression of sodium transporters in distal nephrons of MN patients. More surprisingly, a group of proximal tubule epithelial cells showed significantly higher expression levels of sodium transporters. Among them, the expression of SLC5A12 encoding SMCT2 increased significantly. Conclusion We have systematic revealed the cell-type specific molecular features of PMN patients from circulation to renal tissue. Our research provides valuable evidence for the molecular diagnosis of PMN in children and insights into pathogenic mechanism of classical nephritogenic autoantibody-negative PMN.

ERα prevents tumorigenesis of both liver and breast cancer cells through CCN5

Estrogen receptor alpha (ERα)-mediated estrogen signaling has also shown to prevent hepatic tumorigenesis in mice. Consistent with this, hormone replacement therapy with estrogen supplementation dramatically reduced the risk of hepatocellular carcinoma. Silencing of ERα is also a key event for the transformation of ERα-positive breast cancer cells into malignant triple-negative breast cancer cells. However, the mechanisms underlying ERα-mediated prevention of both hepatic and mammary tumorigenesis in humans are still unclear. Here, we present a functional genomics study of ERα targeting by comparing human liver cancer cells with human breast cancer cells using “loss or gain of function” genetic assays of ERα in vitro and in vivo. We discover that cellular communication network factor 5 (CCN5) is a direct downstream target of ERα; ERα suppresses growth and prevents tumorigenesis and malignant transformation of both liver and breast cancer cells through CCN5 in humans. The ERα-CCN5 regulatory axis functions as suppressors for both hepatic and mammary tumors, which is a common mechanism of preventing tumorigenesis for both liver cancer and breast cancer in humans.

Changes and related factors of blood CCN1 levels in diabetic patients.

To study the differences in blood cellular communication network factor 1 (CCN1) levels between patients with diabetes mellitus (DM) and healthy individuals and to explore the relationship between CCN1 and diabetic retinopathy (DR). Plasma CCN1 levels were detected using ELISA in 50 healthy controls, 74 patients with diabetes without diabetic retinopathy (DM group), and 69 patients with diabetic retinopathy (DR group). Correlations between CCN1 levels and age, body mass index, mean arterial pressure, hemoglobin A1c, and other factors were analyzed. The relationship between CCN1 expression and DR was explored using logistic regression after adjusting for confounding factors. Blood mRNA sequencing analysis was performed for all subjects, and the molecular changes that may be related to CCN1 were explored. The retinal vasculature of streptozotocin-induced diabetic rats was examined using fundus fluorescein angiography; in addition, retinal protein expression was examined using western blotting. Plasma CCN1 levels in patients with DR were significantly higher than in the control and DM groups; however, no significant differences were observed between healthy controls and patients with DM. CCN1 levels negatively correlated with body mass index and positively correlated with the duration of diabetes and urea levels. It was observed that high (OR 4.72, 95% CI: 1.10-20.25) and very high (OR 8.54, 95% CI: 2.00-36.51) levels of CCN1 were risk factors for DR. Blood mRNA sequencing analysis revealed that CCN1-related pathways were significantly altered in the DR group. The expression of hypoxia-, oxidative stress-, and dephosphorylation-related proteins were elevated, while that of tight junction proteins were reduced in the retinas of diabetic rats. Blood CCN1 levels are significantly elevated in patients with DR. High and very high levels of plasma CCN1 are risk factors for DR. Blood CCN1 level may be a potential biomarker for diagnosis of DR. The effects of CCN1 on DR may be related to hypoxia, oxidative stress, and dephosphorylation.

Reinforcement learning for communication load balancing: approaches and challenges

The amount of cellular communication network traffic has increased dramatically in recent years, and this increase has led to a demand for enhanced network performance. Communication load balancing aims to balance the load across available network resources and thus improve the quality of service for network users. Most existing load balancing algorithms are manually designed and tuned rule-based methods where near-optimality is almost impossible to achieve. Furthermore, rule-based methods are difficult to adapt to quickly changing traffic patterns in real-world environments. Reinforcement learning (RL) algorithms, especially deep reinforcement learning algorithms, have achieved impressive successes in many application domains and offer the potential of good adaptabiity to dynamic changes in network load patterns. This survey presents a systematic overview of RL-based communication load-balancing methods and discusses related challenges and opportunities. We first provide an introduction to the load balancing problem and to RL from fundamental concepts to advanced models. Then, we review RL approaches that address emerging communication load balancing issues important to next generation networks, including 5G and beyond. Finally, we highlight important challenges, open issues, and future research directions for applying RL for communication load balancing.

Recent progress on the role of cellular communication network factors (CCN) 3, 4 and 6 in regulating adiposity, liver fibrosis and pancreatic islets.

CCN/WISP (cellular communication network factors, or Wnt-inducted secreted proteins) family of proteins consists of six extracellular matrix (ECM)-associated proteins that regulate development, cell adhesion and proliferation, ECM remodeling, inflammation, and tumorigenesis. In the last two decades, metabolic regulation by these matricellular proteins has been studied extensively, several excellent reviews have covered the roles of CCN1, -2 and - 5. In this brief review, we will focus on those lesser-known members and more recent discoveries, together with other recent articles presenting a more complete picture of the current state of knowledge. We have found that CCN2, -4, and - 5 promote pancreatic islet function, while CCN3 plays a unique and negative role. CCN3 and - 4 are pro-adiposity leading to insulin resistance, but CCN5 and - 6 are anti-adiposity. While CCN2 and - 4 promote tissue fibrosis and inflammation, all other four members are clearly anti-fibrotic. As for cellular signaling, they are known to interact with integrins, other cell membrane proteins and ECM thereby regulate Akt/protein kinase B, myocardin-related transcription factor (MRTF), and focal adhesion kinase. Yet, a cohesive mechanism of action to comprehensively explain those major functions is still lacking.