Transcriptional atlas analysis from multiple tissues reveals the expression specificity patterns in beef cattle.

BACKGROUND: A comprehensive analysis of gene expression profiling across tissues can provide necessary information for an in-depth understanding of their biological functions. We performed a large-scale gene expression analysis and generated a high-resolution atlas of the transcriptome in beef cattle. RESULTS: Our transcriptome atlas was generated from 135 bovine tissues in adult beef cattle, covering 51 tissue types of major organ systems (e.g., muscular system, digestive system, immune system, reproductive system). Approximately 94.76% of sequencing reads were successfully mapped to the reference genome assembly ARS-UCD1.2. We detected a total of 60,488 transcripts, and 32% of them were not reported before. We identified 2654 housekeeping genes (HKGs) and 477 tissue-specific genes (TSGs) across tissues. Using weighted gene co-expression network analysis, we obtained 24 modules with 237 hub genes (HUBGs). Functional enrichment analysis showed that HKGs mainly maintain the basic biological activities of cells, while TSGs were involved in tissue differentiation and specific physiological processes. HKGs in bovine tissues were more conserved in terms of expression pattern as compared to TSGs and HUBGs among multiple species. Finally, we obtained a subset of tissue-specific differentially expressed genes (DEGs) between beef and dairy cattle and several functional pathways, which may be involved in production and health traits. CONCLUSIONS: We generated a large-scale gene expression atlas across the major tissues in beef cattle, providing valuable information for enhancing genome assembly and annotation. HKGs, TSGs, and HUBGs further contribute to better understanding the biology and evolution of multiple tissues in cattle. DEGs between beef and dairy cattle also fill in the knowledge gaps about differential transcriptome regulation of bovine tissues underlying economically important traits.

A Multiscale Recursive Attention Gate Federation Method for Multiple Working Conditions Fault Diagnosis.

Federated learning (FL) is an effective method when a single client cannot provide enough samples for multiple condition fault diagnosis of bearings since it can combine the information provided by multiple clients. However, some of the client's working conditions are different; for example, different clients are in different stages of the whole life cycle, and different clients have different loads. At this point, the status of each client is not equal, and the traditional FL approach will lead to some clients' useful information being ignored. The purpose of this paper is to investigate a multiscale recursive FL framework that makes the server more focused on the useful information provided by the clients to ensure the effectiveness of FL. The proposed FL method can build reliable multiple working condition fault diagnosis models due to the increased focus on useful information in the FL process and the full utilization of server information through local multiscale feature fusion. The validity of the proposed method was verified with the Case Western Reserve University benchmark dataset. With less local client training data and complex fault types, the proposed method improves the accuracy of fault diagnosis by 23.21% over the existing FL fault diagnosis.

Dynamic Semi-Supervised Federated Learning Fault Diagnosis Method Based on an Attention Mechanism.

In cases where a client suffers from completely unlabeled data, unsupervised learning has difficulty achieving an accurate fault diagnosis. Semi-supervised federated learning with the ability for interaction between a labeled client and an unlabeled client has been developed to overcome this difficulty. However, the existing semi-supervised federated learning methods may lead to a negative transfer problem since they fail to filter out unreliable model information from the unlabeled client. Therefore, in this study, a dynamic semi-supervised federated learning fault diagnosis method with an attention mechanism (SSFL-ATT) is proposed to prevent the federation model from experiencing negative transfer. A federation strategy driven by an attention mechanism was designed to filter out the unreliable information hidden in the local model. SSFL-ATT can ensure the federation model's performance as well as render the unlabeled client capable of fault classification. In cases where there is an unlabeled client, compared to the existing semi-supervised federated learning methods, SSFL-ATT can achieve increments of 9.06% and 12.53% in fault diagnosis accuracy when datasets provided by Case Western Reserve University and Shanghai Maritime University, respectively, are used for verification.

Comparative transcriptomic analysis reveals region-specific expression patterns in different beef cuts.

BACKGROUND: Beef cuts in different regions of the carcass have different meat quality due to their distinct physiological function. The objective of this study was to characterize the region-specific expression differences using comparative transcriptomics analysis among five representative beef cuts (tenderloin, longissimus lumborum, rump, neck, chuck). RESULTS: We obtained 15,701 expressed genes in 30 muscle samples across five regions from carcass meat. We identified a total of 80 region-specific genes (RSGs), ranging from three (identified in the rump cut) to thirty (identified in the longissimus lumborum cut), and detected 25 transcription factors (TFs) for RSGs. Using a co-expression network analysis, we detected seven region-specific modules, including three positively correlated modules and four negatively correlated modules. We finally obtained 91 candidate genes related to meat quality, and the functional enrichment analyses showed that these genes were mainly involved in muscle fiber structure (e.g., TNNI1, TNNT1), fatty acids (e.g., SCD, LPL), amino acids (ALDH2, IVD, ACADS), ion channel binding (PHPT1, SNTA1, SUMO1, CNBP), protein processing (e.g., CDC37, GAPDH, NRBP1), as well as energy production and conversion (e.g., ATP8, COX8B, NDUFB6). Moreover, four candidate genes (ALDH2, CANX, IVD, PHPT1) were validated using RT-qPCR analyses which further supported our RNA-seq results. CONCLUSIONS: Our results provide valuable insights into understanding the transcriptome regulation of meat quality in different beef cuts, and these findings may further help to improve the selection for health-beneficial meat in beef cattle.

ARID3A promotes the chemosensitivity of colon cancer by inhibiting AKR1C3.

ARID3A is upregulated in colorectal cancer and can promote the proliferation and metastasis of cancer cells. However, patients with higher level of ARID3A have a better prognosis. This study aimed to uncover the mechanism by which ARID3A benefits the prognosis of colon cancer. Our results indicated that ARID3A upregulation enhanced the chemosensitivity of colon cancer cells to 5-fluorouracil (5-FU), whereas ARID3A downregulation inhibited the chemosensitivity of colon cancer cells to 5-FU. Through database analysis, we found that AKR1C3, a drug resistance-related gene, was the target of ARID3A. Moreover, AKR1C3 was downregulated in colon cancer tissues compared to normal tissues. Next, we assessed the interaction between AKR1C3 and ARID3A, and found that ARID3A inhibited the transcription of AKR1C3, leading to the downregulation of AKR1C3 in colon cancer cells. We also verified that AKR1C3 inhibited the chemosensitivity of colon cancer cells to 5-FU. Moreover, patients with higher ratio of ARID3A to AKR1C3 had a better prognosis. This study suggested that ARID3A promoted chemosensitivity of colon cancer cells by inhibiting AKR1C3 in colon cancer. The ratio of ARID3A to AKR1C3 is a good marker to predict the prognosis of colon cancer patients.

The clinical prediction factors for non-culprit lesion progression in patients with acute ST elevation myocardial infarction after primary percutaneous coronary intervention.

BACKGROUND: To investigate the relationship between the clinical features and progression of non-culprit lesions in patients with ST-elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PPCI). METHODS: A total of 480 patients (57.1 ± 9.2 y) with STEMI who underwent PPCI between January 2016 and December 2017 in Beijing Anzhen Hospital were enrolled in this study. All patients underwent PPCI as a treatment for culprit lesions. Clinical and angiographic follow-up were performed for 12 months. All patients were divided into a non-culprit lesions (NCL) progression group (205 cases) and a control group (275 cases) based on angiographic follow-up outcomes at 12 months. The clinical and angiographic features were analyzed. RESULTS: Body mass index (BMI), serum creatinine (Scr), fasting blood glucose (FBG), glycated serum albumin, glycated hemoglobin and homocysteine levels in the NCL progression group were significantly higher than those in the control group (P < 0.05). A logistic regression analysis showed that FBG (odds ratio 1.274, 95% confidence interval 1.077-1.505, P = 0.005) and Scr (odds ratio 1.020, 95% confidence interval 1.002-1.038, P = 0.027) were independent predictors of NCL progression. A partial correlation analysis showed that FBG was positively correlated with NCL progression (r = 0.231, P = 0.001). A receiver operating characteristic curve showed that the boundary point of FBG to predict NCL progression was 5.715 mmol/L, and the sensitivity was 74.4% and the specificity was 46.4%. CONCLUSION: FBG is a valuable predictor for NCL progression in patients with STEMI after PPCI.

Integration of selection signatures and multi-trait GWAS reveals polygenic genetic architecture of carcass traits in beef cattle.

Carcass merits are widely considered as economically important traits affecting beef production in the beef cattle industry. However, the genetic basis of carcass traits remains to be well understood. Here, we applied multiple methods, including the Composite of Likelihood Ratio (CLR) and Genome-wide Association Study (GWAS), to explore the selection signatures and candidate variants affecting carcass traits. We identified 11,600 selected regions overlapping with 2214 candidate genes, and most of those were enriched in binding and gene regulation. Notably, we identified 66 and 110 potential variants significantly associated with carcass traits using single-trait and multi-traits analyses, respectively. By integrating selection signatures with single and multi-traits associations, we identified 12 and 27 putative genes, respectively. Several highly conserved missense variants were identified in OR5M13D, NCAPG, and TEX2. Our study supported polygenic genetic architecture of carcass traits and provided novel insights into the genetic basis of complex traits in beef cattle.

Cis-eQTL Analysis and Functional Validation of Candidate Genes for Carcass Yield Traits in Beef Cattle.

Carcass yield traits are of considerable economic importance for farm animals, which act as a major contributor to the world's food supply. Genome-wide association studies (GWASs) have identified many genetic variants associated with carcass yield traits in beef cattle. However, their functions are not effectively illustrated. In this study, we performed an integrative analysis of gene-based GWAS with expression quantitative trait locus (eQTL) analysis to detect candidate genes for carcass yield traits and validate their effects on bovine skeletal muscle satellite cells (BSCs). The gene-based GWAS and cis-eQTL analysis revealed 1780 GWAS and 1538 cis-expression genes. Among them, we identified 153 shared genes that may play important roles in carcass yield traits. Notably, the identified cis-eQTLs of PON3 and PRIM2 were significantly (p < 0.001) enriched in previous GWAS loci for carcass traits. Furthermore, overexpression of PON3 and PRIM2 promoted the BSCs' proliferation, increased the expression of MYOD and downregulated the expression of MYOG, which indicated that these genes may inhibit myogenic differentiation. In contrast, PON3 and PRIM2 were significantly downregulated during the differentiation of BSCs. These findings suggested that PON3 and PRIM2 may promote the proliferation of BSCs and inhibit them in the pre-differentiation stage. Our results further contribute to the understanding of the molecular mechanisms of carcass yield traits in beef cattle.

ARID3A promotes the development of colorectal cancer by upregulating AURKA.

Colorectal cancer (CRC) is one of the most common malignant tumours, and its morbidity and mortality rates are relatively high. However, the aetiology and pathogenesis of CRC have not been clearly elucidated to date. AT-rich interaction domain 3A (ARID3A) is a member of the ARID3 family and a transcription factor that can bind to specific DNA sites to regulate gene expression. It was reported that ARID3A is involved in various biological processes and may be related to carcinogenesis. In this study, by assessing the mRNA level of ARID3A in TCGA database, we found that ARID3A expression increased in CRC tissues, and proposed that ARID3A could act as a tumour-promoting factor in the development of CRC. To verify this hypothesis, we used cell proliferation, migration and invasion assays to assess the effect of ARID3A on CRC cells. We revealed that ARID3A overexpression enhanced tumour cell proliferation, migration and invasion. ARID3A could target Aurora kinase A (AURKA) to facilitate the malignant phenotype of CRC cells, and patients with a higher ratio of AURKA and ARID3A had a better overall survival. Conclusively, this study showed that ARID3A targeted AURKA to facilitate the development of CRC. The ratio of ARID3A and AURKA could be used as a potential biomarker to predict prognosis, providing a new strategy for the diagnosis and prognosis of CRC.

Alternative splicing: An important regulatory mechanism in colorectal carcinoma.

Alternative splicing (AS) is a process that produces various mRNA splicing isoforms via different splicing patterns of mRNA precursors (pre-mRNAs). AS is the primary mechanism for increasing the types and quantities of proteins to improve biodiversity and influence multiple biological processes, including chromatin modification, signal transduction, and protein expression. It has been reported that AS is involved in the tumorigenesis and development of colorectal carcinoma (CRC). In this review, we delineate the concept, types, regulatory processes, and technical advances of AS and focus on the role of AS in CRC initiation, progression, treatment, and prognosis. This summary of the current knowledge about AS will contribute to our understanding of CRC initiation and development. This study will help in the discovery of novel biomarkers and therapeutic targets for CRC prognosis and treatment.

Imbalance Fault Detection Based on the Integrated Analysis Strategy for Marine Current Turbines under Variable Current Speed.

The conversion of marine current energy into electricity with marine current turbines (MCTs) promises renewable energy. However, the reliability and power quality of marine current turbines are degraded due to marine biological attachments on the blades. To benefit from all the information embedded in the three phases, we created a fault feature that was the derivative of the current vector modulus in a Concordia reference frame. Moreover, because of the varying marine current speed, fault features were non-stationary. A transformation based on new adaptive proportional sampling frequency (APSF) transformed them into stationary ones. The fault indicator was derived from the amplitude of the shaft rotating frequency, which was itself derived from its power spectrum. The method was validated with data collected from a test bed composed of a marine current turbine coupled to a 230 W permanent magnet synchronous generator. The results showed the efficiency of the method to detect an introduced imbalance fault with an additional mass of 80-220 g attached to blades. In comparison to methods that use a single piece of electrical information (phase current or voltage), the fault indicator based on the three currents was found to be, on average, 2.2 times greater. The results also showed that the fault indicator increased monotonically with the fault severity, with a 1.8 times-higher variation rate, as well as that the method is robust for the flow current speed that varies from 0.95 to 1.3 m/s.

The proteasome activator REGγ counteracts immunoproteasome expression and autoimmunity.

For quite a long time, the 11S proteasome activator REGɑ and REGß, but not REGγ, are known to control immunoproteasome and promote antigen processing. Here, we demonstrate that REGγ functions as an inhibitor for immunoproteasome and autoimmune disease. Depletion of REGγ promotes MHC class I-restricted presentation to prime CD8+ T cells in vitro and in vivo. Mice deficient for REGγ have elevation of CD8+ T cells and DCs, and develop age-related spontaneous autoimmune symptoms. Mechanistically, REGγ specifically interacts with phosphorylated STAT3 and promotes its degradation in vitro and in cells. Inhibition of STAT3 dramatically attenuates levels of LMP2/LMP7 and antigen presentation in cells lacking REGγ. Importantly, treatment with STAT3 or LMP2/7 inhibitor prevented accumulation of immune complex in REGγ-/- kidney. Moreover, REGγ-/- mice also expedites Pristane-induced lupus. Bioinformatics and immunohistological analyses of clinical samples have correlated lower expression of REGγ with enhanced expression of phosphorylated STAT3, LMP2 and LMP7 in human Lupus Nephritis. Collectively, our results support the concept that REGγ is a new regulator of immunoproteasome to balance autoimmunity.

A Sparse Autoencoder and Softmax Regression Based Diagnosis Method for the Attachment on the Blades of Marine Current Turbine.

The development and application of marine current energy are attracting more and more attention around the world. Due to the hardness of its working environment, it is important and difficult to study the fault diagnosis of a marine current generation system. In this paper, an underwater image is chosen as the fault-diagnosing signal, after different sensors are compared. This paper proposes a diagnosis method based on the sparse autoencoder (SA) and softmax regression (SR). The SA is used to extract the features and SR is used to classify them. Images are used to monitor whether the blade is attached by benthos and to determine its corresponding degree of attachment. Compared with other methods, the experiment results show that the proposed method can diagnose the blade attachment with higher accuracy.

Necroptosis in cancer: An angel or a demon?

In the past few decades, apoptosis has been regarded as the only form of programmed cell death. However, the traditional view has been challenged by the identification of several forms of regulated necrosis, including necroptosis. Necroptosis is typified by a necrotic cell death morphology and is controlled by RIP1, RIP3, and mixed lineage kinase domain-like protein. The physiological role of necroptosis is to serve as a "fail-safe" form of cell death for cells that fail to undergo apoptosis during embryonic development and disease defense. Currently, established studies have indicated that necroptosis is involved in cancer initiation and progression. Although elevated necroptosis contributes to cancer cell death, extensive cell death also increases the risk of proliferation and metastasis of the surviving cells by inducing the generation reactive oxygen species, activation of inflammation, and suppression of the immune response. Thus, questions regarding the overall impact of necroptosis on cancer remain open. In this review, we introduce the basic knowledge regarding necroptosis, summarize its dual effects on cancer progression, and analyze its advantages and disadvantages in clinical applications.

Hepatitis B virus x protein induces epithelial-mesenchymal transition of hepatocellular carcinoma cells by regulating long non-coding RNA.

BACKGROUND: It has been widely accepted that hepatitis B virus X protein (HBx) plays an important role in hepatocellular carcinoma (HCC). This study aimed to explore the function of long non-coding RNAs (lncRNAs) in the epithelial-mesenchymal transition (EMT) induced by HBx. METHODS: The association between HBx and EMT markers was detected using immunohistochemistry in HCC tissues. The effect of HBx on HCC EMT was assessed through morphological analysis, transwell assay, metastatic in vivo study and detection of EMT markers. LncRNA microarray was used to screen the differently expressed lncRNAs. Small interfering RNA and Western blot were used to analyse the function and mechanism of the locked lncRNA. RESULTS: HBx was negatively correlated with the epithelial marker E-cadherin but positively correlated with the mesenchymal marker vimentin in HCC tissues. HBx induced the mesenchymal phenotype and improved the metastatic ability of HCC cells. Meanwhile, HBx down-regulated E-cadherin, whereas it up-regulated vimentin. In HCC cells, HBx altered the expression of 2002 lncRNAs by more than 2-fold. One of them was ZEB2-AS1. Inhibition of ZEB2-AS1 can compensate for the EMT phenotype and reverse the expression of EMT markers regulated by HBx. Additionally, HBx affected the Wnt signalling pathway. CONCLUSIONS: HBx promotes HCC cell metastasis by inducing EMT, which is at least partly mediated by lncRNAs.

DOA Finding with Support Vector Regression Based Forward-Backward Linear Prediction.

Direction-of-arrival (DOA) estimation has drawn considerable attention in array signal processing, particularly with coherent signals and a limited number of snapshots. Forward-backward linear prediction (FBLP) is able to directly deal with coherent signals. Support vector regression (SVR) is robust with small samples. This paper proposes the combination of the advantages of FBLP and SVR in the estimation of DOAs of coherent incoming signals with low snapshots. The performance of the proposed method is validated with numerical simulations in coherent scenarios, in terms of different angle separations, numbers of snapshots, and signal-to-noise ratios (SNRs). Simulation results show the effectiveness of the proposed method.

Plasma Gelsolin Induced Glomerular Fibrosis via the TGF-ß1/Smads Signal Transduction Pathway in IgA Nephropathy.

Glomerular fibrosis has been shown to be closely related to the progression and prognosis of IgA nephropathy (IgAN). However, mechanism underlying IgAN glomerular fibrosis remains unclear. Recently, our study showed that plasma gelsolin (pGSN) was decreased in the serum of an IgAN mouse model and that pGSN deposition was found in the glomeruli. Another cytokine, TGF-ß1, which is closely related to glomerular fibrosis, was also found to be highly expressed in the glomeruli. In the present study, we report that pGSN induces glomerular fibrosis through the TGF-ß1/Smads signal transduction pathway. This is supported by the following findings: human mesangial cells (HMCs) show remarkable morphological changes and proliferation in response to co-stimulation with pGSN and polymeric IgA1 (pIgA1) from IgAN patients compared to other controls. Moreover, ELISA assays showed that more TGF-ß1 secretion was found in HMCs supernatants in the co-stimulation group. Further experiments showed increased TGF-ß1, Smad3, p-Smad2/3, Smad4, and collagen 1 and decreased Smad7 expression in the co-stimulation group. Our present study implied that the synergistic effect of pGSN and pIgA induced glomerular fibrosis via the TGF-ß1/Smads signal transduction pathway. This might be a potential mechanism for the glomerular fibrosis observed in IgAN patients.

Plasma Gelsolin Promotes Proliferation of Mesangial Cell in IgA Nephropathy.

BACKGROUND/AIMS: Plasma gelsolin (pGSN) is an actin-binding protein that plays a critical role in the pathogenesis of rheumatoid arthritis. However, whether pGSN is involved in other immunological diseases remains unknown. This study focused on the relationship between pGSN and immunoglobulin A (IgA) nephropathy (IgAN). METHODS: Two hundred patients with IgAN, 200 patients each with several other types of nephropathy and healthy controls (HCs) who underwent kidney biopsies between 2000 and 2014 were enrolled in the study. The Oxford classification system was used to predict the risk of disease progression. Serum and renal tissue were used to detect pGSN, and the correlations between pGSN and IgA, galactose-deficient IgA1 (Gd-IgA1), transforming growth factor beta1 (TGF-ß1), fibronectin (FN) content, clinical symptoms, and kidney function were analyzed. RESULTS: We found that the pGSN levels were significantly decreased in sera from IgAN patients compared to sera from patients with other forms of glomerular nephritis and HCs. Furthermore, the serum pGSN levels were negatively correlated with the serum IgA1, FN, and TGF-ß1 levels, and positively correlated with the estimated glomerular filtration rate. Conversely, the glomerular pGSN content was significantly elevated in the IgAN patients and was positively correlated with TGF-ß1 and FN levels. In renal tissue, the pGSN levels were significantly higher in IgAN patients with M1 and S1 compared to patients with M0 and S0 (p < 0.05). Meanwhile, pGSN promoted human mesangial cell (HMC) proliferation by facilitating cell mitosis in vitro. pGSN also promoted integrin α2ß1 expression in HMCs and enhanced the integrin α2ß1-pGSN interaction. CONCLUSION: Our study suggested that pGSN may play an important role in the development of IgAN by promoting the proliferation of mesangial cells and that serum and glomerular pGSN levels may be new markers for predicting IgAN progression and prognosis.

Lin28A enhances chemosensitivity of colon cancer cells to 5-FU by promoting apoptosis in a let-7 independent manner.

RNA-binding protein Lin28A is frequently over-expressed in human malignant tumors and is associated with tumor advance and poor prognosis. However, the expression pattern and functions of Lin28A in colon cancer are unknown. In this study, we detected the expression of Lin28A in colon cancer patients and tested the effect of Lin28A on the chemotherapeutic sensitivity of colon cancer cells to 5-fluorouracil (5-FU). As expected, we showed that Lin28A is up-regulated in 73.3 % of colon cancer patients. However, to our surprise, we found that oncogenic protein Lin28A-enforced expression in colon cancer cells enhanced the chemosensitivity of cancer cells to 5-FU via promoting the cell apoptosis. Further mechanisms study revealed that the effect of Lin28A increasing chemosensitivity of cancer cells is in a let-7 independent manner, but which is associated with decreasing the expression of DNA damage repair protein H2AX. Conclusively, here we reported an unexpected function of Lin28A, which may shed lights on fully understanding the physiological and pathological roles of this oncogene.

Aberrant regulation of the LIN28A/LIN28B and let-7 loop in human malignant tumors and its effects on the hallmarks of cancer.

RNA binding proteins (RBPs) and microRNAs (miRNAs) are two of the most important post-transcriptional regulators of gene expression, and their aberrant expression contributes to the development of human malignancies. Let-7, one of the most well-known tumor suppressors, is frequently down-regulated in a variety of human cancers. The RBP LIN28A/LIN28B, a direct target of the let-7 family of miRNAs, is an inhibitor of let-7 biogenesis and is frequently up-regulated in cancers. Aberrant regulation of the LIN28A/LIN28B and let-7 loop in human malignant tumors is reportedly involved in cancer development, contributing to cellular proliferation, cell death resistance, angiogenesis, metastasis, metabolism reprogramming, tumor-associated inflammation, genome instability, acquiring immortality and evading immune destruction. In this review, we summarized the mechanisms of LIN28A/LIN28B and let-7 loop aberrant regulation in human cancer and discussed the roles and potential mechanisms of the LIN28A/LIN28B and let-7 loop in regulating the hallmarks of cancer. The crosstalk between LIN28A/LIN28B and let-7 loop and certain oncogenes (such as MYC, RAS, PI3K/AKT, NF-κB and ß-catenin) in regulating hallmarks of cancer has also been discussed.