A Simulation-based Approach for Quantifying the Impact of Interactive Label Correction for Machine Learning.

Recent years have witnessed growing interest in understanding the sensitivity of machine learning to training data characteristics. While researchers have claimed the benefits of activities such as a human-in-the-loop approach of interactive label correction for improving model performance, there have been limited studies to quantitatively probe the relationship between the cost of label correction and the associated benefit in model performance. We employ a simulation-based approach to explore the efficacy of label correction under diverse task conditions, namely different datasets, noise properties, and machine learning algorithms. We measure the impact of label correction on model performance under the best-case scenario assumption: perfect correction (perfect human and visual systems), serving as an upper-bound estimation of the benefits derived from visual interactive label correction. The simulation results reveal a trade-off between the label correction effort expended and model performance improvement. Notably, task conditions play a crucial role in shaping the trade-off. Based on the simulation results, we develop a set of recommendations to help practitioners determine conditions under which interactive label correction is an effective mechanism for improving model performance.

Inhibition of N-acetylglucosaminyltransferase V alleviates diabetic cardiomyopathy in mice by attenuating cardiac hypertrophy and fibrosis.

BACKGROUND: The pathogenesis of diabetic cardiomyopathy is closely linked to abnormal glycosylation modifications. N-acetylglucosaminyltransferase V (GnT-V), which catalyzes the production of N-linked -1-6 branching of oligosaccharides, is involved in several pathophysiological mechanisms of many disorders, including cardiac hypertrophy and heart failure. However, the mechanism by which GnT-V regulates cardiac hypertrophy in diabetic cardiomyopathy is currently poorly understood. In this study, we investigated the role of GnT-V on myocardial hypertrophy in diabetic cardiomyopathy and elucidated the underlying mechanisms. MATERIAL AND METHODS: Streptozotocin (STZ) was intraperitoneally injected into mice to induce diabetic cardiomyopathy. An adeno-associated virus (AAV) carrying negative control small hairpin RNA (shNC) or GnT-V-specifc small hairpin RNA (shGnT-V) was used to manipulate GnT-V expression. In our study, forty male C57BL/6J mice were randomly divided into four groups (10 mice per group): control mice with AAV-shNC, diabetic cardiomyopathy mice with AAV-shNC, control mice with AAV-shGnT-V, and diabetic cardiomyopathy mice with AAV-shGnT-V. In addition, H9C2 cells and primary neonatal cardiac fibroblasts treated with high glucose were used as a cell model of diabetes. Analysis of cardiac hypertrophy and fibrosis, as well as functional studies, were used to investigate the underlying molecular pathways. RESULTS: AAV-mediated GnT-V silencing dramatically improved cardiac function and alleviated myocardial hypertrophy and fibrosis in diabetic mice. In vitro experiments demonstrated that GnT-V was elevated in cardiomyocytes and induced cardiomyocyte hypertrophy in response to high glucose stimulation. GnT-V knockdown significantly reduced the expression of the integrinß1 signaling pathway, as evidenced by decreased downstream ERK1/2 activity, which inhibited cardiomyocyte hypertrophy accompanied by reduced ANP, BNP, and ß-MHC expression. Furthermore, knocking down GnT-V expression lowered the TGF-ß1-Smads signaling pathway, which reduced the expression of α-SMA, collagen I, and collagen III. CONCLUSIONS: Overall, our research indicated that GnT-V may be a useful therapeutic target to treat diabetic cardiomyopathy, primarily in the inhibition of myocardial hypertrophy and fibrosis.

L-arginine alleviates heat stress-induced mammary gland injury through modulating CASTOR1-mTORC1 axis mediated mitochondrial homeostasis.

As global warming intensifies, extreme heat is becoming increasingly frequent. These extreme heatwaves have decreased the milk production of dairy animals such as cows and goats and have caused significant damage to the entire dairy industry. It is known that heat stress (HS) can induce the apoptosis and autophagy of mammary epithelial cells (MECs), leading to a decrease in lactating MECs. L-arginine can effectively attenuate HS-induced decreases in milk yield, but the exact mechanisms are not fully understood. In this study, we found that HS upregulated the arginine sensor CASTOR1 in mouse MECs. Arginine activated mTORC1 activity through CASTOR1 and promoted mitochondrial biogenesis through the mTORC1/PGC-1α/NRF1 pathway. Moreover, arginine inhibited mitophagy through the CASTOR1/PINK1/Parkin pathway. Mitochondrial homeostasis ensures ATP synthesis and a stable cellular redox state for MECs under HS, further alleviating HS-induced damage and improving the lactation performance of MECs. In conclusion, these findings reveal the molecular mechanisms by which L-arginine relieves HS-induced mammary gland injury, and suggest that the intake of arginine-based feeds or feed additives is a promising method to increase the milk yield of dairy animals in extreme heat conditions.

Mechanism exploration of Zoledronic acid combined with PD-1 in the treatment of hepatocellular carcinoma.

How to increase the response of immune checkpoint inhibitors (ICIs) is a challenge. In clinical, we found that Zoledronic acid (ZA) may increase the anti-tumor effect of immunotherapy for hepatocellular carcinoma (HCC). To explore the underlying mechanism, we established a mouse model of HCC by subcutaneously injecting Hepa1-6 cell line. The result showed that the tumor volume in the ZA plus anti-PD-1 monocloning antibody (anti-PD-1 mAb) treatment groups was significantly smaller than that of control group, and the onset time of tumor inhibition was even shorter than that of the anti-PD-1 mAb group. Using flow cytometry (FC) to detect the proportion of major immune cell subsets in tumor tissues of each group of mice, we found that the synergistic anti-tumor effect of ZA and anti-PD-1 mAb may be related to ZA-induced polarization of macrophages toward the M1 phenotype. Next, we performed bulk RNA sequencing on tumor samples from different groups to obtain differentially expressed genes (DEGs), which were then input DEGs into pathway enrichment analysis. Data indicated that ZA participated in the M1-type polarization via ferroptosis-related pathways. Our results revealed how ZA involves in the anti-tumor effect of PD-1 monoclonal antibody and provided a potential therapeutic candidate for patients with HCC.

MolSieve: A Progressive Visual Analytics System for Molecular Dynamics Simulations.

Molecular Dynamics (MD) simulations are ubiquitous in cutting-edge physio-chemical research. They provide critical insights into how a physical system evolves over time given a model of interatomic interactions. Understanding a system's evolution is key to selecting the best candidates for new drugs, materials for manufacturing, and countless other practical applications. With today's technology, these simulations can encompass millions of unit transitions between discrete molecular structures, spanning up to several milliseconds of real time. Attempting to perform a brute-force analysis with data-sets of this size is not only computationally impractical, but would not shed light on the physically-relevant features of the data. Moreover, there is a need to analyze simulation ensembles in order to compare similar processes in differing environments. These problems call for an approach that is analytically transparent, computationally efficient, and flexible enough to handle the variety found in materials-based research. In order to address these problems, we introduce MolSieve, a progressive visual analytics system that enables the comparison of multiple long-duration simulations. Using MolSieve, analysts are able to quickly identify and compare regions of interest within immense simulations through its combination of control charts, data-reduction techniques, and highly informative visual components. A simple programming interface is provided which allows experts to fit MolSieve to their needs. To demonstrate the efficacy of our approach, we present two case studies of MolSieve and report on findings from domain collaborators.

VEGF signaling governs the initiation of biliary-mediated liver regeneration through the PI3K-mTORC1 axis.

Biliary epithelial cells (BECs) are a potential source to repair the damaged liver when hepatocyte proliferation is compromised. Promotion of BEC-to-hepatocyte transdifferentiation could be beneficial to the clinical therapeutics of patients with end-stage liver diseases. However, mechanisms underlying the initiation of BEC transdifferentiation remain largely unknown. Here, we show that upon extreme hepatocyte injury, vegfaa and vegfr2/kdrl are notably induced in hepatic stellate cells and BECs, respectively. Pharmacological and genetic inactivation of vascular endothelial growth factor (VEGF) signaling would disrupt BEC dedifferentiation and proliferation, thus restraining hepatocyte regeneration. Mechanically, VEGF signaling regulates the activation of the PI3K-mammalian target of rapamycin complex 1 (mTORC1) axis, which is essential for BEC-to-hepatocyte transdifferentiation. In mice, VEGF signaling exerts conserved roles in oval cell activation and BEC-to-hepatocyte differentiation. Taken together, this study shows VEGF signaling as an initiator of biliary-mediated liver regeneration through activating the PI3K-mTORC1 axis. Modulation of VEGF signaling in BECs could be a therapeutic approach for patients with end-stage liver diseases.

Evaluating the Impact of Uncertainty Visualization on Model Reliance.

Machine learning models have gained traction as decision support tools for tasks that require processing copious amounts of data. However, to achieve the primary benefits of automating this part of decision-making, people must be able to trust the machine learning model's outputs. In order to enhance people's trust and promote appropriate reliance on the model, visualization techniques such as interactive model steering, performance analysis, model comparison, and uncertainty visualization have been proposed. In this study, we tested the effects of two uncertainty visualization techniques in a college admissions forecasting task, under two task difficulty levels, using Amazon's Mechanical Turk platform. Results show that (1) people's reliance on the model depends on the task difficulty and level of machine uncertainty and (2) ordinal forms of expressing model uncertainty are more likely to calibrate model usage behavior. These outcomes emphasize that reliance on decision support tools can depend on the cognitive accessibility of the visualization technique and perceptions of model performance and task difficulty.

Effects of exercise by type and duration on quality of life in patients with digestive system cancers: A systematic review and network meta-analysis.

BACKGROUND: There is scant evidence regarding the effects of exercise type and duration on quality of life (QoL) in digestive system cancer (DSC) survivors. We aim to investigate the optimal type and duration of exercise to improve QoL for DSC survivors through a systematic review and network meta-analysis. METHODS: A systematic literature search of PubMed, Embase, and Web of Science was performed. Eligibility for study inclusion was limited to studies that were randomized controlled trials involving all kinds of exercise in adult patients with DSCs, and the comparator was in standard care or other types of exercise. The primary outcome was QoL, including general health, physical health, mental health, and role function. Secondary outcomes included cancer-related symptoms such as fatigue, insomnia, depression, anxiety, and duration of hospital stay. The network meta-analyses were performed using a random-effect model. RESULTS: The analysis included 32 eligible articles and a total of 2558 participants. Our primary outcome indicated that short-term aerobic exercise significantly enhanced general health (standardized mean difference (SMD) = 0.66, 95% credible intervals (CrIs): 0.05 to 1.30), and also contributed to a better mental health (SMD = 0.38, 95%CrI: -0.05 to 0.81) and role function (SMD = 0.48, 95%CrI: -0.27 to 1.20). Although without significant changes, short-term resistance exercise tended to increase the physical health of patients with DSCs (SMD = 0.69, 95%CrI: -0.07 to 1.50) and effective in alleviating fatigue (SMD = -0.77, 95%CrI: -1.50 to 0.01). Short-term aerobic exercise was related to a lower score of insomnia (SMD = -1.20, 95%CrI: -2.40 to 0.06), depression (SMD = -0.51, 95%CrI: -1.50 to 0.45), and anxiety (SMD = -0.45, 95%CrI: -1.30 to 0.34). All types of exercise related to a trend of declined hospital stays (-0.87 to -5.00 day). Long-term resistance exercise, however, was negatively associated with general health (SMD = -0.33, 95%CrI: -1.70 to 1.00), physical health (SMD = -0.18, 95%CrI: -1.30 to 0.90), and role function (SMD = -1.20, 95%CrI: -2.50 to 0.11). CONCLUSION: This study suggests that short-term aerobic exercise, with or without resistance exercise programs, enhances QoL (especially for general health) as well as relieves cancer-related symptoms for DSC survivors, while long-term resistance exercise may have negative effects, and thus should be adopted cautiously. These results provide important evidence for the management of DSCs.

Value of 5-Hydroxymethylcytosine in HBV-Carrying High-Risk Hepatocellular Carcinoma Population: An Evaluation Based on Differential Analysis.

Objective: To clarify the application value of 5-hydroxymethylcytosine (5hmC) in evaluating the progression of chronic hepatitis B (CHB) to hepatocellular carcinoma (HCC) based on difference analysis. Methods: A total of 180 patients were enrolled. Among them, 84 patients with chronic hepatitis B virus (HBV) infection while no progression to hepatocellular carcinoma (HCC) were included in the control group (CG), and 96 patients with HCC developed from HBV infection were included in the research group (RG). Two-thirds of the samples were used in the training set and 1/3 samples in the validation set to detect the level of 5hmC in both groups based on the modified nano-hmC-Seal technique. The expression levels of 5hmC-related genes TET2 and TET3 were quantified by qPCR, and the correlation between TET3 and 5hmC was analyzed by Pearson's correlation coefficients. Receiver operating characteristic (ROC) curves were drawn to evaluate the application value of the TET3-based 5hmC prediction model in the early diagnosis of HCC. Results: (i) The expression of 5hmC in RG was lower than that in CG, no matter in the training set or the validation set. (ii) 5hmC was significantly enriched in the region between the transcription initiation site and the transcription end site but was depleted in the flanking region. (iii) 5hmC-related genes TET2 and TET3 were significantly downregulated in HCC patients, whether in the training set or the validation set. (iv) In both the training and validation sets, TET3 showed a positive association with 5hmC. (v) ROC analysis results showed that the 5hmC prediction model could be used to predict the progression of CHB to HCC (training set: AUC = 0.81, 0.729-0.893; validation set: AUC = 0.84, 0.739-0.936). Conclusions: TET3 expression based on 5hmC sequencing is a landmark molecule for evaluating the progression of HCC in CHB patients, which is worthy of further study and promotion.

Coronary Atherosclerotic Disease and Cancer: Risk Factors and Interrelation.

Background: In our clinical work, we found that cancer patients were susceptible to coronary atherosclerotic heart disease (CAD). However, less is known about the relationship between CAD and cancer. The present study aimed to identify the risk factors for CAD and cancer, as well as the relationship between CAD and cancer. Methods: In this retrospective study, 1600 patients between January 2012 and June 2019 were enrolled and divided into groups according to whether they had CAD or cancer. Single-factor and multivariate analysis methods were applied to examine the risk factors for CAD and cancer. Results: (1) Cancer prevalence was significantly higher in patients with CAD than in patients without CAD (47.2 vs. 20.9%). The prevalence of CAD in cancer and non-cancer patients was 78.9 and 52.4%, respectively. (2) Multivariable logistic regression showed that patients with cancer had a higher risk of developing CAD than non-cancer patients (OR: 2.024, 95% CI: 1.475 to 2.778, p < 0.001). Respiratory (OR: 1.981, 95% CI: 1.236-3.175, p = 0.005), digestive (OR: 1.899, 95% CI: 1.177-3.064, p = 0.009) and urogenital (OR: 3.595, 95% CI: 1.696-7.620, p = 0.001) cancers were significantly associated with a higher risk of CAD compared with no cancer. (3) Patients with CAD also had a higher risk of developing cancer than non-CAD patients (OR = 2.157, 95% CI: 1.603 to 2.902, p < 0.001). Patients in the Alanine aminotransferase (ALT) level ≥ 40 U/L group had a lower risk of cancer than patients in the ALT level < 20 U/L group (OR: 0.490, 95% CI: 0.333-0.722, p < 0.001). (4) An integrated variable (Y = 0.205 × 10-1 age - 0.595 × 10-2 HGB - 0.116 × 10-1 ALT + 0.135 FIB) was identified for monitoring the occurrence of cancer among CAD patients, with an AUC of 0.720 and clinical sensitivity/specificity of 0.617/0.711. Conclusion: (1) We discovered that CAD was an independent risk factor for cancer and vice versa. (2) Digestive, respiratory and urogenital cancers were independent risk factors for CAD. (3) We created a formula for the prediction of cancer among CAD patients. (4) ALT, usually considered a risk factor, was proven to be a protective factor for cancer in this study.

Downregulation of CASTOR1 Inhibits Heat-Stress-Induced Apoptosis and Promotes Casein and Lipid Synthesis in Mammary Epithelial Cells.

Heat stress is one of the most important factors limiting the milk yields of dairy animals. This decline can be attributed to the heat-stress-induced apoptosis of mammary epithelial cells (MECs). The cytosolic arginine sensor for mTORC1 subunit 1 (CASTOR1) is a crucial upstream regulator of the mechanistic target of rapamycin complex 1 (mTORC1) signaling, which has close connections with apoptosis. However, the specific roles of CASTOR1 in regulating the apoptosis and lactation of MECs are still obscure. In the present study, we found that heat stress promotes apoptosis and CASTOR1's expression in HC11 cells. Downregulation of CASTOR1 inhibits heat-stress-induced apoptosis through a ROS-independent pathway. In addition, silencing of CASTOR1 promotes cell proliferation, cell cycle progression, and milk component synthesis, and overexpressing of CASTOR1 reverses these observations. Furthermore, we found that silencing of CASTOR1 contributes to the nuclear transport of SREBP1 and promotes lipid synthesis. This study demonstrates the pivotal roles of CASTOR1 in heat-stress-induced apoptosis and milk component synthesis in MECs.

Genome-wide analysis of the mouse LIM gene family reveals its roles in regulating pathological cardiac hypertrophy.

LIM-domain proteins have been shown to be associated with heart development and diseases. Systematic studies of LIM family members at the genome-wide level, which are crucial to further understand their functions in cardiac hypertrophy, are currently lacking. Here, 70 LIM genes were identified and characterised in mice. The expression patterns of LIM genes differ greatly during cardiac development and in the case of hypertrophy. Both Crip2 and Xirp2 are differentially expressed in cardiac hypertrophy and during heart failure. In addition, the hypertrophic state of cardiomyocytes is controlled by the relative expression levels of Crip2 and Xirp2. This study provides a foundation for further understanding of the special roles of LIM proteins in mammalian cardiac development and hypertrophy.

Farnesoid X Receptor Is Required for the Redifferentiation of Bipotential Progenitor Cells During Biliary-Mediated Zebrafish Liver Regeneration.

BACKGROUND AND AIMS: Liver regeneration after extreme hepatocyte loss occurs through transdifferentiation of biliary epithelial cells (BECs), which includes dedifferentiation of BECs into bipotential progenitor cells (BPPCs) and subsequent redifferentiation into nascent hepatocytes and BECs. Although multiple molecules and signaling pathways have been implicated to play roles in the BEC-mediated liver regeneration, mechanisms underlying the dedifferentiation-redifferentiation transition and the early phase of BPPC redifferentiation that is pivotal for both hepatocyte and BEC directions remain largely unknown. APPROACH AND RESULTS: The zebrafish extreme liver damage model, genetic mutation, pharmacological inhibition, transgenic lines, whole-mount and fluorescent in situ hybridizations and antibody staining, single-cell RNA sequencing, quantitative real-time PCR, and heat shock-inducible overexpression were used to investigate roles and mechanisms of farnesoid X receptor (FXR; encoded by nuclear receptor subfamily 1, group H, member 4 [nr1h4]) in regulating BPPC redifferentiation. The nr1h4 expression was significantly up-regulated in response to extreme liver injury. Genetic mutation or pharmacological inhibition of FXR was ineffective to BEC-to-BPPC dedifferentiation but blocked the redifferentiation of BPPCs to both hepatocytes and BECs, leading to accumulation of undifferentiated or less-differentiated BPPCs. Mechanistically, induced overexpression of extracellular signal-related kinase (ERK) 1 (encoded by mitogen-activated protein kinase 3) rescued the defective BPPC-to-hepatocyte redifferentiation in the nr1h4 mutant, and ERK1 itself was necessary for the BPPC-to-hepatocyte redifferentiation. The Notch activities in the regenerating liver of nr1h4 mutant attenuated, and induced Notch activation rescued the defective BPPC-to-BEC redifferentiation in the nr1h4 mutant. CONCLUSIONS: FXR regulates BPPC-to-hepatocyte and BPPC-to-BEC redifferentiations through ERK1 and Notch, respectively. Given recent applications of FXR agonists in the clinical trials for liver diseases, this study proposes potential underpinning mechanisms by characterizing roles of FXR in the stimulation of dedifferentiation-redifferentiation transition and BPPC redifferentiation.

Tannic acid alleviates lipopolysaccharide­induced H9C2 cell apoptosis by suppressing reactive oxygen species­mediated endoplasmic reticulum stress.

Sepsis­induced myocardial dysfunction is one of the features of multiple organ dysfunction in sepsis, which is associated with extremely high mortality and is characterized by impaired myocardial compliance. To date, there are few effective treatment options available to cure sepsis. Tannic acid (TA) is reportedly protective during sepsis; however, the underlying mechanisms by which TA protects against septic heart injury remain elusive. The present study investigated the potential effects and underlying mechanisms of TA in alleviating lipopolysaccharide (LPS)­induced H9C2 cardiomyocyte cell apoptosis. H9C2 cells were treated with LPS (15 µg/ml), TA (10 µM) and TA + LPS; control cells were treated with medium only. Apoptosis was measured using flow cytometry, reverse transcription­quantitative PCR (RT­qPCR) and western blot analysis. Additionally, the levels of cellular reactive oxygen species (ROS), malondialdehyde and nicotinamide adenine dinucleotide phosphate were evaluated. Western blotting and RT­qPCR were also employed to detect the expression levels of endoplasmic reticulum (ER) stress­associated functional proteins. The present findings demonstrated that TA reduced the degree of LPS­induced H9C2 cell injury, including inhibition of ROS production and ER stress (ERS)­associated apoptosis. ERS­associated functional proteins, including activating transcription factor 6, protein kinase­like ER kinase, inositol­requiring enzyme 1, spliced X box­binding protein 1 and C/EBP­homologous protein were suppressed in response to TA treatment. Furthermore, the expression levels of ERS­associated apoptotic proteins, including c­Jun N­terminal kinase, Bax, cytochrome c, caspase­3, caspase­12 and caspase­9 were reduced following treatment with TA. Additionally, the protective effects of TA on LPS­induced H9C2 cells were partially inhibited following treatment with the ROS inhibitor N­acetylcysteine, which demonstrated that ROS mediated ERS­associated apoptosis and TA was able to decrease ROS­mediated ERS­associated apoptosis. Collectively, the present findings demonstrated that the protective effects of TA against LPS­induced H9C2 cell apoptosis may be associated with the amelioration of ROS­mediated ERS. These findings may assist the development of potential novel therapeutic methods to inhibit the progression of myocardial cell injury.

Whole Genome Level Analysis of the Wnt and DIX Gene Families in Mice and Their Coordination Relationship in Regulating Cardiac Hypertrophy.

The Wnt signaling pathway is an evolutionarily conserved signaling pathway that plays essential roles in embryonic development, organogenesis, and many other biological activities. Both Wnt proteins and DIX proteins are important components of Wnt signaling. Systematic studies of Wnt and DIX families at the genome-wide level may provide a comprehensive landscape to elucidate their functions and demonstrate their relationships, but they are currently lacking. In this report, we describe the correlations between mouse Wnt and DIX genes in family expansion, molecular evolution, and expression levels in cardiac hypertrophy at the genome-wide scale. We observed that both the Wnt and DIX families underwent more expansion than the overall average in the evolutionarily early stage. In addition, mirrortree analyses suggested that Wnt and DIX were co-evolved protein families. Collectively, these results would help to elucidate the evolutionary characters of Wnt and DIX families and demonstrate their correlations in mediating cardiac hypertrophy.

Corrections to "Visual Analytics for Decision-Making During Pandemics".

[This corrects the article DOI: 10.1109/MCSE.2020.3023288.].

Metoprolol alleviates arginine vasopressin-induced cardiomyocyte hypertrophy by upregulating the AKT1-SERCA2 cascade in H9C2 cells.

BACKGROUND: Arginine vasopressin (AVP) is elevated in patients with heart failure, and the increase in the AVP concentration in plasma is positively correlated with disease severity and mortality. Metoprolol (Met) is a beta blocker that is widely used in the clinic to treat pathological cardiac hypertrophy and to improve heart function. However, the specific mechanism by which Met alleviates AVP-induced pathological cardiac hypertrophy is still unknown. Our current study aimed to evaluate the inhibitory effects of Met on AVP-induced cardiomyocyte hypertrophy and the underlying mechanisms. METHODS: AVP alone or AVP plus Met was added to the wild type or AKT1-overexpressing rat cardiac H9C2 cell line. The cell surface areas and ANP/BNP/ß-MHC expressions were used to evaluate the levels of hypertrophy. Western bolting was used to analyze AKT1/P-AKT1, AKT2/P-AKT2, total AKT, SERCA2, and Phospholamban (PLN) expression. Fluo3-AM was used to measure the intracellular Ca2+ stores. RESULTS: In the current study, we found that AKT1 but not AKT2 mediated the pathogenesis of AVP-induced cardiomyocyte hypertrophy. Sustained stimulation (48 h) with AVP led to hypertrophy in the H9C2 rat cardiomyocytes, resulting in the downregulation of AKT1 (0.48 fold compared to control) and SERCA2 (0.62 fold), the upregulation of PLN (1.32 fold), and the increase in the cytoplasmic calcium concentration (1.52 fold). In addition, AKT1 overexpression increased the expression of SERCA2 (1.34 fold) and decreased the expression of PLN (0.48 fold) in the H9C2 cells. Moreover, we found that Met could attenuate the AVP-induced changes in AKT1, SERCA2 and PLN expression and decreased the cytoplasmic calcium concentration in the H9C2 cells. CONCLUSIONS: Our results demonstrated that the AKT1-SERCA2 cascade served as an important regulatory pathway in AVP-induced pathological cardiac hypertrophy.

Genome-wide identification and characterization of Toll-like receptors (TLRs) in housefly (Musca domestica) and their roles in the insecticide resistance.

Toll-like receptors (TLRs) are the earliest reported pathogen recognition receptors (PRRs), and these receptors play pivotal roles in the innate immune system. Systematic studies of TLR family at the genome-wide level are important to understand its functions but are currently lacking in the insect lineage. Here, 6 TLR genes were identified and characterized in housefly (Musca domestica). The TLR genes of housefly were classified into five families according to the phylogenetic analysis of insect TLRs. The domain organization analyses indicated that the TLRs were composed by three major components: a leucine-rich repeat (LRR) domain, a transmembrane region (TM) and a Toll/interleukin-1 receptor (TIR) domain. Primary and tertiary structure analysis showed that the ectodomains of arthropod TLRs were longer than that of other phyla or classes. The mRNA expression levels of all 6 TLRs downregulated in the resistant housefly strain. Moreover, the expression levels of 6 TLRs varied between tissue and gender. Additionally, the 3D structures of the TIR domain were highly conserved during evolution. Collectively, these results help elucidate the crucial roles of TLRs in the immune response of housefly and provide a foundation for further understanding of innate immunity of the housefly.

VASSL: A Visual Analytics Toolkit for Social Spambot Labeling.

Social media platforms are filled with social spambots. Detecting these malicious accounts is essential, yet challenging, as they continually evolve to evade detection techniques. In this article, we present VASSL, a visual analytics system that assists in the process of detecting and labeling spambots. Our tool enhances the performance and scalability of manual labeling by providing multiple connected views and utilizing dimensionality reduction, sentiment analysis and topic modeling, enabling insights for the identification of spambots. The system allows users to select and analyze groups of accounts in an interactive manner, which enables the detection of spambots that may not be identified when examined individually. We present a user study to objectively evaluate the performance of VASSL users, as well as capturing subjective opinions about the usefulness and the ease of use of the tool.