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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.

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.

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.

We introduce a trans-disciplinary collaboration between researchers, healthcare practitioners, and community health partners in the Southwestern U.S. to enable improved management, response, and recovery to our current pandemic and for future health emergencies. Our Center work enables effective and efficient decision-making through interactive, human-guided analytical environments. We discuss our PanViz 2.0 system, a visual analytics application for supporting pandemic preparedness through a tightly coupled epidemiological model and interactive interface. We discuss our framework, current work, and plans to extend the system with exploration of what-if scenarios, interactive machine learning for model parameter inference, and analysis of mitigation strategies to facilitate decision-making during public health crises.

Oxidative carbonylation has attracted broad interest from both academia and industry in recent years. Oxycarbonylation of ethanol to diethyl carbonate (DEC) has been of great challenge due to the difficulty in the simultaneous activation of ethanol and CO. This work reports a heterogeneous Cu-Pd pair catalysis for simultaneous activation of ethanol and CO, affording a selectivity of 85.4% to DEC and a space–time yield (STY) of up to 207 mg∙g−1∙h−1. Well distributed Cu-Pd pair affords more Cu (I) sites, promoting CO activation and the followed insertion to adsorbed ethanol. Further increasing ratio of Cu (I) species via the pre-treatment of catalyst with CO and ethanol promotes simultaneously the activation of ethanol and CO, affording a STY of 325 mg∙g−1∙h−1 of DEC.

H2 production from aqueous phase reforming (APR) is of great importance, but an enhancement in the H2 production efficiency is required. Our previous work reported the catalytic production of H2 over metal oxide (MMO)-supported Ni derived from Ni-containing layered double hydroxides (Ni-MgAl-LDHs). Herein, we report the catalytic production of H2 from APR of cellulose over MMO-supported defect-rich Ni derived from Ni-MgAl-LDHs with abundant Mg(II) vacancies (VMg). The well-retained VMg during calcination under an H2 atmosphere induced the formation of Ni vacancies not only at the Ni–MMO interface, but also on the surface of the Ni particles. An H2 yield of up to 70.4% was achieved via the APR of cellulose over the defect-rich Ni–MMO, which is almost 2.5 times that from the APR of cellulose reported to date (∼30%). A combined investigation via quasi in situ XPS, EPR, PAS, and in situ FT-IR verified that the Mg vacancies on the support surface facilitate the cleavage of the C–H bond, while the Ni vacancies on the Ni particles boost the breakage of the C–C bond.

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.

Background: Sepsis-induced myocardial dysfunction (SIMD), which is one of the features of multiple organ dysfunction in sepsis with extremely high mortality, is characterized by impaired myocardial compliance. To date, there are few effective treatment options to cure sepsis. Tannic acid (TA) is reportedly protective during sepsis. However, the underlying mechanisms by which TA protects against septic heart injury remains elusive. Methods: We 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 media only. Apoptosis was measured using flow cytometry, RT-PCR, and Western blotting analysis. Additionally, laser confocal immunofluorescence analysis detected the production of reactive oxygen species (ROS). Western blot and RT-PCR were employed to detect ER stress-associated functional proteins. Results: The results demonstrated that TA reduced the degree of LPS-induced H9C2 cells injury, including the inhibition of ROS production and endoplasmic reticulum (ER) stress-associated apoptosis. ER stress-associated functional proteins, including ATF6, PERK, IRE1, XBP1s, and CHOP were suppressed in response to TA treatment. Furthermore, the expression levels of ER stress-associated apoptotic proteins, including JNK, Bax, Cyt, Caspase3, Caspase12, and Caspase9 were reduced following treatment with TA. Additionally, the protective effects of TA on LPS-induced H9C2 cells were strengthened following treatment with the ROS inhibitor, N-Acetylcysteine (NAC), which demonstrated that ROS-mediated ER stress-associated apoptosis and TA decreased ROS-mediated ER stress-associated apoptosis. Conclusion: Our findings demonstrated that the protective effects of TA against LPS-induced H9C2 cells apoptosis may be associated with the amelioration of ROS-mediated ER stress. These findings may assist the development of potential novel therapeutic methods to inhibit the progression of myocardial cell injury. (TA alleviates LPS-induced H9C2 cell apoptosis.)

Deep learning plays an important role in the field of artificial intelligence, but in most situation, deep learning requires a larger number of training samples to complete high-precision learning. Few-shot learning, which only uses a small dataset to learn different tasks, has been extensively researched. It can be summarized into three methods: metric learning, optimization-based and model-based. In this paper, we develop a novel method based on Matching Networks: focusing on the relation between samples. We have proposed a simple method based on the idea that we can aggregate intra-class samples and separate inter-class samples. Our experiments on the Omniglot dataset and miniImageNet dataset show that our method outperforms the baseline networks.

Sepsis‑induced 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 transcription‑quantitative PCR (RT‑qPCR) and western blot analysis. Additionally, the levels of cellular reactive oxygen species (ROS), malondialdehyde and nicotinamide adenine dinucleotide phosphate were evaluated. Western blotting and RT‑qPCR were also employed to detect the expression levels of endoplasmic reticulum (ER) stress‑associated functional proteins. The present findings demonstrated that TA reduced the degree of LPS‑induced H9C2 cell injury, including inhibition of ROS production and ER stress (ERS)‑associated apoptosis. ERS‑associated functional proteins, including activating transcription factor 6, protein kinase‑like ER kinase, inositol‑requiring enzyme 1, spliced X box‑binding protein 1 and C/EBP‑homologous protein were suppressed in response to TA treatment. Furthermore, the expression levels of ERS‑associated apoptotic proteins, including c‑Jun N‑terminal kinase, Bax, cytochrome c, caspase‑3, caspase‑12 and caspase‑9 were reduced following treatment with TA. Additionally, the protective effects of TA on LPS‑induced H9C2 cells were partially inhibited following treatment with the ROS inhibitor N‑acetylcysteine, which demonstrated that ROS mediated ERS‑associated apoptosis and TA was able to decrease ROS‑mediated ERS‑associated apoptosis. Collectively, the present findings demonstrated that the protective effects of TA against LPS‑induced H9C2 cell apoptosis may be associated with the amelioration of ROS‑mediated ERS. These findings may assist the development of potential novel therapeutic methods to inhibit the progression of myocardial cell injury.

Ribosome biogenesis is a significant process in cells. Dysfunction in this process will result in the defects of protein synthesis and consequently cause the development of specific diseases called ribosomopathies. Mutations in ribosome biogenesis protein Rps19, Rpl5, or Rpl11 can lead to hematopoietic defects in human, thus triggering the disease Diamond Blackfan anemia. However, the regulatory mechanisms of ribosome biogenesis in hematopoiesis remain incompletely understood. In this study, we describe a zebrafish mutant cq42, which carries a nonsense mutation in the gene that encodes ribosome biogenesis 2 homolog (Urb2). Urb2 is strongly expressed in the caudal hematopoietic tissue (CHT) during hematopoietic stem cells (HSCs) expanding. Molecular characterization of urb2cq42 larvae suggest that urb2 deficiency notably decrease the population of HSCs in CHT and early T cells in thymus. Further analysis shows that compromised cell proliferation and superfluous apoptosis are observed in the CHT of urb2cq42 mutant. P53 pathway is upregulated in the urb2cq42 larvae and loss-of-function of P53 can fully rescue the hematopoietic defects in urb2cq42 mutant. These data demonstrate that urb2 is essential for HSCs development through the regulation of P53 pathway.

The role of the AKT2/NBA1/SPK1 signaling cascade in macrophage migration regulation and post-ischemic cardiac remodeling was investigated. We determined that the AKT2/NBA1/SPK1 signaling cascade regulated macrophage migration. A novel role for NBA1 in macrophage migration was discovered. Elevated AKT2 phosphorylation, NBA1, SPK1 (along with phosphorylated SPK1) levels, macrophage recruitment, apoptosis, and fibrosis were found within the infarct area. Atorvastatin had a beneficial effect on cardiac remodeling following myocardial infarction by inhibiting AKT2/NBA1/SPK1-mediated macrophage recruitment, apoptosis, and collagen deposition while increasing angiogenesis in the infarct area. Atorvastatin-related protection of cardiac remodeling following myocardial infarction was abolished in SPK1-KO mice. The AKT2/NAB1/SPK1 pathway is a novel regulating factor of macrophage migration and cardiac remodeling after myocardial infarction.

Visualizations in organizational research have primarily been used in the context of traditional survey data, where individual data points (e.g., responses) can typically be plotted, and qualitative (e.g., language data) and quantitative (e.g., frequency data) information are not typically combined. Moreover, visualizations are typically used in a hypothetico-deductive fashion to showcase significant hypothesized results. With the advent of big data, which has been characterized as being particularly high in volume, variety, and velocity of collection, visualizations need to more explicitly and formally consider the issues of (a) identification (isolating or highlighting relevant data pertaining to the phenomena of interest), (b) integration (combining different modes of data to reveal insights about a phenomenon of interest), (c) immediacy (examining real-time data in a time-sensitive manner), and (d) interactivity (inductively uncovering and identifying new patterns). We discuss basic ideas for addressing these issues and provide illustrative examples of visualizations that incorporate and highlight ways of addressing these issues. Examples in our article include visualizing multiple performance criteria for police officers, publication network of organizational researchers, and social media language of Fortune 500 companies.