Chronic hepatitis B virus (HBV) infection, affecting approximately 240 million people worldwide, is a major public health problem that elevates the risk of developing liver cirrhosis and ...hepatocellular carcinoma. Given that current anti-HBV drugs are limited to interferon-based regimens and nucleos(t)ide analogs, the development of new anti-HBV agents is urgently needed. The viral entry process is generally an attractive target implicated in antiviral strategies. Using primary cells from humans and Tupaia belangeri, as well as HepaRG cells, important determinants of viral entry have been achieved. Recently, sodium taurocholate cotransporting polypeptide (NTCP) was identified as an HBV entry receptor and enabled the establishment of a susceptible cell line that can efficiently support HBV infection. This finding will allow a deeper understanding of the requirements for efficient HBV infection, including the elucidation of the molecular entry mechanism. In addition, pharmacological studies suggest that NTCP is able to serve as a therapeutic target. This article summarizes our current knowledge on the mechanisms of HBV entry and the role of NTCP in this process.
In order to investigate whether handwriting has an advantage in learning word form, sound, and meaning, this study randomly selected 40 elementary school student participants (20 males, 20 females, ...aged 11.4 ± 1.34 years). Using an experimental approach, we compared the learning outcomes of word sound matching, word meaning matching, and word form judgment tasks under two conditions: handwriting and visual learning. After three consecutive days of learning and testing, we found that handwriting generally outperformed visual learning in terms of accuracy and response time in word form, sound, and meaning learning. Additionally, we observed differences in the timing of significant discrepancies in learning outcomes between the two methods across the three tasks. Specifically, in terms of accuracy, discrepancies first appeared in the word sound matching task on the first day, followed by the word form judgment task, and lastly the word meaning matching task. Regarding response time, significant differences between learning methods first emerged in the word form judgment task, followed by the word sound and word meaning tasks. Thus, combining accuracy and response time data, we conclude that handwriting is more advantageous than visual learning for word acquisition, with a differential impact on word form, sound, and meaning, where word form and sound are prioritized over meaning.
Chronic hepatitis B is caused by prolonged infection with the hepatitis B virus (HBV), which can substantially increase the risk of developing liver disease. Despite the development of preventive ...vaccines against HBV, a therapeutic vaccine inducing an effective antibody response still remains elusive. The preS1 domain of the large HBV surface protein is the major viral attachment site on hepatocytes and thus offers a therapeutic target; however, its poor immunogenicity limits clinical translation. Here, we design a ferritin nanoparticle vaccine that can deliver preS1 to specific myeloid cells, including SIGNR1
dendritic cells (which activate T follicular helper cells) and lymphatic sinus-associated SIGNR1
macrophages (which can activate B cells). This nanoparticle vaccine induces a high-level and persistent anti-preS1 response that results in efficient viral clearance and partial serological conversion in a chronic HBV mouse model, offering a promising translatable vaccination strategy for the functional cure of chronic hepatitis B.
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•The tissue distribution and bioaccumulation of OBS were firstly investigated.•OBS displayed specific tissue distribution similar to that of PFOS.•OBS interactions with proteins and ...phospholipids control its internal distribution.•The BAF value of OBS was higher than the regulatory bioaccumulation criterion.
The emergence of novel per- and polyfluoroalkyl substances (PFASs) has enabled researchers to determine their bioaccumulation, which is important for understanding their internal doses and environmental risks. Here, for the first time, we report on the occurrence of a novel PFAS, p-perfluorous nonenoxybenzenesulfonate (OBS) in wild crucian carp and explore its tissue distribution and bioaccumulation. The highest levels of OBS were observed in blood (mean/median: 144/133 ng/ml) with the mean tissue/blood ratios (TBRs) consistently below 1, ranging from 0.090 (muscle) to 0.644 (liver). This followed the pattern of perfluorooctane sulfonate (PFOS), implying that their distributions were similar. The calculated tissue-specific LogBAF values, except for muscle, 3.78 (gill)–4.14 (blood) over the regulatory bioaccumulation criterion (Log value: 3.70) indicated its obvious bioaccumulative potency in crucian carp. Molecular docking with estimated binding energies at −8.5 and −9.0 kcal/mol corroborated the strong interactions of OBS with human serum albumin and liver fatty acid binding protein, even though the binding energies were lower than those of PFOS. This, to some extent, explained the lower bioaccumulation of OBS than PFOS. Considering its bioaccumulative potential, large production volume, and wide use, further investigation into the environmental risk and in vivo toxicology of OBS is required.
To achieve the scheme of "magic bullets" in antitumor therapy, antibody-drug conjugates (ADCs) were developed. ADCs consist of antibodies targeting tumor-specific antigens, chemical linkers, and ...cytotoxic payloads that powerfully kill cancer cells. With the approval of ado-trastuzumab emtansine (T-DM1) and fam-trastuzumab deruxtecan (T-DXd), the therapeutic potentials of ADCs in breast cancer have come into the spotlight. Nearly 30 ADCs for breast cancer are under exploration to move targeted therapy forward. In this review, we summarize the presenting and emerging agents and targets of ADCs. The ADC structure and development history are also concluded. Moreover, the challenges faced and prospected future directions in this field are reviewed, which give insights into novel treatments with ADCs for breast cancer.
The contemporary comprehension of breast cancer has progressed to the molecular level. As a heterogeneous malignancy, conventional pathological diagnosis and histological classification could no ...longer meet the needs of precisely managing breast cancer. Genetic testing based on gene expression profiles and gene mutations has emerged and substantially contributed to the precise diagnosis and treatment of breast cancer. Multigene assays (MGAs) are explored for early-stage breast cancer patients, aiding the selection of adjuvant therapy and predicting prognosis. For metastatic breast cancer patients, testing specific genes indicates potentially effective antitumor agents. In this review, genetic testing in early-stage and metastatic breast cancer is summarized, as well as the advantages and challenges of genetic testing in breast cancer.
Carotenoids are a class of terpenoid pigments that contribute to the color and nutritional value of many fruits. Their biosynthetic pathways have been well established in a number of plant species; ...however, many details of the regulatory mechanism controlling carotenoid metabolism remain to be elucidated. Apricot is one of the most carotenoid-rich fruits, making it a valuable system for investigating carotenoid metabolism. The purpose of this study was to identify key genes and regulators associated with carotenoid metabolism in apricot fruit based on transcriptome sequencing.
During fruit ripening in the apricot cultivar 'Luntaixiaobaixing' (LT), the total carotenoid content of the fruit decreased significantly, as did the levels of the carotenoids β-carotene, lutein and violaxanthin (p < 0.01). RNA sequencing (RNA-Seq) analysis of the fruit resulted in the identification of 44,754 unigenes and 6916 differentially expressed genes (DEGs) during ripening. Among these genes, 33,498 unigenes were annotated using public protein databases. Weighted gene coexpression network analysis (WGCNA) showed that two of the 13 identified modules ('blue' and 'turquoise') were highly correlated with carotenoid metabolism, and 33 structural genes from the carotenoid biosynthetic pathway were identified. Network visualization revealed 35 intramodular hub genes that putatively control carotenoid metabolism. The expression levels of these candidate genes were determined by quantitative real-time PCR analysis, which showed ripening-associated carotenoid accumulation. This analysis revealed that a range of genes (NCED1, CCD1/4, PIF3/4, HY5, ERF003/5/12, RAP2-12, AP2, AP2-like, BZR1, MADS14, NAC2/25, MYB1R1/44, GLK1/2 and WRKY6/31/69) potentially affect apricot carotenoid metabolism during ripening. Based on deciphering the molecular mechanism involved in ripening, a network model of carotenoid metabolism in apricot fruit was proposed.
Overall, our work provides new insights into the carotenoid metabolism of apricot and other species, which will facilitate future apricot functional studies and quality breeding through molecular design.
Metabolic reprogramming, immune evasion and tumor-promoting inflammation are three hallmarks of cancer that provide new perspectives for understanding the biology of cancer. We aimed to figure out ...the relationship of tumor glycolysis and immune/inflammation function in the context of breast cancer, which is significant for deeper understanding of the biology, treatment and prognosis of breast cancer.
Using mRNA transcriptome data, tumor-infiltrating lymphocytes (TILs) maps based on digitized H&E-stained images and clinical information of breast cancer from The Cancer Genome Atlas projects (TCGA), we explored the expression and prognostic implications of glycolysis-related genes, as well as the enrichment scores and dual role of different immune/inflammation cells in the tumor microenvironment. The relationship between glycolysis activity and immune/inflammation function was studied by using the differential genes expression analysis, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene set enrichment analyses (GSEA) and correlation analysis.
Most glycolysis-related genes had higher expression in breast cancer compared to normal tissue. Higher phosphoglycerate kinase 1 (PGK1) expression was associated with poor prognosis. High glycolysis group had upregulated immune/inflammation-related genes expression, upregulated immune/inflammation pathways especially IL-17 signaling pathway, higher enrichment of multiple immune/inflammation cells such as Th2 cells and macrophages. However, high glycolysis group was associated with lower infiltration of tumor-killing immune cells such as NKT cells and higher immune checkpoints expression such as PD-L1, CTLA4, FOXP3 and IDO1.
In conclusion, the enhanced glycolysis activity of breast cancer was associated with pro-tumor immunity. The interaction between tumor glycolysis and immune/inflammation function may be mediated through IL-17 signaling pathway.
Fault diagnosis methods based on deep learning and big data have achieved good results on rotating machinery. However, the conventional deep learning method of bearing fault diagnosis is mostly based ...on laboratory artificial simulation data, and there is an error with actual fault data, which will reduce the generalization performance of the deep learning method. In addition, labeled data are very precious in real industrial environment. Due to expensive equipment and personnel safety issues, it is difficult to obtain a large amount of high-quality fault labeling data. Therefore, in this paper, we propose a metric-based meta-learning method named Reinforce Relation Network (RRN) for diagnosing bearing faults with few-shot samples. In the proposed method, a 1D convolution neural network is used to extract fault features, and a metric learner is used to predict the similarity between samples under different transfer conditions. Label smoothing and the Adabound algorithm are utilized to further improve the performance of network classification. The performance of the proposed method is verified on a dataset which contains artificial damage and natural damage data. The comparison studies with other methods demonstrate the superiority of the proposed method in the few-shot scenario.
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