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      Vol. 25 ， Issue 8 ， 2024

        Review

      • Huayuan XIANG,Chenxuan BAO,Qiaoqiao CHEN,Qing GAO,Nan WANG,Qianqian GAO,Lingxiang MAO
        Vol. 25, Issue 8, Pages: 633-655(2024) DOI: 10.1631/jzus.B2300566
        Abstract：Extracellular vesicles (EVs) are nano-sized bilayer vesicles that are shed or secreted by virtually every cell type. A variety of biomolecules, including proteins, lipids, coding and non-coding RNAs, and mitochondrial DNA, can be selectively encapsulated into EVs and delivered to nearby and distant recipient cells, leading to alterations in the recipient cells, suggesting that EVs play an important role in intercellular communication. EVs play effective roles in physiology and pathology and could be used as diagnostic and therapeutic tools. At present, although the mechanisms of exosome biogenesis and secretion in donor cells are well understood, the molecular mechanism of EV recognition and uptake by recipient cells is still unclear. This review summarizes the current understanding of the molecular mechanisms of EVs’ biological journey in recipient cells, from recognition to uptake and cargo release. Furthermore, we highlight how EVs escape endolysosomal degradation after uptake and thus release cargo, which is crucial for studies applying EVs as drug-targeted delivery vehicles. Knowledge of the cellular processes that govern EV uptake is important to shed light on the functions of EVs as well as on related clinical applications.  
        Keywords：Extracellular vesicle (EV);Exosome;Endocytosis;Uptake;Release   
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        Published：2024-08-19
      • Qinmeng ZHANG,Luyao SONG,Mengdie FU,Jin HE,Guoli YANG,Zhiwei JIANG
        Vol. 25, Issue 8, Pages: 656-671(2024) DOI: 10.1631/jzus.B2300322
        Abstract：Optogenetics combines optics and genetic engineering to control specific gene expression and biological functions and has the advantages of precise spatiotemporal control, noninvasiveness, and high efficiency. Genetically modified photosensory sensors are engineered into proteins to modulate conformational changes with light stimulation. Therefore, optogenetic techniques can provide new insights into oral biological processes at different levels, ranging from the subcellular and cellular levels to neural circuits and behavioral models. Here, we introduce the origins of optogenetics and highlight the recent progress of optogenetic approaches in oral and craniofacial research, focusing on the ability to apply optogenetics to the study of basic scientific neural mechanisms and to establish different oral behavioral test models in vivo (orofacial movement, licking, eating, and drinking), such as channelrhodopsin (ChR), archaerhodopsin (Arch), and halorhodopsin from Natronomonas pharaonis (NpHR). We also review the synergic and antagonistic effects of optogenetics in preclinical studies of trigeminal neuralgia and maxillofacial cellulitis. In addition, optogenetic tools have been used to control the neurogenic differentiation of dental pulp stem cells in translational studies. Although the scope of optogenetic tools is increasing, there are limited large animal experiments and clinical studies in dental research. Potential future directions include exploring therapeutic strategies for addressing loss of taste in patients with coronavirus disease 2019 (COVID-19), studying oral bacterial biofilms, enhancing craniomaxillofacial and periodontal tissue regeneration, and elucidating the possible pathogenesis of dry sockets, xerostomia, and burning mouth syndrome.  
        Keywords：Lasers;Cell differentiation;Bacterial virulence;Nervous system;Neurophysiology;Behavioral science   
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        Published：2024-08-19
      • Lingjian ZHANG,Fangfang ZHANG,Zhiyuan MA,Jie JIN
        Vol. 25, Issue 8, Pages: 672-685(2024) DOI: 10.1631/jzus.B2300261
        Abstract：BackgroundHepatitis B virus (HBV) is one of the most widespread viruses worldwide and a major cause of hepatitis, cirrhosis, and hepatocellular carcinoma. Previous studies have revealed the impacts of HBV infection on fertility. An increasing number of infertile couples with chronic hepatitis B (CHB) virus infection choose assisted reproductive technology (ART) to meet their fertility needs. Despite the high prevalence of HBV, the effects of HBV infection on assisted reproduction treatment remain limited and contradictory.ObjectiveThe aim of this study was to provide a comprehensive overview of the effect of HBV infection on fertility and discuss its effects on pregnancy outcomes, vertical transmission, pregnancy complications, and viral activity during ART treatment.MethodsWe conducted a literature search in PubMed for studies on HBV infection and ART published from 1996 to 2022.ResultsHBV infection negatively affected fertility in both males and females. Existing research shows that HBV infection may increase the risk of pregnancy complications in couples undergoing assisted reproduction treatment. The impact of HBV infection on the pregnancy outcomes of ART is still controversial. Current evidence does not support that ART increases the risk of vertical transmission of HBV, while relevant studies are limited. With the development of ART, the risk of HBV reactivation (HBVr) is increasing, especially due to the wide application of immunosuppressive therapy.ConclusionsRegular HBV infection screening and HBVr risk stratification and management are essential to prevent HBVr during ART. The determination of optimal strategy and timing of prophylactic anti-HBV therapy during ART still needs further investigation.  
        Keywords：Assisted reproductive technology (ART);Hepatitis B virus (HBV);Immunosuppressive agent;Pregnancy   
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        Published：2024-08-19

        Research Article

      • Junfen XU,Mengyan TU
        Vol. 25, Issue 8, Pages: 686-699(2024) DOI: 10.1631/jzus.B2300407
        Abstract：ObjectiveThe present study used single-cell RNA sequencing (scRNA-seq) to characterize the cellular composition of ovarian carcinosarcoma (OCS) and identify its molecular characteristics.MethodsscRNA-seq was performed in resected primary OCS for an in-depth analysis of tumor cells and the tumor microenvironment. Immunohistochemistry staining was used for validation. The scRNA-seq data of OCS were compared with those of high-grade serous ovarian carcinoma (HGSOC) tumors and other OCS tumors.ResultsBoth malignant epithelial and malignant mesenchymal cells were observed in the OCS patient of this study. We identified four epithelial cell subclusters with different biological roles. Among them, epithelial subcluster 4 presented high levels of breast cancer type 1 susceptibility protein homolog (BRCA1) and DNA topoisomerase 2-α (TOP2A) expression and was related to drug resistance and cell cycle. We analyzed the interaction between epithelial and mesenchymal cells and found that fibroblast growth factor (FGF) and pleiotrophin (PTN) signalings were the main pathways contributing to communication between these cells. Moreover, we compared the malignant epithelial and mesenchymal cells of this OCS tumor with our previous published HGSOC scRNA-seq data and OCS data. All the epithelial subclusters in the OCS tumor could be found in the HGSOC samples. Notably, the mesenchymal subcluster C14 exhibited specific expression patterns in the OCS tumor, characterized by elevated expression of cytochrome P450 family 24 subfamily A member 1 (CYP24A1), collagen type XXIII α1 chain (COL23A1), cholecystokinin (CCK), bone morphogenetic protein 7 (BMP7), PTN, Wnt inhibitory factor 1 (WIF1), and insulin-like growth factor 2 (IGF2). Moreover, this subcluster showed distinct characteristics when compared with both another previously published OCS tumor and normal ovarian tissue.ConclusionsThis study provides the single-cell transcriptomics signature of human OCS, which constitutes a new resource for elucidating OCS diversity.  
        Keywords：Ovarian carcinosarcoma;Single-cell RNA sequencing (scRNA-seq);Tumor heterogeneity   
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        Published：2024-08-19
      • Liming LIN,Jingjing TAO,Ying MENG,Yichao GAN,Xin HE,Shu LI,Jiawei ZHANG,Feiqiong GAO,Dijia XIN,Luyao WANG,Yili FAN,Boxiao CHEN,Zhimin LU,Yang XU
        Vol. 25, Issue 8, Pages: 700-710(2024) DOI: 10.1631/jzus.B2300555
        Abstract：Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia (AML) in recent years, chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients. Here, we demonstrated the antileukemia activity of a novel small molecular compound NL101, which is formed through the modification on bendamustine with a suberanilohydroxamic acid (SAHA) radical. NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells. It induces DNA damage and caspase 3-mediated apoptosis. A genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) library screen revealed that phosphatase and tensin homologous (PTEN) gene is critical for the regulation of cell survival upon NL101 treatment. The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome (MDS) cells, accompanied by the activation of protein kinase B (AKT) signaling pathway. The inhibition of mammalian target of rapamycin (mTOR) by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death. These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.  
        Keywords：Genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) library;Phosphatase and tensin homologous (PTEN);Rapamycin;Acute myeloid leukemia (AML);Chemotherapy   
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        Published：2024-08-19
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