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Digital pathology-based artificial intelligence models for differential diagnosis and prognosis of sporadic odontogenic keratocysts

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International Journal of oral Science 2024年第2期16卷 349-358页

作者： Xinjia Cai Heyu Zhang Yanjin Wang Jianyun Zhang Tiejun Li department of oral pathology Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijingChina Central Laboratory Peking University School and Hospital of StomatologyBeijingChina department of oral pathology Shanghai Stomatological Hospital&School of StomatologyFudan UniversityShanghaiChina Research Unit of Precision Pathologic diagnosis in Tumors of the oral and Maxillofacial Regions Chinese Academy of Medical Sciences(2019RU034)BeijingChina

Odontogenic keratocyst(OKC)is a common jaw cyst with a high recurrence *** combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin ***,OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw *** of the different prognosis,differential diagnosis of several cysts can contribute to clinical *** collected 519 cases,comprising a total of 2157 hematoxylin and eosinstained images,to develop digital pathology-based artificial intelligence(AI)models for the diagnosis and prognosis of *** Inception_v3 neural network was utilized to train and test models developed from patch-level ***,whole slide imagelevel AI models were developed by integrating deep learning-generated pathology features with several machine learning *** AI models showed great performance in the diagnosis(AUC=0.935,95%CI:0.898–0.973)and prognosis(AUC=0.840,95%CI:0.751–0.930)of *** advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide ***,the study investigates the correlation between AI features generated by deep learning and pathological findings,highlighting the interpretative potential of AI models in the ***,we have developed the robust diagnostic and prognostic models for *** AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.

关键词： diagnosis pathology prognosis

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The spatial transcriptomic landscape of human gingiva in health and periodontitis

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Science China(Life Sciences) 2024年第4期67卷 720-732页

作者： Zongshan Shen Ran Zhang Yunjia Huang Jiayao Chen Mengjun Yu Chunhua Li Yong Zhang Lingling Chen Xin Huang Jichen Yang Zhengmei Lin Songlin Wang Bin Cheng Hospital of Stomatology Guangdong Provincial Key Laboratory of StomatologyGuanghua School of StomatologySun Yat-sen UniversityGuangzhou 510055China Beijing Laboratory of oral Health Capital Medical UniversityBeijing 100050China department of oral pathology Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100050China Research Unit of Precision Pathologic diagnosis in Tumors of the oral and Maxillofacial Regions Chinese Academy of Medical SciencesBeijing 100050China BGI-Qingdao BGI-ShenzhenQingdao 266555China

The gingiva is a key oral barrier that protects oral tissues from various stimuli.A loss of gingival tissue homeostasis causes periodontitis,one of the most prevalent inflammatory diseases in *** human gingiva exists as a complex cell network comprising specialized *** understand the tissue-specific pathophysiology of the gingiva,we applied a recently developed spatial enhanced resolution omics-sequencing(Stereo-seq)technique to obtain a spatial transcriptome(ST)atlas of the gingiva in healthy individuals and periodontitis *** utilizing Stereo-seq,we identified the major cell types present in the gingiva,which included epithelial cells,fibroblasts,endothelial cells,and immune cells,as well as subgroups of epithelial cells and immune *** further observed that inflammation-related signalling pathways,such as the JAK-STAT and NF-κB signalling pathways,were significantly upregulated in the endothelial cells of the gingiva of periodontitis patients compared with those of healthy ***,we characterized the spatial distribution of periodontitis risk genes in the gingiva and found that the expression of IFI16 was significantly increased in endothelial cells of inflamed *** conclusion,our Stereo-seq findings may facilitate the development of innovative therapeutic strategies for periodontitis by mapping periodontitis-relevant genes and pathways and effector cells.

关键词： spatial transcriptomics gingiva periodontal disease periodontitis risk genes

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Cisplatin-based miRNA delivery strategy inspired by the circCPNE1/miR-330-3p pathway for oral squamous cell carcinoma

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2748-2760页

作者： Hua-yang Fan Ming-da Zhao Hong-jie Jiang Zhen-wei Yu Yu-jiang Fan Xin-hua Liang Ya-ling Tang Yong Sun State Key Laboratory of oral Diseases&National Center for Stomatology&National Clinical Research Center for oral Diseases&department of oral and Maxillofacial Surgery West China Hospital of StomatologySichuan UniversityChengdu 610041China National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610065China State Key Laboratory of oral Diseases&National Center for Stomatology&National Clinical Research Center for oral Diseases&department of oral pathology West China Hospital of StomatologySichuan UniversityChengdu 610041China

Circular RNAs(circRNAs)are ideal biomarkers of oral squamous cell carcinoma(OSCC)because of their highly stable closed-loop structure,and they can act as microRNA(miRNA)sponges to regulate OSCC *** analyzing clinical samples,we identified circCPNE1,a dysregulated circRNA in OSCC,and its expression level was negatively correlated with the clinical stage of OSCC ***-of-function assays revealed the tumor-suppressive effect of circCPNE1,which was then identified as a miR-330-3p ***-330-3p was recognized as a tumor promoter in multiple studies,consistent with our finding that it could promote the proliferation,migration,and invasion of OSCC *** results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC ***,we designed cationic polylysine-cisplatin prodrugs to deliver antagomiR-330-3p(a miRNA inhibitory analog)via electrostatic interactions to form PP@miR nanoparticles(NPs).Paratumoral administration results revealed that PP@miR NPs effectively inhibited subcutaneous tumor progression and achieved partial tumor elimination(2/5),which confirmed the critical role of miR-330-3p in OSCC *** findings provide a new perspective for the development of OSCC treatments.

关键词： oral squamous cell carcinoma CircRNA MiRNA sponge Antagomir MiRNA delivery Cisplatin-based nanoparticles Drug delivery systems Tumor elimination

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FUT8-mediated aberrant N-glycosylation of SEMA7A promotes head and neck squamous cell carcinoma progression

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International Journal of oral Science 2024年第2期16卷 333-348页

作者： Zhonglong Liu Xiaoyan Meng Yuxin Zhang Jingjing Sun Xiao Tang Zhiyuan Zhang Liu Liu Yue He department of oral Maxillofacial&Head and Neck Oncology Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNational Clinical Research Center for Oral DiseaseShanghaiChina department of oral Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghaiChina department of oral pathology Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNational Clinical Research Center for Oral Disease ShanghaiShanghaiChina

SEMA7A belongs to the Semaphorin family and is involved in the oncogenesis and tumor *** glycosylation has been intricately linked with immune escape and tumor ***7A is a highly glycosylated protein with five glycosylated *** underlying mechanisms of SEMA7A glycosylation and its contribution to immunosuppression and tumorigenesis are ***,we identify overexpression and aberrant N-glycosylation of SEMA7A in head and neck squamous cell carcinoma,and elucidate fucosyltransferase FUT8 catalyzes aberrant core fucosylation in SEMA7A at N-linked oligosaccharides(Asn 105,157,258,330,and 602)via a direct protein‒protein interaction.A glycosylated statue of SEMA7A is necessary for its intra-cellular trafficking from the cytoplasm to the *** EGF triggers SEMA7A N-glycosylation through increasing the binding affinity of SEMA7A toward FUT8,whereas TGF-β1 promotes abnormal glycosylation of SEMA7A via induction of epithelial–mesenchymal *** N-glycosylation of SEMA7A leads to the differentiation of CD8^(+)T cells along a trajectory toward an exhausted state,thus shaping an immunosuppressive microenvironment and being resistant immunogenic cell *** of SEMA7A significantly improves the clinical outcome of EGFR-targeted and anti-PD-L1-based ***,we also define RBM4,a splice regulator,as a downstream effector of glycosylated SEMA7A and a pivotal mediator of PD-L1 alternative *** findings suggest that targeting FUT8-SEMA7A axis might be a promising strategy for improving antitumor responses in head and neck squamous cell carcinoma patients.

关键词： aberrant squamous SEMA

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CD97 inhibits osteoclast differentiation via Rap1a/ERK pathway under compression

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International Journal of oral Science 2024年第1期16卷 134-144页

作者： Xuan Zhou Xinjia Cai Fengyang Jing Xuefen Li Jianyun Zhang Heyu Zhang Tiejun Li department of oral pathology Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of Stomatology&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental MaterialsBeijingChina Research Unit of Precision Pathologic diagnosis in Tumors of the oral and Maxillofacial Regions Chinese Academy of Medical Sciences(2019RU034)BeijingChina Central Laboratory Peking University School and Hospital of StomatologyBeijingChina

Acceleration of tooth movement during orthodontic treatment is challenging, with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step. Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages, especially adhesion G protein-coupled receptors (aGPCRs), play important roles in force ***, its role in the regulation of osteoclast differentiation remains unclear. Herein, through single-cell analysis, we revealed that CD97, a novel mechanosensitive aGPCR, was expressed in macrophages. Compression upregulated CD97 expression and inhibited osteoclast differentiation;while knockdown of CD97 partially rescued osteoclast differentiation. It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation. RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression. Consistently, we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity, thereby accelerating tooth movement. In conclusion,our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.

关键词： CD97 osteoclast inhibited

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Spatial transcriptomics reveals that metabolic characteristics define the tumor immunosuppression microenvironment via iCAF transformation in oral squamous cell carcinoma

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International Journal of oral Science 2024年第1期16卷 110-121页

作者： Zheqi Liu Zhen Zhang Yu Zhang Wenkai Zhou Xu Zhang Canbang Peng Tong Ji Xin Zou Zhiyuan Zhang Zhenhu Ren department of oral and Maxillofacial-Head and Neck Oncology Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of Stomatology&Shanghai Research Institute of StomatologyShanghaiChina department of oral and Maxillofacial Surgery Zhongshan HospitalFudan UniversityShanghaiChina School and Hospital of Stomatology Kunming Medical UniversityKunmingChina Center for Tumor diagnosis&Therapy Jinshan HospitalFudan UniversityShanghaiChina department of pathology Jinshan HospitalFudan UniversityShanghaiChina Hainan Western Central Hospital Academician Zhang Zhiyuan Team Innovation CenterDanzhouChina

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-βexpression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.

关键词： CXCL12 microenvironment squamous

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Comprehensive analysis of the gut microbiome and posttranslational modifications elucidates the route involved in microbiota-host interactions

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Zoological Research 2024年第1期45卷 95-107页

作者： Hai-Yang Wang Lan-Xiang Liu Xue-Yi Chen Yang-Dong Zhang Wen-Xia Li Wen-Wen Li Lian Wang Xiao-Long Mo Hong Wei Ping Ji Peng Xie NHC Key Laboratory of diagnosis and Treatment on Brain Functional Diseases First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China College of Stomatology and Affiliated Stomatological Hospital of Chongqing Medical University Chongqing 401147China Chongqing Key Laboratory for oral Diseases and Biomedical Sciences Chongqing 401147China department of Neurology Yongchuan Hospital of Chongqing Medical UniversityChongqing 402160China department of pathology Faculty of Basic MedicineChongqing Medical UniversityChongqing 400016China department of Neurology First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Yu-Yue pathology Scientific Research Center Chongqing 401329China

The gut microbiome interacts with the host to maintain body homeostasis,with gut microbial dysbiosis implicated in many ***,the underlying mechanisms of gut microbe regulation of host behavior and brain functions remain *** study aimed to elucidate the influence of gut microbiota on brain functions via post-translational modification mechanisms in the presence or absence of bacteria without any *** conducted succinylome analysis of hippocampal proteins in germ-free(GF)and specific pathogen-free(SPF)mice and metagenomic analysis of feces from SPF *** results were integrated with previously reported hippocampal acetylome and phosphorylome data from the same batch of *** bioinformatics analyses revealed 584 succinylation sites on 455 proteins,including 54 up-regulated succinylation sites on 91 proteins and 99 down-regulated sites on 51 proteins in the GF mice compared to the SPF *** constructed a panoramic map of gut microbiota-regulated succinylation,acetylation,and phosphorylation,and identified cross-talk and relative independence between the different types of post-translational modifications in modulating complicated intracellular *** correlation analysis indicated that 13 taxa,predominantly belonging to the Bacteroidetes phylum,were correlated with the biological functions of post-translational *** correlations between these taxa and succinylation and negative correlations between these taxa and acetylation were identified in the modulation of intracellular *** study highlights the hippocampal physiological changes induced by the absence of gut microbiota,and proteomic quantification of succinylation,phosphorylation,and acetylation,contributing to our understanding of the role of the gut microbiome in brain function and behavioral phenotypes.

关键词： Gut microbiota Hippocampal protein Post-translational modifications Succinylation Acetylation Phosphorylation

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Advances in oral mesenchymal stem cell-derived extracellular vesicles in health and disease

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Genes & Diseases 2024年第1期11卷 346-357页

作者： Huanyu Luo Anahid Ahmadi Birjandi Feilong Ren Tianmeng Sun Paul T.Sharpe Hongchen Sun Zhengwen An department of oral Biology Jilin Provincial Key Laboratory of Tooth Development and Bone RemodelingSchool and Hospital of StomatologyJilin UniversityChangchunJilin 130021China Faculty of Dentistry Oral&Craniofacial SciencesCentre for Craniofacial and Regenerative BiologyKing's College LondonLondonSE19RTUK department of oral pathology Jilin Provincial Key Laboratory of Tooth Development and Bone RemodelingSchool and Hospital of StomatologyJilin UniversityChangchunJilin 130021China

Extracellular vesicles(EVs)are nano-size vesicles secreted naturally by all cells into the extracellular space and have been recognized as important cell-cell mediators in multicel-lular *** contain nucleic acids,proteins,lipids,and other cellular components,regulating many basic biological processes and playing an important role in regenerative med-icine and *** can be traced to their cells of origin and exhibit a similar ***,EVs demonstrate low immunogenicity,good biocompatibility,and fewer side ef-fects,compared to their parent *** stem cells(MsCs)are one of the most important resource cells for EVs,with a great capacity for self-renewal and multipotent differ-entiation,and play an essential role in stem cell *** mechanism of MsC therapy was thought to be attributed to the differentiation of MsCs after targeted migration,as previously ***,emerging evidence shows the previously unknown role of MsC-derived para-crine factors in stem cell *** EVs derived from oral tissue MSCs(OMSC-EVs),show more advantages than those of all other MsCs in tissue repair and regeneration,due to their lower invasiveness and easier accessibility for sample ***,we systematically review the biogenesis and biological characteristics of OMSC-EVs,as well as the role of OMsC-EVs in intercellular ***,we discuss the potential therapeutic roles of OMSC-EVs in oral and systemic *** highlight the current challenges and future directions of OMSC-EVs to focus more attention on clinical *** aim to provide valuable insights for the explorative clinical application of OMSC-EVs.

关键词： Disease Extracellular vesicles oral tissue MSC Therapeutic application Tissue regeneration

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Comprehensive understanding of glioblastoma molecular phenotypes:classification,characteristics,and transition

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Cancer Biology & Medicine 2024年第5期21卷 363-381页

作者： Can Xu Pengyu Hou Xiang Li Menglin Xiao Ziqi Zhang Ziru Li Jianglong Xu Guoming Liu Yanli Tan Chuan Fang School of Clinical Medicine Hebei UniversityDepartment of NeurosurgeryAffiliated Hospital of Hebei UniversityBaoding 07100China Hebei Key Laboratory of Precise diagnosis and Treatment of Glioma Baoding 071000China School of Basic Medical Sciences Hebei UniversityBaoding 07100China department of pathology Affiliated Hospital of Hebei UniversityBaoding 07100China

Among central nervous system-associated malignancies,glioblastoma(GBM)is the most common and has the highest mortality *** high heterogeneity of GBM cell types and the complex tumor microenvironment frequently lead to tumor recurrence and sudden relapse in patients treated with *** precision medicine,research on GBM treatment is increasingly focusing on molecular subtyping to precisely characterize the cellular and molecular heterogeneity,as well as the refractory nature of GBM toward *** understanding of the different molecular expression patterns of GBM subtypes is *** have recently proposed tetra fractional or tripartite methods for detecting GBM molecular *** various molecular subtypes of GBM show significant differences in gene expression patterns and biological *** subtypes also exhibit high plasticity in their regulatory pathways,oncogene expression,tumor microenvironment alterations,and differential responses to standard ***,we summarize the current molecular typing scheme of GBM and the major molecular/genetic characteristics of each ***,we review the mesenchymal transition mechanisms of GBM under various regulators.

关键词： Glioblastoma molecular phenotype classification characteristic mesenchymal transition

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Dysbiosis of oral and gut microbiota and its association with metabolites in patients with different degrees of coronary artery stenosis

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Chinese Medical Journal 2024年第9期137卷 1121-1123页

作者： Zekun Wang Long Li Chenyang Wang Qian Wang Fengzhi Wang Xin Xu Xuedong Zhou State Key Laboratory of oral Diseases and National Clinical Research Center for oral Diseases West China Hospital of StomatologySichuan UniversityChengduSichuan 610041China department of Cariology and Endodontics West China Hospital of StomatologySichuan UniversityChengduSichuan 610041China department of Cardiology Shanxi Provincial Key Laboratory of Cardiovascular Disease DiagnosisTreatment and Clinical PharmacologyThe Second Hospital of Shanxi Medical UniversityTaiyuanShanxi 030001China

To the Editor:Coronary atherosclerotic heart disease(CAD)arises from coronary atherosclerosis(CAS)plaque buildup,resulting in coronary stenosis(CS)and occlusion,ultimately causing myocardial ischemia,hypoxia,or *** showed that the high-grade CS may be an important predictor of ST segment elevation myocardial infarction in subsequent months.

关键词： coronary stenosis occlusion

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