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Fully automatic AI segmentation of oral surgery-related tissues based on cone beam computed tomography images

International Journal of Oral Science 2024年第3期16卷 413-424页

作者： Yu Liu Rui Xie Lifeng Wang Hongpeng Liu Chen Liu Yimin Zhao Shizhu Bai Wenyong Liu Beijing Yakebot Technology Co. Ltd.BeijingChina School of Mechanical Engineering and Automation Beihang UniversityBeijingChina State Key laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Key Laboratory of StomatologyDigital CenterSchool of StomatologyThe Fourth Military Medical UniversityXi’anChina Key laboratory of Biomechanics and Mechanobiology of the Ministry of Education Beijing Advanced Innovation Center for Biomedical EngineeringSchool of Biological Science and Medical EngineeringBeihang UniversityBeijingChina

Accurate segmentation of oral surgery-related tissues from cone beam computed tomography(CBCT)images can significantly accelerate treatment planning and improve surgical *** this paper,we propose a fully automated tissue segmentation system for dental implant ***,we propose an image preprocessing method based on data distribution histograms,which can adaptively process CBCT images with different *** on this,we use the bone segmentation network to obtain the segmentation results of alveolar bone,teeth,and maxillary *** use the tooth and mandibular regions as the ROI regions of tooth segmentation and mandibular nerve tube segmentation to achieve the corresponding *** tooth segmentation results can obtain the order information of the *** corresponding experimental results show that our method can achieve higher segmentation accuracy and efficiency compared to existing *** average Dice scores on the tooth,alveolar bone,maxillary sinus,and mandibular canal segmentation tasks were 96.5%,95.4%,93.6%,and 94.8%,*** results demonstrate that it can accelerate the development of digital dentistry.

关键词： surgery CBCT beam

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Degradation of FAK-targeting by proteolytic targeting chimera technology to inhibit the metastasis of hepatocellular carcinoma

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Oncology research 2024年第4期32卷 679-690页

作者： XINFENG ZHANG SHUANG LI MEIRU SONG YUE CHEN LIANGZHENG CHANG ZHERUI LIU HONGYUAN DAI YUTAO WANG GANGQI YANG YUN JIANG YINYING LU The PLA 307 clinical College of Anhui medical University The Fifth Clinical Medical College of Anhui Medical UniversityHefei230032China Liver Tumor Diagnosis and research center 5th Medical Center of the PLA General HospitalBeijing100039China Department of Infection Diseases Guizhou Medical UniversityGuiyang550025China 4302 clinical medical School Peking UniversityBeijingChina Cell and Gene Therapy Innovation center Beijing Lotuslake BiomedicalScience and Technology ParkBeijing102206China State Key laboratory of Chemical Oncogenomics and the Institute of Biopharmaceutical and Health Engineering(iBHE) Shenzhen International Graduate SchoolTsinghua UniversityShenzhen518055China

Liver cancer is a prevalent malignant cancer,ranking third in terms of mortality *** and recurrence primarily contribute to the high mortality rate of liver *** carcinoma(HCC)has low expression of focal adhesion kinase(FAK),which increases the risk of metastasis and ***,the efficacy of FAK phosphorylation inhibitors is currently ***,investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC *** study examined the correlation between FAK expression and the prognosis of ***,we explored the impact of FAK degradation on HCC metastasis through wound healing experiments,transwell invasion experiments,and a xenograft tumor *** expression of proteins related to epithelial-mesenchymal transition(EMT)was measured to elucidate the underlying *** results showed that FAK PROTAC can degrade FAK,inhibit the migration and invasion of HCC cells in vitro,and notably decrease the lung metastasis of HCC in *** expression of E-cadherin and decreased expression of vimentin indicated that EMT was ***,degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis,holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.

关键词： Hepatocellular carcinoma(HCC) Focal adhesion kinase(FAK) Proteolytic targeting chimera technology(PROTAC) Epithelial-mesenchymal transformation(EMT) Metastasis

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Beyond ribosomal function:RPS6 deficiency suppresses cholangiocarcinoma cell growth by disrupting alternative splicing

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Acta Pharmaceutica Sinica B 2024年第9期14卷 3931-3948页

作者： Wenkang Fu Yanyan Lin Mingzhen Bai Jia Yao Chongfei Huang Long Gao Ningning Mi Haidong Ma Liang Tian Ping Yue Yong Zhang Jinduo zhang Yanxian Ren Liyun Ding Lunzhi Dai Joseph WLeung Jinqiu Yuan Wenhua Zhang Wenbo Meng The First School of clinical Medicne Lanzhou UniversityLanzhou 730030China Department of General Surgery the First Hospital of Lanzhou UniversityLanzhou 730030China Key laboratory of Biotherapy and Regenerative Medicine of Gansu Province the First Hospital of Lanzhou UniversityLanzhou 730000China School of Physical Science and Technology Lanzhou UniversityLanzhou 730000China National clinical research center for Geriatrics and Department of General Practice State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Division of Gastroenterology UC Davis Medical Center and Sacramento VA Medical CenterSacramentoCA 95817USA clinical research center Big Data Centerthe Seventh Affiliated HospitalSun Yat-sen UniversityShenzhen 518107China School of Life Sciences Lanzhou UniversityLanzhou 730000China

Cholangiocarcinoma(CCA)is a bile duct malignancy with a dismal *** study systematically investigated the role of the ribosomal protein S6(RPS6)gene,which is dependent in *** found that RPS6 upregulation in CCA tissues was correlated with a poor *** investigations have shown that alterations in RPS6 expression,both gain-and loss-of function could affect the proliferation of CCA *** xenograft tumor models,RPS6 overexpression enhances tumorigenicity,whereas RPS6 silencing reduces *** analysis using RNA-seq and proteomics elucidated downstream signaling pathways of RPS6 depletion by affecting the cell cycle,especially DNA *** followed by mass spectrometry has identified numerous spliceosome complex proteins associated with *** profiling revealed that RPS6 affects numerous alternative splicing(AS)events,and combined with RNA immunoprecipitation sequencing,revealed that minichromosome maintenance complex component 7(MCM7)binds to RPS6,which regulates its AS and increases oncogenic activity in *** RPS6 with vivo phosphorodiamidate morpholino oligomer(V-PMO)significantly inhibited the growth of CCA cells,patient-derived organoids,and subcutaneous xenograft *** together,the data demonstrate that RPS6 is an oncogenic regulator in CCA and that RPS6-V-PMO could be repositioned as a promising strategy for treating CCA.

关键词： Cholangiocarcinoma Ribosomal protein S6 Alternative splicing p53 Minichromosome maintenance complex component 7 Vivo morpholino Patient-derived organoids

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Immunoglobulin G-mediated food intolerance and metabolic syndrome influence the occurrence of reflux esophagitis in Helicobacter pylori-infected patients

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World Journal of Gastroenterology 2024年第8期30卷 855-862页

作者： Li-Hui Wang Bin-Bin Su Sheng-Shu Wang Guan-Chao Sun Kun-Ming Lv Yi Li Hui Shi Qian-Qian Chen College Chinese PLA General HospitalBeijing 100853China Department of Gastroenterology Second Medical Center of Chinese PLA General HospitalBeijing 100853China Institute of Geriatrics The 2nd Medical CenterBeijing Key Laboratory of Aging and GeriatricsNational Clinical Research Center for Geriatrics DiseasesSecond Medical Center of Chinese PLA General HospitalBeijing 100853China Department of Gastroenterology First Medical Center of Chinese PLA General HospitalBeijing 100853China

BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse *** its risk factors is crucial to understanding the etiology,prevention,and management of the *** occurrence of reflux esophagitis may be associated with food reactions,Helicobacter pylori(***)infection,and metabolic *** To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin(Ig)G-mediated food intolerance,*** infection,and metabolic syndrome on reflux *** Outpatients attending the Second medical center of the PLA General Hospital between 2017 and 2021 were retrospectively *** patients’basic information,test results,gastroscopy results,*** test results,and IgG-mediated food intolerance results were *** logistic regression analysis was used to analyze risk factors for reflux *** mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on *** infection affecting reflux *** A total of 7954 outpatients were included;the prevalence of reflux esophagitis,IgG-mediated food intolerance,*** infection,and metabolic syndrome were 20.84%,61.77%,35.91%,and 60.15%,*** analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance(OR=1.688,95%CI:1.497-1.903,P<0.00001)and metabolic syndrome(OR=1.165,95%CI:1.030-1.317,P=0.01484),and the independent protective factor for reflux esophagitis was *** infection(OR=0.400,95%CI:0.351-0.456,P<0.00001).IgG-mediated food intolerance had a partially positive mediating effect on *** infection as it was associated with reduced occurrence of reflux esophagitis(P=0.0200).Metabolic syndrome had a partially negative mediating effect on *** infection and reduced the occurrence of reflux esophagitis(P=0.0220).CONCLUSION Patients with IgG-mediated food intol

关键词： Gastroesophageal reflux Esophagitis Food intolerance Metabolic syndrome Helicobacter pylori Chemokines

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New insights shed light on the enigma of genetic diversity and species complexity

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Science China Life Sciences 2024年

作者： Zuobin Zhu Conghui Han Shi Huang Xuzhou Engineering research center of medical Genetics and Transformation Key Laboratory of Genetic Foundation and Clinical Application Xuzhou Medical University Department of Urology Xuzhou Clinical School of Xuzhou Medical University Xuzhou Central Hospital center for medical Genetics School of Life Sciences Central South University

Genetic diversity remains poorly understood, but several recent Science papers may shed new light on this long-standing puzzle (Exposito-Alonso et al., 2022; Gao et al., 2023; Kuderna et al., 2023).Exposito-Alonso et al.(2022) demonstrated that a reduction in environmental diversity, including species habitat and living environment complexity, leads to a decrease in genetic diversity.

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Advances in the Treatment of Autoimmune Hepatitis

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Journal of clinical and Translational Hepatology 2024年第10期12卷 878-885页

作者： Zelu Meng Yida Yang State Key laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesDepartment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina

Autoimmune hepatitis(AIH)is a chronic,progressive inflammatory liver disease caused by autoimmune reactions,with an unknown *** left untreated,it can progress to cirrhosis,liver failure,or even *** most patients respond well to first-line treatments,a significant number experience poor responses or intolerance,requiring the use of second-or third-line *** research into the pathogenesis of AIH is leading to the development of novel therapeutic *** review summarized recent advancements in the treatment of AIH both domestically and internationally.

关键词： Hepatitis,Autoimmune Immunosuppression Treatment Management Update Remission Induction Long-term Prognosis

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miR-429-3p mediates memory decline by targeting MKP-1 to reduce surface GluA1- containing AMPA receptors in a mouse model of Alzheimer’s disease

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Acta Pharmaceutica Sinica B 2024年第2期14卷 635-652页

作者： Man Luo Yayan Pang Junjie Li Lilin Yi Bin Wu Qiuyun Tian Yan He Maoju Wang Lei Xia Guiqiong He Weihong Song Yehong Du Zhifang Dong Pediatric research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren’s Hospital of Chongqing Medical UniversityChongqing 400014China Department of Anatomy Basic Medical CollegeChongqing Medical UniversityChongqing 400016China Townsend Family Laboratories Department of PsychiatryThe University of British ColumbiaVancouver BC V6T 1Z3Canada Oujiang laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Institute of AgingKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceZhejiang Clinical Research Center for Mental DisordersSchool of Mental Health and the Affiliated Kangning HospitalWenzhou Medical UniversityWenzhou 325000China Institute for Brain Science and Disease of Chongqing medical University Chongqing 400016China

Alzheimer ’s disease(AD) is a leading cause of dementia in the ***-activated protein kinase phosphatase 1(MKP-1) plays a neuroprotective role in ***,the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively ***(miRNAs) regulate gene expression at the post-transcriptional level,thereby repressing mRNA ***,we reported that the microRNA-429-3p(miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPPAD model *** further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3’-untranslated region(3’ UTR).Inhibition of miR-429-3p by its antagomir(A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ *** importantly,intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase(ERK1/2)-mediated GluAl hyperphosphorylation at Ser831 site,thereby increasing the surface expression of GluAl-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors(AMPARs).Together,these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice,suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

关键词： Alzheimer's disease MKP-1 miR-429-3p AMPAreceptor Learning and memory Long-term potentiation

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Multi-omics integration reveals potential stage-specific druggable targets in T-cell acute lymphoblastic leukemia

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Genes & Diseases 2024年第5期11卷 374-389页

作者： Zijun Yan Jie Xia Ziyang Cao Hongyang Zhang Jinxia Wang Tienan Feng Yi Shu Lin Zou clinical research Unit Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200062China Institute of Pediatric Infection Immunityand Critical Care MedicineShanghai Jiao Tong University School of MedicineShanghai 200062China center for clinical Molecular laboratory Medicine of Children’s Hospital of Chongqing medical University Chongqing 400014China clinical research Institute Shanghai Jiao Tong University School of MedicineShanghai 200025China Bioinformatics and Biomedical Bigdata Mining laboratory School of Big HealthGuizhou Medical UniversityGuiyangGuizhou 554300China

T-cell acute lymphoblastic leukemia(T-ALL),a heterogeneous hematological malignancy,is caused by the developmental arrest of normal T-cell *** development of targeted therapeutic regimens is impeded by poor knowledge of the stage-specific aberrances in this *** this study,we performed multi-omics integration analysis,which included mRNA expression,chromatin accessibility,and gene-dependency database analyses,to identify potential stage-specific druggable targets and repositioned drugs for this *** multi-omics integration helped identify 29 potential pathological genes for *** genes exhibited tissue-specific expression profiles and were enriched in the cell cycle,hematopoietic stem cell differentiation,and the AMPK signaling *** these,four known druggable targets(CDK6,TUBA1A,TUBB,and TYMS)showed dysregulated and stage-specific expression in malignant T cells and may serve as stage-specific targets in *** TUBA1A expression level was higher in the early T cell precursor(ETP)-ALL cells,while TUBB and TYMS were mainly highly expressed in malignant T cells arrested at the CD4 and CD8 double-positive or single-positive ***6 exhibited a U-shaped expression pattern in malignant T cells along the naıve to maturation ***,mebendazole and gemcitabine,which target TUBA1A and TYMS,respectively,exerted stage-specific inhibitory effects on T-ALL cell lines,indicating their potential stage-specific antileukemic role in ***,our findings might aid in identifying potential stage-specific druggable targets and are promising for achieving more precise therapeutic strategies for T-ALL.

关键词： Multi-omics Stage-specific druggable targets Targeted therapeutic strategies T-cell acute lymphoblastic leukemia Drug repositioning

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SRY-Box transcription factor 9 triggers YAP nuclear entry via direct interaction in tumors

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2285-2297页

作者： Hui Qian Chen-Hong Ding Fang Liu Shi-Jie Chen Chen-Kai Huang Meng-Chao Xiao Xia-Lu Hong Ming-Chen Wang Fang-Zhi Yan Kai Ding Ya-Lu Cui Bai-Nan Zheng Jin Ding Cheng Luo Xin Zhang Wei-Fen Xie Department of Gastroenterology Changzheng HospitalNaval Medical UniversityShanghaiChina Department of Gastroenterology Shanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina Drug Discovery and Design center CAS Key Laboratory of Receptor ResearchState Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina Department of Gastroenterology First Affiliated Hospital of Nanchang UniversityNanchangChina clinical Cancer Institute Center for Translational MedicineNaval Medical UniversityShanghaiChina

The translocation of YAP from the cytoplasm to the nucleus is critical for its activation and plays a key role in tumor ***,the precise molecular mechanisms governing the nuclear import of YAP are not fully *** this study,we have uncovered a crucial role of SOX9 in the activation of ***9 promotes the nuclear translocation of YAP by direct ***,we have identified that the binding between Asp-125 of SOX9 and Arg-124 of YAP is essential for SOX9-YAP interaction and subsequent nuclear entry of ***,we have discovered a novel asymmetrical dimethylation of YAP at Arg-124(YAP-R124me2a)catalyzed by ***-R124me2a enhances the interaction between YAP and SOX9 and is associated with poor prognosis in multiple ***,we disrupted the interaction between SOX9 and YAP using a competitive peptide,S-A1,which mimics anα-helix of SOX9 containing Asp-125.S-A1 significantly inhibits YAP nuclear translocation and effectively suppresses tumor *** study provides the first evidence of SOX9 as a pivotal regulator driving YAP nuclear translocation and presents a potential therapeutic strategy for YAP-driven human cancers by targeting SOX9-YAP interaction.

关键词： interaction interaction precise

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A biocompatible Horner-Wadsworth-Emmons(HWE)reaction triggered by a bioorthogonal proximity-induced platform

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Chinese Chemical Letters 2024年第8期35卷 217-220页

作者： Yayue Wang Haojie Yang Jie Li Qiao Kong Siming Zhou Hongbao Sun Lili Pan Qiyong Gong Ping Feng Haoxing Wu Department of Radiology and Huaxi MR research center(HMRRC) Functional and Molecular Imaging Key Laboratory of Sichuan ProvinceFrontiers Science Center for Disease Related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041China Key laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan UniversityChengdu 610041China Department of Nuclear Medicine Laboratory of Clinical Nuclear MedicineWest China HospitalSichuan UniversityChengdu 610041China Reseacrch Unit of Psychoradiology Chinese Academy of Medical SciencesChengdu 610041China Department of Pharmacy West China HospitalSichuan UniversityChengdu 610041China clinical Trial center and National medical Products Administration Key laboratory for clinical research and Evaluation of Innovative Drugs West China HospitalSichuan UniversityChengdu 610041China

Here,we present a novel bioorthogonal platform that enables precise positioning of attached moieties in close proximity,thereby facilitating the discovery and optimization of biocompatible *** this platform,we achieve a Horner-Wadsworth-Emmons(HWE)reaction under physiological conditions,generating a fluorophore in situ with a yield of up to 93%.This proximity platform should facilitate the discovery of various types of biocompatible reactions,making it a versatile tool for biomedical applica-tions.

关键词： Biocompatible reactions Horner-Wadsworth-Emmons reaction Bioorthogonal reactions Tetrazines Proximity effects

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