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Sirt5 desuccinylates Cdc42 to mediate osteoclastogenesis and bone remodeling in mice

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Genes & Diseases 2024年第3期11卷 75-78页

作者： Yuang Zhanngg Jing Wang Jing Luan Chuanju Liu Yazhou Cui Jinxiang Han department of Orthopedics The First Affiliated Hospital of Shandong First Medical University&Shandong Provincial Qianfoshan HospitalJi'nanShandong 250014China Biomedical Sciences College&Shandong Medicinal biotechnology Centre Shandong First Medical University&Shandong Academy of Medical SciencesJi'nanShandong 250117China NHC Key Laboratory of biotechnology Drugs(Shandong Academy of medical Sciences) Ji'nanShandong 250117China Key Lab for Rare&Uncommon Diseases of Shandong Province Ji'nanShandong250117China department of Orthopaedic Surgery New York University Grossman School of MedicineNew YorkNY 10003USA department of Cell Biology New York University Grossman School of MedicineNewYorkNY10016USA

Post-translational modifications(PTMs)play a critical role in bone remodeling,with phosphorylation and acetylation being particularly well characterized.Recently,succinylation,a relatively uncommon PTM on lysine,has received considerable research attention for its influence on several physiological and pathological processes and conditions.1 Several substrates involved in mitochondrial pathways have been validated as substrates for the desuccinylase sirtuin 5(Sirt5),a key regulator of succinylation.2 Bone is one of the most metabolically active organs,but the role of succinylation during bone remodeling is not well characterized.

关键词： remodeling organs media

Does progress in microfracture techniques necessarily translate into clinical effectiveness?

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World Journal of Orthopedics 2024年第3期15卷 266-284页

作者： Sathish Muthu Vibhu Krishnan Viswanathan Manoharan Sakthivel Mohammed Thabrez department of Orthopaedics Orthopaedic Research GroupCoimbatore 641045Tamil NaduIndia department of biotechnology Karpagam Academy of Higher EducationCoimbatore 641021Tamil NaduIndia Manoharan Sakthivel Department of OrthopaedicsGovernment Medical CollegeKarur 639004Tamil NaduIndia department of Orthopaedics Devadoss Multispecialty HospitalMadurai 625007Tamil NaduIndia department of medical Oncology Aster Medcity HospitalKochi 682034India

BACKGROUND Multitudinous advancements have been made to the traditional microfracture(MFx)technique,which have involved delivery of various acellular 2nd generation MFx and cellular MFx-III components to the area of cartilage defect.The relative benefits and pitfalls of these diverse modifications of MFx technique are still not widely understood.AIM To comparatively analyze the functional,radiological,and histological outcomes,and complications of various generations of MFx available for the treatment of cartilage defects.METHODS A systematic review was performed using PubMed,EMBASE,Web of Science,Cochrane,and Scopus.Patients of any age and sex with cartilage defects undergoing any form of MFx were considered for analysis.We included only randomized controlled trials(RCTs)reporting functional,radiological,histological outcomes or complications of various generations of MFx for the management of cartilage defects.Network meta-analysis(NMA)was conducted in Stata and Cochrane’s Confidence in NMA approach was utilized for appraisal of evidence.RESULTS Forty-four RCTs were included in the analysis with patients of mean age of 39.40(±9.46)years.Upon comparing the results of the other generations with MFX-I as a constant comparator,we noted a trend towards better pain control and functional outcome(KOOS,IKDC,and Cincinnati scores)at the end of 1-,2-,and 5-year time points with MFx-III,although the differences were not statistically significant(P>0.05).We also noted statistically significant Magnetic resonance observation of cartilage repair tissue score in the higher generations of microfracture(weighted mean difference:17.44,95%confidence interval:0.72,34.16,P=0.025;without significant heterogeneity)at 1 year.However,the difference was not maintained at 2 years.There was a trend towards better defect filling on MRI with the second and third generation MFx,although the difference was not statistically significant(P>0.05).CONCLUSION The higher generations of traditional MFx technique utilizing acellular and cellular comp

关键词： Cartilage injury Microfracture Mesenchymal stem cells Platelet-rich plasma Bone marrow aspiration concentrates Clinical outcome Radiological outcome Meta-analysis Network meta-analysis

Activatable fluorescent probes for imaging and diagnosis of rheumatoid arthritis

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Military medical Research 2024年第2期11卷 287-307页

作者： Pan Luo Fu-Qiang Gao Wei Sun Jun-You Li Cheng Wang Qing-Yu Zhang Zhi-Zhuo Li Peng Xu department of Joint Surgery Honghui HospitalXi'an Jiaotong UniversityXi'an 710054China department of Orthopedics China-Japan Friendship HospitalBeijing 100029China department of Orthopaedic Surgery of the Perelman School of Medicine University of PennsylvaniaPhiladelphiaPA 19104USA School of Mechanical engineering Sungkyunkwan UniversitySuwon 16419South Korea department of Orthopaedic Surgery Peking University Third HospitalPeking UniversityBeijing 100191China department of Orthopedics Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021China State Key Laboratory of Pharmaceutical biotechnology Division of Sports Medicine and Adult Reconstructive SurgeryDepartment of Orthopedic SurgeryNanjing Drum Tower Hospitalthe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China

Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.

关键词： Rheumatoid arthritis Fluorescent probe Imaging Diagnosis Biomarker

Recent advances of mechanosensitive genes in vascular endothelial cells for the formation and treatment of atherosclerosis

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Genes & Diseases 2024年第3期11卷 206-219页

作者： Shuyu Li Zichen Xu Yi Wang Lizhao Chen Xiangxiu Wang Yanghao Zhou Daoxi Lei Guangchao Zang Guixue Wang Key Laboratory of Biorheological Science and Technology of Ministry of Education National and Local Joint Engineering Laboratory for Vascular ImplantsBioengineering College of Chongqing UniversityChongqing 400030China College of Basic medical Sciences Chongqing Medical UniversityChongqing 400016China department of Neurosurgery Daping HospitalArmy Medical Center of PLAArmy Medical UniversityChongqing 400042China

Atherosclerotic cardiovascular disease and its complications are a high-incidence disease worldwide.Numerous studies have shown that blood flow shear has a huge impact on the function of vascular endothelial cells,and it plays an important role in gene regulation of pro-inflammatory,pro-thrombotic,pro-oxidative stress,and cell permeability.Many impor-tant endothelial cell mechanosensitive genes have been discovered,including KLK10,CCN gene family,NRP2,YAP,TAZ,HIF-1α,NF-kB,FOS,JUN,TFEB,KLF2/KLF4,NRF2,and ID1.Some of them have been intensively studied,whereas the relevant regulatory mechanism of other genes remains unclear.Focusing on these mechanosensitive genes will provide new strategies for therapeutic intervention in atherosclerotic vascular disease.Thus,this article reviews the mechanosensitive genes affecting vascular endothelial cells,including classical pathways and some newly screened genes,and summarizes the latest research progress on their roles in the pathogenesis of atherosclerosis to reveal effective therapeutic targets of drugs and provide new insights foranti-atherosclerosis.

关键词： Atherosclerosis Blood flow Endothelial cell Mechanosensitive gene Therapeutic target

The activity and immune dynamics of PD-1 inhibition on high-risk pulmonary ground glass opacity lesions:insights from a single-arm,phase II trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2202-2214页

作者： Bo Cheng Caichen Li Jianfu Li Longlong Gong Peng Liang Ying Chen Shuting Zhan Shan Xiong Ran Zhong Hengrui Liang Yi Feng Runchen Wang Haixuan Wang Hongbo Zheng Jun Liu Chengzhi Zhou Wenlong Shao Yuan Qiu Jiancong Sun Zhanhong Xie Zhu Liang Chenglin Yang Xiuyu Cai Chunxia Su Wei Wang Jianxing He Wenhua Liang department of Thoracic Surgery and Oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina medical department Genecast Biotechnology Co.LtdWuxiChina department of Radiation Oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina department of Respiratory Medicine the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina department of Cardiothoracic Surgery Affiliated Hospital of Guangdong Medical UniversityZhanjiangChina department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenChina department of VIP Inpatient Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaSun Yat-sen UniversityGuangzhouChina department of medical Oncology Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina

Immune checkpoint inhibitors targeting the programmed cell death-1(PD-1)protein significantly improve survival in patients with advanced non-small-cell lung cancer(NSCLC),but its impact on early-stage ground-glass opacity(GGO)lesions remains unclear.This is a single-arm,phase II trial(NCT04026841)using Simon’s optimal two-stage design,of which 4 doses of sintilimab(200 mg per 3 weeks)were administrated in 36 enrolled multiple primary lung cancer(MPLC)patients with persistent high-risk(Lung-RADS category 4 or had progressed within 6 months)GGOs.The primary endpoint was objective response rate(ORR).T/B/NK-cell subpopulations,TCR-seq,cytokines,exosomal RNA,and multiplexed immunohistochemistry(mIHC)were monitored and compared between responders and non-responders.Finally,two intent-to-treat(ITT)lesions(pure-GGO or GGO-predominant)showed responses(ORR:5.6%,2/36),and no patients had progressive disease(PD).No grade 3-5 TRAEs occurred.The total response rate considering two ITT lesions and three non-intent-to-treat(NITT)lesions(pure-solid or solid-predominant)was 13.9%(5/36).The proportion of CD8^(+)T cells,the ratio of CD8^(+)/CD4^(+),and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over time.Correspondingly,the mIHC analysis showed more CD8^(+)T cells infiltrated in responders.Besides,responders’cytokine concentrations of EGF and CTLA-4 increased during treatment.The exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among responders.Collectively,PD-1 inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety concerns.Such effects were associated with specific T-cell re-distribution,EGF/CTLA-4 cytokine compensation,and regulation of metabolism pathways.

关键词： lesions metabolism doses

Effects of Bisphenol A and Its Substitute, Bisphenol F, on the Gut Microbiota in Mice

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Biomedical and Environmental Sciences 2024年第1期37卷 19-30页

作者： MENG Li Ying TAO Wen Fu LI Jing ZHU Min ZHONG De Bin ZHOU Jing QIN Xue WEI Rong Guo department of Clinical Laboratory The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021GuangxiChina department of Clinical Laboratory The Fifth Affiliated Hospital of Guangxi Medical UniversityNanning 530021GuangxiChina Jiangsu Key Laboratory of Environmental engineering Jiangsu Academy of Environmental SciencesNanjing 210000JiangsuChina

Objective The aim of this study was to assess the impact of bisphenol A(BPA)and its substitute,bisphenol F(BPF),on the colonic fecal community structure and function of mice.Methods We exposed 6–8-week-old male C57BL/6 mice to 5 mg/(kg∙day)and 50μg/(kg∙day)of BPA or BPF for 14 days.Fecal samples from the colon were analyzed using 16S rRNA sequencing.Results Gut microbiome community richness and diversity,species composition,and function were significantly altered in mice exposed to BPA or BPF.This change was characterized by elevated levels of Ruminococcaceae UCG-010 and Oscillibacter and decreased levels of Prevotella 9 and Streptococcus.Additionally,pathways related to carbohydrate and amino acid metabolism showed substantial enrichment.Conclusion Mice exposed to different BP analogs exhibited distinct gut bacterial community richness,composition,and related metabolic pathways.Considering the essential role of gut bacteria in maintaining intestinal homeostasis,our study highlights the intestinal toxicity of BPs in vertebrates.

关键词： Bisphenol A(BPA) Bisphenol F(BPF) 16S rRNA Microbiota

A modular microfluidic platform to study how fluid shear stress alters estrogen receptor phenotype in ER+breast cancer cells

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Microsystems & Nanoengineering 2024年第1期10卷 287-299页

作者： Braulio Andrés Ortega Quesada Jonathan Cuccia Rachael Coates Blake Nassar Ethan Littlefield Elizabeth C.Martin Adam T.Melvin Cain department of Chemical engineering Louisiana State UniversityBaton RougeLA 70803USA department of Chemical and Biological engineering Clemson UniversityClemsonSC 29634USA Biological and Agricultural engineering Louisiana State UniversityBaton RougeLA 70803USA department Medicine Section Hematology and Medical OncologyTulane UniversityNew OrleansLA 70118USA

Metastatic breast cancer leads to poor prognoses and worse outcomes in patients due to its invasive behavior and poor response to therapy.It is still unclear what biophysical and biochemical factors drive this more aggressive phenotype in metastatic cancer;however recent studies have suggested that exposure to fluid shear stress in the vasculature could cause this.In this study a modular microfluidic platform capable of mimicking the magnitude of fluid shear stress(FSS)found in human vasculature was designed and fabricated.This device provides a platform to evaluate the effects of FSS on MCF-7 cell line,an estrogen receptor positive(ER+)breast cancer cell line,during circulation in the vessels.Elucidation of the effects of FSS on MCF-7 cells was carried out utilizing two approaches:single cell analysis and bulk analysis.For single cell analysis,cells were trapped in a microarray after exiting the serpentine channel and followed by immunostaining on the device(on-chip).Bulk analysis was performed after cells were collected in a microtube at the outlet of the microfluidic serpentine channel for western blotting(off-chip).It was found that cells exposed to an FSS magnitude of 10 dyn/cm^(2) with a residence time of 60 s enhanced expression of the proliferation marker Ki67 in the MCF-7 cell line at a single cell level.To understand possible mechanisms for enhanced Ki67 expression,on-chip and off-chip analyses were performed for pro-growth and survival pathways ERK,AKT,and JAK/STAT.Results demonstrated that after shearing the cells phosphorylation of p-AKT,p-mTOR,and p-STAT3 were observed.However,there was no change in p-ERK1/2.AKT is a mediator of ER rapid signaling,analysis of phosphorylated ERαwas carried out and no significant differences between sheared and non-sheared populations were observed.Taken together these results demonstrate that FSS can increase phosphorylation of proteins associated with a more aggressive phenotype in circulating cancer cells.These findings provide additional information that may help

关键词： fluid breast estrogen

Method for the extraction of circulating nucleic acids based on MOF reveals cell-free RNA signatures in liver cancer

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National Science Review 2024年第1期11卷 94-106页

作者： Yuqing Sun Haixin Yu Shaoqing Han Ruoxi Ran Ying Yang Yongling Tang Yuhao Wang Wenhao Zhang Heng Tang Boqiao Fu Boshi Fu Xiaocheng Weng Song-Mei Liu Hexiang Deng Shuang Peng Xiang Zhou College of Chemistry and Molecular Sciences Key Laboratory of Biomedical Polymers-Ministry of Education Wuhan University department of Digestive Surgical Oncology Union Hospital Tongji Medical College Huazhong University of Science and Technology Cancer Center Union HospitalTongji Medical CollegeHuazhong University of Science and Technology department of Clinical Laboratory Center for Gene Diagnosis and Program of Clinical Laboratory Zhongnan Hospital of Wuhan University College of Chemistry and Materials Science Hubei Engineering University department of Pharmacology School of Pharmacy China Medical University Taikang Center for Life and medical Sciences Wuhan University department of Hematology Zhongnan Hospital of Wuhan University

Cell-free RNA(cf RNA) allows assessment of health, status, and phenotype of a variety of human organs and is a potential biomarker to non-invasively diagnose numerous diseases. Nevertheless, there is a lack of highly efficient and bias-free cf RNA isolation technologies due to the low abundance and instability of cf RNA.Here, we developed a reproducible and high-efficiency isolation technology for different types of cell-free nucleic acids(containing cf RNA and viral RNA) in serum/plasma based on the inclusion of nucleic acids by metal-organic framework(MOF) materials, which greatly improved the isolation efficiency and was able to preserve RNA integrity compared with the most widely used research kit method. Importantly, the quality of cf RNA extracted by the MOF method is about 10-fold that of the kit method, and the MOF method isolates more than three times as many different RNA types as the kit method. The whole transcriptome mapping characteristics of cf RNA in serum from patients with liver cancer was described and a cf RNA signature with six cf RNAs was identified to diagnose liver cancer with high diagnostic efficiency(area under curve = 0.905 in the independent validation cohort) using this MOF method. Thus, this new MOF isolation technique will advance the field of liquid biopsy, with the potential to diagnose liver cancer.

关键词： MOF circulating cell-free RNA biomarker liver cancer diagnosis

Early Detection of Colletotrichum Kahawae Disease in Coffee Cherry Based on Computer Vision Techniques

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Computer Modeling in engineering & Sciences 2024年第4期139卷 759-782页

作者： Raveena Selvanarayanan Surendran Rajendran Youseef Alotaibi department of Computer Science and engineering Saveetha School of EngineeringSaveetha Institute of Medical and Technical ScienceChennai602105India department of Computer Science College of Computer and Information SystemsUmm Al-Qura UniversityMakkah21955Saudi Arabia

Colletotrichum kahawae(Coffee Berry Disease)spreads through spores that can be carried by wind,rain,and insects affecting coffee plantations,and causes 80%yield losses and poor-quality coffee beans.The deadly disease is hard to control because wind,rain,and insects carry spores.Colombian researchers utilized a deep learning system to identify CBD in coffee cherries at three growth stages and classify photographs of infected and uninfected cherries with 93%accuracy using a random forest method.If the dataset is too small and noisy,the algorithm may not learn data patterns and generate accurate predictions.To overcome the existing challenge,early detection of Colletotrichum Kahawae disease in coffee cherries requires automated processes,prompt recognition,and accurate classifications.The proposed methodology selects CBD image datasets through four different stages for training and testing.XGBoost to train a model on datasets of coffee berries,with each image labeled as healthy or diseased.Once themodel is trained,SHAP algorithmto figure out which features were essential formaking predictions with the proposed model.Some of these characteristics were the cherry’s colour,whether it had spots or other damage,and how big the Lesions were.Virtual inception is important for classification to virtualize the relationship between the colour of the berry is correlated with the presence of disease.To evaluate themodel’s performance andmitigate excess fitting,a 10-fold cross-validation approach is employed.This involves partitioning the dataset into ten subsets,training the model on each subset,and evaluating its performance.In comparison to other contemporary methodologies,the model put forth achieved an accuracy of 98.56%.

关键词： Computer vision coffee berry disease colletotrichum kahawae XG boost shapley additive explanations