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Prediction of cell-cell communication patierns of dorsal root ganglion cells: single-cell RNA sequencing data analysis

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Neural Regeneration Research 2024年第6期19卷 1367-1374页

作者： Yanna Lian Cheng Wu Li Liu Xiangyao Li National Health Commission and Chinese Academy of medical sciences Key Laboratory of medical Neurobiology Ministry of Education Frontier Science Center for Brain Research and Brain-Machine Integration School of Brain Science and Brain Medicine Zhejiang University International Institutes of Medicine the Fourth Affiliated Hospital of Zhejiang University School of Medicine Zhejiang University-University of edinburgh Institute Zhejiang University School of Medicine Zhejiang University 4. Biomedical Sciences College of Medicine and Veterinary Medicine The University of Edinburgh Core Facilities of the school of Medicine Zhejiang University

Dorsal root ganglion neurons transmit peripheral somatic information to the central nervous system, and dorsal root ganglion neuron excitability affects pain perception. Dorsal root ganglion stimulation is a new approach for managing pain sensation. Knowledge of the cell-cell communication among dorsal root ganglion cells may help in the development of new pain and itch management strategies. Here, we used the single-cell RNA-sequencing(scRNA-seq) database to investigate intercellular communication networks among dorsal root ganglion cells. We collected scRNA-seq data from six samples from three studies, yielding data on a total of 17,766 cells. Based on genetic profiles, we identified satellite glial cells, Schwann cells, neurons, vascular endothelial cells, immune cells, fibroblasts, and vascular smooth muscle cells. Further analysis revealed that eight types of dorsal root ganglion neurons mediated proprioceptive, itch, touch, mechanical, heat, and cold sensations. Moreover, we predicted several distinct forms of intercellular communication among dorsal root ganglion cells, including cell-cell contact, secreted signals, extracellular matrix, and neurotransmitter-mediated signals. The data mining predicted that Mrgpra3-positive neurons robustly express the genes encoding the adenosine Adora2b(A2B) receptor and glial cell line-derived neurotrophic factor family receptor alpha 1(GFRα-1). Our immunohistochemistry results confirmed the coexpression of the A2B receptor and GFRα-1. Intrathecal injection of the A2B receptor antagonist PSB-603 effectively prevented histamine-induced scratching behaviour in a dose-dependent manner. Our results demonstrate the involvement of the A2B receptor in the modulation of itch sensation. Furthermore, our findings provide insight into dorsal root ganglion cell-cell communication patterns and mechanisms. Our results should contribute to the development of new strategies for the regulation of dorsal root ganglion excitability.

关键词： cell-cell communications CellChat dorsal root ganglion scRNA-Seq database

A novel medical image data protection scheme for smart healthcare system

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CAAI Transactions on Intelligence Technology 2024年第4期9卷 821-836页

作者： Mujeeb Ur Rehman Arslan Shafique Muhammad Shahbaz Khan Maha Driss Wadii Boulila Yazeed Yasin Ghadi Suresh Babu Changalasetty Majed Alhaisoni Jawad Ahmad school of Computer Science and Informatics Cyber Technology InstituteDe Montfort UniversityLeicesterUK Department of biomedical Engineering University of GlasgowGlasgowUK school of Computing Engineering and the Built EnvironmentEdinburgh Napier UniversityEdinburghUK Robotics and Internet‐of‐Things Laboratory Prince Sultan UniversityRiyadhSaudi Arabia Department of Computer Science Al Ain UniversityAl AinUnited Arab Emirates Department of Computer Engineering College of Computer Science King Khalid UniversityAbhaSaudi Arabia Computer sciences Department College of Computer and Information SciencesPrincess Nourah bint Abdulrahman UniversityRiyadhSaudi Arabia

The Internet of Multimedia Things(IoMT)refers to a network of interconnected multimedia devices that communicate with each other over the ***,smart healthcare has emerged as a significant application of the IoMT,particularly in the context of knowledge‐based learning *** healthcare systems leverage knowledge‐based learning to become more context‐aware,adaptable,and auditable while maintain-ing the ability to learn from historical *** smart healthcare systems,devices capture images,such as X‐rays,Magnetic Resonance *** security and integrity of these images are crucial for the databases used in knowledge‐based learning systems to foster structured decision‐making and enhance the learning abilities of ***,in knowledge‐driven systems,the storage and transmission of HD medical images exert a burden on the limited bandwidth of the communication channel,leading to data trans-mission *** address the security and latency concerns,this paper presents a lightweight medical image encryption scheme utilising bit‐plane decomposition and chaos *** results of the experiment yield entropy,energy,and correlation values of 7.999,0.0156,and 0.0001,*** validates the effectiveness of the encryption system proposed in this paper,which offers high‐quality encryption,a large key space,key sensitivity,and resistance to statistical attacks.

关键词： data analysis medical image processing security

Development of biomedical hydrogels for rheumatoid arthritis treatment

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Asian Journal of Pharmaceutical sciences 2024年第1期19卷 35-48页

作者： Mirza Muhammad Faran Ashraf Baig Lee KiWong Abdul Wasy Zia Hongkai Wu Department of Chemistry Hong Kong University of Science and TechnologyHong Kong 999077China Institute of Mechanical Process and Energy Engineering(IMPEE)School of Engineering and Physical SciencesHeriot-Watt UniversityEdinburghUnited Kingdom

Rheumatoid Arthritis(RA)is an autoimmune disorder that hinders the normal functioning of bones and joints and reduces the quality of human *** year,millions of people are diagnosed with RA worldwide,particularly among elderly individuals and ***,there is a global need to develop new biomaterials,medicines and therapeutic methods for treating *** will improve the Healthcare Access and Quality Index and also relieve administrative and financial burdens on healthcare service providers at a global *** are soft and cross-linked polymeric materials that can store a chunk of fluids,drugs and biomolecules for hydration and therapeutic *** are biocompatible and exhibit excellent mechanical properties,such as providing elastic cushions to articulating joints by mimicking the natural synovial ***,hydrogels create a natural biological environment within the synovial cavity to reduce autoimmune reactions and *** also lubricate the articulating joint surfaces to prevent degradation of synovial surfaces of bones and cartilage,thus exhibiting high potential for treating *** work reviews the progress in injectable and implantable hydrogels,synthesis methods,types of drugs,advantages and ***,it discusses the role of hydrogels in targeted drug delivery,mechanistic behaviour and tribological performance for RA treatment.

关键词： Rheumatoid arthritis Orthopeadic joints Hydrogel Therapeutics Mechanical properties Medicine

TMB相关免疫浸润调控评分(MOTIF)预测免疫治疗响应并指导联合增效

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Science Bulletin 2024年第6期69卷 803-822页

作者：钱政宇潘艺芊李薛鑫陈衍行吴灏祥刘泽先 Martin Kosar Jiri Bartek 王梓贤徐瑞华 Department of medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangdong Provincial Clinical Research Center for CancerResearch Unit of Precision Diagnosis and Treatment for Gastrointestinal CancerChinese Academy of Medical SciencesGuangzhou 510060China Science for Life Laboratory Division of Genome BiologyDepartment of Medical Biochemistry and BiophysicsKarolinska InstituteStockholm S-17121Sweden Department of General Surgery The Fourth Affiliated HospitalChina Medical UniversityShenyang 110032China Bioinformatics Platform Sun Yat-sen University Cancer CenterGuangzhou 510060China Zhejiang University-University of edinburgh Institute Zhejiang University School of MedicineHaining 314400China edinburgh medical school Biomedical SciencesCollege of Medicine and Veterinary MedicineThe University of EdinburghEdinburgh EH11LTUK Danish Cancer Society Research Center Copenhagen DK-2100Denmark Laboratory of Artificial Intelligence and Data Science Sun Yat-sen University Cancer CenterGuangzhou 510060China

Patients with high tumor mutational burden(TMB)levels do not consistently respond to immune checkpoint inhibitors(ICIs),possibly because a high TMB level does not necessarily result in adequate infiltration of CD8^(+)T *** bulk ribonucleic acid sequencing(RNA-seq)data from 9311 tumor samples across 30 cancer types,we developed a novel tool called the modulator of TMB-associated immune infiltration(MOTIF),which comprises genes that can determine the extent of CD8^(+)T cell infiltration prompted by a certain TMB *** confirmed that MOTIF can accurately reflect the integrity and defects of the cancer-immunity *** analyzing 84 human single-cell RNA-seq datasets from 32 types of solid tumors,we revealed that MOTIF can provide insights into the diverse roles of various cell types in the modulation of CD8^(+)T cell *** pretreatment RNA-seq data from 13 ICI-treated cohorts,we validated the use of MOTIF in predicting CD8^(+)T cell infiltration and ICI *** the components of MOTIF,we identified EMC3 as a negative regulator of CD8^(+)T cell infiltration,which was validated via in vivo ***,MOTIF provided guidance for the potential combinations of programmed death 1 blockade with certain immunostimulatory drugs to facilitate CD8^(+)T cell infiltration and improve ICI efficacy.

关键词： Tumor mutational burden Immunotherapy Cancer-immunity cycle Treatment efficacy prediction CD8^(+)T cell infiltration Combination therapy

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Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

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Stroke & Vascular Neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： Jason Philip Appleton Lisa J Woodhouse Craig S Anderson Sandeep Ankolekar Lesley Cala Mark Dixon Timothy J England Kailash Krishnan Grant Mair Keith W Muir John Potter Christopher I Price Marc Randall Thompson G Robinson Christine Roffe Else C Sandset Jeffrey L Saver Angela Shone Aloysius Niroshan Siriwardena Joanna M Wardlaw Nikola Sprigg Philip M Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied HealthResearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Faculty of Medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Health Science Center BeijingChina Neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia Department of Neurology King's College Hospital NHS Foundation TrustLondonUK Faculty of Health and medical sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East Midlands Ambulance Service NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK Centre for Clinical Brain sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurology and Psychology University of GlasgowGlasgowUK Bob Champion Research and Education Building University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK Department of Neurology Leeds Teaching Hospitals NHS TrustLeedsUK Department of Cardiovascular sciences and NIHR Leicester biomedical Research Centre University of LeicesterLeicesterUK Stroke Research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK Department of Neurology Oslo University HospitalOsloNorway Research and Development Norwegian Air Ambulance FoundationOsloNorway Department of Neurology and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Research and Graduate Services University of NottinghamNottinghamUK Community and Health Research Unit University of LincolnLincolnUK

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is ***,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).Methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of *** primary outcome was a shift in scores on the modified Rankin scale(mRS)at day *** outcomes included death;a global analysis(Wei-Lachin test)containing Barthel Index,EuroQol-5D,mRS,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’*** were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%*** 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow Coma Scale 14(2)and time from onset to randomisation 67[45,108]***‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTN did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(MWD 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe *** In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital *** IS ALREADY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those w

关键词： Glasgow nitrate random

Progress towards dog-mediated rabies elimination in PR China:a scoping review

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Infectious Diseases of Poverty 2023年第2期12卷 19-35页

作者： Tianren Shen Susan Christina Welburn Long Sun Guo-Jing Yang Key Laboratory of Tropical Translational Medicine of Ministry of Education The School of Tropical MedicineThe First Affiliated HospitalHainan Medical UniversityHaikou571199HainanPeople’s Republic of China Zhejiang University-University of edinburgh Joint Institute Zhejiang UniversityInternational Campus718 East Haizhou RoadHaining314400People’s Republic of China Infection Medicine Deanery of Biomedical SciencesEdinburgh Medical SchoolCollege of Medicine and Veterinary MedicineThe University of Edinburgh1 George SquareEdinburghEH89JZScotlandUK Department of Infectious Diseases The First Affiliated Hospital of Hainan Medical UniversityHainan Medical UniversityHaikouHainanPeople’s Republic of China

Background Rabies continues to be a serious threat to global public health endangering people’s health and public health *** the People’s Republic of China,multi-sectoral and comprehensive prevention and control strategies have aimed to extensively curb human rabies ***,we examine the current state of rabies infection in China,explore strategic interventions put in place in response to WHO’s ambition of“Zero rabies deaths by 2030”and critically assess the constraints and feasibility of dog-mediated rabies elimination in *** This study analyzed and evaluated the process towards dog-mediated rabies elimination in China from five perspectives:namely,human,dog,policy,challenge,and ***-based data on progress of dog-mediated rabies elimination in China was derived from a number of sources;a literature search was undertaken using PubMed,Web of Science and CNKI databases,distribution data for human rabies cases as derived from the Data-center of the China Public Health Science and policy and document data were obtained from official websites of the relevant China ministries and *** The incidence of human rabies cases in China have shown a downward trend year-on-year since *** of a government-led,multi-sectoral“One Health”approach to combating rabies has driven down the total number of rabies deaths nationwide to around 200 in *** number of provincial-level administrative divisions(PLADs)reporting human cases of rabies has also decreased to 21 in 2020,13 of which reported less than 10 ***,the number of outpatient visits seeking rabies post-exposure prophylaxis has risen dramatically over the past two decades,with demand being 15 times higher than it was *** remain however,significant gaps in rabies elimination outcomes across the different regions of *** date the target of achieving a canine rabies vaccination rate of>75%has not been *** challenges of rabies i

关键词： Rabies Lyssavirus China Elimination Dog Epidemics One Health Neglected Tropical Underreporting

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Monkeypox:A comprehensive review of a multifaceted virus

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Infectious Medicine 2023年第2期2卷 74-88页

作者： Randa Elsheikh Abdelrahman M.Makram Tamilarasy Vasanthakumaran Shubham Tomar Khizer Shamim Nguyen Dong Tranh Sara S.Elsheikh Nguyen Thanh Van Nguyen Tien Huy deanery of biomedical sciences at edinburgh medical school University of EdinburghEdinburgh EH105HFUnited Kingdom Online Research Club(http://***) Nagasaki 852-8523Japan school of Public Health Imperial College LondonLondon SW72BXUnited Kingdom Global Clinical Scholars Research Training Harvard Medical SchoolBostonMA 02115USA Tata Memorial Hospital Varanasi 400012India DataQ Health Karachi 75100Pakistan Department of Infection Control Binh Dinh Provincial General HospitalBinh Dinh 55000Vietnam Faculty of Medicine Zagazig UniversityZagazig 44519Egypt school of Tropical Medicine and Global Health Nagasaki UniversityNagasaki 852-8523Japan

In May 2022,the world witnessed the re-emergence of the zoonotic disease *** this was not the first epidemic of this disease,what differentiated the outbreak was the rapid global spread and increase of cases,which led the WHO to declare monkeypox a global health *** the disease spreads mainly through inadequately cooked meat of various rodent species,this virus also shows droplet,respiratory,sexual,and even vertical *** further multiplies in lymphoproliferative organs and presents with a classical smallpox-like rash,fever,headache,and muscle *** is confirmed with a polymerase-chain-reaction test and is managed largely supportively with possible usage of some antivirals and ***,some pre-exposure and postexposure prophylactic vaccines have been *** paper aims to conduct an in-depth review of the historical epidemics,transmission,pathophysiology,clinical presentation,and management of the monkeypox disease.

关键词： Monkeypox Orthopoxvirus Outbreak Smallpox

YTHDF2-mediated regulations bifurcate BHPF-induced programmed cell deaths

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National Science Review 2023年第12期10卷 83-97页

作者： Jiebo Lin Guankai Zhan Jinfeng Liu Yasen Maimaitiyiming Zhiping Deng Baohua Li Kunhui Su Jiafeng Chen Siqi Sun Wanlin Zheng Xianghui Yu Feng He Xiaodong Cheng Lingfang Wang Bin Shen Ziqin Yao Xinquan Yang Jian Zhang Wentao He Hengyu Wu Hua Naranmandura Kao-Jung Chang Junxia Min Jun Ma Mikael Bj?rklund Peng-Fei Xu Fudi Wang Chih-Hung Hsu Women's Hospital The Fourth Affiliated Hospitaland Department of Environmental MedicineZhejiang University School of Medicine Institute of Genetics International School of MedicineZhejiang University The Second Affiliated Hospital School of Public Health State Key Laboratory of Experimental Hematology Zhejiang University School of Medicine Department of Hematology of First Affiliated Hospital and Department of Public Health Zhejiang University School of Medicine State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products Institute of Virology and Biotechnology Zhejiang Academy of Agricultural Sciences Department of Obstetrics Women's Hospital School of Medicine Zhejiang University Women's Hospital and Institute of Genetics Zhejiang University School of Medicine Zhejiang Provincial Key Lab of Genetic and Developmental Disorders Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women's HospitalZhejiang University School of Medicine State Key Laboratory of Reproductive Medicine Center for Global HealthGusu School Women's Hospital of Nanjing Medical University Nanjing Maternity and Child Health Care Hospital Nanjing Medical University The First Affiliated Hospital Basic Medical SciencesSchool of Public HealthSchool of Pharmaceutical Science Hengyang Medical School University of South China Department of medical Research Taipei Veterans General Hospital The First Affiliated Hospital Institute of Translational MedicineCancer Center Zhejiang University School of Medicine Zhejiang University-University of edinburgh (ZJU-UoE) Institute University of edinburgh medical school Biomedical SciencesCollege of Medicine & Veterinary MedicineUniversity of Edinburgh

N6-methyladenosine(m6A) is a critical regulator in the fate of RNA, but whether and how m6A executes its functions in different tissues remains largely obscure. Here we report downregulation of a crucial m6A reader, YTHDF2, leading to tissue-specific programmed cell deaths(PCDs) upon fluorene-9-bisphenol(BHPF) exposure. Currently, Bisphenol A(BPA) substitutes are widely used in plastic *** eight common BPA substitutes, we detected BHPF in 14% serum samples of pregnant participants. In a zebrafish model, BHPF caused tissue-specific PCDs triggering cardiac and vascular ***, BHPF-mediated downregulation of YTHDF2 reduced YTHDF2-facilitated translation of m6A-gch1 for cardiomyocyte ferroptosis, and decreased YTHDF2-mediated m6A-sting1 decay for caudal vein plexus(CVP) apoptosis. The two distinct YTHDF2-mediated m6A regulations and context-dependent co-expression patterns of gch1/ythdf2 and tnfrsf1a/ythdf2 contributed to YTHDF2-mediated tissue-specific PCDs, uncovering a new layer of PCD regulation. Since BHPF/YTHDF2-medaited PCD defects were also observed in mammals, BHPF exposure represents a potential health threat.

关键词： RNA m6A modification programmed cell deaths bifurcation role of YTHDF2 environmental stress and m6A regulation fluorene-9-bisphenol (BHPF)

Investigating materials and orientation parameters for the creation of a 3D musculoskeletal interface co-culture model

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Regenerative Biomaterials 2020年第4期7卷 413-425页

作者： Hamad Alsaykhan Jennifer Z.Paxton Anatomy@edinburgh Edinburgh Medical School:Biomedical SciencesThe University of EdinburghTeviot PlaceEdinburgh EH89AGUK Department of Basic medical sciences College of Medicine and Health SciencesQassim UniversityPO Box 99151911 Unaizah CampusAl-Qassim 51911Saudi Arabia

Musculoskeletal tissue interfaces are a common site of injury in the young,active *** particular,the interface between the musculoskeletal tissues of tendon and bone is often injured and to date,no single treatment has been able to restore the form and function of damaged tissue at the bone-tendon *** engineering and regeneration hold great promise for the manufacture of bespoke in vitro models or implants to be used to advance repair and so this study investigated the material,orientation and culture choices for manufacturing a reproducible 3D model of a musculoskeletal interface between tendon and bone cell *** models are essential for future studies focussing on the regeneration of musculoskeletal interfaces in ***-encapsulated fibrin hydrogels,arranged in a horizontal orientation though a simple moulding procedure,were shown to best support cellular growth and migration of cells to form an in vitro tendon-bone *** study highlights the importance of acknowledging the material and technical challenges in establishing co-cultures and suggests a reproducible methodology to form 3D co-cultures between tendon and bone,or other musculoskeletal cell types,in vitro.

关键词： tendon bone 3D co-culture hydrogels musculoskeletal interface