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The RNA m^(6)A demethylase ALKBH5 drives emergency granulopoiesis and neutrophil mobilization by upregulating G-CSFR expression

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Cellular & Molecular Immunology 2024年第1期21卷 6-18页

作者： Yang Liu Renjie Song Zhike Lu Lu Zhao Xinyi Zhan Yini Li Xuetao Cao Department of Immunology Center for ImmunotherapyInstitute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina Suzhou institute of Systems Medicine Chinese Academy of Medical SciencesSuzhouChina Frontier research Center for Cell Response Institute of ImmunologyCollege of Life SciencesNankai UniversityTianjinChina School of Life Sciences Westlake UniversityHangzhouChina

Emergency granulopoiesis and neutrophil mobilization that can be triggered by granulocyte colony-stimulating factor(G-CSF)through its receptor G-CSFR are essential for antibacterial innate defense.However,the epigenetic modifiers crucial for intrinsically regulating G-CSFR expression and the antibacterial response of neutrophils remain largely unclear.N6-methyladenosine(m^(6)A)RNA modification and the related demethylase alkB homolog 5(ALKBH5)are key epigenetic regulators of immunity and inflammation,but their roles in neutrophil production and mobilization are still unknown.We used cecal ligation and puncture(CLP)-induced polymicrobial sepsis to model systemic bacterial infection,and we report that ALKBH5 is required for emergency granulopoiesis and neutrophil mobilization.ALKBH5 depletion significantly impaired the production of immature neutrophils in the bone marrow of septic mice.In addition,Alkbh5-deficient septic mice exhibited higher retention of mature neutrophils in the bone marrow and defective neutrophil release into the circulation,which led to fewer neutrophils at the infection site than in their wild-type littermates.During bacterial infection,ALKBH5 imprinted production-and mobilization-promoting transcriptome signatures in both mouse and human neutrophils.Mechanistically,ALKBH5 erased m^(6)A methylation on the CSF3R mRNA to increase the mRNA stability and protein expression of G-CSFR,consequently upregulating cell surface G-CSFR expression and downstream STAT3 signaling in neutrophils.The RIP-qPCR results confirmed the direct binding of ALKBH5 to the CSF3R mRNA,and the binding strength declined upon bacterial infection,accounting for the decrease in G-CSFR expression on bacteria-infected neutrophils.Considering these results collectively,we define a new role of ALKBH5 in intrinsically driving neutrophil production and mobilization through m^(6)A demethylation-dependent posttranscriptional regulation,indicating that m^(6)A RNA modification in neutrophils is a potential target for treating bacteria

关键词： Emergency granulopoiesis Neutrophil mobilization ALKBH5 m^(6)A RNA modification G-CSF receptor

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Comparative study between three carbonaceous nanoblades and nanodarts for antimicrobial applications

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Journal of Environmental Sciences 2024年第2期136卷 594-605页

作者： Mohamed S.Selim Ahmed M.Azzam Mohamed A.Shenashen Shimaa A.Higazy Bayaumy B.Mostafa Sherif A.El-Safty National institute for Materials Science(NIMS) 1-2-1 SengenTsukuba-ShiIbaraki-Ken 305-0047Japan Petroleum Application Department Egyptian Petroleum Research InstituteNasr City 11727Egypt Department of Environmental research Theodor Bilharz Research InstituteGizaEgypt

The design of nanostructured materials occupies a privileged position in the development and management of affordable and effective technology in the antibacterial sector.Here,we discuss the antimicrobial properties of three carbonaceous nanoblades and nanodarts materials of graphene oxide(GO),reduced graphene oxide(RGO),and single-wall carbon nanotubes(SWCNTs)that have a mechano-bactericidal effect,and the ability to piercing or slicing bacterial membranes.To demonstrate the significance of size,morphology and composition on the antibacterial activity mechanism,the designed nanomaterials have been characterized.The minimum inhibitory concentration(MIC),standard agar well diffusion,and transmission electron microscopy were utilized to evaluate the antibacterial activity of GO,RGO,and SWCNTs.Based on the evidence obtained,the three carbonaceous materials exhibit activity against all microbial strains tested by completely encapsulating bacterial cells and causing morphological disruption by degrading the microbial cell membrane in the order of RGO>GO>SWCNTs.Because of the external cell wall structure and outer membrane proteins,the synthesized carbonaceous nanomaterials exhibited higher antibacterial activity against Gram-positive bacterial strains than Gram-negative and fungal microorganisms.RGO had the lowest MIC values(0.062,0.125,and 0.25 mg/mL against B.subtilis,S.aureus,and E.coli,respectively),as well as minimum fungal concentrations(0.5 mg/mL for both A.fumigatus and C.albicans).At 12 hr,the cell viability values against tested microbial strains were completely suppressed.Cell lysis and death occurred as a result of severe membrane damage caused by microorganisms perched on RGO nanoblades.Our work gives an insight into the design of effective graphene-based antimicrobial materials for water treatment and remediation.

关键词： Antimicrobial properties Nanoblades Mechano-bactericidal effect RGO nanosheets Gram-positive bacteria Cell viability

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Aptamers targeting SARS-CoV-2 nucleocapsid protein exhibit potential ant1ip1 an-coronavirus activity

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1186-1198页

作者： Minghui Yang Chunhui Li Guoguo Ye Chenguang Shen Huiping Shi Liping Zhong Yuxin Tian Mengyuan Zhao Pengfei Wu Abid Hussain Tian Zhang Haiyin Yang Jun Yang Yuhua Weng Xinyue Liu Zhimin Wang Lu Gan Qianyu Zhang Yingxia Liu Ge Yang Yuanyu Huang Yongxiang Zhao School of Life Science Advanced Research Institute of Multidisciplinary ScienceKey Laboratory of Molecular Medicine and BiotherapyBeijing Institute of TechnologyBeijing 100081China National Clinical research Center for infectious disease Shenzhen Third People’s HospitalSecond Hospital Affiliated to Southern University of Science and TechnologyShenzhen 518112China Guangdong Provincial Key Laboratory of Tropical Disease research School of Public HealthSouthern Medical UniversityGuangzhou 510515China State Key Laboratory of Targeting Oncology National Center for International Research of Biotargeting TheranosticsGuangxi Key Laboratory of Biotargeting TheranosticsCollaborative Innovation Center for Targeting Tumor Diagnosis and TherapyGuangxi Medical UniversityNanning 530021China CAMS Key Laboratory of Antiviral Drug research Beijing Key Laboratory of Antimicrobial AgentsInstitute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Emerging and recurrent infectious diseases caused by human coronaviruses(HCoVs)continue to pose a significant threat to global public health security.In light of this ongoing threat,the development of a broad-spectrum drug to combat HCoVs is an urgently priority.Herein,we report a series of anti-pan-coronavirus ssDNA aptamers screened using Systematic Evolution of Ligands by Exponential Enrichment(SELEX).These aptamers have nanomolar affinity with the nucleocapsid protein(NP)of Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and also show excellent binding efficiency to the N proteins of both SARS,MERS,HCoV-OC43 and-NL63 with affinity KD values of 1.31 to 135.36 nM.Such aptamer-based therapeutics exhibited potent antiviral activity against both the authentic SARS-CoV-2 prototype strain and the Omicron variant(BA.5)with EC50 values at 2.00 nM and 41.08 nM,respectively.The protein docking analysis also evidenced that these aptamers exhibit strong affinities for N proteins of pan-coronavirus and other HCoVs(−229E and-HKU1).In conclusion,we have identified six aptamers with a high pan-coronavirus antiviral activity,which could potentially serve as an effective strategy for preventing infections by unknown coronaviruses and addressing the ongoing global health threat.

关键词： acute threat conclusion

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Post-discharge follow-up of patients with spine trauma in the National Spinal Cord Injury Registry of Iran during the COVID-19 pandemic:Challenges and lessons learned

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Chinese Journal of Traumatology 2024年第3期27卷 173-179页

作者： Zahra Azadmanjir Moein Khormali Mohsen Sadeghi-Naini Vali Baigi Habibollah Pirnejad Mohammad Dashtkoohi Zahra Ghodsi Seyed Behnam Jazayeri Aidin Shakeri Mahdi Mohammadzadeh Laleh Bagheri Mohammad-Sajad Lotfi Salman Daliri Amir Azarhomayoun Homayoun Sadeghi-Bazargani Gerard O'reilly Vafa Rahimi-Movaghai Health Information Management Department School of Allied Medical SciencesTehran University of Medical SciencesTehranIran Sina Trauma and Surgery research Center Tehran University of Medical SciencesTehranIran Department of Neurosurgery Lorestan University of Medical SciencesKhoram-AbadIran Department of Epidemiology and Biostatistics School of Public HealthTehran University of Medical SciencesTehranIran Patient Safety research Center Clinical Rsearch institute Urma Universty of Medical SciencesUrmaIran Erasmus School of Health Policy&Management(ESHPM) Erasmus University RotterdamRoterdamthe Netherlands Brain and Spinal Cord Injury research Center Neuroscience InstituteTehran University of Medical SciencesTehranIran Students Scientifc research Center(SSRC) Tehran University of Medical SciencesTehranIran Department of Neurosurgery Arak University of Medical SciencesArakIran Trauma research Center Kashan University of Medical SciencesKashanIran Shahid Rahnemoun Hospital Shahid Sadoughi University of Medical SciencesYazdIran Trauma Nuring Rearch entre Faculty of Nursing and Midwifry Kahan Universty of Medical Sciences Kahan Iran Clinical research Development Unit Imam Hossein HospitalShahroud University of Medical SciencesShahroudIran research Center for Evidence Based Medicine Faculty of MedicineTabriz University of Medical SciencesTabrizIran Road Trafic Injury research Center Tabriz University of Medical SciencesTabrizIran School of Public Health and Preventive Medicine Monash UniversityMelbourneAustralia National Trauma research institute The AlfredMelbourneAustralia Department of Neurosurgery Shariati HospitalTehran University of Medical SciencesTehranIran Universal Scientific Education and research Network(USERN) TehranIran institute of Biochemistry and Biophysics University of TehranTehranIran

Purpose:The purpose of the National Spinal Cord Injury Registry of Iran(NSCIR-IR)is to create an infrastructure to assess the quality of care for spine trauma and in this study,we aim to investigate whether the NSCIR-IR successfully provides necessary post-discharge follow-up data for these patients.Methods:An observational prospective study was conducted from April 11,2021 to April 22,2022 in 8 centers enrolled in NSCIR-IR,respectively Arak,Rasht,Urmia,Shahroud,Yazd,Kashan,Tabriz,and Tehran.Patients were classified into 3 groups based on their need for care resources,respectively:(1)non-spinal cord injury(SCI)patients without surgery(group 1),(2)non-SCI patients with surgery(group 2),and(3)SCI patients(group 3).The assessment tool was a self-designed questionnaire to evaluate the care quality in 3 phases:pre-hospital,in-hospital,and post-hospital.The data from the first 2 phases were collected through the registry.The post-hospital data were collected by conducting follow-up assessments.Telephone follow-ups were conducted for groups 1 and 2(non-SCI patients),while group 3(SCI patients)had a face-to-face visit.This study took place during the COVID-19 pandemic.Data on age and time interval from injury to follow-up were expressed as mean±standard deviation(SD)and response rate and follow-up loss as a percentage.Results:Altogether 1538 telephone follow-up records related to 1292 patients were registered in the NSCIR-IR.Of the total calls,918(71.05%)were related to successful follow-ups,but 38 cases died and thus were excluded from data analysis.In the end,post-hospital data from 880 patients alive were gathered.The success rate of follow-ups by telephone for groups 1 and 2 was 73.38%and 67.05%respectively,compared to 66.67%by face-to-face visits for group 3,which was very hard during the COVID-19 pandemic.The data completion rate after discharge ranged from 48%-100%,22%-100%and 29%-100%for groups 1-3.Conclusions:To improve patient accessibility,NSCIR-IR should take measures during data gathering to increase the acc

关键词： Follow-up studies Spinal injuries Spinal cord injuries COVID-19 NSCIR-IR

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Asialoglycoprotein receptor 1 promotes SARS-CoV-2 infection of human normal hepatocytes

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1199-1208页

作者： Xinyi Yang Xu Zheng Yuqi Zhu Xiaying Zhao Jun Liu Jiangna Xun Songhua Yuan Jun Chen Hanyu Pan Jinlong Yang Jing Wang Zhimin Liang Xiaoting Shen Yue Liang Qinru Lin Huitong Liang Min Li Fei Peng Daru Lu Jianqing Xu Hongzhou Lu Shibo Jiang Ping Zhao Huanzhang Zhu State Key Laboratory of Genetic Engineering and Engineering research Center of Gene Technology Ministry of EducationInstitute of GeneticsSchool of Life SciencesYiwu Research InstituteFudan UniversityShanghaiChina Department of Microbiology Faculty of Naval MedicineNaval Medical UniversityShanghai 200433China Scientific research Center Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Department of Infectious Diseases and Immunology Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Changzheng Hospital Naval Medical UniversityShanghaiChina Key Laboratory of medical Molecular Virology(MOE/NHC/CAMS) Shanghai Institute of Infectious Disease and BiosecuritySchool of Basic Medical SciencesFudan UniversityShanghaiChina Department of Infectious Diseases and Nursing research Institution National Clinical Research Center for Infectious DiseasesThe Third People’s Hospital of ShenzhenShenzhenGuangdongChina

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)causes multi-organ damage,which includes hepatic dysfunction,as observed in over 50%of COVID-19 patients.Angiotensin I converting enzyme(peptidyl-dipeptidase A)2(ACE2)is the primary receptor for SARS-CoV-2 entry into host cells,and studies have shown the presence of intracellular virus particles in human hepatocytes that express ACE2,but at extremely low levels.Consequently,we asked if hepatocytes might express receptors other than ACE2 capable of promoting the entry of SARS-CoV-2 into cells.To address this question,we performed a genome-wide CRISPR-Cas9 activation library screening and found that Asialoglycoprotein receptor 1(ASGR1)promoted SARS-CoV-2 pseudovirus infection of HeLa cells.In Huh-7 cells,simultaneous knockout of ACE2 and ASGR1 prevented SARS-CoV-2 pseudovirus infection.In the immortalized THLE-2 hepatocyte cell line and primary hepatic parenchymal cells,both of which barely expressed ACE2,SARSCoV-2 pseudovirus could successfully establish an infection.However,after treatment with ASGR1 antibody or siRNA targeting ASGR1,the infection rate significantly dropped,suggesting that SARS-CoV-2 pseudovirus infects hepatic parenchymal cells mainly through an ASGR1-dependent mechanism.We confirmed that ASGR1 could interact with Spike protein,which depends on receptor binding domain(RBD)and N-terminal domain(NTD).Finally,we also used Immunohistochemistry and electron microscopy to verify that SARS-CoV-2 could infect primary hepatic parenchymal cells.After inhibiting ASGR1 in primary hepatic parenchymal cells by siRNA,the infection efficiency of the live virus decreased significantly.Collectively,these findings indicate that ASGR1 is a candidate receptor for SARS-CoV-2 that promotes infection of hepatic parenchymal cells.

关键词： ACE2 infection glycoprotein

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Neuroprotective effects of resveratrol on retinal ganglion cells in glaucoma in rodents:A narrative review

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Animal Models and Experimental Medicine 2024年第3期7卷 195-207页

作者： Maryam Golmohammadi Seyed Arash Aghaei Meibodi Sulieman Ibraheem Shelash Al-Hawary Jitendra Gupta Ibrohim B.Sapaev Mazin A.A.Najm Marim Alwave Mozhgan Nazifi Mohammadreza Rahmani Mohammad Yasin Zamanian Gervason Moriasi School of Medicine Shahid Beheshti University of Medical SciencesTehranIran Department of Business Administration Business SchoolAl al-Bayt UniversityMafraqJordan institute of Pharmaceutical research GLA UniversityMathuraIndia Tashkent institute of Irrigation and Agricultural Mechanization Engineers TashkentUzbekistan New Uzbekistan University TashkentUzbekistan Pharmaceutical Chemistry Department College of PharmacyAl-Ayen UniversityThi-QarIraq medical Technical College Al-Farahidi UniversityBaghdadIraq Department of Neurology Hamadan University of Medical SciencesHamadanIran Physiology-Pharmacology research Center Research Institute of Basic Medical SciencesRafsanjan University of Medical SciencesRafsanjanIran Department of Physiology and Pharmacology School of MedicineRafsanjan University of Medical SciencesRafsanjanIran Neurophysiology research Center Hamadan University of Medical SciencesHamadanIran Department of Pharmacology and Toxicology School of PharmacyHamadan University of Medical SciencesHamadanIran Department of medical Biochemistry School of MedicineCollege of Health SciencesMount Kenya UniversityThikaKenya

Glaucoma,an irreversible optic neuropathy,primarily affects retinal ganglion cells(RGC)and causes vision loss and blindness.The damage to RGCs in glaucoma occurs by various mechanisms,including elevated intraocular pressure,oxidative stress,inflammation,and other neurodegenerative processes.As the disease progresses,the loss of RGCs leads to vision loss.Therefore,protecting RGCs from damage and promoting their survival are important goals in managing glaucoma.In this regard,resveratrol(RES),a polyphenolic phytoalexin,exerts antioxidant effects and slows down the evolution and progression of glaucoma.The present review shows that RES plays a protective role in RGCs in cases of ischemic injury and hypoxia as well as in ErbB2 protein expression in the retina.Additionally,RES plays protective roles in RGCs by promoting cell growth,reducing apoptosis,and decreasing oxidative stress in H_(2)O_(2)-exposed RGCs.RES was also found to inhibit oxidative stress damage in RGCs and suppress the activation of mitogen-activated protein kinase signaling pathways.RES could alleviate retinal function impairment by suppressing the hypoxia-i nducible factor-1 alpha/vascular endothelial growth factor and p38/p53 axes while stimulating the PI3K/Akt pathway.Therefore,RES might exert potential therapeutic effects for managing glaucoma by protecting RGCs from damage and promoting their survival.

关键词： glaucoma ischemic-reperfusion injury oxidative stress resveratrol retinal ganglion cells

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Virus-like nanoparticle vaccines for inducing long-lasting immunity against infectious diseases

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National Science Review 2024年第4期11卷 13-15页

作者： Yi-Nan Zhang Sarah Auclair Jiang Zhu Department of Integrative Structural and Computational Biology The Scripps Research Institute Department of Immunology and Microbiology The Scripps Research Institute

Prophylactic vaccines that can generate long-lasting protective immune responses are needed for many infectious diseases. Efficient vaccination requires vaccine antigens to be retained and presented to B cells in lymp...

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Simulation and fabrication of in vitro microfluidic microelectrode array chip for patterned culture and electrophysiological detection of neurons

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Nanotechnology and Precision Engineering 2024年第2期7卷 1-10页

作者： Yan Yang Shihong Xu Yu Deng Yaoyao Liu Kui Zhang Shiya Lv Longze Sha Qi Xu Xinxia Cai Jinping Luo State Key Laboratory of Transducer Technology Aerospace Information Research InstituteChinese Academy of SciencesBeijing 100190China School of Electronic Electrical and Communication EngineeringUniversity of Chinese Academy of SciencesBeijing 100049China State Key Laboratory of medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China

To enable the detection and modulation of modularized neural networks in vitro,this study proposes a microfluidic microelectrode array chip for the cultivation,compartmentalization,and control of neural cells.The chip was designed based on the specific structure of neurons and the requirements for detection and modulation.Finite-element analysis of the chip’s flow field was conducted using the COMSOL Multiphysics software,and the simulation results show that the liquid within the chip can flow smoothly,ensuring stable flow fields that facilitate the uniform growth of neurons within the microfluidic channels.By employing MEMS technology in combination with nanomaterial modification techniques,the microfluidic microelectrode array chip was fabricated successfully.Primary hippocampal neurons were cultured on the chip,forming a well-defined neural network.Spontaneous electrical activity of the detected neurons was recorded,exhibiting a 23.7%increase in amplitude compared to neuronal discharges detected on an open-field microelectrode array.This study provides a platform for the precise detection and modulation of patterned neuronal growth in vitro,potentially serving as a novel tool in neuroscience research.

关键词： Microﬂuidic Microelectrode array In vitro Neural chip

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RIOK1 synergizes with TRIP13 by regulating the E2F-Rb signaling pathway to promote the proliferation of esophageal cancer cells

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Genes & Diseases 2024年第3期11卷 55-58页

作者： Chengyu Li Deyuan Pan Wan Lin Danxia Deng Yingxin Zhou Hui Zhao Feng Pan Liyan Xu Enmin Li Lin Long The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area Department of Biochemistry and Molecular BiologyShantou University Medical CollegeShantouGuangdong 515041China Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology Institute of Oncologic PathologyShantou University Medical CollegeShantouGuangdong 515041China institute of Basic medical Science Cancer Research CenterShantou University Medical CollegeShantouGuangdong 515041China Clinical research Center Shantou Central HospitalShantouGuangdong 515041China

Esophageal cancer is one of the leading causes of cancer death in the world,with approximately half of the new cases occurring in China every year.^(1)Esophageal squamous cell carcinoma(ESCC)is the main subtype,accounting for more than 90%,and the five-year survival rate is less than 10%.Using large-scale genome analysis,many driver mutations and key pathways associated with ESCC have been identified.However,these genomic signatures have not improved the clinical management of EscC patients,or established effective targeted therapy.^(2)Esophageal cancer still lacks representative molecular markers.

关键词： cancer esophageal Esophageal

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Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction (STRATEGY): protocol for a multicentre, randomised controlled trial

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Stroke & Vascular Neurology 2024年第1期9卷 75-81,I0047-I0052页

作者： Xiaoling Liao Shuo Feng Yicong Wang Yuesong Pan Weiqi Chen Hui Qu Xingquan Zhao Liping Liu Yongjun Wang Yilong Wang Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical research Center for Neurological Diseases Beijing TiantanHospitalCapital Medical UniversityBeijingChina Chinese institute for Brain research BeijingChina National Center for Neurological Diseases BeijingChina Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijingChina Beijing Laboratory of Oral Health Capital Medical UniversityBeijingChina

Background Perforating artery territorial infarction(PAI)caused by branch atheromatous disease(BAD)is prone to recurrence and early progression without an effective and well-documented antiplatelet treatment regimen.Tirofiban,an adjunctive antiplatelet agent,has shown great potential to treat acute ischaemic stroke.However,whether the combination of tirofiban and aspirin can improve the prognosis of PAI remains unclear.Aim To explore an effective and safe antiplatelet regimen for reducing the risk of recurrence and early neurological deterioration(END)in PAI caused by BAD by comparing the tirofiban and aspirin combination with placebo and aspirin combination.Methods Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction(STRATEGY)trial is an ongoing multicentre,randomised,placebo-controlled trial in China.Eligible patients shall be randomly assigned to receive standard aspirin with tirofiban or placebo on the first day and standard aspirin from days 2 to 90.The primary endpoint is a new stroke or END within 90 days.The primary safety endpoint is severe or moderate bleeding within 90 days.Discussion The STRATEGY trial will assess whether tirofiban combined with aspirin is effective and safe in preventing recurrence and END in patients with PAI.Trial registration number NCT05310968.

关键词： Aspirin regimen centre

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