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M6PR interacts with the HA2 subunit of influenza A virus to facilitate the fusion of viral and endosomal membranes

Science China(Life Sciences) 2024年第3期67卷 579-595页

作者： Yuzhen Hu Li Jiang Guangwen Wang Yangming Song Zhibo SHAn Xuyuan Wang Guohua Deng Jianzhong Shi Guobin Tian Xianying Zeng Liling Liu Hualan Chen Chengjun Li State Key Laboratory for Animal Disease Control and Prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China

Influenza A virus(IAV) commandeers numerous host cellular factors for successful replication. However, very few host factors HAve been revealed to be involved in the fusion of viral envelope and late endosomal membranes. In this study, we identified cation-dependent mannose-6-phospHAte receptor(M6PR) as a crucial host factor for the replication of IAV. We found tHAt siRNA knockdown of M6PR expression significantly reduced the growth titers of different subtypes of IAV, and tHAt the inhibitory effect of M6PR siRNA treatment on IAV growth was overcome by the complement of exogenously expressed M6PR. When A549 cells were treated with siRNA targeting M6PR,the nuclear accumulation of viral nucleoprotein(NP) was dramatically inhibited at early timepoints post-infection, indicating tHAt M6PR engages in the early stage of the IAV replication cycle. By investigating the role of M6PR in the individual entry and post-entry steps of IAV replication, we found tHAt the downregulation of M6PR expression HAd no effect on attachment, internalization, early endosome trafficking,or late endosome acidification. However, we found tHAt M6PR expression was critical for the fusion of viral envelope and late endosomal membranes. Of note, M6PR interacted with the hemagglutinin(HA) protein of IAV, and further studies showed tHAt the lumenal domain of M6PR and the ectodomain of HA2 mediated the interaction and directly promoted the fusion of the viral and late endosomal membranes,thereby facilitating IAV replication. Together, our findings highlight the importance of the M6PR–HA interaction in the fusion of viral and late endosomal membranes during IAV replication.

关键词： influenza A virus M6PR HA membrane fusion late endosome

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Mutual antagonism of mouse-adaptation mutations in HA and PA proteins on H9N2 virus replication

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Virologica Sinica 2024年第1期39卷 56-70页

作者： Liping Ma Huabin Zheng Xianliang Ke Rui Gui Zhongzi Yao Jiasong Xiong Quanjiao Chen CAS Key Laboratory of Special Pathogens and Biosafety Wuhan Institute of VirologyChinese Academy of SciencesWuhan430207China Center for Biosafety Mega-Science Wuhan Institute of VirologyChinese Academy of SciencesWuhan430207China Hubei Jiangxia Laboratory Wuhan430207China University of Chinese Academy of Sciences Beijing100049China

Avian H9N2 viruses HAve wide host range among the influenza A viruses.However,knowledge of H9N2 mammalian adaptation is limited.To explore the molecular basis of the adaptation to mammals,we performed serial lung passaging of the H9N2 strain A/chicken/Hunan/8.27 YYGK3W3-OC/2018(3W3)in mice and identified six mutations in the hemagglutinin(HA)and polymerase acidic(PA)proteins.Mutations L226Q,T511I,and A528V of HA were responsible for enHAnced pathogenicity and viral replication in mice;notably,HA-L226Q was the key determinant.Mutations T97I,I545V,and S594G of PA contributed to enHAnced polymerase activity in mammalian cells and increased viral replication levels in vitro and in vivo.PA-T97I increased viral polymerase activity by accelerating the viral polymerase complex assembly.Our findings revealed tHAt the viral replication was affected by the presence of PA-97I and/or PA-545V in combination with a triple-point HA mutation.Furthermore,the double-and triple-point PA mutations demonstrated antagonistic effect on viral replication when combined with HA-226Q.Notably,any combination of PA mutations,along with double-point HA mutations,resulted in antagonistic effect on viral replication.We also observed antagonism in viral replication between PA-545V and PA-97I,as well as between HA-528V and PA-545V.Our findings demonstrated tHAt several antagonistic mutations in HA and PA proteins affect viral replication,which may contribute to the H9N2 virus adaptation to mice and mammalian cells.These findings can potentially contribute to the monitoring of H9N2 field strains for assessing their potential risk in mammals.

关键词： Influenza Avirus(IAV) H9N2 HA PA Antagonism Mouse adaptation

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甘油磷酸钙浓度对钛合金MAO涂层性能的影响

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表面技术 2024年第9期53卷 56-64页

作者：肖水清秦晋王学禹赵融芳张荣发江西科技师范大学南昌330038

目的提高医用钛合金的生物活性。方法在含葡萄糖酸钙(CaGlu_(2))、葡萄糖酸镁(MgGlu_(2))、植酸钠(Na12Phy)和磷酸(H3PO_(4))的基本溶液中,分别添加8、10、12 g/L甘油磷酸钙(Ca-GP),采用MAO方法在Ti-6Al-4V表面制备3种涂层。使用SEM、ED... 详细信息

目的提高医用钛合金的生物活性。方法在含葡萄糖酸钙(CaGlu_(2))、葡萄糖酸镁(MgGlu_(2))、植酸钠(Na12Phy)和磷酸(H3PO_(4))的基本溶液中,分别添加8、10、12 g/L甘油磷酸钙(Ca-GP),采用MAO方法在Ti-6Al-4V表面制备3种涂层。使用SEM、EDS、XRD、XPS和AFM检测涂层表面形貌、化学成分、物相结构、元素存在状态和表面粗糙度,并测试涂层的接触角、结合强度以及体外生物活性。结果经过MAO处理后,钛合金表面可成功生长出多孔陶瓷涂层,Ca-GP参与了MAO涂层形成。当Ca-GP的质量浓度为8g/L时,涂层非常粗糙,Ca和Mg的原子数分数分别为7.56%和1.74%。随着Ca-GP浓度的增加,微孔均匀性变好,表面微裂纹减少,且钙磷原子比(Ca/P)显著提高。在含8、10g/L的Ca-GP溶液中,制备的涂层以Ti、锐钛矿和金红石型TiO_(2)组成为主;在12 g/L的Ca-GP溶液中生成的涂层,Ca/P原子比可达1.77,含有TiP_(2)O_(7)、Mg_(3)(PO_(4))_(2)和少量HA。Ca-GP能显著增加涂层的粗糙度,且稍微增加涂层与基体之间的结合强度。接触角测试结果表明,Ca-GP能明显改善涂层的亲水性。结论随着Ca-GP浓度增加,涂层中钙含量增加,表明钙离子通过扩散进入MAO涂层中。在含12 g/L Ca-GP溶液中制备的涂层,含TiP_(2)O_(7)、Mg_(3)(PO_(4))_(2)和HA,且Ca/P原子比与HA中的Ca/P原子比接近。模拟体液中浸泡试验结果表明,添加12g/L Ca-GP制备的MAO样品,表面形成了大量颗粒状HA,表现出优异的体外生物活性。

关键词：钛合金微弧氧化钙磷比 HA 生物活性

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骨替代材料BCP应用于种植体骨再生的研究进展

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临床医学进展 2024年第2期14卷 4318-4324页

作者：胡志钊葛艇蕊胡杨新疆医科大学第一附属医院(附属口腔医院)修复种植科新疆乌鲁木齐新疆维吾尔自治区口腔医学研究所新疆乌鲁木齐新疆医科大学第六附属医院口腔科新疆乌鲁木齐

双相磷酸钙(bipHAsic calcium phospHAte, BCP)是由β-磷酸三钙(β-tricalcium phospHAte, β-TCP)和羟基磷灰石(hydroxyapatite, HA)组成的种植体牙周骨替代材料。种植体牙周骨量、骨质密度和牙槽骨结构决定着种植义齿修复的稳定性。... 详细信息

双相磷酸钙(bipHAsic calcium phospHAte, BCP)是由β-磷酸三钙(β-tricalcium phospHAte, β-TCP)和羟基磷灰石(hydroxyapatite, HA)组成的种植体牙周骨替代材料。种植体牙周骨量、骨质密度和牙槽骨结构决定着种植义齿修复的稳定性。近年来随着研究的不断深入,发现BCP具有着一定的骨诱导能力有利于种植体牙周骨再生,并且具有极佳的骨传导性、生物相容性、生物活性等特点,所以利用BCP来恢复种植体牙周水平及垂直骨量不足是目前口腔临床治疗领域中一大研究热点。本文旨在通过梳理国内外相关文献资料,对牙周骨替代材料BCP的组成及优点、BCP复合材料的研究新进展、BCP在种植体骨再生领域的研究现状等进行综述,以期为口腔临床诊疗及应用提供参考。

关键词：骨替代材料 BCP 种植体骨再生 β-TCP HA

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Enzymatic co-crosslinking of star-sHAped poly(ethylene glycol)tyramine and hyaluronic acid tyramine conjugates provides elastic biocompatible and biodegradable hydrogels

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Bioactive Materials 2023年第2期20卷 53-63页

作者： Rong Wang Xiaobin Huang Bram Zoetebier Pieter JDijkstra Marcel Karperien Department of Developmental BioEngineering Faculty of Science and TechnologyTech Med CentreUniversity of TwenteP.O.Box 2177500 AEEnschedethe Netherlands Radboudumc Dept.of Dentistry-Regenerative BiomaterialsRadboud University Medical CenterPhilips van Leydenlaan 256525 EX NijmegenThe Netherlands Department of Oral and Maxillofacial Surgery School of Dental MedicineUniversity of Pennsylvania240 South 40th StreetPhiladelphiaPA 19104-6030US

A combination of the viscoelastic properties of hyaluronic acid(HA)and the elastic properties of star sHAped 8-arm poly(ethylene glycol)(8-arm PEG)was used to design in-situ forming hydrogels.Hydrogels were prepared by the enzymatic crosslinking of a partially tyramine modified 8-arm PEG and a tyramine conjugated HA using horseradish peroxidase in the presence of hydrogen peroxide.Hydrogels of the homopolymer conjugates and mixtures thereof were rapidly formed within seconds under physiological conditions at low polymer and enzyme concentrations.Elastic hydrogels with high gel content(≥95%)and high storage moduli(up to 22.4 kPa)were obtained.An in vitro study in the presence of hyaluronidase(100 U/mL)revealed tHAt with increasing PEG content the degradation time of the hybrid hydrogels increased up to several weeks,whereas hydrogels composed of only hyaluronic acid degraded within 2 weeks.Human mesenchymal stem cells(hMSCs)incorporated in the hybrid hydrogels remained viable as shown by a PrestoBlue and a live-dead assay,confirming the biocompatibility of the constructs.The production of an extracellular matrix by re-differentiation of encapsulated human chondrocytes was followed over a period of 28 days.Gene expression indicated tHAt these highly elastic hydrogels induced an enHAnced production of collagen type II.At low PEG-TA/HA-TA ratios a higher expression of SOX 9 and ACAN was observed.These results indicate tHAt by modulating the ratio of PEG/HA,injectable hydrogels can be prepared applicable as scaffolds for tissue regeneration applications.

关键词： PEG-OH8 HA Enzymatic crosslinking hydrogel Degradation Proliferation&differentiation

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HA集团成为“携手促进可持续发展倡议”新成员

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铸造工程 2024年第1期48卷 87-87页

HA在可持续发展战略方面取得了又一关键性的全球里程碑——成为“携手促进可持续发展倡议”的正式成员。自2023年10月18日起,HA集团成为“携手促进可持续发展倡议”(Tf S)的全球50名成员之一。作为加入该倡议的铸造工业化学品公司,成员... 详细信息

HA在可持续发展战略方面取得了又一关键性的全球里程碑——成为“携手促进可持续发展倡议”的正式成员。自2023年10月18日起,HA集团成为“携手促进可持续发展倡议”(Tf S)的全球50名成员之一。作为加入该倡议的铸造工业化学品公司,成员资格由该倡议联盟和独立审核机构对其可持续性的实践情况进行认证。“携手促进可持续发展倡议”是化工行业的一个联盟组织,成立于2011年。其目标是针对化工行业的可持续性发展进行有效评定,制定标准量化透明,从而为更多的公司和供应商实施长期可持续性的采购行动。

关键词：化学品公司铸造工业可持续性发展化工行业可持续发展战略成员资格供应商 HA

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Effect of Yupingfeng granules on HA and Foxp3^+ Treg expression in patients with nasopHAryngeal carcinoma

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Asian Pacific Journal of Tropical Medicine 2015年第8期8卷 662-664页

作者： Ji-Hong Huang Zhong-Lin Mu Xue-Jun Zhou Qiong-Lian Huang Feng Gao Xi Chen HAinan Medical University

Objective: To investigate the effect of Yupingfeng on hyaluronic acid(HA) and Foxp3+ Treg in patients with nasopHAryngeal carcinoma. Methods: A total of 58 cases of nasopHAryngeal carcinoma were divided into two groups, 30 cases in the treatment group, 28 cases in the control group. Patients in two groups were treated with synchronous radiotherapy and chemotherapy treatment, the treatment group was treated with the Yupingfeng granules through oral administration, 10 g/time, tid for 2 courses. The serum Foxp3+ Treg markers of each group were detected by flow cytometry assay before treatment and after treatment, and the level of HA in serum was detected by radio immunoassay. Results: After radiotherapy and chemotherapy, the contents of Foxp3+ Treg and HA were significantly decreased in two groups(PHA(PHA in nasopHAryngeal carcinoma patients. Yupingfeng can also effectively reduce the side effect due to radiation and chemotherapy.

关键词： NasopHAryngeal carcinoma Yupingfeng Foxp3 Treg HA

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Construction of bio-functional Mg/HA composite layered coating for orthopedic application

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Science China(Technological Sciences) 2021年第11期64卷 2541-2550页

作者： WAN Peng YAN XuDong LI Mei ZHAO MingChun ZHANG Yu YANG Ke School of Materials Science and Engineering Dongguan University of TechnologyDongguan 523808China Institute of Metal Research Chinese Academy of SciencesShenyang 110016China School of Materials Science and Engineering Central South UniversityChangsha 410083China Research Center of Medical Sciences Guangdong Provincial People s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China

Magnesium was considered as a revolutionary biodegradable implant material for orthopedic application. Concerning the weakness of intrinsic strength and corrosion beHAvior, a novel strategy of Mg/metal hybrid system was proposed for extension of orthopedic application, especially at load-bearing site. In this work, an Mg and HA composite layered coating was constructed on titanium by means of chemical conversion and vapor deposition. The HA transition interlayer was introduced to enHAnce the bonding between Mg film and Ti substrate. Compared with the bare Mg coating, the Mg/HA coating presented good interface bonding, which avoided the occurrence of Mg film peeling off from the substrate. The Mg/HA coating showed a uniform degradation and kept integrity after immersion of 14 d. The Mg ions release by degradation played a crucial role in osteopromotion and antibacterial effect. Incubation of MC3T3-E1 osteoblasts with the Mg/HA coating showed significant promotion on osteogenic differentiation according to ALP activity and Alizarin Red staining assays. Meanwhile the degradation of Mg exhibited strong suppression of bacteria proliferation. It was believed tHAt this novel Mg/HA composite layered coating could be potentially applied in further development of bio-functional hybrid orthopedic implants.

关键词： magnesium HA composite layered coating titanium orthopedic bio-function

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Bone-like apatite formation on HA/316L stainless steel composite surface in simulated body fluid

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中国有色金属学会会刊：英文版 2009年第2期19卷 347-352页

作者：樊新陈剑邹俭鹏万千周忠诚阮建明 State Key Laboratory of Powder Metallurgy Central South University

HA/316L stainless steel(316L SS) biocomposites were prepared by hot-pressing technique. The formation of bone-like apatite on the biocomposite surfaces in simulated body fluid(SBF) was analyzed by digital pH meter,plasma emission spectrometer,scanning electron microscope(SEM) and energy dispersive X-ray energy spectrometer(EDX). The results indicate tHAt the pH value in SBF varies slightly during the immersion. It is a dynamic process of dissolution-precipitation for the formation of apatite on the surface. With prolonging immersion time,Ca and P ion concentrations increase gradually,and then approach equilibrium. The bone-like apatite layer forms on the composites surface,which possesses benign bioactivity and favorable biocompatibility and achieves osseointegration,and can provide firm fixation between HA60/316L SS composite implants and human body bone.

关键词： 316L不锈钢类骨磷灰石模拟体液复合材料表面 HA 等离子发射光谱仪扫描电子显微镜

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Effect of Hydroxyapatite Coating Surface Morphology on Adsorption BeHAvior of Differently CHArged Proteins

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Journal of Bionic Engineering 2020年第2期17卷 345-356页

作者： Zhihuan He Shili Sun Chunlin Deng School of Materials Science and Engineering South China University of TechnologyGuangzhou 510641China National Engineering Research Center for Tissue Restoration and Reconstruction South China University of TechnologyGuangzhou 510006China Tea Research Institute Guangdong Academy of Agricultural SciencesGuangzhou 510640China Key Laboratory of Biomedical Engineering of Guangdong Province South China University of TechnologyGuangzhou 510006China

The morphology of bone repair materials,such as particle size and roughness of the materials surface,can affect the adsorption of protein molecules.The effects of surface morphology on the absorption of proteins with different cHArges were studied.Submicron and nano hydroxyapatite(HA)powders prepared by the chemical precipitation method were coated on the surface of a gold sheet by electrophoretic deposition.Various hydroxyapatite coating morphologies were obtained by controlling the powder particle size and the deposition time.The coating surface morphology was analyzed by Atomic Force Microscopy(AFM),and the adsorption beHAvior of differently cHArged proteins on the surface was dynamically monitored by Quartz Crystal Microbalance with Dissipation(QCM-D).The adsorption dependence of two proteins with different cHArges upon hydroxyapatite coating surface morphology was investigated.Results show tHAt coating surfaces with smaller deposited particle sizes are favorable for the adsorption of negatively-cHArged bovine albumin,while with larger deposited particles facilitate the adsorption of positively-cHArged lysozyme.This may be because tHAt the negatively-cHArged hydroxyapatite coating exhibits stronger electrostatic effect as the increase in the coating particle size,which facilitates the adsorption of positively-cHArged proteins and hinders the adsorption of negatively-cHArged proteins.Increasing coating surface roughness facilitates protein adsorption,though the particle size exhibits a dominant influence.These results are significant for selective adsorption of proteins on material surfaces.

关键词： HA coating biomedical material electrophoretic deposition surface morphology protein adsorption beHAvior QCM-D

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