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Phase separation of GRP7 facilitated by FERONIAmediated phosphorylation inhibits mRNA translation to modulate plant temperature resilience

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Molecular Plant 2024年第3期17卷 460-477页

作者： Fan Xu Long Wang Yingbin Li junfeng shi Dorothee Staiger Feng Yu state Key Laboratory of Chemo/Biosensing and Chemometrics College of Biologyand Hunan Key Laboratory of Plant Functional Genomics and Developmental RegulationHunanUniversityChangsha 410082P.R.China State Key Laboratory of Hybrid Rice Hunan Agricultural Biotechnology Research InstituteHunan Academy of Agricultural SciencesChangsha 410125P.R.China RNA Biology and Molecular Physiology Faculty of BiologyBielefeld University33615 BielefeldGermany

Changes in ambient temperature profoundly affect plant growth and performance.Therefore,the molecu-larbasis of plant acclimation to temperature fluctuation is of great interest.In this study,we discovered that GLYCINE-RICH RNA-BINDING PROTEIN 7(GRP7)contributes to cold and heat tolerance in Arabidopsis thaliana.We found that exposure to a warm temperature rapidly induces GRP7 condensates in planta,which can be reversed by transfer to a lower temperature.Cell biology and biochemical assays revealed that GRP7 undergoes liquid-liquid phase separation(LLPS)in vivo and in vitro.LLPS of GRP7 in the cyto-plasm contributes to the formation of stress granules that recruit RNA,along with the translation machinery component eukaryotic initiation factor 4E1(elF4E1)and the mRNA chaperones COLD SHOCK PROTEIN 1(CSP1)and CSP3,to inhibit translation.Moreover,natural variations in GRP7 affecting the residue phos-phorylated by the receptorkinase FERONIA alter its capacity to undergo LLPS and correlate with the adap-tation of some Arabidopsis accessions to a widertemperature range.Taken together,ourfindings illustrate the role of translational control mediated by GRP7 LLPS to confer plants with temperature resilience.

关键词： fluctuating temperature glycine-rich RNA-binding protein phase separation cold shock proteins translation

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A novel FGFR1 inhibitor CYY292 suppresses tumor progression,invasion,and metastasis of glioblastoma by inhibiting the Akt/GSK3β/snail signaling axis

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Genes & Diseases 2024年第1期11卷 479-494页

作者： Yanran Bi Ruiling Zheng Jiahao Hu Ruiqing shi junfeng shi Yutao Wang Peng Wang Wenyi Jiang Gyudong Kim Zhiguo Liu Xiaokun Li Li Lin School of Pharmaceutical Science Wenzhou Medical UniversityWenzhouZhejiang 325035China College of Pharmacy and Research Institute of Drug Development Chonnam National UniversityGwangju 61186Republic of Korea Department of Dermatology Wenzhou Hospital of Integrated Traditional Chinese and Western MedicineWenzhouZhejiang 325000China Zhejiang Lab for Regenerative Medicine Oujiang LaboratoryWenzhouZhejiang 325035China

Glioblastoma(GBM)is a malignant brain tumor that grows quickly,spreads widely,and is resistant to treatment.Fibroblast growth factor receptor(FGFR)1 is a receptor tyrosine kinase that regulates cellular processes,including proliferation,survival,migration,and dif-ferentiation.FGFR1 was predominantly expressed in GBM tissues,and FGFR1 expression was negatively correlated with overall survival.We rationally designed a novel small molecule CYY292,which exhibited a strong affinity for the FGFR1 protein in GBM cell lines in vitro.CYY292 also exerted an effect on the conserved Ser777 residue of FGFR1.CYY292 dose-depen-dently inhibited cell proliferation,epithelial-mesenchymal transition,stemness,invasion,and migration in vitro by specifically targeting the FGFR1/AKT/Snail pathways in GBM cells,and this effect was prevented by pharmacological inhibitors and critical gene knockdown.In vivo experiments revealed that CYY292 inhibited U87MG tumor growth more effectively than AZD4547.CYY292 also efficiently reduced GBM cell proliferation and increased survival in orthotopic GBM models.This study further elucidates the function of FGFR1 in the GBM and reveals the effect of CYY292,which targets FGFR1,on downstream signaling pathways directly reducing GBM cell growth,invasion,and metastasis and thus impairing the recruitment,activation,and function of immune cells.

关键词： Blood-brain barrier EMT FGFR1 FGFR1 inhibitor Glioblastoma

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ROR2 promotes invasion and chemoresistance of triple-negative breast cancer cells by activating PI3K/AKT/mTOR signaling

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Oncology Research 2024年第7期32卷 1209-1219页

作者： XIA DA HAN GE junfeng shi CHUNHUA ZHU GUOZHU WANG YUAN FANG JIN XU Department of Breast and Thyroid Nanjing First HospitalNanjing Medical UniversityNanjingChina Department of General Surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjingChina Department of Oncology Nanjing First HospitalNanjing Medical UniversityNanjingChina Department of Pathology Nanjing First HospitalNanjing Medical UniversityNanjingChina

Objective:This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2(ROR2)in triple-negative breast cancer(TNBC).Methods:ROR2 expression in primary TNBC and metastatic TNBC tissues was analyzed by immunohistochemical staining and PCR.ROR2 expression in TNBC cell lines was detected by PCR and Western blot analysis.The migration,invasion and chemosensitivity of TNBC cells with overexpression or knockdown of ROR2 were examined.Results:ROR2 expression was high in metastatic TNBC tissues.ROR2 knockdown suppressed the migration,invasion and chemoresistance of TNBC cells.ROR2 overexpression in MDA-MB-435 cells promoted the migration,invasion,and chemoresistance.Moreover,ROR2 knockdown in HC1599 and MDA-MB-435 adriamycin-resistant cells enhanced chemosensitivity to adriamycin.ROR2 could activate PI3K/AKT/mTOR signaling in TNBC cells.Conclusion:ROR2 is upregulated and promotes metastatic phenotypes of TNBC by activating PI3K/AKT/mTOR signaling.

关键词： Receptor tyrosine kinase-like orphan receptor 2 Triplet-negative breast cancer Proliferation Apoptosis PI3K/AKT/mTOR signaling Metastasis

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Corrigendum to"A novel FGFR1 inhibitor CYY292 suppresses tumor progression,invasion,and metastasis of glioblastoma by inhibiting the Akt/GSK3β/snail signaling axis"[Genes&Diseases 11(2024)479-494]

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Genes & Diseases 2024年第3期11卷 485-490页

作者： Yanran Bi Ruiling Zheng Jiahao Hu Ruiqing shi junfeng shi Yutao Wang Peng Wang Wenyi Jiang Gyudong Kim Zhiguo Liu Xiaokun Li Li Lin School of Pharmaceutical Science Wenzhou Medical UniversityWenzhou 325035China College of Pharmacy and Research Institute of Drug Development Chonnam National UniversityGwangju 61186Republic of Korea Department of Dermatology Wenzhou Hospital of Integrated Traditional Chinese and Western MedicineWenzhou 325000China Zhejiang Lab for Regenerative Medicine Oujiang LaboratoryWenzhou 325035China

The authors regret that in Figure 3C,the Western Blot(WB)image representing GAPDH levels was mistakenly chosen as the same image for ERK(indicated by the red dotted-line rectangle).We have attached the original WB strip for GAPDH to demonstrate that this was an unintentional error in image selection.Additionally,we noticed that the Transwell images in the two upper panels of the right column in Figure 4J are misleading due to errors in image selection.We have attached the original data to show that this was also an unintentional error.We assure you that these two corrections do not alter the scientificconclusionof thearticle.

关键词： GSK3β invasion metastasis

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Rapid characterization of non-volatile phenolic compounds reveals the reliable chemical markers for authentication of traditional Chinese medicine Xiang-ru among confusing Elsholtzia species

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Chinese Journal of Natural Medicines 2024年第4期22卷 375-384页

作者： ZENG Zhen ZHANG Chen HU Jiadong WANG Feiyan WU Ziding WANG Jing ZHANG Jun YANG Shuda CHEN junfeng LI Mingming TONG Qi QIU shi CHEN Wansheng The SATCM Key Laboratory for New Resources&Quality Evaluation of Chinese Medicine Institute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201203China Department of Pharmacy Second Affiliated Hospital of Navy Medical UniversityShanghai 200003China Kunming Plant Classification Biotechnology Co. Ltd.Kunming 650500China School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products Kunming Medical UniversityKunming 650500China State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Beijing100700China

The aerial parts of Mosla chinensis Maxim.and Mosla chinensis cv.'Jiangxiangru'(MCJ)are widely utilized in traditional Chinese medicine(TCM),known collectively as Xiang-ru.However,due to clinical effectiveness concerns and frequent misidentification,the original plants have increasingly been substituted by various species within the genera Elsholtzia and Mosla.The challenge in distinguishing between these genera arises from their similar morphological and metabolic profiles.To address this issue,our study introduced a rapid method for metabolic characterization,employing high-resolution mass spectrometry-based metabolomics.Through detailed biosynthetic and chemometric analyses,we pinpointed five phenolic compounds—salviaflaside,cynaroside,scutellarein-7-O-D-glucoside,rutin,and vicenin-2—among 203 identified compounds,as reliable chemical markers for distinguishing Xiang-ru from closely related Elsholtzia species.This methodology holds promise for broad application in the analysis of plant aerial parts,especially in verifying the authenticity of aromatic traditional medicinal plants.Our findings underscore the importance of non-volatile compounds as dependable chemical markers in the authentication process of aromatic traditional medicinal plants.

关键词： Genus Elsholtzia Genus Mosla Traditional Chinese medicine Xiang-ru Non-volatile phenolic compounds Liquid chromatography-mass spectrometry

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Orchestration of energy metabolism and osteogenesis by Mg^(2+)facilitates low-dose BMP-2-driven regeneration

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Bioactive Materials 2022年第12期7卷 116-127页

作者： Sihan Lin shi Yin junfeng shi Guangzheng Yang Xutao Wen Wenjie Zhang Mingliang Zhou Xinquan Jiang Department of Prosthodontics Shanghai Ninth People’s HospitalShanghai JiaoTong University School of MedicineNo.639 Zhizaoju RoadShanghai200011People’s Republic of China College of Stomatology Shanghai JiaoTong UniversityNo.639 Zhizaoju RoadShanghai200011People’s Republic of China National Center for Stomatology No.639 Zhizaoju RoadShanghai200011People’s Republic of China National Clinical Research Center for Oral Diseases No.639 Zhizaoju RoadShanghai200011People’s Republic of China Shanghai Key Laboratory of Stomatology No.639 Zhizaoju RoadShanghai200011People’s Republic of China Shanghai Engineering Research Center of Advanced Dental Technology and Materials No.639 Zhizaoju RoadShanghai200011People’s Republic of China Department of Oral and Maxillofacial Surgery College and Hospital of StomatologyGuangxi Medical UniversityNo.10 Shuangyong RoadQingxiu DistrictNanningGuangxi530021People’s Republic of China

The clinical application of bone morphogenetic protein-2(BMP-2)is limited by several factors,including ineffectiveness at low doses and severe adverse effects at high doses.To address these efficacy and safety limitations,we explored whether orchestration of energy metabolism and osteogenesis by magnesium ion(Mg^(2+))could reduce the dose and thereby improve the safety of BMP-2.Our results demonstrated that rapid metabolic activation triggered by BMP-2 was indispensable for subsequent osteogenesis.Moreover,inadequate metabolic stimulation was shown to be responsible for the ineffectiveness of low-dose BMP-2.Next,we identified that Mg^(2+),as an"energy propellant",substantially increased cellular bioenergetic levels to support the osteogenesis via the Akt-glycolysis-Mrs2-mitochondrial axis,and consequently enhanced the osteoinductivity of BMP-2.Based on the mechanistic discovery,microgel composite hydrogels were fabricated as low-dose BMP-2/Mg^(2+)codelivery system through microfluidic and 3D printing technologies.An in vivo study further confirmed that rapid and robust bone regeneration was induced by the codelivery system.Collectively,these results suggest that this bioenergetic-driven,cost-effective,low-dose BMP-2-based strategy has substantial potential for bone repair.

关键词： Biomaterials Bone morphogenetic protein-2 Magnesium Energy metabolism Bone regeneration

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Regulating macrophage-MSC interaction to optimize BMP-2-induced osteogenesis in the local microenvironment

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Bioactive Materials 2023年第7期25卷 307-318页

作者： Fei Jiang Xuanyu Qi Xiaolin Wu Sihan Lin junfeng shi Wenjie Zhang Xinquan Jiang Department of Prosthodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineNo.639Zhizaoju RoadShanghai200011China College of Stomatology Shanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Engineering Research Center of Advanced Dental Technology and MaterialsNo.639Zhizaoju RoadShanghai200011China Jiangsu Key Laboratory of Oral Diseases Jiangsu Province Engineering Research Center of Stomatological Translational MedicineNanjing Medical UniversityNo.140Han Zhong RoadNanjing210029China Department of General Dentistry Affiliated Hospital of StomatologyNanjing Medical UniversityNo.136Han Zhong RoadNanjing210029China

Bone morphogenetic protein(BMP-2)has been approved by the FDA to promote bone regeneration,but uncertain osteogenic effect and dose-dependent side effects may occur.Osteoimmunomodulation plays an important role in growth factor-based osteogenesis.Here,we explored how proinflammatory signals affect the dose-dependent osteogenic potential of BMP-2.We observed that the expression level of local IL-1βdid not increase with the dose of BMP-2 in the mouse osteogenesis model.A low dose of BMP-2 could not promote new bone formation,but trigger the release of IL-1βfrom M1 macrophages.As the dose of BMP-2 increased,the IL-1βexpression and M1 infiltration in local microenvironment were inhibited by IL-1Ra from MSCs under osteogenic differentiation induced by BMP-2,and new bone tissues formed,even excessively.Anti-inflammatory drugs(Dexamethasone,Dex)promoted osteogenesis via inhibiting M1 polarization and enhancing BMP-2-induced MSC osteo-differentiation.Thus,we suggest that the osteogenic effect of BMP-2 involves macrophage-MSC interaction that is dependent on BMP-2 dose and based on IL-1R1 ligands,including IL-1βand IL-1Ra.The dose of BMP-2 could be reduced by introducing immunoregulatory strategies.

关键词： BMP-2 Osteogenesis IL-1β IL-1Ra Macrophage-MSC interaction

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Biomineralization inspired 3D printed bioactive glass nanocomposite scaffolds orchestrate diabetic bone regeneration by remodeling micromilieu

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Bioactive Materials 2023年第7期25卷 239-255页

作者： Zeqian Xu Xuanyu Qi Minyue Bao Tian Zhou junfeng shi Zhiyan Xu Mingliang Zhou Aldo R.Boccaccini Kai Zheng Xinquan Jiang Department of Prosthodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineNo.639 Zhizaoju RoadShanghai200011People’s Republic of China College of Stomatology Shanghai Jiao Tong UniversityNo.639 Zhizaoju RoadShanghai200011People’s Republic of China National Center for Stomatology No.639 Zhizaoju RoadShanghai200011People’s Republic of China National Clinical Research Center for Oral Diseases No.639 Zhizaoju RoadShanghai200011People’s Republic of China Shanghai Key Laboratory of Stomatology No.639 Zhizaoju RoadShanghai200011People’s Republic of China Shanghai Engineering Research Center of Advanced Dental Technology and Materials No.639 Zhizaoju RoadShanghai200011People’s Republic of China Department of Oral Maxillofacial-Head and Neck Oncology Shanghai Ninth People’s HospitalCollege of StomatologyShanghai Jiao Tong University School of MedicineShanghai200023People’s Republic of China Institute of Biomaterials University of Erlangen-NurembergCauerstrasse 691058ErlangenGermany Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical UniversityNanjing210029People’s Republic of China Jiangsu Key Laboratory of Oral Diseases Nanjing Medical UniversityNanjing210029People’s Republic of China

TypeⅡdiabetes mellitus(TIIDM)remains a challenging clinical issue for both dentists and orthopedists.By virtue of persistent hyperglycemia and altered host metabolism,the pathologic diabetic micromilieu with chronic inflammation,advanced glycation end products accumulation,and attenuated biomineralization severely impairs bone regeneration efficiency.Aiming to“remodel”the pathologic diabetic micromilieu,we 3D-printed bioscaffolds composed of Sr-containing mesoporous bioactive glass nanoparticles(Sr-MBGNs)and gelatin methacrylate(GelMA).Sr-MBGNs act as a biomineralization precursor embedded in the GelMA-simulated extracellular matrix and release Sr,Ca,and Si ions enhancing osteogenic,angiogenic,and immunomodulatory properties.In addition to angiogenic and anti-inflammatory outcomes,this innovative design reveals that the nanocomposites can modulate extracellular matrix reconstruction and simulate biomineralization by activating lysyl oxidase to form healthy enzymatic crosslinked collagen,promoting cell focal adhesion,modulating osteoblast differentiation,and boosting the release of OCN,the noncollagenous proteins(intrafibrillar mineralization dependent),and thus orchestrating osteogenesis through the Kindlin-2/PTH1R/OCN axis.This 3D-printed bioscaffold provides a multifunctional biomineralization-inspired system that remodels the“barren”diabetic microenvironment and sheds light on the new bone regeneration approaches for TIIDM.

关键词： Biomineralization TypeⅡDiabetes mellitus 3D printing Sr-containing mesoporous bioactive glass nanoparticles Enzymatic cross-links

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2023年采油采气工程技术热点回眸

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科技导报 2024年第1期42卷 136-149页

作者：刘合金旭师俊峰中国石油勘探开发研究院北京100083 多资源协同陆相页岩油绿色开采全国重点实验室大庆163712

2023年,采油采气工程围绕新区效益建产、老油气田挖潜增效、数字化智能化发展和绿色低碳转型等方面开展技术攻关并取得突出创新成果。分层注入领域,智能化水平不断提高、技术适应范围进一步拓展,大幅提升了分层注入的精细化水平;人工举... 详细信息

2023年,采油采气工程围绕新区效益建产、老油气田挖潜增效、数字化智能化发展和绿色低碳转型等方面开展技术攻关并取得突出创新成果。分层注入领域,智能化水平不断提高、技术适应范围进一步拓展,大幅提升了分层注入的精细化水平;人工举升领域,新型高效举升技术指标再创新高、机采提效效果明显、数字化水平明显提升,节能降耗成效显著;采气工艺向绿色智能化采气、全生命周期精细采气、复合排水采气等方向发展,有效推动了天然气产量跨越式增长;储层改造技术取得重大进步,非常规水平井体积压裂2.0向精细化、个性化方向发展,压裂理论、装备工具材料、裂缝监测技术等取得创新突破,为油气高效勘探开发提供有力保障;井下作业领域在带压作业、连续油管作业、数字化智能化修井作业和复杂工况井下作业等方面技术进展明显,有效保障了油气水井健康生产。

关键词：采油采气分层注入人工举升储层改造采气工艺井下作业

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NGS-metabarcoding revealing novel foraminiferal diversity in the Western Pacific Magellan Seamount sediments

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Journal of Oceanology and Limnology 2021年第5期39卷 1718-1729页

作者： junfeng shi Yanli LEI Haotian LI Tiegang LI Laboratory of Marine Organism Taxonomy and Phylogeny Institute of OceanologyChinese Academy of SciencesQingdao 266071China Key Laboratory of Marine Sedimentology and Environmental Geology First Institute of OceanographyMinistry of Natural Resources(MNR)Qingdao 266061China Clinical Research Center Affi liated Hospital of Weifang Medical UniversityWeifang 261031China Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai) Zhuhai 519082China Laboratory for Marine Biology and Biotechnology Pilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266237China University of Chinese Academy of Sciences Beijing 100049China Center for Ocean Mega-Science Chinese Academy of SciencesQingdao 266071China

Seamount is a unique deep-sea ecosystem widely distributed in the world.Its biodiversity is vibrant due to its specific geographical and hydrological conditions.However,the diversity and features of foraminifera in such an environment have rarely been studied.We extracted environmental DNA(eDNA)in sedime nts and amplified the partial small subunit ribo somal DNA(SSU rDNA)of fo raminife ra to understand the foraminiferal diversity from four sites in Magellan Seamount(Western Pacific Ocean).Partial S SU rDNA sequencing was conducted and 912979 foraminiferal reads were obtained and gathered into 266 operational taxonomic units(OTUs).In the available dataset,a high proportion of rare OTUs and low identity OTUs in each studied sample showed that the Magellan Seamount foraminiferal community might have a high genetic novelty.The relative abundance of foraminifera varied between replicates probably due to the existence of bias in amplification process and patchiness of the deep-sea floor.It showed that the Magellan Seamount has a relatively high benthic foraminiferal diversity characterized mainly by monothalamiids(76.37%of total reads)in association with rotaliids(19.03%of total reads),including planktic foraminiferal sequences(38.58%of rotaliids;7.36%of total reads).The remaining reads were assigned to miliolids(0.83%of total reads)and textulariids(0.66%of total reads),and 3.11%of total reads are unassigned to a specific family.The co mparative analysis with foraminiferal assemblage s from coastal and deep-sea environme nts indicated that seamounts could aggregate species from a nearby deep-sea.

关键词： metabarcoding Magellan Seamount foraminifera Western Pacific Ocean

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