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WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling

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International Journal of oral Science 2024年第1期16卷 85-96页

作者： Qingling Huang Yi Xiao Ting Lan Youguang Lu Li Huang Dali Zheng Department of Biochemistry and Molecular Biology School of Basic Medical SciencesFujian Medical UniversityFuzhouChina Fujian key laboratory of oral diseases School and Hospital of StomatologyFujian Medical UniversityFuzhouChina Department of Preventive Dentistry School and Hospital of StomatologyFujian Medical UniversityFuzhouChina Department of Dentistry The First Affiliated Hospital of Fujian Medical UniversityFuzhouChina

Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

关键词： WNT squamous tumorigenesis

Controllable surface reconstruction of copper foam for electrooxidation of benzyl alcohol integrated with pure hydrogen production

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SmartMat 2024年第1期5卷 147-157页

作者： Yingnan Han Chang Yu Hongling Huang Qianbing Wei Junting Dong Lin Chen Jieshan Qiu State key Lab of Fine Chemicals School of Chemical EngineeringLiaoning Key Lab for Energy Materials and Chemical EngineeringDalian University of TechnologyDalianChina State key laboratory of Chemical Resource Engineering College of Chemical EngineeringBeijing University of Chemical TechnologyBeijingChina

Electrocatalytic water splitting that is coupled with electrocatalytic chemical oxidation is considered as one of the promising methods for efficiently obtaining hydrogen energy and fine chemicals.Herein,we focus on an electrochemical redox activation strategy to rationally manipulate the microstructure and surface valence states of copper foam(CF)and boost the corresponding performance towards electrocatalytic benzyl alcohol oxidation(EBA),accompanied by the efficient hydrogen production.Correspondingly,the Cu(II)‐dominated species are gradually formed on the CF surface with the dissolution and redeposition of copper in the suitable potential range.The new species containing Cu2O,CuO,and Cu(OH)2 during surface reconstruction process of the CF were confirmed by multiple characterization techniques.After 220‐cycled activation(CF‐220),the activated CF achieves an increase of current density for EBA in anode from 9.5 for the original CF to 29.3 mmol/cm2,while the pure hydrogen yield increases threefold than that of the original CF at 1.5 VRHE.The produced new species can endow the CF‐220 with abundant acidity sites,which can enhance the adsorption toward Lewis‐basicity benzyl alcohol,confirmed by NH3‐temperature‐programmed desorption.In situ Raman result further reveals that the as‐produced CuO,Cu(OH)2,and Cu(OH)42−are the main active species toward the EBA process.

关键词： benzyl alcohol copper electrochemical oxidation Lewis acid surface reconstruction

Reduction of photodynamic damage of blood vessels in the protected region by(–)-epigallocatechin gallate

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Journal of Innovative Optical Health Sciences 2024年第3期17卷 93-104页

作者： Tianlong Chen Yi Shen Li Lin Huiyun Lin Xuejiao Song Defu Chen Buhong Li MOE key laboratory of OptoElectronic Science and Technology for Medicine Fujian Provincial Key Laboratory of Photonics TechnologyFujian Normal UniversityFuzhou 350117P.R.China key laboratory of Flexible Electronics and Institute of Advanced Materials Nanjing Technology UniversityNanjing 211800P.R.China School of Medical Technology Beijing Institute of TechnologyBeijing 100081P.R.China

Photodynamic therapy(PDT)has been increasingly used in the clinical treatment of neoplastic,inflammatory and infectious skin diseases.However,the generation of reactive oxygen species(ROS)may induce undesired side effects in normal tissue surrounding the treatment lesion,which is a big challenge for the clinical application of PDT.To date,(–)-Epigallocatechin gallate(EGCG)has been widely proposed as an antiangiogenic and antitumor agent for the protection of normal tissue from ROS-mediated oxidative damage.This study evaluates the regulation ability of EGCG for photodynamic damage of blood vessels during hematoporphyrin monomethyl ether(Hemoporfin)-mediated PDT.The quenching rate constants of EGCG for the triplet-state Hemoporfin and photosensitized 1O2 generation are determined to be 6.8×10^(8)M^(−1)S^(−1),respectively.The vasoconstriction of blood vessels in the protected region treated with EGCG hydrogel after PDT is lower than that of the control region treated with pure hydrogel,suggesting an efficiently reduced photodamage of Hemoporfin for blood vessels treated with EGCG.This study indicates that EGCG is an efficient quencher for triplet-state Hemoporfin and 1O2,and EGCG could be potentially used to reduce the undesired photodamage of normal tissue in clinical PDT.

关键词： (–)-Epigallocatechin gallate(EGCG) photodynamic therapy hemopor¯n singlet oxygen blood vessel vasoconstriction.

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

Contactin-associated protein-like 2(CNTNAP2)mutations impair the essentialα-secretase cleavages,leading to autism-like phenotypes

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1625-1636页

作者： Qing Zhang Mengen Xing Zhengkai Bao Lu Xu Yang Bai Wanqi Chen Wenhao Pan Fang Cai Qunxian Wang Shipeng Guo Jing Zhang Zhe Wang Yili Wu Yun Zhang Jia-Da Li Weihong Song Oujiang laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Zhejiang Key Laboratory of Alzheimer's DiseaseZhejiang Provincial Clinical Research Center for Mental DisordersSchool of Mental Health and Wenzhou Kangning HospitalThe Second Affiliated Hospital and Yuying Children's HospitalInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang 325035China Townsend Family Laboratories Department of PsychiatryBrain Research CenterThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Chongqing key laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders Ministry of Education Key Laboratory of Child Development and DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Center for Medical Genetics Hunan Key Laboratory of Animal Models for Human DiseasesHunan Key Laboratory of Medical GeneticsHunan International Scientific and Technological Cooperation Base of Animal Models for Human DiseasesSchool of Life SciencesCentral South UniversityChangsha 410078 HunanChina The National Clinical Research Center for Geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijing 100053Chin

Mutations in the Contactin-associated protein-like 2(CNTNAP2)gene are associated with autism spectrum disorder(ASD),and ectodomain shedding of the CNTNAP2 protein plays a role in its function.However,key enzymes involved in the C-terminal cleavage of CNTNAP2 remain largely unknown,and the effect of ASD-associated mutations on this process and its role in ASD pathogenesis remain elusive.In this report we showed that CNTNAP2 undergoes sequential cleavages by furin,ADAM10/17-dependent a-secretase and presenilindependent y-secretase.We identified that the cleavage sites of ADAM10 and ADAM17 in CNTNAP2 locate at its C-terminal residue I79 and L96,and the main a-cleavage product C79 by ADAM10 is required for the subsequent y-secretase cleavage to generate CNTNAP2 intracellular domain(CICD).ASD-associated CNTNAP2 mutations impair the a-cleavage to generate C79,and the inhibition leads to ASDIlike repetitive and social behavior abnormalties in the Cntnap2l1254T knock-in mice.Finaly,exogenous expression of 79 improves autism-ike phenotypes in the Cntnap2^(11254T) knock-in and Cntnap2^(-/-)knockout mice.This data demonstrates that the a-secretase is essential for CNTNAP2 processing and its function.Our study indicates that inhibition of the cleavage by pathogenic mutations underlies ASD pathogenesis,and upregulation of its C-terminal fragments could have therapeutical potentials for ASD treatment.

关键词： NAP2 cleavage subsequent

Surface demineralized freeze-dried bone allograft followed by reimplantation in a failed mandibular dental implant

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Regenerative Biomaterials 2024年第1期3卷 82-93页

作者： Jing Zhang Jie Wang Jiayi You Xuan Qin Huimin Chen Xiantong Hu Yantao Zhao Yang Xia Jiangsu key laboratory of oral diseases Nanjing Medical UniversityNanjingJiangsu 210029PR China Jiangsu Province Engineering Research Center of Stomatological Translational Medicine Nanjing Medical UniversityNanjingJiangsu 210029PR China Department of Restorative Dental Sciences Faculty of DentistryThe University of Hong KongHong Kong SARPR China Senior Department of Orthopedics The Fourth Medical Center of PLA General HospitalBeijing100048PR China Beijing Engineering Research Center of Orthopedics Implants Beijing 100048PR China State key laboratory of Military Stomatology Xi'an 710032PR China

The removal of a failed implant with high torque causes significant damage to the surrounding tissue,compromising bone regeneration and subsequent osseointegration in the defect area.Here,we report a case of carrier screw fracture followed by immediate implant removal,bone grafting and delayed reimplantation.A dental implant with a fractured central carrier screw was removed using the bur-forceps technique.The resulting three-wall bone defect was filled with granular surface demineralized freeze-dried bone allograft(SD-FDBA).Cone-beam computerized tomography was performed at 1week,6months and 15months postoperatively and standardized for quantitative evaluation.The alveolar bone width and height at 15months post-surgery were about 91%of the original values,with a slightly lower bone density,calculated using the gray value ratio.The graft site was reopened and was found to be completely healed with dense and vascularized bone along with some residual bone graft.Reimplantation followed by restoration was performed 8months later.The quality of regenerated bone following SD-FDBA grafting was adequate for osseointegration and longterm implant success.The excellent osteogenic properties of SD-FDBA are attributed to its human origin,cortical bone-like structure,partly demineralized surfaces and bone morphogenetic protein-2-containing nature.Further investigation with more cases and longer follow-up was required to confirm the final clinical effect.

关键词： dental implant implant failure allogeneic bone bone regeneration reimplantation

PCDH17 restricts dendritic spine morphogenesis by regulating ROCK2-dependent control of the actin cytoskeleton,modulating emotional behavior

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Zoological Research 2024年第3期45卷 535-550页

作者： Laidong Yu Fangfang Zeng Mengshu Fan Kexuan Zhang Jingjing Duan Yalu Tan Panlin Liao Jin Wen Chenyu Wang Meilin Wang Jialong Yuan Xinxin Pang Yan Huang Yangzhou Zhang Jia-Da Li Zhuohua Zhang Zhonghua Hu Hunan key laboratory of Molecular Precision Medicine Department of Critical Care MedicineXiangya HospitalCentral South UniversityChangshaHunan 410008China Center for Medical Genetics and Hunan key laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangshaHunan 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China Hunan provincial Clinical Research Center for Critical Care Medicine Xiangya HospitalCentral South UniversityChangshaHunan 410008China Hunan key laboratory of Animal Models for Human diseases School of Life SciencesCentral South UniversityChangshaHunan 410008China MOE key Lab of Rare Pediatric diseases School of Life SciencesCentral South UniversityChangshaHunan 410008China Department of Neurosciences University of South China Medical SchoolHengyangHunan 421001China

Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain function.Synaptic abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric disorders.Protocadherin 17(PCDH17)is associated with major mood disorders,including bipolar disorder and depression.However,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain elusive.In this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory neurons.Selective overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in mice.Mechanistically,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)organization.Specifically,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine development.Hence,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.

关键词： Synapse development Dendritic spine Mood disorder Actin cytoskeleton Animal behavior

Preparation of Corncob-Like WO₃ Nanomaterials and Their Photocatalytic Treatment of Toluene

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Journal of Materials Science and Chemical Engineering 2024年第2期12卷 84-93页

作者： Jianhai Wang Lu Lu Bing Xu Hongfeng Xu Hongwen Liu liaoning provincial key laboratory of Metal Air New Energy Battery Dalian Jiaotong University Dalian China Dalian Ecological Environment Monitoring Center of liaoning Province Dalian China

Corn rod-like WO3 nanomaterials were successfully synthesized by a simple hydrothermal method. The morphology, structure and optical absorption properties of the prepared samples were characterized by SEM, XRD, FTIR and UV-Vis-DRS. The WO3 materials were corn rod-like morphology with about 800 nm for length and 150 nm for diameter, especially there were plenty of corn particles (about 20 nm) on the surface of corn rods. The X-ray diffraction peaks of the products corresponded with WO3 standard card, and the characteristic peak of W-O bond was found in the infrared spectrum. The absorption band edge of the products was about 480 nm, indicating their potential visible-light-induced photocatalytic activity. In situ FTIR technology research showed that the prepared WO3 nanomaterials had visible photocatalytic activity to gas-phase toluene. After a photocatalytic reaction for 8 hours toluene was effectively degraded, and carboxylic acid and aldehyde could be regarded as the intermediate products, and CO2 was produced as the final product during the reaction process.

关键词： WO3 Nanomaterials Visiblelight Photocatalytic Degradation Toluene In Situ FTIR

ELABELA-derived peptide ELA13 attenuates kidney fibrosis by inhibiting the Smad and ERK signaling pathways

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第4期25卷 341-353页

作者： Zhibin YAN Ying SHI Runling YANG Jijun XUE Caiyun FU Zhejiang provincial key laboratory of Silkworm Bioreactor and Biomedicine College of Life Sciences and MedicineZhejiang Sci-Tech UniversityHangzhou310018China State key laboratory of Applied Organic Chemistry College of Chemistry and Chemical EngineeringLanzhou University Lanzhou 730000China key laboratory of Preclinical Study for New Drugs of Gansu Province School of Basic Medical Sciences&Research Unit of Peptide ScienceChinese Academy of Medical Sciences2019RU066Lanzhou UniversityLanzhou 730000China

Kidney fibrosis is an inevitable result of various chronic kidney diseases(CKDs)and significantly contributes to end-stage renal failure.Currently,there is no specific treatment available for renal fibrosis.ELA13(amino acid sequence:RRCMPLHSRVPFP)is a conserved region of ELABELA in all vertebrates;however,its biological activity has been very little studied.In the present study,we evaluated the therapeutic effect of ELA13 on transforming growth factor-β1(TGF-β1)-treated NRK-52E cells and unilateral ureteral occlusion(UUO)mice.Our results demonstrated that ELA13 could improve renal function by reducing creatinine and urea nitrogen content in serum,and reduce the expression of fibrosis biomarkers confirmed by Masson staining,immunohistochemistry,real-time polymerase chain reaction(RT-PCR),and western blot.Inflammation biomarkers were increased after UUO and decreased by administration of ELA13.Furthermore,we found that the levels of essential molecules in the mothers against decapentaplegic(Smad)and extracellular signal-regulated kinase(ERK)pathways were reduced by ELA13 treatment in vivo and in vitro.In conclusion,ELA13 protected against kidney fibrosis through inhibiting the Smad and ERK signaling pathways and could thus be a promising candidate for anti-renal fibrosis treatment.

关键词： ELA13 Kidney fibrosis Inflammation Smad Extracllular signal-regulated kinase(ERK)