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Rare loss-of-function variants in FLNB cause non-syndromic orofacial clefts

Journal of Genetics and Genomics 2024年第2期51卷 222-229页

作者： Wenbin Huang shiying zhang Jiuxiang Lin Yi Ding Nan Jiang Jieni zhang Huaxiang Zhao Feng Chen Department of Orthodontics Peking University School and Hospital of StomatologyBeijing100081China Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of StomatologyXi’an Jiaotong UniversityXi’anShaanxi710004China Guangdong Provincial High-level Clinical Key Specialty Guangdong Province Engineering Research Center of Oral Disease Diagnosis and TreatmentDepartment of OrthodonticsStomatological CenterPeking University Shenzhen HospitalShenzhen Peking University-The Hong Kong University of Science and Technology Medical CenterShenzhenGuangdong 518036China Department of Physiology and Pathophysiology School of Basic Medical SciencesXi'an Jiaotong UniversityXi'anShaanxi710049China National Center for Stomatology National Clinical Research Center for Oral DiseasesNational Engineering Laboratory for Digital and Material Technology of StomatologyBeijing Key Laboratory for Digital StomatologyResearch Center of Engineering and Technology for Computerized Dentistry Ministry of HealthNMPA Key Laboratory for Dental MaterialsBeijing100101China Central Laboratory Peking University School and Hospital of StomatologyBeijing100081China

Orofacial clefts (OFCs) are the most common congenital craniofacial disorders, of which the etiology is closely related to rare coding variants. Filamin B (FLNB) is an actin-binding protein implicated in bone formation. FLNB mutations have been identified in several types of syndromic OFCs and previous studies suggest a role of FLNB in the onset of non-syndromic OFCs (NSOFCs). Here, we report two rare heterozygous variants (p.P441T and p.G565R) in FLNB in two unrelated hereditary families with NSOFCs. Bioinformatics analysis suggests that both variants may disrupt the function of FLNB. In mammalian cells, p.P441T and p.G565R variants are less potent to induce cell stretches than wild type FLNB, suggesting that they are loss-of-function mutations. Immunohistochemistry analysis demonstrates that FLNB is abundantly expressed during palatal development. Importantly, Flnb^(−/−) embryos display cleft palates and previously defined skeletal defects. Taken together, our findings reveal that FLNB is required for development of palates in mice and FLNB is a bona fide causal gene for NSOFCs in humans.

关键词： Or ofacial clefts FLNB Loss-of-function mutati on Cleft palate Filamin B Actin flannent Knockout mouse

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Regulating the crystal phase of bismuth-based semiconductors for promoted photocatalytic performance

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Science China Chemistry 2024年第6期67卷 1839-1864页

作者： Zhaohui Wu Mei-Chi Chong shiying zhang Junshan Li Yongfa Zhu Hunan Key Laboratory of Applied Environmental Photocatalysis Changsha UniversityChangsha410022China Department of Chemistry Tsinghua UniversityBeijing100084China Institute for Advanced Study Chengdu UniversityChengdu610106China

Numerous bismuth-based semiconductors(BBSs)with sophisticated and desirable structures used as photocatalysts for efficient photocatalytic degradation of water organic contaminants have attracted considerable attention.However,regulating the crystal phases and phase transition of BBSs for promoted photocatalytic performance is ignored.Herein,the unique crystal structure and band structure features of each typical BBSs,and the vital roles on phase controlling of each phase were systematically presented based on the classification of BBSs.Notably,the critical factors for the phase transition of BBSs and intrinsic driving forces endowed by phases of BBSs for enhanced photocatalytic performance of organic contaminants removal were also elucidated.This review will provide systematical guidelines and horizons for regulating the crystal phase and phase transition of BBSs,promoting photocatalytic degradation and mineralization of organic contaminants.

关键词： bismuth-based semiconductors phase regulation photocatalytic performances organic contaminants

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U-Pb zircon geochronology of basaltic pyroclastic rocks from the basement beneath the Xisha Islands in the northwestern South China Sea and its geological significance

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Acta Oceanologica Sinica 2024年第2期43卷 83-93页

作者： Yu zhang Kefu Yu shiying Li Guangxi Laboratory on the Study of Coral Reefs in the South China Sea Guangxi UniversityNanning 530004China Coral Reef Research Center of China Guangxi UniversityNanning 530004China School of Marine Sciences Guangxi UniversityNanning 530004China Key Laboratory of Ocean and Marginal Sea Geology South China Sea Institute of OceanologyChinese Academy of ScienceGuangzhou 510301China

As one of the micro-blocks dispersed in the South China Sea(SCS), the basement of the Xisha Islands has rarely been drilled because of the thick overlying Cenozoic sediments, which has led to a confused understanding of the pre-Cenozoic basement of the Xisha Islands. Well CK-1, a kilometer-scale major scientific drill in the Xisha Islands in the northwestern SCS, penetrated thick reefal limestone(0–888.4 m) and the underlying basement rocks(888.4–901.4 m). In this study, we present the zircon U-Pb ages of basement basaltic pyroclastic rocks from Well CK-1 in the Xisha Islands of the northwestern SCS to investigate the basement nature of the Xisha microblock. The basement of Well CK-1 consists of basaltic pyroclastic rocks on the seamount. The zircon grains yielded apparent ages ranging from ca. 2 138.9 Ma to ca. 36 Ma. The old group of zircon grains from Well CK-1 was considered to be inherited zircons. Two Cenozoic zircons gave a weighted mean 206Pb/238U age of(36.3 ± 1.1) Ma,Mean Squared Weighted Deviations(MSWD) = 1.2, which may represent the maximum age of the volcano eruption. The Yanshanian inherited zircons(116.9–105.7 Ma and 146.1–130.2 Ma) from Well CK-1 are consistent with the zircons from Well XK-1, indicating that the basement of Chenhang Island may be similar to that of Well XK-1. We propose that the Xisha micro-block may have developed on a uniform Late Jurassic metamorphic crystalline basement, intruded by Cretaceous granitic magma.

关键词： South China Sea Xisha Islands basaltic pyroclastic rocks zircon

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Genomic alterations in oral multiple primary cancers

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International Journal of Oral Science 2024年第1期16卷 145-153页

作者： Wen Wang Qian Wang shiying Sun Pengfei zhang Yuyu Li Weimin Lin Qiwen Li Xiao zhang Zhe Ma Haiyan Lu Hebei Key Laboratory of Stomatology Hebei Clinical Research Center for Oral DiseasesHebei Medical UniversityShijiazhuangChina Department of Orthodontics School and Hospital of StomatologyHebei Medical UniversityShijiazhuangChina State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina Department of Preventive Dentistry School and Hospital of StomatologyHebei Medical UniversityShijiazhuangHebeiChina

Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer, while some patients may develop oral multiple primary cancers (MPCs) with unclear etiology. This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs. Clinicopathological data from patients with oral single primary carcinoma (SPC, n=202) and oral MPCs (n=34) were collected and compared. Copy number alteration (CNA) analysis was conducted to identify chromosomal-instability differences among oral MPCs, recurrent OSCC cases, and OSCC patients with lymph node metastasis. Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients. Additionally, CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients. Our findings revealed that, in contrast to oral SPC, females predominated the oral MPCs (70.59%), while smoking and alcohol use were not frequent in MPCs.Moreover, long-term survival outcomes were poorer in oral MPCs. From a CNA perspective, no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis. In addition to commonly mutated genes such as CASP8, TP53 and MUC16, in oral MPCs we also detected relatively rare mutations, such as HS3ST6 and RFPL4A. Furthermore, this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals, and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.

关键词： alterations metastasis oral

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Green Synthesis of Iron(Ⅱ,Ⅲ)-polyphenol Nanoparticles and Their Adsorption of Malachite Green

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Journal of Wuhan University of Technology(Materials Science) 2024年第4期39卷 1025-1030页

作者：胡玉 ZHOU Fan zhang Nan PAN Xiaobin LI shiying zhang Dong LI Li 张玲帆 Department of Chemistry and Environmental Engineering Hanjiang Normal UniversityShiyan 442000China Shiyan Hydrological and Water Resources Survey Bureau of Hubei Province Shiyan 442000China School of Chemistry and Molecular Engineering East China University of Science and TechnologyShanghai 200237China

Three kinds of iron nanoparticles(FeNPs)were prepared via green route based on pomegranate(PG),green tea(GT),and mulberry(ML)extracts under ambient conditions.The obtained materials were characterized by scanning electron microscopy(SEM),transmission electronic microscopy(TEM),X-ray energy-dispersive spectrometer(EDS),X-ray diffraction(XRD),fourier transform infrared spectroscopy(FTIR),and X-ray photoelectron spectroscopy(XPS)techniques.The experimental results show that FeNPs were in the form of amorphous iron(Ⅱ,Ⅲ)-polyphenol complex with different dispersity and morphologies.GT-Fe has the smallest size range of 25-35 nm,PG-Fe has a moderate size-distribution of 30-40 nm,while ML-Fe formed a tuberous net-type with a sheeting structure.PG-Fe displays the highest removal efficiency of 90.2%in 20 min towards cationic dye of malachite green(16.6%by ML-Fe and 69.3%by GT-Fe),which is attributed to its highest polyphenol content,lowest zeta potential,as well as the most Fe^(2+)on the surface of FeNPs.The removal mechanism was mainly induced by electrostatic adsorption based on pH and zeta potential tests.

关键词： iron nanoparticles pomegranate green tea mulberry adsorption

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Efficient interfacial charge transfer of BiOCl-In_(2)O_(3) step-scheme heterojunction for boosted photocatalytic degradation of ciprofloxacin

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Journal of Materials Science & Technology 2022年第26期121卷 236-244页

作者： Kaiqiang Xu Jie Shen shiying zhang Difa Xu Xiaohua Chen College of Materials Science and Engineering Hunan UniversityChangsha 410082China Hunan Key Laboratory of Applied Environmental Photocatalysis Changsha UniversityChangsha 410005China

BiOCl as a representative layered bismuth-based photocatalyst with Sillén-structure has aroused wide public concern on photocatalytic degradation.However,the photocatalytic efficiency of pristine BiOCl is currently restricted by its low optical absorption and charge separation efficiency.Herein,step-scheme(S-scheme)heterojunctions of In_(2)O_(3) nanoparticle and BiOCl micron-sheet were constructed by a convenient molten salt method by using a LiNO_(3)-KNO_(3) system.The In_(2)O_(3)-BiOCl heterojunctions exhibit higher optical absorption performance from 380 nm to 700 nm than the pristine BiOCl and enhanced photocatalytic property toward ciprofloxacin(CIP)degradation under Xenon lamp illumination.The sample 20%In_(2)O_(3) -BiOCl showed the highest photodegradation efficiency,attaining 91%removal of CIP within 35 min,which was 39.6 times and 3.2 times higher than that of pristine In_(2)O_(3) and BiOCl,respectively.The improved photodegradation property mainly resulted from the novel S-scheme mechanism,which boosted highly efficient separation of the photo-induced carriers.The photoluminescence spectrometric test and transient photocurrent response results demonstrated that In_(2)O_(3)-BiOCl composite exhibited efficient separation of photo-generated charge carriers.This work would provide new insights into the design of novel S-scheme photocatalytic systems with applicability in photocatalytic water treatment.

关键词： Step-scheme photocatalyst In_(2)O_(3) BiOCl Photocatalytic activity Ciprofloxacin

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CD97 inhibits osteoclast differentiation via Rap1a/ERK pathway under compression

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International Journal of Oral Science 2024年第1期16卷 134-144页

作者： Xuan Zhou Xinjia Cai Fengyang Jing Xuefen Li Jianyun zhang Heyu zhang Tiejun Li Department of Oral Pathology Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of Stomatology&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental MaterialsBeijingChina Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions Chinese Academy of Medical Sciences(2019RU034)BeijingChina Central Laboratory Peking University School and Hospital of StomatologyBeijingChina

Acceleration of tooth movement during orthodontic treatment is challenging, with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step. Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages, especially adhesion G protein-coupled receptors (aGPCRs), play important roles in force sensing.However, its role in the regulation of osteoclast differentiation remains unclear. Herein, through single-cell analysis, we revealed that CD97, a novel mechanosensitive aGPCR, was expressed in macrophages. Compression upregulated CD97 expression and inhibited osteoclast differentiation;while knockdown of CD97 partially rescued osteoclast differentiation. It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation. RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression. Consistently, we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity, thereby accelerating tooth movement. In conclusion,our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.

关键词： CD97 osteoclast inhibited

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The transcriptome analysis of cleft lip/palate-related PTCH1 variants in GMSM-K cells show carcinogenic potential

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BIOCELL 2023年第1期47卷 205-214页

作者： MINGZHAO LI QIAN zhang WENBIN HUANG shiying zhang NAN JIANG XIAOSHUAI HUANG FENG CHEN Department of Orthodontics Peking University School and Hospital of StomatologyBeijingChina Central Laboratory Peking University School and Hospital of StomatologyBeijingChina Biomedical Engineering Department Peking UniversityBeijingChina

Cancer progression involves the sonic hedgehog(SHH)pathway,in which the receptor PTCH1 actives the downstream pathways.Dysfunction of PTCH1 can lead to nevoid basal cell carcinoma Syndrome(NBCCs)including neoplastic disease and congenital disorder.To evaluate the relationship between PTCH1 and cancer,we applied the CRISPR/Cas9 system to knock out PTCH1 in oral nontumorous epithelial cells(GMSM-K).Then we screened six PTCH1 variants associated with cleft lip/palate(CL/P),one of the congenital disorders in NBCCs,and generated PTCH1 variant and wild-type recombinant PTCH1^(−/−)GMSM-K cell lines.Transcriptome sequencing was conducted in these cell lines.The results revealed that differentially expressed genes(DEGs)in PTCH1^(−/−)GMSM-K were enriched in extracellular compartments,contributing epithelial diseases by pathway enrichment analysis.RT-PCR confirmed that KRT34,KRT81,KRT86,PDGFB,and WNT10B genes,associated with extracellular compartments were highly expressed in PTCH1^(−/−).The Kyoto Encyclopedia of Genes and Genomes analysis also suggested that DEGs are closely related to focal adhesion,transcriptional misregulation,and proteoglycans in breast and gastric cancers.Comparative analysis of samples revealed that the CL/P-associated PTCH1 variants A443G and V908G are potentially carcinogenic.These findings provide new insights into the carcinogenic potential of PTCH1 dysfunction.

关键词： CRISPR/Cas9 PTCH1 variant Carcinogenic potential Transcriptome sequencing

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靶向肿瘤驱动基因的胃癌治疗研究进展

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浙江大学学报（医学版） 2024年第1期53卷 73-83页

作者：吴世英徐平龙张飞浙江工商大学食品与生物工程学院浙江杭州310018 浙江大学生命系统稳态与保护教育部重点实验室、浙江省癌症分子细胞生物学重点实验室浙江杭州310058 浙江大学杭州国际科创中心智能医药研究所浙江杭州311200 浙江大学生命科学研究院浙江杭州310058 浙江大学癌症研究院浙江杭州310058

随着胃癌致病机制深入解析及胃癌驱动基因的鉴定,靶向胃癌驱动基因的药物逐渐应用临床。其中,曲妥珠单抗作为首个胃癌靶向药物,通过靶向过表达的人表皮生长因子受体2(HER2)抑制肿瘤细胞的增殖、生存和转移等过程,已成为HER2阳性胃癌患... 详细信息

随着胃癌致病机制深入解析及胃癌驱动基因的鉴定,靶向胃癌驱动基因的药物逐渐应用临床。其中,曲妥珠单抗作为首个胃癌靶向药物,通过靶向过表达的人表皮生长因子受体2(HER2)抑制肿瘤细胞的增殖、生存和转移等过程,已成为HER2阳性胃癌患者的一线治疗药物。雷莫芦单抗则通过靶向血管内皮生长因子受体2(VEGFR2)抑制肿瘤血管生成,用于晚期胃癌患者的二线治疗。此外,贝马利珠单抗和佐妥昔单抗分别靶向过度表达的成纤维细胞生长因子受体2(FGFR2)和紧密连接蛋白18.2(CLDN18.2),在临床试验中显著延长胃癌患者的无进展生存期和总生存期。本文回顾了靶向HER2、VEGF、FGFR2、CLDN18.2和MET等肿瘤驱动基因的胃癌治疗策略,介绍了肿瘤驱动基因在胃癌进程中的作用及其靶向药物的应用,以期为胃癌靶向治疗药物的研发和临床应用提供参考。

关键词：胃癌驱动基因靶向治疗临床试验综述

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Piezoelectric nanofoams with the interlaced ultrathin graphene confining Zn–N–C dipoles for efficient piezocatalytic H_(2) evolution under low-frequency vibration

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Journal of Energy Chemistry 2022年第6期31卷 115-122,I0004页

作者： Penghui Hu Yan Xu Yanhua Lei Jie Yuan Rui Lei Rong Hu Junkang Chen Difa Xu shiying zhang Ping Liu Xiangchao zhang Xiaoqing Qiu Wenhui Feng These authors contributed equally to this work.a.Hunan Province Key Laboratory of Applied Environmental Photocatalysis Changsha UniversityChangsha 410022HunanChina College of Chemistry and Chemical Engineering Central South UniversityChangsha 410083HunanChina State Key Laboratory of Photocatalysis on Energy and Environment Fuzhou UniversityFuzhou 350116FujianChina Hunan Provincial Key Laboratory of Xiangnan Rare-Precious Metals Compounds and Application Department of Chemistry and Life ScienceXiangnan UniversityChenzhou 423000HunanChina

Unique nanofoams consisting of interweaved ultrathin graphene confining Zn–N–C dipoles (ZnNG) are constructed via calcination of Zn-coordinated precursor.Due to the introduction of local polar Zn–N–C configurations,with hypersensitivity for mechanical stress,the piezoelectricity is created on the nonpiezoelectric graphene,and the hierarchical ZnNG exhibits obvious piezocatalytic activity of water splitting for H_(2) production even under mild agitation.The corresponding rate of H_(2) production is about 14.65 μmol g^(-1)h^(-1).It triggers a breakthrough in piezocatalytic H_(2) evolution under low-frequency vibration,and takes a significant step forward for piezocatalysis towards practical applications.Furthermore,the presented concept of confining atomic polar configuration for engineering piezoelectricity would open up new horizon for constructing new-type piezoelectrics based on both piezoelectric and nonpiezoelectric materials.

关键词： Piezocatalysis Water splitting for H_(2)production Low-frequency vibration Ultrathin graphene confining Zn–N–C dipoles

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