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RNA m^(6)A reader YTHDF2 facilitates precursor miR-126 maturation to promote acute myeloid leukemia progression

Genes & Diseases 2024年第1期11卷 382-396页

作者： Zheng Zhang Keren Zhou Li Han Andrew Small Jianhuang Xue Huilin Huang Hengyou Weng Rui Su Brandon Tan Chao Shen Wei Li Zhicong Zhao Ying Qing Xi Qin Kitty Wang Keith Leung Mark Boldin Chun-Wei Chen David Ann Zhijian Qian xiaolan deng Jianjun Chen Zhenhua Chen Department of Systems Biology Beckman Research Institute of City of HopeMonroviaCA 91016USA Irell and Manella Graduate School of Biological Sciences Beckman Research Institute of City of HopeDuarteCA 91010USA Gehr Family Center for Leukemia Research City of HopeDuarteCA 91010USA Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdong 510060China Guangzhou Laboratory GuangzhouGuangdong 510005China Bioland Laboratory GuangzhouGuangdong 51005China Department of Liver Surgery Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China Department of Diabetes Complications and Metabolism Beckman Research Institute of City of HopeDuarteCA 91010USA Department of Biochemistry and Molecular Biology University of FloridaGainesvilleFL 32603USA Tongji Hospital Affiliated to Tongji University Frontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China School of Pharmacy China Medical UniversityShenyangLiaoning 110001China

As the most common internal modification of mRNA,Ne-methyladenosine(m^(6)A)and its regulators modulate gene expression and play critical roles in various biological and patholog-ical processes including tumorigenesis.It was reported previously that m^(6)A methyltransferase(writer),methyltransferase-like 3(METTL3)adds m^(6)A in primary microRNAs(pri-miRNAs)and fa-cilitates its processing into precursor miRNAs(pre-miRNAs).However,it is unknown whether m^(6)A modification also plays a role in the maturation process of pre-miRNAs and(if so)whether such a function contributes to tumorigenesis.Here,we found that YTHDF2 is aberrantly overexpressed in acute myeloid leukemia(AML)patients,especially in relapsed patients,and plays an onco-genic role in AML.Moreover,YTHDF2 promotes expression of miR-126-3p(also known as miR-126,as it is the main product of precursor miR-126(pre-miR-126)),a miRNA that was reported as an oncomiRNA in AML,through facilitating the processing of pre-miR-126 into mature miR-126.Mechanistically,YTHDF2 recognizes m^(6)A modification in pre-miR-126 and recruits AGO2,a regulator of pre-miRNA processing,to promote the maturation of pre-miR-126.YTHDF2 posi-tively and negatively correlates with miR-126 and miR-126's downstream target genes,respec-tively,in AML patients,and forced expression of miR-126 could largely rescue YTHDF2/Ythdf2 depletion-mediated suppression on AML cell growth/proliferation and leukemogenesis,indi-cating that miR-126 is a functionally important target of YTHDF2 in AML.Overall,our studies not only reveal a previously unappreciated YTHDF2/miR-126 axis in AML and highlight the ther-apeutic potential of targeting this axis for AML treatment,but also suggest that m^(6)A plays a role in pre-miRNA processing that contributes to tumorigenesis.

关键词： AML miR-126 N^(6)-methyladenosine Pre-miRNA maturation YTHDF2

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Flexible quasi-solid-state dual-ion asymmetric supercapacitor based on Ni（OH）2 and Nb2O5 nanosheet arrays

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Green Energy & Environment 2019年第4期4卷 382-390页

作者： xiaolan deng Yuqi Jiang Zengxi Wei Minglei Mao Ramyakrishna Pothu Hongxia Wang Caiyun Wang Jinping Liu Jianmin Ma School of Physics and Electronics Hunan UniversityChangsha410082China School of Chemistry Chemical Engineering and Life Science State Key Laboratory of Advanced Technology for Materials Synthesis and ProcessingWuhan University of TechnologyWuhan430070China School of Chemistry Physics and Mechanical EngineeringQueensland University of TechnologyBrisbaneQLD4001Australia ARC Centre of Excellence for Electromaterials Science Intelligent Polymer Research InstituteAIIMInnovation CampusUniversity of WollongongNorth WollongongNSWAustralia Key Laboratory of Materials Processing and Mold(Zhengzhou University) Ministry of EducationZhengzhou UniversityZhengzhou450002China

Increasing the energy density, power density as well as widening the operation voltage are essential to electrochemical capacitors to meet the practical energy demands. Herein, a novel flexible quasi-solid-state dual-ion asymmetric supercapacitor(ASC) with Ni(OH)2 and Nb2O5 nanosheets directly grown on stainless steel mesh is developed. In the dual-ion ASC, Nb2O5 negative and Ni(OH)2 positive electrodes react with Li+ and OH- respectively in alkaline gel electrolyte to store energy, which is quite different from conventional alkali metal ion SCs and alkaline SCs. The as-assembled flexible device has an extended working voltage of 1.7 V and delivers a capacity of 5.37 mAh cm-2, a maximum energy density and power density of 0.52 mWh cm-3 and 170 mW cm-3 , respectively. The device maintains around 60% capacity retention after long cycling up to 1000 cycles. Moreover, our device can light up a LED light efficiently upon fast charging. The proposed quasi-solid-state dual-ion ASC has potential applications in future portable electronics and flexible energy storage devices.

关键词： Nickel hydroxide Niobium pentoxide Nanoarrays Flexible supercapacitor Dual ion capacitor

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细节管理结合风险评估在医院感染管理中的应用效果

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中西医结合护理（中英文） 2024年第2期10卷 154-156页

作者：邓风清刘婷陈小兰暨南大学附属顺德医院广东佛山528305

目的明确细节管理结合风险评估对于医院感染管理的实践效果。方法将暨南大学附属顺德医院2021年8月至2023年2月收治的116例住院患者按照入院时间分别纳入对照组(2021年8月至2022年4月,58例)和观察组(2022年5月至2023年2月,58例),2组... 详细信息

目的明确细节管理结合风险评估对于医院感染管理的实践效果。方法将暨南大学附属顺德医院2021年8月至2023年2月收治的116例住院患者按照入院时间分别纳入对照组(2021年8月至2022年4月,58例)和观察组(2022年5月至2023年2月,58例),2组患者在住院期间均接受风险评估及综合护理,观察组加用细节管理。对比2组的医院感染发生率、住院时间及住院费用,并评估2组的医院感染管理质量评分变化。结果观察组的医院感染发生率为1.72%,较对照组的12.07%更低(P<0.05)。观察组的住院时间较对照组更短,住院费用较对照组更少,差异均有统计学意义(P均<0.05)。2组在管理3个月后的消毒隔离、手卫生、医疗废弃物管理、抗生素使用和院感专业技能教学管理质量评分均较管理前升高,观察组在管理3个月后的上述评分均高于对照组,差异均有统计学意义(P均<0.05)。结论在风险评估的基础上结合细节管理,不仅能够降低住院患者的医院感染发生率,还有助于缩短患者的住院时间、减轻住院经济负担,并提高医院感染管理质量。

关键词：医院感染细节管理风险评估管理质量

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A multifunctional flexible sensor based on PI-MXene/SrTiO_(3) hybrid aerogel for tactile perception

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The Innovation 2024年第3期5卷 44-54页

作者： Shihao deng Yue Li Shengzhao Li Shen Yuan Hao Zhu Ju Bai Jingyi Xu Lu Peng Tie Li Ting Zhang Nano Science and Technology Institute University of Science and Technology of China(USTC)Suzhou 215123China i-lab Nano-X Vacuum Interconnected WorkstationKey Laboratory of Multifunctional Nanomaterials and Smart SystemsSuzhou Institute of Nano-Tech and Nano-Bionics(SINANO)Chinese Academy of Sciences(CAS)Suzhou 215123China School of Nano-Tech and Nano-Bionics University of Science and Technology of China(USTC)Hefei 230026China Jiangxi Institute of Nanotechnology 278 Luozhu RoadXiaolan Economic and Technological Development ZoneNanchang 330200China

The inadequacy of tactile perception systems in humanoid robotic manipulators limits the breadth of available robotic applications.Here,we designed a multifunctional flexible tactile sensor for robotic fingers that provides capabilities similar to those of human skin sensing modalities.This sensor utilizes a novel PI-MXene/SrTiO_(3) hybrid aerogel developed as a sensing unit with the additional abilities of electromagnetic transmission and thermal insulation to adapt to certain complex environments.Moreover,polyimide(PI)provides a high-strength skeleton,MXene realizes a pressure-sensing function,and MXene/SrTiO_(3) achieves both thermoelectric and infrared radiation response behaviors.Furthermore,via the pressure response mechanism and unsteady-state heat transfer,these aerogel-derived flexible sensors realize multimodal sensing and recognition capabilities with minimal cross-coupling.They can differentiate among 13 types of hardness and four types of material from objects with accuracies of 94%and 85%,respectively,using a decision tree algorithm.In addition,based on the infrared radiation-sensing function,a sensory array was assembled,and different shapes of objects were successfully recognized.These findings demonstrate that this PI-MXene/SrTiO_(3) aerogel provides a new concept for expanding the multifunctionality of flexible sensors such that the manipulator can more closely reach the tactile level of the human hand.This advancement reduces the difficulty of integrating humanoid robots and provides a new breadth of application scenarios for their possibility.

关键词： utilize integrating insulation

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Controlling the morphology, size and phase of Nb_2O_5 crystals for high electrochemical performance

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Chinese Chemical Letters 2018年第12期29卷 1785-1790页

作者： Jiaqin Liao Rou Tan Zhixiang Kuang Chunyu Cui Zengxi Wei xiaolan deng Zhanheng Yan Yuezhan Feng Fang Li Caiyun Wang Jianmin Ma School of Physics and Electronics Hunan University Key Laboratory of Materials Processing and Mold (Zhengzhou University) Ministry of EducationZhengzhou University ARC Centre of Excellence for Electromaterials Science Intelligent Polymer Research InstituteAIIM FacilityUniversity of Wollongong Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education) Nankai University

The morphology, size and phase of the material play a crucial role in its electrochemical performance.Herein, the nano-sized niobium pentoxide(Nb2O5) with different morphologies and phase structures are synthesized through a very simple thermal treatment method, including the pseudo hexagonal Nb2O5nanosheets and pseudo hexagonal Nb2O5nanoparticles, orthorhombic Nb2O5nanoparticles. The synthesized pseudohexagonal Nb2O5 nanosheets and orthorhombic Nb2O5nanoparticles exhibit better cycling and rate performance than the pseudohexagonal Nb2 O5 nanoparticles due to the different morphologies and phase structures. The T-Nb2O5-700 nanoparticles show the higher capacity(175 mAh/g) than that of TT-Nb2O5-500 nanosheets(127 mAh/g) and TT-Nb2O5-600 nanoparticles(39 mAh/g) at a current density of 50 mA/g and good rate performance with a capacity of 140 mAh/g at 1.0 A/g. The excellent rate capability and cycling stability of orthorhombic T-Nb2O5may be ascribed to the dominant contribution of pseudocapacitive effect. This material has the great potential as a practical high-rate anode material for lithium-ion batteries.

关键词： Nb_2O_5 Lithium-ion battery Pseudocapacitance Anode Crystal phase

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Chang Wei Qing Decoction enhances the anti-tumor effect of PD-1 inhibitor therapy by regulating the immune microenvironment and gut microbiota in colorectal cancer

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Chinese Journal of Natural Medicines 2023年第5期21卷 333-345页

作者： WANG Ting WU Linguangjin WANG Shuyun SHI xiaolan LIU Hui deng Wanli Department of Oncology Putuo HospitalShanghai University of Traditional Chinese MedicineShanghai 200062China Shanghai University of Traditional Chinese Medicine Shanghai 201203China

The anti-tumor effect of anti-PD-1 antibody has long been shown to be strongly related to the tumor immune microenvironment(TIME).This study aimed to mechanistically assess whether Chang Wei Qing(CWQ)Decoction can enhance the anti-tumor effect of PD-1 inhibitor therapy.PD-1 inhibitor therapy showed the significant anti-tumor effect in patients with mismatch repairdeficient/microsatellite instability-high(dMMR/MSI-H)colorectal cancer(CRC),rather than those with mismatch repairproficient/microsatellite stable(pMMR/MSS)CRC.Hence,immunofluorescence double-label staining was utilized to explore the difference in the TIME between dMMR/MSI-H and pMMR/MSS CRC patients.Flow cytometry was used to analyze T-lymphocytes in tumors from mice.Western blot was used to measure the expression of PD-L1 protein in mouse tumors.The intestinal mucosal barrier of mice was evaluated by hematoxylin-eosin staining and immunohistochemistry.16S rRNA-gene sequencing was used to examine the structure of the gut microbiota in mice.Subsequently,Spearman’s correlation analysis was used to analyze the relationship between the gut microbiota and tumor-infiltrating T-lymphocytes.The results showed that dMMR/MSI-H CRC patients had more CD8+T cells and higher expression of PD-1 and PD-L1 proteins.In vivo,CWQ enhanced the anti-tumor effect of anti-PD-1 antibody and increased the infiltration of CD8+and PD-1+CD8+T cells in tumors.Additionally,the combination of CWQ with anti-PD-1 antibody resulted in lower inflammation in the intestinal mucosa than that induced by anti-PD-1 antibody alone.CWQ and anti-PD-1 antibody co-treatment upregulated PD-L1 protein and reduced the abundance of Bacteroides in the gut microbiota but increased the abundance of Akkermansia,Firmicutes,and Actinobacteria.Additionally,the proportion of infiltrated CD8+PD-1+,CD8+,and CD3+T cells were found to be positively correlated with the abundance of Akkermansia.Accordingly,CWQ may modulate the TIME by modifying the gut microbiota and consequently enhance the anti-tumor effect of PD-

关键词： Tumor immune microenvironment PD-1 inhibitor therapy Gut microbiota CD8+T cells Chang Wei Qing

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Clinical heterogeneity of NLRP12-associated autoinflammatory diseases

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Genes & Diseases 2023年第3期10卷 1090-1100页

作者： Yue Li Mengyue deng Yulu Li xiaolan Mao Shi Yan Xuemei Tang Huawei Mao Department of Rheumatology and Immunology Children's Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of Child Infection and ImmunityChongqing 400014China Department of Rheumatology and Immunology Children's Hospital of Chongqing Medical UniversityChongqing 400014China

Nod-like receptor family pyrin domain-containing protein 12 (NLRP12) is one of the critical pattern recognition receptors which participates in the regulation of multiple inflammatory responses. Mutations in NLRP12 cause exceptionally rare NLRP12-associated autoinflammatory disease (NLRP12-AID). So far, very few patients with NLRP12-AID have been identified worldwide;therefore, data on the clinical phenotype and genetic profile are limited. In this study, we reported 10 patients who presented mainly with periodic fever syndrome or arthritis. Next-generation sequencing (NGS) identified 6 heterozygous mutations of NLRP12, including 2 novel null mutations. Of the patients, some with same mutations showed different clinical features. Compared to healthy controls, the increased levels of cytokines were revealed in the patients' plasmas, as well as in the supernatants of patients’ cells stimulated with lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α). The missense mutations did not change the protein expression;but decreased level of NLRP12 protein was shown in the null mutations. And in vitro expression assay demonstrated a truncating protein induced by the frameshift mutation. Further functional studies revealed the deleterious effect of mutations on nuclear factor-kappa B (NF-κB) signaling. Both the null and missense mutations impaired their inhibition of NF-κB activation induced by p65. Collectively, this study reported a relatively large NLRP12-AID case series. Our findings expand the clinical spectrum, and reinforce the diversity of genetic mutations and clinical phenotypes. The NLRP12-associated disorder should be considered when autoinflammatory diseases are encountered in the clinical practice, especially for patients presenting with periodic fever but no other genetic cause identified.

关键词： Autoinflammatory diseases Fanilial cold autoinflammatory syndr ome type 2(FCAS2) NLRP12-Associated autoinflammatory disease(NLRP12-AID) Nod-like receptor family pyrin domain-containing protein 12(NLRP12) Nuclear factor-Kappa B(NF-kB)

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莫诺苷调控糖尿病周围神经病变大鼠坐骨神经氧化应激损伤的机制

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中国当代医药 2024年第18期31卷 4-8页

作者：邓小兰那丽莎于雪张凯曲娜成都市双流区妇幼保健院药学部四川成都610299 牡丹江医学院附属红旗医院药学部黑龙江牡丹江157011

目的探讨莫诺苷对糖尿病周围神经病变(DPN)大鼠坐骨神经氧化应激损伤的影响。方法48只大鼠分为对照组、DPN组、莫诺苷组、莫诺苷+Brusatol组,每组12只。检测空腹血糖、机械痛阈值、热痛阈值、坐骨神经传导速度的变化;透射电镜观察坐骨... 详细信息

目的探讨莫诺苷对糖尿病周围神经病变(DPN)大鼠坐骨神经氧化应激损伤的影响。方法48只大鼠分为对照组、DPN组、莫诺苷组、莫诺苷+Brusatol组,每组12只。检测空腹血糖、机械痛阈值、热痛阈值、坐骨神经传导速度的变化;透射电镜观察坐骨神经超微结构变化;ELISA法检测坐骨神经中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性;Western blot检测坐骨神经中核因子E2相关因子2(Nrf2)、沉默信息调节因子2相关酶1(SIRT_(1))、叉头转录因子o3(Foxo3)蛋白。结果DPN组、莫诺苷组、莫诺苷+Brusatol组坐骨神经髓鞘受损,空腹血糖、热痛阈值、坐骨神经中IL-6、TNF-α、MDA含量高于对照组,机械痛阈值、感觉和运动神经传导速度、坐骨神经中SOD活性及Nrf2、SIRT_(1)、Foxo3蛋白低于对照组,差异有统计学意义(P<0.05);莫诺苷组坐骨神经组织超微结构损伤改善,空腹血糖、热痛阈值、坐骨神经中IL-6、TNF-α、MDA含量低于DPN组,机械痛阈值、感觉和运动神经传导速度、坐骨神经中SOD活性及Nrf2、SIRT_(1)、Foxo3蛋白表达高于DPN组,差异有统计学意义(P<0.05);在莫诺苷组基础上给予Nrf2抑制剂Brusatol后,莫诺苷的保护作用被逆转。结论莫诺苷可能通过激活Nrf2/SIRT_(1)/Foxo3通路改善DPN大鼠坐骨神经氧化应激损伤。

关键词：莫诺苷糖尿病周围神经病变核因子E2相关因子2 沉默信息调节因子2相关酶1 叉头转录因子o3 坐骨神经氧化应激

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Reduced smooth muscle-fibroblasts transformation potentially decreases intestinal wound healing and colitis-associated cancer in ageing mice

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Signal Transduction and Targeted Therapy 2023年第9期8卷 4267-4283页

作者： Yi Liu Yanhong Ji Ruiyi Jiang Chao Fang Gang Shi Lin Cheng Yinan Zuo Yixin Ye xiaolan Su Junshu Li Huiling Wang Yuan Wang Yi Lin Lei Dai Shuang Zhang Hongxin deng Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan University610041 ChengduSichuanThe People’s Republic of China Department of Gastrointestinal Surgery West China Hospital and State Key Laboratory of BiotherapySichuan University610041 ChengduSichuanThe People’s Republic of China Respiratory Microbiome Laboratory Institute of Respiratory HealthFrontiers Science Center for Disease-related Molecular NetworkWest China HospitalSichuan University610041 ChengduSichuanThe People’s Republic of China Department of Biotherapy Cancer CenterWest China HospitalSichuan University and Collaborative Innovation Center for Biotherapy610041 ChengduSichuanThe People’s Republic of China

Cancer and impaired tissue wound healing with ageing are closely related to the quality of life of the elderly population.Given the increased incidence of cancer and the population ageing trend globally,it is very important to explore how ageing impairs tissue wound healing and spontaneous cancer.In a murine model of DSS-induced acute colitis and AOM/DSS-induced colitis-associated cancer(CAC),we found ageing significantly decreases intestinal wound healing and simultaneous CAC initiation,although ageing does not affect the incidence of AOM-induced,sporadic non-inflammatory CRC.Mechanistically,reduced fibroblasts were observed in the colitis microenvironment of ageing mice.Through conditional lineage tracing,an important source of fibroblasts potentially derived from intestinal smooth muscle cells(ISMCs)was identified orchestrating intestinal wound healing and CAC initiation in young mice.However,the number of transformed fibroblasts from ISMCs significantly decreased in ageing mice,accompanied by decreased intestinal wound healing and decreased CAC initiation.ISMCs-fibroblasts transformation in young mice and reduction of this transformation in ageing mice were also confirmed by ex-vivo intestinal muscular layer culture experiments.We further found that activation of YAP/TAZ in ISMCs is required for the transformation of ISMCs into fibroblasts.Meanwhile,the reduction of YAP/TAZ activation in ISMCs during intestinal wound healing was observed in ageing mice.Conditional knockdown of YAP/TAZ in ISMCs of young mice results in reduced fibroblasts in the colitis microenvironment,decreased intestinal wound healing and decreased CAC initiation,similar to the phenotype of ageing mice.In addition,the data from intestine samples derived from inflammatory bowel disease(IBD)patients show that activation of YAP/TAZ also occurs in ISMCs from these patients.Collectively,our work reveals an important role of the ageing stromal microenvironment in intestinal wound healing and CAC initiation.Furthermore,our work also identified a p

关键词： healing wound impaired

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On Almost Type α-F-Z-Weak Contraction in Metric Spaces

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Open Journal of Applied Sciences 2022年第4期12卷 528-540页

作者： Jia deng xiaolan Liu Yan Sun Laxmi Rathour College of Mathematics and Statistics Sichuan University of Science and Engineering Zigong China Key Laboratory of Higher Education of Sichuan Province for Enterprise Informationalization and Internet of Things Zigong China South Sichuan Center for Applied Mathematics Zigong China Ward Number-16 Anuppur Madhya Pradesh India

In this article, we introduce a new type of contraction named almost type α-F-Z-weak contraction, which comes from a combination of F-contraction, Z-contraction, and almost contraction, and then we provide sufficient conditions for the existence and uniqueness of fixed point of such contractions in complete metric spaces and give some related fixed point results. In addition, some related fixed point results can derive from our main results.

关键词： Fixed Point α-Admissible α-F-Z-Weak Contraction Almost Contraction

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