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Acidic/hypoxia dual-alleviated nanoregulators for enhanced treatment of tumor chemo-immunotherapy

Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 136-152页

作者： Xiaoju Guo Xiaoxiao Chen Jiayi Ding Feng Zhang shunyang Chen Xin Hu Shiji Fang Lin Shen Chenying Lu Zhongwei Zhao Jianfei Tu gaofeng shu Minjiang Chen Jiansong Ji Lishui Central Hospital Shaoxing UniversityShaoxing 312000China Zhejiang Key Laboratory of Imaging and Interventional Medicine Imaging Diagnosis and Interventional Minimally Invasive InstituteThe Fifth Affiliated Hospital of Wenzhou Medical UniversityLishui 323000China Clinical College of The Affiliated Central Hospital School of MedicineLishui UniversityLishui 323000China Key Laboratory of Precision Medicine of Lishui Lishui 323000China

Chemotherapy plays a crucial role in triple-negative breast cancer (TNBC) treatment as it not only directly kills cancer cells but also induces immunogenic cell death. However, the chemotherapeutic efficacy was strongly restricted by the acidic and hypoxic tumor environment. Herein, we have successfully formulated PLGA-based nanoparticles concurrently loaded with doxorubicin (DOX), hemoglobin (Hb) and CaCO3 by a CaCO3-assisted emulsion method, aiming at the effective treatment of TNBC. We found that the obtained nanomedicine (DHCaNPs) exhibited effective drug encapsulation and pH-responsive drug release behavior. Moreover, DHCaNPs demonstrated robust capabilities in neutralizing protons and oxygen transport. Consequently, DHCaNPs could not only serve as oxygen nanoshuttles to attenuate tumor hypoxia but also neutralize the acidic tumor microenvironment (TME) by depleting lactic acid, thereby effectively overcoming the resistance to chemotherapy. Furthermore, DHCaNPs demonstrated a notable ability to enhance antitumor immune responses by increasing the frequency of tumor-infiltrating effector lymphocytes and reducing the frequency of various immune-suppressive cells, therefore exhibiting a superior efficacy in suppressing tumor growth and metastasis when combined with anti-PD-L1 (αPD-L1) immunotherapy. In summary, this study highlights that DHCaNPs could effectively attenuate the acidic and hypoxic TME, offering a promising strategy to figure out an enhanced chemo-immunotherapy to benefit TNBC patients.

关键词： CaCO3-based nanoparticles Hypoxia attenuation Acidity neutralization Reversal of chemotherapy resistance Enhanced chemo-immunotherapy

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Mucosal immune responses to Ichthyophthirius multifiliis in the ocular mucosa of rainbow trout(Oncorhynchus mykiss,Walbaum),an ancient teleost fish

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Marine Life Science & Technology 2024年第2期6卷 266-279页

作者： Weiguang Kong Guangyi Ding gaofeng Cheng Peng Yang Zhen Xu Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture Institute of HydrobiologyChinese Academy of SciencesWuhan 430072China Department of Aquatic Animal Medicine College of FisheriesHuazhong Agricultural UniversityWuhan 430070China

The eye,as a specialized visual organ,is directly exposed to the external environment,and,therefore,it faces constant chal-lenges from external pathogenic organisms and toxins.In the ocular mucosa(OM)of mammals,mucosal-associated lymphoid tissues(MALTs)constitute the primary line of defense.However,the immune defense role of the OM remains unknown in aquatic vertebrates.To gain insights into the immune processes within the OM of teleost fish,we developed an infection model of rainbow trout(Oncorhynchus mykiss)OM using a parasite,Ichthyophthirius multifiliis(Ich).Immunofluorescence,qPCR,and H&E staining revealed that Ich successfully infiltrates the OM of rainbow trout,leading to pathological struc-tural changes,as evidenced by A&B staining.Importantly,the qPCR results indicate an up-regulation of immune-related genes following Ich infection in the OM.Moreover,transcriptome analyses were conducted to detect immune responses and impairments in eye function within the OM of rainbow trout with Ich infection.The results of the transcriptome analysis that Ich infection can cause an extensive immune response in the OM,ultimately affecting ocular function.To the best of our knowledge,our findings represent for the first time that the teleost OM could act as an invasion site for parasites and trigger a strong mucosal immune response to parasitic infection.

关键词： Ocular mucosa Mucosal immunity Transcriptome analysis Oncorhynchus mykiss Ichthyophthirius multifiliis

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Identification of tumor-suppressor genes in lung squamous cell carcinoma through integrated bioinformatics analyses

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Oncology Research 2024年第1期32卷 187-197页

作者： HENG LI YOUMING LEI gaofeng LI YUNCHAO HUANG The 2nd Department of Thoracic Surgery The Third Affiliated Hospital of Kunming Medical UniversityYunnan Tumor HospitalKunming650118China The 1st Department of Thoracic Surgery The Third Affiliated Hospital of Kunming Medical UniversityYunnan Tumor HospitalKunming650118China Department of Geriatric Thoracic Surgery The First Affiliated Hospital of Kunming Medical UniversityKunming650032China

Lung cancer is a prevalent malignancy,and fatalities of the disease exceed 400,000 cases worldwide.Lung squamous cell carcinoma(LUSC)has been recognized as the most common pathological form of lung cancer.The comprehensive understanding of molecular features related to LUSC progression has great significance in LUSC prognosis assessment and clinical management.In this study,we aim to identify a panel of signature genes closely associated with LUSC,which can provide novel insights into the progression of LUSC.Gene expression profiles were retrieved from public resources including gene expression omnibus(GEO)and the cancer genome atlas(TCGA)database.Differentially expressed genes(DEGs)between LUSC specimens and normal lung tissues were identified by bioinformatics analyses.A total of 66 DEGs were identified based on two cohorts of data.CytoHubba plugin of Cytoscape software was utilized for the further analyses of the top 10 candidate hub genes including OGN,ABI3BP,MAMDC2,FGF7,FAM107A,SPARCL1,DCN,COL14A1,and MFAP4 and CHRDL1,which showed significant downregulation in LUSC.Two LUSC cell lines were used to validate the functions of CHRDL1 and FAM107A through overexpression experiment.Together,our data revealed novel candidate tumor-suppressor genes in LUSC,suggesting previously unappreciated mechanisms in the progression of LUSC.

关键词： LUSC DEGs WGCNA PPI network Tumor-suppressor

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Co-Sharing Waveform Design for Millimeter-Wave Radar Communication Systems

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China Communications 2024年第6期21卷 305-318页

作者： Cui gaofeng He Mengmin Xu Lexi Wang Changheng Wang Weidong School of Electronic Engineering Beijing University of Posts and TelecommunicationsBeijing 100876China Key Laboratory of Universal Wireless Communications Ministry of EducationBeijing University of Posts and TelecommunicationsBeijing 100876China China United Network Communications Corporation Beijing 100048China

Millimeter-wave(mmWave)radar communication has emerged as an important technique for future wireless systems.However,the interference between the radar signal and communication data is the main issue that should be considered for the joint radar communication system.In this paper,a co-sharing waveform(CSW)is proposed to achieve communication and radar sensing simultaneously.To eliminate the co-interference between the communication and sensing signal,signal splitting and processing methods for communication data demodulation and radar signal processing are given respectively.Simulation results show that the bit error rate(BER)of CSW is close to that of the pure communication waveform.Moreover,the proposed CSW can achieve better performance than the existing waveforms in terms of range and velocity estimation.

关键词： co-sharing waveform millimeter-wave radar communication radar sensing range and velocity estimation

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The use of electrokinetics promises a sustainable mining future

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The Innovation 2024年第3期5卷 17-18页

作者： gaofeng Wang Xiaoliang Liang Jianxi Zhu Hongping He CAS Key Laboratory of Mineralogy and Metallogeny/Guangdong Provincial Key Laboratory of Mineral Physics and Material Guangzhou Institute of GeochemistryChinese Academy of SciencesGuangzhou 510640China CAS Center for Excellence in Deep Earth Science Guangzhou 510640China University of the Chinese Academy of Sciences Beijing 100049China

Moving toward a zero-carbon economy is an ambitious goal of all human beings.Utilization of various metal resources plays a central role in such a transition.Rare earth elements(REEs),especially heavy REEs(HREEs),are crucial for the development of future green and zero-carbon economies due to their irreplaceable roles in many applications of renewable energy technologies;e.g.,solar panels,wind turbines,and hybrid vehicle batteries.Ion-adsorption rare earth deposits(IADs)are the primary repositories for HREEs and supply more than 95%of the global HREE demand.1 However,current mining technologies using excessive ammonium salts have caused devastating harm to the local environment while exhibiting a low recovery rate of REEs,a long mining period,and landslide risks.Since 2018,the adoption of ammonium salt-based techniques in REE mining has been prohibited,exacerbating the scarcity of REEs that could lead to disruptions of the supply chain.Moreover,metals are currently almost exclusively extracted from their ores via physical excavation or chemical leaching.These energy-intensive and environmentally damaging techniques remain among the foremost CO_(2) emitters.The mining industry is in desperate need of a new generation of mining technology.

关键词： mining replace earth

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采用改进特征子空间投影的SAR脉冲式直达波干扰抑制方法

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电子与信息学报 2024年第4期46卷 1382-1390页

作者：舒高峰刘明月李宁河南大学计算机与信息工程学院开封475004 河南大学河南省大数据分析与处理重点实验室开封475004 河南大学河南省空间信息处理工程研究中心开封475004

射频干扰(RFI)会污染合成孔径雷达(SAR)回波信号,增加SAR图像解译难度。脉冲式直达波干扰(PDWI)作为典型的RFI,在原始回波域以明亮条纹状掩盖SAR回波信息,对SAR成像质量产生严重影响。现有的干扰抑制方法中,传统的特征子空间投影(ESP)... 详细信息

射频干扰(RFI)会污染合成孔径雷达(SAR)回波信号,增加SAR图像解译难度。脉冲式直达波干扰(PDWI)作为典型的RFI,在原始回波域以明亮条纹状掩盖SAR回波信息,对SAR成像质量产生严重影响。现有的干扰抑制方法中,传统的特征子空间投影(ESP)方法对整条含干扰脉冲进行干扰抑制,造成了脉冲中非干扰位置有用信号损失。为了保护有用信号,该文提出一种改进ESP的SAR脉冲式直达波干扰抑制方法。首先,通过两次检测干扰,获取PDWI在时域中的具体位置。其次,仅对检测的干扰位置数据,采用ESP将有用信号和干扰信号分离。最后,从原始数据中减去ESP重构的干扰数据以实现干扰抑制。仿真和实测数据处理表明,与现有方法相比,该方法能够有效避免SAR原始数据中有用信号的损失,抑制了脉冲式直达波干扰。

关键词：射频干扰合成孔径雷达脉冲式直达波干扰特征子空间投影

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SHARP MORREY REGULARITY THEORY FOR A FOURTH ORDER GEOMETRICAL EQUATION

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Acta Mathematica Scientia 2024年第2期44卷 420-430页

作者：向长林郑高峰 Three Gorges Mathematical Research Center China Three Gorges UniversityYichang443002China School of Mathematics and Statistics Central China Normal UniversityWuhan430079China

This paper is a continuation of recent work by Guo-Xiang-Zheng[10].We deduce the sharp Morrey regularity theory for weak solutions to the fourth order nonhomogeneous Lamm-Rivière equation △^{2}u=△(V▽u)+div(w▽u)+(▽ω+F)·▽u+f in B^(4),under the smallest regularity assumptions of V,ω,ω,F,where f belongs to some Morrey spaces.This work was motivated by many geometrical problems such as the flow of biharmonic mappings.Our results deepens the Lp type regularity theory of[10],and generalizes the work of Du,Kang and Wang[4]on a second order problem to our fourth order problems.

关键词： fourth order elliptic equation regularity theory Morrey space decay estimates Riesz potential

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Elevated peripheral levels of receptor-interacting protein kinase 1(RIPK1)and IL-8 as biomarkers of human amyotrophic lateral sclerosis

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Signal Transduction and Targeted Therapy 2024年第1期9卷 271-278页

作者： Jun Wei Min Li Zhi Ye Xinqian Hu Xiaoyan He Jia Wang gaofeng Chen Chengyu Zou Daichao Xu Hongbing Zhang Junying Yuan Yunhong Zha Institute of Neural Regeneration and Repair and Department of Neurology The First College of Clinical Medical ScienceYichang Central HospitalCollege of Basic Medical ScienceChina Three Gorges UniversityHubei Province Clinical Medical Research Center for Rare Diseases of Nervous SystemYichang 443000China Interdisciplinary Research Center on Biology and Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai Key Laboratory of Aging StudiesShanghai 201210China State Key Laboratory of Common Mechanism Research for Major Diseases Haihe Laboratory of Cell EcosystemDepartment of PhysiologyInstitute of Basic Medical Sciences and School of Basic MedicineChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Amyotrophic lateral sclerosis(ALS)is a devastating fatal neurodegenerative disease with no cure.Receptor-interacting protein kinase 1(RIPK1)has been proposed to mediate pathogenesis of ALS.Primidone has been identified as an old drug that can also inhibit RIPK1 kinase.We conducted a drug-repurposing biomarker study of primidone as a RIPK1 inhibitor using SOD1G93A mice and ALS patients.SOD1G93A mice treated with primidone showed significant delay of symptomatic onset and improved motor performance.One-hundred-sixty-two ALS participants dosed daily with primidone(62.5 mg)completed 24-week follow-up.A significant reduction was showed in serum levels of RIPK1 and IL-8,which were significantly higher in ALS patients than that of healthy controls(P<0.0001).Serum RIPK1 levels were correlated positively with the severity of bulbar symptoms(P<0.05).Our study suggests that serum levels of RIPK1 and IL-8 in peripheral can be used as clinical biomarkers for the activation of RIPK1 in central nervous system in human ALS patients.Repurposing primidone may provide a promising therapeutic strategy for ALS.The effect of primidone for the treatment of other inflammatory diseases may also be considered,since the activation of RIPK1 has been implicated in mediating a variety of inflammatory diseases including COVID-19-associated cytokine release syndrome(CRS).(ChiCTR2200060149).

关键词： RIPK1 diseases Serum

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Fucoidan-based dual-targeting mesoporous polydopamine for enhanced MRI-guided chemo-photothermal therapy of HCC via P-selectin-mediated drug delivery

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Asian Journal of Pharmaceutical Sciences 2022年第6期17卷 908-923页

作者： gaofeng shu Lin Shen Jiayi Ding Junchao Yu Xiaoxiao Chen Xiaoju Guo Enqi Qiao Yaning Chen Chenying Lu Zhongwei Zhao Yongzhong Du Minjiang Chen Jiansong Ji Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research Institute of Imaging Diagnosis and Minimally Invasive Intervention ResearchThe Fifth Affiliated Hospital of Wenzhou Medical UniversityLishui 323000China Department of radiology Lishui Hospital of Zhejiang UniversitySchool of MedicineLishui 323000China Institute of Pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Shaoxing University School of Medcine Shaoxing 312000China

The development of novel theranostic agents with outstanding diagnostic and therapeutic performances is still strongly desired in the treatment of hepatocellular carcinoma(HCC).Here,a fucoidan-modified mesoporous polydopamine nanoparticle dual-loaded with gadolinium iron and doxorubicin(FMPDA/Gd^(3+)/DOX)was prepared as an effective theranostic agent for magnetic resonance imaging(MRI)-guided chemo-photothermal therapy of HCC.It was found that FMPDA/Gd^(3+)/DOX had a high photothermal conversion efficiency of 33.4%and excellent T1-MRI performance with a longitudinal relaxivity(r1)value of 14.966 m M^(-1)·s^(-1).Moreover,the results suggested that FMPDA/Gd^(3+)/DOX could effectively accumulate into the tumor foci by dual-targeting the tumor-infiltrated platelets and HCC cells,which resulted from the specific interaction between fucoidan and overexpressed p-selectin receptors.The excellent tumor-homing ability and MRI-guided chemo-photothermal therapy therefore endowed FMPDA/Gd^(3+)/DOX with a strongest ability to inhibit tumor growth than the respective single treatment modality.Overall,our study demonstrated that FMPDA/Gd^(3+)/DOX could be applied as a potential nanoplatform for safe and effective cancer theranostics.

关键词： Mesoporous polydopamine Fucoidan P-selectin target Platelets bridge Cancer theranostics

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Flexible capacitive pressure sensor based on interdigital electrodes with porous microneedle arrays for physiological signal monitoring

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Nanotechnology and Precision Engineering 2024年第1期7卷 18-31页

作者： Jiahui Xu Minghao Wang Minyi Jin Siyan Shang Chuner Ni Yili Hu Xun Sun Jun Xu Bowen Ji Le Li Yuhua Cheng gaofeng Wang School of Electronics&Information MOE Engineering Research Center of Smart Microsensors and MicrosystemsHangzhou Dianzi UniversityHangzhou 310018China Wenzhou Institute of Hangzhou Dianzi University Wenzhou 310018China Key Laboratory of Intelligent Operation and Maintenance Technology&Equipment for Urban Rail Transit of Zhejiang Province College of EngineeringInstitute of Precision Machinery and Smart StructureZhejiang Normal UniversityJinhua 321004China Institute of Guizhou Aerospace Measuring and Testing Technology Guiyang 550009China Unmanned System Research Institute Northwestern Polytechnical UniversityXi’an 710072China Research&Development Institute of Northwestern Polytechnical University in Shenzhen Shenzhen 518057China

Flexible pressure sensors have many potential applications in the monitoring of physiological signals because of their good biocompatibil-ity and wearability.However,their relatively low sensitivity,linearity,and stability have hindered their large-scale commercial application.Herein,aﬂexible capacitive pressure sensor based on an interdigital electrode structure with two porous microneedle arrays(MNAs)is pro-posed.The porous substrate that constitutes the MNA is a mixed product of polydimethylsiloxane and NaHCO3.Due to its porous and interdigital structure,the maximum sensitivity(0.07 kPa-1)of a porous MNA-based pressure sensor was found to be seven times higher than that of an imporous MNA pressure sensor,and it was much greater than that of aﬂat pressure sensor without a porous MNA structure.Finite-element analysis showed that the interdigital MNA structure can greatly increase the strain and improve the sensitivity of the sen-sor.In addition,the porous MNA-based pressure sensor was found to have good stability over 1500 loading cycles as a result of its bilayer parylene-enhanced conductive electrode structure.Most importantly,it was found that the sensor could accurately monitor the motion of aﬁnger,wrist joint,arm,face,abdomen,eye,and Adam’s apple.Furthermore,preliminary semantic recognition was achieved by monitoring the movement of the Adam’s apple.Finally,multiple pressure sensors were integrated into a 33 array to detect a spatial pressure distribu-×tion.Compared to the sensors reported in previous works,the interdigital electrode structure presented in this work improves sensitivity and stability by modifying the electrode layer rather than the dielectric layer.

关键词： Capacitive pressure sensor Microneedle array Porous PDMS Interdigital electrode

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