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Tumor microenvironment-activatable neuropeptide-drug conjugates enhanced tumor penetration and inhibition via multiple delivery pathways and calcium deposition

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Chinese Chemical Letters 2024年第4期35卷 292-297页

作者： Yi Cao Xiaojiao Ge Yuanyuan Wei Lulu He Aiguo Wu Juan Li Ningbo key laboratory of biomedical Imaging Probe Materials and technology Zhejiang International Cooperation Base of Biomedical Materials Technology and ApplicationChinese Academy of Sciences(CAS)Key Laboratory of Magnetic Materials and DevicesNingbo Cixi Institute of Biomedical EngineeringZhejiang Engineering Research Center for Biomedical MaterialsNingbo Institute of Materials Technology and EngineeringChinese Academy of SciencesNingbo 315201China University of Chinese Academy of Sciences Beijing 100049China Advanced Energy Science and technology guangdong laboratory Huizhou 516000China

Peptide-drug conjugates have achieved considerable development and application as a novel strategy for targeted delivery of anticancer drugs. Bioactive peptides induced calcium deposition can irreversibly assist inhibition of tumors. However, active regulation of calcium level through signal transduction of bioactive substances has not been reported yet. In this study, novel neuropeptide-doxorubicin conjugates(NP-DOX) with lysosome-specific acid response were described for neuropeptide Y_1 receptor(Y_1R)-overexpressed triple-negative breast cancer. The delivery mechanism of NP-DOX was clarified that diverse pathways were involved, including intracellular and intercellular transport. Importantly, up-regulation of Y_1 R-mediated intracellular calcium level via second messenger inositol triphosphate was presented in NP-DOX treated MDA-MB-231 cells. In vivo antitumor efficacy demonstrated that NP-DOX showed less organ toxicity and enhanced tumor inhibition benefited from its controlled release and Y_1R-mediated calcium deposition, compared with free DOX. This bioconjugate is a proof-of-concept confirming that neuropeptide-mediated control of signaling responses in neuropeptide-drug conjugates enables great potential for further applications in tumor chemotherapy.

关键词： Neuropeptide-drug conjugate Tumor penetration Calcium deposition Tumor inhibition Triple-negative breast cancer

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Microstructured Cantilever Probe on Optical Fiber Tip for Microforce Sensor

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Photonic Sensors 2024年第2期14卷 89-99页

作者： Famei WANG Changrui LIAO Mengqiang ZOU Dejun LIU Haoqiang HUANG Chao LIU Yiping WANG Shenzhen key laboratory of Ultrafast Laser Micro/Nano Manufacturing Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education/Guangdong ProvinceCollege of Physics and Optoelectronic EngineeringShenzhen UniversityShenzhen 518060China Shenzhen key laboratory of Photonic Devices and sensing Systems for Internet of Things Guangdong and Hong Kong Joint Research Centre for Optical Fibre SensorsState Key Laboratory of Radio Frequency Heterogeneous IntegrationShenzhen UniversityShenzhen 518060China School of Electronics Science Northeast Petroleum UniversityDaqing 163318China

Benefiting from the great advances of the femtosecond laser two-photon polymerization(TPP)technology,customized microcantilever probes can be accurately 3-dimensional(3D)manufactured at the nanoscale size and thus have exhibited considerable potentials in the fields of microforce,micro-vibration,and microforce *** this work,a controllable microstructured cantilever probe on an optical fiber tip for microforce detection is demonstrated both theoretically and *** static performances of the probe are firstly investigated based on the finite element method(FEM),which provides the basis for the structural *** proposed cantilever probe is then 3D printed by means of the TPP *** experimental results show that the elastic constant k of the proposed cantilever probe can be actively tuned from 2.46N/m to 62.35N/*** force sensitivity is 2.5nm/μN,the Q-factor is 368.93,and the detection limit is ***,the mechanical properties of the cantilever probe can be flexibly adjusted by the geometric configuration of the ***,it has an enormous potential for matching the mechanical properties of biological samples in the direct contact mode.

关键词： Optical fiber sensor microforce sensing microstructured cantilever two-photon polymerization

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Multi-omics Approach Reveals Influenza-A Virus Target Genes Associated Genomic,Clinical and Immunological Characteristics in Cancers

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biomedical and Environmental Sciences 2024年第7期37卷 698-715页

作者： Jiaojiao Wang Yong Liao Pinglian Yang Weile Ye Yong Liu Chunxia Xiao Weixiong Liao Chunbo Chen Zhiping Liu Zunnan Huang Center of Scientific Research Department of CardiologyMaoming People’s HospitalMaoming 525000GuangdongChina Department of Pharmacy Maoming People’s HospitalMaoming 525000GuangdongChina State key laboratory of Bioactive Molecules and Druggability Assessment Jinan UniversityGuangzhou 510632GuangdongChina guangdong province key laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research College of PharmacyJinan UniversityGuangzhou 510632GuangdongChina key laboratory of Big Data Mining and Precision Drug Design of guangdong Medical University Key Laboratory of Computer-Aided Drug Design of Dongguan CityKey Laboratory for Research and Development of Natural Drugs of Guangdong ProvinceSchool of PharmacyGuangdong Medical UniversityDongguan 523808GuangdongChina Department of Critical Care Medicine Maoming People’s HospitalMaoming 525000GuangdongChina

Objective To examine the precise function of influenza A virus target genes(IATGs)in *** Using multi-omics data from the TCGA and TCPA datasets,33 tumor types were evaluated for *** expression in cancer cells was analyzed using transcriptome *** number variation(CNV)was assessed using GISTICS ***’s analysis was used to correlate mRNA expression with methylation *** was used for the enrichment ***’s correlation analysis was used to examine the association between IATG mRNA expression and *** ImmuCellAI algorithm was used to calculate the infiltration scores of 24 immune cell *** In 13 solid tumors,IATG mRNA levels were atypically *** for UCS,UVM,KICH,PCPG,THCA,CHOL,LAMI,and MESO,most cancers contained somatic IATG *** main types of CNVs in IATGs are heterozygous amplifications and *** most tumors,IATG mRNA expression is adversely associated with ***-PCR demonstrated that EGFR,ANXA5,CACNA1C,CD209,UVRAG were upregulated and CLEC4M was downregulated in KIRC cell lines,consistent with the TCGA and GTEx *** Genomic changes and clinical characteristics of IATGs were identified,which may offer fresh perspectives linking the influenza A virus to cancer.

关键词： Genomic changes Immune microenvironment Prognosis Drug resistance Experimental validation

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Mandarin fish von Hippel-Lindau protein regulates the NF-κB signaling pathway via interaction with IκB to promote fish ranavirus replication

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Zoological Research 2024年第5期45卷 990-1000页

作者： Zhi-Min Li Xiao-Wei Qin Qi Zhang Jian He Min-Cong Liang Chuan-Rui Li Yang Yu Weng-Hui Liu Shao-Ping Weng Jian-Guo He Chang-Jun Guo School of Marine Sciences State Key Laboratory for BiocontrolSouthern Marine Science and Engineering Guangdong Laboratory(Zhuhai)Guangdong Province Key Laboratory of Aquatic Economic Animals&Guangdong Provincial Observation and Research Station for Marine Ranching of the Lingdingyang BaySun Yat-sen UniversityGuangzhouGuangdong 510275China guangdong laboratory for Lingnan Modern Agriculture South China Agricultural UniversityGuangzhouGuangdong 510640China

The von Hippel-Lindau tumor suppressor protein(VHL),an E3 ubiquitin ligase,functions as a critical regulator of the oxygen-sensing pathway for targeting hypoxia-inducible *** evidence suggests that mammalian VHL may also be critical to the NF-κB signaling pathway,although the specific molecular mechanisms remain ***,the roles of mandarin fish(Siniperca chuatsi)VHL(scVHL)in the NF-κB signaling pathway and mandarin fish ranavirus(MRV)replication were *** transcription of scVHL was induced by immune stimulation and MRV infection,indicating a potential role in innate ***-luciferase reporter gene assays and reverse transcription quantitative PCR(RT-qPCR)results demonstrated that scVHL evoked and positively regulated the NF-κB signaling *** with NF-κB signaling pathway inhibitors indicated that the role of scVHL may be mediated through scIKKα,scIKKβ,scIκBα,or ***-immunoprecipitation(Co-IP)analysis identified scIκBαas a novel target protein of ***,scVHL targeted scIκBαto catalyze the formation of K63-linked polyubiquitin chains to activate the NF-κB signaling *** MRV infection,NF-κB signaling remained activated,which,in turn,promoted MRV *** findings suggest that scVHL not only positively regulates NF-κB but also significantly enhances MRV *** study reveals a novel function of scVHL in NF-κB signaling and viral infection in fish.

关键词： VHL NF-κB IκBα Ranavirus Mandarin fish

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Recent progress of ultrasound-responsive titanium dioxide sonosensitizers in cancer treatment

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Chinese Chemical Letters 2024年第10期35卷 63-72页

作者： Hajing Cui Weihao Zhu Chuning Yue Ming Yang Wenzhi Ren Aiguo Wu Cixi biomedical Research Institute Wenzhou Medical UniversityNingbo 315300China Ningbo key laboratory of biomedical Imaging Probe Materials and technology Zhejiang International Cooperation Base of Biomedical Materials Technology and ApplicationChinese Academy of Sciences(CAS)Key Laboratory of Magnetic Materials and DevicesNingbo Cixi Institute of Biomedical EngineeringZhejiang Engineering Research Center for Biomedical MaterialsNingbo Institute of Materials Technology and EngineeringChinese Academy of Sciences Ningbo315201China C Advanced Energy Science and Technology Guangdong LaboratoryHuizhou 516000China

Sonodynamic therapy(SDT)exhibits promising clinical applications in cancer treatment owing to its ad-vantages,including ultrasonic cavitation effect,mechanical effect,and deep tissue *** dioxide(TiO_(2))nanomaterials,recognized as excellent sonosensitizers,have been extensively studied in cancer *** review first outlines the mechanism of TiO_(2)-based SDT,then systematically discusses the regulation of TiO_(2) sonosensitivity,covering aspects such as morphology,particle size,element doping,defect engineering,heterojunction structure,and interactions with the tumor ***-more,the review generalizes ultrasound-responsive TiO_(2)-based therapeutic modalities for tumor treat-ment,including SDT,SDT combined with chemotherapy,chemodynamic therapy,photothermal therapy,immunotherapy,and treatment ***,the review navigates the ongoing challenges and prospects in TiO_(2)-based cancer SDT.

关键词： Titanium dioxide Sonodynamic therapy Reactive oxygen species Cavitation effects Combined therapy

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Strain-promoted S-arylation and alkenylation of sulfinamides using arynes and cyclic alkynes

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Science China Chemistry 2024年第3期67卷 928-935页

作者： Xi Zou Boming Shen Gao-lin Li Qian Liang Yanhua Ouyang Binghe Yang Peiyuan Yu Bing Gao State key laboratory of Chemo/Bio-sensing and Chemometrics College of Chemistry and Chemical EngineeringInstitute of Chemical Biology and NanomedicineHunan UniversityChangsha 410082China Department of Chemistry and Shenzhen Grubbs Institute Guangdong Provincial Key Laboratory of CatalysisSouthern University of Science and TechnologyShenzhen 518055China

The conversion of commercially available chiral sulfinamides into pharmaceutically useful chiral sulfoximines via direct SIVfunctionalization is synthetically attractive but challenging due to the competitive reaction of N-functionalization. Herein, we disclose a novel strain-release strategy to access stereospecific and chemoselective SIV-arylation and alkenylation of sulfinamides using arynes and strained cyclic alkynes. This method tolerates an unprecedented chemical diversity of functional groups attached to the nitrogen center(N-R). The origin of the high SIV-selectivity is elucidated by density functional theory calculations, suggesting a stepwise mechanism for the aryne substrates and a concerted mechanism for the cyclic alkynes.

关键词： arylation alkenylation sulfoximines sulfinamides arynes

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Broadband,Polarization-Sensitive,and Self-Powered High-Performance Photodetection of Hetero-Integrated MoS_(2)on Lithium Niobate

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Research 2024年第2期2023卷 203-212页

作者： Zhigang He Heyuan Guan Xijie Liang Junteng Chen Manyan Xie Kaiwen Luo Ran An Liang Ma Fengkai Ma Tiefeng Yang Huihui Lu guangdong Provincial key laboratory of Optical Fiber sensing and Communications Jinan UniversityGuangzhou 510632China key laboratory of Optoelectronic Information and sensing Technologies of guangdong Higher Education Institutes Jinan UniversityGuangzhou 510632China institute of Fluid Physics China Academy of Engineering PhysicsMianyang 621900China College of Physics and Electronic Engineering Hengyang Normal UniversityHengyang 421008China

High-performance photodetectors hold promising potential in optical communication and imaging ***,conventional counterparts are suffering narrow detection range,high power consumption,and poor polarization *** originating from switchable polarization in ferroelectrics can be used to optimize the photo-to-electric procedure and improve the photodetection *** this regard,we constructed a configuration by integrating 2-dimensional molybdenum disulfide(MoS_(2))with ferroelectric lithium niobate(LiNbO_(3)),resulting in the MoS_(2)/LiNbO_(3)heterostructured *** from the pyroelectric effect of LiNbO_(3),the limitation of bandgap on the detection range can be broken,thus broadening the response band of the detector to 365 to 1,064 nm,as well as enabling the self-powered ***,high carrier mobility and decent light absorbance of MoS_(2)introduce robust light-matter interactions with the underlying LiNbO_(3),leading to ultrafast rise/fall times of≈150μs/250μs and switching ratios of up to≈***,the highest responsivity,specific detectivity,and external quantum efficiency achieved were 17.3 A·W^(-1),4.3×10^(11)Jones,and 4,645.78%,***,because of the anisotropy of the spontaneous-polarized LiNbO_(3)substrate,the photocurrent of the device achieved a dichroic ratio of 7.42,comparing favorably to most MoS_(2)-based *** work demonstrates the integration potential between ferroelectric LiNbO_(3)and 2-dimensional materials for high-performance photodetection.

关键词： polarization ferroelectric Polarization

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Self-shrinking supramolecular nanoparticles syndicate energy suppression and NIR-II mild photothermal amplification of mitochondrial oxidative stress for breast cancer therapy

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Nano Research 2024年第5期17卷 4314-4328页

作者： Hongmei Liu Jiming Xu Mengjie Ye Hengbo Zhang Linlin Han Jingting Wang Peng Xue Yuejun Kang Zhigang Xu key laboratory of Luminescence Analysis and Molecular sensing Ministry of EducationSchool of Materials and Energy&Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and DevicesSouthwest UniversityChongqing 400715China key laboratory of Laser technology and Optoelectronic Functional Materials of Hainan province College of Chemistry and Chemical EngineeringHainan Normal UniversityHaikou 571158China Yibin Academy of Southwest University Yibin 644000China

Photothermal therapy(PTT)may lead to healthy tissue damage,tumor metastasis,and recurrence,which makes mild photothermal therapy(mild PTT)stand ***,overcoming heat resistance,insufficient therapeutic effect,and poor photothermal conversion efficiency has become new ***,we report a dynamic supramolecular nanocarrier formed from amide-sericin and aldehyde-polyhydroxy glucan(denoted as SDA),the loose cavity of which can be filled by using the pharmaceutical combination of lonidamine(LND)and NIR-II photothermal agent of IR-1061,producing SDLI with a tighter inner hole,smaller and uniform particle size and excellent stability due to multiple pulling ***,the intricate internal network structure prevents the hydrophobic IR-1061 from forming aggregates in the small cavity,and the photothermal conversion efficiency(PCE)can reach 48.9%.At the acidic tumor microenvironment of pH 6.5,the controlled release of LND can solve the problem of heat resistance of NIR-II mild PTT and significantly improve the therapeutic effect of NIR-II mild ***,SDLI also shows a reasonable tumor inhibition rate,so the synergistic strategy of inhibiting tumor energy metabolism and NIR-II mild PTT to magnify mitochondrial oxidative stress,continuous cell stress state-induced immunogenic cell death to promote the induction of tumor apoptosis is proposed to achieve more effective cancer treatment.

关键词： self-shrinkage dynamic supramolecular nanoparticles tumor energy metabolism NIR-II mild photothermal therapy mitochondrial oxidative stress

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A double-network porous hydrogel based on high internal phase emulsions as a vehicle for potassium sucrose octasulfate delivery accelerates diabetic wound healing

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Regenerative Biomaterials 2024年第4期3卷 82-97页

作者： Zhiwei Wang Lingshun Sun Weixing Wang Zheng Wang Ge Shi Honglian Dai Aixi Yu Department of Orthopedics Trauma and Microsurgery Zhongnan Hospital of Wuhan UniversityWuhan 430070China State key laboratory of Advanced technology for Materials Synthesis and Processing Biomedical Materials and Engineering Research Center of Hubei ProvinceWuhan University of TechnologyWuhan 430070China

Diabetic wounds are a difficult medical *** secretion of matrix metalloproteinase-9(MMP-9)in diabetic wounds further degrades the extracellular matrix and growth factors and causes severe vascular damage,which seriously hinders diabetic wound *** solve these issues,a double-network porous hydrogel composed of poly(methyl methacrylate-co-acrylamide)(p(MMA-co-AM))and polyvinyl alcohol(PVA)was constructed by the high internal phase emulsion(HIPE)technique for the delivery of potassium sucrose octasulfate(PSO),a drug that can inhibit MMPs,increase angiogenesis and improve *** hydrogel possessed a typical polyHIPE hierarchical microstructure with interconnected porous morphologies,high porosity,high specific surface area,excellent mechanical properties and suitable swelling ***,the p(MMA-co-AM)/PVA@PSO hydrogel showed high drug-loading performance and effective PSO *** addition,both in vitro and in vivo studies showed that the p(MMA-co-AM)/PVA@PSO hydrogel had good biocompatibility and significantly accelerated diabetic wound healing by inhibiting excessive MMP-9 in diabetic wounds,increasing growth factor secretion,improving vascularization,increasing collagen deposition and promoting ***,this study provided a reliable therapeutic strategy for diabetic wound healing,some theoretical basis and new insights for the rational design and preparation of wound hydrogel dressings with high porosity,high drug-loading performance and excellent mechanical properties.

关键词： high internal phase emulsions double-network porous hydrogel drug delivery diabetic wound healing sucrose octasulfate

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Enhancing hydrogen evolution and oxidation kinetics through oxygen insertion into nickel lattice

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Journal of Energy Chemistry 2024年第8期95卷 529-539,I0012页

作者： Wanli Liang Xiyu Gong Jinchang Xu Zixuan Dan Fanyan Xie Hulei Yu Hao-Fan Wang Yanshuo Jin Hongjuan Wang Yonghai Cao Hui Meng Hao Yu School of Chemistry and Chemical Engineering South China University of TechnologyGuangzhou 510641GuangdongChina Siyuan laboratory Guangzhou Key Laboratory of Vacuum Coating Technologies and New Energy MaterialsGuangdong Provincial Engineering Technology Research Center of Vacuum Coating Technologies and New Energy MaterialsGuangdong Provincial Key Laboratory of Optical Fiber Sensing and CommunicationsDepartment of PhysicsJinan UniversityGuangzhou 510632GuangdongChina GBA Branch of Aerospace Information Research Institute Chinese Academy of SciencesGuangzhou 510700GuangdongChina Instrumental Analysis&Research Center Sun Yat-sen UniversityGuangzhou 510275GuangdongChina School of Materials Science and Engineering South China University of TechnologyGuangzhou 510641GuangdongChina

Nickel-based materials,including metallic Ni and Ni oxide,have been widely studied in the exploration of non-precious-metal hydrogen electrocatalysts,but neither pure Ni nor NiO is ideal for the hydrogen evolution reaction(HER)and hydrogen oxidation reaction(HOR).In this paper,an oxygen insertion strategy was applied on nickel to regulate its hydrogen electrocatalytic performance,and the oxygen-inserted nickel catalyst was successfully obtained with the assistance of tungsten dioxide support(denoted as O-Ni/WO_(2)).The partial insertion of oxygen in Ni maintains the face-centered cubic arrangement of Ni atoms,simultaneously expanding the lattice and increasing the lattice ***,the adsorption strength of^(*)H and^(*)OH on Ni is optimized,thus resulting in superior electrocatalytic performance of0-Ni/WO_(2)in alkaline HER/*** Tafel slope of O-Ni/WO_(2)@NF for HER is 56 mV dec^(-1),and the kinetic current density of O-Ni/WO_(2)for HOR reaches 4.85 mA cm^(-2),which is ahead of most currently reported *** proposed strategy of inserting an appropriate amount of anions into the metal lattice could provide more possibilities for the design of high-performance catalysts.

关键词： Hydrogen evolution Hydrogen oxidation Nickel Oxygen insertion Adsorption free energy

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