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Facile intercalation of alkali ions in WO_(3)for modulated electronic and optical properties:Implications for artificial synapses and chromogenic application

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science China(Physics,Mechanics & Astronomy) 2024年第2期67卷 149-160页

作者： Changmeng Huan Zihan Lu Silin Tang Yongqing Cai Qingqing Ke School of Microelectronics science and technology Sun Yat-sen UniversityZhuhai 519082China Guangdong Provincial Key Laboratory of Optoelectronic Information Processing Chips and Systems Sun Yat-sen UniversityZhuhai 519082China Institute of Applied Physics and Materials Engineering University of MacaoTaipaMacao 999078China

Tungsten oxides(WO_(3))are widely recognized as multifunctional systems owing to the existence of rich *** diverse phases exhibit distinct octahedra-tilting patterns,generating substantial tunnels that are ideally suited for ***,a quantitative comprehension regarding the impact of distinct phases on the kinetics of intercalated conducting ions remains ***,we employ first-principles calculations to explore the spatial and orientational correlations of ion transport inγ-and h-WO_(3),shedding light on the relationship between diffusion barriers and the size of the conducting *** findings reveal that different types and concentrations of alkali-metals induce distinct and continuous lattice distortions in WO_(3)***,γ-WO_(3)is more appropriate to accommodate Li+ions,exhibiting a diffusion barrier and coefficient of 0.25 eV and 9.31×10^(-8)cm^(2)s^(-1),***,h-WO_(3)features unidirectional and sizeable tunnels that facilitate the transport of K+ions with an even lower barrier and a high coefficient of 0.11 e V and 2.12×10^(-5)cm^(2)s^(-1),***,the introduction of alkali-metal into WO_(3)tunnels tends to introduce n-type conductivity by contributing s-electrons to the unoccupied W 5d states,resulting in enhanced conductivity and tunable electronic *** alkali metals in WO_(3)tunnels are prone to charge transfer,forming small polaronic states and modulating the light absorption in the visible and nearinfrared *** tunable electronic and optical properties,combined with the high diffusion coefficient,underscore the potential of WO_(3)in applications such as artificial synapses and chromogenic devices.

关键词： WO_(3)polymorphs ion insertion kinetic activity tunable electronic and optical properties iontronics

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Multi-Timescale Distributed Approach to Generalized-Nash-Equilibrium Seeking in Noncooperative Nonconvex Games

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IEEE/CAA Journal of Automatica Sinica 2024年第3期11卷 791-793页

作者： Banghua Huang Yang Liu Kit Ian Kou Weihua Gui the School of Mathematical sciences Zhejiang Normal UniversityJinhua 321004China IEEE the Key Laboratory of Intelligent Education technology and Application of Zhejiang Province Jinhua 321004China the Faculty of science and technology University of MacaoMacaoChina the School of Automation Central South UniversityChangsha 410083China

Dear Editor,The distributed generalized-Nash-equilibrium(GNE)seeking in noncooperative games with nonconvexity is the topic of this *** by the sequential quadratic programming(SQP)method,a multi-timescale multi-agent system(MAS)is developed,and its convergence to a critical point of the game is *** illustrate the qualities and efficacy of the theoretical findings,a numerical example is elaborated.

关键词： letter seeking programming

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Combination strategies for first-line treatment of patients with unresectable hepatocellular carcinoma:prospect of natural products

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Chinese Journal of Natural Medicines 2024年第1期22卷 1-3页

作者： ZHANG Lele LU Jinjian School of Basic Medical sciences Chengdu UniversityChengdu 610106China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078China Department of Pharmaceutical sciences Faculty of Health SciencesUniversity of MacaoMacao 999078China

Liver cancer stands as a significant global health concern,contributing substantially to cancer incidence and mortality,particularly in Asian countries[1].Hepatocellular carcinoma(HCC)accounts for approximately 90%of all liver cancer cases and is characterized by a high-risk profile and a generally poor prognosis[2].To address advanced HCC,systemic therapy has been recommended,leading to the approval of a range of treatment regimens in clinical ***,first-line therapy involved the use of multitargeted tyrosine kinase inhibitors(TKIs)such as sorafenib or lenvatinib,while cabozantinib,ramucirumab.

关键词： Unresectable hepatocellular carcinoma Combination strategies Immunotherapy PD-1/PD-L1 Natural products

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Spreadable Magnetic Soft Robots with On-Demand Hardening

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Research 2024年第3期2023卷 487-498页

作者： Zichen Xu Yuanhe Chen Qingsong Xu Department of Electromechanical Engineering Faculty of Science and TechnologyUniversity of MacaoMacaoChina.

Magnetically actuated mobile robots demonstrate attractive advantages in various medical applications due to their wireless and programmable executions with tiny sizes. Confronted with complex application scenarios, however, it requires more flexible and adaptive deployment and utilization methods to fully exploit the functionalities brought by magnetic robots. Herein, we report a design and utilization strategy of magnetic soft robots using a mixture of magnetic particles and non-Newtonian fluidic soft materials to produce programmable, hardened, adhesive, reconfigurable soft robots. For deployment, their ultrasoft structure and adhesion enable them to be spread on various surfaces, achieving magnetic actuation empowerment. The reported technology can potentially improve the functionality of robotic end-effectors and functional surfaces. Experimental results demonstrate that the proposed robots could help to grasp and actuate objects 300 times heavier than their weight. Furthermore, it is the first time we have enhanced the stiffness of mechanical structures for these soft materials by on-demand programmable hardening, enabling the robots to maximize force outputs. These findings offer a promising path to understanding, designing, and leveraging magnetic robots for more powerful applications.

关键词： execution attractive enable

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Small molecule deoxynyboquinone triggers alkylation and ubiquitination of Keap1 at Cys489 on Kelch domain for Nrf2 activation and inflammatory therapy

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Journal of Pharmaceutical Analysis 2024年第3期14卷 401-415页

作者： Ke-Gang Linghu Tian Zhang Guang-Tao Zhang Peng Lv Wen-Jun Zhang Guan-Ding Zhao Shi-Hang Xiong Qiu-Shuo Ma Ming-Ming Zhao Meiwan Chen Yuan-Jia Hu Chang-Sheng Zhang Hua Yu State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SARChina macao Centre for Research and development in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SARChina Key Laboratory of Tropical Marine Bio-resources and Ecology Guangdong Key Laboratory of Marine Materia MedicaRNAM Center for Marine MicrobiologySouth China Sea Institute of OceanologyChinese Academy of SciencesGuangzhou510301China State Key Laboratory of Functions and Applications of Medicinal Plants&School of Pharmaceutical sciences Guizhou Medical UniversityGuiyang550025China

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory ***,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been ***(DNQ)is a natural small molecule discovered from marine *** current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of *** exhibited significant anti-inflammatory properties both in vitro and in *** pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be theα,β-unsaturated amides moieties by a chemical reaction between DNQ and *** exerted anti-inflammatory effects through activation of Nrf2/ARE ***1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving *** specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass *** triggered the ubiquitination and subsequent degradation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of *** findings revealed that DNQ exhibited potent anti-inflammatory capacity throughα,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

关键词： Deoxynyboquinone Anti-inflammation Target Keap1/Nrf2 Alkylation Ubiquitination

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Debris flow runout behaviors considering the influences of densely populated buildings

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Journal of Mountain science 2024年第8期21卷 2696-2712页

作者： ZHANG Shuai FANG Zhe DAI Cong WANG Shuairong PENG Jingyu ZHOU Yiling SHEN Ping MOE Key Laboratory of Soft Soils and Geoenvironmental Engineering Zhejiang UniversityHangzhou 310058China State Key Laboratory of Internet of Things for Smart City and Department of Ocean science and technology University of MacaoMacao SAR 999078China

Debris flows pose serious risks to communities in mountainous areas,often resulting in large losses of human life and *** impeding presence of urban buildings often affects the runout behavior and deposition of debris *** the impact of different building densities and sizes on debris flow dynamics has yet to be quantified to guide urban planning in debris flow risk *** study focused on a debris flow that occurred in Zhouqu County,Gansu Province,China on August 7th,2010,which was catastrophic and destroyed many *** FLO-2D software was used to simulate this debris flow in two scenarios,*** presence and the absence of buildings,to obtain debris-flow intensity *** developed model was then used to further analyze the influence of large buildings and narrow channels within the urban *** simulation results show that considering the presence of buildings in the simulation is essential for accurate assessment of debris flow intensity and deposition *** layout of buildings in the upstream urban area,such as large buildings or parallel buildings which form narrow channels,can affect the flow velocity and depth of debris flow heading towards downstream *** mitigate damage to downstream buildings,the relative spacing(d/a)between upstream and downstream buildings should not exceed a value of two and should ideally be even *** findings provide valuable insights for improving the resistance of mountainous cities to urban debris flows.

关键词： Debris flow Risk Building blockage effect Zhouqu Urban layout

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Mitophagy and cGAS-STING crosstalk in neuroinflammation

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3327-3361页

作者： Xiaogang Zhou Jing Wang Lu Yu Gan Qiao Dalian Qin Betty Yuen-Kwan Law Fang Ren Jianming Wu Anguo Wu Sichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia MedicaKey Laboratory of Medical Electrophysiology of Ministry of EducationSchool of PharmacySouthwest Medical UniversityLuzhou 646000China State Key Laboratory of Quality Research in Chinese Medicine Macao University of Science and TechnologyMacao SAR 999078China Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine Chongqing Traditional Chinese Medicine HospitalChongqing 400021China

Mitophagy,essential for mitochondrial health,selectively degrades damaged *** is intricately linked to the cGAS-STING pathway,which is crucial for innate *** pathway responds to mitochondrial DNA and is associated with cellular stress *** review explores the molecular details and regulatory mechanisms of mitophagy and the cGAS-STING *** critically evaluate the literature demonstrating how dysfunctional mitophagy leads to neuroinflammatory conditions,primarily through the accumulation of damaged mitochondria,which activates the cGAS-STING *** activation prompts the production of pro-inflammatory cytokines,exacerbating *** review emphasizes the interaction between mitophagy and the cGAS-STING *** mitophagy may suppress the cGAS-STING pathway,offering protection against ***,impaired mitophagy may activate the cGAS-STING pathway,leading to chronic ***,we explored how this interaction influences neurodegenerative disorders,suggesting a common mechanism underlying these *** conclusion,there is a need for additional targeted research to unravel the complexities of mitophagy-cGAS-STING interactions and their role in *** review highlights potential therapies targeting these pathways,potentially leading to new treatments for neuroinflammatory and neurodegenerative *** synthesis enhances our understanding of the cellular and molecular foundations of neuroinflammation and opens new therapeutic avenues for neurodegenerative disease research.

关键词： Neuroinflammation Mitophagy cGAS-STING Innate immunity Mitochondrial DNA Crosstalk Therapeutic avenues Neurodegenerative diseases

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Encoding and display technologies for combinatorial libraries in drug discovery:The coming of age from biology to therapy

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3362-3384页

作者： Yu Fan Ruibing Feng Xinya Zhang Zhen-Liang Wang Feng Xiong Shuihua Zhang Zhang-Feng Zhong Hua Yu Qing-Wen Zhang Zhang Zhang Yitao Wang Guodong Li macao Centre for Research and development in Chinese Medicine State Key Laboratory of Quality Research in Chinese MedicineInstitute of Chinese Medical SciencesUniversity of MacaoMacao SAR 999078China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SAR 999078China International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug development Ministry of Education(MoE)of People’s Republic of ChinaCollege of PharmacyJinan UniversityGuangzhou 510632China Zhuhai UM science and technology Research Institute Zhuhai 519031China Department of Pharmacy Guangzhou Red Cross HospitalFaculty of Medical ScienceJinan UniversityGuangzhou 510632China Geriatric Medicine First People’s Hospital of XinXiang and the Fifth Affiliated Hospital of Xinxiang Medical CollegeXinxiang 453100China Shenzhen Innovation Center for Small Molecule Drug Discovery Co. Ltd.Shenzhen 518000China

Drug discovery is a sophisticated process that incorporates scientific innovations and cuttingedge *** to traditional bioactivity-based screening methods,encoding and display technologies for combinatorial libraries have recently advanced from proof-of-principle experiments to promising tools for pharmaceutical hit discovery due to their high screening efficiency,throughput,and resource *** review systematically summarizes the development history,typology,and prospective applications of encoding and displayed technologies,including phage display,ribosomal display,mRNA display,yeast cell display,one-bead one-compound,DNA-encoded,peptide nucleic acidencoded,and new peptide-encoded technologies,and examples of preclinical and clinical *** discuss the progress of novel targeted therapeutic agents,covering a spectrum from small-molecule inhibitors and nonpeptidic macrocycles to linear,monocyclic,and bicyclic peptides,in addition to *** also address the pending challenges and future prospects of drug discovery,including the size of screening libraries,advantages and disadvantages of the technology,clinical translational potential,and market *** review is intended to establish a comprehensive high-throughput drug discovery strategy for scientific researchers and clinical drug developers.

关键词： Drug screening Phage display DNA-encoded chemical libraries Peptide-encoded chemical libraries Clinical drugs

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Trametinib boosts palbociclib’s efficacy in breast cancer via autophagy inhibition

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Oncology Research 2024年第7期32卷 1197-1207页

作者： ANGUO WU JIAO YAN TING SU CHI FENG XIN LONG YIRU PAN RUPEI YE TIAN XIA HANAN LONG JIANMING WU XIULI XIAO Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia MedicaKey Laboratory of Medical Electrophysiology of Ministry of EducationSchool of PharmacySouthwest Medical UniversityLuzhou646000China The Department of Pathology The Affiliated Hospital of Southwest Medical UniversityLuzhou646000China The Department of Pathology Mianyang Central HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaMianyang621000China The Department of Pathology Yongchuan Hospital of Chongqing Medical UniversityChongqing402160China School of Basic Medical sciences Southwest Medical UniversityLuzhou646000China School of Clinical Medical sciences Southwest Medical UniversityLuzhou646000China

Breast cancer,a predominant global health issue,requires ongoing exploration of new therapeutic ***(PAL),a well-known cyclin-dependent kinase(CDK)inhibitor,plays a critical role in breast cancer *** its efﬁcacy is recognized,the interplay between PAL and cellular autophagy,particularly in the context of the RAF/MEK/ERK signaling pathway,remains insufﬁciently *** study investigates PAL’s inhibitory effects on breast cancer using both in vitro(MCF7 and MDA-MB-468 cells)and in vivo(tumor-bearing nude mice)*** at elucidating the impact of PAL on autophagic processes and exploring the potential of combining it with trametinib(TRA),an MEK inhibitor,our research seeks to address the challenge of PAL-induced drug ***ﬁndings reveal that PAL signiﬁcantly decreases the viability of MCF7 and MDA-MB-468 cells and reduces tumor size in mice while showing minimal cytotoxicity in MCF10A ***,PAL also induces protective autophagy,potentially leading to drug resistance via the RAF/MEK/ERK pathway *** TRA effectively neutralized this autophagy,enhancing PAL’s anti-tumor efﬁcacy.A combination of PAL and TRA synergistically reduced cell viability and proliferation,and in vivo studies showed notable tumor size *** conclusion,the PAL and TRA combination emerges as a promising strategy for overcoming PAL-induced resistance,offering a new horizon in breast cancer treatment.

关键词： Palbociclib Trametinib Protective autophagy RAF/MEK/ERK MCF7 MDA-MB-468

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Pyrotinib and chrysin synergistically potentiate autophagy in HER2-positive breast cancer

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Signal Transduction and Targeted Therapy 2024年第1期9卷 295-307页

作者： Xiaoxiao Liu Xing Zhang Zhiying Shao Xiaorong Zhong Xin Ding Liang Wu Jie Chen Ping He Yan Cheng Kunrui Zhu Dan Zheng Jing Jing Ting Luo Institute for Breast Health Medicine Cancer CenterBreast CenterWest China HospitalSichuan University610041 ChengduSichuanChina Department of Radiation Oncology Cancer CenterAffiliated Hospital of Xuzhou Medical UniversityJiangsu Center for the Collaboration and Innovation of Cancer BiotherapyCancer InstituteXuzhou Medical University221000 XuzhouChina Department of Orthopedics Trauma and Reconstructive SurgeryUniversity Hospital RWTH AachenAachen 52074Germany Cancer Institute Xuzhou Medical University221000 XuzhouJiangsuChina Division of Nephrology and Transplantation Department of Internal MedicineUniversity Medical Center Rotterdam Erasmus MCRotterdam 3015 GDThe Netherlands Institute for Breast Health Medicine Department of General SurgeryBreast CenterWest China HospitalSichuan University610041 ChengduSichuanChina Institute for Breast Health Medicine West China HospitalSichuan University610041 ChengduSichuanChina

Human epidermal growth factor receptor 2(HER2)-positive breast cancer(BC)has been the most challenging subtype of BC,consisting of 20%of BC with an apparent correlation with poor *** that pyrotinib,a new HER2 inhibitor,has led to dramatic improvements in prognosis,the efficacy of pyrotinib monotherapy remains largely restricted due to its acquired ***,identifying a new potential antitumor drug in combination with pyrotinib to amplify therapeutic efficacy is a pressing ***,we reported a novel combination of pyrotinib with chrysin and explored its antitumor efficacy and the underlying mechanism in HER2-positive *** determined that pyrotinib combined with chrysin yielded a potent synergistic effect to induce more evident cell cycle arrest,inhibit the proliferation of BT-474 and SK-BR-3 BC cells,and repress in vivo tumor growth in xenograft mice *** may be attributed to enhanced autophagy induced by endoplasmic reticulum ***,the combined treatment of pyrotinib and chrysin induced ubiquitination and glucose-6-phosphate dehydrogenase(G6PD)degradation by upregulating zinc finger and BTB/POZ domain-containing family protein 16(ZBTB16)in tumorigenesis of ***,we identified that miR-16-5p was a potential upstream regulator of ZBTB16,and it showed a significant inverse correlation with *** of miR-16-5p overexpression by restoring ZBTB16 significantly potentiated the overall antitumor efficacy of pyrotinib combined with chrysin against HER2-positive ***,these findings demonstrate that the combined treatment of pyrotinib and chrysin enhances autophagy in HER2-positive BC through an unrecognized miR-16-5p/ZBTB16/G6PD axis.

关键词： HER2 synergistic Together

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