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Triterpenoids-templated self-assembly nanosystem for biomimetic delivery of CRISPR/Cas9 based on the synergy of TLR-2 and ICB to enhance HCC immunotherapy

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3205-3217页

作者： Bing-Chen Zhang Chun-Mei Lai Bang-Yue Luo jing-wei shao Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy College of ChemistryFuzhou UniversityFuzhou 350116China Department of Laboratory Medicine Dongguan Institute of Clinical Cancer Researchthe Tenth Affiliated Hospital of Southern Medical University(Dongguan People’s Hospital)Dongguan 523058China College of Materials and Chemical Engineering MinjiangUniversityFuzhou350108China

Combination immunotherapy has shown promising potential for enhancing the objective response rate compared to immune checkpoint blockade(ICB)***,combination therapy with multi-drugs is limited by the different properties of the agents and inconsistent synergistic targeted ***,based on a universal triterpene template and the anticancer active agent ursolic acid(UA),a cytomembrane-coated biomimetic delivery nanoplatform(UR@M)prepared by the selfassembly of a PD-L1 targeted CRISPR/Cas9 system and UA was designed for hepatocellular carcinoma(HCC)***@M showed enhanced tumor accumulation in vivo with homologous tumor targeting,and CRISPR in the nanosystem exhibited potent gene-editing efficiency of 76.53% in vitro and 62.42% in vivo with no off-target *** activated the natural immune system through the TLR-2-MyD88-TRAF6 pathway,which synergistically enhanced the proliferation of natural killer cells and dendritic cells and realized excellent immune cytotoxic T cell infiltration by combining with the ICB of *** strategy of work along both lines based on innate immune and adaptive immunity displayed a significant effect in tumor ***,the UA-templated strategy“killed three birds with one stone”by establishing a self-assembly nanosystem,inducing tumor cell death,and promoting synergistic immunostimulation for HCC treatment.

关键词： Ursolic acid Self-assembly Biomimetic nanoplatform Hepatocellular carcinoma CRISPR/Cas9 Immune checkpoint blockade Gene therapy Immunotherapy

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Quantum Properties of Two-Mode Squeezed Even and Odd Coherent States

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Communications in Theoretical Physics 2007年第2期47卷 317-324页

作者： ZHANG jing WU wei MENG shao-Ying Department of Physics Laboratory of Atoms and Radiation Liaoning University Shenyang 110036 China

Two new types of quantum states are constructed by applying the operator s（ξ） = exp（ξ＊ ab - ξa＋b＋） on the two-mode even and odd coherent states. The mathematical and quantum statistical properties of such states are investigated. Various nonclassical features of these states, such as squeezing properties, the inter-mode photon bunching, and the violation of Cauchy-Schwarz inequality, are discussed. The Wigner function in these states are studied in detail.

关键词： two-mode squeezed even/odd coherent states quantum statistical properties

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Cellular senescence-driven transcriptional reprogramming of the MAFB/NOTCH3 axis activates the PI3K/AKT pathway and promotes osteosarcoma progression

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Genes & Diseases 2024年第2期11卷 952-963页

作者： Zhenhao Zhang Doudou jing Baijun Xuan Zhicai Zhang wei Wu Zengwu shao Department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Department of Orthopedics The Second Hospital of Shanxi Medical UniversityTaiyuanShanxi 030001China Department of Cardiology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China

Osteosarcoma is the most common primary malignancy of bones and primarily occurs in adolescents and young ***,a second smaller peak of osteosarcoma incidence was reported in the elderly aged more than *** patients with osteosarcoma exhibit different characteristics compared to young patients,which usually results in a poor *** mechanism underlying osteosarcoma development in elderly patients is intriguing and of significant value in clinical *** cells can accelerate tumor progression by metabolic *** research has shown that methylmalonic acid(MMA)was significantly up-regulated in the serum of older individuals and played a central role in the development of aggressive *** found that the significant accumulation of MMA in elderly patients imparted proliferative potential to osteosarcoma *** expression of MAFB was excessively up-regulated in osteosarcoma specimens and was further enhanced in response to MMA accumulation as the patient ***,we first confirmed a novel molecular mechanism between cellular senescence and cancer,in which the MMA-driven transcriptional reprogramming of the MAFB-NOTCH3 axis accelerated osteosarcoma progression via the activation of PI3K-AKT ***,the down-regulation of the MAFB-NOTCH3 axis increased the sensitivity and effect of AKT inhibitors in osteosarcoma through significant inhibition of AKT *** conclusion,we confirmed that MAFB is a novel age-dependent biomarker for osteosarcoma,and targeting the MAFB-NOTCH3 axis in combination with AKT inhibition can serve as a novel therapeutic strategy for elderly patients with osteosarcoma in experimental and clinical trials.

关键词： Cellular senescence Elderly patients MAFB-NOTCH3axis Methylmalonic acid Osteosarcoma PI3K-AKTpathway

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Aerial target threat assessment based on gated recurrent unit and self-attention mechanism

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Journal of Systems Engineering and Electronics 2024年第2期35卷 361-373页

作者： CHEN Chen QUAN wei shao Zhuang School of Automation Beijing Institute of TechnologyBeijing 100081China State Key Laboratory of Intelligent Control and Decision of Complex Systems Beijing 100081China

Aerial threat assessment is a crucial link in modern air combat, whose result counts a great deal for commanders to make decisions. With the consideration that the existing threat assessment methods have difficulties in dealing with high dimensional time series target data, a threat assessment method based on self-attention mechanism and gated recurrent unit(SAGRU) is proposed. Firstly, a threat feature system including air combat situations and capability features is established. Moreover, a data augmentation process based on fractional Fourier transform(FRFT) is applied to extract more valuable information from time series situation features. Furthermore, aiming to capture key characteristics of battlefield evolution, a bidirectional GRU and SA mechanisms are designed for enhanced ***, after the concatenation of the processed air combat situation and capability features, the target threat level will be predicted by fully connected neural layers and the softmax classifier. Finally, in order to validate this model, an air combat dataset generated by a combat simulation system is introduced for model training and testing. The comparison experiments show the proposed model has structural rationality and can perform threat assessment faster and more accurately than the other existing models based on deep learning.

关键词： target threat assessment gated recurrent unit(GRU) self-attention(SA) fractional Fourier transform(FRFT)

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Left-sided vagus nerve stimulation improves cardiopulmonary resuscitation outcomes in rats as effectively as right-sided vagus nerve stimulation

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World Journal of Emergency Medicine 2021年第4期12卷 309-316页

作者： wei-jing shao Ting-ting Shu Shuang Xu Li-cai Liang Jehane Michael Le Grange Yu-ran Zhou He Huang Yu Cai Qing Zhang Peng Sun Department of Emergency Medicine Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of Intensive Care Unit Wuhan Hospital of Traditional Chinese MedicineWuhan 430000China Department of Emergency Medicine the Second Affi liated Hospital of Zhejiang University School of MedicineHangzhou 310009China Department of Emergency Medicine Hankou Branch of Central Theater General HospitalWuhan 430070China Department of Ultrasound Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of Anesthesiology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China

BACKGROUND: Our group previously reported that right-sided vagus nerve stimulation(RVNS) significantly improved outcomes after cardiopulmonary resuscitation(CPR) in a rat model of cardiac arrest(CA). However, whether left-sided vagus nerve stimulation(LVNS) could achieve the same effect as RVNS in CPR outcomes remains ***: A rat model of CA was established using modified percutaneous epicardial electrical stimulation to induce ventricular fibrillation(VF). Rats were treated with LVNS or RVNS for 30 minutes before the induction of VF. All animals were observed closely within 72 hours after return of spontaneous circulation(ROSC), and their health and behavior were evaluated every 24 ***: Compared with those in the RVNS group, the hemodynamic measurements in the LVNS group decreased more notably. Vagus nerve stimulation(VNS) decreased the serum levels of tumor necrosis factor-alpha(TNF-α) and the arrhythmia score, and attenuated inflammatory infiltration in myocardial tissue after ROSC, regardless of the side of stimulation, compared with findings in the CPR group. Both LVNS and RVNS ameliorated myocardial function and increased the expression of α-7 nicotinic acetylcholine receptor in the myocardium after ROSC. Moreover, a clear improvement in 72-hour survival was shown with VNS pre-treatment, with no significant difference in efficacy when comparing the laterality of stimulation. CONCLUSIONS: LVNS may have similar effects as RVNS on improving outcomes after CPR.

关键词： Vagus nerve stimulation Cardiac arrest Tumor necrosis factor-alpha Myocardial function α-7 nicotinic acetylcholine receptor

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Mixed‑Dimensional Assembly Strategy to Construct Reduced Graphene Oxide/Carbon Foams Heterostructures for Microwave Absorption,Anti‑Corrosion and Thermal Insulation

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Nano-Micro Letters 2024年第11期16卷 1-18页

作者： Beibei Zhan Yunpeng Qu Xiaosi Qi Junfei Ding Jiao‑jing shao Xiu Gong jing‑Liang Yang Yanli Chen Qiong Peng wei Zhong Hualiang Lv College of Physics Guizhou Province Key Laboratory for Photoelectrics Technology and ApplicationGuizhou UniversityGuiyang City 550025People’s Republic of China College of Materials and Metallurgy Guizhou UniversityGuiyang City 550025People’s Republic of China National Laboratory of Solid State Microstructures and Jiangsu Provincial Laboratory for NanoTechnology Nanjing UniversityNanjing 210093People’s Republic of China Department of Materials Science and Laboratory of Advanced Materials Fudan UniversityShanghai 200433People’s Republic of China

Considering the serious electromagnetic wave(EMW)pollution problems and complex application condition,there is a pressing need to amalgamate multiple functionalities within a single ***,the effective integration of diverse functions into designed EMW absorption materials still faces the huge ***,reduced graphene oxide/carbon foams(RGO/CFs)with two-dimensional/three-dimensional(2D/3D)van der Waals(vdWs)heterostructures were meticulously engineered and synthesized utilizing an efficient methodology involving freeze-drying,immersing absorption,secondary freeze-drying,followed by carbonization *** to their excellent linkage effect of amplified dielectric loss and optimized impedance matching,the designed 2D/3D RGO/CFs vdWs heterostructures demonstrated commendable EMW absorption performances,achieving a broad absorption bandwidth of 6.2 GHz and a reflection loss of-50.58 dB with the low matching ***,the obtained 2D/3D RGO/CFs vdWs heterostructures also displayed the significant radar stealth properties,good corrosion resistance performances as well as outstanding thermal insulation capabilities,displaying the great potential in complex and variable ***,this work not only demonstrated a straightforward method for fabricating 2D/3D vdWs heterostructures,but also outlined a powerful mixeddimensional assembly strategy for engineering multifunctional foams for electromagnetic protection,aerospace and other complex conditions.

关键词： Multifunctionality Reduced graphene oxide/carbon foams 2D/3D van der Waals heterostructures Electromagnetic wave absorption Thermal insulation

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Thermodynamic nature of black holes in coexistence region

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Science China(Physics,Mechanics & Astronomy) 2024年第5期67卷 27-32页

作者： shao-Wen wei Yu-Xiao Liu Lanzhou Center for Theoretical Physics Key Laboratory of Theoretical Physics of Gansu Provinceand Key Laboratory of Quantum Theory and Applications of Mo ELanzhou UniversityLanzhou 730000China Institute of Theoretical Physics&Research Center of Gravitation Lanzhou UniversityLanzhou 730000China

Studying the system state of coexistence regions will peek into to reveal microscopic interactions between different phases of a thermodynamic ***,there is no effective method to study thermodynamic nature of the coexistence black hole regions for the failure of the equation of *** at these coexistence states,in this work,we develop a general approach by introducing two new ratio *** first one is the ratio of the horizon radii of the saturated coexistence small and large black holes,and the second one measures that of the small black hole molecule number to the total molecule *** demonstrate that the first parameter can serve as an order parameter to characterize the first-order phase *** study also shows that the black hole state in the coexistence region is uniquely determined by these two introduced parameters bounded between 0 and *** results are quite significant in the analytical study of phase transition and the microscopic nature of black hole in the coexistence regions.

关键词： transition. state. thermodynamic

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Highly active and durable core-shell electrocatalysts for proton exchange membrane fuel cells

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Nano Research 2024年第10期17卷 8772-8784页

作者： Hsiwen Wu Fei Xiao jing Wang Meng Gu Minhua shao Department of Chemical and Biological Engineering The Hong Kong University of Science and TechnologyClear Water BayHong KongChina Department of Materials Science and Engineering Southern University of Science and TechnologyShenzhen 518055China Fok Ying Tung Research Institute The Hong Kong University of Science and TechnologyGuangzhou 511458China Energy Institute and Chinese National Engineering Research Center for Control&Treatment of Heavy Metal Pollution The Hong Kong University of Science and TechnologyClear Water BayHong KongChina

This work presents simple post-treatment methods to selectively and partially remove the Pd core of Pd-Pt core–shell(Pt@Pd/C)*** proton exchange membrane fuel cell with the post-treated Pt@Pd/C cathode(Pt loading:0.10 mg·cm^(-2))delivers an impressive peak power density of 1.2 W·cm^(-2).The partial removal of Pd core endows an ultrahigh oxygen reduction reaction(ORR)mass activity of 0.32 A·g_(PGM)-1 when normalized to the platinum group metal(PGM)mass,or equivalently 0.55 A·mg_(Pt)^(-1) at 0.9 V measured in a fuel *** post-treatment thickens the Pt shells and mitigates the Pd dissolution during potential *** a result,the post-treated core-shell catalyst demonstrates superior durability in ORR mass activity and polarization power density retention than untreated core-shell catalyst and benchmark Pt/***-situ inductively coupled plasmamass spectrometry(ICP-MS)results highlight that the amount of dissolved Pd in post-treated core–shell catalyst is 17-times lower than that of the untreated *** findings highlight the importance of structural tuning of catalysts in enhancing their mass activity and durability.

关键词： core-shell catalyst platinum monolayer proton exchange membrane fuel cell oxygen reduction reaction durability

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Unraveling the role of NiSnPH@OOH/CC perovskite hydroxide for efficient electrocatalytic oxidation of methanol to formate

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Nano Research 2024年第4期17卷 2388-2399页

作者： jing shao Yusheng Fang Xiaobing Wu Muhammad Imran Abdullah Youkun Tao College of Chemistry and Environmental Engineering Shenzhen UniversityShenzhen 518060China School of Science Harbin Institute of TechnologyShenzhen 518055China

The sluggish kinetics of oxygen evolution reaction(OER)is the key tailback for hydrogen production from the water *** OER with thermodynamically auspicious methanol oxidation reaction(MOR)can significantly boost the H_(2) and value-added products ***,it is currently challenging to achieve a synergistic manipulation of product selectivity and performance for MOR ***,we report NiSnPH@OOH/CC(CC=carbon cloth)perovskite hydroxide nanosphere as an efficient MOR electrocatalyst with high activity,stability,and selectivity towards methanol oxidation to formate.A surface amorphous layer of defect rich NiOOH was generated in operando by selective Sn leaching with stable perovskite hydroxide bulk structure,which mitigates the oxidative power and optimizes the local coordination environment of the active NiOOH *** situ Raman combined with electrochemical studies further confirm the key active species,NiOOH,generated in operando enhance the MOR and blocking the over oxidation of methanol to CO_(2).As a result,NiSnPH@OOH/CC effectively masks the OER and attains>99%selectivity with 100%Faradic efficiency for *** results of this study show the advances of NiSnPH@OOH/CC as an efficient electrocatalyst for MOR and also suggest its potential applications for various small organic molecules oxidation.

关键词： perovskite hydroxide small organic molecules nickel oxy(hydroxide) value-added products methanol oxidation reaction

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Molecular Characteristics of Cephalosporin-Resistant Neisseria gonorrhoeae Strains in China:A Retrospective Study

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International Journal of Dermatology and Venereology 2024年第2期7卷 78-83页

作者： Jin Zhang Xiao-Yu Zhu jing-wei Liu Yue-Ping Yin shao-Chun Chen Reference Laboratory for STD Control Hospital for Skin Diseases(Institute of Dermatology)Chinese Academy of Medical Sciences&Peking Union Medical CollegeNanjingJiangsu 210042China National Center for STD Control Chinese Center for Disease Control and PreventionNanjingJiangsu 210042China

Objective:An increasing level of antimicrobial resistance to extended-spectrum cephalosporins has been reported,so we conducted this study to investigate the molecular characteristics of cephalosporin resistant Neisseria gonorrhoeae(NG)strains isolated from China Gonococcal Antimicrobial Resistance Surveillance Programme(China-GRSP).Methods:In total,2,038 NG isolates were collected from the China-GRSP between 2015 and *** multiantigen sequence typing(NG-MAST),multilocus sequence typing(MLST),and NG sequence typing for antimicrobial resistance(NG-STAR)were used to determine characteristics and resistant determinants of cephalosporin-resistant *** results are described as ***:Seventy-four(3.6%)cephalosporin-resistant isolates were ***_(ST7363)was the most prevalent MLST among cefixime-resistant(CFX-R)isolates,whereas MLST_(ST7365)(n=8)in was the most prevalent sequence type among ceftriaxone-resistant(CRO-R)***-R strains were mainly associated with penA-X(n=27,44.3%),penA-XIII(n=6,9.8%),penA-XVIII(n=5,8.2%),and CRO-R strains were mainly related to penA-XVIII(n=10,25.6%),penA-43(n=9,23.1%),penA-XIII(n=7,17.9%).Conclusion:The main conclusion of this study is that the predominant cephalosporin-resistant clones in China include locally emerged and imported *** CFX-R and CRO-R strains are primarily related to penA mutations,and their predominant genotypes are *** the increase in international travel,tracking high-risk-resistant clones and identifying outbreaks and their associations with epidemiological characteristics are critical to improve public health.

关键词： gonorrhea resistance cephalosporin cefixime ceftriaxone

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