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Development of antibody-drug conjugates in cancer:Overview and prospects

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Cancer Communications 2024年第1期44卷 3-22页

作者： Dan-Yun Ruan hao-Xiang wu Qi Meng Rui-hua Xu Department of Clinical Research Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat-sen UniversityGuangzhouGuangdongP.R.China Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer Chinese Academy of Medical SciencesGuangzhouGuangdongP.R.China Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat-sen UniversityGuangzhouGuangdongP.R.China

In recent years,remarkable breakthroughs have been reported on antibody-drug conjugates(ADCs),with 15 ADCs successfully entering the market over the past *** substantial development has positioned ADCs as one of the fastest-growing domains in the realm of anticancer drugs,demonstrating their efficacy in treating awide array of ***,there is still an unmet clin-ical need forwider application,better efficacy,and fewer side effects of *** ADC generally comprises an antibody,a linker and a payload,and the combina-tion has profound effects on drug structure,pharmacokinetic profile and ***,optimization of the key components provides an opportunity to develop ADCs with higher potency and fewer side *** this review,we comprehen-sively reviewed the current development and the prospects of ADC,provided an analysis of marketed ADCs and the ongoing pipelines globally as well as in China,highlighted several ADC platforms and technologies specific to different pharmaceutical enterprises and biotech companies,and also discussed the new related technologies,possibility of next-generation ADCs and the directions of clinical research.

关键词： companies breakthrough payload

Learnware:small models do big

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Science China(Information Sciences) 2024年第1期67卷 39-50页

作者： Zhi-hua ZHOU Zhi-hao TAN National Key Laboratory for Novel Software Technology Nanjing University

There are complaints about current machine learning techniques such as the requirement of a huge amount of training data and proficient training skills,the difficulty of continual learning,the risk of catastrophic forgetting,and the leaking of data privacy/*** research efforts have been focusing on one of those concerned issues separately,paying less attention to the fact that most issues are entangled in *** prevailing big model paradigm,which has achieved impressive results in natural language processing and computer vision applications,has not yet addressed those issues,whereas becoming a serious source of carbon *** article offers an overview of the learnware paradigm,which attempts to enable users not to need to build machine learning models from scratch,with the hope of reusing small models to do things even beyond their original purposes,where the key ingredient is the specification which enables a trained model to be adequately identified to reuse according to the requirement of future users who know nothing about the model in advance.

关键词： artificial intelligence machine learning learnware

Experimental observation of spontaneous symmetry breaking in a quantum phase transition

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Science China(Physics,Mechanics & Astronomy) 2024年第2期67卷 34-39页

作者： Wen Ning Ri-hua Zheng Jia-hao Lu Fan wu Zhen-Biao Yang Shi-Biao Zheng Fujian Key Laboratory of Quantum Information and Quantum Optics College of Physics and Information EngineeringFuzhou UniversityFuzhou 350108China Hefei National Laboratory Hefei 230088China

Spontaneous symmetry breaking(SSB)plays a central role in understanding a large variety of phenomena associated with phase transitions,such as superfluid and *** far,the transition from a symmetric vacuum to a macroscopically ordered phase has been substantially *** process bridging these two distinct phases is critical to understanding how a classical world emerges from a quantum phase transition,but so far remains unexplored in *** here report an experimental demonstration of such a process with a quantum Rabi model engineered with a superconducting *** move the system from the normal phase to the superradiant phase featuring two symmetry-breaking field components,one of which is observed to emerge as the classical *** results demonstrate that the environment-induced decoherence plays a critical role in the SSB.

关键词： quantum phase transition Rabi model spontaneous symmetry breaking superconducting circuit Schrodinger cat states

Regulation of the quantum barrier and carrier transport toward high-efficiency quasi-2D Dion-Jacobson tin perovskite solar cells

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Journal of Energy Chemistry 2024年第8期95卷 200-207,I0005页

作者： huanhuan Yao Chang Shi Tai wu Shurong Wang Mingyu Yin Liming Ding Yong hua Feng hao School of Materials and Energy University of Electronic Science and Technology of ChinaChengdu 611731SichuanChina College of Chemistry and Molecular Engineering Peking UniversityBeijing 100871China Yunnan Key Laboratory for Micro/Nano Materials&Technology School of Materials and EnergyYunnan UniversityKunming 650091YunnanChina Center for Excellence in Nanoscience(CAS) Key Laboratory of Nanosystem and Hierarchical Fabrication(CAS)National Center for Nanoscience and TechnologyBeijing 100190China

Quasi-2D Dion-Jacobson(DJ)tin halide perovskite has attracted much attention due to its elimination of Van der Waals gap and enhanced environmental ***,the bulky organic spacers usually form a natural quantum well structure,which brings a large quantum barrier and poor film quality,further limiting the carrier transport and device ***,we designed three organic spacers with different chain lengths(ethylenediamine(EDA),1,3-propanediamine(PDA),and 1,4-butanediamine(BDA))to investigate the quantum barrier *** and experimental characterizations indicate that EDA with short chain can reduce the lattice distortion and dielectric confinement effect,which is beneficial to the effective dissociation of excitons and the inhibition of trap-free non-radiative *** addition,EDA cation shows strong interaction with the inorganic octahedron,realizing large aggregates in precursor solution and high-quality films with improved structural ***,femtosecond transient absorption proves that EDA cations can also weaken the formation of small n-phases with large quantum barrier to achieve effective carrier transport between different ***,the quasi-2D DJ(EDA)FA_(9)Sn_(10)I_(31)solar cells achieves a 7.07%power conversion efficiency with good environment ***,this work sheds light on the regulation of the quantum barrier and carrier transport through the chain length of organic spacer for qua si-2D DJ lead-free perovskites.

关键词： Chain lengths Organic spacers Quantum well Carrier transport Lattice distortion

A new liquid membrane diffusion model for characterizing the adsorption kinetics of europium by using a continuous measurement of adsorption platform

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Nuclear Science and Techniques 2024年第1期35卷 59-72页

作者： hao-Qi Yu Tao Yu Jian-hua Ye State Key Laboratory of Nuclear Resources and Environment East China University of TechnologyNanchang 330013China CGN Cangnan Nuclear Power Co. Ltd.Cangnan 325800China Jiangxi Province Key Laboratory of Polymer Micro/Nano Manufacturing and Devices East China University of TechnologyNanchang 330013China School of Nuclear Science and Engineering East China University of TechnologyNanchang 330013China

To explore the kinetic adsorption under continuous and nonequilibrium states, an integration of continuous measurement and adsorption platform kinetics method was proposed, which was initially called the ICM-AP kinetics method, and a corresponding kinetic adsorption experimental method was developed. Adsorption experiments of europium(Eu) on Ca-bentonite,Na-bentonite, and the D231 cation exchange resin were performed using the ICM-AP kinetics method and continuous measurements. Because the kinetic experimental results observed in this study were different from those of traditional batch adsorption data, pseudo-first-order or pseudo-second-order kinetic models were unsuitable for fitting the experimental ***, a liquid membrane diffusion(LMD) model was developed based on the assumption of simultaneous adsorption/desorption to discuss the mechanism of kinetic adsorption. The kinetic adsorption mechanism was also studied by using *** results indicated that the proposed adsorption model can fit the experimental data more suitably, and the adsorption/desorption behaviors of Eu on bentonite and the D231 resin were simultaneously observed, suggesting that the adsorption kinetics of Eu(Ⅲ) was mainly dominated by hydrated Eu(Ⅲ) ions on the liquid membrane.

关键词： ICM-AP method LMD model Adsorption mechanism Eu(Ⅲ)

Scutellarein Ameliorated Chondrocyte Inflammation and Osteoarthritis in Rats

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Current Medical Science 2024年第2期44卷 355-368页

作者： Shao-ze JING Shu-han YANG Yun-kun QU Hai-hu hao hua wu Department of Orthopedics Third Hospital of Shanxi Medical UniversityShanxi Bethune HospitalShanxi Academy of Medical SciencesTongji Shanxi HospitalTaiyuan 030032China Department of Orthopedics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Objective:Osteoarthritis(OA)is a degenerative joint disorder characterized by the gradual degradation of joint cartilage and local *** study aimed to investigate the anti-OA effect of scutellarein(SCU),a single-unit flavonoid compound obtained from Scutellaria barbata ***,in ***:The extracted rat chondrocytes were treated with SCU and IL-1β.The chondrocytes were divided into control group,IL-1βgroup,IL-1β+SCU 50µmol/L group,and IL-1β+SCU 100µmol/L *** of rat chondrocytes was observed by toluidine blue and safranin O ***-8 method was used to detect the cytotoxicity of ***,qRT-PCR,Western blotting,immunofluorescence,SAβ-gal staining,flow cytometry,and bioinformatics analysis were applied to evaluate the effect of SCU on rat chondrocytes under IL-1β***,anterior cruciate ligament transection(ACL-T)was used to establish a rat OA *** changes were detected by safranin O/fast green,hematoxylin-eosin(HE)staining,and ***:SCU protected cartilage and exhibited anti-inflammatory effects via multiple ***,it could enhance the synthesis of extracellular matrix in cartilage cells and inhibit its *** addition,SCU partially inhibited the nuclear factor kappa-B/mitogen-activated protein kinase(NF-κB/MAPK)pathway,thereby reducing inflammatory cytokine production in the joint ***,SCU significantly reduced IL-1β-induced apoptosis and senescence in rat chondrocytes,further highlighting its potential role in OA *** vivo experiments revealed that SCU(at a dose of 50 mg/kg)administered for 2 months could significantly delay the progression of cartilage damage,which was reflected in a lower Osteoarthritis Research Society International(OARSI)score,and reduced expression of matrix metalloproteinase 13(MMP13)in ***:SCU is effective in the therapeutic management of OA and could serve as a potential candidate f

关键词： scutellarein osteoarthritis apoptosis mitogen-activated protein kinase(MAPK) nuclear factor kappa-B(NF-κB)

A level line of the Gaussian free field with measure-valued boundary conditions

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Science China Mathematics 2024年第2期67卷 367-404页

作者： Titus Lupu hao wu Laboratoire de Probabilités Statistique et ModélisationSorbonne Universitéand UniversitéParis CitéCNRSParis F-75005France Yau Mathematical Sciences Center Tsinghua UniversityBeijing 100084China

In this article, we construct samples of Schramm-Loewner-evolution-like curves out of samples ofthe conformal loop ensemble and Poisson point processes of Brownian excursions. We show that the laws of thesecurves depend continuously on the intensity measure of the Brownian excursions. Using such a construction ofcurves, we extend the notion of level lines of the Gaussian free field to the case where the boundary conditionis measure-valued.

关键词： Schramm-Loewner evolution conformal loop ensemble Brownian excursion Gaussian free field

Decreased AKAP4/PKA signaling pathway in high DFI sperm affects sperm capacitation

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Asian Journal of Andrology 2024年第1期26卷 25-33页

作者： Kun Zhang Xiu-hua Xu Jian wu Ning Wang Gang Li Gui-Min hao Jin-Feng Cao Hebei Key Laboratory of Infertility and Genetics Department of Reproductive MedicineSecond Hospital of Hebei Medical UniversityShijiazhuang 050000China Department of Reproductive Medicine Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221000China Department of Neurology The 980th Hospital of the People's Liberation Army Joint Logistics Support Force(Bethune International Peace Hospital)Shijiazhuang 050000China.

The sperm DNA fragmentation index(DFI)is a metric used to assess DNA fragmentation within *** in vitro fertilizationembryo transfer(IVF-ET),high sperm DFI can lead to a low fertilization rate,poor embryo development,early miscarriage,etc.A kinase anchoring protein(AKAP)is a scaffold protein that can bind protein kinase A(PKA)to subcellular sites of specific substrates and protects the biophosphorylation *** protein antigen 17(SPA17)can also bind to *** study intends to explore the reason for the decreased fertilization rate observed in high sperm DFI(H-DFI)patients during *** addition,the study investigates the expression of AKAP,protein kinase A regulatory subunit(PKARIl),and SPA17 between H-DFI and low sperm DFI(L-DFI)***17 at the transcriptional level is abnormal,the translational level increases in H-DFI patients,and the expression of AKAP4/PKARIl protein decreases.H,O,has been used to simulate oxidative stress damage to spermatozoa during the formation of sperm *** indicates that H,O,increases the expression of sperm SPA17 protein and suppresses AKAP4/PKARIl protein *** processes inhibit sperm capacitation and reduce acrosomal *** culture data and IVF outcomes have been *** H-DFI group has a lower fertilization ***,the results indicate that the possible causes for the decreased fertilization rate in the H-DFI patients have included loss of sperm AKAP4/PKARIl proteins,blocked sperm capacitation,and reduced occurrence of acrosome reaction.

关键词： AKAP PKA SPA17 sperm capacitation sperm DNA fragmentation index

Method for determining the position of landslide slip-surface with a typical inclinometric curves

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Journal of Mountain Science 2024年第2期21卷 413-432页

作者： CHEN hao wu Hong-gang Ocean College Zhejiang UniversityZhoushan 316000China China Northwest Research Institute Co.Ltd.of CREC Lanzhou 730070China

In the actual monitoring of deep hole displacement,the identification of slip surfaces is primarily based on abrupt changes observed in the inclinometric *** conventional identification methods,inclinometric curves exhibiting indications of sliding can be categorized into three types:B-type,D-type,and *** position of the slip surface is typically determined by identifying the depth corresponding to the point of maximum displacement ***,this method is sensitive to the interval of measurement points and the observation scale of the coordinate axes and suffers from unclear sliding surfaces and uncertain *** on the variation characteristics of these diagonal curves,we classified the landslide into three components:the sliding body,the sliding interval,and the immobile ***,three different generalization models were established to analyze the relationships between the curve form and the slip surface location based on different physical indicators such as displacement rate,relative displacement,and *** results show that the displacement rate curves of an r-type slope exhibit a clustering feature in the sliding interval,and by solving for the depth of discrete points within the step phase,it is possible to determine the location of the slip *** the other hand,D-type slopes have inflection points in the relative displacement curve located at the slip *** acceleration curves of B-type slopes exhibit clustering characteristics during the sliding interval,while the scattered acceleration data demonstrate wandering ***,the slip surface location can be revealed by solving the depth corresponding to the maximum acceleration with cubic spline *** approach proposed in this paper was applied to the monitoring data of a landslide in Yunnan Province,*** results indicate that our approach can accurately identify the slip surface location and enable computability of its po

关键词： Inclinometric curve Slip-surface position Displacement rate Relative displacement Acceleration