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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 decade.This 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 malignancies.Nonetheless,there is still an unmet clin-ical need forwider application,better efficacy,and fewer side effects of ADCs.An ADC generally comprises an antibody,a linker and a payload,and the combina-tion has profound effects on drug structure,pharmacokinetic profile and efficacy.Hence,optimization of the key components provides an opportunity to develop ADCs with higher potency and fewer side effects.In 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

Appendiceal intussusception complicated by adenocarcinoma of the cecum:A case report

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World Journal of Clinical Cases 2024年第8期12卷 1461-1466页

作者： Yu Long Yi-Ning xiang Fei Huang Lei xu Xiao-yun Li yun-Huan Zhen Department of Colorectal Surgery The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550001Guzihou ProvinceChina Department of Colorectal Surgery Guizhou Medical UniversityGuiyang 550001Guizhou ProvinceChina Department of Pathology The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550001Guizhou ProvinceChina

BACKGROUND Appendiceal intussusception is a pathological condition in which the appendix is inverted into the cecum,which may cause symptoms that resemble those of other gastrointestinal disorders and may induce intestinal obstruction.The rarity of this case presentation is the co-occurrence of appendiceal intussusception and cecal adenocarcinoma,a combination that to our knowledge has not previously been reported in the medical literature.This case provides new insights into the complexities of diagnosing and managing overlapping pathologies.CASE SUMMARY A 25-year-old woman presented with persistent periumbilical pain and bloody stools.An initial biopsy showed cecal cancer;however,subsequent colonoscopy and computed tomography findings raised the suspicion of appendiceal intussus-ception,which was later confirmed postoperatively.This unique case was charac-terized by a combination of intussusception and adenocarcinoma of the cecum.The intervention included a laparoscopic right hemicolectomy,which led to the histopathological diagnosis of mucinous adenocarcinoma with appendiceal intussusception.The patient recovered well postoperatively and was advised to initiate adjuvant chemotherapy.This case highlights not only the importance of considering appendiceal intussusception in the differential diagnosis,but also the possibility of appendicitis and the atypical presentation of neoplastic lesions.CONCLUSIONS Physicians should consider the possibility of appendiceal intussusception in cases of atypical appendicitis,particularly when associated with neoplastic presentation.

关键词： Appendiceal intussusception Appendicitis Cecal cancer Target signs Misdiagnosis Case report

Decomposition mechanisms of nuclear-grade cationic exchange resin by advanced oxidation processes:Statistical molecular fragmentation model and DFT calculations

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Journal of Environmental Sciences 2024年第1期135卷 433-448页

作者： xiang Meng Pierre Désesquelles Lejin xu Department of Nuclear Engineering and Technology School of Energy and Power EngineeringHuazhong University of Science&TechnologyWuhan 430074China CNRS Laboratoire de Physique des Gaz et des PlasmasUniversitéParis-SaclayOrsay 91405France State Key Laboratory of Coal Combustion School of Energy and Power EngineeringHuazhong University of Science and TechnologyWuhan 430074China

The treatment and disposal of radioactive waste are presently facing great challenges.Spent ion exchange resins have become a focus of attention due to their high production and serious environmental risks.In this paper,a simplified model of cationic exchange resin is proposed,and the degradation processes of cationic resin monomer initiated by hydroxyl radicals(·OH)are clarified by combining statistical molecular fragmentation(SMF)model and density functional theory(DFT)calculations.The prediction of active sites indicates that the S-O bonds and the C-S bond of the sulfonic group are more likely to react during the degradation.The meta-position of the sulfonic group on the benzene ring is the most active site,and the benzene ring without the sulfonic group has a certain reactivity.The C11-C14 and C17-C20 bonds,on the carbon skeleton,are the most easily broken.It is also found that dihydroxy addition and elimination reactions play a major role in the process of desulfonation,carbon skeleton cleavage and benzene ring separation.The decomposition mechanisms found through the combination of physical models and chemical calculations,provide theoretical guidance for the treatment of complex polycyclic aromatic hydrocarbons.

关键词： Cationic exchange resin Statistical molecular fragmentation model Density functional theory Hydroxyl radical Decomposition mechanism

Perspective of Calcium Imaging Technology Applied to Acupuncture Research

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Chinese Journal of Integrative Medicine 2024年第1期30卷 3-9页

作者： LI Sha LIU yun ZHANG Nan LI Wang xu Wen-jie xu Yi-qian CHEN Yi-yuan CUI xiang ZHU Bing GAO Xin-yan Institute of Acupuncture and Moxibustion China Academy of Chinese Medical SciencesBeijing(100700)China

Acupuncture, a therapeutic treatment defined as the insertion of needles into the body at specific points(ie, acupoints), has growing in popularity world-wide to treat various diseases effectively, especially acute and chronic pain. In parallel, interest in the physiological mechanisms underlying acupuncture analgesia, particularly the neural mechanisms have been increasing. Over the past decades, our understanding of how the central nervous system and peripheral nervous system process signals induced by acupuncture has developed rapidly by using electrophysiological methods. However, with the development of neuroscience, electrophysiology is being challenged by calcium imaging in view field, neuron population and visualization in vivo. Owing to the outstanding spatial resolution, the novel imaging approaches provide opportunities to enrich our knowledge about the neurophysiological mechanisms of acupuncture analgesia at subcellular, cellular, and circuit levels in combination with new labeling, genetic and circuit tracing techniques. Therefore, this review will introduce the principle and the method of calcium imaging applied to acupuncture research. We will also review the current findings in pain research using calcium imaging from in vitro to in vivo experiments and discuss the potential methodological considerations in studying acupuncture analgesia.

关键词： acupuncture research calcium imaging optical imaging nervous system

Millimeter-wave PA design techniques in ISSCC 2024

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Journal of Semiconductors 2024年第4期45卷 16-18页

作者： yun Wang Hongtao xu State Key Laboratory of Integrated Chips and Systems School of MicroelectronicsFudan UniversityShanghai 201203China

Millimeter-wave systems with high integration level have been rapidly developed to enable modern wireless communication,sensing,and imaging.The millimeter-wave power amplifier(PA)is one of the most challenging and critical components in a millimeter-wave transceiver,it is the last active stage in a transmitter amplifying spectrally efficient complex modulation signal for radiation with high output power.

关键词： millimeter Millimeter ISSCC

NFXL1 functions as a transcriptional activator required for thermotolerance at reproductive stage in Arabidopsis

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Journal of Integrative Plant Biology 2024年第1期66卷 54-65页

作者： Qiao‐yun Zhu Lin‐Lin Zhang Jian‐xiang Liu State Key Laboratory of Plant Environmental Resilience College of Life SciencesZhejiang UniversityHangzhou 310027China

Plants are highly susceptible to abiotic stresses,particularly heat stress during the reproductive stage.However,the specific molecular mechanisms underlying this sensitivity remain largely unknown.In the current study,we demonstrate that the Nuclear Transcription Factor,X-box Binding Protein 1-Like 1(NFXL1),directly regulates the expression of DEHYDRATION-RESPONSIVE ELEMENT-BINDING PROTEIN 2A(DREB2A),which is crucial for reproductive thermotolerance in Arabidopsis.NFXL1 is upregulated by heat stress,and its mutation leads to a reduction in silique length(seed number)under heat stress conditions.RNA-Seq analysis reveals that NFXL1 has a global impact on the expression of heat stress responsive genes,including DREB2A,Heat Shock Factor A3(HSFA3)and Heat Shock Protein 17.6(HSP17.6)in flower buds.Interestingly,NFXL1 is enriched in the promoter region of DREB2A,but not of either HSFA3 or HSP17.6.Further experiments using electrophoretic mobility shift assay have confirmed that NFXL1 directly binds to the DNA fragment derived from the DREB2A promoter.Moreover,effector-reporter assays have shown that NFXL1 activates the DREB2A promoter.The DREB2A mutants are also heat stress sensitive at the reproductive stage,and DEREB2A is epistatic to NFXL1 in regulating thermotolerance in flower buds.It is known that HSFA3,a direct target of DREB2A,regulates the expression of heat shock proteins genes under heat stress conditions.Thus,our findings establish NFXL1 as a critical upstream regulator of DREB2A in the transcriptional cassette responsible for heat stress responses required for reproductive thermotolerance in Arabidopsis.

关键词： Arabidopsis DREB2A heat stress NFXL1 reproductive thermotolerance

GM-CSF Promotes the Development of Dysfunctional Vascular Networks in Moyamoya Disease

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Neuroscience Bulletin 2024年第4期40卷 451-465页

作者： Huiqin Li xiang Cao Xinya Gu Mengqi Dong Lili Huang Chenglu Mao Shengnan Xia Haiyan Yang Xinyu Bao Yongbo Yang yun xu Department of Neurology and Neurosurgery Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing210008China Department of Neurology and Neurosurgery Nanjing Drum Tower HospitalState Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical DiseasesNanjing UniversityNanjing210008China Department of Neurology and Neurosurgery Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical UniversityNanjing210008China Department of Neurology and Neurosurgery Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityNanjing210008China Jiangsu Key Laboratory for Molecular Medicine Medical School of Nanjing UniversityNanjing210008China Jiangsu Provincial Key Discipline of Neurology Nanjing210008China Nanjing Neurology Medical Center Nanjing210008China

Moyamoya disease(MMD)is a chronic occlusive cerebrovascular disease with the development of a network of abnormal vessels.Immune inflammation is associated with the occurrence and development of MMD.However,the mechanisms underlying the formation of the abnormal vascular network remain unclear.Twenty-eight patients with MMD,26 ischemic stroke patients,and 26 unrelated healthy volunteers were enrolled in this study The data showed that the levels of granulocyte-macrophage colony-stimulating factor(GM-CSF)were higher in MMD patients than in healthy controls(P<0.01),and GM-CSF was mainly from Th1 and Th17 cells in MMD.We found that increased GM-CSF drove monocytes to secrete a series of cytokines associated with angiogenesis,inflammation,and chemotaxis.In summary,our findings demonstrate for the first time the important involvement of GM-CSF in MMD and that GM-CSF is an important factor in the formation of abnormal vascular networks in MMD.

关键词： Moyamoya disease Vascular endothelial cells GM-CSF VEGF

Comparative evaluation of SPE methods for biotoxicity assessment of water and wastewater:Linkage between chemical extracting efficiency and biotoxicity outcome

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Journal of Environmental Sciences 2024年第8期142卷 33-42页

作者： Jiawei Zhou Shihao Wang Xiwei He Hongqiang Ren xu-xiang Zhang State Key Laboratory of Pollution Control and Resource Reuse School of EnvironmentNanjing UniversityNanjing 210023China

Biotoxicity assessment results of environmental waters largely depend on the sample extraction protocols that enrich pollutants to meet the effect-trigger thresholds of bioassays.However,more chemical mixture does not necessarily translate to higher combined biotoxicity.Thus,there is a need to establish the link between chemical extracting efficiency and biotoxicity outcome to standardize extraction methods for biotoxicity assessment of environmental waters.This study compares the performance of five different extraction phases in solid phase extraction(SPE),namely HLB,HLB+Coconut,C18 cartridge,C18 disk and Strata-X,and evaluated their chemical extracting efficiencies and biotoxicity outcomes.We quantitatively assessed cytotoxicity,acute toxicity,genotoxicity,estrogenic activity,and neurotoxicity of the extracts using in vitro bioassays and characterized the chemical extracting efficiencies of the SPE methods through chemical recoveries of 23 model compounds with different polarities and total organic carbon.Using Pareto ranking,we identified HLB+Coconut as the optimal SPE method,which exhibited the highest level of water sample biotoxicity and recovered the most chemicals in water samples.We found that the biotoxicity outcomes of the extracted water samples significantly and positively correlated with the chemical extracting efficiencies of the SPE methods.Moreover,we observed synchronous changing patterns in biotoxicity outcome and chemical extracting efficiencies in response to increasing sample volumes per cartridge(SVPC)during SPE.Our findings underscore that higher chemical extracting efficiency of SPE corresponds to higher biotoxicity outcome of environmental water samples,providing a scientific basis for standardization of SPE methods for adequate assessment of biotoxicities of environmental waters.

关键词： Biotoxicity Chemical recovery Solid phase extraction Surface water Wastewater

Mechanical Performance of Bio-inspired Bidirectional Corrugated Sandwich Pressure Shell Under External Hydrostatic Pressure

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China Ocean Engineering 2024年第2期38卷 297-312页

作者： ZHANG Yi CHEN Yue yun Lai LIANG xu Ocean College Zhejiang UniversityZhoushan 316000China Hainan Institute Zhejiang UniversitySanya 572000China

This paper aims to enhance the compression capacity of underwater cylindrical shells by adopting the corrugated sandwich structure of cuttlebone.The cuttlebone suffers uniaxial external compression,while underwater cylindrical shells are in a biaxial compressive stress state.To suit the biaxial compressive stress state,a novel bidirectional corrugated sandwich structure is proposed to improve the bearing capacity of cylindrical shells.The static and buckling analysis for the sandwich shell and the unstiffened cylindrical shell with the same volume-weight ratio are studied by numerical simulation.It is indicated that the proposed sandwich shell can effectively reduce the ratio between circumferential and axial stress from 2 to 1.25 and improve the critical buckling load by about 1.63 times.Numerical simulation shows that optimizing and adjusting the structural parameters could significantly improve the advantage of the sandwich shell.Then,the hydrostatic pressure tests for shell models fabricated by 3D printing are carried out.According to the experimental results,the overall failure position of the sandwich shell is at the center part of the sandwich shell.It has been found the average critical load of the proposed sandwich shell models exceeds two times that of the unstiffened shell models.Hence,the proposed bio-inspired bidirectional corrugated sandwich structure can significantly enhance the pressure resistance capability of cylindrical shells.

关键词： bio-inspiration bidirectional corrugation sandwich shell external pressure buckling