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Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/OAK and CHOICE-01 trial

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Science China Life Sciences 2025年第1期 249-262页

作者： Jinliang Wang Wenyong zhou Yu Xu Jianchun Duan Qiaoxia zhou Guoqiang Wang leo Li Chunwei Xu Wenxian Wang Shangli Cai zhijie Wang Jie Wang Department of Oncology The Fifth Medical Center of Chinese PLA General Hospital Department of Thoracic Surgery Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University Burning Rock Biotech CAMS Key Laboratory of Translational Research on Lung Cancer State Key Laboratory of Molecular OncologyDepartment of Medical OncologyNational Cancer Center/National Clinical Research Center for ancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences Department of Clinical Trial The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

In non-small cell lung cancers,the non-squamous and squamous subtypes（nsqNSCLC and sqNSCLC） exhibit disparities in pathophysiology,tumor immunology,and potential genomic correlates affecting responses to immune checkpoint inhibitor（ICI）-based *** our inhouse training cohort（n=85）,the presence of the LRP1B deleterious mutation（LRP1B-del） was associated with longer and shorter progression-free survival（PFS） on ICIs alone in nsqNSCLCs and sqNSCLCs,respectively(Pinteraction=0.008).These results were validated using a larger public ICI cohort(n=208,Pinteractionzolizumab over docetaxel(hazard ratio（HR）=0.70,P=0.046),whereas this benefit was negligible in those without LRP1B-del（HR=1.05,P=0.64）.Conversely,sqNSCLCs without LRP1B-del benefited more from atezolizumab（HR=0.60,P=0.002） than those with LRP1B-del（HR=1.30,P=0.31）.Consistent results were observed in the in-house CHOICE-01 cohort,in which nsqNSCLCs with LRP1B-del and sqNSCLCs without LRP1B-del benefited more from toripalimab plus chemotherapy than from chemotherapy alone(Pinteraction=0.008).This multi-cohort study delineates the antithetical impacts of LRP1B-del in nsqNSCLCs and sqNSCLCs on predicting the benefits from ICI alone or with chemotherapy over chemotherapy *** findings highlight the distinct clinical utility of LRP1B-del in guiding treatment choices for nsqNSCLCs and sqNSCLCs,emphasizing the necessity for a detailed analysis based on pathological subtypes when investigating biomarkers for cancer therapeutics.

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INTERACTION OF SIMILARLY CHARGED SURFACES MEDIATED BY NANOPARTICLES

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Chinese Journal of Polymer Science 2011年第4期29卷 414-420页

作者： Klemen Bohinc leo Lue Faculty of Health Sciences University of LjubljanaSI-1000 LjubljanaSlovenia Department of Chemical and Process Engineering University of StrathclydeJames Weir Building75 Montrose StreetGlasgow G1 1XJUK

We study the interaction between two like charged surfaces embedded in a solution of oppositely charged multivalent rod-like counterions. The counterions consist of two rigidly bonded point charges, each of valency z. The strength of the electrostatic coupling increases with increasing surface charge density or valency of the charges. The system is analyzed by employing a self-consistent field theory, which treats the short and long range interactions of the counterions within different approximations. We find that in the weak coupling limit, the interactions are only repulsive. In the intermediate coupling regime, the multivalent rod-like counterions can mediate attractive interactions between the surfaces. For sufficiently long rods, bridging contributes to the attractive interaction. In the strong coupling limit, the charge correlations can contribute to the attractive interactions at short separations between the charged surfaces. Two minima can then appear in the force curve between surfaces.

关键词： Electrostatics Nanoparticle interactions Theory.

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Comparison of Snellen and Early Treatment Diabetic Retinopathy Study charts using a computer simulation

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International Journal of Ophthalmology(English edition) 2016年第1期9卷 119-123页

作者： Reuben R.Shamir Yael Friedman leo Joskowicz Michael Mimouni Eytan z.Blumenthal School of Engineering and Computer Science the Hebrew University Department of Ophthalmology Hadassah-Hebrew University Medical Center Department of Ophthalmology Rambam Medical Center

AIM：To compare accuracy,reproducibility and test duration for the Snellen and the Early Treatment Diabetic Retinopathy Study（ETDRS）charts,two main tools used to measure visual acuity（VA）.·M ETHODS：A computer simulation was programmed to run multiple virtual patients,each with a unique set of assigned parameters,including VA,false-positive and false-negative error *** each virtual patient,assigned VA was randomly chosen along a continuous scale spanning the range between 1.0 to 0.0 log MAR units（equivalent to 20/200 to 20/20）.Each of 30 000virtual patients were run ten times on each of the two VA charts.·RESULTS：Average test duration（expressed as the total number of characters presented during the test±SD）was12.6±11.1 and 31.2±14.7 characters,for the Snellen and ETDRS,***,defined as the absolute difference（±SD）between the assigned VA and the measured VA,expressed in log MAR units,was superior in the ETDRS charts：0.12±0.14 and 0.08±0.08,for the Snellen and ETDRS charts,***,expressed as test-retest variability,was superior in the ETDRS charts：0.23±0.17 and 0.11±0.09 log MAR units,for the Snellen and ETDRS charts,respectively.·CONCLUSION：A comparison of true（assigned）VA to measured VA,demonstrated,on average,better accuracy and reproducibility of the ETDRS chart,but at the penalty of significantly longer test *** differences were most pronounced in the low VA *** reproducibility using a simulation approach is in line with reproducibility values found in several clinical studies.

关键词： Early Treatment Diabetic RetinopathyStudy Snellen computer simulation visual acuity testing virtual patients

Theorems of Erds-Ko-Rado type in geometrical settings

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Science China Mathematics 2013年第7期56卷 1333-1348页

作者： DE BOECK Maarten STORME leo Department of Mathematics Krijgslaan 281-Building S22 9000 GentFlanders Belgium

The original Erdos-Ko-Rado problem has inspired much research. It started as a study on sets of pairwise intersecting k-subsets in an n-set, then it gave rise to research on sets of pairwise non-trivially intersecting k-dimensional vector spaces in the vector space V（n, q） of dimension n over the finite field of order q, and then research on sets of pairwise non-trivially intersecting generators and planes in finite classical polar spaces. We summarize the main results on the Erdos-Ko-Rado problem in these three settings, mention the ErdSs-Ko-Rado problem in other related settings, and mention open problems for future research.

关键词： Erdos-Ko-Rado theorem finite sets finite vector spaces finite classical polar spaces

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MYC and KRAS cooperation:from historical challenges to therapeutic opportunities in cancer

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Signal Transduction and Targeted Therapy 2024年第9期9卷 3840-3869页

作者： Sílvia Casacuberta-Serra Íñigo González-Larreategui Daniel Capitán-leo Laura Soucek Peptomyc S.L. BarcelonaSpain Models of cancer therapies Laboratory Vall d’Hebron Institute of OncologyCellex CentreHospital University Vall d’Hebron CampusBarcelonaSpain InstitucióCatalana de Recerca i Estudis Avançats BarcelonaSpain Department of Biochemistry and Molecular Biology Universitat Autonoma de BarcelonaBellaterraSpain

RAS and MYC rank amongst the most commonly altered oncogenes in cancer,with RAS being the most frequently mutated and MYC the most *** cooperative interplay between RAS and MYC constitutes a complex and multifaceted phenomenon,profoundly influencing tumor *** and individually,these two oncogenes regulate most,if not all,hallmarks of cancer,including cell death escape,replicative immortality,tumor-associated angiogenesis,cell invasion and metastasis,metabolic adaptation,and immune *** to their frequent alteration and role in tumorigenesis,MYC and RAS emerge as highly appealing targets in cancer ***,due to their complex nature,both oncogenes have been long considered“undruggable”and,until recently,no drugs directly targeting them had reached the *** review aims to shed light on their complex partnership,with special attention to their active collaboration in fostering an immunosuppressive milieu and driving immunotherapeutic resistance in *** this review,we also present an update on the different inhibitors targeting RAS and MYC currently undergoing clinical trials,along with their clinical outcomes and the different combination strategies being explored to overcome drug *** recent clinical development suggests a paradigm shift in the long-standing belief of RAS and MYC“undruggability”,hinting at a new era in their therapeutic targeting.

关键词： therapeutic overcome Together

Transfer of an Aluminum Atom:An Avenue to Aluminum Heterocycles

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CCS Chemistry 2023年第9期5卷 2059-2068页

作者： Xin zhang Hongyu Wang Xiaofang Lan Yanbo Mei David A.Ruiz Liu leo Liu Department of Chemistry and Guangdong Provincial Key Laboratory of Catalysis Southern University of Science and TechnologyShenzhen 518055

Synthetic chemistry enables constructing molecular complexity using simple substrates through simple *** disclose an unprecedented Al-atom transfer strategy for the synthesis of aluminum heterocycles with high atom *** strategy involves an effective cycloaddition of a free carbazolyl-aluminylene with unsaturated hydrocarbons,followed by facile cleavage of the N-Al *** aluminylene formally behaves as a tetra-active ambiphilic[Al+]cation transfer reagent in a two-step manner,and the only byproduct is a carbazolide salt that can be utilized to regenerate the *** carbazolyl Al-heterocycles show unique luminescent properties,in which one exhibits dual *** approach not only has a significant impact on the future design of single-atom addition reactions but also paves the way for emissive materials based on Al-heterocycles.

关键词： aluminum heterocycles atom transfer dual emission alumole aluminylene