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Josephin domain containing 2(JOSD2)promotes lung cancer by inhibiting LKB1(Liver kinase B1)activity

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Signal Transduction and Targeted Therapy 2024年第2期9卷 693-708页

作者： Tao Yuan Chenming Zeng Jiawei liu Chenxi Zhao Fujing Ge Yuekang Li Meijia Qian Jiamin Du Weihua Wang Yonghao Li Yue liu Xiaoyang Dai jianya Zhou Xueqin Chen Shenglin Ma Hong Zhu Qiaojun He Bo Yang Institute of Pharmacology&Toxicology Zhejiang Province Key Laboratory of Anti-Cancer Drug ResearchCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Innovation Institute for Artificial Intelligence in Medicine Zhejiang UniversityHangzhou 311199China Ministry of Education Key Laboratory of Chinese Medicinal Plants Resource from Lingnan Research Center of Medicinal Plants Resource Science and EngineeringGuangzhou University of Chinese MedicineGuangzhou 510006China Center for Drug Safety Evaluation and Research of Zhejiang University Hangzhou 310058China Department of Respiratory Disease Thoracic Disease CenterThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310006China Department of Oncology Hangzhou Cancer HospitalHangzhou 310002China Cancer Center of Zhejiang University HangzhouChina Engineering Research Center of Innovative Anticancer Drugs Ministry of EducationHangzhouChina

Non-small cell lung cancer(NSCLC)ranks as one of the leading causes of cancer-related deaths worldwide.Despite the prominence and effectiveness of kinase-target therapies in NSCLC treatment,these drugs are suitable for and beneficial to a mere~30%of NSCLC patients.Consequently,the need for novel strategies addressing NSCLC remains pressing.Deubiquitinases(DUBs),a group of diverse enzymes with well-defined catalytic sites that are frequently overactivated in cancers and associated with tumorigenesis and regarded as promising therapeutic targets.Nevertheless,the mechanisms by which DUBs promote NSCLC remain poorly understood.Through a global analysis of the 97 DUBs’contribution to NSCLC survival possibilities using The Cancer Genome Atlas(TCGA)database,we found that high expression of Josephin Domain-containing protein 2(JOSD2)predicted the poor prognosis of patients.Depletion of JOSD2 significantly impeded NSCLC growth in both cell/patient-derived xenografts in vivo.Mechanically,we found that JOSD2 restricts the kinase activity of LKB1,an important tumor suppressor generally inactivated in NSCLC,by removing K6-linked polyubiquitination,an action vital for maintaining the integrity of the LKB1-STRAD-MO25 complex.Notably,we identified the first small-molecule inhibitor of JOSD2,and observed that its pharmacological inhibition significantly arrested NSCLC proliferation in vitro/in vivo.Our findings highlight the vital role of JOSD2 in hindering LKB1 activity,underscoring the therapeutic potential of targeting JOSD2 in NSCLC,especially in those with inactivated LKB1,and presenting its inhibitors as a promising strategy for NSCLC treatment.

关键词： LKB1 inhibiting removing

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Foreword

Science China Mathematics 2023年第12期66卷 2665-2666页

作者： Liming Ge jianya liu Jie Wu Academy of Mathematics and Systems Science Chinese Academy of SciencesBeijing 100190China University of New Hampshire DurhamNH 03824USA School of Mathematics Shandong UniversityJinan 250100China CNRS LAMA 8050 Universite Paris-Est Creteil94010 Creteil CedexFrance

This special issue on Analytic Number Theory is dedicated to Jing-run Chen's Theorem(1+2)on the Goldbach Conjecture,the proof of which was first published in SCIENCE CHINA Mathematics exactly 50 years ago.Jing-run Chen was born on May 22,1933 in Fujian province,China.In 1953,he graduated from Xiamen University with a B.Sc.degree in Mathematics.

关键词： China Xiamen proof

Primes in arithmetic progressions with friable indices

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Science China Mathematics 2020年第1期63卷 23-38页

作者： jianya liu Jie Wu Ping X School of Mathematics Shandong UniversityJinan 250100China CNRS LAMA 8050 UniversitéParis-Est CréteilCreteil Cedex 94010France Department of Mathematics Xi’an Jiaotong UniversityXi'an 710049China

We consider the numberπ(x,y;q,a)of primes p≤such that p≡a(mod q)and(p-a)/q is free of prime factors greater than y.Assuming a suitable form of Elliott-Halberstam conjecture,it is proved thatπ(x,y:q,a)is asymptotic to p(log(x/q)/log y)π(x)/φ(q)on average,subject to certain ranges of y and q,where p is the Dickman function.Moreover,unconditional upper bounds are also obtained via sieve methods.As a typical application,we may control more effectively the number of shifted primes with large prime factors.

关键词： primes in arithmetic progression friable numbers shifted primes sieve

Subsampling bias and the best-discrepancy systematic cross validation

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Science China Mathematics 2021年第1期64卷 197-210页

作者： Liang Guo jianya liu Ruodan Lu Data Science Institute Shandong UniversityWeihai264209China Data Science Institute Shandong UniversityJinan250100China School of Architecture Building and Civil EngineeringLoughborough UniversityLoughboroughLE113TUUK Darwin College University of CambridgeCambridgeCB39EUUK

Statistical machine learning models should be evaluated and validated before putting to work.Conventional k-fold Monte Carlo cross-validation(MCCV)procedure uses a pseudo-random sequence to partition instances into k subsets,which usually causes subsampling bias,inflates generalization errors and jeopardizes the reliability and effectiveness of cross-validation.Based on ordered systematic sampling theory in statistics and low-discrepancy sequence theory in number theory,we propose a new k-fold cross-validation procedure by replacing a pseudo-random sequence with a best-discrepancy sequence,which ensures low subsampling bias and leads to more precise expected-prediction-error(EPE)estimates.Experiments with 156 benchmark datasets and three classifiers(logistic regression,decision tree and na?ve bayes)show that in general,our cross-validation procedure can extrude subsampling bias in the MCCV by lowering the EPE around 7.18%and the variances around 26.73%.In comparison,the stratified MCCV can reduce the EPE and variances of the MCCV around 1.58%and 11.85%,respectively.The leave-one-out(LOO)can lower the EPE around 2.50%but its variances are much higher than the any other cross-validation(CV)procedure.The computational time of our cross-validation procedure is just 8.64%of the MCCV,8.67%of the stratified MCCV and 16.72%of the LOO.Experiments also show that our approach is more beneficial for datasets characterized by relatively small size and large aspect ratio.This makes our approach particularly pertinent when solving bioscience classification problems.Our proposed systematic subsampling technique could be generalized to other machine learning algorithms that involve random subsampling mechanism.

关键词： subsampling bias cross validation systematic sampling low-discrepancy sequence best-discrepancy sequence

Double square moments and subconvexity bounds for Rankin-Selberg L-functions of holomorphic cusp forms

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Science China Mathematics 2020年第5期63卷 823-844页

作者： jianya liu Haiwei Sun Yangbo Ye School of Mathematics Shandong UniversityJinan 250100China School of Mathematics and Statistics Shandong UniversityWeihai 264209China Department of Mathematics The University of IowaIowa CityIA 52242-1419USA

Let f and g be holomorphic cusp forms of weights k1 and k2 for the congruence subgroups TO(N1)and Γ0(N2),respectively.In this paper the square moment of the Rankin-Selberg L-function for f and g in the aspect of both... 详细信息

关键词： automorphic L-function congruence subgroup cusp form holomorphic cusp form Rankin-Selberg L-function square moment subconvexity bound

On a certain non-split cubic surface

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Science China Mathematics 2019年第12期62卷 2435-2446页

作者： Regis de la Breteche Kevin Destagnol jianya liu Jie Wu Yongqiang Zhao Institut de Mathematiques de Jussieu Universite Paris-DiderotParis 75205France IST Austria Klosterneuburg 3400Austria School of Mathematics Shandong UniversityJinan 250100China Laboratoire d'Analyse et de Mathematiques Appliquees Univer site Paris-Est CreteilCNRSUMR 8050Creteil 94010France School of Science Westlake UniversityHangzhou 310024China

This paper establishes an asymptotic formula with a power-saving error term for the number of rational points of bounded height on the singular cubic surface of P^3 Q given by the following equation X0(X^21+X^22)-X^33... 详细信息

关键词： Manin-Peyre conjeeture rational points singular cubic surface non-split toric surface descent on torsors asymptotic formula

人工智能背景下大学生劳动精神培育的逻辑理路

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山西高等学校社会科学学报 2024年第3期36卷 47-52页

作者：刘建亚丁颖佳中南大学马克思主义学院湖南长沙410083

弘扬劳动精神是培养社会主义合格建设者和可靠接班人的重要举措,人工智能的发展对大学生劳动精神培育提出了新挑战和新要求。为更好应对人工智能发展带来的对人的意志、道德和社会角色的挑战,在辛勤劳动中承继奉献传统、在诚实劳动中坚... 详细信息

弘扬劳动精神是培养社会主义合格建设者和可靠接班人的重要举措,人工智能的发展对大学生劳动精神培育提出了新挑战和新要求。为更好应对人工智能发展带来的对人的意志、道德和社会角色的挑战,在辛勤劳动中承继奉献传统、在诚实劳动中坚守奋斗本心、在创造性劳动中弘扬创造新风,需注重理论引导与实践践行的结合,推动传统教学模式和现代科学技术相融合,通过理论引领、实践夯实、科技助力等方式培育大学生的劳动精神,推动高校劳动育人的新发展。

关键词：人工智能大学生劳动精神劳动教育

Hua's Theorem on Prime Squares in Short Intervals

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Acta Mathematica Sinica,English Series 2000年第4期16卷 669-690页

作者： jianya liu Tao Zhan Department of Mathematics. Shandong University. Jinan 250100. P. R. China Department of Mathematics Shandong University Jinan 250100 P. R. China

It is proved that every large integer N≡5（mod24）can be written as N=p12+…+p52 with each prime pj satisfying |pJ-（N/5|）1/2≤N11/23.This gives a short interval version of Hua’s theorem on the quadratic Waring-Gol... 详细信息

关键词： Waring-Goldbach problem Hua’s theorem Prime Circle method

阿奇霉素序贯疗法联合红霉素治疗儿童肺炎支原体肺炎的临床效果分析

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中国社区医师 2024年第7期40卷 35-37页

作者：刘毅坚周林秦建亚北京丰台医院儿科北京100071

目的:探讨阿奇霉素序贯疗法联合红霉素治疗儿童肺炎支原体肺炎的临床效果。方法:选取2017年2月—2023年2月北京丰台医院儿科收治的肺炎支原体肺炎患儿71例作为研究对象,采用随机数字表法分为观察组(n=36)和对照组(n=35)。两组均给予退... 详细信息

目的:探讨阿奇霉素序贯疗法联合红霉素治疗儿童肺炎支原体肺炎的临床效果。方法:选取2017年2月—2023年2月北京丰台医院儿科收治的肺炎支原体肺炎患儿71例作为研究对象,采用随机数字表法分为观察组(n=36)和对照组(n=35)。两组均给予退热、平喘、止咳化痰、雾化吸入等对症治疗,对照组采用阿奇霉素序贯治疗,观察组在对照组基础上采用红霉素治疗。比较两组临床症状消失时间、住院时间及肺功能指标。结果:观察组发热、咳嗽、肺部啰音消失时间和住院时间短于对照组,差异有统计学意义(P0.05),治疗后,两组PEF、FEV_(1)、FVC、FEV_(1)/FVC高于治疗前,且观察组高于对照组,差异有统计学意义(P<0.05)。结论:阿奇霉素序贯疗法联合红霉素治疗儿童肺炎支原体肺炎的临床效果显著,可以改善患儿肺功能,促进患儿康复,缩短患儿住院时间。

关键词：肺炎支原体肺炎阿奇霉素红霉素序贯疗法肺功能