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A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance

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Acta Pharmaceutica Sinica B 2024年第1期14卷 223-240页

作者： Lei Sun Arabella H.Wan Shijia Yan Ruonian Liu Jiarui Li Zhuolong Zhou Ruirui Wu Dongshi Chen Xianzhang Bu Jingxing Ou Kai Li Xiongbin Lu Guohui Wan Zunfu Ke department of Pathology the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation National Engineering Research Center for New Drug and Druggability(Cultivation)Guangdong Province Key Laboratory of New Drug Design and EvaluationSchool of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China department of Medical and Molecular Genetics Indiana University School of MedicineIndianapolisIN 46202USA department of Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA department of Hepatic Surgery and liver Transplantation center Third Affiliated HospitalOrgan Transplantation InstituteSun Yat-sen UniversityOrgan Transplantation Research Center of Guangdong ProvinceGuangdong Province Engineering Laboratory for Transplantation MedicineGuangzhou 510630China Guangdong Provincial Key Laboratory of liver Disease research Guangzhou 510630China department of Ultrasound Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Melvin and Bren Simon Comprehensive Cancer center Indiana UniversityIndianapolisIN 46202USA

Lenvatinib,a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer,facing limitations due to drug ***,we applied a multidimensional,high-throughput screening platform comprising patient-derived resistant liver tumor cells(PDCs),organoids(PDOs),and xenografts(PDXs)to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant *** and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment,expediting drug repurposing *** screening identified romidepsin,YM155,apitolisib,NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO ***,romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway.A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX ***,our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer,providing a feasible multidimensional platform for personalized medicine.

关键词： Lenvatinib Drug resistance High-throughput screening Drug discovery Patient-derived model Romidepsin EGFR liver cancer

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A fiducial approach to the nonparametric deconvolution problem:The discrete case

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Science China Mathematics 2024年第11期67卷 2653-2670页

作者： Yifan Cui Jan Hannig center for Data Science Zhejiang University department of Statistics and Operations research University of North Carolina at Chapel Hill

Fiducial inference is applied to nonparametric g-modeling in the discrete *** propose a computationally efficient algorithm to sample from the fiducial distribution and use the generated samples to construct point estimates and confidence *** study the theoretical properties of the fiducial distribution and perform extensive simulations in various *** proposed approach gives rise to good statistical performance in terms of the mean squared error of point estimators and coverage of confidence ***,we apply the proposed fiducial method to estimate the probability of each satellite site being malignant using gastric adenocarcinoma data with 844 patients.

关键词： confidence intervals empirical Bayes fiducial inference nonparametric deconvolution

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Carbon-based supports for the electrocatalysis under industrially relevant conditions

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Science China Chemistry 2024年第4期67卷 1051-1055页

作者： Xue Yang Xianrui Gu Yang Song Guolin Hou Cheng Wang Lichen Liu Wei Lin center for Renewable Energy SINOPEC Research Institute of Petroleum ProcessingBeijing 100083China Engineering research center of Advanced Rare Earth Materials Department of ChemistryTsinghua UniversityBeijing 100084China

1 *** materials are ideal catalyst supports for functional metal components due to their appropriate physicochemical characteristics,such as high surface areas,tunable pore structures,variable morphologies and versatile surface properties based on chemical modifications,low cost and facile preparations from diverse precursors[1,2].

关键词： versatile facile supports

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Advocating for the implementation of SonoVue microbubbles as pressure sensors: a call to action for clinical noninvasive pressure estimation

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Hepatobiliary Surgery and Nutrition 2024年第4期13卷 690-695页

作者： Ao Wen Lingxiao Yang Tao Lv Huayu Yang Fei Li Yilei Mao Gang Xu Jia-Yin Yang liver Transplant center Organ Transplant CenterWest China Hospital of Sichuan UniversityChengduChina Laboratory of liver Transplantation Key Laboratory of Transplant Engineering and ImmunologyNational Health Commission(NHC)West China Hospital of Sichuan UniversityChengduChina West China Hospital West China School of MedicineSichuan UniversityChengduChina department of liver Surgery Peking Union Medical College(PUMC)HospitalPUMC and Chinese Academy of Medical SciencesBeijingChina Paul C.Lauterbur research center for Biomedical Imaging Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenChina

Pressure measurement within the body is of pivotal significance in the diagnosis of vascular and organ-related diseases associated with hydrostatic *** present,the most commonly used clinical method is to insert a catheter along with a pressure sensor and then guide it to the area of interest through vessels such as central venous pressure(CVP).However,the presence of sensors within the vessel of interest will inevitably cause alterations to the circulation and thus affect blood ***,the use of invasive methods does not allow monitoring of every area inside the body.

关键词： SonoVue microbubbles pressure estimation noninvasive

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Retrospective study of the incidence, risk factors, treatment outcomes of bacterial infections at uncommon sites in cirrhotic patients

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World Journal of Hepatology 2024年第3期16卷 418-427页

作者： Sophie Schneitler Christina Schneider Markus Casper Frank Lammert Marcin Krawczyk Sören L Becker Matthias Christian Reichert Institute of Medical Microbiology and Hygiene Saarland UniversityHomburg 66421Germany department of Medicine II Saarland University Medical CenterHomburg 66421Germany Health Sciences Hannover Medical SchoolHannover 30625Germany Laboratory of Metabolic liver Diseases Department of GeneralTransplant and Liver SurgeryCentre for Preclinical ResearchMedical University of WarsawWarsaw 02-097Poland

BACKGROUND Bacterial infections(BI)negatively affect the natural course of *** most frequent BI are urinary tract infections(UTI),pneumonia,and spontaneousbacterial peritonitis(SBP).AIM To assess the relevance of bacterial infections beyond the commonly recognized types in patients with cirrhosis and to investigate their relationship with other clinical *** We retrospectively analyzed patients with cirrhosis and BI treated between 2015 and 2018 at our tertiary care *** were classified as typical and atypical,and clinical as well as laboratory parameters were compared between the two *** In a cohort of 488 patients with cirrhosis,we identified 225 typical BI(95 UTI,73 SBP,72 pulmonary infections)and 74 atypical BIs,predominantly cholangitis and soft tissue infections(21 each),followed by intra-abdominal BIs(n=9),cholecystitis(n=6),head/throat BIs(n=6),osteoarticular BIs(n=5),and endocarditis(n=3).We did not observe differences concerning age,sex,or etiology of cirrhosis in patients with typical vs atypical *** BIs were more common in patients with more advanced cirrhosis,as evidenced by Model of End Stage liver Disease(15.1±7.4 vs 12.9±5.1;P=0.005)and Child-Pugh scores(8.6±2.5 vs 8.0±2;P=0.05).CONCLUSION Atypical BIs in cirrhosis patients exhibit a distinct spectrum and are associated with more advanced stages of the ***,the work-up of cirrhosis patients with suspected BI requires detailed work-up to elucidate whether typical BI can be identified.

关键词： Bacterial infection Empirical antibiotic therapy End-stage liver disease Escherichia coli Multi-resistant pathogens

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Effect of Ball Milling Time on Microstructure and Hydrogen Storage Properties of Nd_(5)Mg_(41)Ni Alloy

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Acta Metallurgica Sinica(English Letters) 2024年第7期37卷 1201-1214页

作者： Zeming Yuan Chenxu Liu Xiaoming Li Yongqi Sui Zhonggang Han Tingting Zhai Dianchen Feng Yanghuan Zhang Instrumental Analysis center Inner Mongolia University of Science and TechnologyBaotou014010China department of Functional Material research Central Iron and Steel Research InstituteBeijing100081China

Mg-based alloys must be dehydrogenated at high pressure and temperatures, limiting their practical application. In this paper, Nd_(5)Mg_(41)Ni alloy was prepared by vacuum melting, and the as-cast alloy was ball milled for 5 h, 10 h, 15 h, and 20 h. The effect of ball milling time on the microstructure and hydrogen storage properties of the alloy was systematically studied. The alloy comprises Nd_(5)Mg_(41), NdMg_(12), NdMg_(3), and Mg_(2)Ni phases. The Nd_(5)Mg_(41)Ni alloy milling for 10 h can reach 95% of the saturated hydrogen absorption at 553 K by 40 s, and the alloy can desorb hydrogen only by 20 min. The dehydrogenation activation energy is only 99.9 kJ/mol H_(2). Ball milling makes the alloy produce many nanocrystalline and amorphous structures. The nano-grain boundary provides a channel for the diffusion of hydrogen atoms, and the high energy at the grain boundary provides energy for the phase deformation nucleus. Ball milling leads to the refinement of alloy particles and shortens the diffusion distance of hydrogen atoms to the interior of alloy particles. Defects such as twins and dislocations generated by milling provide energy for the phase deformation nucleus during the hydrogen absorption and desorption.

关键词： Hydrogen storage materials Magnesium-base alloy Ball milling Nanocrystal Kinetics

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Consideration on immunotherapy of liver metastases of malignant tumors

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World Journal of Gastrointestinal Surgery 2024年第8期16卷 2374-2381页

作者： Chuang Jiang Zhi-Hong Zhang Jia-Xin Li Division of liver Surgery Department of General Surgery and Laboratory of Liver Surgeryand State Key Laboratory of Biotherapy and Collaborative Innovation Center of BiotherapyWest China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina department of General Surgery Dafang County People's HospitalBijie 551600Guizhou ProvinceChina

In this editorial,we comment on the article“Analysis of the impact of immuno-therapy efficacy and safety in patients with gastric cancer and liver metastasis”by Liu et al that was published in the recent issue of the World Journal of Gastroin-testinal *** has prompted us to think and summarize some thoughts on immunotherapy for malignant tumor liver *** plays a crucial role in the treatment of malignant tumors;however,the presence of liver metastases in advanced tumors may impact its *** patients with liver metastases can still benefit from immunotherapy,multiple clinical studies have indicated that,compared to other sites of metastasis,liver metastases may diminish the effectiveness of *** efficacy of immune checkpoint inhibitors in patients with liver metastases often fails to reach the ideal level,primarily due to the liver metastases exploiting the host's peripheral immune to-lerance mechanisms to promote systemic CD8(+)T cell exhaustion,resulting in a systemic immune-tolerant *** article aims to summarize the reasons for the decreased efficacy of immunotherapy following liver metastasis in various malignant tumors and propose potential clinical strategies for manage-ment.

关键词： liver metastasis Immunotherapy Immune tolerance Cancer Treatment

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Investigation of operation and degradation mechanisms in ZnTeSe blue quantum-dot light-emitting diodes by identifying recombination zone

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Nano research 2024年第7期17卷 6527-6533页

作者： Oul Cho Sujin Park Hogeun Chang Jiwhan Kim Jaekwon Kim Sungwoo Kim Taehyung Kim Jeonghun Kwak department of Electrical and Computer Engineering Inter-university Semiconductor Research Centerand Soft Foundry InstituteSeoul National UniversitySeoul 08826Republic of Korea Material research center Samsung Advanced Institute of TechnologySuwonGyeonggi-do 16419Republic of Korea

ZnTeSe quantum dots(QDs),recognized as promising eco-friendly blue electroluminescent emitters,remain under-explored in light-emitting diode(LED)***,to elucidate the operation and degradation mechanisms of ZnTeSe blue QD-LEDs,stacked ZnTeSe QD layers with discernable luminescence are designed by varying Te doping concentrations,and the recombination zones(RZs)of the blue QD-LEDs are *** RZs are identified near the hole-transport layer(HTL),confirmed by angular-dependent electroluminescence measurements and optical *** addition,in order to investigate carrier dynamics in the process of recombination,the transient electroluminescence(tr-EL)signals of the dichromatic QD-LEDs are *** a result,it is inferred that the RZ initially formed near the electron-transport layer(ETL)due to the high injection barriers of ***,due to the fast electron mobility,the RZ shifts toward the HTL as the operating current *** the device lifetime tests,the RZ remains stationary while the photoluminescence(PL)corresponding to the RZ undergoes a substantial decrease,indicating that the degradation is accelerated by the concentrated *** this study contributes to a deeper understanding of the operational mechanisms of ZnTeSe blue QD-LEDs.

关键词： quantum dots light-emitting diodes degradation recombination zones carrier dynamics

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Genetic Variability and Phenotypic Correlations Study among Grain Quality Traits and Mineral Elements Concentrations in Colored and Non-Colored Rice (Oryza sativa L.)

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Phyton-International Journal of Experimental Botany 2024年第7期93卷 1733-1748页

作者： Adel A.Rezk Mohamed M.El-Malky Heba I.Mohamed Hossam S.El-Beltagi Agricultural Biotechnology department College of Agricultural and Food ScienceKing Faisal UniversityAl-Ahsa31982Saudi Arabia Plant Pathology research Institute Agriculture Research CenterGiza12619Egypt Rice research and Training center Field Crop Research InstituteAgriculture Research Center33717Egypt Biological and Geological Sciences department Faculty of EducationAin Shams UniversityCairo11511Egypt Biochemistry department Faculty of AgricultureCairo UniversityGiza12613Egypt

Twenty-four rice genotypes were examined to assess genetic variability,heritability,and correlations for seven-grain quality traits,eight nutritional elements,and *** revealed signiﬁcant differences for the quality traits *** every trait under study,the phenotypic coefﬁcient of variation was higher than the correspon-dence genotypic coefﬁcient of *** in a broad sense varied from 29.75%for grain length to 98.31%for the elongation *** percentage recovery had a highly signiﬁcant positive correlation with milling and head rice ***,milling percentage had a highly positive correlation with head rice *** amylose percentage,all the genotypes belonged to low amylose except the Hassawi-1 variety,which had intermediate amylose *** nutrition contents of magnesium(Mg),sodium(Na),potas-sium(K),calcium(Ca),copper(Cu),manganese(Mn),zinc(Zn),iron(Fe),or protein percentage gave different variations for 24 rice genotypes under all the nutritional *** the 24 genotypes,ten rice genotypes–HighNutrient-1,HighNutrient-2,HighNutrient-9,HighNutrient-8,HighNutrient-3,Hassawi-2,HighNutrient-7,HighNutrient-6,Hassawi-1,and HighNutrient-4–had the highest heist value for all nutritional and protein con-tents,and could be used as a donor to improving new *** was a positive and signiﬁcant correlation between magnesium Mg,K,Zn and ***,K had a positive correlation with zinc Zn,Fe,and protein *** analysis was divided into two groups:theﬁrst group included all genotypes rich in nutri-ents,while the remaining genotypes with low nutritional content were included in the second group.

关键词： Amylose cluster analysis genotypes grain quality mineral nutrition rice

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Absolute partial and total ionization cross sections of carbon monoxide with electron collision from 350 eV to 8000 eV

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Chinese Physics B 2024年第4期33卷 459-464页

作者： Taj Wali Khan 黄伟哲王恩亮单旭陈向军 Hefei National research center of Physical Sciences at the Microscale and department of Modern Physics University of Science and Technology of ChinaHefei 230026China

The absolute partial and total cross sections for electron impact ionization of carbon monoxide are reported for electron energies from 350 eV to 8000 *** product ions(CO^(+),C^(+),O^(+),CO^(2+),C^(2+),and O^(2+))are measured by employing an ion imaging mass spectrometer and two ion-pair dissociation channels(C^(+)+O^(+)and C^(2+)+O^(+))are *** absolute cross sections for producing individual ions and their total,as well as for the ion-pair dissociation channels are obtained by normalizing the data of CO^(+)to that of Ar^(+)from CO-Ar mixture target with a fixed 1:1 *** overall errors are evaluated by considering various kinds of uncertainties.A comprehensive comparison is made with the available data,which shows a good agreement with each other over the energy ranges that are *** work presents new cross-section data with electron energies above 1000 eV.

关键词： electron impact ionization cross sections carbon monoxide ion imaging mass spectrometer

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