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New avenues for the treatment of immunotherapy-resistant pancreatic cancer

World Journal of Gastrointestinal Oncology 2024年第4期16卷 1134-1153页

作者： Luis Guilherme de Oliveira Silva Fabian Fellipe Bueno Lemos Marcel Silva Luz Samuel Luca Rocha Pinheiro Mariana dos Santos Calmon Gabriel Lima Correa Santos Gabriel Reis Rocha Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil

Pancreatic cancer(PC)is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases ***,due to its complexity,it ranks 7th in the list of the most lethal cancers *** pathogenesis of PC involves several complex processes,including familial genetic factors associated with risk factors such as obesity,diabetes mellitus,chronic pancreatitis,and *** in genes such as KRAS,TP53,and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and,consequently,*** this context,some therapies are used for PC,one of which is immunotherapy,which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy *** is therefore clear that the tumor microenvironment(TME)has a huge impact on the resistance process,since cellular and non-cellular elements create an immunosuppressive environment,characterized by a dense desmoplastic stroma with cancerassociated fibroblasts,pancreatic stellate cells,extracellular matrix,and immunosuppressive *** to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells,resulting in a shortage of CD8+T cells and limited expression of activation markers such as *** this way,finding new strategies that make it possible to manipulate resistance mechanisms is ***,techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance,the use of genetic manipulation in specific regions,such as microRNAs,the modulation of extrinsic and intrinsic factors associated with T cells,and,above all,therapeutic models that combine these modulation techniques constitute the promising future of PC ***,this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating thi

关键词： Pancreatic cancer Immunotherapy Resistance Tumor microenvironment manipulation Combined immunotherapy

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An artificial intelligence framework for explainable drift detection in energy forecasting

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Energy and AI 2024年第3期17卷 368-379页

作者： Chamod Samarajeewa Daswin de Silva Milos Manic Nishan Mills Harsha Moraliyage Damminda Alahakoon Andrew Jennings Centre for Data Analytics and Cognition La Trobe UniversityAustralia department of Computer Science Virginia Commonwealth UniversityRichmondUSA

Accurate energy consumption forecasting is crucial for reducing operational costs, achieving net-zero carbon emissions, and ensuring sustainable buildings and cities of the future. despite the frequent use of Artificial Intelligence (AI) algorithms for learning energy consumption patterns and predictions in Building Science, relying solely on these techniques for energy demand prediction addresses only a fraction of the challenge. A drift in energy usage can lead to inaccuracies in these AI models and subsequently to poor decision-making and interventions. While drift detection techniques have been reported, a reliable and robust approach capable of explaining identified discrepancies with actionable insights has not been discussed in extant literature. Hence, this paper presents an Artificial Intelligence framework for energy consumption forecasting with explainable drift detection, aimed at addressing these challenges. The proposed framework is composed of energy embeddings, an optimized dimensional model integrated within a data warehouse, and scalable cloud implementation for effective drift detection with explainability capability. The framework is empirically evaluated in the real-world setting of a multi-campus, mixed-use tertiary education setting in Victoria, Australia. The results of these experiments highlight its capabilities in detecting concept drift, adapting forecast predictions, and providing an interpretation of the changes using energy embeddings.

关键词： Building energy consumption forecasting Explainable drift detection Energy embedding Dimensional modeling

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Solar-driven CO_(2) conversion to methane and methanol using different nanostructured Cu_(2)O-based catalysts modified with Au nanoparticles

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Journal of Energy Chemistry 2024年第4期91卷 287-298页

作者： João Angelo Lima Perini Lilian D.Moura Torquato Juliana Fde Brito Gustavo A.Andolpho Mateus A.Gonçalves Leonardo D.de Angelis Lucas D.Germano Susana I.Córdoba de Torresi Teodorico C.Ramalho Maria V.Boldrin Zanoni São Paulo State University(UNESP) Institute of ChemistryRua Prof.Francisco Degni55AraraquaraSP 14800-060Brazil National Institute of Alternative Technologies for detection Toxicological Evaluation and Removal of Micropollutants and Radioactive Substances(INCT-DATREM)São Paulo State University(UNESP)Institute of ChemistryRua Prof.Francisco Degni55AraraquaraSP 14800-060Brazil Laboratory of Molecular Modelling Department of ChemistryNatural Sciences InstituteFederal University of LavrasLavrasMG 37200-900Brazil department of Chemistry Faculty of ScienceUniversity of Hradec KrálovéHradec Králové50003Czech Republic Instituto de Química Universidade de São PauloAv.Prof.Lineu Prestes 74805508-080São PauloSPBrazil

This work describes the use of TiO_(2)nanotubes-based electrodes(TNT)modified with Cu_(2)O nanostructures and gold nanoparticles for the photoelectroreduction of CO_(2)to produce value-added compounds.A thin layer of polydopamine was used as both an adherent agent and an electron transfer mediator,due to itsπ-conjugated electron *** highest production yield was achieved using a TNT@PDA/Nc/Au40%electrode,with Faradaic efficiencies of 47.4%(110.5μM cm^(-2))and 27.8%(50.4μM cm^(-2))for methanol and methane,*** performance of the photoelectrodes was shown to be Cu_(2)O facet-dependent,with cubic structures leading to greater conversion of CO_(2)to methanol(43%)and methane(27%),compared to the octahedral morphology,while a higher percentage of metallic gold on the nanostructured Cu_(2)O surface was mainly important for *** functional theory(DFT)calculations supported these findings,attributing the superior photoelectrocatalytic performance of the TNT@PDA/Nc/Au40%electrode for CH4generation to the formation of an OCH3intermediate bonded to Au *** using isotope-labeling and analysis by gas chromatograph-mass(GC-MS)demonstrated that13CO_(2)was the source for photoelectrocatalytic generation of13CH3OH and13CH313CH2OH.

关键词： Cu_(2)O nanocubes Photoelectrocatalysis Polydopamine CO_(2) photoelectroreduction DFT calculations

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Structure-based design and optimization lead to the identification of novel dihydrothiopyrano[3,2-d]pyrimidine derivatives as potent HIV-1 inhibitors against drug-resistant variants

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1257-1282页

作者： Zhao Wang Heng Zhang Zhen Gao Zihao Sang Erik de Clercq Christophe Pannecouque Dongwei Kang Peng Zhan Xinyong Liu department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Rega Institute for Medical Research Laboratory of Virology and ChemotherapyK.U.LeuvenLeuven B-3000Belgium China-Belgium Collaborative Research Center for Innovative Antiviral Drugs of Shandong Province Jinan 250012China Suzhou Research Institute Shandong UniversitySuzhou 215123China

With our continuous endeavors in seeking potent anti-HIV-1 agents,we reported here the discovery,biological characterization,and druggability evaluation of a class of nonnucleoside reverse transcriptase *** fully explore the chemical space of the NNRTI-binding pocket,novel series of dihydrothiopyrano[3,2-d]pyrimidines were developed by employing the structure-based design *** of the derivatives were endowed with prominent antiviral activities against HIV-1 wild-type and resistant strains at nanomolar *** them,compound 23h featuring the aminopiperidine moiety was identified as the most potent inhibitor,with EC50values ranging from 3.43 to 21.4 nmol/***,for the challenging double-mutants F227L+V106A and K103N+Y181C,23h exhibited 2.3-to 14.5-fold more potent activity than the first-line drugs efavirenz and ***,the resistance profiles of 23h achieved remarkable improvement compared to efavirenz and *** binding target of 23h was further confirmed to be HIV-1 reverse *** modeling studies were also performed to elucidate the biological evaluation results and give guidance for the optimization ***,no apparent inhibition of the major CYP450 enzymes and hERG channel was observed for *** importantly,23h was characterized by good pharmacokinetic properties and excellent safety in ***,23h holds great promise as a potential candidate for its effective antiviral efficacy and favorable drug-like profiles.

关键词： HIV-1 Reverse transcriptase Dihydrothiopyrano[3,2-d]pyrimidine Antiviral agent

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determining the effective elastic thickness through cross-correlation between isostatic disturbances

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Geodesy and Geodynamics 2024年第3期15卷 241-251页

作者： Nelson Ribeiro-Filho Cristiano Mendel Martins Raissa Moraes Baldez Ivaldevingles Rodrigues de Souza Júnior Franck Eitel Kemgang Ghomsi Instituto Federal do Pará(IFPA) AltamiraParáBrazil Universidade Federal do Pará(UFPA) BelemParáBrazil Nansen-Tutu Center for Marine Environmental Research Department of OceanographyUniversity of Cape TownSouth Africa Geodesy Research Laboratory National Institute of CartographyYaoundeCameroon

The elastic thickness parameter was estimated using the mobile correlation technique between the observed isostatic disturbance and the gravity disturbance calculated through direct gravimetric modeling. We computed the vertical flexure value of the crust for a specific elastic thickness using a given topographic dataset. The gravity disturbance due to the topography was determined after the calculation. A grid of values for the elastic thickness parameter was generated. Then, a moving correlation was performed between the observed gravity data(representing actual surface data) and the calculated data from the forward modeling. The optimum elastic thickness of the particular point corresponded to the highest correlation coefficient. The methodology was tested on synthetic data and showed that the synthetic depth closely matched the original depth, including the elastic thickness value. To validate the results, the described procedure was applied to a real dataset from the Barreirinhas Basin, situated in the northeastern region of Brazil. The results show that the obtained crustal depth is highly correlated with the depth from known models. Additionally, we noted that the elastic thickness behaves as expected, decreasing from the continent towards the ocean. Based on the results, this method has the potential to be employed as a direct estimate of crustal depth and elastic thickness for any region.

关键词： Isostasy Elastic thickness Isostatic disturbance Moho depth Cross-correlation

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Wettability and corrosion behavior between alkaline slag from sodium smelting of vanadium-titanium magnetite and refractory substrates

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Journal of Iron and Steel Research International 2024年第6期31卷 1399-1410页

作者： Fei Zhao Zhi-wei Bian Hong-xin Zhao de-sheng Chen Zhang-fu Yuan Yu-lan Zhen Li-na Wang Tao Qi Collaborative Innovation Center of Steel Technology University of Science and Technology BeijingBeijing 100083China National Engineering Research Center of Green Recycling for Strategic Metal Resources Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China Hebei Zhongke Tongchuang Vanadium&Titanium Technology Co. Ltd.Hengshui 053000HeheiChina

The sodium smelting of vanadium-titanium magnetite can achieve the comprehensive utilization of Fe,V,and ***,the generation of alkaline slag during this process may cause damage to refractory *** wettability and corrosion behavior of alkaline slag on three types of refractory(MgO-C,SiC,and high alumina refractory)substrates were investigated at temperatures up to 1200℃.The effects of duration on the wettability of molten slag on SiC substrates were also *** showed that the high alumina refractory exhibited better wettability with the molten slag than the others,and thus,it is easier to be *** results of scanning electron microscopy coupled with energy dispersive spectroscopy showed that MgO-C and high alumina refractory substrates were severely *** was a visible and regular interfacial reaction layer between the slag and SiC refractory substrate,which was produced by the redox reaction between the metal oxides in the slag and the SiC refractory *** the increase in holding time,the interface layer expands and silico-ferrite phases are generated at the *** redox reaction between Fe_(2)O_(3) and SiC substrate is the main reason for the *** comparing the differences in wettability and corrosion behavior between the alkaline slag from sodium smelting of vanadium-titanium magnetite and MgO-C,SiC and high alumina refractories,it is concluded that SiC refractory has good corrosion resistance to the *** oxides in the slag accelerate the oxidation rate of SiC refractory.

关键词： Wettability Corrosion Alkaline slag-Contact angle Vanadium-titanium magnetite Refractory

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Microstructure and properties of 35 kg large aluminum alloy flywheel housing components formed by squeeze casting with local pressure compensation

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China Foundry 2024年第5期21卷 563-576页

作者： Ju-fu Jiang Jing Yan Ying-ze Liu Ning Ge Ying Wang Chang-jie Ding de-chao Zou School of Materials Science and Engineering Harbin Institute of TechnologyHarbin 150001China School of Mechatronics Engineering Harbin Institute of TechnologyHarbin 150001China Dalian Innovation Die-casting Co. Ltd.Dalian 116600LiaoningChina

The squeeze casting method with local pressure compensation was proposed to form a flywheel housing component with a weight of 35 *** numerical simulation,microstructure observation and phase characterization were performed,and the influence of local pressure compensation on feeding of thick-wall position,microstructure and mechanical properties of the formed components were *** show that the molten metal keeps a good fluidity and the filling is complete during the filling *** the solidification at thick-wall positions of the mounting ports is slow,the local pressure compensation effectively realizes the local forced feeding,significantly eliminating the shrinkage cavity *** the microstructure of AlSi9Mg alloy,α-Al primarily consists of fragmented dendrites and rosette grains,while eutectic Si predominantly comprises needles and short *** impact of local pressure compensation on strength is relatively minimal,yet its influence on elongation is *** local pressure compensation,the average elongation at the compensated areas is 9.18%,which represents a 44.90%higher than that before *** average tensile strength is 209.1 MPa,and the average yield strength is 100.6 *** local pressure compensation can significantly reduce or even eliminate the internal defects in the 35 kg large-weight components formed by squeeze casting.

关键词： squeeze casting local pressure compensation aluminum alloy microstructure mechanical properties large flywheel housing components

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Influence of sintering time on microstructure and properties of hot oscillatory pressing sintered W–Cu refractory alloys

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Tungsten 2024年第2期6卷 323-332页

作者： Zi-Qian Wu Wei Zhao Ka Gao Shi-Hao Du Qing-Quan Kong de-Jian Sun Yang Gao School of Materials Science and Engineering Zhengzhou University of AeronauticsZhengzhou 450015China School of Mechanical Engineering University of Shanghai for Science and TechnologyShanghai 200093China department of General Medicine Changhai HospitalShanghai 200000China Hubei Key Laboratory of Mechanical Transmission and Manufacturing Engineering Wuhan University of Science and TechnologyWuhan 430081China Sichuan Province Engineering Technology Research Center of Powder Metallurgy Chengdu UniversityChengdu 610106China

W–Cu refractory alloys are widely used in aerospace,aviation,electronics,power,and other fi ***,because of its large melting point diff erence between alloy elements,the conventional powder metallurgy method required a long time of high temperature sintering is very likely to cause low density and abnormal grain size ***,90W-10Cu refractory alloys were successfully prepared by hot oscillatory pressing(HOP)under diff erent sintering time in this *** the infl uence of sintering time on the microstructure,grain size,density,Vickers hardness,room-tensile property,and electrical conductivity of the W–Cu refractory alloy was systematically *** results showed that during the short sintering time(30–90 min),the density,Vickers hardness,tensile strength,and electrical conductivity of the W–Cu refractory alloy increased signifi cantly to 98.7%,163.29 HV 30,507.3 MPa,and 14.2%International Annealed Copper Standard with the sintering time increasing,respectively,while its grain size showed no obvious *** the sintering time further increased to 120 min,the density was basically consistent with the sintering time of 90 ***,the prolonged high temperature sintering resulted in the grain growth of the samples,which caused the deterioration of the Vickers hardness,room-tensile strength,and conductivity properties of the W–Cu refractory *** the same sintering time,the density,Vickers hardness,and electrical conductivity of the HOP sintered W–Cu refractory alloy were signifi cantly higher than those of the HP sintered *** was indicated that high density,fi ne-grain,and excellent properties W–Cu refractory alloys could be prepared by hot oscillatory pressing under appropriate sintering time.

关键词： W–Cu refractory alloy Hot oscillatory pressing Sintering time Microstructure Property

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Highly efficient photo-thermal synergistic catalysis of CO_(2)methanation over La_(1-x)Ce_(x)NiO_(3)perovskite-catalyst

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Nano Research 2024年第9期17卷 7945-7956页

作者： Ting Li Zhen-Yu Zhang de-Cun Luo Bo-Yu Xu Rong-Jiang Zhang Ji-Long Yao Dan Li Tao Xie Institute of Industrial Catalysis School of Chemical Engineering and TechnologyXi’an Jiaotong UniversityXi’an 710049China

Solar-driven photo-thermal catalytic CO_(2)methanation reaction is a promising technology to alleviate the problems posed by greenhouse gases ***,designing advanced photo-thermal catalysts remains a research challenge for CO_(2)methanation *** this work,a series of ABO3(A=lanthanide,B=transition metal)perovskite catalysts with Ce-substituted LaNiO3(La_(1-x)Ce_(x)NiO_(3),x=0,0.2,0.5,0.8,1)were synthesized for CO_(2)*** La_(0.2)Ce_(0.8)NiO_(3) exhibited the highest CH_(4) formation rate of 258.9 mmol·g^(-1)·hcat-1,CO_(2)conversion of 55.4%and 97.2%CH_(4) selectivity at 300℃with the light intensity of 2.9 W·cm^(-2).Then the catalysts were thoroughly analyzed by physicochemical structure and optical properties *** partial substitution of the A-site provided more active sites for the adsorption and activation of CO_(2)/H_(2).The sources of the active sites were considered to be the oxygen vacancies(O_(v))created by lattice distortions due to different species of ions(La^(3+),Ce^(4+),Ce^(3+))and exsolved Ni0 by H_(2)*** catalysts have excellent light absorption absorbance and low electron-hole(e^(-)/h^(+))recombination rate,which greatly contribute to the excellent performance in photo-thermal synergistic catalysis(PTC)CO_(2)*** results of in situ irradiated electron paramagnetic resonance spectrometer(ISI-EPR)and ISI-X-ray photoelectron spectroscopy(XPS)indicated that the aggregation of unpaired electrons near the defects and Ni metal(from La and Ce ions to Ov and Ni0)accelerated adsorption and activation of CO_(2)/H_(2).At last,the catalyst properties and structure were correlated with the proposed reaction mechanism from the in situ diffuse reflection infrared Fourier transform spectrum(DRIFTS)*** in situ precipitation of the B-site enhanced the dispersion of Ni,while its enriched photoelectrons upon illumination further promote hydrogen *** H^(*)spillover accelerated t

关键词： photo-thermal catalysis CO_(2)methanation perovskite A-site substitution in situ diffuse reflection infrared Fourier transform spectrum(DRIFTS)

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Genetic Analysis of Two Novel GPI Variants Disrupting H Bonds and Localization Characteristics of 55 Gene Variants Associated with Glucose-6-phosphate Isomerase deficiency

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Current Medical Science 2024年第2期44卷 426-434页

作者： Bi-xin XI Si-ying LIU Yu-ting XU de-dong ZHANG Qun HU Ai-guo LIU department of Pediatrics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Objective:Glucose-6-phosphate isomerase(GPI)deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene *** disorder exhibits wide heterogeneity in its clinical manifestations and molecular characteristics,often posing challenges for precise diagnoses using conventional *** this end,this study aimed to identify the novel variants responsible for GPI deficiency in a Chinese ***:The clinical manifestations of the patient were summarized and analyzed for GPI deficiency phenotype *** compound heterozygous variants of the GPI gene,c.174C>A(***58Lys)and c.1538G>T(***513Leu),were identified using whole-exome and Sanger *** AlphaFold program and Chimera software were used to analyze the effects of compound heterozygous variants on GPI ***:By characterizing 53 GPI missense/nonsense variants from previous literature and two novel missense variants identified in this study,we found that most variants were located in exons 3,4,12,and 18,with a few localized in exons 8,9,and *** study identified novel compound heterozygous variants associated with GPI *** pathogenic variants disrupt hydrogen bonds formed by highly conserved GPI amino ***:Early family-based sequencing analyses,especially for patients with congenital anemia,can help increase diagnostic accuracy for GPI deficiency,improve child healthcare,and enable genetic counseling.

关键词： glucose-6-phosphate isomerase deficiency whole-exome sequencing compound heterozygous variants genetic characterization hydrogen bond

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