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Immunologic tumor microenvironment modulators for turning cold tumors hot

Cancer Communications 2024年第5期44卷 521-553页

作者： Gholam-Reza Khosravi Samaneh Mostafavi Sanaz Bastan Narges Ebrahimi Roya Safari Gharibvand Nahid Eskandari department of Medical Immunology School of MedicineIsfahan University of Medical SciencesIsfahanIran department of Immunology Faculty of Medical SciencesTarbiat Modares UniversityTehranIran department of Immunology School of MedicineAhvaz Jundishapur University of Medical SciencesAhvazIran

Tumors can be classified into distinct immunophenotypes based on the presence and arrangement of cytotoxic immune cells within the tumor microenvironment(TME).Hot tumors,characterized by heightened immune activity and responsiveness to immune checkpoint inhibitors(ICIs),stand in stark contrast to cold tumors,which lack immune infiltration and remain resistant to *** overcome immune evasion mechanisms employed by tumor cells,novel immunologic modulators have emerged,particularly ICIs targeting cytotoxic T-lymphocyte-associated protein 4(CTLA-4)and programmed cell death protein 1/programmed death-ligand 1(PD-1/PD-L1).These agents disrupt inhibitory signals and reactivate the immune system,transforming cold tumors into hot ones and promoting effective antitumor ***,challenges persist,including primary resistance to immunotherapy,autoimmune side effects,and tumor response *** these challenges requires innovative strategies,deeper mechanistic insights,and a combination of immune interventions to enhance the effectiveness of *** the landscape of cancer medicine,where immune cold tumors represent a formidable hurdle,understanding the TME and harnessing its potential to reprogram the immune response is *** review sheds light on current advancements and future directions in the quest for more effective and safer cancer treatment strategies,offering hope for patients with immune-resistant tumors.

关键词： cold tumor hot tumor immunologic modulator immunotherapy therapeutic strategy tumor microenvironment

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Annual growth of Fagus orientalis is limited by spring drought conditions in Iran’s Golestan Province

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Journal of Forestry Research 2024年第1期35卷 128-142页

作者： Khalil Ghorbani Jahangir Mohammadi Laleh Rezaei Ghaleh department of Water Engineering Faculty of Water and Soil EngineeringGorgan University of Agricultural Sciences and Natural ResourcesGorganIran department of Forestry Gorgan University of Agricultural Sciences and Natural ResourcesGorganIran department of Water Engineering Faculty of AgricultureUrmia UniversityUrmiaIran

Due to the lack of a uniform and accurate defi-nition of‘drought’,several indicators have been introduced based on different variables and methods,and the efficiency of each of these is determined according to their relationship with *** relationship between two drought indices,SPI(standardized precipitation index)and SPEI(standard-ized precipitation-evapotranspiration index)in different sea-sons was investigated using annual rings of 15 tree samples to determine the effect of drought on the growth of oriental beech(Fagus orientalis Lipsky)in the Hyrcanian forests of northern *** different evapotranspiration calcula-tion methods were evaluated on SPEI efficiency based on Hargreaves-Samani,Thornthwaite,and Penman-Monteith methods using the step-by-step M5 decision tree regression *** results show that SPEI based on the Penman-Monteith in a three-month time scale(spring)had similar temporal changes and a better relationship with annual tree rings(R^(2)=0.81)at a 0.05 significant *** change and a decreasing trend in the time series of annual tree rings are similar to the variation in the SPEI based on the Penman-Monteith *** affecting evapotranspiration,temperature,wind speed,and sunshine hours(used in the Penman-Monteith method),increased but precipitation *** non-linear modeling methods,SPEI based on Penman-Monteith best illustrated climate changes affecting tree growth.

关键词： Climate change Drought index Hyrcanian forests SPEI'Annual growth rings Fagus orientalis

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High-throughput computational screening and in vitro evaluation identifies 5-(4-oxo-4H-3,1-benzoxazin-2-yl)-2-[3-(4-oxo-4H-3,1-benzoxazin-2-yl)phenyl]-1H-isoindole-1,3(2H)-dione(C3),as a novel EGFR—HER2 dual inhibitor in gastric tumors

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Oncology Research 2024年第2期32卷 251-259页

作者： MESFER AL SHAHRANI REEM GAHTANI MOHAMMAD ABOHASSAN MOHAMMAD ALSHAHRANI YASSER ALRAEY AYED DERA MOHAMMAD RAJEH ASIRI PRASANNA RAJAGOPALAN department of Clinical Laboratory sciences College of Applied Medical SciencesKing Khalid UniversityAbhaSaudi Arabia

Gastric cancers are caused primarily due to the activation and amplification of the EGFR or HER2 kinases resulting in cell proliferation,adhesion,angiogenesis,and *** therapies are ineffective due to the intra-tumoral heterogeneity and concomitant genetic ***,dual inhibition strategies are recommended to increase potency and reduce *** this study,we have conducted computational high-throughput screening of the ChemBridge library followed by in vitro assays and identified novel selective inhibitors that have a dual impediment of EGFR/HER2 kinase ***-based High-throughput Virtual Screening(D-HTVS)was used to screen the whole ChemBridge small molecular library against EGFR and *** atomistic molecular dynamic simulation was conducted to understand the dynamics and stability of the protein-ligand ***/HER2 kinase enzymes,KATOIII,and Snu-5 cells were used for in vitro *** atomistic Molecular Dynamics simulations followed by solvent-based Gibbs binding free energy calculation of top molecules,identified compound C3(5-(4-oxo-4H-3,1-benzoxazin-2-yl)-2-[3-(4-oxo-4H-3,1-benzoxazin-2-yl)phenyl]-1H-isoindole-1,3(2H)-dione)to have a good affinity for both EGFR and *** predicted compound,C3,was promising with better binding energy,good binding pose,and optimum interactions with the EGFR and HER2 residues.C3 inhibited EGFR and HER2 kinases with IC50 values of 37.24 and 45.83 nM,*** GI50 values of C3 to inhibit KATOIII and Snu-5 cells were 84.76 and 48.26 nM,*** on these findings,we conclude that the identified compound C3 showed a conceivable dual inhibitory activity on EGFR/HER2 kinase,and therefore can be considered as a plausible lead-like molecule for treating gastric cancers with minimal side effects,though testing in higher models with pharmacokinetic approach is required.

关键词： Dual inhibitor Drug discovery EGFR/HER2 kinase Gastric cancer High-throughput screening

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Metabolic relationships between marine red algae and algae‑associated bacteria

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Marine Life Science & Technology 2024年第2期6卷 298-314页

作者： Kyung Hyun Kim Jeong Min Kim Ju Hye Baek Sang Eun Jeong Hocheol Kim Hwan Su Yoon Che Ok Jeon department of Biological sciences and Biotechnology Hannam UniversityDaejon 34054Republic of Korea department of Life Science Chung-Ang UniversitySeoul 06974Republic of Korea department of Biological sciences Sungkyunkwan UniversitySuwon 16419Republic of Korea

Mutualistic interactions between marine phototrophs and associated bacteria are an important strategy for their success-ful survival in the ocean,but little is known about their metabolic ***,bacterial communities in the algal sphere(AS)and bulk solution(BS)of nine marine red algal cultures were analyzed,and Roseibium and Phycisphaera were identified significantly more abundantly in AS than in *** metabolic features of Roseibium RMAR6-6(isolated and genome-sequenced),Phycisphaera MAG 12(obtained by metagenomic sequencing),and a marine red alga,Porphyridium purpureum CCMP1328(from GenBank),were analyzed ***6-6 has the genetic capability to fix nitrogen and produce B vitamins(B1,B2,B5,B6,B9,and B12),bacterioferritin,dimethylsulfoniopropionate(DMSP),and phenylacetate that may enhance algal growth,whereas MAG 12 may have a limited metabolic capability,not producing vitamins B9 and B12,DMSP,phenylacetate,and siderophores,but with the ability to produce bacitracin,possibly modulating algal *** CCMP1328 lacks the genetic capability to fix nitrogen and produce vitamin B12,DMSP,phenylacetate,and *** was shown that the nitrogen-fixing ability of RMAR6-6 promoted the growth of ***-pureum,and DMSP reduced the oxidative stress of *** metabolic interactions between strain RMAR6-6 and *** CCMP1328 were also investigated by the transcriptomic analyses of their monoculture and *** together,potential metabolic relationships between Roseibium and *** were *** study provides a bet-ter understanding of the metabolic relationships between marine algae and algae-associated bacteria for successful growth.

关键词： Metabolic relationship Marine red algae Symbiotic bacteria Roseibium Phycisphaera Porphyridium

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Electricity demand forecasting at distribution and household levels using explainable causal graph neural network

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Energy and AI 2024年第2期16卷 385-395页

作者： Amir Miraki Pekka Parviainen Reza Arghandeh department of Computer Science Electrical Engineering and Mathematical SciencesWestern Norway University of Applied SciencesBergenNorway department of Informatics University of BergenBergenNorway

Forecasting electricity demand is an essential part of the smart grid to ensure a stable and reliable power grid. With the increasing integration of renewable energy resources into the grid, forecasting the demand for electricity is critical at all levels, from the distribution to the household. Most existing forecasting methods, however, can be considered black-box models as a result of deep digitalization enablers, such as deep neural networks, which remain difficult to interpret by humans. Moreover, capture of the inter-dependencies among variables presents a significant challenge for multivariate time series forecasting. In this paper we propose eXplainable Causal Graph Neural Network (X-CGNN) for multivariate electricity demand forecasting that overcomes these limitations. As part of this method, we have intrinsic and global explanations based on causal inferences as well as local explanations based on post-hoc analyses. We have performed extensive validation on two real-world electricity demand datasets from both the household and distribution levels to demonstrate that our proposed method achieves state-of-the-art performance.

关键词： Causal inference Electricity demand forecasting Explainable artificial intelligence(XAI) Graph neural network

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Influence of upstream solar wind on magnetic field distribution in the Martian nightside ionosphere

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Earth and Planetary Physics 2024年第5期8卷 728-741页

作者： JiaWei Gao ZhaoJin Rong Qi Zhang Anna Mittelholz Chi Zhang Yong Wei Key Laboratory of Earth and Planetary Physics Institute of Geology and Geophysics Chinese Academy of Sciences College of Earth and Planetary sciences University of Chinese Academy of Sciences Swedish Institute of Space Physics department of Earth sciences Center for Space Physics and department of Astronomy Boston University

Using over eight years of Mars Atmosphere and Volatile Evolutio N （MAVEN） data,from November 2014 to May 2023,we have investigated the Martian nightside ionospheric magnetic field distribution under the influence of upstream solar wind drivers,including the interplanetary magnetic field intensity (∣BIMF∣),solar wind dynamic pressure （PSW）,solar extreme ultraviolet flux （EUV）,and Martian seasons （Ls）.Our analysis reveals pronounced correlations between magnetic field residuals and both∣BIMF∣and *** observed with EUV flux and Lswere weaker—notably,magnetic field residuals increased during periods of high EUV flux and at Mars *** find that the IMF penetrates to an altitude of 200 km under a wide range of upstream conditions,penetrating notably deeper under high∣BIMF∣*** analysis also indicates that EUV flux and IMF cone angle have minimal impact on IMF penetration *** findings provide useful constraints on the dynamic nature of Martian atmospheric escape processes and their evolution,suggesting that historical solar wind conditions may have facilitated deeper IMF penetration and higher rates of ionospheric escape than are observed ***,by establishing criteria for magnetic‘quiet’conditions,this study offers new insights into the planet’s magnetic environment under varying solar wind influences,knowledge that should help refine models of the Martian crustal magnetic field.

关键词： Martian magnetic field external magnetic field upstream solar wind drivers IMF penetration altitude magnetic field activity indices

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Rosmarinic acid improves tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats

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Asian Pacific Journal of Tropical Biomedicine 2024年第3期14卷 100-105页

作者： Vahideh Abbasnia Mohsen Foadoddini Delaram Eslimi Esfahani Mohammad Reza Khazdair Shahrbanoo Oryan department of Biology Payame Noor UniversityTehranIran Cardiovascular Diseases Research Center Birjand University of Medical SciencesBirjandIran department of Animal sciences Faculty of Biological SciencesKharazmi UniversityTehranIran

Objective:To evaluate the effect of rosmarinic acid on tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized ***:Rats were randomly divided into six groups:the control group,the asthmatic group,and the asthmatic groups treated with dexamethasone(1 mg/kg;oral gavage)or three doses of rosmarinic acid(0.5,1,and 2 mg/kg;oral gavage).For induction of asthma,rats received intraperitoneal injections and inhalation of *** 21 days,bronchoalveolar lavage fluid and lung samples were collected for histopathological ***,total and differential white blood cell counts were ***:The rosmarinic acid-treated group had significantly lower tracheal smooth muscle responses to methacholine than the asthmatic *** addition,rosmarinic acid reduced white blood cell count and the percentages of eosinophils,monocytes,and neutrophils while increasing the percentage of ***-induced lung pathological changes were significantly improved by treatment with rosmarinic ***:Rosmarinic acid improves tracheal smooth muscle responsiveness and lung pathological changes in ovalbumin-sensitized rats.

关键词： Rosmarinic acid Asthma Ovalbumin Tracheal responsiveness Inflammation White blood cell

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Enantioselective iridium-catalyzed allylic substitution with a Reformatsky reagent: direct construction of β-stereogenic homoallylic esters

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Science China Chemistry 2024年第11期67卷 3791-3797页

作者： Debasis Pal Kirana D.Veeranna Yuk Fai Wong P.Andrew Evans department of Chemistry Queen's University Xiangya School of Pharmaceutical sciences Central South University

The Reformatsky reagent derived from ethyl bromoacetate circumvents the challenge associated with the direct regio-and enantioselective iridium-catalyzed allylic alkylation with an unstabilized aliphatic ester enolate. Notably, this work represents the first example of using a Reformatsky reagent in a metal-allyl reaction, which permits the direct construction of enantioenriched β-stereogenic homoallylic esters without preactivation of the pronucleophile or post-reaction modification of the product(e.g., thermal decarboxylation of a 1,3-dicarbonyl). Moreover, the process allows the coupling of a broad range of sterically and electronically diverse electrophiles bearing aryl, heteroaryl and alkenyl derivatives, including the significantly more challenging alkyl-substituted allylic carbonates. The versatility of the ester product is exemplified by a series of functional group manipulations and the development of a concise and efficient enantioselective total synthesis of the natural product,(+)-descurainolide A. Finally, mechanistic studies indicate that the zinc enolate behaves as a soft nucleophile that undergoes outer-sphere alkylation.

关键词： allylic substitution asymmetric catalysis mechanistic studies natural product synthesis Reformatsky reagent

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Investigation of tungsten halogen lamp for possible usage as heat source for testing solar collector

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Energy and Built Environment 2024年第4期5卷 517-528页

作者： Rapeepong Peamsuwan Pathiwat Waramit Ittipon Worapun Bundit Krittacom Tanakorn Phoo-Ngernkham Ratinun Luampon department of Applied Physics Faculty of Science and Liberal ArtsRajamangala University of Technology Isan744Suranarai Rd.Nai mueangMueangNakhon Ratchasima 30000Thailand department of Mechanical Engineering Faculty of Engineering and TechnologyRajamangala University of Technology Isan744Suranarai Rd.Nai mueangMueangNakhon Ratchasima 30000Thailand department of Civil Engineering Faculty of Engineering and TechnologyRajamangala University of Technology Isan744Suranarai Rd.Nai mueangMueangNakhon Ratchasima 30000Thailand Development in Technology of Porous Materials Research Laboratory:DiTo-Lab Thailand

Artificial sunlight is a heat source in solar collector testing,where the light intensity and ambient conditions are controlled to provide uniformity in each *** this study,twenty-five tungsten halogen lamps of 300 W 220 V were investigated for possible usage as the heat *** experiment was conducted by varying the height of the lamps to the light field(H_(d)).The EN-12975-2 Standard was used to control the quality of the heat source on the light *** results showed that the average light intensity(I_(avg))decreased with an increase in *** H_(d) was low,the%uniformity values(%u_(xy))met the *** small light field area met the EN-12975-2 Standard better than the large area.A comparison of solar collector testing under a heat source from tungsten halogen lamps and natural sunlight was subsequently performed,and the experimental results were in accordance with the EN-12975-2 Standard.A single-channel flat plate solar collector was used as the test device and air was used as the working *** experimental results revealed that the solar collector thermal efficiency(η_(avg))trends were similar for both the heat source from tungsten halogen lamps and natural sunlight testing.A low%u_(xy) resulted in a𝜂avg that was more similar to that of natural sunlight.

关键词： Solar simulator EN-12975-2 Standard Light intensity Uniformity value Thermal efficiency

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Dieback of managed spruce stands in western Germany promotes beetle diversity

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Journal of Forestry Research 2024年第3期35卷 55-71页

作者： Eva Plath Chantal Trauth Jan Gerhards Laura Griebel Klaus Fischer department Biology Institute of Integrated Natural SciencesKoblenz-Landau University56070 KoblenzGermany

Biodiversity loss is a significant problem at a global scale and may be amplified by climate *** recent years,coniferous forests have had substantial die-back across Europe due to drought and subsequent bark-beetle *** many studies on the consequences of disturbance and subsequent management have focused on natural stands,management implications for managed spruce stands are not well understood,even though such stands are widespread throughout *** this study,beetle taxonomy,conservation value,and community com-position are compared among spruce plantations and four post-disturbance management approaches:standing dead-wood,lying deadwood,clear cuts,and long-term *** and community composition differed significantly among management categories,while different beetle fami-lies responded *** spruce stands harbored the lowest beetle diversity while the highest taxonomic diver-sity and conservation value was on clear cuts and stands with lying or standing *** proportion of forest specialists was highest in successional *** summary,different forest management categories harbored distinct beetle communities at the family-,species-,and ecological guild ***,post-disturbance management should consider the landscape scale and include different management *** enhances landscape heterogeneity and thus overall biodiversity but could also mitigate negative impacts of natural disturbances on ecosystem services.

关键词： Bark-beetle outbreak Forest dieback Spruce Deadwood Nature conservation Beetle biodiversity-Coleoptera Coniferous forests

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