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Thymoquinone affects hypoxia-inducible factor-1αexpression in pancreatic cancer cells via HSP90 and PI3K/AKT/mTOR pathways

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World Journal of Gastroenterology 2024年第21期30卷 2793-2816页

作者： zhan-xue zhao Shuai Li Lin-Xun Liu Department of General Surgery Qinghai Provincial People's HospitalXining 810007Qinghai ProvinceChina Department of Clinical Pharmacy The Affiliated Hospital of Qinghai UniversityXining 810001Qinghai ProvinceChina

BACKGROUND Pancreatic cancer(PC)is associated with some of the worst prognoses of all major cancers.Thymoquinone(TQ)has a long history in traditional medical practice and is known for its anti-cancer,anti-inflammatory,anti-fibrosis and antioxidant pharmacological activities.Recent studies on hypoxia-inducible factor-1α(HIF-1α)and PC have shown that HIF-1αaffects the occurrence and development of PC in many aspects.In addition,TQ could inhibit the development of renal cancer by decreasing the expression of HIF-1α.Therefore,we speculate whether TQ affects HIF-1αexpression in PC cells and explore the mechanism.AIM To elucidate the effect of TQ in PC cells and the regulatory mechanism of HIF-1αexpression.METHODS Cell counting kit-8 assay,Transwell assay and flow cytometry were performed to detect the effects of TQ on the proliferative activity,migration and invasion ability and apoptosis of PANC-1 cells and normal pancreatic duct epithelial(hTERTHPNE)cells.Quantitative real-time polymerase chain reaction and western blot assay were performed to detect the expression of HIF-1αmRNA and protein in PC cells.The effects of TQ on the HIF-1αprotein initial expression pathway and ubiquitination degradation in PANC-1 cells were examined by western blot assay and co-immunoprecipitation.RESULTS TQ significantly inhibited proliferative activity,migration,and invasion ability and promoted apoptosis of PANC-1 cells;however,no significant effects on hTERT-HPNE cells were observed.TQ significantly reduced the mRNA and protein expression levels of HIF-1αin PANC-1,AsPC-1,and BxPC-3 cells.TQ significantly inhibited the expression of the HIF-1αinitial expression pathway(PI3K/AKT/mTOR)related proteins,and promoted the ubiquitination degradation of the HIF-1αprotein in PANC-1 cells.TQ had no effect on the hydroxylation and von Hippel Lindau protein mediated ubiquitination degradation of the HIF-1αprotein but affected the stability of the HIF-1αprotein by inhibiting the interaction between HIF-1αand HSP90,thus promoting its ubiquitination

关键词： Thymoquinone Pancreatic cancer Hypoxia-inducible factor-1α PI3K/AKT/mTOR HSP90

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Kinetic model of vibration screening for granular materials based on biological neural network

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Particuology 2024年第5期88卷 98-106页

作者： zhan zhao Yan zhang Fang Qin Mingzhi Jin School of Agricultural Engineering Jiangsu UniversityZhenjiang212013China Shandong Academy of Agricultural Machinery Sciences Ji'nan250100China

The kinetic model is the theoretical basis for optimizing the structure and operation performance of vibration screening devices.In this paper,a biological neurodynamic equation and neural connections were established according to the motion and interaction properties of the material under vibration excitation.The material feeding to the screen and the material passing through apertures were considered as excitatory and inhibitory inputs,respectively,and the generated stable neural activity landscape was used to describe the material distribution on the 2D screen surface.The dynamic process of material vibration screening was simulated using discrete element method(DEM).By comparing the similarity between the material distribution established using biological neural network(BNN)and that obtained using DEM simulation,the optimum coefficients of BNN model under a certain screening parameter were determined,that is,one relationship between the BNN model coefficients and the screening operation parameters was established.Different screening parameters were randomly selected,and the corresponding relationships were established as a database.Then,with straw/grain ratio,aperture diameter,inclination angle,vibration strength in normal and tangential directions as inputs,five independent adaptive neuro-fuzzy inference systems(ANFIS)were established to predict the optimum BNN model coefficients,respectively.The training results indicated that ANFIS models had good stability and accuracy.The flexibility and adaptability of the proposed BNN method was demonstrated by modeling material distribution under complex feeding conditions such as multiple regions and non-uniform rate.

关键词： Kinetic model Material distribution Vibration screening Biological neural network DEM simulation Adaptive neuro-fuzzy inference systems

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Testing Linearity in Functional Partially Linear Models

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Acta Mathematicae Applicatae Sinica 2024年第3期40卷 875-886页

作者： Fan-rong zhao Bao-xue zhanG School of Mathematical Sciences Shanxi UniversityTaiyuan 030006China School of Statistics Capital University of Economics and BusinessBeijing 100070China

For the functional partially linear models including flexible nonparametric part and functional linear part,the estimators of the nonlinear function and the slope function have been studied in existing literature.How to test the correlation between response and explanatory variables,however,still seems to be missing.Therefore,a test procedure for testing the linearity in the functional partially linear models will be proposed in this paper.A test statistic is constructed based on the existing estimators of the nonlinear and the slope functions.Further,we prove that the approximately asymptotic distribution of the proposed statistic is a chi-squared distribution under some regularity conditions.Finally,some simulation studies and a real data application are presented to demonstrate the performance of the proposed test statistic.

关键词： asymptotic theory functional partially linear model Nadaraya-Watson estimate test statistic

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Coherence phase spectrum analyzer for a randomly fluctuated fractional vortex beam

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Photonics Research 2024年第1期12卷 33-39页

作者： ZHUOYI WANG XINGYUAN LU JIANBO GAO xueCHUN zhao QIWEN zhan YANGJIAN CAI CHENGLIANG zhao School of Physical Science and Technology Soochow UniversitySuzhou 215006China School of Optical-Electrical and Computer Engineering University of Shanghai for Science and TechnologyShanghai 200093China Shandong Provincial Engineering and Technical Center of Light Manipulations&Shandong Provincial Key Laboratory of Optics and Photonic Device School of Physics and ElectronicsShandong Normal UniversityJinan 250358China Shandong Joint Research Center of Light Manipulation Science and Photonics Integrated Chip of East China Normal University and Shandong Normal University East China Normal UniversityShanghai 200241China

Fractional vortex beams exhibit a higher degree of modulation dimensions than conventional vortices,thus inheriting superior anti-turbulent transmission properties through the incorporation of additional coherence modulation.However,aliasing the mixed modes induced by coherence degradation makes the quantitative measurement of the topological charge in fractional vortex beams challenging.In this study,a coherence phase spectrum was introduced,and experimental demonstrations to quantitatively determine the fractional topological charge of partially coherent fractional vortex beams were performed.By leveraging the four-dimensional measurement of a partially coherent light field,the source coherence function was inversely reconstructed,and fractional topological charges were determined with high precision by extracting the phase spectrum of the coherence function.Laguerre–Gaussian,elliptical Gaussian,and plane-wave-fraction vortex beams with various degrees of coherence were used to demonstrate measurement precision.The proposed method is applicable to X-rays and electron vortices.It has potential applications in optical encryption,high-capacity optical communication,and quantum entanglement.

关键词： function fractional vortex

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BMSC-derived Exosomes Ameliorate Peritoneal Dialysis-associated Peritoneal Fibrosis via the Mir-27a-3p/TP53 Pathway

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Current Medical Science 2024年第2期44卷 333-345页

作者： Jun-li zhao Lin zhao Qiu-nan zhan Miao LIU Ting zhanG Wen-wen CHU Department of Nephrology Shanghai University of Medicine&Health Sciences Ailiated Zhoupu HospitalShanghai 201318China Orthopedic Department Guangming Traditional Chinese Medicine Hospital of Pudong New AreaShanghai 201399China

Objective:Peritoneal fibrosis(PF)is the main cause of declining efficiency and ultrafiltration failure of the peritoneum,which restricts the long-term application of peritoneal dialysis(PD).This study aimed to investigate the therapeutic effects and mechanisms of bone marrow mesenchymal stem cells-derived exosomes(BMSC-Exos)on PF in response to PD.Methods:Small RNA sequencing analysis of BMSC-Exos was performed by second-generation sequencing.C57BL/6J mice were infused with 4.25%glucose-based peritoneal dialysis fluid(PDF)for 6 consecutive weeks to establish a PF model.A total of 36 mice were randomly divided into 6 groups:control group,1.5%PDF group,2.5%PDF group,4.25%PDF group,BMSC-Exos treatment group,and BMSC-Exos+TP53 treatment group.Reverse transcription quantitative polymerase chain reaction(RT-qPCR)was performed to measure the expression level of miR-27a-3p in BMSC-Exos and peritoneum of mice treated with different concentrations of PDF.HE and Masson staining were performed to evaluate the extent of PF.The therapeutic potential of BMSC-Exos for PF was examined through pathological examination,RT-qPCR,Western blotting,and peritoneal function analyses.Epithelial-mesenchymal transition(EMT)of HMrSV5 was induced with 4.25%PDF.Cells were divided into control group,4.25%PDF group,BMSC-Exos treatment group,and BMSC-Exos+TP53 treatment group.Cell Counting Kit-8 assay was used to measure cell viability,and transwell migration assay was used to verify the capacity of BMSC-Exos to inhibit EMT in HMrSV5 cells.Results:Small RNA sequencing analysis showed that miR-27a-3p was highly expressed in BMSC-derived exosomes compared to BMSCs.The RT-qPCR results showed that the expression of miR-27a-3p was upregulated in BMSC-Exos,but decreased in PD mice.We found that PF was glucose concentration-dependently enhanced in the peritoneum of the PD mice.Compared with the control mice,the PD mice showed high solute transport and decreased ultrafiltration volume as well as an obvious fibroproliferative response,with markedly increas

关键词： peritoneal fibrosis bone marrow mesenchymal stem cell-derived exosomes miR-27a-3p TP53 epithelialmesenchymal transition

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A Unifi ed View of Carbon Neutrality:Solar-Driven Selective Upcycling of Waste Plastics

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Transactions of Tianjin University 2024年第1期30卷 1-26页

作者： Zhiyong zhao Shuai Yue Gaohua Yang Pengfei Wang Sihui zhan MOE Key Laboratory of Pollution Processes and Environmental Criteria Tianjin Key Laboratory of Environmental Remediation and Pollution ControlCollege of Environmental Science and EngineeringTianjin 300350China

With the rapid development of plastic production and consumption globally,the amount of post-consumer plastic waste has reached levels that have posed environmental threats.Considering the substantial CO_(2)emissions throughout the plastic lifecycle from material production to its disposal,photocatalysis is considered a promising strategy for eff ective plastic recycling and upcycling.It can upgrade plastics into value-added products under mild conditions using solar energy,realizing zero carbon emissions.In this paper,we explain the basics of photocatalytic plastic reformation and underscores plastic feedstock reformation pathways into high-value-added products,including both degradation into CO_(2)followed by reformation and direct reformation into high-value-added products.Finally,the current applications of transforming plastic waste into fuels,chemicals,and carbon materials and the outlook on upcycling plastic waste by photocatalysis are presented,facilitating the realization of carbon neutrality and zero plastic waste.

关键词： Photocatalysis Photoreforming Plastics upcycling Carbon neutrality Energy storage and conversion

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Identification of anti-gastric cancer effects and molecular mechanisms of resveratrol: From network pharmacology and bioinformatics to experimental validation

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 493-513页

作者： Ying-Qian Ma Ming zhang Zhen-Hua Sun Hong-Yue Tang Ying Wang Jiang-xue Liu zhan-xue zhang Chao Wang Department of Oncology Hebei General HospitalShijiazhuang 050051Hebei ProvinceChina School of Graduate Studies Hebei Medical UniversityShijiazhuang 050017Hebei ProvinceChina Clinical Medical Research Center Hebei General HospitalShijiazhuang 050051Hebei ProvinceChina Department of Gastrointestinal Surgery Second Hospital of Hebei Medical UniversityShijiazhuang 050000Hebei ProvinceChina

BACKGROUND Gastric cancer(GC)is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis.Resveratrol,a non-flavonoid poly-phenolic compound found in a variety of Chinese medicinal materials,has shown excellent anti-GC effect.However,its exact mechanisms of action in GC have not been clarified.AIM To identify the effects of resveratrol on GC progression and explore the related molecular mechanisms.METHODS Action targets of resveratrol and GC-related targets were screened from public databases.The overlapping targets between the two were confirmed using a Venn diagram,and a“Resveratrol-Target-GC”network was constructed using Cyto-scape software version 3.9.1.The protein-protein interaction(PPI)network was constructed using STRING database and core targets were identified by PPI network analysis.The Database for Annotation,Visualization and Integrated A total of 378 resveratrol action targets and 2154 GC disease targets were obtained from public databases,and 181 intersection targets between the two were screened by Venn diagram.The top 20 core targets were identified by PPI network analysis of the overlapping targets.GO function analysis mainly involved protein binding,identical protein binding,cytoplasm,nucleus,negative regulation of apoptotic process and response to xenobiotic stimulus.KEGG enrichment analysis suggested that the involved signaling pathways mainly included PI3K-AKT signaling pathway,MAPK signaling pathway,IL-17 signaling pathway,TNF signaling pathway,ErbB signaling pathway,etc.FBJ murine osteosarcoma viral oncogene homolog(FOS)and matrix metallopeptidase 9(MMP9)were selected by differential expression analysis,and they were closely associated with immune infiltration.Molecular docking results showed that resveratrol docked well with these two targets.Resveratrol treatment arrested the cell cycle at the S phase,induced apoptosis,and weakened viability,migration and invasion in a dose-dependent manner.Furthermore,resveratrol could exhibit anti-GC effect by regula

关键词： Resveratrol Gastric cancer Network pharmacology Bioinformatics Molecular docking

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Switchable shape memory polymer bio-inspired adhesive and its application for unmanned aerial vehicle landing

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Chinese Journal of Aeronautics 2024年第3期37卷 380-390页

作者： Qingsong HE Zefang zhao Qiyun ZHONG Siyuan LIU Kai DENG Yongqi LIU Ning zhanG Zijie zhao Fengjiang zhan Jianfeng zhao Jiangsu Provincial Key Laboratory of Bionic Functional Materials College of Mechanical and Electrical EngineeringNanjing University of Aeronautics and AstronauticsNanjing 210016China Key Laboratory of Advanced Technology for Small and Medium-Sized UAV Ministry of Industry and Information TechnologyUnmanned Aerial Vehicles Research InstituteNanjing University of Aeronautics and AstronauticsNanjing 210016China State Key Laboratory of Mechanics and Control of Aerospace Structures Nanjing University of Aeronautics and AstronauticsNanjing 210016China Functional Morphology and Biomechanics Institute of ZoologyKiel UniversityKiel 24098Germany

Controlled and switchable adhesion is commonly observed in biological systems.In recent years,many scholars have focused on making switchable bio-inspired adhesives.However,making a bio-inspired adhesive with high adhesion performance and excellent dynamic switching properties is still a challenge.A Shape Memory Polymer Bio-inspired Adhesive(SMPBA)was successfully developed,well realizing high adhesion(about 337 kPa),relatively low preload(about90 kPa),high adhesion-to-preload ratio(about 3.74),high switching ratio(about 6.74),and easy detachment,which are attributed to the controlled modulus and contact area by regulating temperature and the Shape Memory Effect(SME).Furthermore,SMPBA exhibits adhesion strength of80–337 kPa on various surfaces(silicon,iron,and aluminum)with different roughness(Ra=0.021–10.280)because of the conformal contact,reflecting outstanding surface adaptability.The finite element analysis verifies the bending ability under different temperatures,while the adhesion model analyzes the influence of preload on contact area and adhesion.Furthermore,an Unmanned Aerial Vehicle(UAV)landing device with SMPBA was designed and manufactured to achieve UAV landing on and detaching from various surfaces.This study provides a novel switchable bio-inspired adhesive and UAV landing method.

关键词： Bio-inspired adhesive Shape memory polymers Switchable adhesive Unmanned aerial vehicle Landing

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Underlying anti-hypertensive mechanism of the Mizuhopecten yessoensis derived peptide NCW in spontaneously hypertensive rats via widely targeted kidney metabolomics

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Food Science and Human Wellness 2024年第1期13卷 472-481页

作者： Wenjun xue Wenzhu zhao Sijia Wu Zhipeng Yu School of Food Science and Engineering Hainan UniversityHaikou 570228China College of Food Science and Engineering Bohai UniversityJinzhou 121013China Lab of Nutrition and Functional Food Jilin UniversityChangchun 130062China

The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is still not fully clarified.This study established a UPLC-Q-TRAP-MS/MS-based widely targeted kidney metabolomics approach to explore the changes of kidney metabolic profiles and to clarify the antihypertensive mechanism of peptide NCW in spontaneously hypertensive rats(SHRs).Multivariate statistical analysis indicated that the kidney metabolic profiles were clearly separated between the SHR-NCW and SHRUntreated groups.A total of 85 metabolites were differentially regulated,and 16 metabolites were identified as potential kidney biomarkers,e.g.,3-hydroxybutyrate,malonic acid,deoxycytidine,and L-aspartic acid.The peptide NCW might regulate kidney metabolic disorder of SHRs to alleviate hypertension by suppressing inflammation and improving nitric oxide production under the regulation of linoleic acid metabolism,folate related pathways,synthesis and degradation of ketone bodies,pyrimidine metabolism,β-alanine metabolism,and retinal metabolism.

关键词： ACE inhibitory peptide Kidney Mechanism Metabolomics Spontaneously hypertensive rats

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Discovery of GluN2A subtype-selective N-methyl-d-aspartate(NMDA)receptor ligands

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Acta Pharmaceutica Sinica B 2024年第5期14卷 1987-2005页

作者： Liyang Jiang Na Liu Fabao zhao Boshi Huang 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

The N-methyl-d-aspartate(NMDA)receptors,which belong to the ionotropic Glutamate receptors,constitute a family of ligand-gated ion channels.Within the various subtypes of NMDA receptors,the GluN1/2A subtype plays a significant role in central nervous system(CNS)disorders.The present article aims to provide a comprehensive review of ligands targeting GluN2A-containing NMDA receptors,encompassing negative allosteric modulators(NAMs),positive allosteric modulators(PAMs)and competitive antagonists.Moreover,the ligands’structure–activity relationships(SARs)and the binding models of representative ligands are also discussed,providing valuable insights for the clinical rational design of effective drugs targeting CNS diseases.

关键词： NMDA receptors GluN2A subtype Subtype-selective ligands SARs Protein ligand interactions

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