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Yanggan Jiangmei Formula alleviates hepatic inflammation and lipid accumulation in non-alcoholic steatohepatitis by inhibiting the NF-κB/NLRP3 signaling pathway

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Chinese Journal of Natural Medicines 2024年第3期22卷 224-234页

作者： wu yuanyuan ZHOU Jingwen ZUO Xinchen KUANG Yufeng SUN Lixia ZHANG Xiaolong The First Clinical Medical College Nanjing University of Chinese MedicineNanjing 210023China The Affiliated Hospital of Nanjing University of Chinese Medicine Jiangsu Province Hospital of Chinese MedicineNanjing 210029China

The role of NF-κB and the NLRP3 inflammasome in the chronic inflammatory microenvironment of non-alcoholic steatohepatitis(NASH)has been posited as crucial.The Yanggan Jiangmei Formula(YGJMF)has shown promise in ameliorating hepatic steatosis in NASH patients,yet its pharmacological mechanisms remain largely unexplored.This study was conducted to investigate the efficacy of YGJMF in NASH and to elucidate its pharmacological underpinnings.To simulate NASH both in vivo and in vitro,high-fat-diet(HFD)rats and HepG2 cells stimulated with free fatty acids(FFAs)were utilized.The severity of liver injury and lipid deposition was assessed using serum indicators,histopathological staining,micro-magnetic resonance imaging(MRI),and the liver-tomuscle signal intensity ratio(SIRL/M).Furthermore,a combination of enzyme-linked immunosorbent assay(ELISA),immunohistochemistry(IHC),immunofluorescence,real-time quantitative polymerase chain reaction(RT-qPCR),and Western blotting analyses was employed to investigate the NF-κB/NLRP3 signaling pathway and associated cytokine levels.The results from liver pathology,MRI assessments,and biochemical tests in rat models demonstrated YGJMF’s significant effectiveness in reducing liver damage and lipid accumulation.Additionally,YGJMF markedly reduced hepatocyte inflammation by downregulating inflammatory cytokines in both liver tissue and serum.Furthermore,YGJMF was found to disrupt NF-κB activation,consequently inhibiting the assembly of the NLRP3 inflammasome in both the in vitro and in vivo models.The preliminary findings of this study suggest that YGJMF may alleviate hepatic steatosis and inhibit the NF-κB/NLRP3 signaling pathway,thereby exerting anti-inflammatory effects in NASH.

关键词： Non-alcoholic steatohepatitis Nuclear factor kappa B NLRP3 inflammasome Yanggan Jiangmei Formula

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Analysis and Characterization of the GABA Transaminase and Succinate Semialdehyde Dehydrogenase Genes in the Microalga Isochrysis zhanjiangensis in Response to Abiotic Stresses

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Journal of Ocean University of China 2024年第3期23卷 775-785页

作者： TIAN Jiaojiao ZHANG Lin LU Xinyue YE Lingzhi wu yuanyuan CHEN Deshui CAO Jiayi JIANG Jiaxin XU Jilin YAN Xiaojun Key Laboratory of Marine Biotechnology of Zhejiang Province School of Marine SciencesNingbo UniversityNingbo 315211China Key Laboratory of Aquacultural Biotechnology Ministry of Education Ningbo UniversityNingbo 315211China Laizhou Bay Marine Technology Co. Ltd.Yantai 261400China Fujian Dalai Seed Science and Technology Co. Ltd.Ningde 352101China

Gamma-aminobutyric acid(GABA),widely existing in different organisms,is rapidly accumulated in plants in response to environmental stresses.The main biosynthesis and degradation pathways of GABA constitute the GABA shunt,which is tied to the tricarboxylic acid(TCA)cycle.GABA transaminase(GABA-T)and succinate semialdehyde dehydrogenase(SSADH)are two essential enzymes for the GABA degradation pathway.While there are abundant studies on GABA shunt in higher plants at the physiological and genetic levels,research on its role in microalgae remains limited.This study aimed at exploring the function of GABA-T and SSADH genes in Isochrysis zhanjiangensis,an important diet microalga,under different stresses.We cloned two GABA-T genes,IzGABA-T1 and IzGABA-T2,and one SSADH gene IzSSADH from Isochrysis zhanjiangensis and conducted heterologous expression experiments.The results showed that the overexpression of IzGABA-T1 or IzGABA-T2 enhanced the survival rates of yeast transformants under heat or NaCl stress,while the overexpression of IzSSADH improved yeast tolerance to NaCl stress but had no obvious effect on heat stress.Additionally,the results of quantitative real-time polymerase chain reaction(qPCR)showed that IzGABA-T1 transcription increased in the HT(salinity 25,35℃)and LS(salinity 15,25℃)groups.At 24 h,the IzGABA-T2 transcriptions increased in the HT,LS,and HS(salinity 35,25℃)groups,but their transcription levels decreased in all groups at 48 h.IzSSADH transcription increased in the LS group.These results suggest that IzGABA-T1,IzGABA-T2,and IzSSADH are associated with temperature and salinity stresses and possess a certain preference for different stresses.

关键词： abiotic stress GABA heterologous expression Isochrysis zhanjiangensis transcription

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Progress in clinical diagnosis and treatment of colorectal cancer with rare genetic variants

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Cancer Biology & Medicine 2024年第6期21卷 473-483页

作者： Shuyi Chen Jing Gu Kaichun wu Xiaodi Zhao yuanyuan Lu State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases Xijing Hospital of Digestive Diseases Fourth Military Medical University School of Basic Medical Sciences Fourth Military Medical University

Targeted therapy is crucial for advanced colorectal cancer(CRC) positive for genetic drivers. With advances in deep sequencing technology and new targeted drugs, existing standard molecular pathological detection systems and therapeutic strategies can no longer meet the requirements for careful management of patients with advanced CRC. Thus, rare genetic variations require diagnosis and targeted therapy in clinical practice. Rare gene mutations, amplifications, and rearrangements are usually associated with poor prognosis and poor response to conventional therapy. This review summarizes the clinical diagnosis and treatment of rare genetic variations, in genes including erb-b2 receptor tyrosine kinase 2(ERBB2), B-Raf proto-oncogene, serine/threonine kinase(BRAF), ALK receptor tyrosine kinase/ROS proto-oncogene 1, receptor tyrosine kinase(ALK/ROS1), neurotrophic receptor tyrosine kinases(NTRKs), ret proto-oncogene(RET), fibroblast growth factor receptor 2(FGFR2), and epidermal growth factor receptor(EGFR), to enhance understanding and identify more accurate personalized treatments for patients with rare genetic variations.

关键词： Genetic variation gene amplification gene mutation gene rearrangement targeted therapy

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A Nonlinear Grey Bernoulli Model with Conformable Fractional-Order Accumulation and Its Application to the Gross Regional Product in the Cheng-Yu Area

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Journal of Systems Science and Information 2024年第2期12卷 245-273页

作者： Wenqing wu Xin MA Bo ZENG yuanyuan ZHANG School of Science Civil Aviation Flight University of ChinaDeyang 618307China School of Mathematics and Physics Southwest University of Science and TechnologyMianyang 621010China College of Business Planning Chongqing Technology and Business UniversityChongqing 400067China

This study considers a nonlinear grey Bernoulli forecasting model with conformable fractionalorder accumulation,abbreviated as CFNGBM(1,1,λ),to study the gross regional product in the ChengYu area.The new model contains three nonlinear parameters,the power exponentγ,the conformable fractional-orderαand the background valueλ,which increase the adjustability and flexibility of the CFNGBM(1,1,λ)model.Nonlinear parameters are determined by the moth flame optimization algorithm,which minimizes the mean absolute prediction percentage error.The CFNGBM(1,1,λ)model is applied to the gross regional product of 16 cities in the Cheng-Yu area,which are Chongqing,Chengdu,Mianyang,Leshan,Zigong,Deyang,Meishan,Luzhou,Suining,Neijiang,Nanchong,Guang’an,Yibin,Ya’an,Dazhou and Ziyang.With data from 2013 to 2021,several grey models are established and results show that the new model has higher accuracy in most cases.

关键词： nonlinear grey Bernoulli model conformable fractional-order operator moth flame optimization algorithm gross regional product the Cheng-Yu area

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Tumor microenvironment-activatable neuropeptide-drug conjugates enhanced tumor penetration and inhibition via multiple delivery pathways and calcium deposition

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Chinese Chemical Letters 2024年第4期35卷 292-297页

作者： Yi Cao Xiaojiao Ge yuanyuan Wei Lulu He Aiguo wu Juan Li Ningbo Key Laboratory of Biomedical Imaging Probe Materials and Technology Zhejiang International Cooperation Base of Biomedical Materials Technology and ApplicationChinese Academy of Sciences(CAS)Key Laboratory of Magnetic Materials and DevicesNingbo Cixi Institute of Biomedical EngineeringZhejiang Engineering Research Center for Biomedical MaterialsNingbo Institute of Materials Technology and EngineeringChinese Academy of SciencesNingbo 315201China University of Chinese Academy of Sciences Beijing 100049China Advanced Energy Science and Technology Guangdong Laboratory Huizhou 516000China

Peptide-drug conjugates have achieved considerable development and application as a novel strategy for targeted delivery of anticancer drugs. Bioactive peptides induced calcium deposition can irreversibly assist inhibition of tumors. However, active regulation of calcium level through signal transduction of bioactive substances has not been reported yet. In this study, novel neuropeptide-doxorubicin conjugates(NP-DOX) with lysosome-specific acid response were described for neuropeptide Y_1 receptor(Y_1R)-overexpressed triple-negative breast cancer. The delivery mechanism of NP-DOX was clarified that diverse pathways were involved, including intracellular and intercellular transport. Importantly, up-regulation of Y_1 R-mediated intracellular calcium level via second messenger inositol triphosphate was presented in NP-DOX treated MDA-MB-231 cells. In vivo antitumor efficacy demonstrated that NP-DOX showed less organ toxicity and enhanced tumor inhibition benefited from its controlled release and Y_1R-mediated calcium deposition, compared with free DOX. This bioconjugate is a proof-of-concept confirming that neuropeptide-mediated control of signaling responses in neuropeptide-drug conjugates enables great potential for further applications in tumor chemotherapy.

关键词： Neuropeptide-drug conjugate Tumor penetration Calcium deposition Tumor inhibition Triple-negative breast cancer

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Structural Optimization of the Inlet Header of Supercritical Carbon Dioxide Printed Circuit Board Heat Exchanger

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Journal of Thermal Science 2024年第4期33卷 1458-1467页

作者： WANG Yanquan LU Yuanwei WANG yuanyuan HAN Xinlong wu Yuting GAO Qi MOE Key Laboratory of Enhanced Heat Transfer and Energy Conservation Beijing Key Laboratory of Heat Transfer and Energy ConversionBeijing University of Technology

Supercritical carbon dioxide printed circuit board heat exchangers are expected to be applied in third-generation solar thermal power generation.However,the uniformity of supercritical carbon dioxide entering the heat exchanger has a significant impact on the overall performance of the heat exchanger.In order to improve the uniformity of flow distribution in the inlet header,this article studies and optimizes the inlet header of a printed circuit board heat exchanger through numerical simulation.The results indicate that when supercritical carbon dioxide flows through the header cavity,eddy currents will be generated,which will increase the uneven distribution of flow rate,while reducing the generation of eddy currents will improve the uniform distribution of flow rate.When the dimensionless factor of the inlet header is 6,the hyperbolic configuration is the optimal structure.We also reduced the eddy current region by adding transition segments,and the results showed that the structure was the best when the dilation angle was 10°,which reduced the non-uniformity by 21% compared to the hyperbolic configuration,providing guidance for engineering practice.

关键词： third-generation solar thermal power generation inlet header PCHE numerical simulation

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Sub-10-nm-sized Au@AuxIr1-x metal-core/alloy-shell nanoparticles as highly durable catalysts for acidic water splitting

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National Science Review 2024年第4期11卷 130-140页

作者： Huimin Wang Zhe-ning Chen yuanyuan Wang Dongshuang wu Minna Cao Fanfei Sun Rong Cao State Key Laboratory of Structural Chemistry Fujian Institute of Research on the Structure of Matter Chinese Academy of Sciences University of Chinese Academy of Sciences School of Materials Science and Engineering Nanyang Technological University Shanghai Synchrotron Radiation Facility Shanghai Institute of Applied Physics Chinese Academy of Sciences Fujian Science & Technology Innovation Laboratory for Optoelectronic Information of China

The absence of efficient and durable catalysts for oxygen evolution reaction（OER） is the main obstacle to hydrogen production through water splitting in an acidic ele ctrolyte.Here,we report a controllable synthesis method of surface IrOxwith changing Au/Ir compositions by constructing a range of sub-10-nm-sized core-shell nanocatalysts composed of an Au core and AuxIr1-xalloy shell.In particular,Au@Au0.43Ir0.57exhibits 4.5 times higher intrinsic OER activity than that of the commercial Ir/C.Synchrotron X-ray-based spectroscopies,electron microscopy and density functional theory calculations revealed a balanced binding of reaction intermediates with enhanced activity.The water-splitting cell using a load of 0.02 mgIr/cm2of Au@Au0.43Ir0.57as both anode and cathode can reach 10 mA/cm2at 1.52 V and maintain activity for at least194 h,which is better than the cell using the commercial couple Ir/C‖Pt/C（1.63 V,0.2 h）.

关键词： controllable synthesis of surface IrOx oxygen evolution reaction acidic water splitting catalytic stability transition metal catalysts

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Self-sufficient nanoparticles with dual-enzyme activity trigger radical storms and activate cascade-amplified antitumor immunologic responses

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Acta Pharmaceutica Sinica B 2024年第2期14卷 821-835页

作者： Liping Bai Jin Yang Siting Yu Zhongzheng Xiang yuanyuan Zeng Meiling Shen Xiaorong Kou Qinjie wu Changyang Gong Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Radiotherapy(RT) can potentially induce systemic immune responses by initiating immunogenic cell death(ICD) of tumor cells.However,RT-induced antitumor immunologic responses are sporadic and insufficient against cancer metastases.Herein,we construct multifunctional self-sufficient nanoparticles(MARS) with dual-enzyme activity(GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic relapse.In addition to limiting the Warburg effect to actualize starvation therapy,MARS catalyzes glucose to produce hydrogen peroxide(H_(2)O_(2)),which is then used in the Cu^(+)-mediated Fenton-like reaction and RT sensitization.RT and chemodynamic therapy produce reactive oxygen species in the form of radical storms,which have a robust ICD impact on mobilizing the immune system.Thus,when MARS is combined with RT,potent systemic antitumor immunity can be generated by activating antigen-presenting cells,promoting dendritic cells maturation,increasing the infiltration of cytotoxic T lymphocytes,and reprogramming the immuno suppre ssive tumor microenvironment.Furthermore,the synergistic therapy of RT and MARS effectively suppresses local tumor growth,increases mouse longevity,and results in a 90% reduction in lung metastasis and postoperative recurrence.Overall,we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.

关键词： Dual-enzyme activity Radiotherapy Chemodynamic therapy Fenton-likereaction Radical storms Immunogeniccell death Tumormicroenvironment Systemicimmunity

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Numerical Study on Heat Transfer and Frictional Resistance of Two Types of Molten Salts in Straight Channels and Supercritical Carbon Dioxide in Airfoil Channels

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Journal of Thermal Science 2024年第4期33卷 1443-1457页

作者： WANG Yanquan LU Yuanwei GAO Qi LI Feng MA Yancheng WANG yuanyuan wu Yuting MOE Key Laboratory of Enhanced Heat Transfer and Energy Conservation Beijing Key Laboratory of Heat Transfer and Energy ConversionBeijing University of Technology

Molten salt and supercritical carbon dioxide（sCO2） are considered to be one of the most promising combined heat transfer refrigerants for third-generation solar thermal power generation.To evaluate the potential of chloride salts and carbonates in third-generation solar thermal power generation,this paper uses molten salts and sCO2as the working media of printed circuit board heat exchangers（PCHE）,and uses numerical simulation to study the heat transfer and friction of PCHE channels with different molten salts and sCO2,and establishes predictive correlations respectively.A local heat transfer and friction study was conducted on the sCO2side of the airfoil channel,and it was found that the inlet mass flow rate has a significant impact on it,while the inlet temperature has a relatively small impact.A comprehensive comparison was made between the heat transfer and friction of two molten salts,and the comprehensive performance of chloride salts was 70%-80% higher than that of carbonates.The results indicate that the potential of chloride salts in third-generation solar thermal power generation is much greater than that of carbonates.

关键词： third generation solar thermal power generation sCO 2 PCHE molten salt

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2.4 V ultrahigh-voltage aqueous MXene-based asymmetric micro-supercapacitors with high volumetric energy density toward a self-sufficient integrated microsystem

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Fundamental Research 2024年第2期4卷 307-314页

作者： yuanyuan Zhu Shuanghao Zheng Jieqiong Qin Jiaxin Ma Pratteek Das Feng Zhou Zhong-Shuai wu State Key Laboratory of Catalysis Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China University of Chinese Academy of Sciences Shijingshan DistrictBeijing 100049China College of Science Henan Agricultural UniversityZhengzhou 450002China Dalian National Laboratory for Clean Energy Chinese Academy of SciencesDalian 116023China Key Laboratory of Spin Electron and Nanomaterials of Anhui Higher Education Institutes Suzhou UniversitySuzhou 234000China

Two-dimensional MXenes are key high-capacitance electrode materials for micro-supercapacitors(MSCs)catering to integrated microsystems.However,the narrow electrochemical voltage windows of conventional aqueous electrolytes(≤1.23 V)and symmetric MXene MSCs(typically≤0.6 V)substantially limit their output voltage and energy density.Highly concentrated aqueous electrolytes exhibit lower water molecule activity,which inhibits water splitting and consequently widens the operating voltage window.Herein,we report ultrahigh-voltage aqueous planar asymmetric MSCs(AMSCs)based on a highly concentrated LiCl-gel quasi-solid-state electrolyte with MXene(Ti3C2Tx)as the negative electrode and MnO_(2) nanosheets as the positive electrode(MXene//MnO_(2)-AMSCs).The MXene//MnO_(2)-AMSCs exhibit a high voltage of up to 2.4 V,attaining an ultrahigh volumetric energy density of 53 mWh cm−3.Furthermore,the in-plane geometry and the quasi-solid-state electrolyte enabled excellent mechanical flexibility and performance uniformity in the serially/parallel connected packs of our AMSCs.Notably,the MXene//MnO_(2)-AMSC-based integrated microsystem,in conjunction with solar cells and consumer electronics,could efficiently realize simultaneous energy harvesting,storage,and conversion.The findings of this study provide insights for constructing high-voltage aqueous MXene-based AMSCs as safe and self-sufficient micropower sources in smart integrated microsystems.

关键词： Asymmetric micro-supercapacitors MXene MnO_(2) Aqueous electrolyte High voltage Integrated microsystem

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