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Cycloastragenol induces apoptosis and protective autophagy through AMPK/ULK1/mTOR axis in human non-small cell lung cancer cell lines

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Journal of Integrative Medicine 2024年第4期22卷 503-514页

作者： Li-hua zhu yu-pei liang Lian Yang Feng zhu Li-jun Jia He-gen Lia Department of Oncology Longhua Hospital Shanghai University of Traditional Chinese Medicine Cancer Institute of Traditional Chinese Medicine Longhua Hospital Shanghai University of Traditional Chinese Medicine Department of Laboratory Medicine Huadong Hospital Fudan University

Objective:Studies have demonstrated that cycloastragenol induces antitumor effects in prostate, colorectal and gastric cancers; however, its efficacy for inhibiting the proliferation of lung cancer cells is largely unexplored. This study explores the efficacy of cycloastragenol for inhibiting non-small cell lung cancer(NSCLC) and elucidates the underlying molecular mechanisms.Methods:The effects of cycloastragenol on lung cancer cell proliferation were assessed using an adenosine triphosphate monitoring system based on firefly luciferase and clonogenic formation assays.Cycloastragenol-induced apoptosis in lung cancer cells was evaluated using dual staining flow cytometry with an annexin V-fluorescein isothiocyanate/propidium iodide kit. To elucidate the role of cycloastragenol in the induction of apoptosis, apoptosis-related proteins were examined using Western blots.Immunofluorescence and Western blotting were used to determine whether cycloastragenol could induce autophagy in lung cancer cells. Genetic techniques, including small interfering RNA technology,were used to investigate the underlying mechanisms. The effects against lung cancer and biosafety of cycloastragenol were evaluated using a mouse subcutaneous tumor model.Results:Cycloastragenol triggered both autophagy and apoptosis. Specifically, cycloastragenol promoted apoptosis by facilitating the accumulation of phorbol-12-myristate-13-acetate-induced protein 1(NOXA), a critical apoptosis-related protein. Moreover, cycloastragenol induced a protective autophagy response through modulation of the adenosine 5?-monophosphate-activated protein kinase (AMPK)/unc-51-like autophagy-activating kinase (ULK1)/mammalian target of rapamycin (mTOR) pathway.Conclusion:Our study sheds new light on the antitumor efficacy and mechanism of action of cycloastragenol in NSCLC. This insight provides a scientific basis for exploring combination therapies that use cycloastragenol and inhibiting the AMPK/ULK1/mTOR pathway as a promising approach to combating lung cancer.

关键词： Non-small cell lung cancer Cycloastragenol Autophagy Apoptosis

A Plasma Membrane Polarity Sensor Harnessing Conjoined Twisted Intramolecular Charge Transfer Modulation and Charge Number Control Strategy

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CCS Chemistry 2024年第3期6卷 733-748页

作者： yu-Qiang Zhao Le yu Liping zhu Jinsong liang Ying Zhou Jong Seung Kim College of Chemical Science and Technology Yunnan UniversityKunming 650091 Department of Chemistry Korea UniversitySeoul 02841 TheranoChem Incorporation Seoul 02856

Polarity is a critical microenvironmental factor of the plasma membrane,which can offer valuable insights into various biological processes.Herein,we proposed a novel strategy for the construction of fluorescent agents to measure plasma membrane polarity by conjoining twisted intramolecular charge transfer(TICT)modulation and charge number control.It is shown that compounds with a stronger TICT tendency are more sensitive to polarity shifts due to the number of dialkylated amino groups present(from 1 to 3),and the molecules with two or more charged centers remain in the plasma membrane.Therefore,we developed two fluorescent agents with high polarity sensitivity,excellent turn-on ratios,and superior ability,to target the plasma membrane.In the wash-free fluorescence imaging and fluorescence lifetime tests,our designed agent could detect plasma membrane polarity with high precision,allowing effective distinction between cancer cells and normal cells based on their differences in plasma membrane polarity.Moreover,both fluorescence and fluorescence lifetime changes of the plasma membrane in the ferroptosis model established by Sorafenib confirmed an increase in plasma membrane polarity during cell ferroptosis.

关键词： membrane polarity fluorescence agents fluorescence imaging fluorescence lifetime imaging

Soil and microbial C:N:P stoichiometries play vital roles in regulating P transformation in agricultural ecosystems:A review

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Pedosphere 2024年第1期34卷 44-51页

作者： Guanglei CHEN Jiahui yuAN Shenqiang WANG yuting liang Dengjun WANG Yiyong zhu yu WANG State Key Laboratory of Soil and Sustainable Agriculture Changshu National Agro-Ecosystem Observation and Research StationInstitute of Soil ScienceChinese Academy of SciencesNanjing 210008China School of Life Sciences Jiangsu Normal UniversityXuzhou 221000China School of Fisheries Aquacultureand Aquatic SciencesAuburn UniversityAuburn AL 36849USA Jiangsu Collaborative Innovation Center for Solid Organic Waste Resource Utilization College of Resources and Environmental ScienceNanjing Agricultural UniversityNanjing 210095China

Stoichiometry plays a crucial role in biogeochemical cycles and can modulate soil nutrient availability and functions. In agricultural ecosystems,phosphorus(P) fertilizers(organic or chemical) are often applied to achieve high crop yields. However, P is readily fixed by soil particles, leading to low P use efficiency. Therefore, understanding the role of carbon:nitrogen:P stoichiometries of soil and microorganisms in soil P transformation is of great significance for P management in agriculture. This paper provides a comprehensive review of the recent research on stoichiometry effect on soil P transformation in agricultural ecosystems. Soil microorganisms play an important role in the transformation of soil non-labile inorganic P to microbial biomass P by regulating microbial biomass stoichiometry. They also mobilize soil unavailable organic P into available P by changing ecoenzyme stoichiometry. Organic materials, such as manure and straw, play an important role in promoting the transformation of insoluble P into available P as well. Additionally, periphytic biofilms can reduce P loss from rice field ecosystems. Agricultural stoichiometries are different from those of natural ecosystems and thereby should receive more attention due to the influences of anthropogenic factors. Therefore, it is necessary to conduct further stoichiometry research on the soil biochemical mechanisms underlying P transformation in agricultural ecosystems. In conclusion, understanding stoichiometry impact on soil P transformation is crucial for P management in agricultural ecosystems.

关键词： ecoenzyme microbial biomass microbial community microorganism P availability periphytic biofilm soil P transformation

Topological Stability and Entropy for Certain Set-valued Maps

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Acta Mathematica Sinica,English Series 2024年第4期40卷 962-984页

作者： yu ZHANG yu Jun zhu School of Mathematical Sciences Xiamen UniversityXiamen 361005P.R.China

In this paper,the dynamics(including shadowing property,expansiveness,topological stability and entropy)of several types of upper semi-continuous set-valued maps are mainly considered from differentiable dynamical systems points of view.It is shown that(1)if f is a hyperbolic endomorphism then for eachε>0 there exists a C^(1)-neighborhood U of f such that the induced set-valued map F_(f,U)has theε-shadowing property,and moreover,if f is an expanding endomorphism then there exists a C^(1)-neighborhood U of f such that the induced set-valued map F_(f,U)has the Lipschitz shadowing property;(2)when a set-valued map F is generated by finite expanding endomorphisms,it has the shadowing property,and moreover,if the collection of the generators has no coincidence point then F is expansive and hence is topologically stable;(3)if f is an expanding endomorphism then for eachε>0 there exists a C^(1)-neighborhood U of f such that h(F_(f,U,ε))=h(f);(4)when F is generated by finite expanding endomorphisms with no coincidence point,the entropy formula of F is given.Furthermore,the dynamics of the set-valued maps based on discontinuous maps on the interval are also considered.

关键词： Set-valued map orbit space hyperbolic endomorphism perturbation shadowing expansiveness topological stability entropy

Acute suppurative terminal cholangitis:Clinical characteristics of a new subtype of acute cholangitis

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 293-299页

作者： Rong-Tao zhu Ye Li Chi-Xian Zhang Wei-Jie Wang Ruo-Peng liang Jian Li Kai Bai yu-Ling Sun Department of Hepatobiliary and Pancreatic Surgery the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Zhengzhou Key Laboratory of Hepatobiliary and Pancreatic Diseases Zhengzhou 450052China Institute of Hepatobiliary and Pancreatic Diseases Zhengzhou UniversityZhengzhou 450052China Department of Pathology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

Background:Acute suppurative terminal cholangitis(ASTC)is rarer than acute obstructive cholangitis and is not well studied.To explore this subtype of acute cholangitis,we described our clinical experience with ASTC.Methods:We performed a retrospective review of patients with ASTC admitted to our center from September 2014 to August 2020.We analyzed their clinical characteristics,including etiology,clinical manifestations,imaging features,treatment and prognosis.Results:A total of 32 ASTC patients were included in the analysis.The majority of the patients had a history of biliary operations,and clinical manifestations were occult and atypical.The positive rate of bacterial culture was 46.9%.All the patients had typical imaging features on computed tomography and magnetic resonance imaging.Treatment with effective antibiotics was provided as soon as diagnosis was established.After treatment,most patients had a good outcome.Elevated levels of total bilirubin,aspartate aminotransferase,procalcitonin and gamma-glutamyltransferase were the characteristics of critically ill patients and were associated with relatively poor prognosis.Conclusions:Our results demonstrated that ASTC should be recognized as a new subtype of acute cholangitis,and that earlier diagnosis and more personalized treatments are needed.

关键词： Acute suppurative terminal cholangitis Acute cholangitis Gram-negative bacterial infections Diagnosis Treatment

The journey towards physiology and pathology: Tracing the path of neuregulin 4

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Genes & Diseases 2024年第2期11卷 687-700页

作者： Min Chen Jieying zhu Hongyang Luo Wangjing Mu liang Guo School of Exercise and Health and Shanghai Frontiers Science Research Base of Exercise and Metabolic Health Shanghai University of SportShanghai 200438China

Neuregulin 4 (Nrg4),an epidermal growth factor (EGF) family member,can bind to and activate the ErbB4 receptor tyrosine kinase.Nrg4 has five different isoforms by alternative splicing and performs a wide variety of functions.Nrg4 is involved in a spectrum of physiological processes including neurobiogenesis,lipid metabolism,glucose metabolism,thermogenesis,and angiogenesis.In pathological processes,Nrg4 inhibits inflammatory factor levels and suppresses apoptosis in inflammatory diseases.In addition,Nrg4 could ameliorate obesity,insulin resistance,and cardiovascular diseases.Furthermore,Nrg4 improves non-alcoholic fatty liver disease (NAFLD) by promoting autophagy,improving lipid metabolism,and inhibiting cell death of hepatocytes.Besides,Nrg4 is closely related to the development of cancer,hyperthyroidism,and some other diseases.Therefore,elucidation of the functional role and mechanisms of Nrg4 will provide a clearer view of the therapeutic potential and possible risks of Nrg4.

关键词： Angiogenesis Cardiovascular diseases Inflammation Insulin resistance Lipid and glucose metabolism NAFLD Neurobiogenesis Obesity

Cholesterol-induced deformation of the gramicidin A channel inhibiting potassium ion binding and transport

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Chinese Physics B 2024年第5期33卷 696-702页

作者：肖盼曹宇朱瑾梁清 Center for Statistical and Theoretical Condensed Matter Physics & Department of Physics Zhejiang Normal UniversityJinhua 321004China Zhejiang Institute of Photoelectronics & Zhejiang Institute for Advanced Light Source Zhejiang Normal UniversityJinhua 321004China

Gramicidin A(gA)is a kind of antibiotic peptide produced by bacillus brevis and it can dimerize across lipid bilayers to form a monovalent cation channel.In this work,we investigate the impact of cholesterol in the lipid bilayer on the binding of potassium ions with the gA channel and the transport of the ions across the channel.The results indicate that cholesterol can significantly influence the conformational stability of the gA channel and cause the channel deformation which inhibits the potassium ion binding with the channel and transport across the channel.The work provides some molecular insights into understanding of influence of lipids on the activity of gA channel in both model membranes and plasma membranes of intact cells.

关键词： gramicidin A lipid bilayer molecular dynamics interaction

Calcium-chelating peptides from rabbit bone collagen:characterization,identification and mechanism elucidation

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Food Science and Human Wellness 2024年第3期13卷 1485-1493页

作者： Fuhuan yuan yu Fu liang Ma Hankun zhu Yong yu Xin Feng Yi Sun Hongjie Dai Xin Liu Zhengfang Liu yuhao Zhang College of Food Science Southwest UniversityChongqing 400715China Chongqing Key Laboratory of Speciality Food Co-Built by Sichuan and Chongqing Chongqing 400715China Key Laboratory of Luminescence Analysis and Molecular Sensing(Southwest University) Ministry of EducationChongqing 400715China Angel Yeast Co. Ltd.Yichang 443003China

This study aimed to characterize and identify calcium-chelating peptides from rabbit bone collagen and explore the underlying chelating mechanism.Collagen peptides and calcium were extracted from rabbit bone by instant ejection steam explosion(ICSE)combined with enzymatic hydrolysis,followed by chelation reaction to prepare rabbit bone peptide-calcium chelate(RBCP-Ca).The chelating sites were further analyzed by liquid chromatography-tandem mass(LC-MS/MS)spectrometry while the chelating mechanism and binding modes were investigated.The structural characterization revealed that RBCP successfully chelated with calcium ions.Furthermore,LC-MS/MS analysis indicated that the binding sites included both acidic amino acids(Asp and Glu)and basic amino acids(Lys and Arg),Interestingly,three binding modes,namely Inter-Linking,Loop-Linking and Mono-Linking were for the first time found,while Inter-Linking mode accounted for the highest proportion(75.1%),suggesting that chelation of calcium ions frequently occurred between two peptides.Overall,this study provides a theoretical basis for the elucidation of chelation mechanism of calcium-chelating peptides.

关键词： Rabbit bone Collagen peptide Peptide-calcium chelate Chelation mechanism Liquid chromatography-tandem mass(LC-MS/MS)

Plant RNA-binding proteins:Phase separation dynamics and functional mechanisms underlying plant development and stress responses

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Molecular Plant 2024年第4期17卷 531-551页

作者： Sheng Fan yu Zhang Shaobo zhu Lisha Shen Temasek Life Sciences Laboratory 1 Research LinkNational University of Singapore1 Research LinkSingapore 117604Singapore Department of Biological Sciences National University of Singapore14 Science Drive 4Singapore 117543Singapore

RNA-binding proteins(RBPs)accompany RNA from synthesis to decay,mediating every aspect of RNA metabolism and impacting diverse cellular and developmental processes in eukaryotes.Many RBPs undergo phase separation along with their bound RNA to form and function in dynamic membraneless biomolecular condensates for spatiotemporal coordination or regulation of RNA metabolism.Increasing evidence suggests that phase-separating RBPs with RNA-binding domains and intrinsically disordered regions play important roles in plant development and stress adaptation.Here,we summarize the current knowledge about how dynamic partitioning of RBPs into condensates controls plant development and enables sensing of experimental changes to confer growth plasticity under stress conditions,with a focus on the dynamics and functional mechanisms of RBP-rich nuclear condensates and cytoplasmic granules in mediating RNA metabolism.We also discuss roles of multiple factors,such as environmental signals,protein modifications,and N6-methyladenosine RNA methylation,in modulating the phase separation behaviors of RBPs,and highlight the prospects and challenges for future research on phase-separating RBPs in crops.

关键词： RNA-binding proteins phase separation biomolecular condensates RNA metabolism development stress resilience