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Amphipathicity mediated endocytosis of mesoporous silica nanoparticles with tunable frameworks

Nano Research 2024年第9期17卷 8350-8359页

作者： Runfeng Lin Tiancong Zhao Liang Chen Minchao Liu Hongyue Yu Ruicong Wang Minjia Yuan Xiaomin Li Dongyuan Zhao department of Chemistry State Key Laboratory of Molecular Engineering of PolymersiChemShanghai Key Laboratory of Molecular Catalysis and Innovative MaterialsFudan UniversityShanghai 200433China Shanghai Qiran Biotechnology Co. Ltd.Shanghai 201702China

Due to the amphiphilic nature of phospholipids in the cell membrane,the amphipathicity of the nanomedicine plays a crucial role in the ***,limited biological characterization methods restrict the study of the state of nanoparticles with different amphiphilicities on cell *** understanding of interaction of amphiphilic particle with cell membrane is still ***,by combining the dissipative particle dynamics(DPD)with the framework construction of mesoporous silica nanoparticles(MSNs),we demonstrate the enhanced endocytosis induced by the *** results confirm that the presence of hydrophobic groups on the surface of nanoparticles can disturb the integrity of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine(POPC)membrane and induce activation of phospholipids to a higher energy level,thereby facilitating the wrapping of *** validate the simulation findings,uniform MSNs with hydrophilic pure silica framework and two types of amphiphilic MSNs with varying hydrophilic organic groups in the framework are rationally synthesized by using different silane *** obtained three kinds of MSNs show similar diameter(~100 nm)and mesopores(~2 nm),but distinct hydrophobicity/hydrophilicity *** phenyl-bridged MSN with a carbon content of 27.1%exhibits enhanced cellular uptake,consistent with the theoretical simulation *** work sheds light on how the surface amphipathicity influences endocytosis through the interaction with cell membrane.

关键词： mesoporous silica nanoparticles mesoporous organosilica endocytosis cell membrane amphipathicity

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Genomic Mosaicism of the Brain:Origin,Impact,and Utility

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Neuroscience Bulletin 2024年第6期40卷 759-776页

作者： Jared H.Graham Johannes C.M.Schlachetzki Xiaoxu Yang Martin W.Breuss department of Pediatrics Section of Clinical Genetics and MetabolismUniversity of Colorado School of MedicineAurora80045-2581COUSA department of cellular and molecular Medicine University of California San DiegoLa Jolla92093-0021San DiegoCAUSA department of Neurosciences University of California San DiegoLa Jolla92093-0021San DiegoCAUSA Rady Children’s Institute for Genomic Medicine San Diego92123CAUSA

Genomic mosaicism describes the phenomenon where some but not all cells within a tissue harbor unique genetic ***,research focused on the impact of genomic mosaicism on clinical phenotype—motivated by its involvement in cancers and overgrowth *** recently,we increasingly shifted towards the plethora of neutral mosaic variants that can act as recorders of cellular lineage and environmental ***,we summarize the current state of the field of genomic mosaicism research with a special emphasis on our current understanding of this phenomenon in brain development and *** the field of genomic mosaicism has a rich history,technological advances in the last decade have changed our approaches and greatly improved our *** will provide current definitions and an overview of contemporary detection approaches for genomic ***,we will discuss the impact and utility of genomic mosaicism.

关键词： Genomics Brain development Brain homeostasis Genomic mosaicism

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Acoustical properties of a 3D printed honeycomb structure filled with nanofillers:Experimental analysis and optimization for emerging applications

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Defence Technology（防务技术） 2024年第5期35卷 248-258页

作者： Jeyanthi Subramanian Vinoth kumar Selvaraj Rohan Singh Ilangovan S Naresh Kakur Ruban Whenish School of Mechanical Engineering Vellore Institute of TechnologyChennai600127Tamil NaduIndia department of Mechanical Engineering SRM Institute of Science and TechnologyRamapuramChennai600089India department of Chemical Engineering and Materials Science University of Southern CaliforniaLos Angeles90089USA Advanced Materials Research Centre Technology Innovation InstituteAbu Dhabi9639UAE Center for Biomaterials Cellular and Molecular TheranosticsVellore Institute of TechnologyVellore632014Tamil NaduIndia

The novelty of this research lies in the successful fabrication of a 3D-printed honeycomb structure filled with nanofillers for acoustic properties,utilizing an impedance tube setup in accordance with ASTM standard E *** Creality Ender-3,a 3D printer,was used for printing the honeycomb structures,and polylactic acid(PLA)material was employed for their *** organic,inorganic,and polymeric compounds within the composites were identified using fourier transformation infrared(FTIR)*** structure and homogeneity of the samples were examined using a field emission scanning electron microscope(FESEM).To determine the sound absorption coefficient of the 3D printed honeycomb structure,numerous samples were systematically developed using central composite design(CCD)and analysed using response surface methodology(RSM).The RSM mathematical model was established to predict the optimum values of each factor and noise reduction coefficient(NRC).The optimum values for an NRC of 0.377 were found to be 1.116 wt% carbon black,1.025 wt% aluminium powder,and 3.151 mm distance between parallel ***,the results demonstrate that a 3Dprinted honeycomb structure filled with nanofillers is an excellent material that can be utilized in various fields,including defence and aviation,where lightweight and acoustic properties are of great importance.

关键词： 3D printing Honeycomb structure Acoustics Field emission scanning electron microscope Response surface methodology

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Targeting TLR4 and regulating the Keap1/Nrf2 pathway with andrographolide to suppress inflammation and ferroptosis in LPS-induced acute lung injury

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Chinese Journal of Natural Medicines 2024年第10期22卷 914-928页

作者： LI Yichen HUANG Liting LI Jilang LI Siyuan LV Jianzhen ZHONG Guoyue GAO Ming YANG Shilin HAN Shan HAO Wenhui Life Sciences Institute Guangxi Medical University College of Pharmacy Guangxi University of Chinese Medicine National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal.Medicine Jiangxi University of Traditional Chinese Medicine Xinjiang Key Laboratory of molecular biology for Endemic Diseases Department of Biochemistry and Molecular BiologySchool of Basic Medical Sciences Xinjiang Medical University

Acute lung injury（ALI） is a severe inflammatory condition with a high mortality rate, often precipitated by sepsis. The pathophysiology of ALI involves complex mechanisms, including inflammation, oxidative stress, and ferroptosis, a novel form of regulated cell death. This study explores the therapeutic potential of andrographolide（AG）, a bioactive compound derived from Andrographis, in mitigating Lipopolysaccharide（LPS）-induced inflammation and ferroptosis. Our research employed in vitro experiments with RAW264.7 macrophage cells and in vivo studies using a murine model of LPS-induced ALI. The results indicate that AG significantly suppresses the production of pro-inflammatory cytokines and inhibits ferroptosis in LPS-stimulated RAW264.7 cells. In vivo, AG treatment markedly reduces lung edema, decreases inflammatory cell infiltration, and mitigates ferroptosis in lung tissues of LPS-induced ALI mice. These protective effects are mediated via the modulation of the Toll-like receptor 4（TLR4）/Kelch-like ECH-associated protein 1（Keap1）/Nuclear factor erythroid 2-related factor 2（Nrf2） signaling pathway. molecular docking simulations identified the binding sites of AG on the TLR4 protein(Kd value:-33.5 kcal·mol-1), and these interactions were further corroborated by cellular Thermal Shift Assay（CETSA） and SPR assays. Collectively, our findings demonstrate that AG exerts potent anti-inflammatory and anti-ferroptosis effects in LPS-induced ALI by targeting TLR4 and modulating the Keap1/Nrf2 pathway. This study underscores AG's potential as a therapeutic agent for ALI and provides new insights into its underlying mechanisms of action.

关键词： Acute lung injury Andrographolide Ferroptosis Kelch-like ECH-associated protein 1/Nuclear factor erythroid 2-related factor 2 Toll-like receptor 4

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Research advances in smart responsive-hydrogel dressings with potential clinical diabetic wound healing properties

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Military Medical Research 2024年第4期11卷 543-566页

作者： Ying Chen Xing Wang Sheng Tao Qi Wang Pan-Qin Ma Zi-Biao Li Yun-Long Wu Da-Wei Li Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of cellular Stress biology School of Pharmaceutical SciencesXiamen UniversityXiamen 361102FujianChina Beijing National Laboratory for molecular Sciences Institute of ChemistryChinese Academy of SciencesBeijing 100090China University of Chinese Academy of Sciences Beijing 100049China Senior department of Orthopedics the Fourth Medical Center of Chinese PLA General HospitalBeijing 100091China Institute of Materials Research and Engineering A*STAR(Agency for ScienceTechnology and Research)Singapore 138634Singapore

The treatment of chronic and non-healing wounds in diabetic patients remains a major medical *** reports have shown that hydrogel wound dressings might be an effective strategy for treating diabetic wounds due to their excellent hydrophilicity,good drug-loading ability and sustained drug release *** a typical example,hyaluronic acid dressing(Healoderm)has been demonstrated in clinical trials to improve wound-healing efficiency and healing rates for diabetic foot ***,the drug release and degradation behavior of clinically-used hydrogel wound dressings cannot be adjusted according to the wound *** to the intricacy of diabetic wounds,antibiotics and other medications are frequently combined with hydrogel dressings in clinical practice,although these medications are easily hindered by the hostile *** this case,scientists have created responsive-hydrogel dressings based on the microenvironment features of diabetic wounds(such as high glucose and low pH)or combined with external stimuli(such as light or magnetic field)to achieve controllable drug release,gel degradation,and microenvironment improvements in order to overcome these clinical *** responsive-hydrogel dressings are anticipated to play a significant role in diabetic therapeutic wound ***,we review recent advances on responsive-hydrogel dressings towards diabetic wound healing,with focus on hydrogel structure design,the principle of responsiveness,and the behavior of *** but not least,the advantages and limitations of these responsive-hydrogels in clinical applications will also be *** hope that this review will contribute to furthering progress on hydrogels as an improved dressing for diabetic wound healing and practical clinical application.

关键词： Responsive-hydrogel Diabetic wound Anti-inflammation Tissue remodeling

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The biosynthetic pathway of the hallucinogen mescaline and its heterologous reconstruction

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molecular Plant 2024年第7期17卷 1129-1150页

作者： Paula Berman Luis Alejandro de Haro Ana-Rita Cavaco Sayantan Panda Younghui Dong Nikolay Kuzmich Gabriel Lichtenstein Yoav Peleg Hila Harat Adam Jozwiaki Jianghua Cai Uwe Heinig Sagit Meir Ilana Rogachev Asaph Aharoni department of Plant and Environmental Sciences Weizmann Institute of ScienceRehovot 7610001Israel Life Sciences Core Facilities Weizmann Institute of ScienceRehovot 7610001Israel The Maurice and Vivienne Wohl Institute for Drug Discovery Weizmann Institute of ScienceRehovot 7610001Israel Present address:department of Cell and Metabolic biology Leibniz Institute of Plant BiochemistryWeinberg 306120 Halle(Saale)Germany department of molecular&cellular Pharmacology University of Miami Miler School of MedicineMiamiFL 33136USA department of Botany and Plant Sciences University of California RiversideRiversideCA 92521USA Laboratory of Plant Hormones and Development Regulation of Chongqing School of Life SciencesChongqing UniversityChongqing 401331China

Mescaline,among the earliest identified natural hallucinogens,holds great potential in psychotherapy ***,despite the existence of a postulated biosynthetic pathway for more than half a century,the specific enzymes involved in this process are yet to be *** this study,we investigated the cactus Lophophora williamsii(Peyote),the largest known natural producer of the phenethylamine *** employed a multi-faceted approach,combining de novo whole-genome and transcriptome sequencing with comprehensive chemical profiling,enzymatic assays,molecular modeling,and pathway engineering for pathway *** identified four groups of enzymes responsible for the six catalytic steps in the mescaline biosynthetic pathway,and an N-methyltransferase enzyme that N-methylates all phenethylamine intermediates,likely modulating mescaline levels in ***,we reconstructed the mescaline biosynthetic pathway in both Nicotiana benthamiana plants and yeast cells,providing novel insights into several challenges hindering complete heterologous mescaline *** together,our study opens up avenues for exploration of sustainable production approaches and responsible utilization of mescaline,safeguarding this valuable natural resource for future generations.

关键词： mescaline Lophophora williamsi Peyote biosynthetic pathway de novo genome sequencing mo-lecular modeling

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Automated screening of primary cell-based aptamers for targeting and therapy of pancreatic cancer

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Chinese Chemical Letters 2024年第2期35卷 300-304页

作者： Zhukang Guo Baijiang Jin Yile Fang Lian Jin Song Li Yan Deng Zhu Chen Hui Chen Yuanying Zhang Rabia Usman Nongyue He State Key Laboratory of Digital Medical Engineering School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Hunan Key Laboratory of Biomedical Nanomaterials and Devices Hunan University of TechnologyZhuzhou 412007China department of molecular biology Jiangsu Cancer HospitalNanjing 210009China

Although it has been developed for many years, nucleic acid aptamer screening technology still fails to be widely used, a considerable part of it is due to the variability of tumor cell morphology, which leads to the use of immortalized cell lines in the laboratory to screen nucleic acid aptamers for recognition ability of tumor cells in the diseased *** address this, primary cells that can be stably passaged were isolated and extracted from spontaneous tumors of genetically engineered pancreatic ductal adenocarcinoma model mice in this ***, an automated screening instrument for nucleic acid aptamers developed autonomously by our group was used to perform efficient aptamer screening using a limited number of cells, and the obtained nucleic acid aptamers were affinity verified at the cellular ***, to answer the question of the cell growth environment difference on the recognition ability of nucleic acid aptamers, we verified its targeting ability to tumors in vivo on a nude mice xenograft tumor model, and further used a common antitumor drug doxorubicin combined with nucleic acid aptamers to verify the drug loading ability of this aptamer combined with the targeting therapeutic ability.

关键词： Aptamer Cell-SELEX Automatic instrument Combination therapy Pancreatic cancer

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Id2 epigenetically controls CD8^(+)T-cell exhaustion by disrupting the assembly of the Tcf3-LSD1 complex

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cellular & molecular Immunology 2024年第3期21卷 292-308页

作者： Yiming Li Mingwei Han Haolin Wei Wan Huang Zhinan Chen Tianjiao Zhang Meirui Qian Lin Jing Gang Nan Xiuxuan Sun Shuhui Dai Kun Wang Jianli Jiang Ping Zhu Liang Chen department of Cell biology of National Translational Science Center for molecular Medicine and department of Clinical Immunology of Xijing Hospital Fourth Military Medical UniversityXi’anShaanxi 710032China State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases GanzhouJiangxi341000Xi’anShaanxi 710032China School of Medicine Shanghai UniversityShanghai 200444China

CD8^(+)T-cell exhaustion is a state of dysfunction that promotes tumor progression and is marked by the generation of Slamf6^(+)progenitor exhausted(Tex^(prog))and Tim-^(3+)terminally exhausted(Tex^(term))*** of DNA binding protein 2(Id2)has been shown to play important roles in T-cell development and CD8^(+)T-cell ***,the role of Id2 in CD8^(+)T-cell exhaustion is ***,we found that Id2 transcriptionally and epigenetically regulates the generation of Texprog cells and their conversion to Texterm *** deletion of Id2 dampens CD8^(+)T-cell-mediated immune responses and the maintenance of stem-like CD8^(+)T-cell subpopulations,suppresses PD-1 blockade and increases tumor ***,through its HLH domain,Id2 binds and disrupts the assembly of the Tcf3-Tal1 transcriptional regulatory complex,and thus modulates chromatin accessibility at the Slamf6 promoter by preventing the interaction of Tcf3 with the histone lysine demethylase ***,Id2 increases the abundance of the permissive H3K4me2 mark on the Tcf3-occupied E-boxes in the Slamf6 promoter,modulates chromatin accessibility at the Slamf6 promoter and epigenetically regulates the generation of Slamf6+Texprog *** LSD1 inhibitor GSK2879552 can rescue the Id2 knockout phenotype in tumor-bearing *** of LSD1 increases the abundance of Slamf6^(+)Tim-3^(−)Tex^(prog) cells in tumors and the expression level of Tcf1 in Id2-deleted CD8+T *** study demonstrates that Id2-mediated transcriptional and epigenetic modification drives hierarchical CD8^(+)T-cell exhaustion,and the mechanistic insights gained may have implications for therapeutic intervention with tumor immune evasion.

关键词： Id2 T-cell exhaustion Epigenetic modification Immune evasion

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Flavonoid Myricetin as Potent Anticancer Agent: A Possibility towards Development of Potential Anticancer Nutraceuticals

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Chinese Journal of Integrative Medicine 2024年第1期30卷 75-84页

作者： Anchal Trivedi Adria Hasan Rumana Ahmad Sahabjada Siddiqui Aditi Srivastava Aparna Misra Snober S.Mir department of Biochemistry Era's Lucknow Medical College&HospitalEra UniversityLucknow(226003)India molecular Cell biology Laboratory Integral Information and Research Centre-4(IIRC-4)Department of BioengineeringFaculty of EngineeringIntegral UniversityLucknow(226026)India department of Biotechnology Era's Lucknow Medical College&HospitalEra UniversityLucknow(226003)India department of Biosciences Faculty of ScienceIntegral UniversityLucknow(226026)India

Good nutrition plays a crucial role in maintaining a balanced lifestyle. The beneficial effects of nutrition have been found to counteract nutritional disturbances with the expanded use of nutraceuticals to treat and manage cardiovascular diseases, cancer, and other developmental defects over the last decade. Flavonoids are found abundantly in plant-derived foods such as fruits, vegetables, tea, cocoa, and wine. Fruits and vegetables contain phytochemicals like flavonoids, phenolics, alkaloids, saponins, and terpenoids. Flavonoids can act as anti-inflammatory, anti-allergic, anti-microbial(antibacterial, antifungal, and antiviral) antioxidant, anti-cancer, and anti-diarrheal agents. Flavonoids are also reported to upregulate apoptotic activity in several cancers such as hepatic, pancreatic, breast, esophageal, and colon. Myricetin is a flavonol which is naturally present in fruits and vegetables and has shown possible nutraceutical value. Myricetin has been portrayed as a potent nutraceutical that may protect against cancer. The focus of the present review is to present an updated account of studies demonstrating the anticancer potential of myricetin and the molecular mechanisms involved therein. A better understanding of the molecular mechanism(s) underlying its anticancer activity would eventually help in its development as a novel anticancer nutraceutical having minimal side effects.

关键词： myricetin flavonoids anticancer nutraceuticals Chinese medicine Ayurveda complementary and alternative medicine

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Correlative factors of poor prognosis and abnormal cellular immune function in patients with Alzheimer’s disease

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World Journal of Clinical Cases 2024年第6期12卷 1063-1075页

作者： Hua Bai Hong-Mei Zeng Qi-Fang Zhang Yue-Zhi Hu Fei-Fei Deng department of Neurology The Third Affiliated Hospital of Guizhou Medical University in ChinaDuyun 558099Guizhou ProvinceChina department of Neurology Guizhou Medical UniversityDuyun 558099Guizhou ProvinceChina Key Laboratory of Medical molecular biology Guizhou Medical UniversityGuiyang 550004Guizhou ProvinceChina

BACKGROUND Alzheimer’s disease(AD)is a serious disease causing human dementia and social *** quality of life and prognosis of AD patients have attracted much *** role of chronic immune inflammation in the pathogenesis of AD is becoming more and more *** To study the relationship among cognitive dysfunction,abnormal cellular immune function,neuroimaging results and poor prognostic factors in *** A retrospective analysis of 62 hospitalized patients clinical diagnosed with AD who were admitted to our hospital from November 2015 to November *** cognitive dysfunction performance characteristics,laboratory test data and neuroimaging data from medical records within 24 h of admission,including Mini Mental State Examination Scale score,drawing clock test,blood T lymphocyte subsets,and neutrophils and lymphocyte ratio(NLR),disturbance of consciousness,extrapyramidal symptoms,electroencephalogram(EEG)and head nucleus magnetic spectroscopy(MRS)and other *** logistic regression analysis was used to determine independent prog-nostic *** modified Rankin scale(mRS)was used to determine whether the prognosis was *** correlation between drug treatment and prognostic mRS score was tested by the rank sum *** Univariate analysis showed that abnormal cellular immune function,extrapyramidal symptoms,obvious disturbance of consciousness,abnormal EEG,increased NLR,abnormal MRS,and complicated pneumonia were related to the poor prognosis of AD *** logistic regression analysis showed that the decrease in the proportion of T lym-phocytes in the blood after abnormal cellular immune function(odd ratio:2.078,95%confidence interval:1.156-3.986,P<0.05)was an independent risk factor for predicting the poor prognosis of *** number of days of donepezil treatment to improve cognitive function was negatively correlated with mRS score(r=0.578,P<0.05).CONCLUSION The decrease in the proportion of T

关键词： Alzheimer’s disease cellular immunity Prognosis T lymphocytes Magnetic resonance spectroscopy

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