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Multiplexed fluorescence and scatter detection with single cell resolution using on-chip fiber optics for droplet microfluidic applications

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Microsystems & Nanoengineering 2024年第2期10卷 207-218页

作者： Preksha Gupta Ambili Mohan Apurv Mishra Atindra Nair Neeladri Chowdhury Dhanush Balekai Kavyashree Rai Anil Prabhakar Taslimarif Saiyed Discovery Innovation Accelerator Centre for Cellular and Molecular PlatformsBellary RoadBengaluru560065KarnatakaIndia Department of Electrical Engineering Indian Institute of Technology MadrasChennai600036Tamil NaduIndia

Droplet microfluidics has emerged as a critical component of several high-throughput single-cell analysis techniques in biomedical research and *** significant progress in the development of individual assays,multiparametric optical sensing of droplets and their encapsulated contents has been *** current approaches,most commonly involving microscopy-based high-speed imaging of droplets,are technically complex and require expensive instrumentation,limiting their widespread *** address these limitations,we developed the OptiDrop platform;this platform is a novel optofluidic setup that leverages the principles of flow *** platform enables on-chip detection of the scatter and multiple fluorescence signals from the microfluidic droplets and their contents using optical *** highly customizable on-chip optical fiber-based signal detection system enables simplified,miniaturized,low-cost,multiparametric sensing of optical signals with high sensitivity and single-cell resolution within each *** demonstrate the ability of the OptiDrop platform,we conducted a differential expression analysis of the major histocompatibility complex(MHC)protein in response to IFNγ*** results showed the platform’s ability to sensitively detect cell surface biomarkers using fluorescently labeled ***,the OptiDrop platform combines the versatility of flow cytometry with the power of droplet microfluidics to provide wide-ranging,scalable optical sensing solutions for research and diagnostics.

关键词： scatter enable resolution

Tailoring Classical Conditioning Behavior in TiO_(2) Nanowires:ZnO QDs-Based Optoelectronic Memristors for Neuromorphic Hardware

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Nano-Micro Letters 2024年第7期16卷 265-280页

作者： Wenxiao Wang Yaqi Wang Feifei Yin Hongsen Niu Young-Kee Shin Yang Li Eun-Seong Kim Nam-Young Kim School of Information Science and Engineering University of JinanJinan 250022People’s Republic of China RFIC centre NDAC CentreKwangwoon UniversityNowon-guSeoul 139-701South Korea Department of Electronics Engineering Kwangwoon UniversityNowon-GuSeoul 139-701South Korea School of Microelectronics Shandong UniversityJinan 250101People’s Republic of China Department of molecular medicine and Biopharmaceutical Sciences Seoul National UniversitySeoul 08826South Korea

Neuromorphic hardware equipped with associative learn-ing capabilities presents fascinating applications in the next generation of artificial ***,research into synaptic devices exhibiting complex associative learning behaviors is still ***,an optoelec-tronic memristor based on Ag/TiO_(2) Nanowires:ZnO Quantum dots/FTO was proposed and constructed to emulate the biological associative learning *** implementation of synaptic behaviors,including long and short-term plasticity,and learning-forgetting-relearning behaviors,were achieved in the device through the application of light and electrical *** the optoelectronic co-modulated characteristics,a simulation of neuromorphic computing was conducted,resulting in a handwriting digit recognition accuracy of 88.9%.Furthermore,a 3×7 memristor array was constructed,confirming its application in artificial visual *** importantly,complex biological associative learning behaviors were emulated by mapping the light and electrical stimuli into conditioned and unconditioned stimuli,*** training through associative pairs,reflexes could be triggered solely using light ***-sively,under specific optoelectronic signal applications,the four features of classical conditioning,namely acquisition,extinction,recovery,and generalization,were elegantly *** work provides an optoelectronic memristor with associative behavior capabilities,offering a pathway for advancing brain-machine interfaces,autonomous robots,and machine self-learning in the future.

关键词： Artificial intelligence Classical conditioning Neuromorphic computing Artificial visual memory Optoelectronic memristors ZnO Quantum dots

Elucidating the anti-obesity phytochemicals in Chenpi and their molecular mechanisms

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Food Science and Human Wellness 2024年

作者： Jinhai Luo Weiqi Yan Zhi Chen Baojun Xu Guangdong Provincial Key Laboratory IRADS and Department of Life Sciences， BNU-HKBU United International College centre for Cancer and Inflammation Research， School of Chinese medicine， Hong Kong Baptist University Faculty of Biochemistry and molecular medicine， University of Oulu

Obesity has become a significant global public health issue. Previous studies have found that the Chenpi has the anti-obesity activity. However， the anti-obesity phytochemicals and their mechanisms are still unclear. This study investigated the anti-obesity phytochemicals and molecular mechanisms involved in treating obesity by Chenpi through network pharmacology and molecular docking. Seventeen bioactive phytochemicals from Chenpi and its 475 related anti-obesity targets have been identified. The KEGG pathway analysis showed that the PI3K/Akt signaling pathway， MAPK signaling pathway， AMPK signaling pathway， and NF-kappa B signaling pathway are the main signaling pathways involved in the anti-obesity effect of Chenpi. According to molecular docking analysis， the phytochemicals of Chenpi can bind to central anti-obesity targets. Based on the ADMET analysis and network pharmacology results， tangeretin exhibited the lowest predicted toxicity and the highest potential for anti-obesity effects. In the in vitro lipid accumulation model， tangeretin effectively suppressed the FFA-induced lipid in HepG2 cells by upregulating the PI3K/Akt/GSK3β signaling pathway based on the result of q-PCR and Western Blotting. The outcomes of this research give insights for future research on the anti-obesity phytochemicals and molecular mechanisms derived from Chenpi， also providing the theoretical basis for developing anti-obesity functional foods based on Chenpi.

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Immune checkpoint inhibition mediated with liposomal nanomedicine for cancer therapy

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Military Medical Research 2024年第1期11卷 98-114页

作者： Guang-Long Ma Wei-Feng Lin Faculty of medicine Centre for Cancer ImmunologyUniversity of SouthamptonSouthampton SO166YDUK Department of molecular Chemistry and Materials Science Weizmann Institute of Science76100 RehovotIsrael Key Laboratory of Bio-Inspired Smart Interfacial Science and Technology of Ministry of Education School of ChemistryBeihang UniversityBeijing 100191China

Immune checkpoint blockade(ICB)therapy for cancer has achieved great success both in clinical results and on the *** the same time,success drives more attention from scientists to improve ***,only a small portion of patients are responsive to this therapy,and it comes with a unique spectrum of side effects termed immunerelated adverse events(irAEs).The use of nanotechnology could improve ICBs’delivery to the tumor,assist them in penetrating deeper into tumor tissues and alleviate their *** nanomedicine has been investigated and used for decades,and is well-recognized as the most successful nano-drug delivery *** successful combination of ICB with liposomal nanomedicine could help improve the efficacy of ICB *** this review,we highlighted recent studies using liposomal nanomedicine(including new emerging exosomes and their inspired nanovesicles)in associating ICB therapy.

关键词： Liposome Exosome Immune checkpoint blockade(ICB)

A 3D In-vitro model of the human dentine interface shows long-range osteoinduction from the dentine surface

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International Journal of Oral Science 2024年第2期16卷 225-237页

作者： William Macalester Asme Boussahel Rafael O.Moreno-Tortolero Mark R.Shannon Nicola West Darryl Hill Adam Perriman School of Cellular and molecular medicine Biomedical Sciences BuildingUniversity of BristolUniversity WalkBristolUnited Kingdom Bristol centre for Functional Nanomaterials HH Wills Physics LaboratoryUniversity of BristolTyndall AvenueBristolUnited Kingdom centre for Protolife Research School of ChemistryUniversity of BristolCantocks CloseBristolUnited Kingdom Max Planck-Bristol centre for Minimal Biology School of ChemistryUniversity of BristolBristolUnited Kingdom Periodontology Bristol Dental SchoolUniversity of BristolLower Maudlin StreetBristolUnited Kingdom

Emerging regenerative cell therapies for alveolar bone loss have begun to explore the use of cell laden hydrogels for minimally invasive surgery to treat small and spatially complex maxilla-oral ***,the oral cavity presents a unique and challenging environment for in vivo bone tissue engineering,exhibiting both hard and soft periodontal tissue as well as acting as key biocenosis for many distinct microbial communities that interact with both the external environment and internal body systems,which will impact on cell fate and subsequent treatment ***,we design and bioprint a facile 3D in vitro model of a human dentine interface to probe the effect of the dentine surface on human mesenchymal stem cells(hMSCs)encapsulated in a microporous hydrogel *** demonstrate that the dentine substrate induces osteogenic differentiation of encapsulated hMSCs,and that both dentine andβ-tricalcium phosphate substrates stimulate extracellular matrix production and maturation at the gel-media interface,which is distal to the gel-substrate *** findings demonstrate the potential for long-range effects on stem cells by mineralized surfaces during bone tissue engineering and provide a framework for the rapid development of 3D dentine-bone interface models.

关键词： interface den surface

Exercised blood plasma promotes hippocampal neurogenesis in the Alzheimer's disease rat brain

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Journal of Sport and Health Science 2024年第2期13卷 245-255页

作者： Cecilie Skarstad Norevik Aleksi M.Huuha Ragnhild N.RФsbjФrgen Linda Hildegard Bergersen Kamilla Jacobsen Rodrigo Miguel-dos-Santos Liv Ryan Belma Skender Jose Bianco N.Moreira Asgeir Kobro-Flatmoen Menno P.Witter Nathan Scrimgeour Atefe R.Tari Cardiac Exercise Research Group(CERG) Department of Circulation and Medical ImagingNorwegian University of Science and Technology7491TrondheimNorway Department of Neurology and Clinical Neurophysiology St.Olavs University Hospital7030TrondheimNorway Institute of Oral Biology University of Oslo0372OsloNorway Department of Physiology Federal University of SergipeS~ao Cristov~ao49100-000SergipeBrazil centre of molecular Inflammation Research Department of Clinical and Molecular MedicineNorwegian University of Science and Technology7491TrondheimNorway Kavli Institute for Systems Neuroscience Centre for Neural Computationand Egil and Pauline Braathen and Fred Kavli Centre for Cortical MicrocircuitsNorwegian University of Science and Technology7030TrondheimNorway K.G.Jebsen centre for Alzheimer’s Disease Norwegian University of Science and Technology7030TrondheimNorway

Background:Exercise training promotes brain plasticity and is associated with protection against cognitive impairment and Alzheimer’s disease(AD).These beneficial effects may be partly mediated by blood-borne *** we used an in vitro model of AD to investigate effects of blood plasma from exercise-trained donors on neuronal viability,and an in vivo rat model of AD to test whether such plasma impacts cognitive function,amyloid pathology,and ***:Mouse hippocampal neuronal cells were exposed to AD-like stress using amyloid-βand treated with plasma collected from human male donors 3 h after a single bout of high-intensity *** in vivo studies,blood was collected from exercise-trained young male Wistar rats(high-intensity intervals 5 days/week for 6 weeks).Transgenic AD rats(McGill-R-Thyl-APP)were inj ected 5 times/fortnight for 6 weeks at2 months or 5 months of age with either(a)plasma from the exercise-trained rats,(b)plasma from sedentary rats,or(c)*** function,amyloid plaque pathology,and neurogenesis were *** plasma used for the treatment was analyzed for 23 ***:Plasma from exercised donors enhanced cell viability by 44.1%(p=0.032)and reduced atrophy by 50.0%(p<0.001)in amyloid-β-treated *** vivo exercised plasma treatment did not alter cognitive function or amyloid plaque pathology but did increase hippocampal neurogenesis by~3 fold,regardless of pathological stage,when compared to saline-treated *** of 7 cytokines were significantly reduced in exercised plasma compared to sedentary ***:Our proof-of-concept study demonstrates that plasma from exercise-trained donors can protect neuronal cells in culture and promote adult hippocampal neurogenesis in the AD rat *** effect may be partly due to reduced pro-inflammatory signaling molecules in exercised plasma.

关键词： Cytokines High-intensity interval training Inflammation Neurons Plasma transfusion

Drosophila X virus-like particles as delivery carriers for improved oral insecticidal efficacy of scorpion Androctonus australis peptide against the invasive fruit fly,Drosophila suzukii

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Insect Science 2024年第3期31卷 847-858页

作者： Qi Xue Luc Swevers Clauvis Nji Tizi Taning Faculty of Bioscience Engineering Department of Plants and CropsGhent UniversityGhentBelgium Insect molecular Genetics and Biotechnology Institute of Biosciences and ApplicationsNational Centre for Scientific Research"Demokritos"AthensGreece

Insect-specific neurotoxic peptides derived from the venoms of scorpions and spiders can cause acute paralysis and death when injected into insects,offering a promising insecticidal component for insect pest ***,effective delivery systems are required to help neurotoxic peptides pass through the gut barrier into the hemolymph,where they can ***,we investigated the potential of a novel nanocarrier,Drosophila X virus-like particle(DXV-VLP),for delivering a neurotoxin from the scorpion Androctonus australis Hector(AaIT)against the invasive pest fruit fly,Drosophila *** results show that the fusion proteins of DXV polyproteins with AalT peptide at their Ctermini could be sufficiently produced in Lepidoptera Hi5 cells in a soluble form using the recombinant baculovirus expression system,and could self-assemble into VLPs with similar particle morphology and size to authentic DXV *** addition,the AalT peptides displayed on DXV-VLPs retained their toxicity,as demonstrated in injection bioassays that resulted in severe mortality(72%)in adults after 72 *** fed to adults,mild mortality was observed in the group treated with DXV-AalT(38%),while no mortality occurred in the group treated with AaIT peptide,thus indicating the significant role of DXV-VLPs in delivering AalT ***,this proof-of-concept study demonstrates for the first time that VLPs can be exploited to enhance oral delivery of insect-specific neurotoxic peptides in the context of pest ***,it provides insights for further improvements and potentially the development of neurotoxin-based bioinsecticides and/or transgenic crops for insect pest control.

关键词： AalT Drosophila suzuki nanocarrier neurotoxic peptides pest control virus-like particle(VLP)

Single-cell RNA sequencing facilitates the elucidation of the complete biosynthesis of the antidepressant hyperforin in St. John's wort

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molecular Plant 2024年第9期17卷 1439-1457页

作者： Song Wu Ana Luisa Malaco Morotti Jun Yang Ertao Wang Evangelos C.Tatsis National Key Laboratory of Plant molecular Genetics CASs Center for Excellence in Molecular Plant SciencesShanghai lnstitute of Plant Physiology and EcologyChineseAcademy of SciencesShanghai 200032China University of Chinese Academy of Sciences Shanghai 200032China UEPAMS-CAS-JICs centre of Excellencefor Plant anamlcroblalSclence Snangnal 200032Cnina

Hyperforin is the compound responsible for the effectiveness of ***'s wort(Hypericum perforatum)as an antidepressant,but its complete biosynthetic pathway remains *** discovery based on co-expression analysis of bulk RNA-sequencing data or genome mining failed to discover the missing steps in hyperforin *** this study,we sequenced the 1.54-Gb tetraploid *** genome assem-bled into 32 chromosomes with the scaffold N50 value of 42.44 *** single-cell RNA sequencing,we iden-tified a type of cell,“Hyper cells”,wherein hyperforin biosynthesis de novo takes place in both the leaves and *** pathway reconstitution in yeast and tobacco,we identified and characterized four transmembrane prenyltransferases(HpPT1-4)that are localized at the plastid envelope and complete the hyperforin biosynthetic *** hyperforin polycyclic scaffold is created by a reaction cascade involving an irregular isoprenoid coupling and a tandem *** findings reveal how and where hy-perforin is biosynthesized,enabling synthetic-biology reconstitution of the complete ***,this study not only deepens our comprehension of specialized metabolism at the cellularlevel but also provides strategic guidance for elucidation of the biosynthetic pathways of other specializied metabolites in plants.

关键词： hyperforin Hypericum perforatum de novo genome sequencing single-cell RNA sequencing biosyn-thetic pathway meroterpenoids

Mitochondria-specific near-infrared photoactivation of peroxynitrite upconversion luminescent nanogenerator for precision cancer gas therapy

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Acta Pharmaceutica Sinica B 2024年第1期14卷 378-391页

作者： Hui Yu Aliya Tiemuer Xufeng Yao Mingyuan Zuo Hai-Yan Wang Yi Liu Xiaoyuan Chen Department of Biomedical Engineering School of EngineeringChina Pharmaceutical UniversityNanjing 211198China School of Mechanical Engineering Southeast UniversityNanjing 211189China Departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and College of Design and EngineeringNational University of SingaporeSingapore 119074Singapore Clinical Imaging Research centre Centre for Translational MedicineYong Loo Lin School of MedicineNational University of SingaporeSingapore 117599Singapore Nanomedicine Translational Research Program Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117597Singapore Institute of molecular and Cell Biology Agency for ScienceTechnologyand Research(A*STAR)ProteosSingapore 138673Singapore

Gas therapy is emerging as a highly promising therapeutic strategy for cancer ***,there are limitations,including the lack of targeted subcellular organelle accuracy and spatiotemporal release precision,associated with gas *** this study,we developed a series of photoactivatable nitric oxide(NO)donors NRh-R-NO(R=Me,Et,Bn,iPr,and Ph)based on an N-nitrosated upconversion luminescent rhodamine *** the irradiation of 808 nm light,only NRh-Ph-NO could effectively release NO and NRh-Ph with a significant turn-on frequency upconversion luminescence(FUCL)signal at 740 nm,ascribed to lower N-N bond dissociation *** also investigated the involved multistage near-infrared-controlled cascade release of gas therapy,including the NO released from NRh-Ph-NO along with one NRh-Ph molecule generation,the superoxide anion O_(2)^(⋅−)produced by the photodynamic therapy(PDT)effect of NRh-Ph,and highly toxic peroxynitrite anion(ONOO‒)generated from the co-existence of NO and O_(2)^(⋅−).After mild nano-modification,the nanogenerator(NRh-Ph-NO NPs)empowered with superior biocompatibility could target *** an 808 nm laser irradiation,NRh-Ph-NO NPs could induce NO/ROS to generate RNS,causing a decrease in the mitochondrial membrane potential and initiating apoptosis by caspase-3 activation,which further induced tumor immunogenic cell death(ICD).In vivo therapeutic results of NRh-Ph-NO NPs showed augmented RNS-potentiated gas therapy,demonstrating excellent biocompatibility and effective tumor inhibition guided by real-time FUCL ***,this versatile strategy defines the targeted RNS-mediated cancer therapy.

关键词： Near infrared Photo-triggered Mitochondrion Upconversion luminescent bioimaging Peroxynitrite Nanogenerator Gas therapy In vivo