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A sphingolipid message promotes neuronal health across generations

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Neural Regeneration Research 2024年第11期19卷 2325-2326页

作者： Wenyue Wang Roger Pocock Development and Stem Cells Program Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental BiologyMonash UniversityMelbourneVICAustralia

Maternal nutrition can affect brain function of offspring in later life(Fitzgerald et al.,2020).Emerging studies have also shown that the maternal environment can modify susceptibility to neurodegenerative disease(Boots et al.,2023).Transmission of environmental information from mother to offspring depends on maternal nutrient provisioning.In the nematode Caenorhabditis elegans,maternal yolk,which is synthesized in the intestine and transferred to nourish oocytes and early embryos,can provide extranuclear inheritance factors to mediate phenotypic plasticity across generations.However,the molecular mechanisms of regulating such intergenerational effects remain largely unknown.

关键词： mother intestine transferred

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 diagnostics.Despite significant progress in the development of individual assays,multiparametric optical sensing of droplets and their encapsulated contents has been challenging.The current approaches,most commonly involving microscopy-based high-speed imaging of droplets,are technically complex and require expensive instrumentation,limiting their widespread adoption.To address these limitations,we developed the OptiDrop platform;this platform is a novel optofluidic setup that leverages the principles of flow cytometry.Our platform enables on-chip detection of the scatter and multiple fluorescence signals from the microfluidic droplets and their contents using optical fibers.The 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 droplet.To demonstrate the ability of the OptiDrop platform,we conducted a differential expression analysis of the major histocompatibility complex(MHC)protein in response to IFNγstimulation.Our results showed the platform’s ability to sensitively detect cell surface biomarkers using fluorescently labeled antibodies.Thus,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

Complement-dependent neuroinflammation in spinal cord injury:from pathology to therapeutic implications

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Neural Regeneration Research 2025年第5期20卷 1324-1335页

作者： Hassan Saad Bachar El Baba Ali Tfaily Firas Kobeissy Juanmarco Gutierrez Gonzalez Daniel Refai Gerald R.Rodts Christian Mustroph David Gimbel Jonathan Grossberg Daniel L.Barrow Matthew F.Gary Ali M.Alawieh department of Neurosurgery Emory University School of MedicineAtlantaGAUSA department of Neurology Yale UniversityNew HavenCTUSA Center for Neurotrauma Multiomics&Biomarkers(CNMB)Morehouse School of MedicineAtlantaGAUSA

Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery in this population.Following the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation,a similar role for complement in spinal neuroinflammation is a focus of ongoing research.In this work,we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins,triggers of complement activation,and role of effector functions in the pathology.We study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris,and or activation via antibody binding to damage-associated molecular patterns.Several effector functions of complement have been implicated in spinal cord injury,and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord injury.Following this pathophysiological review,we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human subjects.This review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury,to evaluate the phases of involvement of opsonins and anaphylatoxins,and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.

关键词： complement neuroinflammation neuroplasticity regeneration spinal cord injury targeted therapy

A REDUCED ORDER SCHWARZ METHOD FOR NONLINEAR MULTISCALE ELLIPTIC EQUATIONS BASED ON TWO-LAYER NEURAL NETWORKS

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Journal of Computational Mathematics 2024年第2期42卷 570-596页

作者： Shi Chen Zhiyan Ding Qin Li Stephen J.Wright Mathematics department University of Wisconsin-MadisonMadisonWI 53706USA department of Mathematics University of California-BerkeleyBerkeley CA 94720USA Mathematics department and discovery Institute University of Wisconsin-Madison MadisonWI 53706USA Computer Sciences department University of WisconsinMadisonWI 53706USA

Neural networks are powerful tools for approximating high dimensional data that have been used in many contexts,including solution of partial differential equations(PDEs).We describe a solver for multiscale fully nonlinear elliptic equations that makes use of domain decomposition,an accelerated Schwarz framework,and two-layer neural networks to approximate the boundary-to-boundarymap for the subdomains,which is the key step in the Schwarz procedure.Conventionally,the boundary-to-boundary map requires solution of boundary-value elliptic problems on each subdomain.By leveraging the compressibility of multiscale problems,our approach trains the neural network offline to serve as a surrogate for the usual implementation of the boundary-to-boundary map.Our method is applied to a multiscale semilinear elliptic equation and a multiscale p-Laplace equation.In both cases we demonstrate significant improvement in efficiency as well as good accuracy and generalization performance.

关键词： Nonlinear homogenization Multiscale elliptic problem Neural networks Do-main decomposition

IL-17 induces NSCLC cell migration and invasion by elevating MMP19 gene transcription and expression through the interaction of p300-dependent STAT3-K631 acetylation and its Y705-phosphorylation

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Oncology Research 2024年第4期32卷 625-641页

作者： WEN GE YA LI YUTING RUAN NINGXIA WU PEI MA TONGPENG XU YONGQIAN SHU YINGWEI WANG WEN QIU CHENHUI ZHAO department of Immunology Nanjing Medical UniversityNanjing210000China Key Laboratory of Immunological Environment and Disease Nanjing Medical UniversityNanjing210000China department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing210000China Jiangsu Key Laboratory of Cancer biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing210000China

The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.

关键词： NSCLC cell migration and invasion IL-17 p300 STAT3 MMP19 Acetylation and phosphorylation

Ergothioneine and its congeners:anti-ageing mechanisms and pharmacophore

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Protein & Cell 2024年第3期15卷 191-206页

作者： Li Chen Liping Zhang Xujun Ye Zixin Deng Changming Zhao department of Geriatrics Zhongnan Hospital of Wuhan UniversityWuhan UniversityWuhan 430072China Key Laboratory of Combinatory Biosynthesis and Drug discovery School of Pharmaceutical SciencesMinistry of EducationWuhan UniversityWuhan 430072China tThese authors contributed equally.

Ergothioneine,Ovothiol,and Selenoneine are sulfur/selenium-containing histidine-derived natural products widely distributed across different organisms.They exhibit significant antioxidant properties,making them as potential lead compounds for promoting health.Increasing evidence suggests that Ergothioneine is positively correlated with healthy ageing and longevity.The mechanisms underlying Ergothioneine's regulation of the ageing process at cellular and molecular levels are beginning to be understood.In this review,we provide an in-depth and extensive coverage of the anti-ageing studies on Ergothioneine and discuss its possible intracellular targeting pathways.In addition,we highlight the recent efforts in elucidating the biosynthetic details for Ergothioneine,Ovothiol,and Selenoneine,with a particular focus on the study of their pharmacophore-forming enzymology.

关键词： Ergothioneine antioxidant anti-ageing longevity biosynthesis enzymology

Total synthesis of a putative yuzurimine-type Daphniphyllum alkaloid C_(14)–epi-deoxycalyciphylline H

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Chinese Chemical Letters 2024年第4期35卷 336-339页

作者： Jingping Hu Jing Xu Shenzhen Grubbs Institute and department of Chemistry and Guangdong Provincial Key Laboratory of Catalysis and Shenzhen Key Laboratory of Small Molecule Drug discovery and Synthesis Southern University of Science and TechnologyShenzhen 518055China

One of the largest subfamilies within the famous Daphniphyllum alkaloid family is made up of the yuzurimine-type(or macrodaphniphyllamine-type) alkaloids. Their complex aza-polycyclic caged structures, several contiguous stereogenic centers, and vicinal all-carbon quaternary centers make these alkaloids formidable challenge for synthetic chemists. Recently, synthesis of these alkaloids has received extensive attention from our community. Herein, we wish to report the total synthesis of C_(14)–epideoxycalyciphylline H, a putative member of yuzurimine-type alkaloid subfamily. Key transformations employed in our approach include an intramolecular Prins reaction and a Pd-catalyzed enyne cycloisomerization. In addition, synthesis of a daphnezomine L-type alkaloid, paxdaphnidine A, was also studied.

关键词： Total synthesis Daphniphyllum alkaloids Yuzurimine-type alkaloids Prins reaction Enyne cycloisomerization

Bio-analysis of Saliva Using Paper Devices and Colorimetric Assays

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Journal of Analysis and Testing 2024年第1期8卷 114-132页

作者： Adhan Narasimhan Harshil Jain Kowshika Muniandy Raja Chinnappan Naresh Kumar Mani Microfluidics Sensors and Diagnostics(μSenD)LaboratoryCentre for MicrofluidicsBiomarkersPhotoceutics&Sensors(μBioPS)Department of BiotechnologyManipal Institute of TechnologyManipal Academy of Higher EducationManipalKarnataka 576104India College of Medicine Alfaisal UniversityRiyadh 11533SaudiArabia Tissue/Organ Bioengineering&BioMEMS Lab Organ Transplant Centre of ExcellenceTransplant Research&Innovation DepartmentKing Faisal Specialist Hospital and Research CentreRiyadhSaudi Arabia

In light of the evolving nature of various diseases,time becomes a crucial factor in diagnosis and identifying the underlying causes.A point-of-care device provides a rapid diagnosis of a disease without using complex and advanced instruments,which are costly and difficult to transport.A paper-based device is a relatively frugal solution wherein the paper is used as a substratum in which the reactions are carried out.These methods are non-invasive,and the sample collection is relatively easy.Saliva is one such body fluid in which various biomarkers are present for numerous diseases.Bioanalysis of saliva has attracted more attention recently due to its non-invasiveness and robustness.Exploiting the discovery of clinical biomarkers from salivary analysis has the potential to revolutionize the healthcare sector by providing crucial information to monitor the health status of individuals and disease progression which enables personalized treatment.This review provides the limitation of the traditional methods in clinical applications and highlights the significance of saliva as a non-invasive biological fluid that is a source of multiple biomarkers associated with various diseases.It also provides insights into the different paper-based colorimetric microfluidic devices developed against salivary biomarkers in the past decade.The major challenges in the point-of-care application and the future prospects have been discussed as well.Further,we also emphasize the importance of this approach in dental disease diagnosis which is least explored and holds potential applications.

关键词： Paper-based assay Salivary analysis Non-invasive Point-of-care Body fluids biomarkers Qualitative detection

Ultrasound-responsive spherical nucleic acid against c-Myc/PD-L1 to enhance anti-tumoral macrophages in triple-negative breast cancer progression

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Science China(Life Sciences) 2024年第4期67卷 698-710页

作者： Runtian Wang Gaigai Li Fangyan Gao Feng Xu Xintong Li Jian Zhang Jinbo Li Xiaoxiang Guan department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China State Key Laboratory of Analytical Chemistry for Life Sciences Jiangsu Key Laboratory of Advanced Organic MaterialsSchool of Chemistry and Chemical EngineeringChemistry and Biomedicine Innovation Center(ChemBIC)Nanjing UniversityNanjing 210023China department of Medical Oncology Fudan University Shanghai Cancer CenterDepartment of OncologyShanghai Medical CollegeFudan UniversityShanghai 200032China Jiangsu Key Lab of Cancer biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing 211166China

Triple-negative breast cancer(TNBC)is the most challenging breast cancer subtype because of its aggressive behavior and limited therapeutic targets.c-Myc is hyperactivated in the majority of TNBC tissues,however,it has been considered an“undruggable”target due to its disordered structure.Herein,we developed an ultrasound-responsive spherical nucleic acid(SNA)against c-Myc and PD-L1 in TNBC.It is a self-assembled and carrier-free system composed of a hydrophilic small-interfering RNA(si RNA)shell and a hydrophobic core made of a peptide nucleic acid(PNA)-based antisense oligonucleotide(ASO)and a sonosensitizer.We accomplished significant enrichment in the tumor by enhanced permeability and retention(EPR)effect,the controllable release of effective elements by ultrasound activation,and the combination of targeted therapy,immunotherapy and physiotherapy.Our study demonstrated significant anti-tumoral effects in vitro and in vivo.Mass cytometry showed an invigorated tumor microenvironment(TME)characterized by a significant alteration in the composition of tumor-associated macrophages(TAM)and decreased proportion of PD-1-positive(PD-1+)T effector cells after appropriate treatment of the ultrasound-responsive SNA(USNA).Further experiments verified that tumor-conditioned macrophages residing in the TME were transformed into the anti-tumoral population.Our finding offers a novel therapeutic strategy against the“undruggable”c-Myc,develops a new targeted therapy for c-Myc/PD-L1 and provides a treatment option for the TNBC.

关键词： triple-negative breast cancer c-Myc spherical nucleic acid self-assembly