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Clinical Peptidomics: Advances in Instrumentation, Analyses, and Applications

Biomedical Engineering Frontiers 2023年第1期4卷 116-132页

作者： Lin Li Jing Wu Christopher JLyon Li Jiang tony y.hu Center for Cellular and Molecular Diagnostics Department of Biochemistry and Molecular BiologySchool of MedicineTulane UniversityNew OrleansLAUSA Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for human Disease Gene Study Sichuan Academy of Medical Sciences and Sichuan Provincial People’s HospitalChengduChina Department of Clinical Laboratory Third Central Hospital of TianjinTianjin Institute of Hepatobiliary DiseaseTianjin Key Laboratory of Artificial CellArtificial Cell Engineering Technology Research Center of Public Health MinistryTianjinChina Department of Biomedical Engineering School of Science and EngineeringTulane UniversityNew OrleansLAUSA

Extensive effort has been devoted to the discovery,development,and validation of biomarkers for early disease diagnosis and prognosis as well as rapid evaluation of the response to therapeutic interventions.Genomic and transcriptomic profiling are well-established means to identify disease-associated biomarkers.However,analysis of disease-associated peptidomes can also identify novel peptide biomarkers or signatures that provide sensitive and specific diagnostic and prognostic information for specific malignant,chronic,and infectious diseases.Growing evidence also suggests that peptidomic changes in liquid biopsies may more effectively detect changes in disease pathophysiology than other molecular methods.Knowledge gained from peptide-based diagnostic,therapeutic,and imaging approaches has led to promising new theranostic applications that can increase their bioavailability in target tissues at reduced doses to decrease side effects and improve treatment responses.However,despite major advances,multiple factors can still affect the utility of peptidomic data.This review summarizes several remaining challenges that affect peptide biomarker discovery and their use as diagnostics,with a focus on technological advances that can improve the detection,identification,and monitoring of peptide biomarkers for personalized medicine.

关键词： doses gained devoted

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Extracellular vesicles:Emerging tools as therapeutic agent carriers

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Acta Pharmaceutica Sinica B 2022年第10期12卷 3822-3842页

作者： Shan Liu Xue Wu Sutapa Chandra Christopher Lyon Bo Ning Li jiang Jia Fan tony y.hu Sichuan Provincial Key Laboratory for human Disease Gene Study Department of Medical GeneticsDepartment of Laboratory MedicineSichuan Academy of Medical Sciences&Sichuan Provincial People’s HospitalChengdu 610072China Department of Biochemistry and Molecular Biology Center for Cellular and Molecular DiagnosisSchool of MedicineTulane UniversityNew OrleansLA 70112USA The M.O.E.Key Laboratory of Laboratory Medical Diagnostics the College of Laboratory MedicineChongqing Medical UniversityChongqing 400016China

Extracellular vesicles(EVs)are secreted by both eukaryotes and prokaryotes,and are present in all biological fluids of vertebrates,where they transfer DNA,RNA,proteins,lipids,and metabolites from donor to recipient cells in cell-to-cell communication.Some EV components can also indicate the type and biological status of their parent cells and serve as diagnostic targets for liquid biopsy.EVs can also natively carry or be modified to contain therapeutic agents(e.g.,nucleic acids,proteins,polysaccharides,and small molecules)by physical,chemical,or bioengineering strategies.Due to their excellent biocompatibility and stability,EVs are ideal nanocarriers for bioactive ingredients to induce signal transduction,immunoregulation,or other therapeutic effects,which can be targeted to specific cell types.Herein,we review EV classification,intercellular communication,isolation,and characterization strategies as they apply to EV therapeutics.This review focuses on recent advances in EV applications as therapeutic carriers from in vitro research towards in vivo animal models and early clinical applications,using representative examples in the fields of cancer chemotherapeutic drug,cancer vaccine,infectious disease vaccines,regenerative medicine and gene therapy.Finally,we discuss current challenges for EV therapeutics and their future development.

关键词： Extracellular vesicle Therapeutic agent Delivery carrier Outer membrane vesicle Cancer therapy Infectious disease vaccine Regenerative medicine Gene therapy

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Nanotechnology Powered CRISPR-Cas Systems for Point of Care Diagnosis and Therapeutic

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Research 2023年第3期2022卷 155-156页

作者： Chen-zhong Li tony y.hu Center for Cellular and Molecular Diagnostics Department of Biochemistry and Molecular BiologyTulane University School of Medicine1324Tulane Ave.New OrleansLA70112US

Inspired by the successful application of Cas9 gene editing for“genome surgery,”we are looking back at what has been accomplished in the ten years of CRISPR editing.Intense effort is now focused on how to utilize the unique functions of CRISPR-Cas systems for molecular diagnostics and the next generation of therapeutic tools.CRISPR-Cas systems have two major advantages for gene editing that render them attractive for these new applications,specifically the ability to easily control their target recognition specificity and to couple this specificity to a targeted or secondary cleavage activity.However,despite the great potential of CRISPR/Cas for both gene editing and diagnosis,its medical applications have yet to be fully realized due factors that limit their delivery or utility for point-of-care(POC)applications.In this editorial note,we discuss how nanotechnology can address challenges associated with new CRISPR applications and what nanotechnology-specific advances are needed to circumvent remaining barriers that limit the development or use of new CRISPR/CAS-based genome editing and diagnostic approaches.

关键词： limit specificity utilize

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Strategies for advanced personalized tuberculosis diagnosis:Current technologies and clinical approaches

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Precision Clinical Medicine 2021年第1期4卷 35-44页

作者： Xuerong Chen tony y.hu Department of Respiratory and Critical Care Medicine West China HospitalSichuan UniversityChengdu 610041China Center for Cellular and Molecular Diagnostics School of MedicineTulane UniversityNew OrleansLA 70112USA

Diagnosis of tuberculosis can be difficult as advances in molecular diagnosis approaches(especially nanoparticles combined with high-throughput mass spectrometry for detecting mycobacteria peptide)and personalized medicine result in many changes to the diagnostic framework.This review will address issues concerning novel technologies from bench to bed and new strategies for personalized tuberculosis diagnosis.

关键词： tuberculosis molecular diagnosis personalized medicine

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Extracellular vesicle activities regulating macrophage- and tissue-mediated injury and repair responses

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Acta Pharmaceutica Sinica B 2021年第6期11卷 1493-1512页

作者： Qian hu Christopher J.Lyon Jesse K.Fletcher Wenfu Tang Meihua Wan tony y.hu Department of Integrated Traditional Chinese and Western Medicine West China HospitalSichuan UniversityChengdu 610041China Center of Cellular and Molecular Diagnosis Tulane University School of MedicineNew OrleansLA 70112USA Department of Biochemistry&Molecular Biology Tulane University School of MedicineNew OrleansLA 70112USA

Macrophages are typically identified as classically activated(M1) macrophages and alternatively activated(M2) macrophages,which respectively exhibit pro-and anti-inflammatory phenotypes,and the balance between these two subtypes plays a critical role in the regulation of tissue inflammation,injury,and repair processes.Recent studies indicate that tissue cells and macrophages interact via the release of small extracellular vesicles(EVs) in processes where EVs released by stressed tissue cells can promote the activation and polarization of adjacent macrophages which can in turn release EVs and factors that can promote cell stress and tissue inflammation and injury and vice versa.This review discusses the roles of such EVs in resulating such interactions to influence tissue inflammation and injury in a number of acute and chronic inflammatory disease conditions,and the potential applications,advantage and concerns for using EV-based therapeutic approaches to treat such conditions,including their potential role of drug carriers for the treatment of infectious diseases.

关键词： Extracellular vesicles Macrophage Tissue injury Inflammatory disease Interaction loop Stem cell Sepsis Targeted therapy

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Optimization of chemistry and process parameters for control of intermetallic formation in Mg sludges

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Journal of Magnesium and Alloys 2024年第4期12卷 1431-1448页

作者： y.Fu G.G.Wang A.hu y.Li K.B.Thacker J.P.Weiler H.hu Department of Mechanical Automotive and Materials EngineeringUniversity of Windsor401 Sunset AveWindsorOntario N9B 3P4Canada Global Technology Centre Meridian Lightweight Technologies25 MacNab AveStrathroyOntario N7G 4H6Canada

Intermetallic formation in sludge during magnesium(Mg)melting,holding and high pressure die casting practices is a very important issue.But,very often it is overlooked by academia,original equipment manufacturers(OEM),metal ingot producers and even die casters.The aim of this study was to minimize the intermetallic formation in Mg sludge via the optimization of the chemistry and process parameters.The Al8Mn5 intermetallic particles were identified by the microstructure analysis based on the Al and Mn ratio.The design of experiment(DOE)technique,Taguchi method,was employed to minimize the intermetallic formation in the sludge of Mg alloys with various chemical compositions of Al,Mn,Fe,and different process parameters,holding temperature and holding time.The sludge yield(Sy)and intermetallic size(IS)was selected as two responses.The optimum combination of the levels in terms of minimizing the intermetallic formation were 9 wt.%Al,0.15 wt.%Mn,0.001 wt.%(10 ppm)Fe,690℃ for the holding temperature and holding at 30 mins for the holding time,respectively.The best combination for smallest intermetallic size were 9 wt.%Al,0.15 wt.%Mn,0.001 wt.%(10 ppm)Fe,630℃ for the holding temperature and holding at 60 mins for the holding time,respectively.Three groups of sludge factors,Chemical Sludge(CSF),Physical Sludge(PSF)and Comprehensive Sludge Factors(and CPSF)were established for prediction of sludge yields and intermetallic sizes in Al-containing Mg alloys.The CPSF with five independent variables including both chemical elements and process parameters gave high accuracy in prediction,as the prediction of the PSF with only the two processing parameters of the melt holding temperature and time showed a relatively large deviation from the experimental data.The Chemical Sludge Factor was primarily designed for small ingot producers and die casters with a limited melting and holding capacity,of which process parameters could be fixed easily.The Physical Sludge Factor could be used for mass production with a single type of Mg allo

关键词： Magnesium sludge Al-Mn intermetallic Optimization Taguchi method Sludge factor Chemical composition Process parameter

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Research Progress of Anti-Icing Technology of Superhydrophobic Coating

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Materials China 2024年第4期43卷 301-310页

作者： Chen X. hu L. Du y. School of Electrical Engineering Xinjiang University Urumqi 830017 China

Icing always threatens the safe operation of power system. In the past few decades, researchers have taken various measures to prevent the icing on the surface of power equipments, but these measures can not fundamentally solve this problem. Due to its unique micro-nano structure and low surface energy materials, superhydrophobic coating can delay icing and reduce the adhesion ability of surface ice at low temperature. Therefore, started with the anti-icing mechanism of superhydrophobic coating, this paper focuses on the experimental research status of anti-icing of superhydrophobic coating at home and abroad, divides the factors affecting the anti-icing performance into environmental factors and substrate factors, analyzes the limitations of the current schemes, and expounds the latest design and preparation progress on improving the mechanical robustness of superhydrophobic coating. Finally, the problems existing in the application of superhydrophobic coating in power system and the future development direction are put forward. This review is helpful for researchers to establish test specifications for evaluating the anti-icing performance of superhydrophobic coatings and promote their application in power system. © 2024 Materials China. All rights reserved.

关键词： anti-icing mechanism environmental factors power system substrate factors superhydrophobic coating

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Physics-informed deep learning for fringe pattern analysis

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Opto-Electronic Advances 2024年第1期7卷 4-15页

作者： Wei yin yuxuan Che Xinsheng Li Mingyu Li yan hu Shijie Feng Edmund y.Lam Qian Chen Chao Zuo Smart Computational Imaging Laboratory(SCILab) School of Electronic and Optical EngineeringNanjing University of Science and TechnologyNanjing 210094China Smart Computational Imaging Research Institute(SCIRI)of Nanjing University of Science and Technology Nanjing 210019China Jiangsu Key Laboratory of Spectral Imaging&Intelligent Sense Nanjing 210094China Department of Electrical and Electronic Engineering The University of Hong KongPokfulamHong Kong SAR 999077China

Recently,deep learning has yielded transformative success across optics and photonics,especially in optical metrology.Deep neural networks (DNNs) with a fully convolutional architecture (e.g.,U-Net and its derivatives) have been widely implemented in an end-to-end manner to accomplish various optical metrology tasks,such as fringe denoising,phase unwrapping,and fringe analysis.However,the task of training a DNN to accurately identify an image-to-image transform from massive input and output data pairs seems at best naive,as the physical laws governing the image formation or other domain expertise pertaining to the measurement have not yet been fully exploited in current deep learning practice.To this end,we introduce a physics-informed deep learning method for fringe pattern analysis (PI-FPA) to overcome this limit by integrating a lightweight DNN with a learning-enhanced Fourier transform profilometry (Le FTP) module.By parameterizing conventional phase retrieval methods,the Le FTP module embeds the prior knowledge in the network structure and the loss function to directly provide reliable phase results for new types of samples,while circumventing the requirement of collecting a large amount of high-quality data in supervised learning methods.Guided by the initial phase from Le FTP,the phase recovery ability of the lightweight DNN is enhanced to further improve the phase accuracy at a low computational cost compared with existing end-to-end networks.Experimental results demonstrate that PI-FPA enables more accurate and computationally efficient single-shot phase retrieval,exhibiting its excellent generalization to various unseen objects during training.The proposed PI-FPA presents that challenging issues in optical metrology can be potentially overcome through the synergy of physics-priors-based traditional tools and data-driven learning approaches,opening new avenues to achieve fast and accurate single-shot 3D imaging.

关键词： optical metrology deep learning physics-informed neural networks fringe analysis phase retrieval

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Rational design of AgGaS/ZnS/ZnS quantum dots with a near-unity photoluminescence quantum yield via double shelling scheme

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Journal of Materials Science & Technology 2024年第2期169卷 235-242页

作者： H.X.Lu H.Liu Z.Z.Fu y.y.Chen H.Q.Dai Z.hu W.L.Zhang R.Q.Guo Institute for Electric Light Sources School of Information Science and TechnologyFudan UniversityShanghai 200433China Institute of Future Lighting Academy for Engineering and TechnologyFudan UniversityShanghai 200433China yiwu Research Institute of Fudan University YiwuZhejiang 322000China Zhongshan-Fudan Joint Innovation Center Zhongshan 528437China

In this study,a two-step method was used to synthesize highly luminescent AgGaS/ZnS/ZnS quantum dots(QDs).In the first step,an inner ZnS shell was formed via a one-pot method,which resulted in a smaller lattice mismatch between the AgGaS core and the outer ZnS shell,thereby facilitating the formation of a thick outer shell.After the two-step shelling process,the synthesized AgGaS/ZnS/ZnS QDs showed an excellent photoluminescence quantum yield(PLQy)of 96.4%with a peak wavelength of 508 nm,repre-senting the highest PLQy reported thus far for AgGaS QDs.Furthermore,the effect of halogen ions in Zn precursors on the shelling process was investigated.It was proposed that the capacity of halogen ions to coordinate with the QDs influenced the balance between Zn cation diffusion and ZnS shelling reaction.Specifically,the ZnS shelling reaction was dominant when ZnCl_(2)was employed,while Zn cation diffusion was the dominant process under the I^(−)-rich environment.This work provides insights into the interfacial restructuring during the ZnS shelling and offers a clear map for the tailored synthesis of core/shell QDs.

关键词： AgGaS Quantum dots Photoluminescence Core/shell Alloyed core/shell interface

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Impact of Polymer Matrix on Polymer Mechanochromism from Excited State Intramolecular Proton Transfer

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Chinese Journal of Chemistry 2024年第6期42卷 611-616页

作者： yu Wu Xin Cheng huan hu Shui hu Zhimin Ma Zhiyong Ma Beijing Advanced Innovation Center for Soft Matter Science and Engineering Beijing State Key Laboratory of Organic-Inorganic CompositesCollege of Chemical EngineeringBeijing University of Chemical TechnologyBeijing100029 China Center of Advanced Elastomer Materials College of Materials Science and EngineeringBeijing University of Chemical TechnologyBeijing100029 China College of Engineering Peking UniversityBeijing100871 China

Mechanochromic polymers based on non-covalent changes have attracted much attention recently.Herein,we report the impact of inter/intramolecular hydrogen bonds on polymer mechanochromism from the excited state intramolecular proton transfer (ESIPT) process.PhMz-NH2-OH and PhMz=2A are designed and obtained by simple and high-yield synthesis,and are connected into polyurethane and poly(methyl acrylate-co-2-ethylhexyl acrylate),respectively.In the initial state,the PhMz-NH2-OH@PU sample shows blue fluorescence from the excited enol form (E*) excitons,owing to intermolecular hydrogen bonds that interrupt the ESIPT reactions but the PhMz=2A@PMA-2-EA sample expresses cyan fluorescence belonging to the excited keto form (K*) emission,implying that the intramolecular hydrogen bonds matter.Furthermore,under stretching,external force can tune the emission of the PhMz=2A@PMA-2-EA sample from K* to E* state.Though external force can putatively still promote a bond rotation,ESIPT reactions remain equivalently interrupted in both the relaxed and stressed states in a hydrogen-bond donating environment.DFT calculation confirms the force-induced increase in dihedral angle for the transition of ESIPT-on/off.Thus,PhMz-NH2-OH@PU and PhMz=2A@PMA-2-EA showed disparate initial ESIPT states and further different responses/sensitivity to force.This study reports a novel and efficient strategy for enriching mechanochromic investigation and extending the applications of ESIPT reactions.

关键词： Polymer mechanochromism Excited state intramolecular proton transfer Hydrogen bonding Supramolecular chemistry Elastomers

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