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Label-free SARS-CoV-2 detection and classification using phase imaging with computational specificity

Light(Science & Applications) 2021年第9期10卷 1797-1808页

作者： Neha Goswami Yuchen R.He Yu-Heng Deng Chamteut Oh Nahil Sobh Enrique Valera Rashid Bashir Nahed Ismail Hyunjoon Kong Thanh H.Nguyen Catherine Best-Popescu Gabriel Popescu Department of Bioengineering University of Illinois Urbana-ChampaignUrbanaIllinois61801USA Beckman Institute of Advanced Science and Technology University of Illinois Urbana-ChampaignUrbanaIllinois61801USA Department of Electrical and Computer Engineering University of Illinois Urbana-ChampaignUrbanaIllinois61801USA Department of Chemical and Biomolecular Engineering University of Illinois at Urbana-ChampaignUrbanaIL61801USA Department of Civil and Environmental Engineering University of Illinois at Urbana-ChampaignUrbanaIL61801USA NCSA Center for Artificial Intelligence Innovation University of Illinois at Urbana-ChampaignUrbanaIL61801USA Holonyak Micro and Nanotechnology Laboratory University of Illinois at Urbana-ChampaignUrbanaIllinois61801USA Biomedical Research Center Carle Foundation Hospital509W University Ave.UrbanaIllinois61801USA Carle illinois college of medicine 807 South Wright St.UrbanaIllinois61801USA Mayo-illinois Alliance for Technology Based Healthcare UrbanaIllinois61801USA Department of Pathology College of MedicineUniversity of Illinois at ChicagoChicagoILUSA

Efforts to mitigate the COVID-19 crisis revealed that fast,accurate,and scalable testing is crucial for curbing the current impact and that of future *** propose an optical method for directly imaging unlabeled viral particles and using deep learning for detection and *** ultrasensitive interferometric method was used to image four virus types with nanoscale optical path-length *** these data with fluorescence images for ground truth,we trained semantic segmentation models based on U-Net,a particular type of convolutional neural *** trained network was applied to classify the viruses from the interferometric images only,containing simultaneously SARS-CoV-2,H1N1(influenza-A virus),HAdV(adenovirus),and ZIKV(Zika virus).Remarkably,due to the nanoscale sensitivity in the input data,the neural network was able to identify SARS-CoV-2 *** other viruses with 96%*** inference time for each image is 60 ms,on a common graphic-processing *** approach of directly imaging unlabeled viral particles may provide an extremely fast test,of less than a minute per *** the imaging instrument operates on regular glass slides,we envision this method as potentially testing on patient breath *** necessary high throughput can be achieved by translating concepts from digital pathology,where a microscope can scan hundreds of slides automatically.

关键词： testing neural hundreds

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Knockout of butyrophilin subfamily 1 member A1(BTN1A1) alters lipid droplet formation and phospholipid composition in bovine mammary epithelial cells

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Journal of Animal Science and Biotechnology 2020年第4期11卷 975-985页

作者： Liqiang Han Menglu Zhang Zhiyang Xing Danielle N.Coleman Yusheng Liang Juan J.Loor Guoyu Yang college of Animal Science and Veterinary medicine Henan Agricultural UniversityZhengzhou 450002PR China Department of Animal Sciences and Division of Nutritional Sciences University of IllinoisUrbanaIllinois 61801USA.

Background: Milk lipids originate from cytoplasmic lipid droplets(LD) that are synthesized and secreted from mammary epithelial cells by a unique membrane-envelopment process. Butyrophilin 1 A1(BTN1 A1) is one of the membrane proteins that surrounds LD, but its role in bovine mammary lipid droplet synthesis and secretion is not well ***: The objective was to knockout BTN1 A1 in bovine mammary epithelial cells(BMEC) via the CRISPR/Cas9 system and evaluate LD formation, abundance of lipogenic enzymes, and content of cell membrane phospholipid(PL) species. Average LD diameter was determined via Oil Red O staining, and profiling of cell membrane phospholipid species via liquid chromatography-tandem mass spectrometry(LC-MS/MS).Results: Lentivirus-mediated infection of the Cas9/sg RNA expression vector into BMEC resulted in production of a homozygous clone BTN1 A1^((-/-)). The LD size and content decreased following BTN1 A1 gene knockout. The m RNA abundance of fatty acid synthase(FASN) and peroxisome proliferator-activated receptor-gamma(PPARG) was downregulated in the BTN1 A1^((-/-))clone. Subcellular analyses indicated that BTN1 A1 and LD were co-localized in the cytoplasm. BTN1 A1 gene knockout increased the percentage of phosphatidylethanolamine(PE) and decreased phosphatidylcholine(PC), which resulted in a lower PC/PE ***: Results suggest that BTN1 A1 plays an important role in regulating LD synthesis via a mechanism involving membrane phospholipid composition.

关键词： Lipid droplet Mammary epithelial cell Milk fat globule Phospholipid

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Inhibiting Protein Aggregation by Small Molecule-Based Colloidal Nanoparticles

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Accounts of Materials Research 2022年第1期3卷 54-66页

作者： Koushik Debnath Ankan Kumar Sarkar Nihar R.Jana Nikhil R.Jana Department of Pharmacology and Regenerative medicine College of MedicineUniversity of Illinois at ChicagoChicagoIllinois 60612United States Department of Biomedical Engineering College of MedicineUniversity of Illinois at ChicagoChicagoIllinois 60607United States School of Materials Sciences Indian Association for the Cultivation of ScienceKolkata 700032India

CONSPECTUS:Protein aggregation is associated with different human diseases such as Alzheimer’s,Huntington’s,Parkinson’s,diabetes type II,and *** no effective treatment exists for many of these diseases,particularly for neurological *** research focuses on understanding the origin of protein aggregation,nucleation−growth mechanism of protein aggregation,origin of cytotoxicity of protein aggregates,cellular response of toxic protein aggregates,progress of diseases at intra/extracellular space,and drug developments for respective *** issues are the identification of molecular drugs that can inhibit protein aggregation at early stage,lowering of toxicity due to protein aggregates,delivery of drugs to remote organ and intracellular space,clearing matured protein aggregates from cell/extracellular space/brain,and design of effective therapeutic *** and materials scientists have identified a wide variety of antiamyloidogenic small molecules,macromolecules,and *** is shown that antiamyloidogenic molecules prevent protein oligomerization via binding to protein,masking metal ions(via chelating with metal ions)that are responsible for protein aggregation via generating reactive oxygen species(ROS),and lowering protein−protein interaction via macromolecular crowding ***,nanoscale materials with curved surface and multiple chemical functional groups act as adsorption/binding sites of proteins,modulate nucleation−growth kinetics of protein aggregation,and delay/inhibit protein aggregation in many ***,performance of all these antiamyloidogenic materials needs significant improvement,and proper therapeutic strategies are required for effective drug *** this Account,we describe that the performance of antiamyloidogenic molecules can be greatly improved via appropriate design into colloidal and nanoparticle *** first discuss different human diseases that are linked with protein agg

关键词： integrating Huntington curved

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Allopregnanolone targets nucleoprotein as a novel influenza virus inhibitor

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Virologica Sinica 2023年第6期38卷 931-939页

作者： Meiyue Dong Yanyan Wang Ping Li Zinuo Chen Varada Anirudhan Qinghua Cui Lijun Rong Ruikun Du Innovative Institute of Chinese medicine and Pharmacy Shandong University of Traditional Chinese MedicineJinan250355China college of Pharmacy Shandong University of Traditional Chinese MedicineJinan250355China Department of Microbiology and Immunology College of MedicineUniversity of Illinois at ChicagoChicago60612USA Qingdao Academy of Chinese Medical Sciences Shandong University of Traditional Chinese MedicineQingdao266122China

Influenza A virus(IAV)poses a global public health concern and remains an imminent threat to human *** antiviral resistance to the currently approved influenza drugs emphasizes the urgent need for new therapeutic entities against ***(ALLO)is a natural product that has been approved as an antidepressant *** the present study,we repurposed ALLO as a novel inhibitor against *** studies demonstrated that ALLO inhibited virus replication by interfering with the nucleus translocation of viral nucleoprotein(NP).In addition,ALLO showed significant synergistic activity with compound 16,a hemagglutinin inhibitor of *** summary,we have identified ALLO as a novel influenza virus inhibitor targeting NP,providing a promising candidate that deserves further investigation as a useful anti-influenza strategy in the future.

关键词： Allopregnanolone(ALLO) Antivirall Influenza A virus(IAV) Nucleoprotein Nucleus translocation

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SARS-CoV-2 cell entry and targeted antiviral development

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Acta Pharmaceutica Sinica B 2021年第12期11卷 3879-3888页

作者： Zinuo Chen Ruikun Du Jazmin M.Galvan Achi Lijun Rong Qinghua Cui college of Pharmacy Shandong University of Traditional Chinese MedicineJinan 250355China Qingdao Academy of Chinese Medicinal Sciences Shandong University of Traditional Chinese MedicineQingdao 266122China Experimental Center Shandong University of Traditional Chinese MedicineJinan 250355China Department of Microbiology and Immunology College of MedicineUniversity of Illinois at ChicagoChicagoIL 60612USA

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the causative agent of the pandemic coronavirus disease 2019(COVID-19),which threatens human health and public *** the urgent campaign to develop anti-S ARS-CoV-2 therapies,the initial entry step is one of the most appealing *** this review,we summarize the current understanding of SARS-CoV-2 cell entry,and the development of targeted antiviral ***,we speculate upon future directions toward nextgeneration of SARS-CoV-2 entry inhibitors during the upcoming post-pandemic era.

关键词： SARS-CoV-2 Cell entry Spike protein Antiviral development Post-pandemic

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Flu Universal Vaccines: New Tricks on an Old Virus

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Virologica Sinica 2021年第1期36卷 13-24页

作者： Ruikun Du Qinghua Cui Lijun Rong college of Pharmacy Shandong University of Traditional Chinese MedicineJinan 250355China Qingdao Academy of Chinese Medicinal Sciences Shandong University of Traditional Chinese MedicineQingdao 266122China Experimental Center Shandong University of Traditional Chinese MedicineJinan 250355China Department of Microbiology and Immunology College of MedicineUniversity of Illinois at ChicagoChicagoIL 60612USA

Conventional influenza vaccines are based on predicting the circulating viruses year by year,conferring limited effectiveness since the antigenicity of vaccine strains does not always match the circulating *** necessitates development of universal influenza vaccines that provide broader and lasting protection against pan-influenza *** discovery of the highly conserved immunogens(epitopes)of influenza viruses provides attractive targets for universal vaccine *** we review the current understanding with broadly protective immunogens(epitopes)and discuss several important considerations to achieve the goal of universal influenza vaccines.

关键词： Influenza virus Universal vaccine Conserved epitopes Broadly protection

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Revisiting influenza A virus life cycle from a perspective of genome balance

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Virologica Sinica 2023年第1期38卷 1-8页

作者： Ruikun Du Qinghua Cui Zinuo Chen Xiujuan Zhao Xiaojing Lin Lijun Rong Innovation Research Institute of Traditional Chinese medicine Shandong University of Traditional Chinese MedicineJinan250355China Qingdao Academy of Chinese Medicinal Sciences Shandong University of Traditional Chinese MedicineQingdao266122China college of Pharmacy Shandong University of Traditional Chinese MedicineJinan250355China Department of Microbiology and Immunology College of MedicineUniversity of Illinois at ChicagoChicago60612USA

Influenza A virus(IAV)genome comprises eight negative-sense RNA segments,of which the replication is well orchestrated and the delicate balance of multiple segments are dynamically regulated throughout IAV life ***,previous studies seldom discuss these balances except for functional hemagglutinin-neuraminidase balance that is pivotal for both virus entry and ***,we attempt to revisit IAV life cycle by highlighting the critical role of“genome balance”.Moreover,we raise a“balance regression”model of IAV evolution that the virus evolves to rebalance its genome after reassortment or interspecies transmission,and direct a“balance compensation”strategy to rectify the“genome imbalance”as a result of artificial modifications during creation of recombinant *** review not only improves our understanding of IAV life cycle,but also facilitates both basic and applied research of IAV in future.

关键词： Influenza A virus(IAV) Segmented genome Genome balance Balance regression Balance compensation

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May-Thurner syndrome: High output cardiac failure as a result of iatrogenic iliac fistula

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World Journal of Clinical Cases 2015年第3期3卷 318-321页

作者： Shantanu Singh Shivank Singh Juthika Jyothimallika Teresa J Lynch Department of medicine University of Illinois College of Medicine at Peoria Department of medicine Southern Medical University Division of Pulmonology Duke LPMP 27536United States

May-Thurner syndrome(MTS) also termed iliocaval compression or Cockett-Thomas syndrome is a common, although rarely diagnosed, condition in which the patient has an anatomical variant wherein theright common iliac artery overlies and compresses the left common iliac vein against the fifth lumbar spine resulting in increased risk of iliofemoral deep venous thrombosis. This variant has been shown to be present in over 23% of the population but most go undetected. We present a patient with MTS who developed high output cardiac failure due to an iatrogenic iliac fistula. The patient underwent an extensive workup for a left to right shunt including MRI and arterial duplex in the vascular lab. He was ultimately found to have a 2.1 cm left common iliac artery aneurysm and history of common iliac stent. We took the patient to the operating room for aortogram with placement of an endovascular plug of the left internal iliac artery and aorto-biiliac stent graft placement with CO2 and Ⅳ contrast. Subsequently the patient underwent successful stent placement in the area that was compressed followed by 6 mo of anticoagulation with warfarin. The flow from the fistula decreased significantly.

关键词： May-Thurner syndrome Cardiac failure Echocardiogram Cockett-Thomas syndrome Iliocaval compression

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Recent advances in DNAzyme-based gene silencing

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Science China Chemistry 2017年第5期60卷 591-601页

作者： Huanhuan Fan Xiaobing Zhang Yi Lu Molecular Science and Biomedicine Laboratory State Key Laboratory of Chemo/Bio-Sensing and Chemometrics Collaborative Innovation Center for Chemistry and Molecular MedicineCollege of Chemistry and Chemical Engineering College of Biology Hunan University Changsha 410082 China Department of Chemistry Materials Science and Engineering University of Illinois at Urbana-Champaign Urbana Illinois 61801 USA

DNAzymes, generated through in vitro selection processes, are single-stranded DNA catalysts that can catalyze a wide variety of reactions, such as RNA or DNA cleavage and ligation or DNA phosphorylation. Based on specific cofactor dependence and potent catalytic ability, DNAzymes have been extensively used to develop highly sensitive and specific sensing platforms for metal ions,small molecules, and biomacromolecules. However, in spite of their multiple strong enzymatic turnover properties, few reports have addressed the potential application of RNA-cleaving DNAzymes as therapeutic gene-silencing agents. The main challenges are being met with low efficiency of cellular uptake, instability and the lack of sufficient cofactors for cellular or in vivo study, which have limited the development of DNAzymes for clinical application. In recent years, substantial progress has been made to enhance the delivery efficiency and stability of DNAzymes by developing variety of methods. Smart metal oxide nanomaterials have also been used to meet the requirement of cofactors in situ. This review focuses on the gene silencing application of DNAzymes as well as their physicochemical properties. Methods of increasing the efficacy of DNAzymes in gene therapy are also discussed: delivery systems to enhance the cellular uptake, modifications to enhance the stability and smart systems to generate sufficient cofactors in situ. Finally, some future trends and perspectives in these research areas are outlined.

关键词： DNAzymes gene-silencing delivery stability cofactors

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黄曲霉素B_1与tRNA的结合作用

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中国药理学与毒理学杂志 1993年第3期7卷 227-230页

作者：黄光琦 Fu L YU 华西医科大学肿瘤研究所 Department of Biomedical Sciences University of IllinoisCollege of Medicine at Rockford1601 Parkview AveRockfordIL 61107 USA

本文应用肝微粒体系统在体外激活黄曲霉素B_1(AFB_1), 研究了其与tRNA的结合作用,结果表明AFB_1能与tRNA结合形成加成物,tRNA与AFB_1不同的结合量呈直线关系,光谱分析显示AFB_1-tRNA加成物的最大吸收峰为339nm,而tRNA的λ_(max)为260nm,... 详细信息

本文应用肝微粒体系统在体外激活黄曲霉素B_1(AFB_1), 研究了其与tRNA的结合作用,结果表明AFB_1能与tRNA结合形成加成物,tRNA与AFB_1不同的结合量呈直线关系,光谱分析显示AFB_1-tRNA加成物的最大吸收峰为339nm,而tRNA的λ_(max)为260nm,AFB_1的λ_(max)为360nm,本文研究结果表明AFB_1-tRNA加成物对tRNA与氨基酸结合活性有明显的抑制作用。

关键词：黄曲霉毒素转移核糖核酸光谱分析

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