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Absolute Quantification of MicroRNAs in a Single Cell with Chemiluminescence Detection Based on Rolling Circle Amplification on a Microchip Platform.

Anal Chem 2021 Jun 15. Epub 2021 Jun 15.

State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin 541004, China.

The absolute quantification of miRNAs in a single cell allows to better understand the heterogeneity of cells and the relationship between miRNAs and diseases. However, seldom methods for miRNA quantification in a single cell have been reported because the miRNA content in a single cell is very low. Herein, an ultrasensitive chemiluminescence assay strategy based on rolling circle amplification (RCA) on a microchip platform was proposed for the absolute quantification of miRNAs in a single cell. Read More

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Modulating Cas9 activity for precision gene editing.

Prog Mol Biol Transl Sci 2021 18;181:89-127. Epub 2021 Mar 18.

Graduate School of Natural and Applied Sciences, Yeditepe University, Istanbul, Turkey; Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, Istanbul, Turkey. Electronic address:

The CRISPR/Cas9 is a RNA-guided nuclease complex that can be specifically programmed to target a user-specified DNA sequence. It has been a powerful and effective tool of genome editing. However, off-target activity of the Cas9 nuclease limits its potential use in the correction of inherited diseases and bona fide gene editing. Read More

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Nanoparticle Delivery of CD147 Antagonistic Peptide-9 Protects against Acute Ischemic Brain Injury and tPA-Induced Intracerebral Hemorrhage in Mice.

ACS Appl Bio Mater 2020 Apr 3;3(4):1976-1985. Epub 2020 Mar 3.

Department of Neurosurgery, The Pennsylvania State, University College of Medicine, Hershey, Pennsylvania 17033, United States.

CD147 has emerged as a potential therapeutic target in many human diseases. We have demonstrated that inhibition of CD147 using its function-blocking antibody ameliorates acute ischemic brain injury and promotes long-term functional recovery in mice. Recently, peptide-nanoparticle conjugates have emerged as powerful tools for biomedical applications. Read More

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Toward a quantitative theoretical method for infrared and Raman spectroscopic studies on single-crystal electrode/liquid interfaces.

Chem Sci 2019 Dec 10;11(5):1425-1430. Epub 2019 Dec 10.

State Key Laboratory of Physical Chemistry of Solid Surfaces (PCOSS), Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University Xiamen 361005 China

electrochemical infrared spectroscopy and Raman spectroscopy are powerful tools for probing potential-dependent adstructures at solid/liquid electrochemical interfaces. However, it is very difficult to quantitatively interpret the observed spectral features including potential-dependent vibrational frequency and spectral intensity, even from model systems such as single-crystal electrode/liquid interfaces. The clear understanding of electrochemical vibrational spectra has remained as a fundamental issue for four decades. Read More

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December 2019

Kinetics of heterochiral strand displacement from PNA-DNA heteroduplexes.

Nucleic Acids Res 2021 Jun 14. Epub 2021 Jun 14.

Department of Chemistry, Texas A&M University, College Station, TX 77843, USA.

Dynamic DNA nanodevices represent powerful tools for the interrogation and manipulation of biological systems. Yet, implementation remains challenging due to nuclease degradation and other cellular factors. Use of l-DNA, the nuclease resistant enantiomer of native d-DNA, provides a promising solution. Read More

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Is behaviourism really dead? A scoping review to document the presence of behaviourism in current medical education.

J Pak Med Assoc 2021 Apr;71(4):1214-1220

Department of Community Medicine, Wah Medical College, Wah Cantt, Rawalpindi, Pakistan.

Behaviourism is the underpinning learning theory of many teaching and assessment tools utilised to enhance the effectiveness of learning. Feedback, reinforcements, motivation, learning outcomes and objectives are a few among many which are implied by the medical teachers while teaching both basic and clinical sciences to students. The claim of behaviourism being redundant or dead is not based on realities. Read More

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Spatial transcriptomics and proteomics technologies for deconvoluting the tumor microenvironment.

Biotechnol J 2021 Jun 14:e2100041. Epub 2021 Jun 14.

Mills Institute for Personalized Cancer Care, Fynn Biotechnologies Ltd., Gangxing 3rd Rd, High-Tech and Innovation Zone, Bldg. 2, Rm. 2201, Jinan City, Shandong Province, 250101, P. R. China.

The tumor microenvironment (TME) harbors heterogeneous contents and plays critical roles in tumorigenesis, metastasis, and drug resistance. Therefore, the deconvolution of the TME becomes increasingly essential to every aspect of cancer research and treatment. Novel spatially-resolved high-plex molecular profiling technologies have been emerging rapidly as powerful tools to obtain in-depth understanding from TME perspectives due to their capacity to allow high-plex protein and RNA profiling while keeping valuable spatial information. Read More

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Label-Free Imaging of Lipid Storage Dynamics in Caenorhabditis elegans using Stimulated Raman Scattering Microscopy.

J Vis Exp 2021 May 28(171). Epub 2021 May 28.

Huffington Center on Aging, Baylor College of Medicine; Department of Molecular and Human Genetics, Baylor College of Medicine; Howard Hughes Medical Institute, Baylor College of Medicine.

Lipid metabolism is a fundamental physiological process necessary for cellular and organism health. Dysregulation of lipid metabolism often elicits obesity and many associated diseases including cardiovascular disorders, type II diabetes, and cancer. To advance the current understanding of lipid metabolic regulation, quantitative methods to precisely measure in vivo lipid storage levels in time and space have become increasingly important and useful. Read More

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A Method to Quantify Behavioral Activities Induced by GABA Agonist Muscimol.

M Rezaul Karim

Bio Protoc 2021 Apr 20;11(8):e3982. Epub 2021 Apr 20.

Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.

Muscimol is a psychoactive isoxazole derived from the mushroom . As a potent GABA receptor agonist, muscimol suppresses the activity of the central nervous system, reduces anxiety and induces sleep. We investigated the effects of muscimol on behavior. Read More

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Immunotherapy in the Treatment of Urothelial Bladder Cancer: Insights From Single-Cell Analysis.

Front Oncol 2021 26;11:696716. Epub 2021 May 26.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Urothelial bladder cancer (UBC) is a global challenge of public health with limited therapeutic options. Although the emergence of cancer immunotherapy, most notably immune checkpoint inhibitors, represents a major breakthrough in the past decade, many patients still suffer from unsatisfactory clinical outcome. A thorough understanding of the fundamental cellular and molecular mechanisms responsible for antitumor immunity may lead to optimized treatment guidelines and new immunotherapeutic strategies. Read More

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Cell/Bacteria-Based Bioactive Materials for Cancer Immune Modulation and Precision Therapy.

Adv Mater 2021 Jun 13:e2100241. Epub 2021 Jun 13.

Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab for Biomaterials, Shenzhen Engineering Laboratory of Nanomedicine and Nanoformulations, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen, 518055, China.

Numerous clinical trials for cancer precision medicine research are limited due to the drug resistance, side effects, and low efficacy. Unsatisfactory outcomes are often caused by complex physiologic barriers and abnormal immune events in tumors, such as tumor target alterations and immunosuppression. Cell/bacteria-derived materials with unique bioactive properties have emerged as attractive tools for personalized therapy in cancer. Read More

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Controlling ion channel trafficking by targeted ubiquitination and deubiquitination.

Methods Enzymol 2021 7;654:139-167. Epub 2021 Apr 7.

Department of Molecular Pharmacology and Therapeutics, Columbia University, Vagelos College of Physicians and Surgeons, New York, NY, United States; Department of Physiology and Cellular Biophysics, Columbia University, Vagelos College of Physicians and Surgeons, New York, NY, United States. Electronic address:

Plasma membrane-localized ion channels are essential for diverse physiological processes such as neurotransmission, muscle contraction, and osmotic homeostasis. The surface density of such ion channels is a major determinant of their function, and tuning this variable is a powerful way to regulate physiology. Dysregulation of ion channel surface density due to inherited or de novo mutations underlies many serious diseases, and molecules that can correct trafficking deficits are potential therapeutics and useful research tools. Read More

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Electronic Family History Screening Tool for Detection of Inherited Cancer Risk: A Prospective Pilot Study.

Am J Med Qual 2021 Jun 10. Epub 2021 Jun 10.

Department of Obstetrics and Gynecology, Kaiser Permanente San Francisco Medical Center, San Francisco, CA Division of Research, Kaiser Permanente Northern California, Oakland, CA Department of Genetics, Kaiser Permanente San Francisco Medical Center, San Francisco, CA National Quality, Kaiser Permanente, Oakland, CA Kaiser Permanente Northern California Gynecologic Cancer Program, San Francisco, CA.

Family history screening to identify individuals at increased risk for hereditary cancers could be a powerful strategy to prevent cancer but is used inconsistently in primary care. The objective was to improve identification of women with at-risk family histories using a point-of-care family history screening tool administered on an electronic tablet device during well-woman appointments. A total of 288 women were invited to participate and 136 women (47. Read More

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Quantum Interferences in Ultraclean Carbon Nanotubes.

Phys Rev Lett 2021 May;126(21):216802

Department of Physics and Astronomy, University of Utah, Salt Lake City, Utah 84112, USA.

Electronic analogs of optical interferences are powerful tools to investigate quantum phenomena in condensed matter. In carbon nanotubes (CNTs), it is well established that an electronic Fabry-Perot interferometer can be realized. Other types of quantum interferences should also arise in CNTs, but have proven challenging to realize. Read More

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Waveguide Enhanced Raman Spectroscopy for Biosensing: A Review.

ACS Sens 2021 Jun 11. Epub 2021 Jun 11.

Zepler Institute for Photonics and Nanoelectronics, University of Southampton, Southampton SO17 1BJ, United Kingdom.

Waveguide enhanced Raman spectroscopy (WERS) utilizes simple, robust, high-index contrast dielectric waveguides to generate a strong evanescent field, through which laser light interacts with analytes residing on the surface of the waveguide. It offers a powerful tool for the direct identification and reproducible quantification of biochemical species and an alternative to surface enhanced Raman spectroscopy (SERS) without reliance on fragile noble metal nanostructures. The advent of low-cost laser diodes, compact spectrometers, and recent progress in material engineering, nanofabrication techniques, and software modeling tools have made realizing portable and cheap WERS Raman systems with high sensitivity a realistic possibility. Read More

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Seeking Illumination: The Path to Chemiluminescent 1,2-Dioxetanes for Quantitative Measurements and Imaging.

Acc Chem Res 2021 Jun 10. Epub 2021 Jun 10.

Department of Chemistry, Southern Methodist University, Dallas, Texas 75275-0314, United States.

ConspectusChemiluminescence is a fascinating phenomenon that evolved in nature and has been harnessed by chemists in diverse ways to improve life. This Account tells the story of our research group's efforts to formulate and manifest spiroadamantane 1,2-dioxetanes with triggerable chemiluminescence for imaging and monitoring important reactive analytes in living cells, animals, and human clinical samples. Analytes like reactive sulfur, oxygen and nitrogen species, as well as pH and hypoxia can be indicators of cellular function or dysfunction and are often implicated in the causes and effects of disease. Read More

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Diversity of dimethylsulfide-degrading methanogens and sulfate-reducing bacteria in anoxic sediments along the Medway Estuary, UK.

Environ Microbiol 2021 Jun 10. Epub 2021 Jun 10.

School of Biological and Chemical Sciences, Queen Mary University of London, London, UK.

Methane is a powerful greenhouse gas but the microbial diversity mediating methylotrophic methanogenesis is not well-characterized. One overlooked route to methane is via the degradation of dimethylsulfide (DMS), an abundant organosulfur compound in the environment. Methanogens and sulfate-reducing bacteria (SRB) can degrade DMS in anoxic sediments depending on sulfate availability. Read More

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Simple and versatile imaging of genomic loci in live mammalian cells and early pre-implantation embryos using CAS-LiveFISH.

Sci Rep 2021 Jun 9;11(1):12220. Epub 2021 Jun 9.

Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.

Visualizing the 4D genome in live cells is essential for understanding its regulation. Programmable DNA-binding probes, such as fluorescent clustered regularly interspaced short palindromic repeats (CRISPR) and transcription activator-like effector (TALE) proteins have recently emerged as powerful tools for imaging specific genomic loci in live cells. However, many such systems rely on genetically-encoded components, often requiring multiple constructs that each must be separately optimized, thus limiting their use. Read More

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How Deep Learning Tools Can Help Protein Engineers Find Good Sequences.

J Phys Chem B 2021 Jun 9. Epub 2021 Jun 9.

Department of Computer Science, Jacobs Building, University of Haifa, 199 Aba Houshi Road, Mount Carmel, Haifa, Israel 3498838.

The deep learning revolution introduced a new and efficacious way to address computational challenges in a wide range of fields, relying on large data sets and powerful computational resources. In protein engineering, we consider the challenge of computationally predicting properties of a protein and designing sequences with these properties. Indeed, accurate and fast deep network oracles for different properties of proteins have been developed. Read More

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A plug-and-play modular microcapillary platform for the generation of multicompartmental double emulsions using glass or fluorocarbon capillaries.

Lab Chip 2021 Jun 8. Epub 2021 Jun 8.

Department of Chemistry, University of Victoria, Victoria, Canada.

Although multiple emulsions have a wide range of applications in biology, medicine, chemistry and cosmetics, the use of microfluidic devices to generate them remains limited to specialist laboratories. This is because of the expertise required to design and operate these technologies. Here we show a plug-and-play microcapillary platform for the generation of multicompartmental double emulsions which only requires a low cost 3D printer for fabrication and syringe pumps for operation. Read More

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Targeted Drug Delivery for Sustainable Crop Protection: Transport and Stability of Polymeric Nanocarriers in Plants.

Adv Sci (Weinh) 2021 06 19;8(11):e2100067. Epub 2021 Mar 19.

Max-Planck-Institut für Polymerforschung, Ackermannweg 10, Mainz, 55128, Germany.

Spraying of agrochemicals (pesticides, fertilizers) causes environmental pollution on a million-ton scale. A sustainable alternative is target-specific, on-demand drug delivery by polymeric nanocarriers. Trunk injections of aqueous nanocarrier dispersions can overcome the biological size barriers of roots and leaves and allow distributing the nanocarriers through the plant. Read More

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UV Photochromism in Transition Metal Oxides and Hybrid Materials.

Small 2021 Jun 8:e2100621. Epub 2021 Jun 8.

Functional Materials and Microsystems Research Group and the Micro Nano Research Facility, RMIT University, Melbourne, Australia.

Limited levels of UV exposure can be beneficial to the human body. However, the UV radiation present in the atmosphere can be damaging if levels of exposure exceed safe limits which depend on the individual the skin color. Hence, UV photochromic materials that respond to UV light by changing their color are powerful tools to sense radiation safety limits. Read More

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Rapid and accurate alignment of nucleotide conversion sequencing reads with HISAT-3N.

Genome Res 2021 Jun 8. Epub 2021 Jun 8.

University of Texas Southwestern Medical Center

Sequencing technologies utilizing nucleotide conversion techniques such as cytosine-to-thymine in bisulfite-seq and thymine-to-cytosine in SLAM-seq are powerful tools to explore the chemical intricacies of cellular processes. To date, no one has developed a unified methodology for aligning converted sequences and consolidating alignment of these technologies in one package. In this paper, we describe HISAT-3N (hierarchical indexing for spliced alignment of transcripts - 3 nucleotides), which can rapidly and accurately align sequences consisting of any nucleotide conversion by leveraging the powerful hierarchical index and repeat index algorithms originally developed for the HISAT software. Read More

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Going deep into schizophrenia with artificial intelligence.

Schizophr Res 2021 Jun 5. Epub 2021 Jun 5.

Department of Electrical Engineering, University of Chile, Santiago, Chile.

Despite years of research, the mechanisms governing the onset, relapse, symptomatology, and treatment of schizophrenia (SZ) remain elusive. The lack of appropriate analytic tools to deal with the heterogeneity and complexity of SZ may be one of the reasons behind this situation. Deep learning, a subfield of artificial intelligence (AI) inspired by the nervous system, has recently provided an accessible way of modeling and analyzing complex, high-dimensional, nonlinear systems. Read More

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Thiophene-Based Optical Ligands That Selectively Detect Aβ Pathology in Alzheimer's Disease.

Chembiochem 2021 Jun 8. Epub 2021 Jun 8.

Linköping University: Linkopings universitet, The Department of Physics,Chemistry and Biology, Linköpings university, 581 83, Linköping, SWEDEN.

In several neurodegenerative diseases, the presence of aggregates of specific proteins in the brain is a significant pathological hallmark; thus, developing ligands able to bind to the aggregated proteins is essential for any effort related to imaging and therapeutics. Here we report the synthesis of thiophene-based ligands containing nitrogen heterocycles. The ligands selectively recognized amyloid-β (Aβ) aggregates in brain tissue from individuals diagnosed neuropathologically as having Alzheimer's disease (AD). Read More

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Impaired humoral and cellular immunity after SARS-CoV2 BNT162b2 (Tozinameran) prime-boost vaccination in kidney transplant recipients.

J Clin Invest 2021 Jun 8. Epub 2021 Jun 8.

Department for General and Visceral Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Novel mRNA-based vaccines have been proven powerful tools to combat the global pandemic caused by SARS-CoV2 with BNT162b2 (trade name: Comirnaty) efficiently protecting individuals from COVID-19 across a broad age range. Still, it remains largely unknown how renal insufficiency and immunosuppressive medication affect development of vaccine induced immunity. We therefore comprehensively analyzed humoral and cellular responses in kidney transplant recipients after the standard second vaccination dose. Read More

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Longitudinal Methods for Modeling Exposures in Pharmacoepidemiologic Studies in Pregnancy.

Epidemiol Rev 2021 Jun 8. Epub 2021 Jun 8.

Department for Health Evidence, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands.

In many perinatal pharmacoepidemiologic studies, exposure to a medication is classified as "ever exposed" versus "never exposed" within each trimester or even over the entire pregnancy. This approach is often far from real-world exposure patterns, may lead to exposure misclassification, and fails to incorporate important aspects such as dosage, timing of exposure, and treatment duration. Alternative exposure modeling methods can better summarize complex individual level medication utilization trajectories or time-varying exposures from information on medication dosage, gestational timing of use, and frequency of use. Read More

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Application of Recombinant Rabies Virus to Xenopus Tadpole Brain.

eNeuro 2021 Jun 7. Epub 2021 Jun 7.

Neuroscience Department and The Dorris Neuroscience Center, The Scripps Research Institute, La Jolla CA

The Xenopus laevis experimental system has provided significant insight into the development and plasticity of neural circuits. Xenopus neuroscience research would be enhanced by additional tools to study neural circuit structure and function. Rabies viruses are powerful tools to label and manipulate neural circuits and have been widely used to study mesoscale connectomics. Read More

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Determining the interactions between postural variability structure and discomfort development using nonlinear analysis techniques during prolonged standing work.

Appl Ergon 2021 Jun 4;96:103489. Epub 2021 Jun 4.

Social Determinants of Health Research Center, Urmia University of Medical Sciences, Urmia, Iran.

Purpose: Nonlinear analysis techniques provide a powerful approach to explore dynamics of posture-related time-varying signals. The aim of this study was to investigate the fundamental interactions between postural variability structure and discomfort development during prolonged standing.

Methods: Twenty participants, with equal distribution for gender and standing work experience (SWE), completed a simulated long-term standing test. Read More

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Rate-Distortion Optimized Graph Coarsening and Partitioning for Light Field Coding.

IEEE Trans Image Process 2021 11;30:5518-5532. Epub 2021 Jun 11.

Graph-based transforms are powerful tools for signal representation and energy compaction. However, their use for high dimensional signals such as light fields poses obvious problems of complexity. To overcome this difficulty, one can consider local graph transforms defined on supports of limited dimension, which may however not allow us to fully exploit long-term signal correlation. Read More

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