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2022 ◽  
Vol 122 ◽  
pp. 108342
Qingsen Yan ◽  
Dong Gong ◽  
Javen Qinfeng Shi ◽  
Anton van den Hengel ◽  
Jinqiu Sun ◽  

2022 ◽  
Vol 8 ◽  
Na Wang ◽  
Shuai Yuan ◽  
Cheng Fang ◽  
Xiao Hu ◽  
Yu-Sen Zhang ◽  

Extracellular vesicles (EVs) are natural nanoparticles secreted by cells in the body and released into the extracellular environment. They are associated with various physiological or pathological processes, and considered as carriers in intercellular information transmission, so that EVs can be used as an important marker of liquid biopsy for disease diagnosis and prognosis. EVs are widely present in various body fluids, among which, urine is easy to obtain in large amount through non-invasive methods and has a small dynamic range of proteins, so it is a good object for studying EVs. However, most of the current isolation and detection of EVs still use traditional methods, which are of low purity, time consuming, and poor efficiency; therefore, more efficient and highly selective techniques are urgently needed. Recently, inspired by the nanoscale of EVs, platforms based on nanomaterials have been innovatively explored for isolation and detection of EVs from body fluids. These newly developed nanotechnologies, with higher selectivity and sensitivity, greatly improve the precision of isolation target EVs from urine. This review focuses on the nanomaterials used in isolation and detection of urinary EVs, discusses the advantages and disadvantages between traditional methods and nanomaterials-based platforms, and presents urinary EV-derived biomarkers for prostate cancer (PCa) diagnosis. We aim to provide a reference for researchers who want to carry out studies about nanomaterial-based platforms to identify urinary EVs, and we hope to summarize the biomarkers in downstream analysis of urinary EVs for auxiliary diagnosis of PCa disease in detail.

2022 ◽  
Fred Lee ◽  
Xinhao Shao ◽  
Yu Gao ◽  
Alexandra Naba

The extracellular matrix (ECM) is a complex and dynamic meshwork of proteins providing structural support to cells. It also provides biochemical signals governing cellular processes including proliferation and migration. Alterations of ECM structure and/or composition has been shown to lead to, or accompany, many pathological processes including cancer and fibrosis. To understand how the ECM contributes to diseases, we first need to obtain a comprehensive characterization of the ECM of tissues and of its changes during disease progression. Over the past decade, mass-spectrometry-based proteomics has become the state-of-the-art method to profile the protein composition of ECMs. However, existing methods do not fully capture the broad dynamic range of protein abundance in the ECM, nor do they permit to achieve the high coverage needed to gain finer biochemical information, including the presence of isoforms or post-translational modifications. In addition, broadly adopted proteomic methods relying on extended trypsin digestion do not provide structural information on ECM proteins, yet, gaining insights into ECM protein structure is critical to better understanding protein functions. Here, we present the optimization of a time-lapsed proteomic method using limited proteolysis of partially denatured samples and the sequential release of peptides to achieve superior sequence coverage as compared to standard ECM proteomic workflow. Exploiting the spatio-temporal resolution of this method, we further demonstrate how 3-dimensional time-lapsed peptide mapping can identify protein regions differentially susceptible to trypsin and can thus identify sites of post-translational modifications, including protein-protein interactions. We further illustrate how this approach can be leveraged to gain insight on the role of the novel ECM protein SNED1 in ECM homeostasis. We found that the expression of SNED1 expression by mouse embryonic fibroblasts results in the alteration of overall ECM composition and the sequence coverage of certain ECM proteins, raising the possibility that SNED1 could modify accessibility to trypsin by engaging in protein-protein interactions.

2022 ◽  
Karel Miettinen ◽  
Nattawat Leelahakorn ◽  
Aldo Almeida ◽  
Yong Zhao ◽  
Lukas Hansen ◽  

Abstract The decriminalization of cannabis and the growing interest in cannabinoids as therapeutics require efficient methods to discover novel compounds and monitor cannabinoid levels in human samples and products. However, current methods are limited by the structural diversity of the active compounds. Here, we construct a G-protein coupled receptor-based yeast whole-cell biosensor, optimize it to achieve high sensitivity and dynamic range, and prove its effectiveness in three real-life applications. First, we screen a library of compounds to discover two novel agonists and four antagonists and demonstrate that our biosensor can democratize GPCR drug discovery by enabling low-cost high-throughput analysis using open-source automation. Subsequently, we bioprospect 54 plants to discover a novel phytocannabinoid, dugesialactone. Finally, we develop a robust portable device, analyze body-fluid samples, and confidently detect illicit synthetic drugs like “Spice”/“K2”. Taking advantage of the extensive sensing repertoire of GPCRs, this technology can be extended to detect numerous other compounds.

Sensors ◽  
2022 ◽  
Vol 22 (2) ◽  
pp. 600
Krzysztof Maniak ◽  
Remigiusz Mydlikowski

This paper analyses the function of an innovative integrated receiver for the measurement of electromagnetic field emissions. The autonomous receiver measures and registers the elevated emission levels of both components of the EM field originating from rocks subjected to increased mechanical stress. The receiver’s sensitivity of 60 µV/m, its dynamic range of 98 dB, and its impulse response of 0.23 V/µs were determined in laboratory conditions. Real EM field signals from hard coal samples subjected to crushing force were recorded using an autonomous receiver. The observed and recorded results confirm that the receiver operates in the full range of amplitudes of the EM field signal emitted from the rock. The results determine the band of characteristic signals for EM field emission from hard coal. The system created on the basis of autonomous EM receivers can support the existing seismic safety systems in real mine conditions by predicting the possibility of mine collapse hazards.

2022 ◽  
Jae-Ik Lee ◽  
Richard Seist ◽  
Stephen McInturff ◽  
Daniel J Lee ◽  
Christian Brown ◽  

Cochlear implants (CIs) strive to restore hearing to those with severe to profound hearing loss by artificially stimulating the auditory nerve. While most CI users can understand speech in a quiet environment, hearing that utilizes complex neural coding (e.g., appreciating music) has proved elusive, probably because of the inability of CIs to create narrow regions of spectral activation. Several novel approaches have recently shown promise for improving spatial selectivity, but substantial design differences from conventional CIs will necessitate much additional safety testing before clinical viability is established. Outside the cochlea, magnetic stimulation from small coils (micro-coils) has been shown to confine activation more narrowly than that from conventional micro-electrodes, raising the possibility that coil-based stimulation of the cochlea could improve the spectral resolution of CIs. To explore this, we delivered magnetic stimulation from micro-coils to multiple locations of the cochlea and measured the spread of activation utilizing a multi-electrode array inserted into the inferior colliculus; responses to magnetic stimulation were compared to analogous experiments with conventional micro-electrodes as well as to the responses to auditory monotones. Encouragingly, the extent of activation with micro-coils was ~60% narrower than that from electric stimulation and largely similar to the spread arising from acoustic stimulation. The dynamic range of coils was more than three times larger than that of electrodes, further supporting a smaller spread of activation. While much additional testing is required, these results support the notion that coil-based CIs can produce a larger number of independent spectral channels and may therefore improve functional performance. Further, because coil-based devices are structurally similar to existing CIs, fewer impediments to clinical translational are likely to arise.

Micromachines ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 118
Jiamin Chen ◽  
Chenyang Xue ◽  
Yongqiu Zheng ◽  
Jiandong Bai ◽  
Xinyu Zhao ◽  

The ideal development direction of the fiber-optic acoustic sensor (FOAS) is toward broadband, a high sensitivity and a large dynamic range. In order to further promote the acoustic detection potential of the Fabry–Pérot etalon (FPE)-based FOAS, it is of great significance to study the acoustic performance of the FOAS with the quality (Q) factor of FPE as the research objective. This is because the Q factor represents the storage capability and loss characteristic of the FPE. The three FOASs with different Q factors all achieve a broadband response from 20 Hz to 70 kHz with a flatness of ±2 dB, which is consistent with the theory that the frequency response of the FOAS is not affected by the Q factor. Moreover, the sensitivity of the FOAS is proportional to the Q factor. When the Q factor is 1.04×106, the sensitivity of the FOAS is as high as 526.8 mV/Pa. Meanwhile, the minimum detectable sound pressure of 347.33 μPa/Hz1/2  is achieved. Furthermore, with a Q factor of 0.27×106, the maximum detectable sound pressure and dynamic range are 152.32 dB and 107.2 dB, respectively, which is greatly improved compared with two other FOASs. Separately, the FOASs with different Q factors exhibit an excellent acoustic performance in weak sound detection and high sound pressure detection. Therefore, different acoustic detection requirements can be met by selecting the appropriate Q factor, which further broadens the application range and detection potential of FOASs.

2022 ◽  
Lauren Gambill ◽  
August Staubus ◽  
Andrea Ameruoso ◽  
James Chappell

Individual RNA remains a challenging signal to synthetically transduce into different types of cellular information. Here, we describe Ribozyme-ENabled Detection of RNA (RENDR), a plug-and-play strategy that uses cellular transcripts to template the assembly of split ribozymes, triggering splicing reactions that generate orthogonal protein outputs. To identify split ribozymes that require templating for splicing, we used laboratory evolution to evaluate the activities of different split variants of the Tetrahymena thermophila ribozyme. The best design delivered a 93-fold dynamic range of splicing with RENDR controlling fluorescent protein production in response to an RNA input. We resolved a thermodynamic model to guide RENDR design, showed how input signals can be transduced into diverse visual, chemical, and regulatory outputs, and used RENDR to detect an antibiotic resistance phenotype in bacteria. This work shows how transcriptional signals can be monitored in situ using RNA synthetic biology and converted into different types of biochemical information.

2022 ◽  
Hsiao Chiang ◽  
Daniel Koo ◽  
Masahiro Kitano ◽  
Jay Unruh ◽  
Le Trinh ◽  

Abstract The expanded application of fluorescence imaging in biomedical and biological research towards more complex systems and geometries requires tools that can analyze a multitude of components at widely varying time- and length-scales. The major challenge in such complex imaging experiments is to cleanly separate multiple fluorescent labels with overlapping spectra from one another and background autofluorescence, without perturbing the sample with high levels of light. Thus, there is a requirement for efficient and robust analysis tools capable of quantitatively separating these signals. In response, we have combined multispectral fluorescence microscopy with hyperspectral phasors and linear unmixing to create Hybrid Unmixing (HyU). Here we demonstrate its capabilities in the dynamic imaging of multiple fluorescent labels in live, developing zebrafish embryos. HyU is more sensitive to low light levels of fluorescence compared to conventional linear unmixing approaches, permitting better multiplexed volumetric imaging over time, with less bleaching. HyU can also simultaneously image both bright exogenous and dim endogenous labels because of its high dynamic range. This allows studies of cellular behaviors, tagged components, and cell metabolism within the same specimen, offering a powerful window into the orchestrated complexity of biological systems.

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