Loss of tactile sensation is a common occurrence in patients with traumatic peripheral nerve injury or soft tissue loss, but as yet, solutions for restoring such sensation are limited. Implanted neuro-prosthetics are a promising direction for tactile sensory restoration, but available technologies have substantial shortcomings, including complexity of use and of production and the need for an external power supply. In this work, we propose, fabricate, and demonstrate the use of a triboelectric nanogenerator (TENG) as a relatively simple, self-powered, biocompatible, sensitive, and flexible device for restoring tactile sensation. This integrated tactile TENG (TENG-IT) device is implanted under the skin and translates tactile pressure into electrical potential, which it relays via cuff electrodes to healthy sensory nerves, thereby stimulating them, to mimic tactile sensation. We show that the device elicits electrical activity in sensory neurons in vitro, and that the extent of this activity is dependent on the level of tactile pressure applied to the device. We subsequently demonstrate the TENG-IT in vivo, showing that it provides tactile sensation capabilities (as measured by a von Frey test) to rats in which sensation in the hindfoot was blocked through transection of the distal tibial nerve. These findings point to the substantial potential of self-powered TENG-based implanted devices as a means of restoring tactile sensation.This review will focus on the process of amyloid-type protein aggregation. Amyloid fibrils are an important hallmark of protein misfolding diseases and therefore have been investigated for decades. Only recently, however, atomic or near-atomic resolution structures have been elucidated from various in vitro and ex vivo obtained fibrils. In parallel, the process of fibril formation has been studied in vitro under highly artificial but comparatively reproducible conditions. The review starts with a summary of what is known and speculated from artificial in vitro amyloid-type protein aggregation experiments. https://www.selleckchem.com/products/tp0427736-hcl.html A partially hypothetic fibril selection model will be described that may be suitable to explain why amyloid fibrils look the way they do, in particular, why at least all so far reported high resolution cryo-electron microscopy obtained fibril structures are in register, parallel, cross-β-sheet fibrils that mostly consist of two protofilaments twisted around each other. An intrinsic feature of the model is the prion-like nature of all amyloid assemblies. Transferring the model from the in vitro point of view to the in vivo situation is not straightforward, highly hypothetic, and leaves many open questions that need to be addressed in the future.Forensic analysis of seized drug evidence often involves determining whether the components of an unknown mixture are illicit compounds. One approach to this task is to screen the evidence using direct analysis in real time mass spectrometry (DART-MS) to make presumptive identifications. This manuscript introduces a new library-search algorithm that enhances presumptive identifications of mixture components using a series of in-source collision-induced dissociation mass spectra collected through DART-MS. The multistage search, titled the Inverted Library-Search Algorithm (ILSA), identifies potential components in a mixture by first searching the lowest fragmentation mass spectrum for target peaks, assuming these peaks are protonated molecules, and then scoring each target peak with possible library matches. As a proof of concept, the ILSA is demonstrated through several example searches of model seized drug mixtures of acetyl fentanyl, benzyl fentanyl, amphetamine, and methamphetamine searched against a small library of select compounds and the freely available NIST DART-MS Forensics Database. Discussion of the search results and several open areas of research to further extend the method are provided. This new approach for presumptive identification provides analysts with refined information about mixture components and will be of immediate importance in forensic analysis using DART-MS. A prototype implementation of the ILSA is available at https//github.com/asm3-nist/DART-MS-DST.Metalloproteins are an important class of proteins involved in metal uptake, transport, and electron-transfer reactions. Mimicking the active sites of these proteins through miniaturization is an active area of research with applications in biotechnology and medicine. Azurin is a 128-residue copper-binding cupredoxin protein involved in electron-transfer reactions. Previous studies have reported on the copper-binding-induced spectroscopic and structural properties of peptide loops (11 and 13 residues) from azurin. These azurin peptides exhibited novel stoichiometries. However, the underlying mechanism of fluorescence quenching upon copper binding remains to be understood, whether it is due to electron transfer, energy transfer, or both. Here, we report nickel-binding-associated spectroscopic and structural properties of the azurin peptides. They develop a β-turn upon nickel binding as seen in circular dichroism and exhibit electronic transitions centered at 270 and 450 nm. Unlike copper, which exhibited 11 and 12 peptidemetal stoichiometries, nickel exhibited only a 11 stoichiometry. Tryptophan-containing peptides showed fluorescence quenching upon nickel binding, which is due to electron transfer. These results further suggest that the quenching in copper-bound peptides is also due to electron transfer, which could not be ascertained in previous studies. Overall, azurin peptides provide a platform for studying metal-induced structural and spectroscopic properties using transition-metal ions.Pancreatic adenocarcinoma (PA) is one of the deadliest human malignancies. However, early detection, prediction of surgical resectability, and prognosis of PA are challenging with current conventional imaging technologies in the clinic. Molecular imaging technologies combined with novel imaging probes could be useful for early detection and accurate staging of PA. Integrin αvβ6 and α5β1 are found to be overexpressed in PA. In this study, integrin αvβ6/α5β1-bitargeted probes 99mTc-HYNIC-isoDGR (99mTc-isoDGR) and 99mTc-HYNIC-PEG4-PisoDGR2 (99mTc-3PisoDGR2) were prepared and evaluated in the BxPC-3 human pancreatic tumor model. Both subcutaneous and in situ BxPC-3 tumors could be clearly visualized by 99mTc-isoDGR nanoScan SPECT/CT imaging with a high ratio of tumor to background. The blocking study with excess nonradioactive peptide showed a significantly reduced tumor uptake, which confirmed the specificity of 99mTc-isoDGR. Biodistribution results confirmed the imaging results. The dimer tracer 99mTc-3PisoDGR2 significantly enhanced tumor uptake compared with 99mTc-isoDGR, and the spontaneous PA lesion in the mouse model could be clearly visualized by 99mTc-3PisoDGR2.
Loss of tactile sensation is a common occurrence in patients with traumatic peripheral nerve injury or soft tissue loss, but as yet, solutions for restoring such sensation are limited. Implanted neuro-prosthetics are a promising direction for tactile sensory restoration, but available technologies have substantial shortcomings, including complexity of use and of production and the need for an external power supply. In this work, we propose, fabricate, and demonstrate the use of a triboelectric nanogenerator (TENG) as a relatively simple, self-powered, biocompatible, sensitive, and flexible device for restoring tactile sensation. This integrated tactile TENG (TENG-IT) device is implanted under the skin and translates tactile pressure into electrical potential, which it relays via cuff electrodes to healthy sensory nerves, thereby stimulating them, to mimic tactile sensation. We show that the device elicits electrical activity in sensory neurons in vitro, and that the extent of this activity is dependent on the level of tactile pressure applied to the device. We subsequently demonstrate the TENG-IT in vivo, showing that it provides tactile sensation capabilities (as measured by a von Frey test) to rats in which sensation in the hindfoot was blocked through transection of the distal tibial nerve. These findings point to the substantial potential of self-powered TENG-based implanted devices as a means of restoring tactile sensation.This review will focus on the process of amyloid-type protein aggregation. Amyloid fibrils are an important hallmark of protein misfolding diseases and therefore have been investigated for decades. Only recently, however, atomic or near-atomic resolution structures have been elucidated from various in vitro and ex vivo obtained fibrils. In parallel, the process of fibril formation has been studied in vitro under highly artificial but comparatively reproducible conditions. The review starts with a summary of what is known and speculated from artificial in vitro amyloid-type protein aggregation experiments. https://www.selleckchem.com/products/tp0427736-hcl.html A partially hypothetic fibril selection model will be described that may be suitable to explain why amyloid fibrils look the way they do, in particular, why at least all so far reported high resolution cryo-electron microscopy obtained fibril structures are in register, parallel, cross-β-sheet fibrils that mostly consist of two protofilaments twisted around each other. An intrinsic feature of the model is the prion-like nature of all amyloid assemblies. Transferring the model from the in vitro point of view to the in vivo situation is not straightforward, highly hypothetic, and leaves many open questions that need to be addressed in the future.Forensic analysis of seized drug evidence often involves determining whether the components of an unknown mixture are illicit compounds. One approach to this task is to screen the evidence using direct analysis in real time mass spectrometry (DART-MS) to make presumptive identifications. This manuscript introduces a new library-search algorithm that enhances presumptive identifications of mixture components using a series of in-source collision-induced dissociation mass spectra collected through DART-MS. The multistage search, titled the Inverted Library-Search Algorithm (ILSA), identifies potential components in a mixture by first searching the lowest fragmentation mass spectrum for target peaks, assuming these peaks are protonated molecules, and then scoring each target peak with possible library matches. As a proof of concept, the ILSA is demonstrated through several example searches of model seized drug mixtures of acetyl fentanyl, benzyl fentanyl, amphetamine, and methamphetamine searched against a small library of select compounds and the freely available NIST DART-MS Forensics Database. Discussion of the search results and several open areas of research to further extend the method are provided. This new approach for presumptive identification provides analysts with refined information about mixture components and will be of immediate importance in forensic analysis using DART-MS. A prototype implementation of the ILSA is available at https//github.com/asm3-nist/DART-MS-DST.Metalloproteins are an important class of proteins involved in metal uptake, transport, and electron-transfer reactions. Mimicking the active sites of these proteins through miniaturization is an active area of research with applications in biotechnology and medicine. Azurin is a 128-residue copper-binding cupredoxin protein involved in electron-transfer reactions. Previous studies have reported on the copper-binding-induced spectroscopic and structural properties of peptide loops (11 and 13 residues) from azurin. These azurin peptides exhibited novel stoichiometries. However, the underlying mechanism of fluorescence quenching upon copper binding remains to be understood, whether it is due to electron transfer, energy transfer, or both. Here, we report nickel-binding-associated spectroscopic and structural properties of the azurin peptides. They develop a β-turn upon nickel binding as seen in circular dichroism and exhibit electronic transitions centered at 270 and 450 nm. Unlike copper, which exhibited 11 and 12 peptidemetal stoichiometries, nickel exhibited only a 11 stoichiometry. Tryptophan-containing peptides showed fluorescence quenching upon nickel binding, which is due to electron transfer. These results further suggest that the quenching in copper-bound peptides is also due to electron transfer, which could not be ascertained in previous studies. Overall, azurin peptides provide a platform for studying metal-induced structural and spectroscopic properties using transition-metal ions.Pancreatic adenocarcinoma (PA) is one of the deadliest human malignancies. However, early detection, prediction of surgical resectability, and prognosis of PA are challenging with current conventional imaging technologies in the clinic. Molecular imaging technologies combined with novel imaging probes could be useful for early detection and accurate staging of PA. Integrin αvβ6 and α5β1 are found to be overexpressed in PA. In this study, integrin αvβ6/α5β1-bitargeted probes 99mTc-HYNIC-isoDGR (99mTc-isoDGR) and 99mTc-HYNIC-PEG4-PisoDGR2 (99mTc-3PisoDGR2) were prepared and evaluated in the BxPC-3 human pancreatic tumor model. Both subcutaneous and in situ BxPC-3 tumors could be clearly visualized by 99mTc-isoDGR nanoScan SPECT/CT imaging with a high ratio of tumor to background. The blocking study with excess nonradioactive peptide showed a significantly reduced tumor uptake, which confirmed the specificity of 99mTc-isoDGR. Biodistribution results confirmed the imaging results. The dimer tracer 99mTc-3PisoDGR2 significantly enhanced tumor uptake compared with 99mTc-isoDGR, and the spontaneous PA lesion in the mouse model could be clearly visualized by 99mTc-3PisoDGR2.
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