Mcgarryasmussen2058

Although protein therapeutics is of significance in therapeutic intervention of cancers, controlled delivery of therapeutic proteins still faces substantial challenges including susceptibility to degradation and denaturation and poor membrane permeability. Herein, we report a sialic acid (SA)-imprinted biodegradable silica nanoparticles (BS-NPs)-based protein delivery strategy for targeted cancer therapy. Cytotoxic ribonuclease A (RNase A) was effectively caged in the matrix of disulfide-hybridized silica NPs (encapsulation efficiency of ∼64%), which were further functionalized with cancer targeting capability via surface imprinting with SA as imprinting template. Such nanovectors could not only maintain high stability in physiological conditions but also permit redox-triggered biodegradation for both concomitant release of the loaded therapeutic cargo and in vivo clearance. In vitro experiments confirmed that the SA-imprinted RNase A@BS-NPs could selectively target SA-overexpressed tumor cells, promote cells uptake, and subsequently be cleaved by intracellular glutathione (GSH), resulting in rapid release kinetics and enhanced cell cytotoxicity. In vivo experiments further confirmed that the SA-imprinted RNase A@BS-NPs had specific tumor-targeting ability and high therapeutic efficacy of RNase A in xenograft tumor model. Due to the specific targeting and traceless GSH-stimulated intracellular protein release, the SA-imprinted BS-NPs provided a promising platform for the delivery of biomacromolecules in cancer therapy.Antisense oligonucleotides (ASOs) are single-stranded short nucleic acids that silence the expression of target mRNAs and show increasing therapeutic potential. Since ASOs are internalized by many cell types, both normal and diseased cells, gene silencing in unwanted cells is a significant challenge for their therapeutic use. To address this challenge, we created conditional ASOs that become active only upon detecting transcripts unique to the target cell. As a proof-of-concept, we modified an HIF1α ASO (EZN2968) to generate miRNA-specific conditional ASOs, which can inhibit HIF1α in the presence of a hepatocyte-specific miRNA, miR-122, via a toehold exchange reaction. We characterized a library of nucleic acids, testing how the conformation, thermostability, and chemical composition of the conditional ASO impact the specificity and efficacy in response to miR-122 as a trigger signal. Optimally designed conditional ASOs demonstrated knockdown of HIF1α in cells transfected with exogenous miR-122 and in hepatocytes expressing endogenous miR-122. We confirmed that conditional ASO activity was mediated by toehold exchange between miR-122 and the conditional ASO duplex, and the magnitude of the knockdown depended on the toehold length and miR-122 levels. Using the same concept, we further generated another conditional ASO that can be triggered by miR-21. Our results suggest that conditional ASOs can be custom-designed with any miRNA to control ASO activation in targeted cells while reducing unwanted effects in nontargeted cells.Binding agents are a critical component of Si-based anodes for lithium-ion batteries. Herein, we introduce a composite hydrogel binder consisting of carbon black (CB) and guar, which is chemically cross-linked with glutaraldehyde as a means to reinforce the electrode structure during lithiation and improve electronic conductivity. Dynamic rheological measurements are used to monitor the cross-linking reaction and show that rheology plays a significant role in binder performance. The cross-linking reaction occurs at a faster rate and produces stronger networks in the presence of CB, as evidenced from higher gel elastic modulus in guar + CB gels than guar gels alone. Silicon nanoparticle (SiNP) electrodes that use binders with low cross-link densities (trxn 99.8% after 300 cycles at 1-C rate. Low cross-link densities likely increase the capacity of SiNP anodes because of binder-Si hydrogen-bonding interactions that accommodate volume expansions. In addition, the cross-linked binder demonstrates the potential for self-healing, as evidenced by an increased elastic modulus after the gel was mechanically fragmented, which may preserve the electrode microstructure during lithiation and increase capacity retention. The composite hydrogel with integrated conductive additives gives promise to a new type of binder for next-generation lithium-ion batteries.High-performance tactile sensors are urgently demanded in various intensive interactive scenarios, e.g., texture detection, robotic interaction with fragile objects, and motion direction recognition, where dynamic conditions are involved with complex tangential forces or vibrations. Although many microstructured/porous sensors can perceive tangential forces, their isotropic structures that lack programmability lead them to be incapable of sensing the direction of forces and restrain their tunability for complex situations, e.g., a wide sensing range for large forces and high sensitivity for gentle forces. Here, by tuning the programmable microstructures (microcolumns and microfilms) of an elastomeric active layer, we propose a simple principle to flexibly tune the shear sensitivity of an anisotropic porous sensor and bring a 10-fold distinction of anisotropy with a wide range of shear sensitivity (from 0.07 to 0.7 N-1). The fabricated tactile sensors can be used in various robotic manipulations resiliently, for instance, morphology and topology identification of curved surfaces, delicate interactive manipulations, and recognizing the relative motion of two contacting objects. Our work introduces a simple and effective strategy for tailoring flexible shear-sensitive sensors for diverse dexterous robotic manipulations during complex interactions.There is an increasing interest in using photoelectrochemistry for enhancing the signal-to-noise ratio and sensitivity of electrochemical biosensors. Nevertheless, it remains challenging to create photoelectrochemical biosensors founded on stable material systems that are also easily biofunctionalized for sensing applications. Herein, a photoelectrochemical immunosensor is reported, in which the concentration of the target protein directly correlates to a change in the measured photocurrent. The material system for the photoelectrode signal transducer involves using catecholate ligands to modify the properties of TiO2 nanostructures in a three-pronged approach of morphology tuning, photoabsorption enhancement, and facilitating bioconjugation. The catecholate-modified TiO2 photoelectrode is combined with a signal-off direct immunoassay to detect interleukin-6 (IL-6), a key biomarker for diagnosing and monitoring various diseases. Catecholate ligands are added during hydrothermal synthesis of TiO2 to enable the growth of three-dimensional nanostructures to form highly porous photoelectrodes that provide a three-dimensional scaffold for immobilizing capture antibodies. Surface modification by catecholate ligands greatly enhances photocurrent generation of the TiO2 photoelectrodes by improving photoabsorption in the visible range. Additionally, catecholate molecules facilitate bioconjugation and probe immobilization by forming a Schiff-base between their -COH group and the -NH2 group of the capture antibodies. The highest photocurrent achieved herein is 8.89 μA cm-2, which represents an enhancement by a factor of 87 from unmodified TiO2. The fabricated immunosensor shows a limit-of-detection of 3.6 pg mL-1 and a log-linear dynamic range of 2-2000 pg mL-1 for IL-6 in human blood plasma.The following article deals with various considerations concerning the frequently observed occurrence of dental erosion in athletes. It summarizes the basics of erosive tooth wear development as well as special etiologic factors for groups of athletes with increased prevalence of dental erosion and concludes with preventive advice. (Originally published (in German) in Quintessenz Zahnmed 2021;721008-1017).An undescribed species of freshwater ostracod belonging to the genus Pseudostrandesia Savatenalinton and Martens, 2009 was collected from two pet shops in the Kanto region of central Japan. This species, herein named Pseudostrandesia tenebrarum sp. nov., is similar to four species previously reported from Southeast Asia, but can be distinguished by carapace and appendage features. It is the second species of the genus for which males are known. Vorinostat nmr Of the nine previously described species in the genus, one is exclusively known from Turkey, and the others are found in Southeast Asia and the vicinity, one of which is also recorded in India and east China. There are two scenarios to explain the existence of Pseudostrandesia tenebrarum sp. link2 nov. in pet shops in Japan it is either native to Japan but has yet to be discovered in its natural habitat, or it is an alien species, perhaps unwittingly imported with plants or fish for the pet trade. We review the likelihood of both scenarios, and conclude that although there is insufficient evidence to be sure, it is potentially an alien species in Japan. The most likely origin is Southeast Asia, as evidenced by its close morphological resemblance to particular Southeast Asian species. Juveniles as well as adults were recovered, indicating that this species is reproducing in the pet trade, supporting the notion that it has invasive potential to areas outside of its natural range. link3 The description and report of this species highlights a possible introduction of an alien species to Japan, and facilitates further monitoring.Symbioses between invertebrates are common in the ocean although usually the diversity and specificity of their interactions are not well understood. Parazoanthidae (Cnidaria Anthozoa Zoantharia) is one of the most diverse zoantharian families in terms of numbers of genera and species. Species in this family are commonly associated with various other invertebrates that they utilize as their substrate. Previous studies have re-organized the taxonomy of Parazoanthidae and revealed a strong specificity between many parazoanthid species and genera and their substrates. However, our understanding of the species diversity of Parazoanthidae is far from complete, as parazoanthids are often overlooked in sampling surveys. In this study, we establish three subgenera under the genus Umimayanthus Montenegro, Sinniger, and Reimer, 2015; the nominotypical Umimayanthus, Paraumimayanthus subgen nov., and Gorgoniazoanthus subgen. nov., based on the finding of a new species, Umimayanthus (Gorgoniazoanthus) kanabou sp. nov., associated with the sea-whip gorgonian Ellisella sp. from approximately 30 m depth in shallow mesophotic coral reef communities in Oura Bay on Okinawajima Island and in Oshima Strait near Amami-Oshima Island, in the Ryukyu Islands, southern Japan. We additionally report on gastropods and crustaceans observed in association with U. kanabou, and these species are thought to potentially prey upon the zoantharians or on gorgonian polyps. Umimayanthus kanabou is phylogenetically closely related to congeneric sponge-associated Umimayanthus spp., further supporting the recent hypothesis that substrate preferences may change during the evolutionary history of zoantharians.