SARS-CoV‑2 Variant Screening Using a Virus-Receptor-Based Electrical Biosensor

SARS-CoV-2 variants are of particular interest because they can potentially increase the transmissibility and virulence of COVID-19 or reduce the effectiveness of available vaccines. However, screening SARS-CoV-2 variants is a challenge because biosensors target viral components that can mutate. One promising strategy is to screen variants via angiotensin-converting enzyme 2 (ACE2), a virus receptor shared by all known SARS-CoV-2 variants. Here we designed a highly sensitive and portable COVID-19 screening biosensor based on the virus receptor. We chose a dual-gate field-effect transistor to overcome the low sensitivity of virus-receptor-based biosensors. To optimize the biosensor, we introduced a synthetic virus that mimics the important features of SARS-CoV-2 (size, bilayer structure, and composition). The developed biosensor successfully detected SARS-CoV-2 in 20 min and showed sensitivity comparable to that of molecular diagnostic tests (∼165 copies/mL). Our results indicate that a virus-receptor-based biosensor can be an effective strategy for screening infectious diseases to prevent pandemics

Co-Delivery of Protein and Small Molecule Therapeutics Using Nanoparticle-Stabilized Nanocapsules

Combination therapy employing proteins and small molecules provides access to synergistic treatment strategies. Co-delivery of these two payloads is challenging due to the divergent physicochemical properties of small molecule and protein cargos. Nanoparticle-stabilized nanocapsules (NPSCs) are promising for combination treatment strategies since they have the potential to deliver small molecule drugs and proteins simultaneously into the cytosol. In this study, we loaded paclitaxel into the hydrophobic core of the NPSC and self-assembled caspase-3 and nanoparticles on the capsule surface. The resulting combination NPSCs showed higher cytotoxicity than either of the single agent NPSCs, with synergistic action established using combination index values

Direct Delivery of Functional Proteins and Enzymes to the Cytosol Using Nanoparticle-Stabilized Nanocapsules

Intracellular protein delivery is an important tool for both therapeutic and fundamental applications. Effective protein delivery faces two major challenges: efficient cellular uptake and avoiding endosomal sequestration. We report here a general strategy for direct delivery of functional proteins to the cytosol using nanoparticle-stabilized capsules (NPSCs). These NPSCs are formed and stabilized through supramolecular interactions between the nanoparticle, the protein cargo, and the fatty acid capsule interior. The NPSCs are ∼130 nm in diameter and feature low toxicity and excellent stability in serum. The effectiveness of these NPSCs as therapeutic protein carriers was demonstrated through the delivery of fully functional caspase-3 to HeLa cells with concomitant apoptosis. Analogous delivery of green fluorescent protein (GFP) confirmed cytosolic delivery as well as intracellular targeting of the delivered protein, demonstrating the utility of the system for both therapeutic and imaging applications

Livskvalitet hos HIV/Aidspositiva

Syftet med denna studie var att få fördjupad kunskap om hur vuxna kvinnor och män med hiv/aids uppger att de upplever sin livskvalitet. Metoden är en litteraturstudie, enligt Polit et al (2001) och baseras på tio vetenskapliga artiklar. Resultatet visade att fysiska faktorer var de som betonades mest men att det var de emotionella faktorerna som påverkade individen mest för upplevande av livskvalitet. Faktorer som äktenskap, sjukdomsgrad, inkomst, arbete och även utbildning är andra faktorer som påverkar livskvaliteten hos hiv/aidssjuka. Målet med litteraturstudien är att förmedla kunskap för att kunna medverka till en optimal vård till personer med hiv/aids. För god vård krävs både kunskap och förståelse för hur dessa individer upplever sin livskvalitet samt vilka faktorer som kan påverka livskvaliteten.The purpose of this study was to get a deeper knowledge as to how adults with HIV/AIDS express their own experiences of quality of life. The method was a literature study, according to Polit et al (2001) which was based upon scientific articles. Ten articles were included in the study. Results of the study showed that physical factors were those who were most emphasized although the emotional factors did have more impact on the individual concerning their experience of quality of life. Factors such as marriage, level of sickness, income, work and education are other factors which affect the quality of life of people with HIV/AIDS. The aim of the study was to convey knowledge so that people with HIV/AIDS can receive high-quality health care. It takes knowledge and understanding how these individuals experience their quality of life to achieve a high quality health care for them, and also knowledge about what factors affect their life quality

Selective Cell–Cell Adhesion Regulation via Cyclic Mechanical Deformation Induced by Ultrafast Nanovibrations

The adoption of dynamic mechanomodulation to regulate cellular behavior is an alternative to the use of chemical drugs, allowing spatiotemporal control. However, cell-selective targeting of mechanical stimuli is challenging due to the lack of strategies with which to convert macroscopic mechanical movements to different cellular responses. Here, we designed a nanoscale vibrating surface that controls cell behavior via selective repetitive cell deformation based on a poroelastic cell model. The vibrating indentations induce repetitive water redistribution in the cells with water redistribution rates faster than the vibrating rate; however, in the opposite case, cells perceive the vibrations as a one-time stimulus. The selective regulation of cell–cell adhesion through adjusting the frequency of nanovibration was demonstrated by suppression of cadherin expression in smooth muscle cells (fast water redistribution rate) with no change in vascular endothelial cells (slow water redistribution rate). This technique may provide a new strategy for cell-type-specific mechanical stimulation

Stimuli-Responsive Adaptive Nanotoxin to Directly Penetrate the Cellular Membrane by Molecular Folding and Unfolding

Biological nanomachines, including proteins and nucleic acids whose function is activated by conformational changes, are involved in every biological process, in which their dynamic and responsive behaviors are controlled by supramolecular recognition. The development of artificial nanomachines that mimic the biological functions for potential application as therapeutics is emerging; however, it is still limited to the lower hierarchical level of the molecular components. In this work, we report a synthetic machinery nanostructure in which actuatable molecular components are integrated into a hierarchical nanomaterial in response to external stimuli to regulate biological functions. Two nanometers core-sized gold nanoparticles are covered with ligand layers as actuatable components, whose folding/unfolding motional response to the cellular environment enables the direct penetration of the nanoparticles across the cellular membrane to disrupt intracellular organelles. Furthermore, the pH-responsive conformational movements of the molecular components can induce the apoptosis of cancer cells. This strategy based on the mechanical motion of molecular components on a hierarchical nanocluster would be useful to design biomimetic nanotoxins