MicroRNAs are short RNA molecules that regulate gene expression. They have been investigated as potential biomarkers because their expression levels are correlated with various diseases. However, the detection of microRNAs in the bloodstream remains difficult because current methods are not sufficiently selective or sensitive. Here, we show that a nanopore sensor based on the alpha-hemolysin protein selectively detected microRNAs at the single molecular level in plasma samples from lung cancer patients without the need for labelling or amplification. The sensor, which used a programmable oligonucleotide probe to generate a target-specific signature signal, was able to quantify sub-picomolar levels of cancer-associated microRNAs and to discriminate single nucleotide differences between microRNA family members. This approach could prove useful for quantitative microRNA detection, biomarker discovery, and the non-invasive early diagnosis of cancer.
Guanine-rich nucleic acids can form G-quadruplexes that are important in gene regulation, biosensor design and nano-structure construction. In this article, we report on the development of a nanopore encapsulating single-molecule method for exploring how cations regulate the folding and unfolding of the G-quadruplex formed by the thrombin-binding aptamer (TBA, GGTTGGTGTGGTTGG). The signature blocks in the nanopore revealed that the G-quadruplex formation is cation-selective. The selectivity sequence is K+ > NH4+ ∼ Ba2+ > Cs+ ∼ Na+ > Li+, and G-quadruplex was not detected in Mg2+ and Ca2+. Ba2+ can form a long-lived G-quadruplex with TBA. However, the capability is affected by the cation–DNA interaction. The cation-selective formation of the G-quadruplex is correlated with the G-quadruplex volume, which varies with cation species. The high formation capability of the K+-induced G-quadruplex is contributed largely by the slow unfolding reaction. Although the Na+- and Li+-quadruplexes feature similar equilibrium properties, they undergo radically different pathways. The Na+-quadruplex folds and unfolds most rapidly, while the Li+-quadruplex performs both reactions at the slowest rates. Understanding these ion-regulated properties of oligonucleotides is beneficial for constructing fine-tuned biosensors and nano-structures. The methodology in this work can be used for studying other quadruplexes and protein–aptamer interactions.
Flexible electronics, which can be distributed on any surface we need, are highly demanded in the development of Internet of Things (IoT), robot technology and electronic skins. Temperature is a fundamental physical parameter, and it is an important indicator in many applications. Therefore, a flexible temperature sensor is required. Here, we report a simple method to fabricate three lightweight, low-cost and flexible temperature sensors, whose sensitive materials are reduced graphene oxide (r-GO), single-walled carbon nanotubes (SWCNTs) and multi-wall carbon nanotubes (MWCNTs). By comparing linearity, sensitive and repeatability, we found that the r-GO temperature sensor had the most balanced performance. Furthermore, the r-GO temperature sensor showed good mechanical properties and it could be bent in different angles with negligible resistance change. In addition, the performance of the r-GO temperature sensor remained stable under different kinds of pressure and was unaffected by surrounding environments, like humidity or other gases, because of the insulating layer on its sensitive layer. The easy-fabricated process and economy, together with the remarkable performance of the r-GO temperature sensor, suggest that it is suitable for use as a robot skin or used in the environment of IoT.
Nanopores are increasingly utilized as tools for single-molecule detection in biotechnology. Many nanopores are fabricated through procedures that require special materials, expensive facilities and experienced operators, which limiting their usefulness on a wide-scale. We have developed a simple method of fabricating a robust, low-noise nanopore by externally penetrating a nanocavity enclosed in the terminal of a capillary pipette. The nanocavity was shown to have a pore size on the scale of a single molecule, verified by translocation of molecules of known sizes, including double-stranded DNA (2 nm), gold nanoparticles (10 nm) and ring-shaped cyclodextrin (1.5 nm). The small pore size allows entrapment of a single cyclodextrin molecule. Cyclodextrin in the nanopore may prove useful as a molecular adapter for chiral enantiomer discrimination.
Background: Missense mutations have been identified in the HIF2A gene in patients with erythrocytosis. Results: A mouse knock-in line that models the first described HIF2A mutation exhibits erythrocytosis and pulmonary hypertension.
Conclusion:The missense mutation is the cause of erythrocytosis, and is accompanied by pulmonary hypertension. Significance: The study demonstrates sequelae of global Hif-2␣ gain of function.
We propose a flexible wireless pressure sensor, which uses a graphene/polydimethylsiloxane (GR/PDMS) sponge as the dielectric layer. The sponge is sandwiched between two surfaces of a folded flexible printed circuit with patterned Cu as the antenna and electrode. By adjusting graphene and NH
4
HCO
3
concentrations, a composite with 20% concentration of NH
4
HCO
3
and 2% concentration of graphene as the dielectric layer is obtained, which exhibits high sensitivity (2.2 MHz/kPa), wide operating range (0–500 kPa), rapid response time (~7 ms), low detection limit (5 Pa), and good stability, recoverability, and repeatability. In addition, the sensor is sensitive to finger bending and facial muscle movements for smile and frown, that are transmitted using wireless electromagnetic coupling; therefore, it has potential for a wide range of applications such as intelligent robots, bionic-electronic skin and wearable electronic devices.
Background: Tibetans have a genetic signature in the coding region of their PHD2 gene. Results: Tibetan PHD2 variant displays markedly impaired binding to the HSP90 cochaperone p23. Conclusion: Because p23 couples PHD2 to HIF-␣ hydroxylation, Tibetans possess a loss of function PHD2 allele. Significance: This study uncovers a mechanism for Tibetan adaptation to high altitude.
Composite membranes have been fabricated made of ultrafine PVDF fibers via a tip-induced electrospinning (TIE) process and Al2O3 nanoparticles via a dip-coating process.
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