Comparison Study on Single Nucleotide Transport Phenomena in Carbon Nanotubes.

To be considered as a promising candidate for mimicking biological nanochannels, carbon nanotubes (CNTs) have been used to explore the mass transport phenomena in recent years. In this study, the single nucleotide transport phenomena are comparatively studied using individual CNTs with a length of ∼15 µm and diameters ranging from 1.5 to 2.5 nm. In the case of CNTs with a diameter of 1.57-1.98 nm, the current traces of nucleotide transport are independent with the metallicity of CNTs and consist of single peak current pulses, whereas extraordinary stepwise current signals are observed in CNT with a diameter of 2.33 nm. It suggests that there is only one molecule in the nanochannel at a time until the diameter of CNT increases to 2.33 nm. Furthermore, it also demonstrates that the single nucleotides can be identified statistically according to their current pulses, indicating the potential application of CNT-based sensors for nucleotides identification.

Neuroprotective effects of probiotics on anxiety- and depression-like disorders in stressed mice by modulating tryptophan metabolism and the gut microbiota.

Anxiety- and depression-like behaviors are commonly observed clinical features of depression and many other mental disorders. Recent evidence has revealed the crucial role of the microbiota-gut-brain axis in the bidirectional communication between the gastrointestinal tract and the central nervous system. Supplementation with psychobiotics may provide a novel approach for the adjunctive treatment of mental disorders by regulating the intestinal microecology. We isolated and identified a novel probiotic, Lactiplantibacillus plantarum D-9 (D-9), from traditional Chinese fermented foods in our previous work, which exhibited a high yield of gamma-aminobutyric acid (GABA). Herein, it was proved that the oral administration of D-9 could alleviate the depression- and anxiety-like behaviors of Chronic Unpredicted Mild Stress (CUMS) mice, and show non-toxicity or side-effects in the mice. Physiological and biochemical analyses demonstrated that D-9 regulated tryptophan metabolism, the HPA-axis and inflammation in CUMS mice. Moreover, D-9 modulated the structure and composition of the gut microbiota, leading to an increase in the relative abundance of Ligilactobacillus murinus and Lactobacillus johnsonii, and a decrease in the levels of Kineothrix alysoides and Helicobacter bilis compared to those in CUMS mice. Our work demonstrates that D-9 alleviated anxiety- and depression-like disorders in CUMS mice by modulating tryptophan metabolism and the gut microbiota. These findings provide an innovative strategy for the intervention and treatment of depressive disorders.

Bifidobacterium pseudonumeratum W112 alleviated depressive and liver injury symptoms induced by chronic unpredictable mild stress via gut-liver-brain axis.

Introduction: Several studies indicated that depression is associated with liver injury. The role of probiotics in alleviating depression is focused on improving the abnormalities of the central nervous system through the gut-brain axis, while the effect on liver injury is still unclear. The aim of this study was to elucidate the potential link between the antidepressant effect of a potential probiotic strain Bifidobacterium pseudocatenulatum W112 and its effect on alleviating liver injury. Methods: The 4-week-old Kunming mice were exposed to chronic stress for 4 weeks to establish a depression model. Results: The depression-like behavior and related biomakers in chronic unpredictable mild stress (CUMS) mice were altered by supplemented with W112 for 2 weeks. Meanwhile, the modulation effect of W112 the gut microbiota in CUMS mice also result in an increase in the abundance of beneficial bacteria and a decrease in the abundance of harmful bacteria. Significantly, liver injury was observed in CUMS model mice. W112 improved liver injury by reducing AST/ALT in serum. Quantitative PCR results indicated that the mechanism of action of W112 in ameliorating liver injury was that the altered gut microbiota affected hepatic phospholipid metabolism and bile acid metabolism. Discussion: In short, W112 could significantly improve the depressive and liver injury symptoms caused by CUMS. The gut-liver-brain axis is a potential connecting pathway between the antidepressant effects of W112 and its alleviation of liver injury.

Low-noise and high-speed trans-impedance amplifier for nanopore sensor.

The small current detection circuit is the core component of the accurate detection of the nanopore sensor. In this paper, a compact, low-noise, and high-speed trans-impedance amplifier is built for the nanopore detection system. The amplifier consists of two amplification stages. The first stage performs low-noise trans-impedance amplification by using ADA4530-1, which is a high-performance FET operational amplifier, and a high-ohm feedback resistor of 1 GΩ. The high pass shelf filter in the second stage recovers the higher frequency above the 3 dB cutoff in the first stage to extend the maximum bandwidth up to 50 kHz. The amplifier shows a low noise below sub-2 pA rms when tuned to have a bandwidth of around 5 kHz. It also guarantees a stable frequency response in the nanopore sensor.

A novel dielectric breakdown apparatus for solid-state nanopore fabrication with transient high electric field.

The dielectric breakdown used to fabricate solid-state nanopores has separated the device from capital-intensive industries and has been widely adopted by various research teams, but there are still problems with low production efficiency and uncertain location. In this work, based on the transient breakdown phenomenon of nanofilms, a new type of dielectric breakdown apparatus for nanopore fabrication is reported. It integrates both nano-manipulation technology and dielectric breakdown nanopore fabrication technology. The nanometer distance detection method and circuit are introduced in detail. The generation principle and procedures of the transient high electric field are explained step by step. The characterization of the nanopores shows that this apparatus can fabricate sub-2 nm nanopores at a pre-located position. Besides, the nanopore diameter can be easily adjusted by setting the transient high electric field value.

Nanopore Fabrication via Transient High Electric Field Controlled Breakdown and Detection of Single RNA Molecules.

The fabrication of nanopores through a dielectric breakdown method, achieved by simple, low-cost desktop setups, has promoted the research of solid-state nanopore sensing. This paper reports a method for fabricating nanopores. This method uses transient high electric field controlled breakdown (THCBD) to form electric-field-dependent nanopores with different diameters in the order of milliseconds. By manipulating a micropipette with a high electric field to establish the meniscus contact with the SiNx membrane, nanopores can be formed through an "auto-brake" fabrication process. Compared with the traditional dielectric breakdown, THCBD can greatly shorten the breakdown time and form pores of different sizes under higher electric fields without causing additional damage to the SiNx membrane. The nanopores formed by this method can be successfully used to detect two types of RNA molecules. One is transfer RNA from yeast extract and the other is a synthetic RNA oligonucleotide fragment (rArArArArArArArArArArArA).

Reduction chemistry-assisted nanopore determination method for immunoglobulin isotypes.

Immunoglobulins can bind to an unlimited array of foreign antigens presented to the immune system. Among those isotypes, IgG and IgM play crucial roles in initial immune defense associated with innate immunity factors. Hence, the determination of IgG and IgM deficiencies or varying concentrations is widely used as a diagnostic indicator for immune deficiency disorders. Herein, we report a reduction chemistry-assisted nanopore method for IgG and IgM determination. TCEP (tris(2-carboxyethyl)phosphine) was used to cleave Ig proteins in fragments by means of disulfide bond reduction under different experimental conditions. This strategy enabled the observation of distinguishable current signals afforded by separated polypeptide fragments in an αHL nanopore. Together with molecular dynamics (MD) simulation results, highly effective electrostatic potentials and H-bonds, the dominant factors for these current signals, facilitated the capture of Ig fragments in an α-HL nanopore. More importantly, the signature signals were applicable for differentiating between IgG and IgM in blood serum without any problems of protein adsorption and clogging in the nanopore sensing. Furthermore, with comparative sensing sensitivity and selectivity, it is concluded that our method is a label-free single-molecule approach to measuring disease states that present as a result of the absence or over presence of immunoglobulin isotypes.