Analysis and Compensation of Lorentz Force Magnetic Bearing Magnetic Flux Density Uniformity Error.

Aiming at the influence of the magnetic flux density uniformity error (MFDUE) of the Lorentz force magnetic bearing (LFMB) on the sensitivity accuracy of magnetically suspended control and sensing gyroscopes (MSCSGs) on the angular rate of a spacecraft, a high precision measurement method of the angular rate of a spacecraft based on the MFDUE compensation of LFMB is proposed. Firstly, the structure of MSCSG and the sensitivity principle of MSCSG to the spacecraft angular rate are introduced. The mechanism influencing the accuracy of MSCSG to spacecraft angular rate sensitivity is deduced based on the definition of magnetic flux density uniformity. Secondly, the 3D magnetic flux distribution of LFMB is analyzed using ANSYS. The relationship between the rotor tilt angle, tilt angular rate, and magnetic flux density is established. The induced current calculation model due to MFDUE is proposed, and the LFMB magnetic flux density error compensation is realized. Finally, the simulation results show that the estimation accuracy of the induced current by the proposed method can reach 96%, and the simulation and the experiment show that the error compensation method can improve the accuracy of MSCSG in measuring the spacecraft angular rate by 12.5%.

The single strand template shortening strategy improves the sensitivity and specificity of solid-state nanopore detection.

Through controlling the ssDNA product length of rolling circle amplification with AcyNTP, here we develop a nanopore signal enhancement strategy (STSS), which can successfully transfer the short oligonucleotide targets into long ssDNAs with appropriate lengths that can generate significant translocation currents. By labelling the RCA product with tags such as tetrahedral structures and isothermal amplicons, the resolution, signal specificity, and target range of the STSS can be further extended.

Nanopore sensitization based on a double loop hybridization chain reaction and G-quadruplex.

The widespread implementation of solid-state nanopores faces challenges such as lower resolution and increased electrical noise when compared to biological nanopores. Incorporating specific nucleic acid reactions can enhance resolution. In this study, we've developed a nucleic acid amplifier to enhance the sensitivity of solid-state nanopores, utilizing a G-rich sequence and hybridization chain reaction. This amplifier improves target concentration and volume amplification, showing promise in nanopore sensitivity tests.

A Duplex Polymerization Strategy for General, Programmable and High-Resolution Nanopore-Based Sensing.

Nanopore sensing is highly promising in single molecular analysis but their broad applications have been challenged by the limited strategies that can transduce a target-of-interest into a specific and anti-false/inference signal, especially for solid-state nanopores with relatively lower resolution and higher noise. Here we report a high-resolution signal-production concept named target-induced duplex polymerization strategy (DPS). Through linking the same or different duplex substrates (DSs) with a special linker (L) and an optional structure tag (ST), the DPS can generate target-specific DS polymers with highly controllable duration times, duration intervals and even distinguished secondary tagging currents. Experimentally, DPS mono-polymerization of single DS and co-polymerization of multiple DSs has verified the duration time of a DPS product is the sum of those for each DS monomer. Tetrahedron-DNA structures with different sizes are used as the STs to provide needle-like secondary peaks for further resolution enhancement and multiplex assay. With these examples DPS represents a general, programmable and advanced strategy that may simultaneously provide size-amplification, concentration amplification, and signal-specificity for molecular recognition. It is also promisingly in various applications regarding to single molecular investigation, such as polymerization degree, structure/side chain conformation, programmable multiplex decoding and information index.

Single Molecular Nanopores as a Label-Free Method for Homogeneous Conformation Investigation and Anti-Interference Molecular Analysis.

In this paper, we propose a "reciprocal strategy" that, on the one hand, explores the ability of solid-state nanopores in a homogeneous high-fidelity characterization of nucleic acid assembly and, on the other hand, the formed nucleic acid assembly with a large size serves as an amplifier to provide a highly distinguished and anti-interference signal for molecular sensing. Four-hairpin hybridization chain reaction (HCR) with G-rich tail tags is taken as the proof-of-concept demonstration. G-rich tail tags are commonly used to form G-quadruplex signal probes on the side chain of HCR duplex concatemers. When such G-tailed HCR concatemers translocate the nanopore, abnormal, much higher nanopore signals over normal duplexes can be observed. Combined with atomic force microscopy, we reveal the G-rich tail may easily induce the "intermolecular interaction" between HCR concatemers to form "branched assembly structure (BAS)". To the best of our knowledge, this is the first evidence for the formation BAS of the G tailed HCR concatemers in a homogeneous solution. Systematic nanopore measurements further suggest the formation of these BASs is closely related to the types of salt ions, the amount of G, the concentration of substrate hairpins, the reaction time, and so forth. Under optimized conditions, these BASs can be grown to just the right size without being too large to block the pores, while producing a current 14 times that of conventional double-stranded chains. Here, these very abnormal large current blockages have, in turn, been taken as an anti-interference signal indicator for small targets in order to defend the high noises resulting from co-existing big species (e.g., enzymes or other long double-stranded DNA).

Lego-Like Catalytic Hairpin Assembly Enables Controllable DNA-Oligomer Formation and Spatiotemporal Amplification in Single Molecular Signaling.

While the solid-state nanopore shows increasing potential during sensitive and label-free single molecular analysis, target concentration and signal amplification method is in urgent need. In this article, a solution via designing a model nucleic acid circuit reaction that can produce "Y" shape-structure three-way DNA oligomers with controllable size and polymerization degree is proposed. Such a so-called lego-like three-way catalytic hairpin assembly (LK-3W-CHA) can provide both concentration amplification (via CHA circuit) and programmable size control (via lego-like building mode) to enhance spatiotemporal resolution in single molecular sensing of solid-state nanopore. Oligomers containing 1-4 DNA three-way junctions (Y monomers, Y1-Y4) are designed in proof-of-concept experiments and applications. When the oligomers are applied to direct translocation measurements, Y2-Y4 can significantly increase the signal resolution and stability than that of Y1. Meanwhile, Y1 to Y4 can be used as the tags on the long DNA carrier to provide very legible secondary signals for specific identification, multiple assays, and information storage. Compared with other possible tags, Y1-Y4 provides higher signal density and amplitude, and quasi-linear "inner reference" for each other, which may provide more systematic, reliable, and controllable experimental results.

Dexterous Manipulation for Multi-Fingered Robotic Hands With Reinforcement Learning: A Review.

With the increasing demand for the dexterity of robotic operation, dexterous manipulation of multi-fingered robotic hands with reinforcement learning is an interesting subject in the field of robotics research. Our purpose is to present a comprehensive review of the techniques for dexterous manipulation with multi-fingered robotic hands, such as the model-based approach without learning in early years, and the latest research and methodologies focused on the method based on reinforcement learning and its variations. This work attempts to summarize the evolution and the state of the art in this field and provide a summary of the current challenges and future directions in a way that allows future researchers to understand this field.

Integrating Metabolomics and Network Pharmacology to Explore the Protective Effect of Ginsenoside Re against Radiotherapy Injury in Mice.

Ionizing radiation (IR) can cause radiation damage, mutagenesis, or carcinogenesis in the irradiated subject. It is manifested as metabolic disorders of the body and damage to the immune system, nervous system, and endocrine system, which can lead to physiological and pathological changes and endogenous metabolic disorders. Ginsenoside Re (G-Re), a single component of traditional Chinese medicine, has a certain ameliorating effect on radiation damage. However, its mechanism of action in the treatment of radiotherapy injury remains unclear. With this purpose, the hematopoietic function of mice damaged by X-ray radiation was studied, and the protective effect of G-Re on mice damaged by radiation was preliminarily evaluated. Network pharmacology and metabolomics analysis are used to further reveal the mechanism of G-Re to improve radiation damage through metabolomics research. Results of metabolomics analysis showed that 16 potential biomarkers were identified as participating in the therapeutic effect of G-Re on IR. Most of these metabolites are adjusted to recover after G-Re treatment. The pathways involved included glycerophospholipid metabolism, sphingolipid metabolism, and linoleic acid metabolism. According to network pharmacology analysis, we found 10 hub genes, which is partly consistent with the findings of metabolomics. Further comprehensive analysis focused on 4 key targets, including SRC, EGFR, AKT1, and MAPK8, and their related core metabolites and pathways. This study combines metabolomics and network pharmacology analysis to explore the key targets and mechanisms of G-Re in the treatment of IR, in order to provide new strategies for clinical treatment of radiotherapy injury.

Simple and rapid high-throughput assay to identify HSV-1 ICP0 transactivation inhibitors.

Herpes simplex virus 1 (HSV-1) is a ubiquitous virus that results in lifelong infections due to its ability to cycle between lytic replication and latency. As an obligate intracellular pathogen, HSV-1 exploits host cellular factors to replicate and aid in its life cycle. HSV-1 expresses infected cell protein 0 (ICP0), an immediate-early regulator, to stimulate the transcription of all classes of viral genes via its E3 ubiquitin ligase activity. Here we report an automated, inexpensive, and rapid high-throughput approach to examine the effects of small molecule compounds on ICP0 transactivator function in cells. Two HSV-1 reporter viruses, KOS6ß (wt) and dlx3.1-6ß (ICP0-null mutant), were used to monitor ICP0 transactivation activity through the HSV-1 ICP6 promoter:lacz expression cassette. A ≥10-fold difference in ß-galactosidase activity was observed in cells infected with KOS6ß compared to dlx3.1-6ß, demonstrating that ICP0 potently transactivates the ICP6 promoter. We established the robustness and reproducibility with a Z'-factor score of ≥0.69, an important criterium for high-throughput analyses. Approximately 19,000 structurally diverse compounds were screened and 76 potential inhibitors of the HSV-1 transactivator ICP0 were identified. We expect this assay will aid in the discovery of novel inhibitors and tools against HSV-1 ICP0. Using well-annotated compounds could identify potential novel factors and pathways that interact with ICP0 to promote HSV-1 gene expression.

Low-Noise Solid-State Nanopore Enhancing Direct Label-Free Analysis for Small Dimensional Assemblies Induced by Specific Molecular Binding.

Solid-state nanopores show special potential as a new single-molecular characterization for nucleic acid assemblies and molecular machines. However, direct recognition of small dimensional species is still quite difficult due the lower resolution compared with biological pores. We recently reported a very efficient noise-reduction and resolution-enhancement mechanism via introducing high-dielectric additives (e.g., formamide) into conical glass nanopore (CGN) test buffer. Based on this advance, here, for the first time, we apply a bare CGN to directly recognize small dimensional assemblies induced by small molecules. Cocaine and its split aptamer (Capt assembly) are chosen as the model set. By introducing 20% formamide into CGN test buffer, high cocaine-specific distinguishing of the 113 nt Capt assembly has been realized without any covalent label or additional signaling strategies. The signal-to-background discrimination is much enhanced compared with control characterizations such as gel electrophoresis and fluorescence resonance energy transfer (FRET). As a further innovation, we verify that low-noise CGN can also enhance the resolution of small conformational/size changes happening on the side chain of large dimensional substrates. Long duplex concatamers generated from the hybridization chain reaction (HCR) are selected as the model substrates. In the presence of cocaine, low-noise CGN has sensitively captured the current changes when the 26 nt aptamer segment is assembled on the side chain of HCR duplexes. This paper proves that the introduction of the low-noise mechanism has significantly improved the resolution of the solid-state nanopore at smaller and finer scales and thus may direct extensive and deeper research in the field of CGN-based analysis at both single-molecular and statistical levels, such as molecular recognition, assembly characterization, structure identification, information storage, and target index.

Study on the Functionalization and Signaling Efficiency of the Hybridization Chain Reaction Using Traditional and Single Molecular Characterizations.

As an important enzyme-free amplifier, the hybridization chain reaction (HCR) uses an ssDNA to trigger cycled displacement interactions between substrate hairpins and finally form elongated dsDNA concatamer mixtures. In many cases, to provide a signal probe or advanced function, additional oligonucleotides (named hairpin tails) have to be extended upon classic HCR hairpin substrates, but by doing so the HCR assembly efficiency and signal-to-noise ratio (SNR) may get seriously reduced. In this Article, a rational and general model that may guide the study on HCR functionalization and signaling efficiency is provided. We rationally design a four-hairpin model HCR system (4H-HCR) in which one or more hairpin substrates are appended with additional tails as a signaling probe. After HCR assembly, two adjacent tails are supposedly integrating into a full G-quadruplex structure to provide the evidence or signal for the assembly. A systematic study has been applied to reveal the relationship between the "tail-design" with assembly efficiency and SNR. A clear design rule-set guiding the optimized assembly and signal has been provided for traditional electrophoresis and G-quadruplex-enhanced fluorescence signal. Importantly, solid-state nanopore single molecular detection has been innovatively introduced and recommended as an "antirisk" and "mutual benefit" readout to traditional G-quadruplex signaling. Nanopore detection can provide a clear signal distinguished before and after the HCR reaction, especially when the traditional G-quadruplex-enhanced signal only provides low SNR. The G-quadruplex, in turn, may enhance the nanopore signal amplitude via increasing the diameter of the HCR products.

High-throughput serum metabolomics analysis of gouty arthritis rat treated by total saponins of Rhizoma Dioscoreae Makino by UPLC-Q/TOF-MS.

Rhizoma Dioscoreae Makino (RDM) is effective in treating gouty arthritis (GA) and hyperuricacidemia, especially in promoting uric acid excretion and reducing the inflammatory reaction. Bioactive constituents in RDM are mainly steroidal saponins such as dioscin, trillin, protodioscin and protogracillin. However, the mechanism of its anti-GA action is still unclear, owing to the complex pathological and physiological characteristics of GA, and integration of RDM with multiple components, multiple targets and multiple pathways. Herein, a GA rat model was induced with monosodium urate (MSU), and RDM reduced inflammation of rat synovium tissue. Through metabolomics analysis, 35 potential biomarkers with significant changes involved in the pathogenesis of GA induced by MSU were identified, and perturbations were restored after RDM treatment. The most correlated pathways involved in d-galactose, d-mannose, d-glucose, myoinositol, Phosphatidylcholine (PC) (16:0/16:0), LysoPC (15:0), phosphatidic acid (PA) [18:1(9Z)/18:1(11Z)] and glutathione induced by MSU were galactose metabolism, inositol phosphate metabolism, glycerophospholipid metabolism and glutathione metabolism, and the derivations of all those biomarkers could be regulated by RDM treatment. RDM has a therapeutic effect on GA by intervening in changes in endogenous metabolisms and the related metabolic pathways.

UPLC-MS-based serum metabolomics reveals protective effect of Ganoderma lucidum polysaccharide on ionizing radiation injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum Polysaccharide (GLP),traditional Chinese medicine (TCM) active ingredient, has a long history and has good curative effects on radiation injury. However, the mechanism of GLP treating radiation injury has not been clearly elucidated. THE AIM OF THE STUDY: This study was aimed to investigate the preventive effects of GLP on mice with radiation injury and to explore its mechanisms by serum metabolomics. MATERIALS AND METHODS: Thirty mice were randomly divided into three groups,and namely 10 per group. The normal control group and the radiation model with normal saline and GLP group with GLP treatment (96 mg·kg-1) for 14 days. 2 h after 7th day after the intragastric administration, the model group and GLP group were subjected to whole body irradiation by X-rays except the normal control group. The peripheral blood WBC, RBC, HGB, PLT indicators.UPLC-Q-TOF-MS technique was used to analyze the serum of normal group, model group and GLP group, and to explore its potential key biomarkers and corresponding related metabolic pathways. RESULTS: The number of peripheral blood leukocytes (WBC) in the radiation model group was lower than that in the GLP group and the number of platelets (PLT) in the GLP group was significantly higher than that in the model group.Combined with the methods of principal component analysis (PCA), projection to latent structure-discrimination analysis (PLS-DA), three group were clearly distinguished from each other and 18 metabolites were identified as the potential biomarkers in the GLP treated mice. The identified biomarkers indicated that there were perturbations of the taurine and hypotaurine metabolism and glycerophospholipid metabolism. CONCLUSION: GLP can play a role in radiation protection by improving the expression of related potential biomarkers and related metabolic pathways in serum of radiation-induced mice.

An investigation of solid-state nanopores on label-free metal-ion signalling via the transition of RNA-cleavage DNAzyme and the hybridization chain reaction.

Recent advances have proven solid-state nanopores as a powerful analysis platform that enables label-free and separation-free single-molecule analysis. However, the relatively low resolution still limits its application because many chemicals or targets with small sizes could not be recognized in a label-free condition. In this paper, we provide a possible solution that uses solid-state nanopores for small species signaling via the transition of huge DNA assembly products. DNAzyme responding to metal ions and the hybridization chain reaction (HCR) generating nanopore-detectable dsDNA concatamers are used as the transition model set. By the two-step DNAzyme-HCR transition, Pb2+ that was too tiny to be sensed was successfully recognized by the nanopore. The whole process happened in a completely homogeneous solution without any chemical modification. During condition optimization, we also discussed one possible application challenge that may affect the HCR signal-background distinction. Solid-state nanopores provide a potential solution to this challenge due to its ability to profile product length or even 3D structure information.