Flexible-Arranged Biomimetic Array Integrated with Parallel Entropy-Driven Circuits for Ultrasensitive, Multiple, and Reliable Detection of Cancer-Related MicroRNAs.

With the emergence of microRNA (miRNA) as a promising biomarker in cancer diagnosis, it is significant to develop multiple analyses of miRNAs. However, it still faces difficulties in ensuring the sensitivity and accuracy during multiplex detection owing to the low abundance and experimental deviation of miRNAs. In this work, a flexible-arranged biomimetic array integrated with parallel entropy-driven circuits (EDCs) was developed for ultrasensitive, multiplex, reliable, and high-throughput detection of miRNAs. The biomimetic array was fabricated by arrangement of various photonic crystals (PCs) for adjustable photonic band gaps (PBGs) and specific fluorescence enhancement. Meanwhile, two cancer-related miRNAs and one reference miRNA were introduced as multiple analytes as a proof-of-concept. The parallel EDCs with negligible crosstalk were designed based on the modular property. Because of the one-to-one match between the emitted fluorescence of parallel EDCs and the PBGs of the flexible-arranged biomimetic array, the generated fluorescence signal triggered by target miRNAs can be enhanced on the corresponding domain of the array. Furthermore, the amplified signal of the array was detected with high-throughput scanning, which could reveal specific information on cancer-related miRNAs as well as reference miRNA, enhancing the abundance and reliability of the analysis. The proposed array has the merits of a modular design, flexible deployment, simple operation (nonenzymatic and isothermal), improved accuracy, high sensitivity, and multiplex analysis, showing potential in disease diagnosis.

A Highly Active Porous Mo2C-Mo2N Heterostructure on Carbon Nanowalls/Diamond for a High-Current Hydrogen Evolution Reaction.

Developing non-precious metal-based electrocatalysts operating in high-current densities is highly demanded for the industry-level electrochemical hydrogen evolution reaction (HER). Here, we report the facile preparation of binder-free Mo2C-Mo2N heterostructures on carbon nanowalls/diamond (CNWs/D) via ultrasonic soaking followed by an annealing treatment. The experimental investigations and density functional theory calculations reveal the downshift of the d-band center caused by the heterojunction between Mo2C/Mo2N triggering highly active interfacial sites with a nearly zero ∆GH* value. Furthermore, the 3D-networked CNWs/D, as the current collector, features high electrical conductivity and large surface area, greatly boosting the electron transfer rate of HER occurring on the interfacial sites of Mo2C-Mo2N. Consequently, the self-supporting Mo2C-Mo2N@CNWs/D exhibits significantly low overpotentials of 137.8 and 194.4 mV at high current densities of 500 and 1000 mA/cm2, respectively, in an alkaline solution, which far surpass the benchmark Pt/C (228.5 and 359.3 mV) and are superior to most transition-metal-based materials. This work presents a cost-effective and high-efficiency non-precious metal-based electrocatalyst candidate for the electrochemical hydrogen production industry.

Enhancing Interfacial Capacitance by Boron Doping in Vertically Porous Carbon Toward High-Performance AC Filtering Electrochemical Capacitors.

Electrochemical capacitors (ECs) show great perspective in alternate current (AC) filtering once they simultaneously reach ultra-fast response and high capacitance density. Nevertheless, the structure-design criteria of the two key properties are often mutually incompatible in electrode construction. Herein, it is proposed that combining vertically oriented porous carbon with enhanced interfacial capacitance (Ci ) can efficiently solve this issue. Theoretically, the density function theory calculation shows that the Ci of a carbon electrode can be enhanced by boron doping due to the corresponding compact induced charge layer. Experimentally, the vertical-oriented boron-doped graphene nanowalls (BGNWs) electrodes, whose Ci is enhanced from 4.20 to 10.16 µF cm-2 upon boron doping, are prepared on a large scale (480 cm2 ) using a hot-filament chemical vapor deposition technique (HFCVD). Owing to the high Ci and vertically oriented porous structure, BGNWs-based EC has a high capacitance density of 996 µF cm-2 with a phase angle of - 79.4° at 120 Hz in aqueous electrolyte and a high energy density of 1953 µFV2  cm-2 in organic electrolyte. As a result, the EC is capable of smoothing 120 Hz ripples for 60 Hz AC filtering. These results provide enlightening insights on designing high-performance ECs for high-frequency applications.

Combined analysis of microRNA and mRNA profiles provides insights into the pathogenic resistant mechanisms of the lotus rhizome rot.

Lotus rhizome rot caused by Fusarium oxysporum is a common vascular fungal disease in plants that significantly impacts the yield. However, only a few studies have studied the mechanism of Nelumbo nucifera responding to lotus rhizome rot. Here, we investigated the pathogenic genes and miRNAs in lotus rhizome rot to uncover the pathogenic resistant mechanisms by transcriptome and small RNA sequencing of lotus roots after inoculation with Fusarium oxysporum. GO and KEGG functional enrichment analysis showed that differential miRNAs were mostly enriched in starch and sucrose metabolism, biosynthesis of secondary metabolites, glutathione metabolism, brassinosteroid biosynthesis and flavonoid biosynthesis pathways. Twenty-seven upregulated miRNAs, 19 downregulated miRNAs and their target genes were identified. Correlation analysis found that miRNAs negatively regulate target genes, which were also enriched in starch and sucrose metabolism and glutathione metabolism pathways. Their expression was measured by reverse transcription quantitative PCR (qRT-PCR), and the results were consistent with the transcriptome analysis, thus verifying the reliability of transcriptome data. We selected three miRNAs (miRNA858-y, miRNA171-z and a novel miRNA novel-m0005-5p) to test the relationship between miRNAs and their target genes. The activity of the GUS testing assay indicated that miRNA could decrease the GUS activity by inhibiting the expression of their target genes. Collectively, this study provides a comprehensive analysis of transcriptome and small RNA sequencing of lotus root after inoculation with Fusarium oxysporum, and we identified candidate miRNAs and their target genes for breeding strategies of Nelumbo nucifera.

An ultrasensitive J-shaped optical fiber LSPR aptasensor for the detection of Helicobacter pylori.

The development of label-free and sensitive detection of pathogenic bacteria is of great significance for disease prevention and public health protection. In this study, an originally bent structure, named as J-shaped optical fiber probe, was first designed to engineer a localized surface plasmon resonance (LSPR) aptamer biosensor for the rapid and ultrasensitive detection of Helicobacter pylori (H. pylori). The J-shaped optical fiber probe exhibited a significant improvement in refractive index sensitivity (RIS) and LSPR signal response. Meantime, the original sequence of aptamer was truncated in order to effectively capture H. pylori on the optical fiber surface. Besides, a spacer nucleic acid with short stem-loop structure was adopted to control the aptamer density on gold nanoparticles (AuNPs) on the surface of the J-shaped optical fiber probe, which displayed a further enhancement in LSPR signal response. Benefitting from these creative designs, the proposed LSPR biosensor can realize label-free and sensitive detection of H. pylori with a detection limit as low as 45 CFU/mL and a wide linear range from 1.0 × 102 CFU/mL to 1.0 × 108 CFU/mL. At the same time, the sensing strategy can detect the pathogenic bacteria from actual water samples in one step just in 30 min without any sample pretreatment. Due to the advantages of ease-to-preparation, high sensitivity, and rapid analysis, this proposed J-shaped optical fiber LSPR aptasensor can provide a potential strategy for point-of-caring detection of pathogenic bacteria in environmental monitoring and disease diagnosis.

Label-Free, High-Throughput, Sensitive, and Logical Analysis Using Biomimetic Array Based on Stable Luminescent Copper Nanoclusters and Entropy-Driven Nanomachine.

The development of an array for high-throughput and logical analysis of biomarkers is significant for disease diagnosis. DNA-templated copper nanoclusters (CuNCs) have a strong potential to serve as a label-free photoluminescence source in array platforms, but their luminescent stability and sensitivity need to be improved. Herein, we report a facile, sensitive, and robust biomimetic array assay by integrating with stable luminescent CuNCs and entropy-driven nanomachine (EDN). In this strategy, the luminescent stability of CuNCs was improved by adding fructose in CuNCs synthesis to offer a reliable label-free signal. Meanwhile, the DNA template for CuNCs synthesis was introduced into EDN with excellent signal amplification ability, in which the reaction triggered by target miRNA would cause the blunt/protruding conformation change of 3'-terminus accompanied by the production or loss of luminescence. In addition, a biomimetic array fabricated by photonic crystals (PCs) physically enhanced the emitted luminescent signal of CuNCs and achieved high-throughput signal readout by a microplate reader. The proposed assay can isothermally detect as low as 4.5 pM of miR-21. Moreover, the logical EDN was constructed to achieve logical analysis of multiple miRNAs by "AND" or "OR" logic gate operation. Therefore, the proposed assay has the advantages of label-free property, high sensitivity, flexible design, and high-throughput analysis, which provides ideas for developing a new generation of facile and smart platforms in the fields of biological analysis and clinical application.

Dive into the details of self-supervised learning for medical image analysis.

Self-supervised learning (SSL) has achieved remarkable performance in various medical imaging tasks by dint of priors from massive unlabeled data. However, regarding a specific downstream task, there is still a lack of an instruction book on how to select suitable pretext tasks and implementation details throughout the standard "pretrain-then-finetune" workflow. In this work, we focus on exploiting the capacity of SSL in terms of four realistic and significant issues: (1) the impact of SSL on imbalanced datasets, (2) the network architecture, (3) the applicability of upstream tasks to downstream tasks and (4) the stacking effect of SSL and common policies for deep learning. We provide a large-scale, in-depth and fine-grained study through extensive experiments on predictive, contrastive, generative and multi-SSL algorithms. Based on the results, we have uncovered several insights. Positively, SSL advances class-imbalanced learning mainly by boosting the performance of the rare class, which is of interest to clinical diagnosis. Unfortunately, SSL offers marginal or even negative returns in some cases, including severely imbalanced and relatively balanced data regimes, as well as combinations with common training policies. Our intriguing findings provide practical guidelines for the usage of SSL in the medical context and highlight the need for developing universal pretext tasks to accommodate diverse application scenarios. The code of this paper can be found at https://github.com/EndoluminalSurgicalVision-IMR/Medical-SSL.

Contrastive Adversarial Learning for Endomicroscopy Imaging Super-Resolution.

Endomicroscopy is an emerging imaging modality for real-time optical biopsy. One limitation of existing endomicroscopy based on coherent fibre bundles is that the image resolution is intrinsically limited by the number of fibres that can be practically integrated within the small imaging probe. To improve the image resolution, Super-Resolution (SR) techniques combined with image priors can enhance the clinical utility of endomicroscopy whereas existing SR algorithms suffer from the lack of explicit guidance from ground truth high-resolution (HR) images. In this article, we propose an unsupervised SR pipeline to allow stable offline and kernel-generic learning. Our method takes advantage of both internal statistics and external cross-modality priors. To improve the joint learning process, we present a Sharpness-aware Contrastive Generative Adversarial Network (SCGAN) with two dedicated modules, a sharpness-aware generator and a contrastive-learning discriminator. In the generator, an auxiliary task of sharpness discrimination is formulated to facilitate internal learning by considering the rankings of training instances in various sharpness levels. In the discriminator, we design a contrastive-learning module to mitigate the ill-posed nature of SR tasks via constraints from both positive and negative images. Experiments on multiple datasets demonstrate that SCGAN reduces the performance gap between previous unsupervised approaches and the upper bounds defined in supervised settings by more than 50%, delivering a new state-of-the-art performance score for endomicroscopy super-resolution. Further application on a realistic Voronoi-based pCLE downsampling kernel proves that SCGAN attains PSNR of 35.851 dB, improving 5.23 dB compared with the traditional Delaunay interpolation.

Ω-shaped fiber optic LSPR biosensor based on mismatched hybridization chain reaction and gold nanoparticles for detection of circulating cell-free DNA.

Circulating cell-free DNA (cfDNA) is a promising biomarker of liquid biopsy, but it still faces some difficulties in achieving sensitive and convenient detection. Herein, an Ω-shaped fiber optic localized surface plasmon resonance (FO-LSPR) biosensor based on hybridization chain reaction (HCR) coupled with gold nanoparticles (AuNPs) was developed, and applied in simple and sensitive detection of cfDNA. Specifically, one-base mismatch was designed in HCR hairpins (H1 and H2) to obtain high reaction efficiency, and AuNPs was introduced onto H1 through poly-adenine to construct HCR coupled with AuNPs strategy. Meanwhile, target cfDNA was designed into two domains: one could trigger HCR to generate dsDNA concatemer carrying numerous AuNPs, and the other could hybridize with capture DNA on the surface of Ω-shaped fiber optic (FO) probes. Thus, the presence of target cfDNA would initiate HCR, and bring the formed dsDNA concatemer and AuNPs to approach the probe surface, resulting in dramatically amplified LSPR signal. Besides, HCR required simple isothermal and enzyme-free condition, and Ω-shaped FO probe with high refractive index sensitivity just needed to be immersed into HCR solution directly for signal monitoring. Benefiting from the synergetic amplification of mismatched HCR and AuNPs, the proposed biosensor exhibited high sensitivity with a limit of detection of 14.0 pM, and therefore could provide a potential strategy for biomedical analysis and disease diagnosis.

Identification of YABBY Transcription Factors and Their Function in ABA and Salinity Response in Nelumbo nucifera.

The plant-specific transcription factor family YABBY plays important roles in plant responses to biotic and abiotic stresses. Although the function of YABBY has been identified in many species, systematic analysis in lotus (Nelumbo nucifera) is still relatively lacking. The present study aimed to characterize all of the YABBY genes in lotus and obtain better insights into NnYABBYs in response to salt stress by depending on ABA signaling. Here, we identified nine YABBY genes by searching the whole lotus genome based on the conserved YABBY domain. Further analysis showed that these members were distributed on six different chromosomes and named from YABBY1 to YABBY9, which were divided into five subgroups, including YAB1, YAB2, YAB5, INO, and CRC. The analysis of cis-elements in promotors revealed that NnYABBYs could be involved in plant hormone signaling and plant responses to abiotic stresses. Quantitative real-time PCR (qRT-PCR) showed that NnYABBYs could be up-regulated or down-regulated by ABA, fluridone, and salt treatment. Subcellular localization indicated that NnYABBY4, NnYABBY5, and NnYABBY6 were mainly localized in the cell membrane and cytoplasm. In addition, the intrinsic trans-activity of NnYABBY was tested by a Y2H assay, which revealed that NnYABBY4, NnYABBY5, and NnYABBY6 are deprived of such a property. This study provided a theoretical basis and reference for the functional research of YABBY for the molecular breeding of lotus.

Recent advances of catalytic hairpin assembly and its application in bioimaging and biomedicine.

Catalytic hairpin assembly (CHA) appears to be a particularly appealing nucleic acid circuit because of its powerful amplification capability, simple protocols, and enzyme-free and isothermal conditions, and can combine with various signal output modes for the biosensing of various analytes. Especially in the last five years, vast CHA related studies have sprung up. With the deep exploration of the CHA mechanism, some novel and excellent CHA strategies have been proposed; meanwhile the CHA cascade strategies with various amplification techniques further improve the analysis performance. Furthermore, diverse CHA based biosensors have been tactfully engineered and extensively employed in imaging applications in living cells and in vivo ascribed to its gentle reaction, efficient amplification and universality. Hence, we present a comprehensive and systematic summary of the progress in CHA and its application in bioimaging and biomedicine to date. At first, we introduced the mechanism and diversification of CHA in detail, including the newly developed CHA and its ingenious combination with a variety of other technologies. Concurrently, we summarized the latest application progress of different CHA strategies in bioimaging and biomedicine, highlighting the merits and drawbacks of representative approaches. Finally, we put forward some views on the challenges and prospects of CHA in bioimaging and biomedicine in the future.

A universal array platform for ultrasensitive, high-throughput and microvolume detection of heavy metal, nucleic acid and bacteria based on photonic crystals combined with DNA nanomachine.

The development of a universal, sensitive, and rapid assay platform to achieve detections of heavy metal, nucleic acid and bacteria is of great significance but it also faces a thorny challenge. Herein, a novel and universal array platform was developed by combining photonic crystals (PCs) and DNA nanomachine. The developed array platform integrated the physical and biological signal amplification ability of PCs and DNA nanomachine, resulting in ultrasensitive detections of Hg2+, DNA, and Shigella sonnei with limits of detection (LODs) of 22.1 ppt, 31.6 fM, and 9 CFU/mL, respectively. More importantly, by utilizing a microplate reader as signal output device, the array achieved high-throughput scanning (96 samples/3 min) with only 2 µL loading sample, which is advantageous for the detection of infectious dangerous targets. In addition, the PCs array could be obtained easily and rapidly based on self-assembly of colloidal nanospheres, and the DNA nanomachine was operated with enzyme-free and time-saving features. Benefiting from these merits, the proposed PCs array offered a powerful universal platform for large-scale detection of various analytes in the fields of pollution monitoring, epidemic control, and public health.

Influence of Silicone Rubber Coating on the Characteristics of Surface Streamer Discharge.

A pollution flashover along an insulation surface-a catastrophic accident in electrical power system-threatens the safe and reliable operation of a power grid. Silicone rubber coatings are applied to the surfaces of other insulation materials in order to improve the pollution flashover voltage of the insulation structure. It is generally believed that the hydrophobicity of the silicone rubber coating is key to blocking the physical process of pollution flashover, which prevents the formation of continuously wet pollution areas. However, it is unclear whether silicone rubber coating can suppress the generation of pre-discharges such as corona discharge and streamer discharge. In this research, the influence of silicone rubber coating on the characteristics of surface streamer discharge was researched in-depth. The streamer 'stability' propagation fields of the polymer are lower than that of the polymer with silicone rubber coating. The velocities of the streamer propagation along the polymer are higher than those along the polymer with silicone rubber coating. This indicates that the surface properties of the polymer with the silicone rubber coating are less favorable for streamer propagation than those of the polymer.

A highly sensitive fluorescence biosensor for detection of Staphylococcus aureus based on HCR-mediated three-way DNA junction nicking enzyme assisted signal amplification.

Sensitive and efficient monitoring of food-borne bacteria is of great importance for food safety control. Herein, a novel biosensor for highly sensitive detection of Staphylococcus aureus (S. aureus) was constructed by combining hybridization chain reaction (HCR) and nicking enzyme. Different from the upstream-downstream based circuit, the proposed biosensor integrated HCR circuit and three-way DNA junction nicking enzyme assisted signal amplification (3WJ-NEASA) into a virtuous circle of promotion. In the HCR-mediated 3WJ-NEASA sensing strategy, target DNA of S. aureus initiated the self-assembly between HCR hairpins (H1 and H2), which exposed the gap to capture molecular beacon (MB) and construct the 3WJ structure. Meanwhile, MB increased the stability of HCR nanowires and enhanced the efficiency of the HCR circuit, and thus more 3WJ-NEASA circuits were generated in HCR nanowires. Benefiting from the synergistic amplification coupling HCR and 3WJ-NEASA, this isothermal biosensor can detect as low as 6.7 pM of target DNA in one step within only 30 min. Furthermore, the HCR-mediated 3WJ-NEASA assay has been applied in the detection of S. aureus with a limit of detection (LOD) as low as 1.2 × 101 cfu mL-1, and has exhibited reliable practicability in spiked milk. It is the first time that a DNA biosensor combining HCR and 3WJ-NEASA for dual signal amplification was developed and has been adopted to the sensitive analysis of food-borne bacteria. Additionally, this strategy can serve as a universal platform for monitoring other analytes, and therefore possesses broad application prospects in food safety and environmental monitoring.

Nitrogen-doped carbon nanowalls/diamond films as efficient electrocatalysts toward oxygen reduction reaction.

Substitution of commercial Pt/C electrocatalysts with efficient carbon-based ones for oxygen reduction reaction (ORR) still remains a huge challenge. For practical ORR applications it is significant to design robust 3D network nanostructures in that they do not require polymer binders. For conventional powder catalysts, they must be combined with substrate, leading to their shedding and degradation. In this work, vertically-aligned N-doped carbon nanowalls/diamond (N-CNWs/D) films are synthesized by means of a microwave plasma chemical vapor deposition technique, where nitrogen doping is conducted during the growth process and a subsequent facile annealing treatment under Ar atmosphere. The obtained Ar treated N-CNWs/D film exhibits an ORR onset potential of 835 mV (versus reversible hydrogen electrode) in 0.1 mol l-1KOH solution in a four-electron reaction pathway. It also displays excellent tolerance toward methanol crossover and long-term stability (e.g. a current density loss of only 10% even after 16 h measurement). The boosting ORR performance can be attributed to the activated pyridinic N dopant at abundant edge sites and enlarged electrochemical surface areas of N-CNWs/D films. This work not only develops a controllable strategy to fabricate binder-free carbon-based ORR electrocatalysts, but also paves a way to in-depth understand actual active sites in terms of ORR pathway mechanisms.

Electrical Property of Polypropylene Films Subjected to Different Temperatures and DC Electric Fields.

A polypropylene (PP) film is usually used as a dielectric material in capacitors as well as cables. However, PP films may degrade because of the combined effect of temperature and electric field. In an earlier study, plain PP films and PP films loaded with nano-metric natural clay were studied under sinusoidal (AC) electric fields at power frequency and temperatures above the ambient. To better understand the electrical characteristics of PP film under various conditions, the objective of this study is to determine the time-to-breakdown of the plain PP and PP filled with 2% (wt) natural nano-clay when subjected to time-invariant (DC) electric fields at elevated temperatures. In order to achieve this objective, the effects of uniform as well as non-uniform electric fields were compared at the same temperature for the PP film. In this study, experimental results indicated that the time-to-breakdown of all PP films, plain or filled with nano-clay, decreases with the increase in electric field intensity, non-uniformity of the electric field, and temperature. It was also found that the time-to-breakdown of PP film filled with 2% (wt) natural nano-clay under DC electric field is longer and less sensitive to temperature. Furthermore, when compared with the results under the uniform electric field, PP film filled with 2% (wt) nano-metric natural clay indicates shorter time-to-failure under non-uniform DC electric fields. Finally, the morphology of the samples was observed by digital camera, optical micrography, and SEM, to better understand the mechanism of the breakdown.

The Recent Development of Hybridization Chain Reaction Strategies in Biosensors.

With the continuous development of biosensors, researchers have focused increasing attention on various signal amplification strategies to pursue superior performance for more applications. In comparison with other signal amplification strategies, hybridization chain reaction (HCR) as a powerful signal amplification technique shows its certain charm owing to nonenzymatic and isothermal features. Recently, on the basis of conventional HCR, this technique has been developed and improved rapidly, and a variety of HCR-based biosensors with excellent performance have been reported. Herein, we present a systematic and critical review on the research progress of HCR in biosensors in the last five years, including the newly developed HCR strategies such as multibranched HCR, migration HCR, localized HCR, in situ HCR, netlike HCR, and so on, as well as the combination strategies of HCR with isothermal signal amplification techniques, nanomaterials, and functional DNA molecules. By illustrating some representative works, we also summarize the advantage and challenge of HCR in biosensors, and offer a deep discussion of the latest progress and future development trends of HCR in biosensors.