Flexible microfluidic colorimetric detection chip integrated with ABTS·+ and Co@MnO2 nanozyme catalyzed TMB reaction systems for bio-enzyme free detection of sweat uric acid.

BACKGROUND: The development of wearable detection devices that can achieve noninvasive, on-site and real-time monitoring of sweat metabolites is of great demand and practical significance for point-of-care testing and healthcare monitoring. Monitoring uric acid (UA) content in sweat provides a simple and promising way to reduce the risk of gout and hyperuricemia. Traditional bioenzyme based UA assays suffer from high cost, poor stability, inconvenience for storage and easy deactivation of bioenzymes. Wearable microfluidic colorimetric detection device for sweat UA detection has not been reported. The development of novel wearable microfluidic colorimetric detection chip with no requirement of bioenzymes for sweat UA detection is of great importance for health care monitoring. RESULTS: Firstly, Co@MnO2 nanozyme with high oxidase-like activity was synthesized and characterized. Co@MnO2 can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) directly to generate blue-green colored ox-TMB. Green colored 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) radical (ABTS·+) was produced by the oxidation of ABTS by potassium persulfate. UA exhibits distinct quenching effect on Co@MnO2 catalyzed TMB colorimetric reaction system and ABTS·+ based colorimetric system, leading to obvious color fading of the two colorimetric systems. Then, a flexible microfluidic colorimetric detection chip for UA detection was fabricated by assembling Co@MnO2/TMB modified paper chips and ABTS·+ modified paper chips into a polydimethylsiloxane (PDMS) microfluidic chip. The fabricated microfluidic colorimetric detection chip exhibits good linear relationship for sweat UA detection. The linear range is from 20 to 200 µmol/L with detection limit as low as 6.6 µmol/L. Good results were obtained for the detection of UA in actual sweat from three volunteers. SIGNIFICANCE: This work provides two bio-enzyme free colorimetric detection systems for UA detection. Furthermore, a simple, low-cost and selective flexible wearable microfluidic colorimetric detection chip was fabricated for noninvasive and on-site detection of sweat UA, which holds great application potential for personal health monitoring and point-of-care testing.

A wideband high-power microwave radiation source based on gyromagnetic nonlinear transmission line and Vlasov antenna.

The gyromagnetic nonlinear transmission line (GNLTL) is a special kind of coaxial transmission line partially loaded with the ferrite material. A GNLTL system can modulate the input high-power pulses into wideband high-power microwaves without relying on the electron beam and confining magnetic field. The unique working mechanism gives the GNLTL system the potential to be a small portable wideband high-power microwave radiation source. In this study, a wideband high-power microwave radiation source based on a GNLTL system is designed and constructed. In order to effectively radiate the wideband microwaves into the air, a high-power wideband Vlasov antenna and a special absorption high-pass filter are developed. The designs of key subsystems and high-power radiation experiments have been introduced and discussed in detail. In the test experiments, a radiated pulse with a peak electric field strength of 23 kV/m was measured at 20 m away from the transmitting antenna and the effective potential of radiation is 460 kV/m. The pulse width of the radiation pulse is about 4 ns, the center frequency is about 2.25 GHz, and the highest repetition rate can reach 25 Hz.

One-level microstructure-arrayed hydrophobic surface with low surface adhesion and strong anti-wetting function.

To achieve both a low surface adhesion function and a high anti-wetting function, it is generally necessary to introduce multi-level micro-nano-structures on a surface. However, this will bring the difficulty of preparation technology, and the functions will fail due to the fact that the nanostructures can easily be damaged. In this research, the surface adhesion and anti-wetting properties of several typically one-level microstructure-arrayed hydrophobic surfaces are analyzed with the dynamics theory, including a square pillar-arrayed three-dimensional microstructure, a conical table-arrayed microstructure, and square frustum-arrayed microstructure. It is found that the anti-adhesion performance and anti-wetting property cannot achieve the best performance simultaneously on the one-level microstructure arrayed surfaces. Either the critical pressure of anti-wetting is finite when the surface adhesion is the lowest, or both the anti-adhesion and anti-wetting capacities are finite. However, an interesting phenomenon is found in that the square frustum-arrayed surface can not only achieve an almost infinite anti-wetting capacity when the distance between neighboring microstructures vanishes, but also reach near-zero adhesion when the square frustum reduces to a square pyramid. All the theoretical predictions are further verified by precise numerical simulations. The results of this paper should be helpful for the design of surfaces with low surface adhesion and strong anti-wetting functions in practical engineering.

Diversity and co-occurrence networks of picoeukaryotes as a tool for indicating underlying environmental heterogeneity in the Western Pacific Ocean.

Picoeukaryotes are an essential component of microbial communities and play key roles in marine ecosystems. In this study, surface water picoeukaryotes were investigated at 32 stations along a latitudinal cross-section of the Western Pacific (WP) in 2015. Multivariate analyses demonstrated that there were clear spatial patterns in picoeukaryotic community structures which were consistent with the distributions of environmental variables. The spatial patterns of community structures and diversity indices were all significantly correlated with multiple environmental parameters, especially nutrients. Co-occurrence networks linked community variability to environmental heterogeneity. In summary, the construction of picoeukaryotic communities in the WP was significantly affected by numerous environmental variables, and certain variables were revealed as key forcing factors responsible for the main similarities between picoeukaryotic communities. This study details the relationships between the picoeukaryotes and environmental parameters in the WP, and provides insight for application of using picoeukaryotes as indicator in future bioassessment for open waters.

Operation analysis of the wideband high-power microwave sources based on the gyromagnetic nonlinear transmission lines.

The wideband High-Power Microwave (HPM) sources, which combine the advantages of narrowband and ultrawideband sources, have drawn much attention. As a kind of wideband source, the gyromagnetic nonlinear transmission lines (GNLTLs) can directly modulate the incident pulses into radio frequency pulses without relying on the interaction between e-beam and microwaves. Due to the special working mechanism of gyromagnetic precession, the center frequency of the GNLTL can also be adjusted in a certain range. Based on classical magnetism and a simplified model of the GNLTL, this paper semi-quantitatively and theoretically analyzed the generation mechanism of HPM and illustrated the influences of the variations of parameters on the output microwaves. Then, a simple simulation based on 1-dimensional transmission line modeling method was carried out to study the performance of the GNLTL quantitatively, with the coupling of 1D telegraphist equations and the 3D Landau-Lifshitz-Gilbert equation. Simulation results preliminarily verified the conclusions derived from the theoretical analysis, and some working characteristics of the GNLTL were also obtained. This paper may help to understand the special working mechanism of the GNLTL and provide certain guidance for related simulations and experiments.

A novel role of kallikrein-related peptidase 8 in the pathogenesis of diabetic cardiac fibrosis.

Rationale: Among all the diabetic complications, diabetic cardiomyopathy, which is characterized by myocyte loss and myocardial fibrosis, is the leading cause of mortality and morbidity in diabetic patients. Tissue kallikrein-related peptidases (KLKs) are secreted serine proteases, that have distinct and overlapping roles in the pathogenesis of cardiovascular diseases. However, whether KLKs are involved in the development of diabetic cardiomyopathy remains unknown.The present study aimed to determine the role of a specific KLK in the initiation of endothelial-to-mesenchymal transition (EndMT) during the pathogenesis of diabetic cardiomyopathy. Methods and Results-By screening gene expression profiles of KLKs, it was found that KLK8 was highly induced in the myocardium of mice with streptozotocin-induced diabetes. KLK8 deficiency attenuated diabetic cardiac fibrosis, and rescued the impaired cardiac function in diabetic mice. Small interfering RNA (siRNA)-mediated KLK8 knockdown significantly attenuated high glucose-induced endothelial damage and EndMT in human coronary artery endothelial cells (HCAECs). Diabetes-induced endothelial injury and cardiac EndMT were significantly alleviated in KLK8-deficient mice. In addition, transgenic overexpression of KLK8 led to interstitial and perivascular cardiac fibrosis, endothelial injury and EndMT in the heart. Adenovirus-mediated overexpression of KLK8 (Ad-KLK8) resulted in increases in endothelial cell damage, permeability and transforming growth factor (TGF)-ß1 release in HCAECs. KLK8 overexpression also induced EndMT in HCAECs, which was alleviated by a TGF-ß1-neutralizing antibody. A specificity protein-1 (Sp-1) consensus site was identified in the human KLK8 promoter and was found to mediate the high glucose-induced KLK8 expression. Mechanistically, it was identified that the vascular endothelial (VE)-cadherin/plakoglobin complex may associate with KLK8 in HCAECs. KLK8 cleaved the VE-cadherin extracellular domain, thus promoting plakoglobin nuclear translocation. Plakoglobin was required for KLK8-induced EndMT by cooperating with p53. KLK8 overexpression led to plakoglobin-dependent association of p53 with hypoxia inducible factor (HIF)-1α, which further enhanced the transactivation effect of HIF-1α on the TGF-ß1 promoter. KLK8 also induced the binding of p53 with Smad3, subsequently promoting pro-EndMT reprogramming via the TGF-ß1/Smad signaling pathway in HCAECs. The in vitro and in vivo findings further demonstrated that high glucose may promote plakoglobin-dependent cooperation of p53 with HIF-1α and Smad3, subsequently increasing the expression of TGF-ß1 and the pro-EndMT target genes of the TGF-ß1/Smad signaling pathway in a KLK8-dependent manner. Conclusions: The present findings uncovered a novel pro-EndMT mechanism during the pathogenesis of diabetic cardiac fibrosis via the upregulation of KLK8, and may contribute to the development of future KLK8-based therapeutic strategies for diabetic cardiomyopathy.

How to Achieve a Monostable Cassie State on a Micropillar-Arrayed Superhydrophobic Surface.

Superhydrophobic surfaces with a monostable Cassie state possess numerous interesting applications in many fields, such as microfluidics, oil-water separation, drag reduction, self-cleaning, heat dissipation, and so on. How to guarantee a monostable Cassie state of a superhydrophobic surface is still an interesting problem. In this paper, considering the influence of external interferences that may induce the possible wettability transition, the whole wetting process of a droplet on a trapezoidal micropillar-arrayed superhydrophobic surface is divided into six possible stages. Both the Gibbs-free energy in each stage and the energy barrier between adjacent stages are obtained and analyzed theoretically. It is interesting to find that the finally stable wettability of a trapezoidal micropillar-arrayed superhydrophobic surface significantly depends on the apparent contact angle of the lateral surface of a single micropillar, which can be divided into three regions from 0 to 180°, corresponding to the Wenzel state, metastable Cassie state, and monostable Cassie state. Furthermore, the size of each region is explicitly related to and can be well-tuned by the geometry of microstructures. Such a wettability classification is well verified by a number of existing experimental results and our numerical simulations. As a relatively general case, such a trapezoidal micropillar-arrayed superhydrophobic surface can also be conveniently degenerated to the triangular or rectangular micropillar-arrayed surface. All the results should be useful for the precise design of functional surfaces of different wettabilities.

Isolation and Complete Genome Sequence of a Novel Cyanophage S-B68.

Cyanophages, which play a significant role in food web and global biochemical cycle, are one of the main causes of microbial death in aquatic environment. A novel cyanophage S-B68 was isolated from the surface water of the Bohai Sea, northern China. It can infect marine Synechococcus sp. (strain WH7803). The transmission electron microscopy results demonstrate that this cyanophage has an icosahedral head (51 nm in diameter) and a long tail (110 nm in length) and belongs to family Siphophages. The complete genome sequence of cyanophage S-B68 contains a linear, double-stranded 163,982 bp DNA molecule with a 51.7% G+C content. Except for four tRNAs, the genome contains 229 open reading frames (ORFs) which were grouped into six functional modules as follows: structure, hypothetical protein, DNA replication and expression, lysis, packaging, and some additional functions. It was found in one-step growth curve that the latent period of the S-B68 was about 49 h after infection with Synechococcus, and then it entered the rising period, and tended to stable after 61 h. Using the BLASTN tool in the NCBI database for genome comparison, there was no significant similarity between S-B68 and other known cyanophages. Present study adds a novel Siphoviridae genome to marine cyanophage dataset and provides useful basic information for its further research.

Characterization and Genome Analysis of a Novel Alteromonas Phage JH01 Isolated from the Qingdao Coast of China.

A novel Alteromonas phage JH01, with the host strain identified to be Alteromonas marina SW-47(T), was isolated from the Qingdao coast during the summer of 2017. Transmission electron microscopy analysis showed that phage JH01 can be categorized into the Siphoviridae family, with an icosahedral head of 62 ± 5 nm and a long contractile tail of 254 ± 10 nm. The bioinformatic analysis shows that this phage consists of a linear, double-stranded 46,500 bp DNA molecule with a GC content of 44.39%, and 58 ORFs with no tRNA genes. The ORFs are classified into four groups, including phage packaging, phage structure, DNA replication and regulation, and hypothetical protein. The phylogenetic tree, constructed using neighbor-joining analysis, shows that phage JH01 has altitudinal homology with some Vibrio and Pseudoalteromonas phage B8b. Comparative analysis reveals the high similarity between phage JH01 and phage B8b. Additionally, our study of phage JH01 provides useful information for further research on the interaction between Alteromonas phages and their hosts.

Microarray analysis of long non-coding RNA expression profiles uncovers a Toxoplasma-induced negative regulation of host immune signaling.

BACKGROUND: Toxoplasma gondii is an obligate intracellular protozoan parasite that can infect mammalian cells and thereby regulate host gene expression. The long non-coding RNAs (lncRNAs) have been demonstrated to be an important class of RNA molecules that regulate many biological processes, including host-pathogen interactions. However, the role of host lncRNAs in the response to T. gondii infection remains largely unknown. METHODS: We applied a microarray approach to determine the differential expression profiles of both lncRNAs and mRNAs in the human foreskin fibroblast (HFF) cells after T. gondii infection. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to reveal the potential functions of T. gondii-induced genes. Based on the co-expression networks of lncRNAs and immune-related genes, the role of NONSHAT022487 on the regulation of UNC93B1 related immune signaling was investigated by the knockdown and over-expression of lncRNA in human macrophage derived from the PMA-induced promonocytic cell line THP-1. RESULTS: Our data showed that 996 lncRNAs and 109 mRNAs in HFF cells were significantly and differentially expressed following T. gondii infection (fold change ≥ 5, P < 0.05). The results from the GO and KEGG pathway analyses indicated that the mRNAs with differential expression were mainly involved in the host immune response. Remarkably, we identified a novel lncRNA, NONSHAT022487, which suppresses the expression of the immune-related molecule UNC93B1. After T. gondii infection, NONSHAT022487 impaired the secretion of the cytokines IL-12, TNF-α, IL-1ß and IFN-γ by downregulating UNC93B1 expression in human macrophage cells. CONCLUSIONS: Our study identified infection-induced lncRNA expression as a novel mechanism by which the Toxoplasma parasite regulates host immune signaling, which advances our understanding of the interaction of T. gondii parasites and host cells.

Angiostrongylus cantonensis daf-2 regulates dauer, longevity and stress in Caenorhabditis elegans.

The insulin-like signaling (IIS) pathway is considered to be significant in regulating fat metabolism, dauer formation, stress response and longevity in Caenorhabditis elegans. "Dauer hypothesis" indicates that similar IIS transduction mechanism regulates dauer development in free-living nematode C. elegans and the development of infective third-stage larvae (iL3) in parasitic nematodes, and this is bolstered by a few researches on structures and functions of the homologous genes in the IIS pathway cloned from several parasitic nematodes. In this study, we identified the insulin-like receptor encoding gene, Acan-daf-2, from the parasitic nematode Angiostrongylus cantonensis, and determined the genomic structures, transcripts and functions far more thorough in longevity, stress resistance and dauer formation. The sequence of Acan-DAF-2, consisting of 1413 amino acids, contained all of the characteristic domains of insulin-like receptors from other taxa. The expression patterns of Acan-daf-2 in the C. elegans surrogate system showed that pAcan-daf-2:gfp was only expressed in intestine, compared with the orthologue in C. elegans, Ce-daf-2 in both intestine and neurons. In addition to the similar genomic organization to Ce-daf-2, Acan-DAF-2 could also negatively regulate Ce-DAF-16A through nuclear/cytosolic translocation and partially restore the C. elegans daf-2(e1370) mutation in longevity, dauer formation and stress resistance. These findings provided further evidence of the functional conservation of DAF-2 between parasitic nematodes and the free-living nematode C. elegans, and might be significant in understanding the developmental biology of nematode parasites, particularly in the infective process and the host-specificity.

Comparative expression profile of microRNAs in Anopheles anthropophagus midgut after blood-feeding and Plasmodium infection.

BACKGROUND: Anopheles anthropophagus is one of the major vectors of malaria in Asia. MicroRNAs (miRNAs) play important roles in cell development and differentiation as well as in the cellular response to stress and infection. In a former study, we have investigated the global miRNA profiles in relation to sex in An. anthropophagus. However, the miRNAs contributing to the blood-feeding and infection with Plasmodium are still unknown. METHODS: High-throughput sequencing was performed to identify miRNA profiles of An. anthropophagus midguts after blood-feeding and Plasmodium infection. The expression patterns of miRNA in different midgut libraries were compared based on transcripts per million reads (TPM), and further confirmed by Northern blots. Target prediction and pathway analysis were carried out to investigate the role of regulated miRNAs in blood-feeding and Plasmodium infection. RESULTS: We identified 67 known and 21 novel miRNAs in all three libraries (sugar-feeding, blood-feeding and Plasmodium infection) in An. anthropophagus midguts. Comparing with the sugar-feeding, the experssion of nine (6 known and 3 novel) and ten (9 known and 1 novel) miRNAs were significantly upregulated and downregulated respectively after blood-feeding (P < 0.05, fold change ≥ 2 and TPM ≥ 10). Plasmodium infection induced the expression of thirteen (9 known and 4 novel) and eleven (9 known and 2 novel) miRNAs significantly upregulated and downregulated, respectively, compared with blood-feeding. The representative upregulated miR-92a in blood-feeding and downregulated miR-275 in Plasmodium infection were further confirmed by Northern Blot. Putative targets of these regulated miRNAs were further investigated and classified into their pathways. CONCLUSIONS: This study suggests that miRNAs are involved in the blood-feeding and Plasmodium infection in An. anthropophagus midgut. Further studies of the function of these differential expressed miRNAs will facilitate in better understanding of mosquito biology and anti-parasite immunity.