Endogenous AND Logic DNA Nanomachine for Highly Specific Cancer Cell Imaging.

Intracellular cancer-related biomarker imaging strategy has been used for specific identification of cancer cells, which was of great importance to accurate cancer clinical diagnosis and prognosis studies. Localized DNA circuits with improved sensitivity showed great potential for intracellular biomarkers imaging. However, the ability of localized DNA circuits to specifically image cancer cells is limited by off-site signal leakage associated with a single-biomarker sensing strategy. Herein, we integrated the endogenous enzyme-powered strategy with logic-responsive and localized signal amplifying capability to construct a self-assembled endogenously AND logic DNA nanomachine (EDN) for highly specific cancer cell imaging. When the EDN encountered a cancer cell, the overexpressed DNA repairing enzyme apurinic/apyrimidinic endonuclease 1 (APE1) and miR-21 could synergistically activate a DNA circuit via cascaded localized toehold-mediated strand displacement (TMSD) reactions, resulting in amplified fluorescence resonance energy transfer (FRET) signal. In this strategy, both endogenous APE1 and miR-21, served as two "keys" to activate the AND logic operation in cancer cells to reduce off-tumor signal leakage. Such a multiplied molecular recognition/activation nanomachine as a powerful toolbox realized specific capture and reliable imaging of biomolecules in living cancer cells.

Enhanced Aggregation-Induced Delayed Electrochemiluminescence Triggered by Spatial Perturbation of Organic Dots.

Development of highly efficient, heavy-metal-free electrochemiluminescence (ECL) materials is attractive but still challenging. Herein, we report an aggregation-induced delayed ECL (AIDECL) active organic dot (OD) composed of a tert-butoxy-group-substituted benzophenone-dimethylacridine compound, which shows high ECL efficiency. The resultant ODs exhibit 2.1-fold higher ECL efficiency compared to control AIDECL-active ODs. Molecular stacking combined with theoretical calculations suggests that tert-butoxy groups effectively participate in the intermolecular interactions, further inhibiting the molecular motions in the aggregated states and thus accelerating radiative decay. On the basis of these ODs exhibiting excellent ECL performance, a proof-of-concept biosensor is constructed for the detection of miR-16 associated with Alzheimer's disease, which demonstrates excellent detection ability with the limit of detection of 1.7 fM. This work provides a new approach to improve the ECL efficiency and enriches the fundamental understanding of the structure-property relationship.

The impact of different states of type 2 diabetes when stratified by baseline HbA1c on the periodontal outcomes of non-surgical periodontal treatment: A systematic review and network meta-analysis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) has been considered by many studies to have a bidirectional relationship with periodontitis. This systematic review and network meta-analysis aimed to investigate the impact of different states of T2DM when stratified by baseline HbA1c on the clinical outcomes of non-surgical periodontal treatment (NSPT). METHODS: This study followed the Preferred Reporting Items for Meta-Analyses (PRISMA) guidelines and involved an electronic literature search (from inception to the 2nd of January 2023). The study included at least two groups of patients: chronic periodontitis only (No-DM) or periodontitis and well-controlled/poorly controlled type 2 diabetes mellitus (WC/PC-T2DM). Clinical outcomes included probing depth (PD) reduction, bleeding on probing reduction, and clinical attachment level (CAL) gain. Direct and indirect comparisons between groups were assessed by network meta-analysis, thus allowing us to establish a treatment ranking. RESULTS: Ten prospective cohort studies (11 data sets) were included for qualitative analysis and network meta-analysis. The data included in this study had high consistency; in addition, a funnel plot and Egger's test showed that the articles had low publication bias. Network meta-analysis showed that the effect of NSPT in the No-DM group was significantly better than the WC-T2DM group [weighted mean difference (WMD) = 0.09, 95% confidence interval (CI) (0.01, 0.18)] and the PC-T2DM group [WMD = 0.09, 95% CI (0.01, 0.18)] in terms of CAL gain and better than the PC-T2DM group [WMD = 0.15, 95% CI (0.02, 0.28)] in terms of PD reduction. According to the surface under the cumulative ranking value, the No-DM group had the highest probability of achieving the best outcome following NSPT. CONCLUSIONS: Collectively, our analyses show that T2DM exerts significant effects on the outcomes of NSPT.

DNA-Programed Plasmon Rulers Decrypt Single-Receptor Dimerization on Cell Membrane.

Decrypting the dynamics of receptor dimerization on cell membranes bears great importance in identifying the mechanisms regulating diverse cellular activities. In this regard, long-term monitoring of single-molecule behavior during receptor dimerization allows deepening insight into the dimerization process and tracking of the behavior of individual receptors, yet this remains to be realized. Herein, real-time observation of the receptor tyrosine kinases family (RTKs) at single-molecule level based on plasmon rulers was achieved for the first time, which enabled precise regulation and dynamic monitoring of the dimerization process by DNA programming with excellent photostability. Additionally, those nanoprobes demonstrated substantial application in the regulation of RTKs protein dimerization/phosphorylation and activation of downstream signaling pathways. The proposed nanoprobes hold considerable potential for elucidating the molecular mechanisms of single-receptor dimerization as well as the conformational transitions upon dimerization, providing a new paradigm for the precise manipulation and monitoring of specific single-receptor crosslink events in biological systems.

Single-Particle Plasmonic Sensing of Nitric Oxide in Living Cells.

Plasmon resonance energy transfer (PRET), which occurs between plasmonic nanoparticles (NPs) and organic dyes, shows significant potential in sensing chemistry due to its high sensitivity at the single-particle level. In this work, a PRET-based sensing strategy was presented for the ultrasensitive sensing of nitric oxide (NO) in living cells. Supramolecular cyclodextrin (CD) molecules that exhibited different binding abilities to various molecules due to its unique rigid structure and annular cavity was applied and modified on gold NPs (GNPs) to construct the PRET nanosensors. NO-reactive molecules, rhodamine B-derived molecules (RdMs), were further inserted into the cavity of CD molecules through hydrophobic interactions to form host-guest structures. In the presence of NO, RdMs reacted with the target and generated rhodamine (RdB). Due to the spectral overlap between GNPs@CD and RdB molecules, PRET occurred and further led to a decrease in the scattering intensity of GNPs@CD, which was sensitive to the concentration of NO. The proposed sensing platform not only provides quantitative detection of NO in solution but also realized the single-particle imaging analysis of exogenous and endogenous NO in living cells. The single-particle plasmonic probes exhibit great potential in the in vivo sensing of biomolecules and metabolic processes.

Integrated microcavity optomechanics with a suspended photonic crystal mirror above a distributed Bragg reflector.

Increasing the interaction between light and mechanical resonators is an ongoing endeavor in the field of cavity optomechanics. Optical microcavities allow for boosting the interaction strength through their strong spatial confinement of the optical field. In this work, we follow this approach by realizing a sub-wavelength-long, free-space optomechanical microcavity on-chip fabricated from an (Al,Ga)As heterostructure. A suspended GaAs photonic crystal mirror is acting as a highly reflective mechanical resonator, which together with a distributed Bragg (DBR) reflector forms an optomechanical microcavity. We demonstrate precise control over the microcavity resonance by change of the photonic crystal parameters. We find that the microcavity mode can strongly couple to the transmissive modes of the DBR. The interplay between the microcavity mode and a guided resonance of the photonic crystal modifies the cavity response and results in a stronger dynamical backaction on the mechanical resonator compared to conventional optomechanical dynamics.

Comparative Transcriptomics and Metabolomics Analyses of Avicennia marina and Kandelia obovata under Chilling Stress during Seedling Stage.

One of the most productive ecosystems in the world, mangroves are susceptible to cold stress. However, there is currently insufficient knowledge of the adaptation mechanisms of mangrove plants in response to chilling stress. This study conducted a comparative analysis of transcriptomics and metabolomics to investigate the adaptive responses of Kandelia obovata (chilling-tolerant) and Avicennia marina (chilling-sensitive) to 5 °C. The transcriptomics results revealed that differentially expressed genes (DEGs) were mostly enriched in signal transduction, photosynthesis-related pathways, and phenylpropanoid biosynthesis. The expression pattern of genes involved in photosynthesis-related pathways in A. marina presented a downregulation of most DEGs, which correlated with the decrease in total chlorophyll content. In the susceptible A. marina, all DEGs encoding mitogen-activated protein kinase were upregulated. Phenylpropanoid-related genes were observed to be highly induced in K. obovata. Additionally, several metabolites, such as 4-aminobutyric acid, exhibited higher levels in K. obovata than in A. marina, suggesting that chilling-tolerant varieties regulated more metabolites in response to chilling. The investigation defined the inherent distinctions between K. obovata and A. marina in terms of signal transduction gene expression, as well as phenylpropanoid and flavonoid biosynthesis, during exposure to low temperatures.

Pterostilbene pre-treatment reduces LPS-induced acute lung injury through activating NR4A1.

CONTEXT: Pterostilbene (PTE), a common polyphenol compound, exerts an anti-inflammatory effect in many diseases, including acute lung injury (ALI). OBJECTIVE: This study explores the potential mechanism of PTE pre-treatment against lipopolysaccharide (LPS)-induced ALI. MATERIALS AND METHODS: Sixty Sprague-Dawley rats were divided into control, ALI, 10 mg/kg PTE + LPS, 20 mg/kg PTE + LPS, and 40 mg/kg PTE + LPS groups. At 24 h before LPS instillation, PTE was administered orally. At 2 h before LPS instillation, PTE was again administered orally. After 24 h of LPS treatment, the rats were euthanized. The levels of inflammatory cells and inflammatory factors in the bronchoalveolar lavage fluid (BALF), the expression of nuclear receptor subfamily 4 group A member 1 (NR4A1), and the nuclear factor (NF)-κB pathway-related protein levels were detected. NR4A1 agonist was used to further investigate the mechanism of PTE pre-treatment. RESULTS: After PTE pre-treatment, the LPS induced inflammation was controlled and the survival rate was increased to 100% from 70% after LPS treatment 24 h. For lung injury score, it decreased to 1.5 from 3.5 after treating 40 mg/kg PTE. Compared with the control group, the expression of NR4A1 in the ALI group was decreased by 20-40%. However, the 40 mg/kg PTE pre-treatment increased the NR4A1 expression by 20-40% in the lung tissue. The results obtained with pre-treatment NR4A1 agonist were similar to those obtained by pre-treatment 40 mg/kg PTE. CONCLUSIONS: PTE pre-treatment might represent an appropriate therapeutic target and strategy for preventing ALI induced by LPS.

Value of Combination of Heart, Lung, and Diaphragm Ultrasound in Predicting Weaning Outcome of Mechanical Ventilation.

BACKGROUND Postextubation distress is detrimental to the prognosis of critically ill patients with successful spontaneous breathing trial. The known risk factors of failed weaning are associated with the heart, lungs, and diaphragm. The aim of this study was to explore the role of a combined model including indicators of heart, lung, and diaphragm ultrasound in predicting the weaning outcome. MATERIAL AND METHODS Patients' clinical data and ultrasonic features of heart, lungs, and diaphragm were recorded. Patients were included in either the failed weaning group (n=24) or the successful weaning group (n=81). The association of potential variables with the risk of weaning failure was determined using multivariate logistic regression analysis. The accuracy of potential indicators for predicting the weaning outcome were evaluated and a multiindicator combined model was established to improve the predictive accuracy. RESULTS Brain natriuretic peptide (odds ratio [OR]=1.120, P=0.004), left-atrial pressure (LAP) (OR=1.333, P=0.005), lung ultrasound score (LUS) (OR=1.736, P=0.001), and hemidiaphragm dysfunction (OR=3.942, P=0.014) were associated with an increased risk of weaning failure. However, all of these indicators could not accurately predict the weaning outcome independently (all areas under the curve [AUCs] <0.9). The combination of LAP, LUS, and hemidiaphragm dysfunction showed the highest AUC (AUC=0.919). CONCLUSIONS The combined model including LAP, LUS, and hemidiaphragm dysfunction were the most accurate method for the prediction.

Melatonin delays photoreceptor degeneration in a mouse model of autosomal recessive retinitis pigmentosa.

Retinitis pigmentosa (RP) comprises a group of incurable inherited retinal degenerations. Targeting common processes, instead of mutation-specific treatment, has proven to be an innovative strategy to combat debilitating retinal degeneration. Growing evidence indicates that melatonin possesses a potent activity against neurodegenerative disorders by mitigating cell damage associated with apoptosis and inflammation. Given the pleiotropic role of melatonin in central nervous system, the aim of the present study was to investigate whether melatonin would afford protection against retinal degeneration in autosomal recessive RP (arRP). Rd10, a well-characterized murine model of human arRP, received daily intraperitoneal injection of melatonin (15 mg/kg) between postnatal day (P) 13 and P30. Retinas treated with melatonin or vehicle were harvested for analysis at P30 and P45, respectively. The findings showed that melatonin could dampen the photoreceptors death and delay consequent retinal degeneration. We also observed that melatonin weakened the expression of glial fibrillary acidic protein (GFAP) in Müller cells. Additionally, melatonin could alleviate retinal inflammatory response visualized by IBA1 staining, which was further corroborated by downregulation of inflammation-related genes, such as tumor necrosis factor alpha (Tnf-α), chemokine (C-C motif) ligand 2 (Ccl2), and chemokine (C-X-C motif) ligand 10 (Cxcl10). These data revealed that melatonin could ameliorate retinal degeneration through potentially attenuating apoptosis, reactive gliosis, and microglial activation in rd10 mice. Moreover, these results suggest melatonin as a promising agent improving photoreceptors survival in human RP.

Value of High-frequency Ultrasound in the Diagnosis of Peripheral Nerve Compression in Rheumatoid Arthritis Patients.

Objective To evaluate the value of high-frequency ultrasound (HFUS) in diagnosing peripheral nerve compression in patients with rheumatoid arthritis (RA). Methods The upper limb nerves were evaluated by HFUS in 80 RA patients (RA group) and 60 non-RA patients (control group),then the incidence of peripheral nerve compression was recorded respectively. RA patients with/without neurological symptoms were compared in terms of age,disease course,Health Assessment Questionnaire Disability Index (HAQ-DI) score,and clinical disease activity index (CDAI). Results The incidence of upper limb nerve compression in RA group was significantly higher than that in control group(15.0% vs. 3.3%,P=0.046).The patients with nerve compression was older [(60.2±11.4)y vs.(49.2±7.9)y;t=2.343,P=0.039] and had longer disease course [(9.50±5.99) y vs. (5.88±3.87)y;t=2.639,P=0.023] and higher HAQ-DI score (1.58±0.75 vs.0.85±0.67;t=2.490,P=0.030). These two groups had no statistical differences in CDAI (14.50±11.68 vs.16.62±9.24;t=1.141,P=0.278).Conclusions Peripheral neuropathies are common extra-articular manifestations in RA patients. HFUS can be valuable in patients suspected of RA.

Generation of fully pluripotent female murine-induced pluripotent stem cells.

The high quality of induced pluripotent stem cells (iPSCs) has been determined to be high-grade chimeras that are competent for germline transmission, and viable mice can be generated through tetraploid complementation. Most of the high-quality iPSCs described to date have been male. Female iPSCs, especially fully pluripotent female iPSCs, are also essential for clinical applications and scientific research. Here, we show, for the first time, that a gender-mixed induction strategy could lead to a skewed sex ratio of iPSCs. After reprogramming, 50%, 70%, and 90% female initiating mouse embryonic fibroblasts at different male ratios resulted in 14.1 ± 6.8% (P < 0.05), 31.8 ± 5.4% (P < 0.05), and 80.1 ± 2.8% (P < 0.05) female iPSCs, respectively. Furthermore, these female iPSCs had pluripotent properties typical of embryonic stem cells. Importantly, these fully pluripotent female iPSCs could generate viable mice by tetraploid complementation. These findings indicate that high-quality female iPSCs could be derived effectively, and suggest that clinical application of female iPSCs is feasible.

[Hyperspectral Band Selection Based on Spectral Clustering and Inter-Class Separability Factor].

With the development of remote sensing technology and imaging spectrometer, the resolution of hyperspectral remote sensing image has been continually improved, its vast amount of data not only improves the ability of the remote sensing detection but also brings great difficulties for analyzing and processing at the same time. Band selection of hyperspectral imagery can effectively reduce data redundancy and improve classification accuracy and efficiency. So how to select the optimum band combination from hundreds of bands of hyperspectral images is a key issue. In order to solve these problems, we use spectral clustering algorithm based on graph theory. Firstly, taking of the original hyperspectral image bands as data points to be clustered , mutual information between every two bands is calculated to generate the similarity matrix. Then according to the graph partition theory, spectral decomposition of the non-normalized Laplacian matrix generated by the similarity matrix is used to get the clusters, which the similarity between is small and the similarity within is large. In order to achieve the purpose of dimensionality reduction, the inter-class separability factor of feature types on each band is calculated, which is as the reference index to choose the representative bands in the clusters furthermore. Finally, the support vector machine and minimum distance classification methods are employed to classify the hyperspectral image after band selection. The method in this paper is different from the traditional unsupervised clustering method, we employ spectral clustering algorithm based on graph theory and compute the interclass separability factor based on a priori knowledge to select bands. Comparing with traditional adaptive band selection algorithm and band index based on automatically subspace divided algorithm, the two sets of experiments results show that the overall accuracy of SVM is about 94. 08% and 94. 24% and the overall accuracy of MDC is about 87. 98% and 89. 09%, when the band selection achieves a relatively optimal number of clusters using the method propoesd in this paper. It effectively remains spectral information and improves the classification accuracy.

[The linear hyperspectral camera rotating scan imaging geometric correction based on the precise spectral sampling].

As the rotation speed of ground based hyperspectral imaging system is too fast in the image collection process, which exceeds the speed limitation, there is data missed in the rectified image, it shows as the_black lines. At the same time, there is serious distortion in the collected raw images, which effects the feature information classification and identification. To solve these problems, in this paper, we introduce the each component of the ground based hyperspectral imaging system at first, and give the general process of data collection. The rotation speed is controlled in data collection process, according to the image cover area of each frame and the image collection speed of the ground based hyperspectral imaging system, And then the spatial orientation model is deduced in detail combining with the star scanning angle, stop scanning angle and the minimum distance between the sensor and the scanned object etc. The oriented image is divided into grids and resampled with new spectral. The general flow of distortion image corrected is presented in this paper. Since the image spatial resolution is different between the adjacent frames, and in order to keep the highest image resolution of corrected image, the minimum ground sampling distance is employed as the grid unit to divide the geo-referenced image. Taking the spectral distortion into account caused by direct sampling method when the new uniform grids and the old uneven grids are superimposed to take the pixel value, the precise spectral sampling method based on the position distribution is proposed. The distortion image collected in Lao Si Cheng ruin which is in the Zhang Jiajie town Hunan province is corrected through the algorithm proposed on above. The features keep the original geometric characteristics. It verifies the validity of the algorithm. And we extract the spectral of different features to compute the correlation coefficient. The results show that the improved spectral sampling method is better than the direct sampling method. It provides the reference for the similar product used on the ground.

[The hyperspectral camera side-scan geometric imaging in any direction considering the spectral mixing].

In order to correct the image distortion in the hyperspectral camera side-scan geometric Imaging, the image pixel geo-referenced algorithm was deduced in detail in the present paper, which is suitable to the linear push-broom camera side-scan imaging on the ground in any direction. It takes the orientation of objects in the navigation coordinates system into account. Combined with the ground sampling distance of geo-referenced image and the area of push broom imaging, the general process of geo-referenced image divided into grids is also presented. The new image rows and columns will be got through the geo-referenced image area dividing the ground sampling distance. Considering the error produced by round rule in the pixel grids generated progress, and the spectral mixing problem caused by traditional direct spectral sampling method in the process of image correction, the improved spectral sampling method based on the weighted fusion method was proposed. It takes the area proportion of adjacent pixels in the new generated pixel as coefficient and then the coefficients are normalized to avoid the spectral overflow. So the new generated pixel is combined with the geo-referenced adjacent pixels spectral. Finally the amounts of push-broom imaging experiments were taken on the ground, and the distortion images were corrected according to the algorithm proposed above. The results show that the linear image distortion correction algorithm is valid and robust. At the same time, multiple samples were selected in the corrected images to verify the spectral data. The results indicate that the improved spectral sampling method is better than the direct spectral sampling algorithm. It provides reference for the application of similar productions on the ground.

Near-infrared II aggregation-induced electrochemiluminescence of organic dots.

For the first time, we report novel aggregation-induced electrochemiluminescence (AIECL) of organic dots in aqueous media, with near-infrared II (NIR-II) luminescence peaked at 906 nm. Furthermore, a hybrid mechanism of ECL generation is revealed by various experiments in conjunction with theoretical calculations. This work opens a window for exploring efficient organic dye-based NIR-II AIECL emitters.

[Distribution Characteristics of Near Surface Ozone Volume Fraction in Shanxi Province Based on Atmospheric Composition Observation Network].

Based on the continuous data of O3， NO， NO2， and NOx and the meteorological data from March 2019 to February 2020 at six atmospheric composition observation stations in Shanxi Province， the characteristics and influence factors of O3 volume fractions were studied using statistical analysis and backward trajectory analysis. The results showed that O3 volume fractions were generally higher from April to September and lower from October to the following March. During the study period， O3 pollution represented by φ（MDA8O3）， i.e.， the maximum daily 8-h average of O3 volume fractions， was the most serious at the Jincheng and Linfen stations in the south of Shanxi， followed by that in the Wutaishan， Shuozhou， and Datong stations in the north， with the least pollution occurring at the Taiyuan station in the middle. There were differences between the urban and alpine stations， although their seasonal O3 volume fractions were both summer > spring > autumn > winter. O3 volume fractions at the urban station were usually lower than those at the alpine station； O3 at the urban station might have been influenced by photochemical reactions with precursor NOx； however， this was not the main source of high O3 at the alpine station. The peak and valley values appeared at 15：00 and 06：00， respectively， at the urban station， whereas they appeared at 20：00 and 10：00， respectively， at the alpine station， representing diametrically opposite diurnal variation patterns. Further， the daily amplitude of O3 at the urban station was much larger than that at the alpine station. For urban stations specifically， temperature was the most important meteorological factor affecting O3 volume fraction， compared with sunlight hours， precipitation， and total cloud cover. The NO2 volume fraction in the daytime affected the daily amplitude of O3； although the photochemical generation potential of O3 at the Taiyuan station was good， the O3 volume fractions were the lowest among urban stations due to strong NO titration. The higher O3 corresponded to lower NOx in which NO2 was dominant， and the higher NOx was largely composed of NO， under which conditions O3 would be depleted completely. The surface wind that affected O3 volume fractions of all stations primarily came from the southeast， south， and southwest， and specific wind speed led to the increase in O3 volume fraction. The geographical situation of the station would cause the difference in the transport of atmospheric pollutants， whereas the horizontal transmissions of high O3 from the North China Plain and Fenwei Plain were likely to be the common reason for the increase in O3 volume fraction in Shanxi.

[Self-made ultrasound/fluorescent bi-functional contrast agent for rabbit's normal lymph node imaging].

OBJECTIVE: To prepare a lymph node-targeted ultrasound/fluorescence bi-functional imaging contrast agents, and observe its effectiveness both on contrast-enhanced ultrasound (CEUS) and vivo near infrared fluorescence (NIR) imaging through animal experiments. METHODS: The chimeric lymph node-targeted ligand (phosphatidylserine) and near-infrared fluorescent substance were assembled to form bi-functional contrast microbubbles. The morphology and size distribution were detected by optical microscope and Malvern potential tests. Five normal New Zealand white rabbits were subcutaneously injected with the prepared contrast agent in bilateral footpads, and the imaging effectiveness of lymph nodes and lymphatic vessel were observed by CEUS and NIR technique. Then blue dye was subcutaneously injected at the same site, and the rabbits were sacrificed for lymph nodes pathological examination. RESULTS: Lipid ultrasound microbubbles,with a mean size of 3-5 Μm in diameter, appeared to be uniform in distribution and regular in configuration. The images of inflow lymphatic vessel and relevant lymph node were quickly showed up after the subcutaneous injection by CEUS, which was identical to the result detected by NIR. Biopsy confirmed that all the blue-stained lymph nodes could be displayed by NIR. CONCLUSIONS: The self-made bi-functional contrast agent has a good imaging ability in CEUS and NIR imaging. It may be a better agent as lymph node tracer.

Honey Mushroom, Armillaria mellea (Agaricomycetes) and Its Fermentation Products Target Regulation of OAT1/OAT3 Proteins to Reduce Hyperuricemia in Mice.

BACKGROUND: Disorders of purine metabolism are the main cause of hyperuricemia. Current drugs for the treatment of hyperuricemia usually cause a degree of cardiovascular damage. METHODS: This study aimed to investigate the therapeutic effects of Armillaria mellea fruiting body (AFB), Armillaria rhizomorph (AR) and Armillaria mellea fermentation product (after rhizomorphs removal) (AFP) on hyperuricemic mice. The hyperuricemia mouse model was established by oral administration of potassium oxonate 0.9 g⋅kg-1 and hypoxanthine 0.5 g⋅kg-1 for two weeks. Starting from the third week, the intragastric administration of the intervention drug group was as follows: Allopurinol 0.013 g⋅kg-1, AFB (3.9 and 7.8 g⋅kg-1), AR (3.9 and 7.8 g⋅kg-1), AFP (1.95 and 3.9 g⋅kg-1) once daily for 14 days. RESULTS: Results showed that AFB, AR, and AFP reduced the contents of serum uric acid, serum creatinine, and blood urea nitrogen in hyperuricemic mice and the mechanism of action might be through up-regulation of the expression levels of organic anion transporter 1/organic anion transporter 3 proteins in kidney tissue. AR and AFP both exhibited better uric acid-lowering effects than AFB, which may be due to the higher purine content of AFB. CONCLUSIONS: Armillaria mellea and its fermentation products can treat hyperuricemia by up-regulating OAT1 protein and OAT3 protein, reducing uric acid content in mice.

An intelligent DNA nanomachine for amplified MicroRNA imaging and MicroRNA-Guided efficient gene silencing.

The DNA nanomachines as excellent synthetic biological tools have been widely used for the sensitive detection of intracellular microRNA (miRNA) and DNAzyme-involved gene silencing. However, intelligent DNA nanomachines which have the ability to sense intracellular specific biomolecules and respond to external information in complex environments still remain challenging. Herein, we develop a miRNA-responsive DNAzyme cascaded catalytic (MDCC) nanomachine to perform multilayer cascade reactions, enabling the amplified intracellular miRNA imaging and miRNA-guided efficient gene silencing. The intelligent MDCC nanomachine is designed based on multiple DNAzyme subunit-encoded catalyzed hairpin assembly (CHA) reactants sustained by the pH-responsive Zeolitic imidazolate framework-8 (ZIF-8) nanoparticles. After cellular uptake, the MDCC nanomachine degrades in acidic endosome and releases three hairpin DNA reactants and Zn2+, and the latter can act as an effective cofactor for DNAzyme. In the presence of miRNA-21, a catalytic hairpin assembly (CHA) reaction is triggered, which produces a large number of Y-shaped fluorescent DNA constructs containing three DNAzyme modules for gene silencing. The construction of Y-shaped DNA modified with multisite fluorescence and the circular reaction realizes ultrasensitive miRNA-21 imaging of cancer cells. Moreover, miRNA-guided gene silencing inhibits the cancer cell proliferation through the DNAzyme-specific recognition and cleavage of target EGR-1 (Early Growth Response-1) mRNA, which is one key tumor-involved mRNA. The strategy may provide a promising platform for highly sensitive determination of biomolecules and accurate gene therapy of cancer cells.