Pathogenicity and landscape of differential gene expression in mice orally infected with clinical coxsackievirus A6 (CA6).

Hand, foot, and mouth disease (HFMD) is caused by more than 20 pathogenic enteroviruses belonging to the Picornaviridae family and Enterovirus genus. Since the introduction of the enterovirus-71 (EV71) vaccine in 2016, the number of HFMD cases caused by EV71 has decreased. However, cases of infections caused by other enteroviruses, such as coxsackievirus A6 (CA6) and coxsackievirus A10, have been increasing accordingly. In this study, we used a clinical isolate of CA6 to establish an intragastric infection mouse model using 7-day-old mice to mimic the natural transmission route, by which we investigated the differential gene expression profiles associated with virus infection and pathogenicity. After intragastric infection, mice exhibited hind limb paralysis symptoms and weight loss, similar to those reported for EV71 infection in mice. The skeletal muscle was identified as the main site of virus replication, with a peak viral load reaching 2.31 × 107 copies/mg at 5 dpi and increased infiltration of inflammatory cells. RNA sequencing analysis identified differentially expressed genes (DEGs) after CA6 infection. DEGs in the blood, muscle, brain, spleen, and thymus were predominantly enriched in immune system responses, including pathways such as Toll-like receptor signaling and PI3K-Akt signaling. Our study has unveiled the genes involved in the host immune response during CA6 infection, thereby enhancing our comprehension of the pathological mechanism of HFMD.IMPORTANCEThis study holds great significance for the field of hand, foot, and mouth disease (HFMD). It not only delves into the disease's etiology, transmission pathways, and severe complications but also establishes a novel mouse model that mimics the natural coxsackievirus A6 infection process, providing a pivotal platform to delve deeper into virus replication and pathogenic mechanisms. Additionally, utilizing RNA-seq technology, it unveils the dynamic gene expression changes during infection, offering valuable leads for identifying novel therapeutic drug targets. This research has the potential to enhance our understanding of HFMD, offering fresh perspectives for disease prevention and treatment and positively impacting children's health worldwide.

Distinguishable Magnetic Reporter Coordination with Buoyancy-Magnetism Separation for Immobilization-Free Dual-Target Electrochemical Immunosensing.

Simultaneous sensitive and precise determination of multibiomarkers is of great significance for improving detection efficiency, reducing diagnosis and treatment expenses, and elevating survival rates. However, the development of simple and portable biosensors for simultaneous determination of multiplexed targets in biological fluids still faces challenges. Herein, a unique and versatile immobilization-free dual-target electrochemical biosensing platform, which combines distinguishable magnetic signal reporters with buoyancy-magnetism separation, was designed and constructed for simultaneous detection of carcinoembryonic (CEA) and α-fetoprotein (AFP) in intricate biological fluids. To construct such distinguishable magnetic signal reporters with signal transduction, amplification, and output, secondary antibodies of CEA and AFP were respectively functionalized on methylene blue (MB) and 6-(ferrocenyl)hexanethiol (FeC) modified Fe3O4@Au magnetic nanocomposites. Meanwhile, a multifunctional flotation probe with dual target recognition, capture, and isolation capability was prepared by conjugating primary antibodies (Ab1-CEA, Ab1-AFP) to hollow buoyant microspheres. The target antigens of CEA and AFP can trigger a flotation-mediated sandwich-type immunoreaction and capture a certain amount of the distinguishable magnetic signal reporter, which enables the conversion of the target CEA and AFP quantities to the signal of the potential-resolved MB and FeC. Thus, the MB and FeC currents of magnetically adsorbed distinguishable magnetic reporters can be used to determine the CEA and AFP targets simultaneously and precisely. Accordingly, the proposed strategy exhibited a delightful linear response for CEA and AFP in the range of 100 fg·mL-1-100 ng·mL-1 with detection limits of 33.34 and 17.02 fg·mL-1 (S/N = 3), respectively. Meanwhile, no significant nonspecific adsorption and cross-talk were observed. The biosensing platform has shown satisfactory performance in the determination of real clinical samples. More importantly, the proposed approach can be conveniently extended to universal detection just by simply substituting biorecognition events. Thus, this work opens up a new promising perspective for dual and even multiple targets and offers promising potential applications in clinical diagnosis.

Illness uncertainty and dysphagia in Chinese oral cancer patients: the mediation effect of catastrophic cognition.

PURPOSE: Dysphagia, a serious symptom of oral cancer, is also the most common. Further, patients who are more uncertain regarding their illness tend to catastrophize, which may affect their rehabilitation and long-term survival rate. Considering this relationship, this study aimed to investigate the occurrence of dysphagia in Chinese patients with oral cancer and explore the correlation between catastrophic cognition, illness uncertainty, and dysphagia. METHODS: Applying a cross-sectional design, convenience sampling was used to recruit 180 patients with oral cancer. Advanced statistical methods were employed to analyze the mediating effects of catastrophic cognition on illness uncertainty and dysphagia. RESULTS: Chinese patients with oral cancer had a mean dysphagia score of 52.88 ± 10.95. Catastrophic cognition and illness uncertainty in patients with oral cancer were significantly positively correlated (r = 0.447, P < 0.001). There was a significant negative correlation between dysphagia score and catastrophic cognition (r = -0.385, P < 0.001), and between dysphagia and illness uncertainty (r = -0.522, P < 0.001). Bootstrapping results indicated that the mediating effect of catastrophic cognition between illness uncertainty and dysphagia was -0.07 (95% CI: [-0.15, -0.03]) and significant, and the mediation effect accounted for 15.6% of the total effect. CONCLUSIONS: Chinese patients with oral cancer have poor swallowing function. Results suggest that catastrophic cognition partially mediated the relationship between illness uncertainty and dysphagia in patients with oral cancer. Medical staff can improve patients' swallowing function by reducing the level of catastrophic cognition via decreasing the level of illness uncertainty.

A novel dual-signal output strategy for POCT of CEA based on a smartphone electrochemical aptasensing platform.

A smartphone-based electrochemical aptasensing platform was developed for the point-of-care testing (POCT) of carcinoembryonic antigen (CEA) based on the ferrocene (Fc) and PdPt@PCN-224 dual-signal labeled strategy. The prepared PdPt@PCN-224 nanocomposite showed a strong catalytic property for the reduction of H2O2. Phosphate group-labeled aptamer could capture PdPt@PCN-224 by Zr-O-P bonds to form PdPt@PCN-224-P-Apt. Therefore, a dual signal labeled probe was formed by the hybridization between Fc-DNA and PdPt@PCN-224-P-Apt. The presence of CEA forced PdPt@PCN-224-P-Apt to leave the electrode surface due to the specific affinity, leading to the decrease of the reduction current of H2O2. At the same time, the Fc-DNA strand changed to hairpin structure, which made Fc closer to the electrode and resulted in the increase of the oxidation current of Fc. Thus, CEA can be accurately determined through both signals: the decrease of H2O2 reduction current and the increase of Fc oxidation current, which could avoid the false positive signal. Under the optimal conditions, the prepared aptasensor exhibited a wide linear range from 1 pg·mL-1 to 100 ng·mL-1 and low detection limits of 0.98 pg·mL-1 and 0.27 pg·mL-1 with Fc and PdPt@PCN-224 as signal labels, respectively. The aptasensor developed in this study has successfully demonstrated its capability to detect CEA in real human serum samples. These findings suggest that the proposed sensing platform will hold great potential for clinical tumor diagnosis and monitoring.

Fascinating Immobilization-Free Electrochemical Immunosensing Strategy Based on the Cooperation of Buoyancy and Magnetism.

Rapid and accurate detection of biomolecules is of vital importance for the diagnosis of disease and for performing timely treatments. The point-of-care analysis of cancer biomarkers in the blood with low cost and easy processing is still challenging. Herein, an advanced and robust strategy, which integrates the buoyant recognition probe with the magnetic reporter probe in one solution, was first proposed for immobilization-free electrochemical immunosensing. The tumor marker of alpha fetoprotein (AFP) can be captured immune-buoyantly, and then a multifunctional magnetic reporter probe in pseudo-homogeneous solution was further captured to fulfill a sandwich-type immunoreaction. The residual magnetic reporter probe can be firmly and efficiently attracted on a magnetic glassy carbon electrode to fulfill the conversion of the target AFP amount into the residual magnetic electrochemical signal indicator. As a result, the electrochemical signal of methylene blue can accurately reflect the original level of target antigen AFP concentration. By integrating buoyancy-driven quasi-homogenous biorecognition with magnetism-mediated amplification and signal output, the proposed immobilization-free electrochemical immunosensing strategy displayed a wide range of linear response (100 fg mL-1 to 10 ng mL-1), low detection limit (14.52 fg mL-1), and good reproducibility, selectivity, and stability. The designed strategy manifests remarkable advantages including assay simplicity, rapidness, and high sensitivity owing to the in-solution instead of on-electrode biorecognition that could accelerate and improve the biorecognition efficiency. To the best of our knowledge, this is the first cooperation of buoyancy-driven biorecognition with magnetism-mediated signal output in bioanalysis, which would be attractive for rapid clinic biomedical application. Thus, this work provides a fresh perspective for convenient and favorable immobilization-free electrochemical biosensing of universal biomolecules.

Both epilepsy and anti-seizure medications affect bone metabolism in children with self-limited epilepsy with centrotemporal spikes.

OBJECTIVE: Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism. METHODS: Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D3 (VD3 ). RESULTS: A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD3 , other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316). SIGNIFICANCE: Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.

A label-free electrochemical aptasensor based on Bi-Sb alloy materials for potential POCT of HER-2.

As a prognostic biomarker for breast cancer, human epidermal growth factor receptor 2 (HER-2) is of crucial diagnostic value. Here, a label-free electrochemical aptasensor was established for the ultrasensitive detection of HER-2 using a modified electrode of Bi-Sb alloy materials (Bi-Sb AMs). The performance of the aptasensor was enhanced greatly due to the introduction of Bi-Sb alloy materials (Bi-Sb AMs) with high conductivity. Furthermore, by integrating the aptasensor with the Sensit Smart U-disk electrochemical analyzer, the point-of-care testing (POCT) for HER-2 was realized. Under the optimal experimental parameters, the POCT analyzer showed a wide linear response from 0.01 pg mL-1 to 100 ng mL-1, with a low detection limit (LOD) of 5.96 fg mL-1 for the detection of HER-2. The presented POCT analyzer exhibited good specificity, stability, and reproducibility. Benefiting from the simple operation and rapid testing, the developed analyzer will have potential application in the prognostic diagnosis and treatment of breast cancer.

The effects of brominated flame retardants (BFRs) on pro-atherosclerosis mechanisms.

Brominated flame-retardants (BFRs) are environmental endocrine disruptors, comprising several pollutants, which potentially affect the endocrine system and cause dysfunction and disease. Widespread BFR exposure may cause multisystem toxicity, including cardiovascular toxicity in some individuals. Studies have shown that BFRs not only increase heart rate, induce arrhythmia and cardiac hypertrophy, but also cause glycolipid metabolism disorders, vascular endothelial dysfunction, and inflammatory responses, all of which potentially induce pre-pathological changes in atherosclerosis. Experimental data indicated that BFRs disrupt gene expression or signaling pathways, which cause vascular endothelial dysfunction, lipid metabolism-related disease, inflammation, and possibly atherosclerosis. Considerable evidence now suggests that BFR exposure may be a pro-atherosclerotic risk factor. In this study, we reviewed putative BFR effects underpinning pro-atherosclerosis mechanisms, and focused on vascular endothelial cell dysfunction, abnormal lipid metabolism, pro-inflammatory cytokine production and foam cell formation. Consequently, we proposed a scientific basis for preventing atherosclerosis by BFRs and provided concepts for further research.

Ratiometric Electrochemiluminescence Sensing of Carcinoembryonic Antigen Based on Luminol.

Ratiometric electrochemiluminescence (ECL) sensors can efficiently remove environmental interference to attain precise detection. Nonetheless, two eligible luminophores or coreactants were usually needed, increasing the complexity and restricting their practical application. In this study, a single luminophore of luminol with a single coreactant of H2O2 was employed to construct a dual-potential ratiometric ECL sensor for the detection of carcinoembryonic antigen (CEA). The produced palladium nanoclusters (Pd NCs) employing a DNA duplex as a template could not only stimulate luminol to produce cathodic ECL (Icathodic) but also quench its anodic ECL (Ianodic). During the detection process, CEA could damage the double-stranded structure and reduce the Pd NCs' amount, triggering a significant decrease in the ratio of Icathodic to Ianodic (Icathodic/Ianodic) and thereby achieving sensitive CEA's detection. Furthermore, the Icathodic/Ianodic was independent of the H2O2 concentration, which avoided a prejudicial effect from H2O2 decomposition and considerably enhanced the detection's reliability. The developed ratiometric ECL sensor demonstrated a sensitive detection toward CEA with a wide linear range from 100 ag/mL to 10 ng/mL and a detection limit of 87.1 ag/mL (S/N = 3). In conclusion, this study offers a new idea for constructing ratiometric ECL sensors based on a single luminophore and technical support for cancer's early diagnosis.

The identification of polyvalent protective immunogens and immune abilities from the outer membrane proteins of Aeromonas hydrophila in fish.

Among aquaculture vaccines, polyvalent vaccines (for immunoprotection against multiple bacterial species) are more efficient and can better avoid bacterial resistance and antibiotic residues in fish. Here, 15 outer membrane proteins (OMPs) of Aeromonas hydrophila were cloned and purified, and mouse antisera were prepared. Passive immunization to Carassius auratus showed that four OMPs sera (OmpW, OmpAII, P5, and AHA2685) and the entire OMPs serum held effective immunoprotection against A. hydrophila infection. Furthermore, the active immunization of four OMPs to C. auratus showed that OmpW, OmpAII, P5, and AHA2685 held effective immunoprotection against A. hydrophila, and OmpW held active cross-protection against Vibrio alginolyticus. The mechanisms of these four candidate vaccines in triggering immune responses were subsequently explored. They all could activate innate immune responses in active immunization, down-regulate (p < 0.05) the inflammation-related genes expression to reduce the inflammatory reaction induced by A. hydrophila, and down-regulate (p < 0.05) antioxidant-related factors to reduce the antioxidant reaction for bacterial infection. Noteablely, the four OMPs had protective abilities on kidney and spleen tissues of C. auratus after challenged with A. hydrophila and V. alginolyticus by histopathological observation. Collectively, our results identify OmpW as a polyvalent vaccine candidate, and OmpAII, P5, and AHA2685 as vaccine candidates against A. hydrophila infection in fish.

UNC13B variants associated with partial epilepsy with favourable outcome.

The unc-13 homolog B (UNC13B) gene encodes a presynaptic protein, mammalian uncoordinated 13-2 (Munc13-2), which is highly expressed in the brain-predominantly in the cerebral cortex-and plays an essential role in synaptic vesicle priming and fusion, potentially affecting neuronal excitability. However, the functional significance of the UNC13B mutation in human disease is not known. In this study, we screened for novel genetic variants in a cohort of 446 unrelated cases (families) with partial epilepsy without acquired causes by trio-based whole-exome sequencing. UNC13B variants were identified in 12 individuals affected by partial epilepsy and/or febrile seizures from eight unrelated families. The eight probands all had focal seizures and focal discharges in EEG recordings, including two patients who experienced frequent daily seizures and one who showed abnormalities in the hippocampus by brain MRI; however, all of the patients showed a favourable outcome without intellectual or developmental abnormalities. The identified UNC13B variants included one nonsense variant, two variants at or around a splice site, one compound heterozygous missense variant and four missense variants that cosegregated in the families. The frequency of UNC13B variants identified in the present study was significantly higher than that in a control cohort of Han Chinese and controls of the East Asian and all populations in the Genome Aggregation Database (gnomAD). Computational modelling, including hydrogen bond and docking analyses, suggested that the variants lead to functional impairment. In Drosophila, seizure rate and duration were increased by Unc13b knockdown compared to wild-type flies, but these effects were less pronounced than in sodium voltage-gated channel alpha subunit 1 (Scn1a) knockdown Drosophila. Electrophysiological recordings showed that excitatory neurons in Unc13b-deficient flies exhibited increased excitability. These results indicate that UNC13B is potentially associated with epilepsy. The frequent daily seizures and hippocampal abnormalities but ultimately favourable outcome under anti-epileptic therapy in our patients indicate that partial epilepsy caused by UNC13B variant is a clinically manageable condition.

Frequency Stability Prediction of Power Systems Using Vision Transformer and Copula Entropy.

This paper addresses the problem of frequency stability prediction (FSP) following active power disturbances in power systems by proposing a vision transformer (ViT) method that predicts frequency stability in real time. The core idea of the FSP approach employing the ViT is to use the time-series data of power system operations as ViT inputs to perform FSP accurately and quickly so that operators can decide frequency control actions, minimizing the losses caused by incidents. Additionally, due to the high-dimensional and redundant input data of the power system and the O(N2) computational complexity of the transformer, feature selection based on copula entropy (CE) is used to construct image-like data with fixed dimensions from power system operation data and remove redundant information. Moreover, no previous FSP study has taken safety margins into consideration, which may threaten the secure operation of power systems. Therefore, a frequency security index (FSI) is used to form the sample labels, which are categorized as "insecurity", "relative security", and "absolute security". Finally, various case studies are carried out on a modified New England 39-bus system and a modified ACTIVSg500 system for projected 0% to 40% nonsynchronous system penetration levels. The simulation results demonstrate that the proposed method achieves state-of-the-art (SOTA) performance on normal, noisy, and incomplete datasets in comparison with eight machine-learning methods.

A novel ratiometric electrochemical biosensing strategy based on T7 exonuclease-assisted homogenous target recycling coupling hairpin assembly-triggered double-signal output for the multiple amplified detection of miRNA.

A novel ratiometric electrochemical biosensing strategy based on T7 exonuclease (T7 Exo)-assisted homogenous target recycling coupling hairpin assembly triggered dual-signal output was proposed for the accurate and sensitive detection of microRNA-141 (miRNA-141). Concretely, in the presence of target miRNA, abundant signal transduction probes were released via the T7 Exo-assisted homogenous target recycling amplification, which could be captured by the specially designed ferrocene-labeled hairpin probe (Fc-H1) on -electrode interface and triggered the nonenzymatic catalytic hairpin assembly (Fc-H1 + MB-H2) to realize the cascade signal amplification and dual-signal output. Through such a conformational change process, the electrochemical signal of Fc (IFc) and MB (IMB) is proportionally and substantially decreased and increased. Therefore, the signal ratio of IMB/IFc can be employed to accurately reflect the true level of original miRNA. Benefiting from the efficient integration of the T7 Exo-assisted target recycle, nonenzymatic hairpin assembly and dual-signal output mode, the proposed sensor could realize the amplified detection of miRNA-141 effectively with a wide detection range from 1 fM to 100 pM, and a detection limit of 200 aM. Furthermore, it exhibits outstanding sequence specificity to discriminate mismatched RNA, acceptable reproducibility and feasibility for real sample. This strategy effectively integrated the advantages of multiple amplification and ratiometric output modes, which could provide an accurate and efficient method in biosensing and clinical diagnosis.

Graphene-PtPd nanocomposite for low-potential-driven electrochemiluminescent determination of carcinoembryonic antigen using Ru(bpy)32.

As well known, the electrochemiluminescence (ECL) of tris(2,2'-bipyridine)ruthenium(II) (Ru(bpy)32+) heavily relies on highly positive or negative triggered voltage, prejudicing the detection toward the bio-molecules. In this work, Ru(bpy)32+ could generate enhanced and stable ECL at a low potential of 0.05 V (vs. Ag/AgCl) on graphene-PtPd hybrid, attributing to its excellent electrocatalysis from the synergistic effect between Pt and Pd. The obtained low-potential-driven ECL could be quenched by MoS2 nanoflowers. Based on the quenching effect, a sandwich "signal-off" ECL immunosensor was fabricated to sensitively detect carcinoembryonic antigen (CEA). A linear calibration curve from 1 fg mL-1 to 1 ng mL-1 was obtained along with a low detection limit of 0.54 fg mL-1 (S/N = 3) under optimal conditions. The sensor showed satisfactory specificity, stability, and reproducibility and was successfully applied to determine CEA in actual samples. The recoveries ranged from 98.80 to 100.23%, and the relative standard deviation (RSD) was lower than 5%. Above all, this work explored new materials in low-potential-driven ECL system and provided a reliable sensing strategy for clinical applications.

DCSST Multi-Modular Equalization Scheme Based on Distributed Control.

As an important part of the DC micro-grid, DC solid-state transformers (DCSST) usually use a dual-loop control that combines the input equalization and output voltage loop. This strategy fails to ensure output equalization when the parameters of each dual active bridge (DAB) converter module are inconsistent, thus reducing the operational efficiency of the DCSST. To solve the above problems, a DCSST-balancing control strategy based on loop current suppression is presented. By fixing the phase-shifting angle within the bridge and adjusting the phase-shifting angle between bridges, the circulation current of each DAB converter module is reduced. Based on the double-loop control of the DAB, five controllers are nested outside each DAB submodule to achieve distributed control of the DCSST. The proposed control strategy can reduce the system circulation current with different circuit parameters of the submodules, ensure the balance of input voltage and output current of each submodule, and increase the robustness of the system. The simulation results verify the validity of the proposed method.

Restoring extracellular matrix synthesis in senescent stem cells.

Collagen type III (COL3) is one of the 3 major collagens in the body, and loss of expression or mutations in the COL3 gene have been associated with the onset of vascular diseases such the Ehlers-Danlos syndrome. Previous work reported a significant reduction of COL3 in tissues such as skin and vessels with aging. In agreement, we found that COL3 was significantly reduced in senescent human mesenchymal stem cells and myofibroblasts derived from patients with Hutchinson-Gilford progeria syndrome, a premature aging syndrome. Most notably, we discovered that ectopic expression of the embryonic transcription factor Nanog homeobox (NANOG) restored COL3 expression by restoring the activity of the TGF-ß pathway that was impaired in senescent cells. RNA sequencing analysis showed that genes associated with the activation of the TGF-ß pathway were up-regulated, whereas negative regulators of the pathway were down-regulated upon NANOG expression. Chromatin immunoprecipitation sequencing and immunoprecipitation experiments revealed that NANOG bound to the mothers against decapentaplegic (SMAD)2 and SMAD3 promoters, in agreement with increased expression and phosphorylation levels of both proteins. Using chemical inhibition, short hairpin RNA knockdown, and gain of function approaches, we established that both SMAD2 and SMAD3 were necessary to mediate the effects of NANOG, but SMAD3 overexpression was also sufficient for COL3 production. In summary, NANOG restored production of COL3, which was impaired by cellular aging, suggesting novel strategies to restore the impaired extracellular matrix production and biomechanical function of aged tissues, with potential implications for regenerative medicine and anti-aging treatments.-Rong, N., Mistriotis, P., Wang, X., Tseropoulos, G., Rajabian, N., Zhang, Y., Wang, J., Liu, S., Andreadis, S. T. Restoring extracellular matrix synthesis in senescent stem cells.

Enzyme-free and triple-amplified electrochemical sensing of 8-hydroxy-2'-deoxyguanosine by three kinds of short pDNA-driven catalyzed hairpin assemblies followed by a hybridization chain reaction.

A sensitive and enzyme-free electrochemical aptasensor was constructed for the sensing of 8-hydroxy-2'-deoxyguanosine (8-OH-dG). In the process of constructing the aptasensor, triple signal amplification strategies were introduced to enhance the sensitivity. First, every aptamer/pDNA complex immobilized on magnetic beads could release three kinds of pDNAs when 8-OH-dG was introduced, which caused three-fold magnification of the target. Second, the released three kinds of pDNAs initiated catalyzed hairpin assembly between two hairpin DNAs (HP1 and HP2) on a gold electrode. Meanwhile, the three kinds of pDNAs were released again by a strand displacement reaction to obtain the next catalyzed hairpin assembly. Third, the emerging toehold of HP2 further induced a hybridization chain reaction (HCR) between two hairpin DNAs (HP3 and HP4), forming a long double-stranded DNA concatemer on the surface of the electrode. Finally, [Ru(NH3)6]3+, an electroactive cation, was adsorbed onto the long dsDNA concatemer by electrostatic interactions and consequently, an electrochemical signal was generated. Under this triple signal amplification, a low detection limit down to 24.34 fM has been obtained for 8-OH-dG determination, which is superior to those of most previously reported methods.

NANOG Reverses the Myogenic Differentiation Potential of Senescent Stem Cells by Restoring ACTIN Filamentous Organization and SRF-Dependent Gene Expression.

Cellular senescence as a result of organismal aging or progeroid diseases leads to stem cell pool exhaustion hindering tissue regeneration and contributing to the progression of age related disorders. Here we discovered that ectopic expression of the pluripotent factor NANOG in senescent or progeroid myogenic progenitors reversed cellular aging and restored completely the ability to generate contractile force. To elicit its effects, NANOG enabled reactivation of the ROCK and Transforming Growth Factor (TGF)-ß pathways-both of which were impaired in senescent cells-leading to ACTIN polymerization, MRTF-A translocation into the nucleus and serum response factor (SRF)-dependent myogenic gene expression. Collectively our data reveal that cellular senescence can be reversed and provide a novel strategy to regain the lost function of aged stem cells without reprogramming to the pluripotent state. Stem Cells 2017;35:207-221.

[Gene mutations in unexplained infantile epileptic encephalopathy: an analysis of 47 cases].

OBJECTIVE: To investigate the characteristics of gene mutations in unexplained infantile epileptic encephalopathy (EE). METHODS: A total of 47 infants with unexplained infantile EE were enrolled, and next-generation sequencing was used to analyze gene mutations in these infants and their parents. RESULTS: Of all 47 infants, 23 were found to have gene mutations, among whom 13 had de novo mutations and 10 had heterozygous mutations inherited from their father or mother. Among the 23 infants with gene mutations, 17 were found to have the gene mutations related to EE (among whom 14 had ion channel gene mutations), 2 had the gene mutations related to congenital inherited metabolic diseases, 2 had the gene mutations related to brain structural abnormality, and 2 had the gene mutations related to mental retardation. CONCLUSIONS: Unexplained infantile EE may have gene mutations, mainly ion channel gene mutations.