Poly-adenine-mediated tetrahedral DNA nanostructure with multiple target-recognition sites for ultrasensitive and rapid electrochemical detection of Aflatoxin B1.

Tetrahedral DNA nanostructures (TDNs) are widely used in the development of electrochemical biosensors due to their structural stability, programmability, and strong interfacial orderliness. However, the complex modifications on the electrode and the single vertex target recognition of the TDNs limit their applications in electrochemical biosensing. Herein, we developed a universal detection system based on a novel polyadenine-based tetrahedral DNA nanostructure (ATDN) using Aflatoxin B1 (AFB1) as the model target for analysis. In the absence of target AFB1, the signal probes (SP) modified with ferrocene would be anchored by five aptamers on ATDN. The target capture by aptamers led to a release of SP from the electrode surface, resulting in a significant reduction of the electrochemical signal. This new nanostructure was not only dispensed with multi-step electrode modifications and strong mechanical rigidity but also had five modification sites which enhanced the detection sensitivity for the target. As a result, this biosensor shows good analytical performance in the linear range of 1 fg mL-1 to 1 ng mL-1, exhibiting a low detection limit of 0.33 fg mL-1. Satisfactory accuracy has also been demonstrated through good recoveries (95.2%-98.9%). The proposed new tetrahedral DNA nanostructure can provide a more rapid and sensitive alternative to previous electrochemical sensors based on the conventional TDN. Since DNA sequences can be designed flexibly, the sensing platform in this strategy can be extended to detect various targets in different fields.

Altered pupil responses to social and non-social stimuli in Shank3 mutant dogs.

Pupillary response, an important process in visual perception and social and emotional cognition, has been widely studied for understanding the neural mechanisms of neuropsychiatric disorders. However, there have been few studies on pupil response to social and non-social stimuli in animal models of neurodevelopmental disorders including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder. Here, we developed a pupilometer using a robust eye feature-detection algorithm for real-time pupillometry in dogs. In a pilot study, we found that a brief light flash induced a less-pronounced and slower pupil dilation response in gene-edited dogs carrying mutations in Shank3; mutations of its ortholog in humans were repeatedly identified in ASD patients. We further found that obnoxious, loud firecracker sound of 120 dB induced a stronger and longer pupil dilation response in Shank3 mutant dogs, whereas a high reward food induced a weaker pupillary response in Shank3 mutants than in wild-type control dogs. In addition, we found that Shank3 mutants showed compromised pupillary synchrony during dog-human interaction. These findings of altered pupil response in Shank3 mutant dogs recapitulate the altered sensory responses in ASD patients. Thus, this study demonstrates the validity and value of the pupilometer for dogs, and provides an effective paradigm for studying the underlying neural mechanisms of ASD and potentially other psychiatric disorders.

Identification of multi-component metal ion mixtures in complex systems using fluorescence sensor arrays.

The growing co-contamination of multiple metal ions seriously influences human health due to their synergistic and additive toxicological effects, whereas the rapid discrimination of multiple heavy metal ions in complex aquatic systems remains a major challenge. Herein, a high- throughput fluorescence sensor array was fabricated based on three gold nanoclusters (GSH-Au NCs, OVA-Au NCs, and BSA-Au NCs) for the direct identification and quantification of seven heavy metal ions (Pb2+, Fe3+, Cu2+, Co2+, Ag+, Hg2+ and As3+) from environmental waters without sample pretreatment other than filtration. At the detection system, three gold nanoclusters with various ligands possessed distinct binding capacities against metal ions and induced aggregation-induced fluorescence enhancement and quenching, resulting in a unique pattern of fluorescence variations. Meanwhile, integrated the collected fluorescence fingerprints with linear discriminant analysis (LDA) and hierarchical cluster analysis (HCA), a discrete database was obtained for the accurate recognition and sensitive detection of metal ions. Under the optimized conditions, the limit of detection (LOD) of the proposed fluorescence sensor array for metal ions detection at nM concentration level along with a satisfactory accuracy. Importantly, our study indicated that the fluorescence sensor array could be widely used as a general platform in environmental monitoring against multiple targets at low concentrations.

The role of the vagus nerve on dexmedetomidine promoting survival and lung protection in a sepsis model in rats.

BACKGROUND: Sepsis often results in acute lung injury (ALI). Dexmedetomidine (Dex) was reported to protect cells and organs due to its direct cellular effects. This study aims to investigate the role of vagus nerves on Dex induced lung protection in lipopolysaccharide (LPS)-induced ALI rats. METHODS: The bilateral cervical vagus nerve of male Sprague-Dawley rats was sectioned or just exposed as sham surgery. After LPS administration, Dex antagonist yohimbine (YOH) and/or Dex was injected intraperitoneally to rats with or without vagotomy. The severity of ALI was determined with survival curve analysis and lung pathological scores. The plasma concentrations of interleukin 1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), catecholamine and acetylcholine were measured with enzyme-linked immunosorbent assay. RESULTS: The median survival time of LPS-induced ALI rats was prolonged by Dex (22 h, 95% CI, [24.46, 92.20]) vs. 14 h, 95% CI, [14.60, 89.57] of the LPS control group, P < 0.05), and the ALI score was reduced by Dex (6.5, 95% CI, [5.23, 8.10] vs. 11.5, 95% CI, [10.23, 13.10] in the LPS group, P < 0.01). However, these protective effects were significantly decreased by either YOH administration or vagotomy. Dex decreased LPS-induced IL-1ß, TNF-α, and catecholamine but increased acetylcholine in blood serum; these effects of Dex was partially abolished by vagotomy. CONCLUSIONS: Our data suggested that Dex increased vagal nerve tone that partially contributed to its anti-inflammatory and lung-protective effects. The indirect anti-inflammation and direct cytoprotection of Dex are likely through high vagal nerve tone and α2-adrenoceptor activation, respectively.

FHL1 promotes glioblastoma aggressiveness through regulating EGFR expression.

The four-and-a-half LIM domain protein 1 (FHL1) plays a key role in multiple cancers. Here, we characterized its role in glioblastoma (GBM), the most common and incurable form of brain cancer. Overexpression of FHL1 promotes growth, migration, and invasion of GBM cells in vivo and in vitro. In contrast, FHL1 silencing by RNAi exhibits the opposite effects. FHL1 interacts with the transcription factor SP1 to upregulate epidermal growth factor receptor (EGFR) expression and activate the downstream signaling cascades, including Src, Akt, Erk1/2, and Stat3, leading to GBM malignancy. FHL1 is highly expressed and positively correlated with EGFR levels in human GBM, particularly those of the classical subtype. Our results suggest that the FHL1-SP1-EGFR axis plays a tumor-promoting role, and highlight the translational potential of inhibiting FHL1 for GBM treatment.

Two dimensional ZnO/AlN composites used for photocatalytic water-splitting: a hybrid density functional study.

Using hybrid density functionals, we study the interfacial interactions and electronic properties of ZnO/AlN composites with the consideration of rotation angles and biaxial strains in order to enhance the photocatalytic performance for water-splitting. The different rotated composites, and -2% strained, original, and 2% strained ZnO/AlN composites can be easily prepared owing to the negative interface formation energies. The bandgaps and band alignments of ZnO/AlN composites can be significantly tuned by biaxial strains. Particularly, the appropriate bandgap for visible light absorption, proper band alignment for spontaneous water-splitting, and the formed electric field promoting photoinduced carrier separation make the 2% strained ZnO/AlN composite a potential candidate for photocatalytic water-splitting. This work shines some light on designing two dimensional heterostructured photocatalysts.