Enhanced Circular Dichroism for Achiral Sensing Based on a DNA-Origami-Empowered Anapole Metasurface.

Circular dichroism (CD) spectroscopy has been extensively utilized for detecting and distinguishing the chirality of diverse substances and structures. However, CD spectroscopy is inherently weak and conventionally associated with chiral sensing, thus constraining its range of applications. Here, we report a DNA-origami-empowered metasurface sensing platform through the collaborative effect of metasurfaces and DNA origami, enabling achiral/slightly chiral sensing with high sensitivity via the enhanced ΔCD. An anapole metasurface, boasting over 60 times the average optical chirality enhancement, was elaborately designed to synergize with reconfigurable DNA origami. We experimentally demonstrated the detection of achiral/slightly chiral DNA linker strands via the enhanced ΔCD of the proposed platform, whose sensitivity was a 10-fold enhancement compared with the platform without metasurfaces. Our work presents a high-sensitivity platform for achiral/slightly chiral sensing through chiral spectroscopy, expanding the capabilities of chiral spectroscopy and inspiring the integration of multifunctional artificial nanostructures across diverse domains.

SPL16 and SPL23 mediate photoperiodic control of seasonal growth in Populus trees.

Perennial trees in boreal and temperate regions undergo growth cessation and bud set under short photoperiods, which are regulated by phytochrome B (phyB) photoreceptors and PHYTOCHROME INTERACTING FACTOR 8 (PIF8) proteins. However, the direct signaling components downstream of the phyB-PIF8 module remain unclear. We found that short photoperiods suppressed the expression of miR156, while upregulated the expression of miR156-targeted SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE 16 (SPL16) and SPL23 in leaves and shoot apices of Populus trees. Accordingly, either overexpression of MIR156a/c or mutagenesis of SPL16/23 resulted in the attenuation of growth cessation and bud set under short days (SD), whereas overexpression of SPL16 and SPL23 conferred early growth cessation. We further showed that SPL16 and SPL23 directly suppressed FLOWERING LOCUS T2 (FT2) expression while promoted BRANCHED1 (BRC1.1 and BRC1.2) expression. Moreover, we revealed that PIF8.1/8.2, positive regulators of growth cessation, directly bound to promoters of MIR156a and MIR156c and inhibited their expression to modulate downstream pathways. Our results reveal a connection between the phyB-PIF8 module-mediated photoperiod perception and the miR156-SPL16/23-FT2/BRC1 regulatory cascades in SD-induced growth cessation. Our study provides insights into the rewiring of a conserved miR156-SPL module in the regulation of seasonal growth in Populus trees.

Phytochrome-interacting factors play shared and distinct roles in regulating shade avoidance responses in Populus trees.

Plants adjust their growth and development in response to changing light caused by canopy shade. The molecular mechanisms underlying shade avoidance responses have been widely studied in Arabidopsis and annual crop species, yet the shade avoidance signalling in woody perennial trees remains poorly understood. Here, we first showed that PtophyB1/2 photoreceptors serve conserved roles in attenuating the shade avoidance syndrome (SAS) in poplars. Next, we conducted a systematic identification and characterization of eight PtoPIF genes in Populus tomentosa. Knocking out different PtoPIFs led to attenuated shade responses to varying extents, whereas overexpression of PtoPIFs, particularly PtoPIF3.1 and PtoPIF3.2, led to constitutive SAS phenotypes under normal light and enhanced SAS responses under simulated shade. Notably, our results revealed that distinct from Arabidopsis PIF4 and PIF5, which are major regulators of SAS, the Populus homologues PtoPIF4.1 and PtoPIF4.2 seem to play a minor role in controlling shade responses. Moreover, we showed that PtoPIF3.1/3.2 could directly activate the expression of the auxin biosynthetic gene PtoYUC8 in response to shade, suggesting a conserved PIF-YUC-auxin pathway in modulating SAS in tree. Overall, our study provides insights into shared and divergent functions of PtoPIF members in regulating various aspects of the SAS in Populus.

Opportunities and challenges for DNA in atomic and close-to-atomic scale manufacturing.

The revolutionary products obtained from atomic and close-to-atomic scale manufacturing (ACSM) has motivated people to conduct more in-depth research. There is a pressing need to surpass the constraints of current technology and achieve precise construction at the atomic scale. The emergence of DNA nanotechnology has enabled DNA to serve as a template for precisely localizing functional components. These advantages of DNA in bottom-up manufacturing give it great potential in ACSM. From this perspective, we review the ability of DNA to accurately build complex structures and discuss its application and prospects in precise atomic manipulation. Finally, opportunities and challenges for DNA in ACSM are systematically summarized.

Deep brain stimulation of the nucleus basalis of Meynert in an experimental rat model of dementia: Stimulation parameters and mechanisms.

BACKGROUND/OBJECTIVE: Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) has gained interest as a potential therapy for treatment-resistant dementia. However, optimal stimulation parameters and mechanisms of action are yet to be elucidated. METHODS: First, we assessed NBM DBS at different stimulation parameters in a scopolamine-induced rat model of dementia. Rats were tested in the object location task with the following conditions: (i) low and high frequency (20 Hz or 120 Hz), (ii) monophasic or biphasic pulse shape (iii) continuous or intermittent DBS (20s on, 40s off) and 100 µA amplitude. Thereafter, rats were stimulated with the most effective parameter followed by 5-bromo-2'-deoxyuridine (BrdU) administration and perfused 4 weeks later. We then evaluated the effects of NBM DBS on hippocampal neurogenesis, synaptic plasticity, and on cholinergic fibres in the perirhinal and cingulate cortex using immunohistochemistry. We also performed in-vivo microdialysis to assess circuit-wide effects of NBM DBS on hippocampal acetylcholine levels during on and off stimulation. RESULTS: Biphasic, low frequency and intermittent NBM DBS reversed the memory impairing effects of scopolamine when compared to sham rats. We found that acute stimulation promoted proliferation in the dentate gyrus, increased synaptic plasticity in the CA1 and CA3 subregion of the hippocampus, and increased length of cholinergic fibres in the cingulate gyrus. There was no difference regarding hippocampal acetylcholine levels between the groups. CONCLUSION: These findings suggest that the potential mechanism of action of the induced memory enhancement through NBM DBS might be due to selective neuroplastic and neurochemical changes.

Electronic Structure Modulation of Ag2 S by Vacancy Engineering for Efficient Bacterial Infection.

Vacancy engineering can modulate the electronic structure of the material and thus contribute to the formation of coordination unsaturated sites, which makes it easier to act on the substrate. Herein, Ag2 S and Ag2 S-100, which mainly have vacancy associates VAgS and VAgSAg , respectively, are prepared and characterized by positron annihilation spectroscopy. Both experimental and theoretical calculation results indicate that Ag2 S-100 exhibits excellent antibacterial activity due to its appropriate bandgap and stronger bacteria-binding ability, which endow it with a superior antibacterial activity compared to Ag2 S in the absence of light. The in vivo antibacterial experiment using a mouse wound-infection model further confirms that Ag2 S-100 has excellent antibacterial and wound-healing properties. This research provides clues for a deeper understanding of modulating electronic structures through vacancy engineering and develops a strategy for effective treatment of bacterial infections.

Molecularly imprinted electrochemical aptasensor based on functionalized graphene and nitrogen-doped carbon quantum dots for trace cortisol assay.

This paper proposes a novel electrochemical aptasensor that integrates molecular imprinting techniques for trace analysis of cortisol. This sensor is based on functionalized graphene and nitrogen-doped carbon quantum dots. The morphology and structure of the modified electrode were characterized by scanning electron microscopy and Raman spectroscopy. The functional monomer aptamer and the template molecule cortisol were adsorbed on the electrode by electrostatic adsorption to construct an imprinted sensing platform. Under the optimal conditions, such as the concentration of template molecule, the ratio of template to functional monomer, the elution and adsorption time, the sensor exhibits linearity and a low detection limit of 10-12-10-8 M and 3.3 × 10-13 M, which is more sensitive than other reported cortisol analysis methods. In addition, this sensor can realize the determination of cortisol in salivary samples with high recovery values, showing great development potential in the field of life sciences.

Encoding Morphogenesis of Quasi-Triangular Gold Nanoprisms with DNA.

Properties of gold nanoparticles vary with their morphologies. Typically, the research on the properties and applications of the nonequilibrium intermediates generated by the morphological evolution of triangular gold nanoprisms is still incomplete. Herein, we employ thiol-DNA (HS-DNA) to protect the low-stability quasi-nanoprisms with different truncation degrees (R values). The presence of HS-DNA not only increases the stability of the quasi-nanoprisms in different microenvironments, but also facilitates us to investigate their intrinsic plasmonic properties related to morphology. Additionally, we serve quasi-nanoprisms loaded with HS-DNA as assembly modules and nanoplatforms for programmable self-assembly higher-order hybrid structures, as well as carriers for encoding and decoding of orthogonal barcode-like information, which opens new opportunities for developing novel building blocks for light manipulation at nanoscale.

Prescribing Silver Chirality with DNA Origami.

Metal nanostructures of chiral geometry interacting with light via surface plasmon resonances can produce tailorable optical activity with their structural alterations. However, bottom-up fabrication of arbitrary chiral metal nanostructures with precise size and morphology remains a synthetic challenge. Here we develop a DNA origami-enabled aqueous solution metallization strategy to prescribe the chirality of silver nanostructures in three dimensions. We find that diamine silver(I) complexes coordinate with the bases of prescribed single-stranded protruding clustered DNA (pcDNA) on DNA origami via synergetic interactions including coordination, hydrogen bonds, and ion-π interaction, which induce site-specific pcDNA condensation and local enrichment of silver precursors that lowers the activation energy for nucleation. Using tubular DNA origami-based metallization, we obtain helical silver patterns up to a micrometer in length with well-defined chirality and pitches. We further demonstrate tailorable plasmonic optical activity of metallized chiral silver nanostructures. This method opens new pathways to synthesize programmable inorganic materials with arbitrary morphology and chirality.

Toward Smart Information Processing with Synthetic DNA Molecules.

DNA, a biological macromolecule, is a naturally evolved information material. From the structural point of view, an individual DNA strand can be considered as a chain of data with its bases working as single units. For decades, due to the high biochemical stability, large information storage capacity, and high recognition specificity, DNA has been recognized as an attractive material for information processing. Especially, the chemical synthesis strategies and DNA sequencing techniques have been rapidly developed recently, further enabling encoding information with synthetic DNA molecules. Herein, recent progresses are summarized on information processing based on synthetic DNA molecules from three aspects including information storage, computation, and encryption, and proposed the challenges and future development directions.

Correction to: The effect of fornix deep brain stimulation in brain diseases.

After publication of the original article it came to the authors' attention that there was an error under the subheading Traumatic Brain Injury (TBI) as well as Table 1.

The effect of fornix deep brain stimulation in brain diseases.

Deep brain stimulation is used to alleviate symptoms of neurological and psychiatric disorders including Parkinson's disease, epilepsy, and obsessive-compulsive-disorder. Electrically stimulating limbic structures has been of great interest, and in particular, the region of the fornix. We conducted a systematic search for studies that reported clinical and preclinical outcomes of deep brain stimulation within the fornix up to July 2019. We identified 13 studies (7 clinical, 6 preclinical) that examined the effects of fornix stimulation in Alzheimer's disease (n = 9), traumatic brain injury (n = 2), Rett syndrome (n = 1), and temporal lobe epilepsy (n = 1). Overall, fornix stimulation can lead to decreased rates of cognitive decline (in humans), enhanced memory (in humans and animals), visuo-spatial memorization (in humans and animals), and improving verbal recollection (in humans). While the exact mechanisms of action are not completely understood, studies suggest fornix DBS to be involved with increased functional connectivity and neurotransmitter levels, as well as enhanced neuroplasticity.

DNA Origami Radiometers for Measuring Ultraviolet Exposure.

Ultraviolet (UV) light has long been known to damage nucleic acids. In this work, a DNA origami radiometer has been developed for measuring UV exposure by monitoring the morphological evolution of DNA origami nanostructures. Unlike linear DNA strands that tend to be degraded into small segments upon UV exposure, the structural complexity and interstrand connectivity of DNA origami remarkably alter the pathway of UV-induced DNA damage. A general pathway of expansion, distortion, and final disintegration is observed for DNA origami regardless of their shape and size; however the deformation kinetics is positively correlated with the number of nicks in the nanostructure. This structural continuity-dependent deformation can be translated into a DNA-based radiometer for measuring UV dose in the environment.

Prescribing DNA Origami Patterns via Scaffold Decoration.

DNA origami has rapidly emerged as a powerful technique to fabricate user-defined DNA nanostructures. However, the ability to custom-make patterns on DNA origami template is hampered by the heavy workload and high cost of changing staple DNA (up to several hundred strands per set). Here, a scaffold-decorated DNA origami method is developed by prescribing the pattern information to the scaffold DNA. For each pixel of an origami, a designed "pixel strand" (P-strand) is hybridized to the scaffold, strongly preoccupying a specific position and competing with invading staples in a mild origami assembly. To fabricate a new origami pattern, the P-strand set needs to be replaced with a universal staple set. The yield of thus-fabricated DNA origami patterns is comparable to a conventional DNA origami with canonical method. One-pot fabrication of three different nanopatterns in a single test-tube is further demonstrated. Also, dynamic switch of the pattern is shown. This method provides a generic approach and offers large flexibility for scaling up the nanofabrication with DNA origami by kinetically modulating the reaction pathway of the staples with the scaffold DNA, which represents a novel route in the self-assembly of complex biomolecular systems.

Solving mazes with single-molecule DNA navigators.

Molecular devices with information-processing capabilities hold great promise for developing intelligent nanorobotics. Here we demonstrate a DNA navigator system that can perform single-molecule parallel depth-first search on a ten-vertex rooted tree defined on a two-dimensional DNA origami platform. Pathfinding by the DNA navigators exploits a localized strand exchange cascade, which is initiated at a unique trigger site on the origami with subsequent automatic progression along paths defined by DNA hairpins containing a universal traversal sequence. Each single-molecule navigator autonomously explores one of the possible paths through the tree. A specific solution path connecting a given pair of start and end vertices can then be easily extracted from the set of all paths taken by the navigators collectively. The solution path laid out on origami is illustrated with single-molecule imaging. Our approach points towards the realization of molecular materials with embedded computational functions operating at the single-molecule level.

Deep brain stimulation and cognition: Translational aspects.

Many neurological patients suffer from memory loss. To date, pharmacological treatments for memory disorders have limited and short-lasting effects. Therefore, researchers are investigating novel therapies such as deep brain stimulation (DBS) to alleviate memory impairments. Up to now stimulation of the fornix, nucleus basalis of Meynert and entorhinal cortex have been found to enhance memory performance. Here, we provide an overview of the different DBS targets and mechanisms within the memory circuit, which could be relevant for enhancing memory in patients. Future studies are warranted, accelerating the efforts to further unravel mechanisms of action of DBS in memory-related disorders and develop stimulation protocols based on these mechanisms.

Adjustable Ternary FeCoNi Nanohybrids for Enhanced Oxygen Evolution Reaction.

Water splitting as a greatly desired technology to produce clean renewable energy, but is hampered by the sluggish oxygen evolution reaction. So, the development of highly active and durable water oxidation electrocatalysts is of primarily significance for energy conversion. Here, a facial strategy to synthesize FeCoNi nanohybrids with adjustable morphological structures by using fluorine is introduced. The morphology and electrocatalytic activity of the sample is determined by the innovative introduction of fluorine. Among them, the overpotential at 10 mA cm-2 of the best sample is approximately 97 mV lower than the commercial RuO2 toward the oxygen evolution reaction in 1 m KOH. Additionally, the catalysts also have low Tafel slopes and remarkable stability.

[Dexamethasone Blocks Adriamycin-induced Podocytes'Mobility via Impacting Nephrin Expression].

OBJECTIVE: To explore how dexamethasone (Dex) directly restores kidney podocyte function in adriamycin (ADR)-induced nephrotic model and the effects of Dex on the motility of podocytes, to analyze whether nephrin is a key signal molecule in the process. METHODS: The cultured podocytes were divided into three growps: ADR treated group, ADR+Dex group, blank control group. The analyses of podocytes function were performed using scrape-wound, Transwell migration assays and FITC-BSA. Quantitative real-time PCR and Western blot were used to test the expression of nephrin. Male SD rats were used to generate ADR-induced nephrology model, and randomly divided into three groups: ADR group, ADR+Dex group and normal group. At 7 d, 14 d, 21 d and 28 d after ADR injection, 24 h urine protein was measured as well. Podocyte foot process effacement was observed under transmission electron microscopy. RESULTS: Podocytes' motility, permeability of a monolayer of podocytes incubated with FITC-BSA, the expression of nephrin were higher in ADR group than those in blank control group (P<0.05); on the contrary, the indexes above in Dex+ADR group were decreased when compared with ADR group (P<0.05). 24 h urine protein increased significantly at day 14 (vs. normal group P<0.001) and peaked at day 28 in ADR rats (vs. normal group P<0.001), whereas decreased at day 14, 21 and 28 in Dex+ADR group (vs. ADR group, P<0.001). The FWP of ADR-treated rats was greater than normal group and Dex+ADR group (P<0.01). CONCLUSION: Dex impacts the expression of nephrin, relieves the enhanced motility induced by ADR and decreases urine protein level.

DNA Hydrogel with Aptamer-Toehold-Based Recognition, Cloaking, and Decloaking of Circulating Tumor Cells for Live Cell Analysis.

Circulating tumor cells (CTCs) contain molecular information on the primary tumor and can be used for predictive cancer diagnostics. Capturing rare live CTCs and their quantification in whole blood remain technically challenging. Here we report an aptamer-trigger clamped hybridization chain reaction (atcHCR) method for in situ identification and subsequent cloaking/decloaking of CTCs by porous DNA hydrogels. These decloaked CTCs were then used for live cell analysis. In our design, a DNA staple strand with aptamer-toehold biblocks specifically recognizes epithelial cell adhesion molecule (EpCAM) on the CTC surface that triggers subsequent atcHCR via toehold-initiated branch migration. Porous DNA hydrogel based-cloaking of single/cluster of CTCs allows capturing of living CTCs directly with minimal cell damage. The ability to identify a low number of CTCs in whole blood by DNA hydrogel cloaking would allow high sensitivity and specificity for diagnosis in clinically relevant settings. More significantly, decloaking of CTCs using controlled and defined chemical stimuli can release living CTCs without damages for subsequent culture and live cell analysis. We expect this liquid biopsy tool to open new powerful and effective routes for cancer diagnostics and therapeutics.

Real-Time Imaging of Single-Molecule Enzyme Cascade Using a DNA Origami Raft.

The dynamics of enzymes are directly associated with their functions in various biological processes. Nevertheless, the ability to image motions of single enzymes in a highly parallel fashion remains a challenge. Here, we develop a DNA origami raft-based platform for in-situ real-time imaging of enzyme cascade at the single-molecule level. The motions of enzymes are rationally controlled via different tethering modes on a two-dimensional (2D) supported lipid bilayer (SLB). We construct an enzyme cascade by anchoring catalase on cholesterol-labeled double-stranded (ds) DNA and glucose oxidase on cholesterol-labeled origami rafts. DNA functionalized with cholesterol can be readily incorporated in SLB via the cholesterol-lipid interaction. By using a total internal reflection fluorescence microscope (TIRFM), we record the moving trajectory of fluorophore-labeled single enzymes on the 2D surface: the downstream catalase diffuses freely in SLB, whereas the upstream glucose oxidase is relatively immobile. By analyzing the trajectories of individual enzymes, we find that the lateral motion of enzymes increases in a substrate concentration-dependent manner and that the enhanced diffusion of enzymes can be transmitted via the cascade reaction. We expect that this platform sheds new light on studying dynamic interactions of proteins and even cellular interactions.