A Light-Powered Single-Stranded DNA Molecular Motor with Colour-Selective Single-Step Control.

Top-down control of small motion is possible through top-down controlled molecular motors in replacement of larger actuators like MEMS or NEMS (micro- or nano-electromechanical systems) in the current precision technology. Improving top-down control of molecular motors to every single step is desirable for this purpose, and also for synchronization of motor actions for amplified effects. Here we report a designed single-stranded DNA molecular motor powered by alternated ultraviolet and visible light for processive track-walking, with the two light colours each locking the motor in a full directional step to allow saturated driving but no overstepping. This novel nano-optomechanical driving mechanism pushes the top-down control of molecular motors down to every single step, thus providing a key technical capability to advance the molecular motor-based precision technology and also motor synchronization for amplified effects.

Antitoxin MqsA decreases antibiotic susceptibility through the global regulator AgtR in Pseudomonas fluorescens.

Type II toxin-antitoxin systems are highly prevalent in bacterial genomes and play crucial roles in the general stress response. Previously, we demonstrated that the type II antitoxin PfMqsA regulates biofilm formation through the global regulator AgtR in Pseudomonas fluorescens. Here, we found that both the C-terminal DNA-binding domain of PfMqsA and AgtR are involved in bacterial antibiotic susceptibility. Electrophoretic mobility shift assay (EMSA) analyses revealed that AgtR, rather than PfMqsA, binds to the intergenic region of emhABC-emhR, in which emhABC encodes an resistance-nodulation-cell division efflux pump and emhR encodes a repressor. Through quantitative real-time reverse-transcription PCR and EMSA analysis, we showed that AgtR directly activates the expression of the emhR by binding to the DNA motif [5´-CTAAGAAATATACTTAC-3´], leading to repression of the emhABC. Furthermore, we demonstrated that PfMqsA modulates the expression of EmhABC and EmhR. These findings enhance our understanding of the mechanism by which antitoxin PfMqsA contributes to antibiotic susceptibility.

Clinical Electrophysiological Features and Radiofrequency Ablation of Patients with Atrial Fibrillation.

This study aimed to investigate electrophysiological features of radiofrequency ablation surgery in patients with the atrial fibrillation (AF). Fifty patients were included in this study and evenly divided, with 25 AF patients in the experiment group and 25 patients with arrhythmias in the control group. General clinical materials in the two groups were collected. Then, patient number of pulmonary vein antrum potential trial, intra-right atrial conduction time, intra-left atrial conduction time, interatrial conduction time, conduction time between atrium, and pulmonary veins trials were utilized to measure the efficacy of radiofrequency ablation surgery in patients with AF and clarify the relationship between AF and electrophysiological features in the atrium and pulmonary veins. Our study findings showed that conduction time interval between the atrium and pulmonary veins trial by radiofrequency ablation surgery were significantly less than those in pre-treatment AF patients. We can conclude that radiofrequency ablation surgery can effectively treat AF patients by relieving the electrophysiological dysfunction, and radiofrequency ablation can be used to prevent the development of AF.

Site specificity of blastocyst hatching significantly influences pregnancy outcomes in mice.

Blastocysts hatch from the zona pellucida (ZP) to enable implantation into the uterine endometrial epithelium, but little is known regarding the effect of hatching sites on pregnancy outcomes. Murine hatching embryos were categorized into five groups based on initial trophectoderm projection (TEP)/ZP position corresponding to the inner cell mass center. In blastocysts (3.5 dpc) post-12 hours in vitro culture, TEP rates of A-site (44.4%) and B-site (38.6%) embryos were higher than those of C-site (12.5%) and D-site (3.1%) embryos, while the O-site (1.4%) was the lowest (P < .05). Post-ET A-site (55.6%) and B-site (65.6%) birth rates were higher than those of C-site embryos (21.3%) and controls (P < .05). Furthermore, live birth rate of B-site embryos remained higher than C-site embryos (68.8% vs 31.3%; P < .05) when both were transferred into the same recipients. Different TEP site blastocysts exhibited different implantation competences: the implantation rate of C-site embryos was lower than that of both A- and B-site groups (67.7% vs 84.3% and 83.2%, respectively; P < .05) at 2 days post-ET. C-site embryos also had a distinctly higher ratio of developmental defects (47.5%) than A- and B-site embryos (22.5% and 14.6%, respectively), with implantation failure mainly associated with poor birth rate, a finding corroborated by differential gene expression analysis such as LIF, LIFR, and S100a9. Surprisingly, acidified Tyrode's solution (AAH)-treated B-site blastocysts had a significantly increased birth rate (77.1%) than C-site (55.3%) and controls (43.4%). Site specificity and differential gene expression during embryo hatching can be applied in ART screening. More importantly, assisted hatching by AAH is effective and feasible for improving pregnancy and term development, particularly at the B-site, for humans and in animal husbandry.

Dynamic and aberrant patterns of H3K4me3, H3K9me3, and H3K27me3 during early zygotic genome activation in cloned mouse embryos.

Somatic cell nuclear transfer (NT) is associated with aberrant changes in epigenetic reprogramming that impede the development of embryos, particularly during zygotic genome activation. Here, we characterized epigenetic patterns of H3K4me3, H3K9me3, and H3K27me3 in mouse NT embryos up to the second cell cycle (i.e. four-celled stage) during zygotic genome activation. In vivo fertilized and parthenogenetically activated (PA) embryos served as controls. In fertilized embryos, maternal and paternal pronuclei exhibited asymmetric H3K4me3, H3K9me3, and H3K27me3 modifications, with the paternal pronucleus showing delayed epigenetic modifications. Higher levels of H3K4me3 and H3K9me3 were observed in NT and PA embryos than in fertilized embryos. However, NT embryos exhibited a lower level of H3K27me3 than PA and fertilized embryos from pronuclear stage 3 to the four-celled stage. Our finding that NT embryos exhibited aberrant H3K4me3, H3K9me3, and H3K27me3 modifications in comparison with fertilized embryos during early zygotic genome activation help to unravel the epigenetic mechanisms of methylation changes in early NT reprogramming and provide an insight into the role of histone H3 in the regulation of cell plasticity during natural reproduction and somatic cell NT.

A bioinspired design principle for DNA nanomotors: mechanics-mediated symmetry breaking and experimental demonstration.

DNA nanotechnology is a powerful tool to fabricate nanoscale motors, but the DNA nanomotors to date are largely limited to the simplistic burn-the-bridge design principle that prevents re-use of a fabricated motor-track system and is unseen in biological nanomotors. Here we propose and experimentally demonstrate a scheme to implement a conceptually new design principle by which a symmetric bipedal nanomotor autonomously gains a direction not by damaging the traversed track but by fine-tuning the motor's size.

Asymmetric information hiding and noise-free recovery based on rotating analyzer ellipsometry and quick-response code.

We report an asymmetric optical information hiding method based on a rotating analyzer ellipsometry technique. This asymmetric hiding architecture not only avoids the interception of keys during transmission or distribution but also makes the cyphertext more inconspicuous for attackers. A new kind of one-way optical trapdoor function is constructed based on the fact that the state of polarization (SOP) of elliptical polarized light cannot be recovered with only the knowledge of intensity captured after passing through a linear polarizer. Meanwhile, the SOP of a polarization ellipse could be calculated by rotating the polarizer to record two scenes of intensity after it. Introduction of a quick response code as a container leads to noise-free recovery for original information and enhances practicality of the proposed cryptosystem with versatile key sensitivity and fault tolerance capability. Numerical simulation results that support theoretical analysis are presented. Analysis on the relationship between hiding effect or quality of decryption and parameters of the algorithm also is provided.

Optical asymmetric cryptography based on elliptical polarized light linear truncation and a numerical reconstruction technique.

We demonstrate a novel optical asymmetric cryptosystem based on the principle of elliptical polarized light linear truncation and a numerical reconstruction technique. The device of an array of linear polarizers is introduced to achieve linear truncation on the spatially resolved elliptical polarization distribution during image encryption. This encoding process can be characterized as confusion-based optical cryptography that involves no Fourier lens and diffusion operation. Based on the Jones matrix formalism, the intensity transmittance for this truncation is deduced to perform elliptical polarized light reconstruction based on two intensity measurements. Use of a quick response code makes the proposed cryptosystem practical, with versatile key sensitivity and fault tolerance. Both simulation and preliminary experimental results that support theoretical analysis are presented. An analysis of the resistance of the proposed method on a known public key attack is also provided.

Mechanomaterials and Nanomechanics: Toward Proactive Design of Material Properties and Functionalities.

While conventional mechanics of materials offers a passive understanding of the mechanical properties of materials in existing forms, a paradigm shift, referred to as mechanomaterials, is emerging to enable the proactive programming of materials' properties and functionalities by leveraging force-geometry-property relationships. One of the foundations of this new paradigm is nanomechanics, which permits functional and structural materials to be designed based on principles from the nanoscale and beyond. Although the field of mechanomaterials is still in its infancy at the present time, we discuss the current progress in three specific directions closely linked to nanomechanics and provide perspectives on these research foci by considering the potential research directions, chances for success, and existing research capabilities. We believe this new research paradigm will provide future materials solutions for infrastructure, healthcare, energy, and environment.

Overcoming the H4K20me3 epigenetic barrier improves somatic cell nuclear transfer reprogramming efficiency in mice.

Epigenetic reprogramming during fertilization and somatic cell nuclear transfer (NT) is required for cell plasticity and competent development. Here, we characterize the epigenetic modification pattern of H4K20me3, a repressive histone signature in heterochromatin, during fertilization and NT reprogramming. Importantly, the dynamic H4K20me3 signature identified during preimplantation development in fertilized embryos differed from NT and parthenogenetic activation (PA) embryos. In fertilized embryos, only maternal pronuclei carried the canonical H4K20me3 peripheral nucleolar ring-like signature. H4K20me3 disappeared at the 2-cell stage and reappeared in fertilized embryos at the 8-cell stage and in NT and PA embryos at the 4-cell stage. H4K20me3 intensity in 4-cell, 8-cell, and morula stages of fertilized embryos was significantly lower than in NT and PA embryos, suggesting aberrant regulation of H4K20me3 in PA and NT embryos. Indeed, RNA expression of the H4K20 methyltransferase Suv4-20h2 in 4-cell fertilized embryos was significantly lower than NT embryos. Knockdown of Suv4-20h2 in NT embryos rescued the H4K20me3 pattern similar to fertilized embryos. Compared to control NT embryos, knockdown of Suv4-20h2 in NT embryos improved blastocyst development ratios (11.1% vs. 30.5%) and full-term cloning efficiencies (0.8% vs. 5.9%). Upregulation of reprogramming factors, including Kdm4b, Kdm4d, Kdm6a, and Kdm6b, as well as ZGA-related factors, including Dux, Zscan4, and Hmgpi, was observed with Suv4-20h2 knockdown in NT embryos. Collectively, these are the first findings to demonstrate that H4K20me3 is an epigenetic barrier of NT reprogramming and begin to unravel the epigenetic mechanisms of H4K20 trimethylation in cell plasticity during natural reproduction and NT reprogramming in mice.

Research on the Mechanism and Propagation Characteristics of Combustion and Explosion of Natural Gas/Ammonia/Hydrogen Mixed Gas Fuel.

The addition of ammonia and hydrogen into natural gas fuel is an effective method to reduce carbon emissions. This study aims to investigate the effect of adding ammonia and hydrogen on the mechanism of natural gas combustion and emission characteristics. Based on a self-developed mixed gas deflagrate experimental platform, the deflagrate characteristics, emission characteristics, and chemical reaction kinetics mechanism of mixed gas fuels under different composition ratios (natural gas 0-100%, hydrogen 10-85%, and ammonia 0-100%) were studied. The results indicate that the propagation of the deflagration shock wave can be categorized into an initial stage (L < 3 m) and a development stage (L > 3 m) based on the observed trend of shock wave intensity variation with distance. The intensity of the deflagration shock wave for the mixed gases increases monotonically as the hydrogen content ratio rises. In contrast, the impact of the ammonia content ratio on the shock wave intensity exhibits a distinct pattern that varies with changes in the equivalence ratio and hydrogen content ratio. In terms of carbon emissions per unit of heat value produced by the fuel, adding hydrogen to natural gas proves to be more effective at reducing carbon emissions than adding ammonia. When the ammonia content ratio is 50% and the hydrogen content ratio is 40%, the combustion performance of the mixed gas fuel is similar to that of natural gas, but its carbon emissions are lower than 30% of natural gas, making it a new type of mixed fuel with potential application value; the interaction between reflected pressure waves and flames is the main reason for the fluctuation of deflagrate shock wave pressure; ammonia lowers the temperature of the reaction system by reducing the concentration of OH radicals.

Melanoidin-like carbohydrate-containing macromolecules from Shanxi aged vinegar exert immunoenhancing effects on macrophage RAW264.7 cells.

Bioactive macromolecule mining is important for the functional chemome analysis of traditional Chinese vinegar. In this study, we isolated and characterized carbohydrate-containing macromolecules from Shanxi aged vinegar (CCMSAV) and evaluated their immunomodulatory activity. The isolation process involved ethanol precipitation, deproteinization, decolorization, and DEAE-650 M column chromatography, resulting in the acquisition of four sub-fractions. All sub-fractions exhibited a molecular weight range of 6.92 to 16.71 kDa and were composed of 10 types of monosaccharides. Comparative analysis of these sub-fractions with two melanoidins exhibited similarities in elemental composition, spectral signature, and pyrolytic characteristics. Immunological assays confirmed the significantly enhanced cell viability, phagocytic activity, and secretion of nitric oxide, tumor necrosis factor (TNF)-α and interleukin (IL)-6 in RAW264.7 cells by all four sub-fractions. Further investigation of the immunomodulatory mechanism revealed that SAV-RP70-X, the most potent purified sub-fraction, enhanced aerobic glycolysis in macrophages and activated Toll-like receptor 2 (TLR2), TLR4, mannose receptor (MR), scavenger receptor (SR), and the dendritic cell-associated C-type lectin-1 receptor (Dectin-1). Furthermore, the activation of macrophages was associated with the MyD88/PI3K/Akt/NF-κB signaling pathway. Methylation analysis revealed that 1,4-Xylp was the most abundant glycosidic linkage in SAV-RP70-X.

Directional fidelity of nanoscale motors and particles is limited by the 2nd law of thermodynamics--via a universal equality.

Directional motion of nanoscale motors and driven particles in an isothermal environment costs a finite amount of energy despite zero work as decreed by the 2nd law, but quantifying this general limit remains difficult. Here we derive a universal equality linking directional fidelity of an arbitrary nanoscale object to the least possible energy driving it. The fidelity-energy equality depends on the environmental temperature alone; any lower energy would violate the 2nd law in a thought experiment. Real experimental proof for the equality comes from force-induced motion of biological nanomotors by three independent groups - for translational as well as rotational motion. Interestingly, the natural self-propelled motion of a biological nanomotor (F1-ATPase) known to have nearly 100% energy efficiency evidently pays the 2nd law decreed least energy cost for direction production.

Exhaustive classification and systematic free-energy profile study of single-stranded DNA inter-overhang migration.

Migration of a short single-stranded DNA (ssDNA) between DNA overhangs is a basic molecular process that is widely used in dynamic DNA nanotechnology. The migration rate is sensitive to migration gaits, and limits the speed of dynamic DNA systems like DNA nanowalkers and other functional devices. Here, we identify and exhaustively classify all possible inter-overhang migration gaits of a ssDNA into only four categories based on their intrinsic symmetry. Using the oxDNA package, we conduct a systematic computational study for a typical migrator-overhang system to identify the lowest-energy pathway for all four migration categories. The one-dimensional free-energy profile along this pathway allows a parameter-free estimation of migration rates for all the four categories by the first passage time theory plus benchmarking from experimental rates available for one migration category. The obtained rates indicate a big room to improve DNA nanowalkers' speed above 1 µm per minute. The free-energy profile for each migration category possesses distinct and robust symmetric patterns, which largely decide local barriers, trapping states, and thereby a migration's rate-limiting processes and capacity for directional bias. This study thus provides a unified symmetry-based framework to analyze and optimize ssDNA migrations in kinetics, bias capacity, and structural design for better dynamic DNA nanotechnology.

Microwaves affect the formation of volatile compounds in peper powder by changing the nucleophilic addition reactions in Maillard reactions.

We explored the effect of microwave heating (MWH) and electric heating (ETH) on the volatile compounds (VCs) of pepper (Capsicum annuum L.). The spectral of the produced melanoidins by baking were used to screen samples with similar baking degrees. Mass spectrometry was used to detect the differences of VCs in samples. The results showed a dose-dependent effect between the intensity of absorption and fluorescence of melanoidins, which can be utilized as indicators for assessment baking degree. MWH samples produced larger variety of VCs than ETH. Changes in the variety and content of VCs infer changes in the flavor of pepper. According to the mechanism of Maillard reaction (MR) and MWH, it was deduced that MWH changes the type of chemical reaction in MR by affecting the distribution of valence electrons in the compounds. Therefore, MWH can be used as a novel method to modify the VCs and flavor of peppers.

Autonomous DNA molecular motor tailor-designed to navigate DNA origami surface for fast complex motion and advanced nanorobotics.

Nanorobots powered by designed DNA molecular motors on DNA origami platforms are vigorously pursued but still short of fully autonomous and sustainable operation, as the reported systems rely on manually operated or autonomous but bridge-burning molecular motors. Expanding DNA nanorobotics requires origami-based autonomous non-bridge-burning motors, but such advanced artificial molecular motors are rare, and their integration with DNA origami remains a challenge. Here, we report an autonomous non-bridge-burning DNA motor tailor-designed for a triangle DNA origami substrate. This is a translational bipedal molecular motor but demonstrates effective translocation on both straight and curved segments of a self-closed circular track on the origami, including sharp ~90° turns by a single hand-over-hand step. The motor is highly directional and attains a record-high speed among the autonomous artificial molecular motors reported to date. The resultant DNA motor-origami system, with its complex translational-rotational motion and big nanorobotic capacity, potentially offers a self-contained "seed" nanorobotic platform to automate or scale up many applications.

A light-operated integrated DNA walker-origami system beyond bridge burning.

Integrating rationally designed DNA molecular walkers and DNA origami platforms is a promising route towards advanced nano-robotics of diverse functions. Unleashing the full potential in this direction requires DNA walker-origami systems beyond the present simplistic bridge-burning designs for automated repeatable operation and scalable nano-robotic functions. Here we report such a DNA walker-origami system integrating an advanced light-powered DNA bipedal walker and a ∼170 nm-long rod-like DNA origami platform. This light-powered walker is fully qualified as a genuine translational molecular motor, and relies entirely on pure mechanical effects that are complicated by the origami surface but must be preserved for the walker's proper operation. This is made possible by tailor-designing the origami for optimal match with the walker to best preserve its core mechanics. A new fluorescence method is combined with site-controlled motility experiments to yield distinct and reliable signals for the walker's self-directed and processive motion despite origami-complicated fluorophore emission. The resultant integrated DNA walker-origami system provides a 'seed' system for future development of advanced light-powered DNA nano-robots (e.g., for scalable walker-automated chemical synthesis), and also truly bio-mimicking nano-muscles powered by genuine artificial translational molecular motors.

Novel TLR7/8 agonists promote activation of HIV-1 latent reservoirs and human T and NK cells.

Antiretroviral therapy can successfully suppress HIV-1 replication to undetectable levels but fails to eliminate latent and persistent HIV-1 reservoirs. Recent studies have focused on the immunomodulatory agents such as Toll-like receptor 7 and 8 (TLR7 and TLR8) capable of activating, thereby rendering the reservoir susceptible to antiretroviral inhibition and immune recognition and elimination. In this context, this study focused on generating a diverse repertoire of TLR7/8 agonists to identify more potent candidates for activating latent HIV-1 and immune cells' response. Through combinational strategies of computer-aided design and biological characterization, 159 pyrido [3,2-d] pyrimidine and pyridine-2-amine-based derivatives were synthesized. Of which, two TLR7/8 dual and one TLR8-specific agonists with exceptionally high potency in activating HIV-1 latent reservoirs in cell lines and PBMCs of patients with persistent and durable virologic controls were identified. Particularly, these agonists appeared to enhance NK and T cells activity, which were correlated with the degree of surface activation markers. The outcome of this study highlights the remarkable potential of TLR7/8 agonists in simultaneously activating HIV-1 from the latently infected cells and augmenting immune effector cells.

Bipedal nanowalker by pure physical mechanisms.

Artificial nanowalkers are inspired by biomolecular counterparts from living cells, but remain far from comparable to the latter in design principles. The walkers reported to date mostly rely on chemical mechanisms to gain a direction; they all produce chemical wastes. Here we report a light-powered DNA bipedal walker based on a design principle derived from cellular walkers. The walker has two identical feet and the track has equal binding sites; yet the walker gains a direction by pure physical mechanisms that autonomously amplify an intrasite asymmetry into a ratchet effect. The nanowalker is free of any chemical waste. It has a distinct thermodynamic feature that it possesses the same equilibrium before and after operation, but generates a truly nonequilibrium distribution during operation. The demonstrated design principle exploits mechanical effects and is adaptable for use in other nanomachines.

Extract Motive Energy from Single-Molecule Trajectories.

Single-molecule trajectories from nonequilibrium unfolding experiments are widely used to recover a biomolecule's intrinsic free-energy profile. Trajectories of molecular motors from similar single-molecule experiments may be mapped to biased diffusion over an inclined free-energy profile. Such an effective potential is not a static equilibrium property anymore, and how it can benefit molecular motor study is unclear. Here, we introduce a method to deduce this effective potential from motor trajectories with realistic temporal-spatial resolution and find that the potential yields a motor's stall force─a quantity that not only characterizes a motor's force-generating capacity but also largely determines its energy efficiency. Interestingly, this potential allows the extraction of a motor's stall force from trajectories recorded at a single resisting force or even zero force, as verified with trajectories from two molecular motor models and also experimental trajectories from a real artificial motor. This finding drastically reduces the difficulty of stall force measurement, making it accessible even to force-incapable optical tracking experiments (commonly regarded as irrelevant to stall force determination). This study further provides a method for experimentally measuring a second-law-decreed least energy price for submicroscopic directionality─a previously elusive but thermodynamically important quantity pertinent to efficient energy conversion of molecular motors.