A Light-powered single-stranded DNA molecular motor with colour-selective single-step control.

To-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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Enhancing technology innovation performance through alliance capability: The role of standard alliance network and political skill of TMTs.

Given the increasing competition in standards, standard alliances have become a vital choice for enterprises to enhance their competitive advantage. In standard alliances, what decisions must top management teams make to help their enterprises improve their innovation performance? To answer this question, we draw on dynamic capability theory, social network theory, and high-level echelon theory to understand how alliance capabilities and standard alliance networks affect technology innovation performance. We collected questionnaire data from 465 manufacturing enterprises in China, and the empirical findings show that (1) enterprise alliance capabilities and standard alliance networks have a positive impact on technology innovation performance; (2) enterprise alliance capabilities and technology innovation performance are mediated by standard alliance networks; and (3) the political skills of top management teams strengthen this moderating model. The results of this study enrich the literature on standard alliances and provide a reference for enterprises in developing standard alliance strategies, cultivating alliance capabilities, and exercising the requisite political skills of top management teams.

Epigenetic dynamics of H4K20me3 modification during oocyte maturation and early reprogramming of somatic cell nuclear transfer goat embryos.

OBJECTIVE: We examined the epigenetic dynamics of histone H4K20 trimethylation (H4K20me3), a repressive signature in heterochromatin, during goat oocyte meiosis and the reprogramming of somatic cell nuclear transfer (NT) embryos through the first three cell divisions. METHODS: Following NT, oocytes were treated with parthenogenetic activation (PA), by 5 µM calcium ionophore A23187 for 5 min followed by incubation in 2.0 mM 6-dimethylaminopurine with 5 µg/mL cycloheximide for 4 h. NT embryos up to 8-celled stage were incubated with H4K20me3 antibody. RESULTS: Immunofluorescence microscopy revealed the existence of a persistent H4K20me3 signature during oocyte maturation from germinal vesicle phase to metaphase I, anaphase I, telophase I, and metaphase II, with a gradual reduction in staining intensity. NT embryos at the 2-, 4- and 8-celled stage showed lower H4K20me3 intensity than PA and IVF embryos (P < 0.05). CONCLUSION: These results indicate that NT embryos exhibit insufficient H4K20me3 modification compared with IVF and PA embryos during early reprogramming, suggesting the existence of a resistant memory of differentiated cell nuclear architecture. These findings help unravel the epigenetic mechanism of histone H4K20me3 in goat nuclear transfer reprogramming.

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.

HSC-MET: Heterogeneous signcryption scheme supporting multi-ciphertext equality test for Internet of Drones.

Internet of Drones (IoD) is considered as a network and management architecture, which can enable unmanned aerial vehicles (UAVs) to collect data in controlled areas and conduct access control for UAVs. However, the current cloud-assisted IoD scheme cannot efficiently achieve secure communication between heterogeneous cryptosystems, and does not support multi-ciphertext equality tests. To improve the security and performance of traditional schemes, we propose a heterogeneous signcryption scheme (HSC-MET) that supports multi-ciphertext equality test. In this paper, we use a multi-ciphertext equality test technique to achieve multi-user simultaneous retrieval of multiple ciphertexts safely and efficiently. In addition, we adopt heterogeneous signcryption technology to realize secure data communication from public key infrastructure (PKI) to certificateless cryptography (CLC). At the same time, the proposed scheme based on the computation without bilinear pairing, which greatly reduces the computational cost. According to the security and performance analysis, under the random oracle model (ROM), the confidentiality, unforgeability and number security of HSC-MET are proved based on the computational Diffie-Hellman (CDH) problem.

Importance of Sugar-Phosphate Backbone and Counterions to First-Principles Modeling of Nucleobases.

DFT-based first-principles calculations were carried out to understand the electronic structure difference among a backbone-free nucleobase, a backbone-containing Na counterion nucleotide, and a backbone-containing H counterion nucleotide and their difference in the adsorption on graphene and on graphitic-carbon nitride. The study discovered that the inclusion of a sugar-phosphate backbone changes the electron affinity of most nucleobases from electron acceptors to electron donors. The methyl-terminated backbone-free model cannot replicate the steric effect induced by the sugar-phosphate backbone during the adsorption of nucleobases on 2D materials. Overall, we established that the sugar phosphate backbone should be included in the study of DNA nucleobase adsorption on 2D material. We also showed that when it comes to the adsorption on 2D materials, the backbone-containing H counterion model is superior to the Na counterion model because the Na counterion produces a LUMO near the Fermi energy, which may significantly affect the interaction with the 2D material.

Exploring polymerisation of methylglyoxal with NH3 or alanine to analyse the formation of typical polymers in melanoidins.

To investigate the formation of typical melanoidin polymers, methylglyoxal (MGO) with NH3 or alanine (Ala) was used to form coloured compounds, with glyoxal or acetone used as controls. The products were characterised using chromatography, mass spectrometry, and spectroscopy. Spectroscopic results showed that the coloured compounds formed were similar to melanoidins in food. GC-MS results showed that the MGO-based reaction generated similar volatile compounds using the Maillard reaction. Mass spectrometry showed that the molecular weights of structural units in the polymers were mainly 162, 169, and 176 Da, and these could be reassembled using the basic units derived from MGO alone or in combination with nitrogen. Hence, polymers recombined using basic structural units should be considered while determining melanoidin biomarkers. The preparation of coloured compounds using MGO with NH3 can be used as a novel method to produce the control compounds for melanoidin after process optimization.

A high-fidelity light-powered nanomotor from a chemically fueled counterpart via site-specific optomechanical fuel control.

Optically powered nanomotors are advantageous for clean nanotechnology over chemically fuelled nanomotors. The two motor types are further bounded by different physical principles. Despite the gap, we show here that an optically powered DNA bipedal nanomotor is readily created from a high-performing chemically fuelled counterpart by subjecting its fuel to cyclic site-specific optomechanical control - as if the fuel is optically recharged. Optimizing azobenzene-based control of the original nucleotide fuel selects a light-responsive fuel analog that replicates the different binding affinity of the fuel and reaction products. The resultant motor largely retains high-performing features of the original chemical motor, and achieves the highest directional fidelity among reported light-driven DNA nanomotors. This study thus demonstrates a novel strategy for transforming chemical nanomotors to optical ones for clean nanotechnology. The strategy is potentially applicable to many chemical nanomotors with oligomeric fuels like nucleotides, peptides and synthetic polymers, leading to a new class of light-powered nanomotors that are akin to chemical nanomotors and benefit from their generally high efficiency mechanistically. The motor from this study also provides a rare model system for studying the subtle boundary between chemical and optical nanomotors - a topic pertinent to chemomechanical and optomechanical energy conversion at the single-molecule level.

Chromosome-level genome assembly of Scapharca kagoshimensis reveals the expanded molecular basis of heme biosynthesis in ark shells.

Ark shells are commercially important clam species that inhabit in muddy sediments of shallow coasts in East Asia. For a long time, the lack of genome resources has hindered scientific research of ark shells. Here, we report a high-quality chromosome-level genome assembly of Scapharca kagoshimensis, with an aim to unravel the molecular basis of heme biosynthesis, and develop genomic resources for genetic breeding and population genetics in ark shells. Nineteen scaffolds corresponding to 19 chromosomes were constructed from 938 contigs (contig N50 = 2.01 Mb) to produce a final high-quality assembly with a total length of 1.11 Gb and scaffold N50 around 60.64 Mb. The genome assembly represents 93.4% completeness via matching 303 eukaryota core conserved genes. A total of 24,908 protein-coding genes were predicted and 24,551 genes (98.56%) of which were functionally annotated. The enrichment analyses suggested that genes in heme biosynthesis pathways were expanded and positive selection of the haemoglobin genes was also found in the genome of S. kagoshimensis, which gives important insights into the molecular mechanisms and evolution of the heme biosynthesis in mollusca. The valuable genome assembly of S. kagoshimensis would provide a solid foundation for investigating the molecular mechanisms that underlie the diverse biological functions and evolutionary adaptations of S. kagoshimensis.