Erasable and Field Programmable DNA Circuits Based on Configurable Logic Blocks.

DNA is commonly employed as a substrate for the building of artificial logic networks due to its excellent biocompatibility and programmability. Till now, DNA logic circuits are rapidly evolving to accomplish advanced operations. Nonetheless, nowadays, most DNA circuits remain to be disposable and lack of field programmability and thereby limits their practicability. Herein, inspired by the Configurable Logic Block (CLB), the CLB-based erasable field-programmable DNA circuit that uses clip strands as its operation-controlling signals is presented. It enables users to realize diverse functions with limited hardware. CLB-based basic logic gates (OR and AND) are first constructed and demonstrated their erasability and field programmability. Furthermore, by adding the appropriate operation-controlling strands, multiple rounds of programming are achieved among five different logic operations on a two-layer circuit. Subsequently, a circuit is successfully built to implement two fundamental binary calculators: half-adder and half-subtractor, proving that the design can imitate silicon-based binary circuits. Finally, a comprehensive CLB-based circuit is built that enables multiple rounds of switch among seven different logic operations including half-adding and half-subtracting. Overall, the CLB-based erasable field-programmable circuit immensely enhances their practicability. It is believed that design can be widely used in DNA logic networks due to its efficiency and convenience.

Current-Induced Creation of Topological Vortex Rings in a Magnetic Nanocylinder.

Vortex rings are ubiquitous topological structures in nature. In solid magnetic systems, their formation leads to intriguing physical phenomena and potential device applications. However, realizing these topological magnetic vortex rings and manipulating their topology on demand have still been challenging. Here, we theoretically show that topological vortex rings can be created by a current pulse in a chiral magnetic nanocylinder with a trench structure. The creation process involves the formation of a vortex ring street, i.e., a chain of magnetic vortex rings with an alternative linking manner. The created vortex rings can be bounded with monopole-antimonopole pairs and possess a rich and controllable linking topology (e.g., Hopf link and Solomon link), which is determined by the duration and amplitude of the current pulse. Our proposal paves the way for the realization and manipulation of diverse three-dimensional (3D) topological spin textures and could catalyze the development of 3D spintronic devices.

Controllable and reusable seesaw circuit based on nicking endonucleases.

Seesaw circuits are essential for molecular computing and biosensing. However, a notable limitation of seesaw circuits lies in the irreversible depletion of components, precluding the attainment of system recovery and rendering nucleic acid circuits non-reusable. We developed a brand-new method for creating controllable and reusable seesaw circuits. By using the nicking endonucleases Nt.BbvCI and Nt.Alwi, we removed "functional components" while keeping the "skeletal components" for recurrent usage. T-inputs were introduced, increasing the signal-to-noise ratio of AND logic from 2.68 to 11.33 and demonstrating compatibility. We identified the logic switching feature and verified that it does not impair circuit performance. We also built intricate logic circuits, such as OR-AND gate, to demonstrate the versatility of our methodology. This controllable reusability extends the applications of nanotechnology and bioengineering, enhancing the practicality and efficiency of these circuits across various domains.

Influence of crop residue-induced Fe-DOC complexation on nitrate reduction in paddy soil.

Although complexation between dissolved organic matter (DOM) and ubiquitous Fe is known to have a major influence on electron transferring ability in redoximorphic soil, it was unclear whether and how this complexation affected nitrate reduction and N2O productivity. The nitrate reduction of paddy soil in the presence of crop residues returning under flooding conditions was explored in this study. The rate of nitrate reduction in control soil was 0.0677 d-1, while it improved 1.99 times in treatment soil with Chinese milk vetch (CMV) straw returning. During a 28-day incubation period, N2O productivity decreased 0.08-0.91 ppb in CMV soil and 0.43-0.50 ppb in rice straw soil compared with control. The presence of crop residue increased DOC content and Fe (III) reduction rate, which aided in the formation of Fe (II)-DOC complexation. Meanwhile, the addition of CMV increased the content of DOC by 5.14-78.77 mg/kg and HCl extractable Fe (II) by 35.12-1221.03 mg/kg. Crop residues returning to soil increased the relative abundance of iron reductive and electroactive genera, as well as denitrifying genera with more copies of denitrification genes (Archangiaceae, Gemmatimonadaceae, and Burkholderiaceae). The synergistic effect of Fe-DOC complexation, electroactive genera, and denitrifying genera contributed to up-regulated expression of napA and narG (5.84 × 106 and 3.39 × 107 copies increased in the CMV soil compared to the control) numbers and equally accelerated reduction of nitrate to nitrite, while further nitrite reduction was primarily attributed to the abiotic reaction by Fe (II). From a bio-electrochemical point of view, this work provided new insight into the nitrate reduction of paddy soil impacted by Fe-DOC complexation.

Creation of Room-Temperature Sub-100 nm Antiferromagnetic Skyrmions in an Antiferromagnet IrMn through Interfacial Exchange Coupling.

Antiferromagnetic (AFM) skyrmions are magnetic vortices composed of antiparallell-aligned neighboring spins. In stark contrast to conventional skyrmions based on ferromagnetic order, AFM skyrmions have vanished stray fields, higher response frequencies, and rectified translational motion driven by an external force. Therefore, AFM skyrmions promise highly efficient spintronics devices with high bit mobility and density. Nevertheless, the experimental realization of intrinsic AFM skyrmions remains elusive. Here, we show that AFM skyrmions can be nucleated via interfacial exchange coupling at the surface of a room-temperature AFM material, IrMn, exploiting the particular response from uncompensated moments to the thermal annealing and imprinting effects. Further systematic magnetic characterizations validate the existence of such an AFM order at the IrMn/CoFeB interfaces. Such AFM skyrmions have a typical size of 100 nm, which presents pronounced robustness against field and temperature. Our work opens new pathways for magnetic topological devices based on AFM skyrmions.

Robust fragment-based method of calculating hydrogen atom transfer activation barrier in complex molecules.

Dynamic processes driven by non-covalent interactions (NCI), such as conformational exchange, molecular binding, and solvation, can strongly influence the rate constants of reactions with low activation barriers, especially at low temperatures. Examples of this may include hydrogen-atom-transfer (HAT) reactions involved in the oxidative stress of an active pharmaceutical ingredient (API). Here, we develop an automated workflow to generate HAT transition-state (TS) geometries for complex and flexible APIs and then systematically evaluate the influences of NCI on the free activation energies, based on the multi-conformational transition-state theory (MC-TST) within the framework of a multi-step reaction path. The two APIs studied: fesoterodine and imipramine, display considerable conformational complexity and have multiple ways of forming hydrogen bonds with the abstracting radical-a hydroxymethyl peroxyl radical. Our results underscore the significance of considering conformational exchange and multiple activation pathways in activation calculations. We also show that structural elements and NCIs outside the reaction site minimally influence TS core geometry and covalent activation barrier, although they more strongly affect reactant binding and consequently the overall activation barrier. We further propose a robust and economical fragment-based method to obtain overall activation barriers, by combining the covalent activation barrier calculated for a small molecular fragment with the binding free energy calculated for the whole molecule.

EEG brain network variability is correlated with other pathophysiological indicators of critical patients in neurology intensive care unit.

Continuous electroencephalogram (cEEG) plays a crucial role in monitoring and postoperative evaluation of critical patients with extensive EEG abnormalities. Recently, the temporal variability of dynamic resting-state functional connectivity has emerged as a novel approach to understanding the pathophysiological mechanisms underlying diseases. However, little is known about the underlying temporal variability of functional connections in critical patients admitted to neurology intensive care unit (NICU). Furthermore, considering the emerging field of network physiology that emphasizes the integrated nature of human organisms, we hypothesize that this temporal variability in brain activity may be potentially linked to other physiological functions. Therefore, this study aimed to investigate network variability using fuzzy entropy in 24-hour dynamic resting-state networks of critical patients in NICU, with an emphasis on exploring spatial topology changes over time. Our findings revealed both atypical flexible and robust architectures in critical patients. Specifically, the former exhibited denser functional connectivity across the left frontal and left parietal lobes, while the latter showed predominantly short-range connections within anterior regions. These patterns of network variability deviating from normality may underlie the altered network integrity leading to loss of consciousness and cognitive impairment observed in these patients. Additionally, we explored changes in 24-hour network properties and found simultaneous decreases in brain efficiency, heart rate, and blood pressure between approximately 1 pm and 5 pm. Moreover, we observed a close relationship between temporal variability of resting-state network properties and other physiological indicators including heart rate as well as liver and kidney function. These findings suggest that the application of a temporal variability-based cEEG analysis method offers valuable insights into underlying pathophysiological mechanisms of critical patients in NICU, and may present novel avenues for their condition monitoring, intervention, and treatment.

Dysregulated CD200-CD200R signaling in early diabetes modulates microglia-mediated retinopathy.

Diabetic retinopathy (DR) is a neurovascular complication of diabetes. Recent investigations have suggested that early degeneration of the neuroretina may occur prior to the appearance of microvascular changes; however, the mechanisms underlying this neurodegeneration have been elusive. Microglia are the predominant resident immune cell in the retina and adopt dynamic roles in disease. Here, we show that ablation of retinal microglia ameliorates visual dysfunction and neurodegeneration in a type I diabetes mouse model. We also provide evidence of enhanced microglial contact and engulfment of amacrine cells, ultrastructural modifications, and transcriptome changes that drive inflammation and phagocytosis. We show that CD200-CD200R signaling between amacrine cells and microglia is dysregulated during early DR and that targeting CD200R can attenuate high glucose-induced inflammation and phagocytosis in cultured microglia. Last, we demonstrate that targeting CD200R in vivo can prevent visual dysfunction, microglia activation, and retinal inflammation in the diabetic mouse. These studies provide a molecular framework for the pivotal role that microglia play in early DR pathogenesis and identify a potential immunotherapeutic target for treating DR in patients.

A Route Planning Method for UAV Swarm Inspection of Roads Fusing Distributed Droneport Site Selection.

Current methods that use Unmanned Aerial Vehicle (UAV) swarms to inspect roads still have many limitations in practical applications, such as the lack of or difficulty in the route planning, the unbalanced utilization rate of the UAV swarm and the difficulty of the site selection for the distributed droneports. To solve the limitations, firstly, we construct the inspection map and remove the redundant information irrelevant to the road inspection. Secondly, we formulate both the route planning problem and the droneport site selection problem in a unified multi-objective optimization model. Thirdly, we redesign the encoding strategy, the updating rules and the decoding strategy of the particle swarm optimization method to effectively solve both the route planning problem and the droneport site selection problem. Finally, we introduce the comprehensive evaluation indicators to verify the effectiveness of the route planning and the droneport site selection. The experimental results show that (1) with the proposed method, the overlapped part of the optimized inspection routes is less than 7% of the total mileage, and the balanced utilization rate of the UAVs is above 75%; (2) the reuse rate of the distributed droneports is significantly improved after optimization; and (3) the proposed method outperforms the ant colony optimization (ACO) method in all evaluation indicators. To this end, the proposed method can effectively plan the inspection routes, balance the utilization of the UAVs and select the sites for the distributed droneports, which has great significance for a fully autonomous UAV swarm inspection system for road inspection.

Fatigue Performance Analysis of Welded T-Joints in Orthotropic Steel Bridge Decks with Ultrasonic Impact Treatment.

This study aims to assess the effect of ultrasonic impact treatment (UIT) on the exterior weld seam of S355J2 T-joints used in orthotropic steel bridge decks. The microstructure and mechanical behavior of T-joints after UIT was investigated in this study. Fatigue tests of T-joints before and after UIT were performed. The stress concentration at the interior and exterior weld toe of T-joints was considered using the traction structural stress method. The results showed that hardness increases by 10% due to the localized grain refinement caused by UIT. UIT significantly improves the fatigue life of T-joint specimens by 350% and 150% at stress ratios of 0.1 and 0.3, respectively. As the transition angle between the weld profile and the base metal profile increases, the stress concentration factor decreases.

Self-Assembly Properties of an Amphiphilic Phosphate Ester Prodrug Designed for the Treatment of COVID-19.

PF-07304814 is a water-soluble phosphate ester prodrug of a small molecule inhibitor for the SARS CoV-2 3CL protease designed for the treatment of COVID-19. The amphiphilicity and self-assembly behavior of the prodrug was investigated computationally and experimentally via multiple orthogonal techniques to better design formulations for intravenous infusion. The self-assembly of PF-07304814 into micellar structures enabled an increase in the solubility of lipophilic impurities by up to 1900x in clinically relevant formulations. The observed solubilization could help extend the drug product shelf-life and in use stability through inhibition of precipitation, without the need for solubilizing excipients. The work presented in this manuscript provides a roadmap for the characterization of prodrug self-assembly and highlights the potential for prodrug modifications to enhance solubility of both active ingredients and impurities and to extend drug product shelf-life.

Nonlinear Optical Modulation Characteristics of MXene Cr2C for 2 µm Pulsed Lasers.

MXene materials have shown numerous useful mechanical and electronic properties, and have been found to possess nice potential in the field of optical modulation. Here, we fabricated a MXene Cr2C saturable absorber by the liquid-phase exfoliation method, and systemically analyzed the surface morphology and nonlinear properties of the Cr2C sample. Applying the Cr2C saturable absorber as a Q-switch in a thulium-doped yttrium aluminum perovskite (Tm: YAP) laser, the shortest single pulse was obtained with a width of 602 ns under an absorbed pump power of 3.3 W at a repetition rate of 55 kHz with a T = 1% output coupler. The maximum output power was obtained with a T = 5% output coupler at a repetition rate of 58 kHz. The obtained maximum pulse energy and peak power were 3.96 µJ and 4.36 W, separately, which reveal that the MXene Cr2C can be applied as a promising modulation material in the near-infrared pulsed lasers.

High-power, sub-100-fs, 1600-1700-nm all-fiber laser for deep multiphoton microscopy.

The 1600-1700-nm ultrafast fiber lasers attract great interests in the deep multiphoton microscopy, due to the reduced levels of the tissue scattering and absorption. Here, we report on the 86.7-MHz, 717-mW, 91.2-fs, all-fiber laser located in the spectral range from 1600 nm to 1700nm. The soliton self-frequency shift (SSFS) was introduced into the Er:Yb co-doped fiber amplifier (EYDFA) to generate the high-power, 1600-1700-nm Raman soliton. Detailed investigations of the nonlinear fiber amplification process were implemented in optimizing the generated Raman soliton pulses. The miniature multiphoton microscopy was further realized with this home-built laser source. The clearly imaging results can be achieved by collecting the generated harmonic signals from the mouse tail skin tissue with a penetration depth of ∼500 µm. The experimental results indicate the great potential in utilizing this 1600-1700-nm fiber laser in the deep multiphoton microscopy.

Shexiang Tongxin Dropping Pill alleviates M1 macrophage polarization-induced inflammation and endothelial dysfunction to reduce coronary microvascular dysfunction via the Dectin-1/Syk/IRF5 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Shexiang Tongxin Dropping Pill (STDP), a traditional Chinese medicine compound, is fragrant, invigorates the qi, unblocks pulses, activates the blood circulation, removes blood stasis, and relieves pain. It is used clinically to treat coronary heart disease and angina pectoris. Coronary microvascular dysfunction (CMD) is associated with increased morbidity and mortality from cardiovascular events. Endothelial dysfunction and inflammation have been verified as its underlying causes. STDP can ameliorate CMD, but the mechanism has not been fully elucidated. AIM OF THE STUDY: To explore the effects of STDP on M1 macrophage polarization-induced inflammation and endothelial dysfunction as an inhibitor of CMD, and to determine its mechanisms of action. MATERIALS AND METHODS: The CMD rat model was established by left anterior descending artery (LAD) ligation. The efficacy of STDP against CMD was evaluated by echocardiography, optical microangiography, Evans blue staining, and histological examination. The OGD/R-induced endothelial injury model, the endothelial injury-induced sterile inflammation model, the Dectin-1 overexpression model, and the Dectin-1-overexpressing RAW264.7 macrophage supernatant-stimulated HUVEC-induced secondary injury of endothelial function model were established to confirm the efficacy of STDP against M1 macrophage polarization-induced inflammation and endothelial dysfunction. RESULTS: STDP blunted the deterioration of cardiac function and ameliorated CMD by reducing inflammatory cell infiltration and endothelial dysfunction in CMD rats. Endothelial injury and Dectin-1 overexpression induced M1 macrophage polarization and inflammation. Mechanically, STDP hindered M1 macrophage polarization and inflammation by inhibiting the Dectin-1/Syk/IRF5 pathway both in vivo and in vitro. STDP alleviated endothelial dysfunction induced by Dectin-1 overexpression in macrophages. CONCLUSION: STDP can alleviate M1 macrophage polarization-induced inflammation and endothelial dysfunction against CMD via the Dectin-1/Syk/IRF5 pathway. Dectin-1-associated M1 macrophage polarization might be developed as a novel target for ameliorating CMD.

100-mJ, 100-W cryogenically cooled Yb:YLF laser.

We present a diode-pumped Yb:YLF laser system generating 100-mJ sub-ps pulses at a 1-kHz repetition rate (100 W average power) by chirped-pulse amplification. The laser consists of a cryogenically cooled 78 K, regenerative, eight-pass booster amplifier seeded by an all-fiber front end. The output pulses are compressed to 980 fs in a single-grating Treacy compressor with a throughput of 89%. The laser will be applied to multi-cycle THz generation and pumping of high average power parametric amplifiers.

Evolution of Emergent Monopoles into Magnetic Skyrmion Strings.

Topological defects are fundamental concepts in physics, but little is known about the transition between distinct types across different dimensionalities. In topological magnetism, as in field theory, the transition between 1D strings and 0D monopoles is a key process whose observation has remained elusive. Here, we introduce a novel mechanism that allows for the controlled stabilization of emergent monopoles and show that magnetic skyrmion strings can be folded into monopoles. Conversely, they act as seeds out of which the entire string structure can unfold, containing its complete information. In chiral magnets, this process can be observed by resonant elastic X-ray scattering when the objects are in proximity to a polarized ferromagnet, whereby a pure monopole lattice is emerging on the surface. Our experimental proof of the reversible evolution from monopole to string sheds new light on topological defects and establishes the emergent monopole lattice as a new 3D topological phase.

Electrical switching of ferro-rotational order in nanometre-thick 1T-TaS2 crystals.

Hysteretic switching of domain states is a salient characteristic of all ferroic materials and the foundation for their multifunctional applications. Ferro-rotational order is emerging as a type of ferroic order that features structural rotations, but control over state switching remains elusive due to its invariance under both time reversal and spatial inversion. Here we demonstrate electrical switching of ferro-rotational domain states in the charge-density-wave phases of nanometre-thick 1T-TaS2 crystals. Cooling from the high-symmetry phase to the ferro-rotational phase under an external electric field induces domain state switching and domain wall formation, which is realized in a simple two-terminal configuration using a volt-scale bias. Although the electric field does not couple with the order due to symmetry mismatch, it drives domain wall propagation to give rise to reversible, durable and non-volatile isothermal state switching at room temperature. These results offer a route to the manipulation of ferro-rotational order and its nanoelectronic applications.

Obtaining non-digestible polysaccharides from distillers' grains of Chinese baijiu after extrusion with enhanced antioxidation capability.

Distillers' grains of Chinese Baijiu (DGS) presents a significant challenge to the environmentally-friendly production of the brewing industry. This study utilized screw extrusion to modify the morphological and crystalline characteristics of DGS, resulting in a 316 % increase in the yield of non-digestible polysaccharides extraction. Physiochemical characteristics of extracted polysaccharides were variated, including infrared spectrum, monosaccharide composition, and molecular weight. Polysaccharides extracted from extruded DGS exhibited enhanced inhibitory capacity on α-amylase activity and starch hydrolyzation, as compared to those extracted from unextruded DGS. Additionally, the ABTS, DPPH, and OH radical scavenging efficiencies took a maximum increase of 1.20, 1.38, and 1.02-fold, correspondingly. Extrusion is a novel approach for the recycling non-digestible polysaccharides from DGS, augmenting the bioactivity of extracts and their potential application in functional food.

Maximum Spreading Diameter of Bouncing Droplets at Ultralow Weber Numbers.

In the present work, we study the maximum spreading of bouncing droplets in the capillary regime at ultralow Weber numbers with a fixed static contact angle. In the ultralow Weber number region, experiments reveal that existing spreading laws are inapplicable because of gravity exclusion and change in deformation shape. We propose a theoretical scaling law based on energy conservation, modeling the deformed droplet as an ellipsoid with gravity effects. The proposed scaling law indicates the competition between gravity and inertia at ultralow Weber numbers and distinguishes their dominant regimes. By integrating higher-Weber-number regions, we reveal that viscosity is prominent in the previously assumed inviscid regime. Furthermore, we devise a phase diagram to clarify different impact regimes on the basis of energy analysis.