Role of Fast and Slow Inhibitors in Oscillatory Rhythm Design.

In biological or abiotic systems, rhythms occur, owing to the coupling between positive and negative feedback loops in a reaction network. Using the Semenov-Whitesides oscillatory network for thioester hydrolysis as a prototype, we experimentally and theoretically analyzed the role of fast and slow inhibitors in oscillatory reaction networks. In the presence of positive feedback, a single fast inhibitor generates a time delay, resulting in two saddle-node bifurcations and bistability in a continuously stirred tank reactor. A slow inhibitor produces a node-focus bifurcation, resulting in damped oscillations. With both fast and slow inhibitors present, the node-focus bifurcation repeatedly modulates the saddle-node bifurcations, producing stable periodic oscillations. These fast and slow inhibitions result in a pair of time delays between steeply ascending and descending dynamics, which originate from the positive and negative feedbacks, respectively. This pattern can be identified in many chemical relaxation oscillators and oscillatory models, e.g., the bromate-sulfite pH oscillatory system, the Belousov-Zhabotinsky reaction, the trypsin oscillatory system, and the Boissonade-De Kepper model. This study provides a novel understanding of chemical and biochemical rhythms and suggests an approach to designing such behavior.

Multiple iodide autocatalysis paths of chemo-hydrodynamical patterns in the Briggs-Rauscher reaction.

Autocatalytic feedback is often regarded as the core step for the chemo-hydrodynamical patterns in the nonlinear reaction system. The Briggs-Rauscher (BR) reaction shows sequential chemo-hydrodynamical patterns with three states, i.e. labyrinth, high iodine state, and rotating dendritic patterns. The short-lived labyrinth patterns, depending on [Mn2+]0, the ratio of [CH2(COOH)2]0 and [KIO3]0 and light intensities, result from iodide autocatalytic loop, which has three paths (involving Mn2+-induced radical reactions, the oxidation of iodomalonic compounds, and light-induced radical reactions, respectively). The high iodine state appears in a high ratio of [CH2(COOH)2]0 and [KIO3]0, relating to the autocatalytic path involving the oxidation of iodomalonic compounds. The light-induced radical autocatalytic path can act as a convenient control parameter to modulate the patterns in the first stage by increasing the iodine radicals. The dendritic patterns in the third stage result from the Marangoni effect caused by the evaporation of the solutions and reactions between H2O2 and iodine-containing species, which is independent of [CH2(COOH)2]0 and [Mn2+]0. This work contributes to a better understanding of the complex spatiotemporal patterns in the chemo-hydrodynamical system.

Peptide-Modulated pH Rhythms.

Many drugs adjust and/or control the spatiotemporal dynamics of periodic processes such as heartbeat, neuronal signaling and metabolism, often by interacting with proteins or oligopeptides. Here we use a quasi-biocompatible, non-equilibrium pH oscillatory system as a biomimetic biological clock to study the effect of pH-responsive peptides on rhythm dynamics. The added peptides generate feedback that can lengthen or shorten the oscillatory period during which the peptides alternate between random coil and coiled-coil conformations. This modulation of a chemical clock supports the notion that short peptide reagents may have utility as drugs to regulate human body clocks.

Al-assisted high frequency self-powered oscillations of liquid metal droplets.

It is of great scientific and practical significance to explore and imitate the rhythmic oscillating behaviors. Achieving oscillating behaviours via liquid metal is regarded as an excellent strategy and the "mercury beating heart" is a well-known representative. However, the oscillating behaviours achieved over the past few decades either require external power supply or exhibit low frequency. Here, intriguing Al-assisted high frequency self-powered oscillations of liquid metal droplets were discovered and the general mechanisms were interpreted. For this dynamic process, Al is added into the liquid metal for generating gas and activating liquid metal by forming countless tiny galvanic cells and an iron plate is used to passivate the liquid metal via electrochemical oxidation. Therefore, the high frequency self-fueled oscillations can be achieved due to the synergistic effect of these two factors. Furthermore, we predict and confirm that the oscillating behaviors can also be achieved on other eligible substrates (e.g., Ni plate) based on the proposed universal mechanism. The ability to achieve high frequency oscillations of liquid metal droplets promises rich opportunities in developing self-powered soft oscillators.

Progress, Mechanisms and Applications of Liquid-Metal Catalyst Systems.

Among the significant growths of liquid metal (LM) research achieved over the past few years, the field of LM as catalysts offers promising opportunities for material scientists to exploit, and thus, burgeoning progress has been made. This article presents an overview of recent progress in developing LM catalysis, which spans from liquid-phase catalysts, photocatalysts, heterogeneous catalysts, and bimetallic catalysts, to catalysts based on liquid-metal/metal-oxide (LM/MO) frameworks. The different types, preparation methods, and typical applications of LM catalysts are classified and reviewed. Typical catalytic applications of LM systems discussed include the growth of graphene films/nanoribbons/carbon nanotube, photocatalytic degradation of CR or PFOA/splitting of H2 O/reduction of CO2 , and catalytic reactions like butane or acetylene dehydrogenation, methanol steam reforming, and reduction of potassium ferricyanide. The prospects, future trends, and challenges of LM catalysts are also mentioned.

Human articular chondrocytes express multiple gap junction proteins: differential expression of connexins in normal and osteoarthritic cartilage.

Osteoarthritis (OA) is the most common joint disease and involves progressive degeneration of articular cartilage. The aim of this study was to investigate if chondrocytes from human articular cartilage express gap junction proteins called connexins (Cxs). We show that human chondrocytes in tissue express Cx43, Cx45, Cx32, and Cx46. We also find that primary chondrocytes from adults retain the capacity to form functional voltage-dependent gap junctions. Immunohistochemistry experiments in cartilage from OA patients revealed significantly elevated levels of Cx43 and Cx45 in the superficial zone and down through the next approximately 1000 µm of tissue. These zones corresponded with regions damaged in OA that also had high levels of proliferative cell nuclear antigen. An increased number of Cxs may help explain the increased proliferation of cells in clusters that finally lead to tissue homeostasis loss. Conversely, high levels of Cxs in OA cartilage reflect the increased number of adjacent cells in clusters that are able to interact directly by gap junctions as compared with hemichannels on single cells in normal cartilage. Our data provide strong evidence that OA patients have a loss of the usual ordered distribution of Cxs in the damaged zones and that the reductions in Cx43 levels are accompanied by the loss of correct Cx localization in the nondamaged areas.

Liquid Metal Memory.

Storage systems are vital components of electronic devices, while significant challenges persist in achieving flexible memory due to the limitations of existing storage methodologies. Inspired by the polarization and depolarization mechanisms in the human brain, here a novel class of storage principles is proposed and achieve a fully flexible memory through introducing the oxidation and deoxidation behaviors of liquid metals. Specifically, reversible electrochemical oxidation is utilized to modulate the overall conductivity of the target liquid metals, creating a substantial 11-order resistance difference for binary data storage. To obtain the best storage performance, systematic optimizations of multiple parameters are conducted. Conceptual experiments demonstrate the memory's stability under extreme deformations (100% stretching, 180° bending, 360° twisting). Further tests reveal that the memory performs better when its unit size gets smaller, warranting superior integrability. Finally, a complete storage system achieves remarkable performance metrics, including rapid storage speed (>33 Hz), long data retention capacity (>43200 s), and stable repeatable operation (>3500 cycles). This groundbreaking method not only overcomes the inherent rigidity limitations of existing electronic storage units but also opens new possibilities for innovating neuromorphic devices, offering fundamental and practical avenues for future applications in soft robotics, wearable electronics, and bio-inspired artificial intelligence systems.

Magnetic and injectable Fe-doped liquid metals for controlled movement and photothermal/electromagnetic therapy.

As a multifunctional material, gallium-based liquid metal (LM) mixtures with metal particles dispersed in the LM environment display many excellent and intriguing properties. In this study, biomaterials were prepared by mixing Fe particles with LM for easily manageable photothermal or electromagnetic therapy and evaluated. Clinically, the fabricated 5%Fe/LM sample was injectable and radiopaque, which allowed its smooth delivery through a syringe to the target tissues, where it could help achieve clear imaging under CT. Meanwhile, because of the loading of Fe particles, the 5%Fe/LM possessed a magnetic property, implying a high manipulation capability. According to the experiments, the capsule containing 5%Fe/LM when placed in an isolated pig large intestine could move as desired to the designated position through an external magnet. Further, the biosafety and low toxicity of the 5%Fe/LM were confirmed by cytotoxicity tests in vitro, and the temperature changes at the interface between the 5%Fe/LM and intestinal tissue after near-infrared (NIR) laser irradiation were determined through theoretical modeling and numerical simulation data analysis. Due to the excellent photothermal and magnetothermal effects of LM, the temperature of the 5%Fe/LM injected into the rabbit abdominal cavity could significantly increase under NIR laser or alternating magnetic field (AMF) administration. As a novel functional biomaterial, the 5%Fe/LM exhibited promising potential for designated position movement and photothermal or magnetothermal therapy in the near future.

Semi-liquid metal-based highly permeable and adhesive electronic skin inspired by spider web.

Soft and stretchable electronics have garnered significant attention in various fields, such as wearable electronics, electronic skins, and soft robotics. However, current wearable electronics made from materials like conductive elastomers, hydrogels, and liquid metals face limitations, including low permeability, poor adhesion, inadequate conductivity, and limited stretchability. These issues hinder their effectiveness in long-term healthcare monitoring and exercise monitoring. To address these challenges, we introduce a novel design of web-droplet-like electronics featuring a semi-liquid metal coating for wearable applications. This innovative design offers high permeability, excellent stretchability, strong adhesion, and good conductivity for the electronic skin. The unique structure, inspired by the architecture of a spider web, significantly enhances air permeability compared to commercial breathable patches. Furthermore, the distribution of polyborosiloxane mimics the adhesive properties of spider web mucus, while the use of semi-liquid metals in this design results in remarkable conductivity (9 × 106 S/m) and tensile performance (up to 850% strain). This advanced electronic skin technology enables long-term monitoring of various physiological parameters and supports machine learning recognition functions with unparalleled advantages. This web-droplet structure design strategy holds great promise for commercial applications in medical health monitoring and disease diagnosis.

Multi-stimulus perception and visualization by an intelligent liquid metal-elastomer architecture.

Multi-stimulus responsive soft materials with integrated functionalities are elementary blocks for building soft intelligent systems, but their rational design remains challenging. Here, we demonstrate an intelligent soft architecture sensitized by magnetized liquid metal droplets that are dispersed in a highly stretchable elastomer network. The supercooled liquid metal droplets serve as microscopic latent heat reservoirs, and their controllable solidification releases localized thermal energy/information flows for enabling programmable visualization and display. This allows the perception of a variety of information-encoded contact (mechanical pressing, stretching, and torsion) and noncontact (magnetic field) stimuli as well as the visualization of dynamic phase transition and stress evolution processes, via thermal and/or thermochromic imaging. The liquid metal-elastomer architecture offers a generic platform for designing soft intelligent sensing, display, and information encryption systems.

Toxicity and Biocompatibility of Liquid Metals.

Recently, room-temperature liquid metals have attracted increasing attention from researchers owing to their excellent material properties. Systematic interpretation of the potential toxicity issues involved is essential for a wide range of applications, especially in the biomedical and healthcare fields. However, even with the exponential growth of related studies, investigation of the toxicological impact and possible hazards of liquid metals to organisms is still in its infancy. This review aims to provide a comprehensive summary of the current frontier of knowledge on liquid metal toxicology and biocompatibility in different environments. Based on recent studies, this review focuses on Ga and Bi-based in different states. It is necessary to evaluate their toxicity considering the rapid increase in research and utilization of such liquid metal composites. Finally, existing challenges are discussed and suggestions are provided for further investigation of liquid metal toxicology to clarify the toxicological mechanisms and strategies are provided to avoid adverse effects. In addition to resolving the doubts of public concern about the toxicity of liquid metals, this review is expected to promote the healthy and sustainable development of liquid metal-based materials and their use in diverse areas, especially those related to health care.

Thermal Interface Materials with High Thermal Conductivity and Low Young's Modulus Using a Solid-Liquid Metal Codoping Strategy.

Thermal interface materials (TIMs), as typical thermal functional materials, are highly required to possess both high thermal conductivity and low Young's modulus. However, the naturally synchronized change in the thermal and mechanical properties seriously hinders the development of high-performance TIMs. To tackle such a dilemma, a strategy of codoping solid fillers and liquid metal fillers into polymer substrates is proposed in this study. This strategy includes a large amount of liquid metals that play the role of thermal paths and a small amount of uniformly dispersed solid fillers that further enhance heat conduction. Through the synergistic effect of the liquid metal and solid fillers, the thermal conductivity can be improved, and Young's modulus can be kept small simultaneously. A typical TIM with a volume of 55% gallium-based liquid metal and 15% copper particles as fillers has a thermal conductivity of 3.94 W/(m·K) and a Young's modulus of 699 kPa, which had the maximum thermomechanical performance coefficient compared with liquid metal TIMs and solid filler-doped TIMs. In addition, the thermal conductivity of the solid-liquid metal codoped TIM increased sharply with an increase of liquid metal content, and Young's modulus increased rapidly with an increase of the volume ratio of copper and polymer. The high-low-temperature cycling test and large-size light-emitting diode (LED) application demonstrated that this TIM had stable physical performance. The synergistic effect of the solid fillers and liquid metal fillers provides a broad space to solve the classic tradeoff issue of the mechanical and thermal properties of composites.

Flexible Skin Patch Enabled Tumor Hybrid Thermophysical Therapy and Adaptive Antitumor Immune Response.

Innovations on materials and technologies have greatly promoted the rapid development of wearable electronics from disease diagnosis to therapeutics. For superficial skin tumors, skin-attachable patches possess the advantages of minimally invasive property, alleviative side effects, and high efficiency. The development of noninvasive techniques and devices is still in urgent demands. Here, a flexible skin patch fabricated through a facile preparation method is reported for noninvasive hybrid thermophysical therapy and adaptative immune function enhancement. The liquid metal enabled skin patch is demonstrated with high conductivity, certain stability, biocompatibility, and an enhanced adhesive merit on skin surfaces for cryoablation therapy and magnetic hyperthermia therapy. The skin patch exhibits remarkably conformable heating and cooling performance toward the treatment of 4T1 breast tumors. The magnetic resonance images also indicate the significant tumor ablation effect. Interestingly, a relatively stable proportion of both CD8+ T and CD4+ T cells in the peripheral blood is identified after tumor therapy in comparison with the decreased trend in the untreated group, representing an efficient antitumor immune response induced by the skin patch. The developed skin patch would provide a promising noninvasive approach for tumor therapies by direct tumor destruction and maintenance of the antitumor immune response.

Locating Multiple Standard Planes in First-Trimester Ultrasound Videos via the Detection and Scoring of Key Anatomical Structures.

OBJECTIVE: This study was aimed at developing a first-trimester standard plane detection (FTSPD) system that can automatically locate nine standard planes in ultrasound videos and investigating its utility in clinical practice. METHODS: The FTSPD system, based on the YOLOv3 network, was developed to detect structures and evaluate the quality of plane images by using a pre-defined scoring system. A total of 220 videos from two different ultrasound scanners were collected to compare detection performance between our FTSPD system and sonographers with different levels of experience. The quality of the detected standard planes was quantitatively rated by an expert according to a scoring protocol. Kolmogorov-Smirnov analysis was used to compare the distributions of scores across all nine standard planes. RESULTS: The expert-rated scores indicated that the quality of the standard planes detected by the FTSPD system was on par with that of the planes detected by senior sonographers. There were no significant differences in the distributions of the scores across all nine standard planes. The FTSPD system performed significantly better than junior sonographers in five standard plane types. CONCLUSION: The results of this study suggest that our FTSPD system has significant potential for detecting standard planes in first-trimester ultrasound screening, which may help to improve the accuracy of fetal ultrasound screening and facilitate early diagnosis of abnormalities. The quality of the standard planes selected by junior sonographers can be significantly improved with the assistance of our FTSPD system.

A Photothermally Enhanced Vancomycin-Coated Liquid Metal Antimicrobial Agent with Targeting Capability.

The targeted antimicrobial efficacy of Vancomycin decreases significantly over time due to bacterial resistance, whereas Ga-based liquid metals, which are less prone to inducing bacterial resistance, face challenges in achieving targeted antimicrobial effects. To tackle these issues, a highly efficient antimicrobial agent with targeting properties has been developed by combining Ga-based liquid metals and Vancomycin. Moreover, the performance of this antimicrobial agent can be greatly enhanced through the use of near-infrared light. Microscopic observations reveal that Vancomycin can be effectively encapsulated on the surface of liquid metal, facilitated by the presence of the oxide layer. The resulting core-shell structured antimicrobial agent demonstrates notable targeted antimicrobial effects against S. aureus. Antibacterial tests indicate that Vancomycin effectively improves the antibacterial properties of pure liquid metal. Additionally, this study unveils the excellent photothermal conversion capabilities of liquid metal, enabling the antimicrobial agent exposed to 808nm near-infrared light to exhibit significantly strengthened bactericidal performance. In this scenario, the antimicrobial agent can achieve nearly 100% effectiveness. This work enriches the investigation of integrating Ga-based antimicrobial agents with traditional antibiotics, showcasing promising antibacterial effects and establishing the groundwork for subsequent clinical applications.

RecON: Online learning for sensorless freehand 3D ultrasound reconstruction.

Sensorless freehand 3D ultrasound (US) reconstruction based on deep networks shows promising advantages, such as large field of view, relatively high resolution, low cost, and ease of use. However, existing methods mainly consider vanilla scan strategies with limited inter-frame variations. These methods thus are degraded on complex but routine scan sequences in clinics. In this context, we propose a novel online learning framework for freehand 3D US reconstruction under complex scan strategies with diverse scanning velocities and poses. First, we devise a motion-weighted training loss in training phase to regularize the scan variation frame-by-frame and better mitigate the negative effects of uneven inter-frame velocity. Second, we effectively drive online learning with local-to-global pseudo supervisions. It mines both the frame-level contextual consistency and the path-level similarity constraint to improve the inter-frame transformation estimation. We explore a global adversarial shape before transferring the latent anatomical prior as supervision. Third, we build a feasible differentiable reconstruction approximation to enable the end-to-end optimization of our online learning. Experimental results illustrate that our freehand 3D US reconstruction framework outperformed current methods on two large, simulated datasets and one real dataset. In addition, we applied the proposed framework to clinical scan videos to further validate its effectiveness and generalizability.

Responsive Liquid Metal Droplets: From Bulk to Nano.

Droplets exist widely in nature and play an extremely important role in a broad variety of industrial processes. Typical droplets, including water and oil droplets, have received extensive attention and research, however their single properties still cannot meet diverse needs. Fortunately, liquid metal droplets emerging in recent years possess outstanding properties, including large surface tension, excellent electrical and thermal conductivity, convenient chemical processing, easy transition between liquid and solid phase state, and large-scale deformability, etc. More interestingly, liquid metal droplets with unique features can respond to external factors, including the electronic field, magnetic field, acoustic field, chemical field, temperature, and light, exhibiting extraordinary intelligent response characteristics. Their development over the past decade has brought substantial breakthroughs and progress. To better promote the advancement of this field, the present article is devoted to systematically summarizing and analyzing the recent fundamental progress of responsive liquid metal droplets, not only involving droplet characteristics and preparation methods, but also focusing on their diverse response behaviors and mechanisms. On this basis, the challenges and prospects related to the following development of liquid metal droplets are also proposed. In the future, responsive liquid metal droplets with a rapid development trend are expected to play a key role in soft robots, biomedicine, smart matter, and a variety of other fields.

Comprehensive Profile Analysis of Differentially Expressed circRNAs in Glucose Deprivation-Induced Human Nucleus Pulposus Cell Degeneration.

Nucleus pulposus (NP) is the core substance to maintain the homeostasis of intervertebral disc and stability of biomechanics. The insufficient supply of nutrition (especially glucose) is an important factor that leads to the degeneration of NP cells. circRNAs play an important role in the process of intervertebral disc degeneration (IDD) by regulating the functions of NP cells. However, glucose deprivation-related circRNAs and their functions in IDD have not been reported. In this study, the differentially expressed circRNAs in NP cells after 0, 6, 12, and 24 h of glucose deprivation culture were detected by a microarray assay. Besides, time series clustering analysis by STEM software obtained the differentially up- and downregulated circRNAs during glucose deficiency. Then, the main functions and pathways of up- and downregulated circRNAs were predicted by the functional enrichment analysis. By constructing the circRNA-miRNA regulatory network, the potential mechanisms of the most differentially expressed circRNAs were predicted. In addition, according to in vitro validation, circ_0075062 was upregulated in degenerating NP tissues and glucose deprivation-induced NP cell degeneration. Based on Sanger sequencing and RNase tolerance assay, circ_0075062 was the circular transcript. Interfering with circ_0075062 expression could potentially alleviate the imbalance of extracellular matrix (ECM) synthesis and degradation in the NP cells induced by glucose deprivation. Together, these findings help us gain a comprehensive understanding of the underlying mechanisms of IDD, and circ_0075062 may be a promising therapeutic target of IDD.

Injectable Affinity and Remote Magnetothermal Effects of Bi-Based Alloy for Long-Term Bone Defect Repair and Analgesia.

As alternatives, metallic/nonmetallic bone graft materials play significant roles in bone defect surgery to treat external trauma or bone disease. However, to date, there are rather limited long-term implantable materials owning to in situ molding incapability of metallics and poor mechanical property of nonmetallics. Here, Bi-based low melting point alloy, with unique properties of injectability, solid-liquid phase transition, mechanical capability, and biocompatibility, present obvious long-lasting bone affinity as the excellent artificial bone-substitute. It is particularly necessary to point out that the targeted injected Bi alloy remains in its original position for up to 210 days without moving, as well as, displays good osseointegration ability to resolve repeated revision trauma caused by losing bone repair material. Additionally, with outstanding electrical and thermal conductivity, an unconventional way using Bi alloy to realize very beneficial hyperthermia analgesia via non-invasive wireless energy delivery is first proposed, which avoids adverse effects on bone remodeling inflicted by traditional drugs. The significantly decreased expression of pain sensitizing factor, such as, interleukin-6, neuropeptide substance, and transient receptor potential vanilloid 1 reveals the potential mechanism of hyperthermia analgesia. The present findings suggest the combination therapy of Bi alloy in bone repair and analgesia, which owns far-reaching clinical application value.

Improving smallholder farmers' maize yields and economic benefits under sustainable crop intensification in the North China Plain.

To meet the food demands of a growing population, the maize production systems deployed by smallholders in China have tended towards extremely intensive planting and excessive use of fertilizers, which have caused serious environmental impacts. This study investigated the balance between the maize yield and nitrogen (N) input in the North China Plain (NCP), which is one of the most important grain-producing region in China. Our study compared yield simulations generated by the DSSAT-CERES-Maize model with actual data from a number of multi-site field experiments and an extensive household surveys encompassing 1671 farmers. The smallholders' maize cultivars, plant population, and amount of N input on the crop yield and how these affects the economic benefits were analyzed. The results showed that the average traditional farming methods' yield was 72% of the attainable yield, which means that farmers have ample room to improve their yields. We also found that the maize yields varied widely between farmers, and that most of them applied excessive amounts of N but failing to achieve an optimal yield due to poor fertilization management techniques. The study found that the economic benefits achieved by the farmers were low, but after deploying high-yield (HY) methods, the yield was increased by 34.9% and the economic benefits by 14.4%. The greenhouse gas (GHG) emissions associated with the traditional farming methods were high and could potentially be reduced by 48.6%. All in all, farmers should be given guidance on how to appropriately increase the plant population, reduce the input of N fertilizer, and optimize farmland management measures, so that China can achieve intensive but sustainable agricultural production at a lower environmental cost. It was concluded that there are still numerous biological and abiotic factors that restrict production increases by smallholders. These factors vary from region to region and require further investigation.