Enhancing cell membrane phase separation for inhibiting cancer metastasis with a stimuli-responsive DNA nanodevice

Phase separation in cell membranes promotes the assembly of transmembrane receptors to initiate signal transduction in response to environmental cues. Many cellular behaviors are manipulated by promoting membrane phase separation through binding to multivalent extracellular ligands. However, available extracellular molecule tools that enable manipulating the clustering of transmembrane receptors in a controllable manner are rare. In the present study, we report a DNA nanodevice that enhances membrane phase separation through the clustering of dynamic lipid rafts. This DNA nanodevice is anchored in the lipid raft region of the cell membrane and initiated by ATP. In a tumor microenvironment, this device could be activated to form a long DNA duplex on the cell membrane, which not only enhances membrane phase separation, but also blocks the interaction between the transmembrane surface adhesion receptor and extracellular matrix, leading to reduced migration. We demonstrate that the ATP-activated DNA nanodevice could inhibit cancer cell migration both in vitro and in vivo. The concept of using DNA to regulate membrane phase separation provides new possibilities for manipulating versatile cell functions through rational design of functional DNA structures.

A DNA nanodevice is developed to enhance the cell membrane phase separation in a tumor microenvironment to weaken the formation of focal adhesion. As a result, the migration of cancer cells is inhibited both in vitro and in vivo.     

Non-covalent reconfigurable microgel colloidosomes with a well-defined bilayer shell

Microgels are extremely interfacially active and are widely used to stabilize emulsions. However, they are commonly used to stabilize oil-in-water emulsions due to their intrinsic hydrophilicity and initially dispersed in water. In addition, there have been no attempts to control microgel structural layers that are formed at the interface and as a result it limits applications of microgel in advanced materials. Here, we show that by introducing octanol into poly(N-isopropylacrylamide-co-methacrylic acid) (PNIPAM-co-MAA) microgels, octanol-swollen microgels can rapidly diffuse from the initially dispersed oil phase onto the water droplet surface. This facilitates the formation of microgel-laden interfacial layers with strong elastic responses and also generates stable inverse water-in-oil Pickering emulsions. These emulsions can be used as templates to produce microgel colloidosomes, herein termed ‘microgelsomes’, with shells that can be fine-tuned from a particle monolayer to a well-defined bilayer. The microgelsomes can then be used to encapsulate and/or anchor nanoparticles, proteins, vitamin C, bio-based nanocrystals or enzymes. Moreover, the programmed release of these substances can be achieved by using ethanol as a trigger to mediate shell permeability. Thus, these reconfigurable microgelsomes with a microgel-bilayer shell can respond to external stimuli and demonstrate tailored properties, which offers novel insights into microgels and promise wider application of Pickering emulsions stabilized by soft colloids.

Inverse W/O Pickering emulsions and reconfigurable microgelsomes with a well-defined bilayer structure are prepared from octanol-swollen PNIPAM-co-MAA microgels and the combination of binary microgels, which promise wider application of soft colloids.     

Why heterogeneous single-atom catalysts preferentially produce CO in the electrochemical CO2 reduction reaction

Formate and CO are competing products in the two-electron CO₂ reduction reaction (2e CO₂RR), and they are produced via *OCHO and *COOH intermediates, respectively. However, the factors governing CO/formate selectivity remain elusive, especially for metal–carbon–nitrogen (M–N–C) single-atom catalysts (SACs), most of which produce CO as their main product. Herein, we show computationally that the selectivity of M–N–C SACs is intrinsically associated with the CO₂ adsorption mode by using bismuth (Bi) nanosheets and the Bi–N–C SAC as model catalysts. According to our results, the Bi–N–C SAC exhibits a strong thermodynamic preference toward *OCHO, but under working potentials, CO₂ is preferentially chemisorbed first due to a charge accumulation effect, and subsequent protonation of chemisorbed CO₂ to *COOH is kinetically much more favorable than formation of *OCHO. Consequently, the Bi–N–C SAC preferentially produces CO rather than formate. In contrast, the physisorption preference of CO₂ on Bi nanosheets contributes to high formate selectivity. Remarkably, this CO₂ adsorption-based mechanism also applies to other typical M–N–C SACs. This work not only resolves a long-standing puzzle in M–N–C SACs, but also presents simple, solid criteria (i.e., CO₂ adsorption modes) for indicating CO/formate selectivity, which help strategic development of high-performance CO₂RR catalysts.

This report discloses a nontrivial role of the CO₂ adsorption mode in governing the CO/formate selectivity of single-atom catalysts towards two-electron CO₂ reduction.     

Towards the rational design of Pt-based alloy catalysts for the low-temperature water-gas shift reaction: from extended surfaces to single atom alloys

The rational design of Pt-based catalysts for the low-temperature water-gas-shift (LT-WGS) reaction is an active research field because of its important role played in the fuel cell-based hydrogen economy, especially in mobile applications. Previous theoretical analyses have suggested that Pt alloys, leading to a weaker CO binding affinity than the Pt metal, could help alleviate CO poisoning and thus should be promising catalysts of the LT-WGS reaction. However, experimental research along this line was rather ineffective in the past decade. In the present work, we employed the state-of-the-art kinetic Monte Carlo (KMC) simulations to examine the influences of the electronic effect by introducing sub-surface alloys and/or core–shell structures, and the synergetic effect by introducing single atom alloys on the catalytic performance of Pt-alloy catalysts. Our KMC simulations have highlighted the importance of the OH binding affinity on the catalyst surfaces to reduce the barrier of water dissociation as the rate determining step, instead of the CO binding affinity as has been emphasized before in conventional mean-field kinetic models. Along this new direction of catalyst design, we found that Pt–Ru synergetic effects can significantly increase the activity of the Pt metal, leading to Ru_1–3@Pt alloys with a tetrahedron site of one surface-three subsurface Ru atoms on the Pt host, showing a turnover frequency of about five orders of magnitude higher than the Pt metal.

KMC simulations show that decreasing the barrier of H₂O decomposition is more beneficial than decreasing the CO binding affinity in LT-WGS, while the latter was overemphasized by MF-MKM. Here Ru_1–3@Pt alloy is proposed as a promising catalyst.     

Intramitochondrial co-assembly between ATP and nucleopeptides induces cancer cell apoptosis

Mitochondria are essential intracellular organelles involved in many cellular processes, especially adenosine triphosphate (ATP) production. Since cancer cells require high ATP levels for proliferation, ATP elimination can be a unique target for cancer growth inhibition. We describe a newly developed mitochondria-targeting nucleopeptide (MNP) that sequesters ATP by self-assembling with ATP inside mitochondria. MNP interacts strongly with ATP through electrostatic and hydrogen bonding interactions. MNP exhibits higher binding affinity for ATP (−637.5 kJ mol⁻¹) than for adenosine diphosphate (ADP) (−578.2 kJ mol⁻¹). To improve anticancer efficacy, the small-sized MNP/ADP complex formed large assemblies with ATP inside cancer cell mitochondria. ATP sequestration and formation of large assemblies of the MNP/ADP–ATP complex inside mitochondria caused physical stress by large structures and metabolic disorders in cancer cells, leading to apoptosis. This work illustrates a facile approach to developing cancer therapeutics that relies on molecular assemblies.

Mitochondria-targeting nucleopeptide (MNP) can sequester ATP by self-assembling with ATP. A small nanosized MNP/ADP complex forms a large assembly with ATP. Thus, intramitochondrial co-assembly causes stress by large structures and apoptosis.     

Machine learning-based real-time visible fatigue crack growth detection

Many large-scale and complex structural components are applied in the aeronautics and automobile industries.However,the repeated alternating or cyclic loads in ...     

Semi-Supervised Cross-Subject Emotion Recognition Based on Stacked Denoising Autoencoder Architecture Using a Fusion of Multi-Modal Physiological Signals

In recent decades, emotion recognition has received considerable attention. As more enthusiasm has shifted to the physiological pattern, a wide range of elaborate physiological emotion data features come up and are combined with various classifying models to detect one’s emotional states. To circumvent the labor of artificially designing features, we propose to acquire affective and robust representations automatically through the Stacked Denoising Autoencoder (SDA) architecture with unsupervised pre-training, followed by supervised fine-tuning. In this paper, we compare the performances of different features and models through three binary classification tasks based on the Valence-Arousal-Dominance (VAD) affection model. Decision fusion and feature fusion of electroencephalogram (EEG) and peripheral signals are performed on hand-engineered features; data-level fusion is performed on deep-learning methods. It turns out that the fusion data perform better than the two modalities. To take advantage of deep-learning algorithms, we augment the original data and feed it directly into our training model. We use two deep architectures and another generative stacked semi-supervised architecture as references for comparison to test the method’s practical effects. The results reveal that our scheme slightly outperforms the other three deep feature extractors and surpasses the state-of-the-art of hand-engineered features.     

A Family of Fitness Landscapes Modeled through Gene Regulatory Networks

Fitness landscapes are a powerful metaphor for understanding the evolution of biological systems. These landscapes describe how genotypes are connected to each other through mutation and related through fitness. Empirical studies of fitness landscapes have increasingly revealed conserved topographical features across diverse taxa, e.g., the accessibility of genotypes and “ruggedness”. As a result, theoretical studies are needed to investigate how evolution proceeds on fitness landscapes with such conserved features. Here, we develop and study a model of evolution on fitness landscapes using the lens of Gene Regulatory Networks (GRNs), where the regulatory products are computed from multiple genes and collectively treated as phenotypes. With the assumption that regulation is a binary process, we prove the existence of empirically observed, topographical features such as accessibility and connectivity. We further show that these results hold across arbitrary fitness functions and that a trade-off between accessibility and ruggedness need not exist. Then, using graph theory and a coarse-graining approach, we deduce a mesoscopic structure underlying GRN fitness landscapes where the information necessary to predict a population’s evolutionary trajectory is retained with minimal complexity. Using this coarse-graining, we develop a bottom-up algorithm to construct such mesoscopic backbones, which does not require computing the genotype network and is therefore far more efficient than brute-force approaches. Altogether, this work provides mathematical results of high-dimensional fitness landscapes and a path toward connecting theory to empirical studies.     

Visible Light-Driven Alkyne-Grafted Ethylene-Bridged Azobenzene Chromophores for Photothermal Utilization

Molecular photoswitches are considered to be important candidates in the field of solar energy storage due to their sensitive and reversible bidirectional optical response. Nevertheless, it is still a daunting challenge to design a molecular photoswitch to improve the low solar spectrum utilization and quantum yields while achieving charging and discharging of heat without solvent assistance. Herein, a series of visible-light-driven ethylene-bridged azobenzene (b-Azo) chromophores with different alkyne substituents which can undergo isomerization reactions promoted in both directions by visible light are reported. Their visible light responsiveness improves their solar spectrum utilization while also having high quantum yields. In addition, as the compounds are liquids, there is no need to dissolve the compounds in order to exploit this switching. The photoisomerization of b-Azo can be adjusted by alkyne-related substituents, and hexyne-substituted b-Azo is able to store and release photothermal energy with a high density of 106.1 J·g⁻¹, and can achieve a temperature increase of 1.8 °C at a low temperature of −1 °C.     

Surface Functionalized Magnetic Nanoparticles as a Selective Sorbent for Affinity Fishing of PPAR-γ Ligands from Choerospondias axillaris

Coronary heart disease (CHD), which has developed into one of the major diseases, was reported to be treated by the target of peroxisome proliferators-activate receptor γ (PPAR-γ). As a natural medicine long used in the treatment of CHD, there are few studies on how to screen the target active compounds with high specific activity from Choerospondias axillaris. To advance the pace of research on target-specific active compounds in natural medicines, we have combined magnetic ligand fishing and functionalized nano-microspheres to investigate the active ingredients of PPAR-γ targets in Choerospondias axillaris. The PPAR-γ functionalized magnetic nano-microspheres have been successfully synthesized and characterized by vibrating sample magnetometer (VSM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The specificity, reusability, and reproducibility of the nano-microspheres were investigated with the help of the specific binding of rosiglitazone to PPAR-γ. In addition, the incubation temperature and the pH of the buffer solution in the magnetic ligand fishing were optimized to improve the specific adsorption efficiency of the analytes. Finally, with the aid of ultraperformance liquid chromatography plus Q-Exactive Orbitrap tandem mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS/MS), the 16 active ligands including 9 organic acids, 5 flavonoids, and 2 phenols were found in the ethanolic extracts of Choerospondias axillaris. Therefore, the study can provide a successful precedent for realizing the designated extraction and rapid isolation of target-specific active ingredient groups in the complex mixtures.