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.     

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.     

Andrographolide Inhibits Biofilm and Virulence in Listeria monocytogenes as a Quorum-Sensing Inhibitor

Listeria monocytogenes is a major foodborne pathogen that can cause listeriosis in humans and animals. Andrographolide is known as a natural antibiotic and exhibits good antibacterial activity. We aimed to investigate the effect of andrographolide on two quorum-sensing (QS) systems, LuxS/AI-2 and Agr/AIP of L. monocytogenes, as well as QS-controlled phenotypes in this study. Our results showed that neither luxS expression nor AI-2 production was affected by andrographolide. Nevertheless, andrographolide significantly reduced the expression levels of the agr genes and the activity of the agr promoter P₂. Results from the crystal violet staining method, confocal laser scanning microscopy (CLSM), and field emission scanning electron microscopy (FE-SEM) demonstrated that andrographolide remarkably inhibited the biofilm-forming ability of L. monocytogenes 10403S. The preformed biofilms were eradicated when exposed to andrographolide, and reduced surviving cells were also observed in treated biofilms. L. monocytogenes treated with andrographolide exhibited decreased ability to secrete LLO and adhere to and invade Caco-2 cells. Therefore, andrographolide is a potential QS inhibitor by targeting the Agr QS system to reduce biofilm formation and virulence of L. monocytogenes.     

Quantum-Inspired Complex-Valued Language Models for Aspect-Based Sentiment Classification

Aiming at classifying the polarities over aspects, aspect-based sentiment analysis (ABSA) is a fine-grained task of sentiment analysis. The vector representations of current models are generally constrained to real values. Based on mathematical formulations of quantum theory, quantum language models have drawn increasing attention. Words in such models can be projected as physical particles in quantum systems, and naturally represented by representation-rich complex-valued vectors in a Hilbert Space, rather than real-valued ones. In this paper, the Hilbert Space representation for ABSA models is investigated and the complexification of three strong real-valued baselines are constructed. Experimental results demonstrate the effectiveness of complexification and the outperformance of our complex-valued models, illustrating that the complex-valued embedding can carry additional information beyond the real embedding. Especially, a complex-valued RoBERTa model outperforms or approaches the previous state-of-the-art on three standard benchmarking datasets.     

Thermo-Responsive ZnPc-g-TiO2-g-PNIPAM Photocatalysts Sensitized with Phthalocyanines for Water Purification under Visible Light

A novel thermo-responsive 2,9(10),16(17),23(24)-tetrakis[(3-carboxyacrylamide) phthalocyaninato] zinc (ZnPc)-g-TiO₂-g-poly(N-isopropylacrylamide) (PNIPAM) photocatalyst modified with phthalocyanines was prepared. The photocatalyst exhibited thermo-responsive properties due to the introduction of PNIPAM, which performed recovery for reuse above the lower critical solution temperature (LCST, about 26 °C). ZnPc-g-TiO₂-g-PNIPAM effectively expanded the light response range to the visible light region and inhibited the recombination of electron–hole pairs, which enhanced the performance of the photocatalyst. As expected, ZnPc-g-TiO₂-g-PNIPAM (0.3 g/L) exhibited excellent photocatalytic performance for the removal of Rhodamine B (RhB, 1.0 × 10⁻⁵ mol/L) and methylene blue (MB, 1.0 × 10⁻⁵ mol/L) under visible light, which reached 97.2% and 88.6% at 20 °C within 40 min, respectively. Furthermore, the influence of temperature upon photocatalytic performance was also investigated. When the temperature increased from 20 °C to 45 °C, the removal of RhB decreased by approximately 53.8%. The stability of the photocatalyst demonstrated that the photocatalytic activity was still above 80% for the removal of RhB after 3 cycles. Above all, this work provided an intelligent thermally responsive photocatalyst based on phthalocyanine for water purification under visible light.     

高频聚焦超声声场和温度场的仿真研究*

为探究临床常用的7 MHz高频聚焦超声在多层生物组织中的声传播以及毫秒级时间内的生物传热规律问题,基于Westervelt方程和Pennes传热方程,使用有限元方法建立高频聚焦超声辐照多层组织的非线性热黏性声传播及传热模型。首先分析了线性模型和非线性模型之间的差异,然后在非线性模型下探究换能器的参数对声场和温度场的影响。仿真结果显示：在7 MHz频率下,当换能器输出声功率超过5 W时,声波传播的非线性效应不可忽视(p <0.05);当声功率从5 W增大到15 W时,非线性模型与线性模型预测的温度偏差从20%增加到34.703%;高频聚焦超声波的非线性行为比低频更加显著,基频能量向高次谐波转移的程度增大,声功率为10 W和15 W时4次谐波与基波之比分别达到7.33%和12.12%;高频换能器参数的改变对组织中声场和温度场分布的影响较大,换能器焦距从12 mm减小到11.2 mm,焦点处最高温度增加了77%。结果表明,7 MHz聚焦超声的非线性声传播需要考虑到4次谐波的影响。该文提出的多层组织非线性仿真模型可为高频聚焦超声换能器参数优化及制定安全、有效的术前治疗方案提供理论参考。     

Carbene-catalyzed activation of cyclopropylcarbaldehydes for mannich reaction and δ-lactam formation: remote enantioselecitvity control and dynamic kinetic asymmetric transformation

An N-heterocyclic carbene(NHC)-catalyzed enantioselective Mannich reaction of the remote γ-carbon of cyclopropylcarbaldehydes is disclosed for the first time. Diastereo-and enantiomerically enriched multicyclic δ-lactam compound is afforded as the main product from 8 possible stereo-specific isomers through dynamic kinetic asymmetric transformation(DYKAT) processes. Multiple chiral functional molecules can be afforded from the lactam products through simple protocols with retentions of the optical purities.     

Rutin Inhibits Ox-LDL-Mediated Macrophage Inflammation and Foam Cell Formation by Inducing Autophagy and Modulating PI3K/ATK Signaling

Atherosclerosis (AS) is one of the leading causes of death among the elderly, and is primarily caused by foam cell generation and macrophage inflammation. Rutin is an anti-inflammatory, anti-oxidant, anti-allergic, and antiviral flavonoid molecule, known to have anti-atherosclerotic and autophagy-inducing properties, but its biological mechanism remains poorly understood. In this study, we uncovered that rutin could suppress the generation of inflammatory factors and reactive oxygen species (ROS) in ox-LDL-induced M2 macrophages and enhance their polarization. Moreover, rutin could decrease foam cell production, as shown by oil red O staining. In addition, rutin could increase the number of autophagosomes and the LC3II/I ratio, while lowering p62 expression. Furthermore, rutin could significantly inhibit the PI3K/ATK signaling pathway. In summary, rutin inhibits ox-LDL-mediated macrophage inflammation and foam cell formation by inducing autophagy and modulating PI3K/ATK signaling, showing potential in treating atherosclerosis.     

A Novel Gelatin-Based Sustained-Release Molluscicide for Control of the Invasive Agricultural Pest and Disease Vector Pomacea canaliculata

Pomacea canaliculata, one of the 100 most destructive invasive species in the world, and it is an important intermediate host of Angiostrongylus cantonensis. The molluscicides in current use are an effective method for controlling snails. However, most molluscicides have no slow-release effect and are toxic to nontarget organisms. Thus, these molluscicides cannot be used on a large scale to effectively act on snails. In this study, gelatin, a safe and nontoxic substance, was combined with sustained-release molluscicide and was found to reduce the toxicity of niclosamide to nontarget organisms. We assessed the effects of gelatin and molluscicide in controlling P. canaliculata snails and eggs. The results demonstrated that the niclosamide retention time with 1.0% and 1.5% gelatin sustained-release agents reached 20 days. Additionally, the mortality rate of P. canaliculata and their eggs increased as the concentration of the niclosamide sustained-release agents increased. The adult mortality rate of P. canaliculata reached 50% after the snails were exposed to gelatin with 0.1 mg/L niclosamide for 48 h. The hatching rate of P. canaliculata was only 28.5% of the normal group after the treatment was applied. The sustained-release molluscicide at this concentration was less toxic to zebrafish, which means that this molluscicide can increase the safety of niclosamide to control P. canaliculata in aquatic environments. In this study, we explored the safety of using niclosamide sustained-release agents with gelatin against P. canaliculata. The results suggest that gelatin is an ideal sustained-release agent that can provide a foundation for subsequent improvements in control of P. canaliculata.