Perfluoropentane-based oxygen-loaded nanodroplets reduce microglial activation through metabolic reprogramming

Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s disease.Nanoscale perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity,but also exhibit remarkable anti-inflammatory properties.However,the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly understood.In this study,we developed perfluoropentane-based oxygen-loaded nanodroplets(PFP-OLNDs)and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo,and suppressed microglial activation in a mouse model of Parkinson’s disease.Microglial suppression led to a reduction in the inflammatory response,oxidative stress,and cell migration capacity in vitro.Consequently,the neurotoxic effects were mitigated,which alleviated neuronal degeneration.Additionally,ultrahigh-performance liquid chromatography–tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic reprogramming.We further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1αpathway.Collectively,our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.

Ginsenoside modified lipid-coated perfluorocarbon nanodroplets: A novel approach to reduce complement protein adsorption and prolong in vivo circulation

Lipid-coated perfluorocarbon nanodroplets(lp-NDs)hold great promise in bio-medicine as vehicles for drug delivery,molecular imaging and vaccine agents.However,their clinical utility is restricted by limited targeted accumulation,attributed to the innate immune system(IIS),which acts as the initial defense mechanism in humans.This study aimed to optimize lp-ND formulations to mini-mize non-specific clearance by the IIS.Ginsenosides(Gs),the principal components of Panax ginseng,possessing complement inhibition ability,structural similarity to cholesterol,and comparable fat solubi-lity to phospholipids,were used as promising candidate IIS inhibitors.Two different types of ginsenoside-based Ip-NDs(Gs Ip-NDs)were created,and their efficacy in reducing IS recognition was examined.The Gs p-NDs were observed to inhibit the adsorption of C3 in the protein corona(PC)and the generation of SC5b-9.Adding Gs to Ip-NDs reduced complement adsorption and phagocytosis,resulting in a longer blood circulation time in vivo compared to lp-NDs that did not contain Gs.These results suggest that Gs can act as anti-complement and anti-phagocytosis adjuvants,potentially reducing non-specific clear-ance by the IS and improving lifespan.

Surface active agents stabilize nanodroplets and enhance haze formation

Although many organic molecules found commonly in the atmosphere are known to be surface-active in aqueous solutions, their effects on the mechanisms underlying haze formation remain unclear. In this paper, based on a simple thermodynamic analysis, we report that the adsorption of amphiphilic organics alone not only lowers the surface tension,but also unexpectedly stabilizes nanodroplets of specific size under water vapor supersaturation. Then we determine how various factors, including relative humidity, water activity effect due to dissolution of inorganic components as well as surface tension effect due to surface adsorption of organic components, cooperatively induce the stability of nanodroplets.The nanodroplet stability behaviors not captured in the current theory would change the formation mechanism of haze droplets, from the hygroscopic growth pathway to a nonclassical two-step nucleation pathway.

Near infrared light-induced dynamic modulation of enzymatic activity through polyphenol-functionalized liquid metal nanodroplets

Dynamic manipulation of enzymatic activity is a challenging task for applications in chemical and pharmaceutical industries due to the difficult modification and variable conformation of various enzymes.Here, we report a new strategy for reversible dynamic modulation of enzymatic activity by near-infrared light-induced photothermal conversion based on polyphenol-functionalized liquid metal nanodroplets(LM). The metal-phenolic nanocoating not only provides colloidal stability of LM nanodroplets but also generates nanointerfaces for the assembly of various enzymes on the LM nanodroplets. Upon near infrared(NIR) irradiation, the localized microenvironmental heating through photothermal effect of the LM nanodroplets allows tailoring the enzymatic activity without affecting the bulk temperature. A library of functional enzymes, including proteinase K, glucoamylase, glucose oxidase, and Bst DNA polymerase, is integrated to perform a reversible control and enhanced activities even after five times of cycles, demonstrating great potential in bacterial fermentation, bacteriostasis, and target gene amplification.

Ultralow friction of ion-containing water nanodroplets

We reveal the ultralow friction or superlubricity of water nanodroplets containing cations and anions on graphene substrates at high ion concentration by molecular dynamics simulations.When the ion concentration is higher than 7 wt.%and the nanodroplet diameter is larger than 10 nm,the friction coefficients of water nanodroplets are lower than 10−2,and can decrease to the order of 10−3 with increasing the ion concentration further.At a certain ion concentration,the optimal nanodroplet diameter of 17–20 nm exists at which the friction coefficient is the lowest.The ultralow friction behaviors of water nanodroplets containing cations and anions are mainly attributed to the opposite variation trends between the interfacial adhesion energy and surface energy of water nanodroplet with ion concentration,and the interfacial hydrophobicity sustained by high ion concentration.These results unveil the essential role of ions in achieving the superlubricity of water nanodroplets.

Color-coded perfluorocarbon nanodroplets for multiplexed ultrasound and photoacoustic imaging

Laser-activated perfluorocarb on n anodroplets are an emerging class of phase-cha nge, dual-c ontrast age nts that can be utilized in ultraso und and photoacoustic imaging. Through the ability to differe ntiate subpopulations of nano droplets via laser activatio n at differe nt wavelengths of n ear-infrared light, optically-triggered color-coded perfluorocarb on nano droplets prese nt themselves as an attractive tool for multiplexed ultrasound and photoacoustic imaging. In particular, laser-activated droplets can be used to provide quantitative spatiotemporal information regarding distinct biological targets, allowing for their potential use in a wide range of diagnostic and therapeutic applications. In the work prese nted, laser-activated color-coded perfluorocarb on nan odroplets are syn thesized to selectively resp ond to laser irradiati on at corresp on ding wavele ngths. The dyn amic ultraso und and photoacoustic signals produced by laser-activated perfluorocarbon nano droplets are evaluated in situ prior to implementation in a murine model. In vivo, these particles are used to distinguish unique particle trafficking mechanisms and are show n to provide ultraso und and photoacoustic contrast for up to 72 hours within lymphatics. Overall, the con ducted studies show that laser-activated color-coded perfluorocarbo n nano droplets are a promising agent for multiplexed ultraso und and photoacoustic imaging.

Coulomb explosion of nanodroplets drives the conversion of laser energy to nuclear energy

Theoretical–computational studies of table-top laser-driven nuclear fusion of high-energy(up to 15 MeV)deuterons with7Li,6Li,and D nuclei demonstrate the attainment of high fusion yields within a source–target reaction design.This constitutes a source of Coulomb-exploding deuterium nanodroplets driven by an ultraintense femtosecond near-infrared laser and a solid hollow cylindrical target containing the second element.The source–target reaction design attains the highest table-top fusion efficiencies(up to 4×109J 1per laser pulse)obtained to date.The highest conversion efficiency of laser energy to nuclear energy(10 2–10 3)for table-top DD fusion attained in the source–target design is comparable to that for DT fusion currently accomplished for‘big science’inertial fusion setups.

A REAL-TIME AFM STUDY ON CRYSTAL NUCLEATION AND GROWTH IN NANODROPLETS OF ISOTACTIC POLYPROPYLENE

Isotactic polypropylene （iPP） nanodroplets were prepared by using the classical droplet method in this study. The formation of nanodroplets allowed the controlled observation of polymer nucleation as well as access to crystal growth at exceptionally high supercooling in /PP. Three cases including the heterogeneous nucleation and fast crystallization in iPP droplets, the formation of multiple independent homogeneous nuclei within a single droplet and a single nucleus within a single droplet were detected by using atomic force microscopy （AFM） during gradually cooling after remelting the nanodroplets. Moreover, it is found that when the volume of droplet is larger than the value of ca. 130000 nm3, the first case was observed. Otherwise, the latter two cases appeared. The temperature at which the onset of nucleation was observed in individual droplets was found to be mainly dependent on height of the droplets when the size scale of the droplet is comparable to the size of the critical nucleus in at least one dimension, which indicates the nucleation behavior under confinement.

Multiphase flow physics of room temperature liquid metals and its applications

Multiphase flow existing everywhere in the motion evolution of nature,industrial processes,and daily life,has been an interdisciplinary cutting-edge frontier covering rather diverse disciplines.Traditional multiphase flow of high melting metals typically involves gas/vapor-liquid two-phase fluidics which usually requests intense energy processes and therefore limits their applications to a large extent.Different from this,the newly emerging room-temperature liquid metals(RTLMs)with fascinating metallic fluidic properties and multifunctional behaviors,not only well resolve the existing challenges facing conventional technologies,but also open up a series of new scientific and engineering subjects.Especially the conceptual introduction of multiphase composites endows liquid metal with many unconventional fluidic capabilities.To further push forward the advancement of this new area,the present article is dedicated to systematically outlining the scientific category of RTLMs multiphase flow physics and interpreting its fundamental and practical issues.The vision is to provide insights into promising developmental directions of RTLMs multiphase flow and thus facilitate synergetic research and progress among different disciplines.First,the traditional metal multiphase flow was briefly introduced.Then,we summarized the physics of RTLMs multiphase flow,the common types of liquid metals,the basic physical and chemical properties of their multiphase flow and governing equations,etc.Following that,various typical driving modalities and manipulation methods of RTLMs were illustrated.Finally,important implementations of RTLMs multiphase flow into thermal management,energy harvesting,catalysis,soft machines,biomedicine,and printed electronics were discussed.Overall,the multiphase flow physics of RTLMs is currently still in its incubation stage and there exist tremendous opportunities and challenges which are worth further pursuing in the coming time.

Real-Time and Spatial Electroanalysis of Biomolecules in One Living Cell Using Liquid-Phase Modified Nanopipette

The well-developed solid-phase modified strategy at the electrode has enabled the preparation of biosensors for the detection of multiple analytes,even in single living cells.However,limited assay elements can be modified at the solid surface,restricting the types of molecules that can be analyzed and the sensitivity of detection.Here,a novel liquid-phase modified strategy at the tip of a nanopipette is designed to realize real-time and local analysis of biomolecules inside the cell that are barely detectable using solid-phase modified nanoelectrodes.This design utilizes the nanotip structure at a platinized carbon open nanopipette to stably retain a nanodroplet that contains the required reagents with high reactivity for the assay of the target analyte.The generated hydrogen peroxide is electrochemically quantified at the Pt layer to carry out the real-time measurement in a living cell with a spatial resolution of 70 nm.Taking advantage of highly spatial and real-time detection,uneven distribution of sphingomyelinase(SMase)in the living CT26 cell is unprecedentedly shown to exhibit the significance in the establishment of liquid-phase modified nanopipette.This new modification strategy opens up a new direction for sensor design and consequently advances the development of biosensors in the chemical and biological research.

Molecular dynamics study of nanodroplet diffusion on smooth solid surfaces

We perform molecular dynamics simulations of Lennard-Jones particles in a canonical ensemble to study the diffusion of nanodroplets on smooth solid surfaces. Using the droplet-surface interaction to realize a hydrophilic or hydrophobic surface and calculating the mean square displacement of the center-of-mass of the nanodroplets, the random motion of nanodroplets could be characterized by short- time subdiffusion, intermediate-time superdiffusion, and long-time normal diffusion. The short-time subdiffusive exponent increases and almost reaches unity （normal diffusion） with decreasing droplet size or enhancing hydrophobicity. The diffusion coefficient of the droplet on hydrophobic surfaces is larger than that on hydrophilie surfaces.

Amphichoterpenoids A-C,unprecedented picoline-derived meroterpenoids from the ascidian-derived fungus Amphichorda felina SYSU-MS7908

Amphichoterpenoids A-C(1-3),unprecedented picoline-derived meroterpenoids possessing a pyrano[3,2-c]pyridinyl-g-pyranone scaffold,were characterized from the ascidian-derived fungus Amphichorda felina SYSU-MS7908.Their structures were elucidated by spectroscopic methods,X-ray diffraction and electronic circular dichroism(ECD)calculations.A plausible biosynthetic pathway was proposed.The isolated compounds displayed moderate inhibitory activity against acetylcholinesterase with 50%inhibiting concentration(IC_(50))values of 18.8-53.2 mmol/L.