Spontaneous Takeoff of Single Sulfur Nanoparticles during Sublimation Studied by Dark-Field Microscopy.

The Leidenfrost effect describes a fascinating phenomenon in which a liquid droplet, when deposited onto a very hot substrate, will levitate on its own vapor layer and undergo frictionless movements. Driven by the significant implications for heat transfer engineering and drag reduction, intensive efforts have been made to understand, manipulate, and utilize the Leidenfrost effect on macrosized objects with a typical size of millimeters. The Leidenfrost effect of nanosized objects, however, remains unexplored. Herein, we report on an unprecedented Leidenfrost effect of single nanosized sulfur particles at room temperature. It was discovered when advanced dark-field optical microscopy was employed to monitor the dynamic sublimation process of single sulfur nanoparticles sitting on a flat substrate. Despite the phenomenological similarity, including the vapor-cushion-induced levitation and the extended lifetime, the Leidenfrost effect at the nanoscale exhibited two extraordinary features that were obviously distinct from its macroscopic counterpart. First, there was a critical size below which single sulfur nanoparticles began to levitate. Second, levitation occurred in the absence of the temperature difference between the nanoparticle and the substrate, which was barely possible for macroscopic objects and underscored the value of bridging the gap connecting the Leidenfrost effect and nanoscience. The sublimation-triggered spontaneous takeoff of single sulfur nanoparticles shed new light on its further applications, such as nanoflight.

Enantiomers Self-Sort into Separate Counter-Twisted Ribbons of the Fddd Liquid Crystal─Antiferrochirality and Parachirality.

The recently discovered orthorhombic liquid crystal (LC) phase of symmetry Fddd is proving to be widespread. In this work, a chiral hydroxybutyrate linkage is inserted into the molecular core of hexacatenar rodlike compounds, containing a thienylfluorenone fluorophore. In addition to more usual tools, the methods used include grazing-incidence X-ray scattering, modulated differential scanning calorimetry (DSC), flash DSC with rates up to 6000 K/s, and chiro-optical spectroscopies using Mueller matrix method, plus conformational mapping. Although pure R and S enantiomers form only a strongly chiral hexagonal columnar LC phase (Colh*), the racemic mixture forms a highly ordered Fddd phase with 4 right- and 4 left-handed twisted ribbon-like columns traversing its large unit cell. In that structure, the two enantiomers locally deracemize and self-sort into the columns of their preferred chirality. The twisted ribbons in Fddd, with a 7.54 nm pitch, consist of stacked rafts, each containing ∼2 side-by-side molecules, the successive rafts rotated by 17°. In contrast, an analogous achiral compound forms only the columnar phase. The multiple methods used gave a comprehensive picture and helped in-depth understanding not only of the Fddd phase but also of the "parachiral" Colh* in pure enantiomers with irregular helicity, whose chirality is compared to the magnetization of a paramagnet in a field. Unusual short-range ordering effects are also described. An explanation of these phenomena is proposed based on conformational analysis. Surprisingly, the isotropic-columnar transition is extremely fast, completing within ∼20 ms. A clear effect of phase on UV-vis absorption and emission is observed.

Single-Molecule Force Spectroscopy Reveals Cation-π Interactions in Aqueous Media Are Highly Affected by Cation Dehydration.

Cation-π interactions underlie many important processes in biology and materials science. However, experimental investigations of cation-π interactions in aqueous media remain challenging. Here, we studied the cation-π binding strength and mechanism by pulling two hydrophobic polymers with distinct cation binding properties, i.e., poly-pentafluorostyrene and polystyrene, in aqueous media using single-molecule force spectroscopy and nuclear magnetic resonance measurement. We found that the interaction strengths linearly depend on the cation concentrations, following the order of Li^{+}

Optical Imaging of the Molecular Mobility of Single Polystyrene Nanospheres.

An ultrathin surface layer with extraordinary molecular mobility has been discovered and intensively investigated on thin-film polymer materials for decades. However, because of the lack of suitable characterization techniques, it remains largely unexplored whether such a surface mobile layer also exists on individual polymeric nanospheres. Here, we propose a thermal-optical imaging technique to determine the glass transition (Tg) and rubber-fluid transition (Tf) temperatures of single isolated polystyrene nanospheres (PSNS) in a high-throughput and nonintrusive manner for the first time. Two distinct steps, corresponding to the glass transition and rubber-fluid transition, respectively, were clearly observed in the optical trace of single PSNS during temperature ramping. Because the transition temperature and size of the same individuals were both determined, single nanoparticle measurements revealed the reduced apparent Tf and increased Tg of single PSNS on the gold substrate with a decreasing radius from 130 to 70 nm. Further experiments revealed that the substrate effect played an important role in the increased Tg. More importantly, a gradual decrease in the optical signal was detected prior to the glass transition, which was consistent with a surface layer with enhanced molecular mobility. Quantitative analysis further revealed the thickness of this layer to be ∼8 nm. This work not only uncovered the existence and thickness of a surface mobile layer in single isolated nanospheres but also demonstrated a general bottom-up strategy to investigate the structure-property relationship of polymeric nanomaterials by correlating the thermal property (Tg and Tf) and structural features (size) at single nanoparticle level.

Dynamic Monte Carlo simulations of strain-induced crystallization in multiblock copolymers: effects of dilution.

Multiblock copolymers containing alternating semicrystalline and molten blocks are good thermoplastic elastomers. Their crystallization in the stretching process is however complicated by the dilution effects, prior microphase separation and contrast chain rigidity of the molten blocks. We designed our systematic investigation with three integrated steps, and herein, as the first step, we considered only the dilution effects without prior microphase separation and contrast chain rigidity. We compared two extreme situations of local dilution separately corresponding to parallel-posited and antiparallel-posited block copolymers upon strain-induced crystallization. Our dynamic Monte Carlo simulations of diblock and tetrablock copolymers demonstrated that the stretching introduces a constraint on the diffusion of locally posited crystallizable blocks along the stretching direction for crystallization and thus enhances the dilution effects to result in a higher diversity in crystal stabilities. We observed that the strain-induced crystallization of parallel-posited copolymers behaved like the melt crystallization of homopolymers; in contrast, the strain-induced crystallization of antiparallel-posited copolymers yielded crystallites near the block junction, which are relatively small and less stable due to their local dilution suppressing their melting points. Similar to the case of spider dragline silks, two contrasting stabilities of crystallites in semicrystalline multiblock copolymers explain their good toughness. Our modeling approach paves the way toward a better understanding of the structure-property relationship in the semicrystalline thermoplastic elastomers.

Nascent structure memory erased in polymer stretching.

Stretching of semicrystalline polymer materials is fundamentally important in their mechanical performance and industrial processing. By means of dynamic Monte Carlo simulations, we compared the parallel stretching processes between the initially bulk amorphous and semicrystalline polymers at various temperatures. In the early stage of stretching, semicrystalline polymers perform local and global melting-recrystallization behaviors at low and high temperatures, while the memory effects occur upon global melting-recrystallization at middle temperatures. However, the final crystallinities, crystalline bond orientations, chain-folding probabilities, residual stresses, and crystallite morphologies at high enough strains appear as the same at each temperature, irrelevant to the initially amorphous and semicrystalline polymers, indicating that the common post-growth melting-reorganization processes determine the final products. In addition, both final products harvest the highest crystallinities in the middle temperature region because the postgrowth stage yields the vast nuclei followed with less extent of crystal growth in the low temperature region and few nuclei followed with large extent of crystal growth in the high temperature region. Our observations imply that a large enough strain can effectively remove the thermal history of polymers, similar to the thermal treatment at a high enough temperature; therefore, the fracture strength of semicrystalline polymers depends upon their final structures in stretching, not related to their nascent semicrystalline structures.

miR-198 inhibits the progression of renal cell carcinoma by targeting BIRC5.

BACKGROUND: miR-198 is involved in the formation, migration, invasion, and metastasis of various malignant cancers. However, the function and mechanism of action of miR-198 in the tumorigenesis of renal cell carcinoma (RCC) remain elusive. Here, we aimed to explore the role of miR198 in RCC. METHODS: Immunohistochemistry was performed to estimate the level of survivin in RCC sections. Quantitative real-time polymerase chain reaction was performed to determine the expression level of miR-198 in fresh RCC tissues. Furthermore, the target relationship between miR-198 and BIRC5 was predicted using the TargetScanHuman 7.2 database and verified via dual-luciferase reporter assay and western blotting. The effects of miR-198 on the viability, apoptosis, invasion, and migration of A498 and ACHN cells were studied using Cell Counting Kit-8, flow cytometry, transwell migration assay, and wound healing assay, respectively. Additionally, a xenograft nude mouse model was established to evaluate the effect of miR-198 on RCC tumorigenesis. RESULTS: The expression levels of BIRC5 and miR-198 were respectively higher and lower in RCC tissues than those in normal adjacent tissues. Furthermore, miR-198 could inhibit luciferase activity and reduce the protein level of survivin without affecting the BIRC5 mRNA levels. miR-198 inhibited cell viability, migration, and invasion and promoted cell apoptosis; co-transfection with BIRC5 could rescue these effects. Moreover, miR-198 could repress tumor growth in the xenograft nude mouse model of RCC. CONCLUSIONS: Our study demonstrates that miR-198 suppresses RCC progression by targeting BIRC5.

Both living and dead Faecalibacterium prausnitzii alleviate house dust mite-induced allergic asthma through the modulation of gut microbiota and short-chain fatty acid production.

BACKGROUND: Asthma is increasingly prevalent worldwide, and novel strategies to prevent or treat this disease are needed. Probiotic intervention has recently been reported to be effective for asthma prevention. Here, we explored the effects of Faecalibacterium prausnitzii on the development of allergic airway inflammation in a murine model of house dust mite (HDM)-induced allergic asthma. RESULTS: Supplementation with living and dead F. prausnitzii blocked eosinophil, neutrophil, lymphocyte and macrophage influx and alleviated the pathological changes. Moreover, both living and dead F. prausnitzii administration decreased the levels of interleukin (IL)-4, IL-5, IL-13 and immunoglobulin G1, elevated regulatory T cell (Tregs) ratio, improved microbial dysbiosis and enhanced short-chain fatty acid (SCFA) production. Network correlation analysis revealed that the immune indicators were strongly associated with SCFA production. Based on the linear discriminant analysis effect size, Turicibacter was found to be the core genus related to HDM-induced asthma. Living F. prausnitzii treatment enriched Faecalibaculum, Dubosiella and Streptococcus, while dead F. prausnitzii treatment increased Muribaculaceae and Parabacteroides. Interestingly, both living and dead F. prausnitzii administration enriched Lachnoclostridium and normalized the pathways involving carbohydrate and lipid metabolism, which might be related to SCFA production. CONCLUSION: Faecalibacterium prausnitzii exerts an anti-asthmatic effect partly by gut microbiota modulation and SCFA production, suggesting its potential as a probiotic agent for allergic asthma prevention. © 2021 Society of Chemical Industry.

Anomalous Ostwald Ripening Enables 2D Polymer Crystals via Fast Evaporation.

We demonstrate by molecular simulations that the Ostwald ripening of crystalline polymer nuclei within the fast-evaporation-induced 2D skin layer is retarded at suitable temperatures and evaporation rates. Such an anomalous ripening can be attributed to the interplay between the thermodynamically driven diffusion of noncrystalline fragments toward the growing nuclei and the diffusive current away from the free surface caused by the densification in the nonequilibrium skin layer. The growth orientation of the nuclei inside the skin plane can be adjusted during this anomalous ripening process, which is beneficial for fabricating 2D polymer crystals.

Cytochrome c folds through foldon-dependent native-like intermediates in an ordered pathway.

Previous hydrogen exchange (HX) studies of the spontaneous reversible unfolding of Cytochrome c (Cyt c) under native conditions have led to the following conclusions. Native Cyt c (104 residues) is composed of five cooperative folding units, called foldons. The high-energy landscape is dominated by an energy ladder of partially folded forms that differ from each other by one cooperative foldon unit. The reversible equilibrium unfolding of native Cyt c steps up through these intermediate forms to the unfolded state in an energy-ordered sequence, one foldon unit at a time. To more directly study Cyt c intermediates and pathways during normal energetically downhill kinetic folding, the present work used HX pulse labeling analyzed by a fragment separation-mass spectrometry method. The results show that 95% or more of the Cyt c population folds by stepping down through the same set of foldon-dependent pathway intermediates as in energetically uphill equilibrium unfolding. These results add to growing evidence that proteins fold through a classical pathway sequence of native-like intermediates rather than through a vast number of undefinable intermediates and pathways. The present results also emphasize the condition-dependent nature of kinetic barriers, which, with less informative experimental methods (fluorescence, etc.), are often confused with variability in intermediates and pathways.

High-resolution epitope mapping by HX MS reveals the pathogenic mechanism and a possible therapy for autoimmune TTP syndrome.

Acquired thrombotic thrombocytopenic purpura (TTP), a thrombotic disorder that is fatal in almost all cases if not treated promptly, is primarily caused by IgG-type autoantibodies that inhibit the ability of the ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) metalloprotease to cleave von Willebrand factor (VWF). Because the mechanism of autoantibody-mediated inhibition of ADAMTS13 activity is not known, the only effective therapy so far is repeated whole-body plasma exchange. We used hydrogen-deuterium exchange mass spectrometry (HX MS) to determine the ADAMTS13 binding epitope for three representative human monoclonal autoantibodies, isolated from TTP patients by phage display as tethered single-chain fragments of the variable regions (scFvs). All three scFvs bind the same conformationally discontinuous epitopic region on five small solvent-exposed loops in the spacer domain of ADAMTS13. The same epitopic region is also bound by most polyclonal IgG autoantibodies in 23 TTP patients that we tested. The ability of ADAMTS13 to proteolyze VWF is impaired by the binding of autoantibodies at the epitopic loops in the spacer domain, by the deletion of individual epitopic loops, and by some local mutations. Structural considerations and HX MS results rule out any disruptive structure change effect in the distant ADAMTS13 metalloprotease domain. Instead, it appears that the same ADAMTS13 loop segments that bind the autoantibodies are also responsible for correct binding to the VWF substrate. If so, the autoantibodies must prevent VWF proteolysis simply by physically blocking normal ADAMTS13 to VWF interaction. These results point to the mechanism for autoantibody action and an avenue for therapeutic intervention.

Stepwise protein folding at near amino acid resolution by hydrogen exchange and mass spectrometry.

The kinetic folding of ribonuclease H was studied by hydrogen exchange (HX) pulse labeling with analysis by an advanced fragment separation mass spectrometry technology. The results show that folding proceeds through distinct intermediates in a stepwise pathway that sequentially incorporates cooperative native-like structural elements to build the native protein. Each step is seen as a concerted transition of one or more segments from an HX-unprotected to an HX-protected state. Deconvolution of the data to near amino acid resolution shows that each step corresponds to the folding of a secondary structural element of the native protein, termed a "foldon." Each folded segment is retained through subsequent steps of foldon addition, revealing a stepwise buildup of the native structure via a single dominant pathway. Analysis of the pertinent literature suggests that this model is consistent with experimental results for many proteins and some current theoretical results. Two biophysical principles appear to dictate this behavior. The principle of cooperativity determines the central role of native-like foldon units. An interaction principle termed "sequential stabilization" based on native-like interfoldon interactions orders the pathway.

Slowing down of accelerated structural relaxation in ultrathin polymer films.

We demonstrate with molecular simulation that the acceleration of structural relaxation, also known as physical aging, commonly experimentally observed in thin polymer films slows down at extremely small thicknesses. This phenomenon can be attributed to an inversed free volume diffusion process caused by the sliding motion of chain molecules. Our findings provide direct evidence of the relationship between the sliding motion of short chain fragments and the structural relaxation of ultrathin polymer films, and also verify the existence of a new confinement effect at the nanoscale.

Thermodynamics of strain-induced crystallization of random copolymers.

Industrial semi-crystalline polymers contain various kinds of sequence defects, which behave like non-crystallizable comonomer units on random copolymers. We performed dynamic Monte Carlo simulations of strain-induced crystallization of random copolymers with various contents of comonomers at high temperatures. We observed that the onset strains of crystallization shift up with the increase of comonomer contents and temperatures. The behaviors can be predicted well by a combination of Flory's theories on the melting-point shifting-down of random copolymers and on the melting-point shifting-up of strain-induced crystallization. Our thermodynamic results are fundamentally important for us to understand the rubber strain-hardening, the plastic molding, the film stretching as well as the fiber spinning.

Tuning bio-inspired skin-core structure of nascent fiber via interplay of polymer phase transitions.

The properties of polymer fibers are determined by their inner structures. We performed dynamic Monte Carlo simulations of early-stage solidification in the fluid filaments of stretched polymer solutions after extrusion into a coagulation bath upon fiber spinning. We observed that the radial temperature gradient dominates polymer crystallization to form an oriented crystalline skin (from single to multiple layers), while the radial non-solvent influx dominates phase separation to form a concentrated but less oriented core. The skin-core structure offers fibers a balanced performance between strength and toughness similar to plant stems, which can be tuned by the interplay of phase transitions. Our molecular-level observations facilitate a systematic understanding of the microscopic mechanism of fiber-spinning, which will pave a way towards making excellent polymer fibers.

Which Coverages of Arc-Shaped Proteins Are Required for Membrane Tubulation?

Arc-shaped BIN/Amphiphysin/Rvs (BAR) domain proteins generate curvature by binding to membranes and induce membrane tubulation at sufficiently large protein coverages. For the amphiphysin N-BAR domain, Le Roux et al., Nat. Commun. 2021, 12, 6550, measured a threshold coverage of 0.44 ± 0.097 for nanotubules emerging from the supported lipid bilayer. In this article, we systematically investigate membrane tubulation induced by arc-shaped protein-like particles with coarse-grained modeling and simulations and determine the threshold coverages at different particle-particle interaction strengths and membrane spontaneous curvatures. In our simulations, the binding of arc-shaped particles induces a membrane shape transition from spherical vesicles to tubules at a particle threshold coverage of about 0.5, which is rather robust to variations of the direct attractive particle interactions or spontaneous membrane curvature in the coarse-grained model. Our study suggests that threshold coverages of around or slightly below 0.5 are a general requirement for membrane tubulation by arc-shaped BAR domain proteins.

Glucomannan promotes Bacteroides ovatus to improve intestinal barrier function and ameliorate insulin resistance.

Bioactive dietary fiber has been proven to confer numerous health benefits against metabolic diseases based on the modification of gut microbiota. The metabolic protective effects of glucomannan have been previously reported in animal experiments and clinical trials. However, critical microbial signaling metabolites and the host targets associated with the metabolic benefits of glucomannan remain elusive. The results of this study revealed that glucomannan supplementation alleviated high-fat diet (HFD)-induced insulin resistance in mice and that its beneficial effects were dependent on the gut microbiota. Administration of glucomannan to mice promoted the growth of Bacteroides ovatus. Moreover, colonization with B. ovatus in HFD-fed mice resulted in a decrease in insulin resistance, accompanied by improved intestinal barrier integrity and reduced systemic inflammation. Furthermore, B. ovatus-derived indoleacetic acid (IAA) was established as a key bioactive metabolite that fortifies intestinal barrier function via activation of intestinal aryl hydrocarbon receptor (AhR), leading to an amelioration in insulin resistance. Thus, we conclude that glucomannan acts through the B. ovatus-IAA-intestinal AhR axis to relieve insulin resistance.

Breviscapine alleviates myocardial ischemia-reperfusion injury in diabetes rats.

PURPOSE: To investigate the protective effect of breviscapine on myocardial ischemia-reperfusion injury (MIRI) in diabetes rats. METHODS: Forty rats were divided into control, diabetes, MIRI of diabetes, and treatment groups. The MIRI of diabetes model was established in the latter two groups. Then, the treatment group was treated with 100 mg/kg breviscapine by intraperitoneal injection for 14 consecutive days. RESULTS: After treatment, compared with MIRI of diabetes group, in treatment group the serum fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance, and glycosylated hemoglobin levels decreased, the serum total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol levels decreased, the serum high-density lipoprotein cholesterol level increased, the heart rate decreased, the mean arterial pressure, left ventricular ejection fraction, and fractional shortening increased, the serum cardiac troponin I, and creatine kinase-MB levels decreased, the myocardial tumor necrosis factor α and interleukin-6 levels decreased, the myocardial superoxide dismutase level increased, and the myocardial malondialdehyde level decreased (all P < 0.05). CONCLUSIONS: For treating MIRI of diabetes in rats, the breviscapine can reduce the blood glucose and lipid levels, improve the cardiac function, reduce the myocardial injury, and decrease the inflammatory response and oxidative stress, thus exerting the alleviating effect.

Thymines in single-stranded oligonucleotides and G-quadruplex DNA are competitive with guanines for binding to an organoruthenium anticancer complex.

Organometallic ruthenium(II) complexes [(η(6)-arene)Ru(en)Cl](+) (arene = e.g., biphenyl (1), dihydrophenanthrene, tetrahydroanthracene) show promising anticancer activity both in vitro and in vivo and are cytotoxic to cisplatin-resistant cancer cells, implying that these monofunctional complexes have a different mechanism of action from that of bifunctional cisplatin. We demonstrate here that complex 1 binds selectively to the guanine base in the 15-mer single-stranded oligodeoxynucleotides (ODNs) 5'-CTCTCTX7G8Y9CTTCTC-3' [X = Y = T; X = C, Y = A; X = A, Y = T; X = T, Y = A] to form thermodynamically stable adducts, but thymine bases (T7/T11 or T6/T11) compete kinetically with guanine for binding to 1. The T-bound monoruthenated species eventually convert to diruthenated products via a second step of binding at G or/and to G-bound monoruthenated species through dissociation of the diruthenated adducts. Complex 1 was further shown to bind preferentially to the middle T in a sequence rather than to a T near the terminus and favor coordination to a 5'-T compared to a 3'-T. Interestingly, the T bases in the human telomeric G-quadruplex sequence (5'-AGGGTTAGGGTTAGGGTTAGGG-3') were found to be more competitive both kinetically and thermodynamically with G bases for binding to 1. These results suggest that thymine bases play a unique role in the pathways of ruthenation of DNA by organoruthenium anticancer complexes and illustrate that kinetic studies can provide new insight into the mechanism of action of metallodrugs in addition to study of the structures and functions of the thermodynamically stable end products.

Molecular simulation of structural relaxation in ultrathin polymer films.

Structural relaxation and physical aging in glassy polymer films have attracted much attention in the past two decades due to their strong correlation with the lifetime of polymer-based nano-devices. Currently, the observed physical aging in polymer films was explained on the basis of a free volume diffusion model (FVDM) that has not yet been validated by simulations at the molecular level. Here we performed a Monte Carlo simulation by introducing the vacancy diffusion mechanism (similar to FVDM) to investigate the structural relaxation in ultrathin polymer films. The results show that the local average density of segments increases linearly with the logarithm of time, similar to the fluorescence intensity and dielectric strength measurements in experiments. The responses of relaxation rates in ultrathin films to temperatures are consistent with that for glassy polymer thin films in experiments. The emergence of a peak of relaxation rates with decreasing temperature can be attributed to the competition of two mechanisms (segment mobility and accurate initial vacancy concentration) from the molecular levels. Our results demonstrate that the simulations with a vacancy diffusion model could indeed provide new insights from the molecular levels to understand the structural relaxation and physical aging in ultrathin polymer films.