An Exploration of Dissolution Tests for Inhalation Aerosols.

This study aimed to establish a feasible dissolution method for inhalation aerosols. A method of collecting fine particles was investigated to capture aerosol particles less than 4 µm in diameter for dissolution tests. This dose collection method enabled the aerosol particles to be uniformly distributed on the glass fiber filter, thus considerably reducing particle agglomeration. Budesonide was used as a model drug. The aerodynamic particle size distribution (APSD) of the meter-dose inhaler (MDI) was compared by replacing actuators with different orifice sizes. Dissolution tests were conducted on fine particle doses collected using various actuators, and the dissolution profiles were modeled. The fine particle dose decreased with an increasing orifice size of the actuator. Actuators with different orifice sizes would affect the dissolution behavior of inhaled drugs. This finding was supported by similarity factor f2 analysis, suggesting the dissolution method has a discriminative capacity. The results of various model fits showed that the dissolution profiles produced by the different actuators could be fitted well using the Weibull mathematical model. The method employed in this study could offer a potential avenue for exploring the relationship between the orifice size of the actuator and the dissolution behavior of inhaled corticosteroids. This dissolution method was simple, reproducible, and suitable for determining the dissolution of inhalation aerosols.

Spindle oscillations emerge at the critical state of electrically coupled networks in the thalamic reticular nucleus.

Spindle oscillation is a waxing-and-waning neural oscillation observed in the brain, initiated at the thalamic reticular nucleus (TRN) and typically occurring at 7-15 Hz. Experiments have shown that in the adult brain, electrical synapses, rather than chemical synapses, dominate between TRN neurons, suggesting that the traditional view of spindle generation via chemical synapses may need reconsideration. Based on known experimental data, we develop a computational model of the TRN network, where heterogeneous neurons are connected by electrical synapses. The model shows that the interplay between synchronizing electrical synapses and desynchronizing heterogeneity leads to multiple synchronized clusters with slightly different oscillation frequencies whose summed-up activity produces spindle oscillation as seen in local field potentials. Our results suggest that during spindle oscillation, the network operates at the critical state, which is known for facilitating efficient information processing. This study provides insights into the underlying mechanism of spindle oscillation and its functional significance.

Pseudo-nanostructure and trapped-hole release induce high thermoelectric performance in PbTe.

Thermoelectric materials can realize direct and mutual conversion between electricity and heat. However, developing a strategy to improve high thermoelectric performance is challenging because of strongly entangled electrical and thermal transport properties. We demonstrate a case in which both pseudo-nanostructures of vacancy clusters and dynamic charge-carrier regulation of trapped-hole release have been achieved in p-type lead telluride-based materials, enabling the simultaneous regulations of phonon and charge carrier transports. We realized a peak zT value up to 2.8 at 850 kelvin and an average zT value of 1.65 at 300 to 850 kelvin. We also achieved an energy conversion efficiency of ~15.5% at a temperature difference of 554 kelvin in a segmented module. Our demonstration shows promise for mid-temperature thermoelectrics across a range of different applications.

BrainPy, a flexible, integrative, efficient, and extensible framework for general-purpose brain dynamics programming.

Elucidating the intricate neural mechanisms underlying brain functions requires integrative brain dynamics modeling. To facilitate this process, it is crucial to develop a general-purpose programming framework that allows users to freely define neural models across multiple scales, efficiently simulate, train, and analyze model dynamics, and conveniently incorporate new modeling approaches. In response to this need, we present BrainPy. BrainPy leverages the advanced just-in-time (JIT) compilation capabilities of JAX and XLA to provide a powerful infrastructure tailored for brain dynamics programming. It offers an integrated platform for building, simulating, training, and analyzing brain dynamics models. Models defined in BrainPy can be JIT compiled into binary instructions for various devices, including Central Processing Unit, Graphics Processing Unit, and Tensor Processing Unit, which ensures high-running performance comparable to native C or CUDA. Additionally, BrainPy features an extensible architecture that allows for easy expansion of new infrastructure, utilities, and machine-learning approaches. This flexibility enables researchers to incorporate cutting-edge techniques and adapt the framework to their specific needs.

Serum LL-37 and inflammatory cytokines levels in psoriasis.

BACKGROUND: Psoriasis (PsO) is a T-cell-associated inflammatory autoimmune dermatitis. Leucine leucine-37 (LL-37) is upregulated in PsO patients and correlated with the area and severity of PsO. However, the exact relation between LL-37 and T cell-associated inflammation is not well understood. It is very important to clarify the relationship between LL-37 and inflammatory response for clinical diagnosis and treatment of PsO. This study investigated the serum levels of LL-37 and inflammatory cytokines, as well as correlations between them in PsO patients, which aimed to provide new ideas for the diagnosis and treatment of PsO. METHODS: PsO patients (n = 50) and healthy volunteers (n = 33) were recruited in this study. Skin specimens were stained with hematoxylin and eosin (H&E). The serum levels of LL-37, T-helper type 1 (Th1, IFN-γ), T-helper type 17 (Th17, IL-17), T-helper type 22 (Th22, IL-22), and T-helper type 2 cytokines (Th2, IL-4) were assessed by enzyme-linked immunosorbent assay. Some of the patients were re-recruited after treatment to evaluate LL-37 and cytokines levels. RESULTS: Pathological changes were observed in PsO skin lesions. LL-37, IFN-γ, IL-17, and IL-22 serum levels were much higher in PsO patients than those in healthy volunteers (p < .001), and posttreatment reduction was observed in five patients. However, no remarkable difference in IL-4 level (p > .05) was found. LL-37 level was positively correlated with IFN-γ, IL-17, and IL-22 levels (p < .001) in PsO patients. CONCLUSION: LL-37 expression was significantly associated with inflammatory response, which may provide us new ideas for diagnosing and monitoring disease activity of PsO.

Selective hydrogenolysis of 5-hydroxymethylfurfural to 2,5-dimethylfuran over cobalt nanoparticle inlaid cobalt phyllosilicate.

Fabrication of biofuels and chemicals from renewable biomass is highly desirable to replace petrochemicals. Hydrogenolysis of biomass derived 5-hydroxymethylfurfural (HMF) is a promising way to obtain furanic fuels. In this paper, we describe the preparation of a CoSi-PS catalyst derived from cobalt phyllosilicate using a silica sol as the silica source. CoSi-PS exhibited excellent catalytic performance for the hydrogenolysis reaction of HMF to produce liquid 2,5-dimethylfuran (DMF) biofuel. 100% conversion of HMF and 97.5% selectivity for DMF were achieved at 170 °C and 1.5 MPa H2 for 4 h, which was superior to most of the reported catalysts. The excellent performance can be attributed to the strong interactions between the metal and support, highly dispersed cobalt nanoparticles and the Lewis acid sites induced by the coordinated unsaturated Co(II) sites in phyllosilicate.

Analysis of the Neuron Dynamics in Thalamic Reticular Nucleus by a Reduced Model.

Strategically located between the thalamus and the cortex, the inhibitory thalamic reticular nucleus (TRN) is a hub to regulate selective attention during wakefulness and control the thalamic and cortical oscillations during sleep. A salient feature of TRN neurons contributing to these functions is their characteristic firing patterns, ranging in a continuum from tonic spiking to bursting spiking. However, the dynamical mechanism under these firing behaviors is not well understood. In this study, by applying a reduction method to a full conductance-based neuron model, we construct a reduced three-variable model to investigate the dynamics of TRN neurons. We show that the reduced model can effectively reproduce the spiking patterns of TRN neurons as observed in vivo and in vitro experiments, and meanwhile allow us to perform bifurcation analysis of the spiking dynamics. Specifically, we demonstrate that the rebound bursting of a TRN neuron is a type of "fold/homo-clinic" bifurcation, and the tonic spiking is the fold cycle bifurcation. Further one-parameter bifurcation analysis reveals that the transition between these discharge patterns can be controlled by the external current. We expect that this reduced neuron model will help us to further study the complicated dynamics and functions of the TRN network.

Simultaneous detection of multiple bacterial and viral aquatic pathogens using a fluorogenic loop-mediated isothermal amplification-based dual-sample microfluidic chip.

Rapid and user-friendly diagnostic tests are necessary for early diagnosis and immediate detection of diseases, particularly for on-site screening of pathogenic microorganisms in aquaculture. In this study, we developed a dual-sample microfluidic chip integrated with a real-time fluorogenic loop-mediated isothermal amplification assay (dual-sample on-chip LAMP) to simultaneously detect 10 pathogenic microorganisms, that is Aeromonas hydrophila, Edwardsiella tarda, Vibrio harveyi, V. alginolyticus, V. anguillarum, V. parahaemolyticus, V. vulnificus, infectious hypodermal and haematopoietic necrosis virus, infectious spleen and kidney necrosis virus, and white spot syndrome virus. This on-chip LAMP provided a nearly automated protocol that can analyse two samples simultaneously, and the tests achieved limits of detection (LOD) ranging from 100 to 10-1  pg/µl for genomic DNA of tested bacteria and 10-4 to 10-5  pg/µl for recombinant plasmid DNA of tested viruses, with run times averaging less than 30 min. The coefficient of variation for the time-to-positive value was less than 10%, reflecting a robust reproducibility. The clinical sensitivity and specificity were 93.52% and 85.53%, respectively, compared to conventional microbiological or clinical methods. The on-chip LAMP assay provides an effective dual-sample and multiple pathogen analysis, and thus would be applicable to on-site detection and routine monitoring of multiple pathogens in aquaculture.

Excitation-Inhibition Balanced Neural Networks for Fast Signal Detection.

Excitation-inhibition (E-I) balanced neural networks are a classic model for modeling neural activities and functions in the cortex. The present study investigates the potential application of E-I balanced neural networks for fast signal detection in brain-inspired computation. We first theoretically analyze the response property of an E-I balanced network, and find that the asynchronous firing state of the network generates an optimal noise structure enabling the network to track input changes rapidly. We then extend the homogeneous connectivity of an E-I balanced neural network to include local neuronal connections, so that the network can still achieve fast response and meanwhile maintain spatial information in the face of spatially heterogeneous signal. Finally, we carry out simulations to demonstrate that our model works well.

SERP1 prevents hypoxia-reoxygenation-induced H9c2 apoptosis through activating JAK2/STAT3 pathway-dependent attenuation of endoplasmic reticulum stress.

The endoplasmic reticulum (ER) stress plays an important role in myocardial ischemia/reperfusion (MI/R) injury. SERP1, the stress-associated endoplasmic reticulum protein 1, is involved in regulating ER stress response. However, whether it associates with MI/R injury is not identified. Here, we show that SERP1 is induced in the mouse heart after MI/R injury as well as in H9c2 cells under hypoxia/reoxygenation (H/R) treatment. Additionally, SERP1 overexpression reduces H/R-induced H9c2 apoptosis. Moreover, SERP1 overexpression suppresses H/R-induced ER stress and activates JAK2/STAT3 pathway. Furthermore, JAK2/STAT3 pathway inhibition by the specific inhibitor JSI-124 minimizes the suppressive effect of SERP1 overexpression on H/R-induced ER stress and H9c2 apoptosis. Together, these results uncover the protection of SERP1 against H/R-induced H9c2 apoptosis and further relate it to JAK2/STAT3 pathway-dependent attenuation of ER stress. This study suggests SERP1 as a potential regulator invovled in the pathophysiology of MI/R injury.

A triply-responsive supramolecular vesicle fabricated by α-cyclodextrin based host-guest recognition and double dynamic covalent bonds.

The supramolecular construction of multi-stimuli assemblies is a challenging task for prospective use. In this work, a novel supramolecular amphiphile was fabricated by introducing molecules with dynamic covalent bonds into host-guest inclusion. The amphiphile formed a vesicle, which was characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), 1H NMR and UV-vis spectra. Furthermore, the vesicular structure could be regulated by pH, light and redox reagent, and thus the loaded dye in the vesicles could be released in a controlled manner.

Zitterbewegung near new Dirac points in graphene superlattices.

New Dirac points may appear when periodic potentials are applied to graphene, and there are many interesting effects near them. Here we investigate the Zitterbewegung effect of fermions described by a Gaussian wave packet in graphene superlattice near these points. The Zitterbewegung near different Dirac points has similar characteristics, while fermions near new ones have different group velocities in both x- and y-direction, which causes the different properties of the Zitterbewegung near them. We also investigate the Zitterbewegung effect influenced by multi Dirac points, and get the evolution with changing potential. Our results suggest that graphene superlattice may provide an appropriate system to study the Zitterbewegung effect near new Dirac points experimentally.

UV and pH-responsive supra-amphiphiles driven by combined interactions for controlled self-assembly behaviors.

In order to fabricate a novel supra-amphiphile with multiple stimulus properties, we developed the strategy of introducing a bi-functional linker to bridge the hydrophilic and hydrophobic building blocks together, by utilizing more than one kind of interaction. We characterized the assembled structure and morphology of the supra-amphiphile using transmission electron microscopy (TEM), dynamic light scattering (DLS) and X-ray diffraction (XRD). 1H NMR and UV-vis spectroscopy studies revealed that the amphiphile was constructed by the effect of host-guest recognition and a dynamic covalent bond, which could be switched ''on'' and ''off'' via UV irradiation and pH variation stimuli, respectively. This responsiveness realized finely controllable self-assembly behaviors of the supra-amphiphile, which was thus able to encapsulate and release the drug model rhodamine B.

Facile Stimuli-Responsive Transformation of Vesicle to Nanofiber to Supramolecular Gel via ω-Amino Acid-Based Dynamic Covalent Chemistry.

This paper reports an interesting type of self-assembly systems based on dynamic covalent bonds. The systems are pH-responsible and reversible, which could be utilized for controlling the morphology transformation of the assemblies. In alkaline conditions, the amine group of 11-aminoundecanoic acid (AUA) can connect with the aldehyde group of benzaldehyde (BA) or 1-naphthaledhyde (NA) by dynamic covalent bond to form a small organic building block accompanied by the morphological transformation from vesicles to fibers. When pH is lowered to a neutral value, the dynamic covalent bonds (imine bonds) can be hydrolyzed, leading to the dissociation of fibers and appearance of spherical aggregates. The transformation was confirmed reversible as fibers appeared again when the pH was changed back to alkaline value. In addition, a reversibly controlled gel was designed based on the nanofiber formation. NaCl, which is capable of greatly enhance the nanofiber density and cross-linking, was used to induce the growth of free-standing gel from free-flowing nanofiber system, and the resultant gel was proven to be pH-reversible.

Visualizing global properties of a molecular dynamics trajectory.

Molecular dynamics (MD) trajectories are very large data sets that contain substantial information about the dynamic behavior of a protein. Condensing these data into a form that can provide intuitively useful understanding of the molecular behavior during the trajectory is a substantial challenge that has received relatively little attention. Here, we introduce the sigma-r plot, a plot of the standard deviation of intermolecular distances as a function of that distance. This representation of global dynamics contains within a single, one-dimensional plot, the average range of motion between pairs of atoms within a macromolecule. Comparison of sigma-r plots calculated from 10 ns trajectories of proteins representing the four major SCOP fold classes indicates diversity of dynamic behaviors which are recognizably different among the four classes. Differences in domain structure and molecular weight also produce recognizable features in sigma-r plots, reflective of differences in global dynamics. Plots generated from trajectories with progressively increasing simulation time reflect the increased sampling of the structural ensemble as a function of time. Single amino acid replacements can give rise to changes in global dynamics detectable through comparison of sigma-r plots. Dynamic behavior of substructures can be monitored by careful choice of interatomic vectors included in the calculation. These examples provide demonstrations of the utility of the sigma-r plot to provide a simple measure of the global dynamics of a macromolecule.

An easy approach for constructing vesicles by using aromatic molecules with ß-cyclodextrin.

Vesicles were formed in aqueous solution using ß-cyclodextrin (ß-CD) complexes with a series of ultra-small aromatic molecules. The vesicles are easy to prepare without a complicated synthesis procedure and their structure was identified and characterized using various techniques, including transmission electron microscopy, atomic force microscopy and dynamic laser light scattering. Using the ß-CD/l-phenylalanine system as a representative example, the structural factors that caused the self-assembly were revealed using proton nuclear magnetic resonance, Fourier transform infrared spectroscopy and X-ray diffraction. In addition, the vesicular architecture could be endowed with a diverse range of stimuli-responses, as a consequence of the selective addition of various guest molecules. It is anticipated that this novel assembly strategy could be further extended, and that it presents new opportunities for the development of nanocarriers and soft materials.

A supramolecular vesicle of camptothecin for its water dispersion and controllable releasing.

Camptothecin, as an antitumor drug, has shown significant antitumor activity against various cancers through the inhibition of topoisomerase I. However, its poor solubility severely limits the clinical applications. Here, we report a camptothecin supramolecular vesicle based on the host-guest interactions, which can uniformly disperse camptothecin into water and greatly enhance camptothecin aqueous solubility. The camptothecin vesicles were identified by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and dynamic light scattering (DLS). X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), UV-vis spectrum, 1H NMR and 2D NMR ROESY were further employed to study the formation mechanism of the vesicles. Furthermore, camptothecin could be controllably released when the competitive guests were added into the vesicles system. Finally, the camptothecin vesicles in aqueous solution exhibited comparable antitumor activity in vitro as natural camptothecin in DMSO to HeLa cells under the same conditions.

Modulation of HIV protease flexibility by the T80N mutation.

The flexibility of HIV protease (HIVp) plays a critical role in enabling enzymatic activity and is required for substrate access to the active site. While the importance of flexibility in the flaps that cover the active site is well known, flexibility in other parts of the enzyme is also critical for function. One key region is a loop containing Thr 80, which forms the walls of the active site. Although not situated within the active site, amino acid Thr80 is absolutely conserved. The mutation T80N preserves the structure of the enzyme but catalytic activity is completely lost. To investigate the potential influence of the T80N mutation on HIVp flexibility, wide-angle X-ray scattering (WAXS) data was measured for a series of HIVp variants. Starting with a calculated WAXS pattern from a rigid atomic model, the modulations in the intensity distribution caused by structural fluctuations in the protein were predicted by simple analytic methods and compared with the experimental data. An analysis of T80N WAXS data shows that this variant is significantly more rigid than the WT across all length scales. The effects of this single point mutation extend throughout the protein, to alter the mobility of amino acids in the enzymatic core. These results support the contentions that significant protein flexibility extends throughout HIVp and is critical to catalytic function.

Melamine as an effective supramolecular modifier and stabilizer in a nanotube-constituted supergel.

Self-assembly of N-fluorenyl-9-methoxycarbonyl glutamic acid (Fmoc-Glu) in water generates metastable single-wall nanotubes. These nanotubes entangle and bundle together to form unstable gels that shrink with time and finally result in lamellar crystalline precipitates. Melamine (Mm) was employed as a supramolecular modifier and stabilizer to improve the stability of the nanotubes. Mm interacts with the carboxyl-rich surfaces of the nanotubes via H-bonds and static electronic forces to diminish the high affinity of individual nanotubes and facilitate Fmoc-Glu supergelation (critical gelation concentration <0.1 wt %). Although the basic process of nanotube formation is not disturbed, Mm inverts the supramolecular helicity of nanotubes from P to M.

Hybrid gels assembled from Fmoc-amino acid and graphene oxide with controllable properties.

A supramolecular gel is obtained from the self-assembly of an ultralow-molecular-weight gelator (N-fluorenyl-9-methoxycarbonyl glutamic acid) in good and poor solvents. The gelators can self-assemble into a lamellar structure, which can further form twisted fibers and nanotubes in the gel phase. Rheological studies show that the gels are robust and rigid, and are able to rapidly self-recover to a gel after being destroyed by shear force. Fluorescence experiments reveal the aggregation-induced emission effects of the gel system; the fluorescence intensity is significantly enhanced by gel formation. Graphene oxide (GO) is introduced into the system efficiently to give a hybrid material, and the interaction between gelators-GO sheets is studied. Rheological and fluorescent studies imply that the mechanical properties and the fluorescent emission of the hybrid materials can be fine-tuned by controlling the addition of GO.