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Ecological design concept is a design concept aimed at advocating green environmental protection and sustainable development, which is widely used in different cases of environmental design including urban and kindergarten. In our study, using literature research, case reference, and field research as research methods, through the theoretical research of domestic and foreign kindergarten environment design and interpretation of typical cases to summarize the ecological design method and design strategy, can be further applied in larger field such as urban, basin, and/or region. Then, take “Chenguang” kindergarten in Beijing as example to analyze ecological element in there. Aiming at ecological landscape, ecological humanities, and ecological experience as the goal, the kindergarten’s architectural appearance and indoor and outdoor environment have been transformed and redesigned. Ecological principle and ecological strategy from our study present an important reference meaning in improving the quality of urban space environment and shaping a good city image which are of great significance.

Control over supramolecular recognition between proteins and nanoparticles (NPs) is of fundamental importance in therapeutic applications and sensor development. Most NP-protein binding approaches use 'tags' such as biotin or His-tags to provide high affinity; protein surface recognition provides a versatile alternative strategy. Generating high affinity NP-protein interactions is challenging however, due to dielectric screening at physiological ionic strengths. We report here the co-engineering of nanoparticles and protein to provide high affinity binding. In this strategy, 'supercharged' proteins provide enhanced interfacial electrostatic interactions with complementarily charged nanoparticles, generating high affinity complexes. Significantly, the co-engineered protein-nanoparticle assemblies feature high binding affinity even at physiologically relevant ionic strength conditions. Computational studies identify both hydrophobic and electrostatic interactions as drivers for these high affinity NP-protein complexes.

Autophagy is a catabolic cellular process in which unwanted proteins and organelles are degraded by lysosomes. It is characterized by the formation of the double-membrane autophagosome decorated with LC3B, a protein that mediates autophagosomal fusion with lysosomes. The cysteine protease ATG4b acts at two stages in the life cycle of LC3B. We set out to characterize the protein-protein interaction between LC3B and ATG4b. Through biochemical and biophysical studies, we show that the ubiquitin-like core of LC3B (residues 1-115; "LC3B-115"), which lacks the C-terminal cleavage site (between residue 120 and 121), binds to full-length ATG4b with a surprisingly tight dissociation constant (KD) in the low nanomolar range; 10-30-fold tighter than that of the substrate pro-LC3B (residues 1-125) or the product LC3B-I (residues 1-120). Consequently, LC3B-115 is a potent inhibitor of the ATG4b-mediated cleavage of pro-LC3B (IC50 = 15 nM). Binding of the LC3B-115 has no effect on the conformation of the active site of ATG4b, as judged by the turnover of a peptide substrate ("substrate-33"), derived from LC3B-I residues 116-120. Conversely, truncations of ATG4b show that binding and proteolysis of LC3B critically depend on the C-terminal tail of ATG4b, whereas proteolysis of the peptide substrate-33 does not require the C-terminal tail of ATG4b. These results support a bipartite model for LC3B-ATG4b binding in which the core of LC3B binds to ATG4b and the C-terminal tail of pro-LC3B organizes the ATG4b active site; additionally, the C-terminal tail of ATG4b contributes at least 1000-fold higher binding affinity to the LC3B-ATG4b interaction and likely wraps around the LC3B-ubiquitin core. PPIs are often described as containing an energetic "hot spot" for binding; in the case of LC3B-ATG4b, however, the substrate-enzyme complex contains multiple, energetically relevant domains that differentially affect binding affinity and catalytic efficiency.

We develop a fully discrete finite volume element scheme of the two-dimensional space-fractional convection–diffusion equation using the finite volume element method to discretize the space-fractional derivative and Crank–Nicholson scheme for time discretization. We also analyze and prove the stability and convergence of the given scheme. Finally, we validate our theoretical analysis by data from three examples.

Protein-protein interactions (PPIs) form complex networks to drive cellular signaling and cellular functions. Precise modulation of a target PPI helps explain the role of the PPI in cellular events and possesses therapeutic potential. For example, valosin-containing protein (VCP/p97) is a hub protein that interacts with more than 30 adaptor proteins involved in various cellular functions. However, the role of each p97 PPI during the relevant cellular event is underexplored. The development of small-molecule PPI modulators remains challenging due to a lack of grooves and pockets in the relatively large PPI interface and the fact that a common binding groove in p97 binds to multiple adaptors. Here, we report an antibody fragment-based modulator for the PPI between p97 and its adaptor protein NSFL1C (p47). We engineered these antibody modulators by phage display against the p97-interacting domain of p47 and minimizing binding to other p97 adaptors. The selected antibody fragment modulators specifically disrupt the intracellular p97/p47 interaction. The potential of this antibody platform to develop PPI inhibitors in therapeutic applications was demonstrated through the inhibition of Golgi reassembly, which requires the p97/p47 interaction. This study presents a unique approach to modulate specific intracellular PPIs using engineered antibody fragments, demonstrating a method to dissect the function of a PPI within a convoluted PPI network.

In this paper, for the initial and boundary value problem of beams with structural damping, by introducing intermediate variables, the original fourth-order problem is transformed into second-order partial differential equations, and the mixed finite volume element scheme is constructed, and the existence, uniqueness and convergence of the scheme are analyzed. Numerical examples are provided to confirm the theoretical results. In the end, we test the value of δ to observe its influence on the model.

Homeobox transcript antisense RNA (HOTAIR) is a long non-coding RNA associated with a number of fibrosis-related diseases. The aim of this study was to investigate the specific role of HOTAIR in the development of endometrial fibrosis and to identify the molecular mechanisms underlying this process. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression levels of HOTAIR in samples of intrauterine adhesion (IUA) tissue and in endometrial stromal cells (ESCs) that had been treated with transforming growth factor beta 1 (TGF-β1). Additionally, we transfected ESCs with either overexpression plasmid (pcDNA-HOTAIR) or silencing construct (si-HOTAIR) and then treated these cells with TGF-β1. We then performed RT-qPCR and western blot analysis, along with cell proliferation and apoptosis assays, to investigate the effects of HOTAIR on the transdifferentiation of ESCs into myofibroblasts. The results showed that the expression levels of HOTAIR were significantly elevated in IUA tissue and in ESCs that had been treated with TGF-β1. The overexpression of HOTAIR had a pro-fibrotic effect on ESCs, while the silencing of HOTAIR exerted an anti-fibrotic effect. Most importantly, the protein expression levels of p-Smad2 and p-Smad3 were significantly upregulated in TGF-β1-treated ESCs transfected with pcDNA-HOTAIR and were downregulated after transfection with si-HOTAIR constructs. These data indicate that HOTAIR promotes endometrial fibrosis by activating the TGF-β1/Smad signaling pathway, suggesting that the inhibition of HOTAIR may represent a promising therapeutic option for suppressing endometrial fibrosis.

The numerical solution of coupled nonlinear Klein-Gordon equations on unbounded domains is considered by applying the artificial boundary method. Based on the unified approach to overcome the coupled nonlinearity, local artificial boundary conditions are designed on the introduced artificial boundaries. The original problem is reduced to an initial boundary value problem on a bounded domain, which can be efficiently solved by the finite difference method. Some numerical examples are provided to verify the accuracy and effectiveness of the proposed method.

The compact finite difference scheme is designed to numerically solve the nonlinear Schrodinger equation and coupled nonlinear Schrodinger equations on an unbounded domain in this paper. The original problem on an unbounded domain is reduced to an initial boundary value problem defined on a bounded computational domain by applying the artificial boundary method. Then, the reduced problem on the bounded computational domain is solved by an efficient semi-implicit compact finite difference scheme, which is a fourth-order scheme with respect to spatial variable. The scheme efficiently avoids the time-consuming iteration procedure necessary for the nonlinear scheme and thus is relatively time-saving. Finally, the stability of the proposed scheme is rigorously analyzed. Numerical examples are given to illustrate the accuracy and effectiveness of the proposed method.

Mitochondria are therapeutic targets in many diseases including cancer, metabolic disorders, and neurodegenerative diseases. Therefore, strategies to deliver therapeutics of interest to mitochondria are important for therapeutic development. As delocalized lipophilic cations (DLCs) preferentially accumulate into mitochondria, DLC-conjugation has been utilized facilitate therapeutic delivery systems with mitochondrial targeting capability. Here we report that upon DLC-conjugation, anionic polymers exhibited significantly improved mitochondrial targeting when compared to cationic polymers and charge-neutral polymers. Considering that cell membrane generally bears net negative charge, the observed phenomenon is unexpected. Notably, the DLC-conjugated anionic polymers circumvented the endosomal entrapment. The rapid mitochondrial accumulation of DLC-conjugated anionic polymers is likely a membrane-potential driven process, along with the involvement of the mitochondrial pyruvate carrier. Moreover, the structural variations on the side chain of DLC-conjugated anionic polymers did not compromise the overall mitochondrial targeting capability, widely extending the applicability of anionic macromolecules in therapeutic delivery systems.

Self-assembly of amphiphilic polymers in aqueous solution builds up versatile carrier platforms for therapeutic delivery. Amphiphilic polymers specifically provide “hydrophobic pockets” for the enc...

The integration of the fifth generation (5G) networks and artificial intelligence (AI) benefits to create a more holistic and better connected ecosystem for industries. User profiling has become an important issue for industries to improve company profit. In the 5G era, smartphone applications have become an indispensable part in our everyday lives. Users determine what apps to install based on their personal needs, interests, and tastes, which is likely shaped by their genders—the behavioral, cultural, or psychological traits typically associated with their sex. It is possible to profile users’ gender based simply on a single snapshot of apps installed on their smartphones. With this inference based on easy to access data, we can make smartphone systems more user-friendly, and provide better personalized products and services. In this article, we explore such possibilities through an empirical study on a large-scale dataset of installed app lists from 15 000 Android users. More specifically, we investigate the following research questions: 1) What differences between females and males can be explored from installed app lists? 2) Can user gender be reliably inferred from a snapshot of apps installed? Which snapshot feature(s) are the most predictive? What is the best combination of features for building the gender prediction model? 3) What are the limitations of a gender prediction model based solely on a snapshot of apps installed on a smartphone? We find significant gender differences in app type, function, and icon design. We then extract the corresponding features from a snapshot of apps installed to infer the gender of each user. We assess the gender predictive ability of individual features and combinations of different features. We achieve an accuracy of 76.62% and area under the curve of 84.23% with the best set of features, outperforming the existing work by around 5% and 10%, respectively. Finally, we perform an error analysis on misclassified users and discussed the implications and limitations of this article.

With the intervention of digital art in recent years, the quality and vitality of urban public space have been greatly enhanced. However, with the wide application of digital art and the gradual maturity of communication technology, especially in the upcoming 6G era, the application scenario of digital art will be an extension of the “line” to “surface” and then to “body.” Digital art design is no longer a single surface or a single dimension, but a comprehensive design in terms of the breadth and depth of information; the network and the user are seen as a unified body, and the user’s needs will be deeply explored and realized. With the most cutting-edge means of communication, artificial intelligence, and big data, these technologies and art merge to create a new way to appreciate art. To this end, digital art will also be in this artificial intelligence and human intelligence in a harmonious symbiosis of the environment in the depth of the user’s needs and the formation of a new dimension of interaction. Based on the “five-in-one” theory, the study introduces media literacy, technology acceptance model, and user experience theory as influencing factors and explores the influence of emotional experience, interaction experience, sensory experience, perceived usefulness, perceived ease of use, and media literacy on users’ willingness to continuously participate through qualitative comparative analysis. The results of the study show that there are three paths that influence users’ willingness to continuously engage, namely, affective experience ∗ interactive experience ∗ sensory experience ∗ perceived usefulness ∗ perceived ease of use; affective experience ∗ interactive experience ∗ perceived usefulness ∗ perceived ease of use ∗ perceived entertainment ∗ medium literacy, and ~ affective experience ∗ interactive experience ∗ sensory experience ∗ ~perceived ease of use ∗ perceived usefulness ∗ medium literacy. The paths suggest that users’ willingness to sustain participation is influenced by a variety of factors, among which interactive experience and perceived usefulness are essential factors affecting the users’ willingness to participate. User participation is an important manifestation of the vitality of urban public space, and the analysis of the factors influencing users’ willingness to sustain participation provides theoretical guidance for the design and application of digital art in the upcoming Internet of everything space.

This paper discusses the origin and evolution of saline springs in north and central Laos, based on chemical and stable isotopes (δD, δ18O, δ11B, and δ37Cl). All the saline springs in this study are of the Na–Cl geochemical type. The geochemical and water isotope values suggest that the saline springs in this study are mainly derived from meteoric water and/or ice and snow melt from the surrounding mountains and that they also experienced strong evaporation and intense rock–water interactions. The ionic ratios, characteristic coefficients, ternary Ca–SO4–HCO3 phase diagrams, and saturation indices of minerals show that the dissolution of halite, sulfate, and carbonate rocks may be the solute sources for saline springs in this study, whereas the underground brines in the Thakhek potash mining area are geochemically influenced by the dissolution of carnallite and sylvite. The global geothermal δ11B–Cl/B relationship and δ11B values (5.50 to 36.01‰) of saline springs suggest a continental origin of B. This B is most likely derived from marine carbonate rocks and marine evaporates (gypsum and halite) of the late Cretaceous, which is similar to the saline springs of the Nangqen–Qamdo–Simao Salt Basin. The δ37Cl value (−0.12 to +0.79) and the Cl/Br ratio (4076 to 9853) show that dissolution of late cretaceous marine halite layers, atmospheric precipitation, and water–rock interactions between volcanic rocks, mudstones, and sandstone can restrict the δ37Cl values in saline springs. Results from silica geothermometry and multi–mineral equilibrium diagrams indicate that the reservoir temperatures for the saline springs range from 87–137 °C and experience deep circulation. Hydrochemical characteristic coefficients suggest that saline springs in the Muang Say basin may have leached sylvinite and carnallite and that the potash exploration prospect in this area is relatively good.

We present a postfunctionalization strategy to formulate noncationic RNA–polymer complexes for RNA delivery. Utilizing the methylated pyridinium moieties on the polymer, RNA–polymer polyelectrolytes were first formed via electrostatic interaction. Next, the polyelectrolytes were partially cross-linked with dithiothreitol, “locking” the RNA inside the complex and leaving the rest of the N-methylated pyridyl disulfide groups to subsequently react with thiols. We carried out the postfunctionalization using thiolated oligoethylene glycol and removed a majority of the cationic moieties among the RNA–polymer complexes. The strategy facilitates the noncationic RNA–polymer complexes with tunable RNA release rates in the presence of intracellularly abundant glutathione. With significantly reduced cytotoxicity, the resultant complexes protect RNA against the enzymatic degradation by ribonuclease A and fetal bovine serum. Moreover, the RNA–polymer complexes demonstrated successful siRNA delivery and gene specific kn...

While cells offer numerous inspiring examples in which membrane morphology and function are controlled by interactions with viruses or proteins, we still lack design principles for controlling membrane morphology in synthetic systems. With experiments and simulations, we show that spherical nanoparticles binding to lipid-bilayer membrane vesicles results in a remarkably rich set of collective morphologies that are controllable via the particle binding energy. We separately study cationic and anionic particles, where the adhesion is tuned by addition of oppositely charged lipids to the vesicles. When the binding energy is weak relative to a characteristic membrane-bending energy, vesicles adhere to one another and form a soft solid gel, a novel and useful platform for controlled release. With larger binding energy, a transition from partial to complete wrapping of the nanoparticles causes a remarkable vesicle destruction process culminating in rupture, nanoparticle-membrane tubules, and an apparent inversion of the vesicles. These findings help unify the diverse phenomena observed previously. They also open the door to a new class of vesicle-based, closed-cell gels that are more than 99% water and can encapsulate and release on demand, and show how to drive intentional membrane remodeling for shape-responsive systems.

Due to the adverse effects of free drugs on the fetus, placental-mediated pregnancy complications still lack effective pharmacotherapy. This study aims to construct a non-spherical drug delivery system based on folate-conjugated pullulan acetate (FPA) for placental targeting and translocation. By adjusting the initial solvent system, FPA nanoparticles with different morphologies were prepared using dialysis method without a surfactant. Cytotoxicity and lactate dehydrogenase release assays indicated the good biocompatibility of FPA nanoparticles in BeWo b30 cells. Cellular uptake and in vitro placental barrier transportation studies showed that FPA nanoparticles entered the cells and transported across the cell monolayer, benefiting from the active target effect mediated by the folate receptor. Moreover, non-spherical FPA nanoparticles showed nuclear translocation due to their shape effect. These findings provide a novel aspect in placental-mediated pregnancy treatment and applications in the obstetrics field of drug use during pregnancy.

RNA interference (RNAi) requires the intracellular delivery of RNA molecules to initiate the neutralization of targeted mRNA molecules, inhibiting the expression or translation of the targeted gene. Current polymers and lipids that are used to deliver RNA molecules are generally required to be positively charged, to achieve complexation with RNA and the cellular internalization. However, positive surface charge has been implicated as the reason for toxicity in many of these systems. Herein, we report a novel strategy to generate noncationic RNA-polymer complexes for RNA delivery with low cytotoxicity. We use an in situ electrostatic complexation using a methylated pyridinium group, which is simultaneously removed during the RNA binding step. The resultant complexes demonstrate successful knockdown in preimplantation mammalian embryos, thus providing a new approach for nucleic acid delivery.