Tuning Phase Transition of Molecular Self-Assembly by Artificial Chaperones through Aromatic-Aromatic Interactions.

The molecular chaperones are essential and play significant roles in controlling the protein phase transition and maintaining physiological homeostasis. However, manipulating phase transformation in biomimetic peptide self-assembly is still challenging. This work shows that an artificial chaperone modulates the energy landscape of supramolecular polymerization, thus controlling the phase transition of amyloid-like assemblies from crystals to hydrogels to solution. The absence of a chaperone allows the NapP to form crystals, while the presence of the chaperone biases the pathway to form nanofibrous hydrogels to soluble oligomers by adjusting the chaperone ratios. Mechanistic studies reveal that the aromatic-aromatic interaction is the key to trapping the molecules in a higher energy fold. Adding the chaperone relieves this restriction, lowers the energy barrier, and transforms the crystal into a hydrogel. This phase transformation can also be achieved in the macromolecular crowding environment, thus providing new insights into understanding molecular self-assembly in multiple component systems.

Confinement of Assemblies of Peptides by Chemical Reactions in Living Cells.

The self-assembly of peptides plays an important role in optics, catalysis, medicine, and disease treatment. In recent years, peptide-based materials have exhibited great potential for cancer therapy and disease imaging due to their excellent biocompatibility, structural tenability, and ease of functionality. Peptides could self-assemble into diverse nanostructures in vivo triggered by endogenous stimuli, which initiated chemical reactions and self-assembled to achieve desired biological functions in the tumor microenvironment. This concept introduces the utilization of endogenous triggers to construct functional nanostructures in vivo and their corresponding biological applications. After briefly discussing the representative example of chemical reactions induced self-assembly of peptides in the living system, we describe the several stimuli triggered self-assembly for constructing therapeutic assemblies and serving as an imaging probe. Finally, we give a brief outlook to discuss the future direction of this exciting new field.

Controlling Intracellular Enzymatic Self-Assembly of Peptide by Host-Guest Complexation for Programming Cancer Cell Death.

Controlling the enzymatic reaction of macromolecules in living systems plays an essential role in determining the biological functions, which remains challenging in the synthetic system. This work shows that host-guest complexation could be an efficient strategy to tune the enzymatic self-assembly of the peptide. The formed host-guest complexation prevents the enzymatic kinetics of peptide assemblies on the cell surface and promotes cellular uptake of assemblies. For uptake inside cells, the host-guest complex undergoes dissociation in the acidic lysosome, and the released peptide further self-assembles inside the mitochondria. Accumulating assemblies at mitochondria induce the ferroptosis of cancer cells, resulting in cancer cell death in vitro and the tumor-bearing mice model. As the first example of using host-guest complexation to modulate the kinetics of enzymatic self-assembly, this work provides a general method to control enzymatic self-assembly in living cells for selective programming cancer cell death.

Controlling supramolecular filament chirality of hydrogel by co-assembly of enantiomeric aromatic peptides.

Supramolecular chirality plays an indispensable role in living and synthetic systems. However, the generation and control of filament chirality in the supramolecular hydrogel of short peptides remains challenging. In this work, as the first example, we report that the heterodimerization of the enantiomeric mixture controls the alignment, chirality, and stiffness of fibrous hydrogels formed by aromatic building blocks. The properties of the resulting racemic hydrogel could not be achieved by either pure enantiomer. Cryo-EM images indicate that the mixture of L and D enantiomers forms chiral nanofibers, the percentage of which can be readily controlled through stoichiometric co-assembly of heterochiral enantiomers. 2D NOESY NMR and diffusion-ordered NMR spectroscopy reveal that heterodimerization of enantiomers plays a crucial role in the formation of chiral nanofibers. Further mechanistic studies unravel the mechanism of supramolecular chirality formation in this two-component system. Molecular dynamics simulations confirm that the intermolecular hydrogen bond and π-π interaction of heterodimers play important roles in forming a chiral hydrogel. Furthermore, regulation of the adhesion and morphology of mammalian cells is achieved by tuning the relative ratio of L and D enantiomers at the same concentration. This work illustrates a novel strategy to control the supramolecular chirality of aromatic peptide hydrogels for materials science.

Spatiotemporal Control over Chemical Assembly in Living Cells by Integration of Acid-Catalyzed Hydrolysis and Enzymatic Reactions.

Spatiotemporal control of chemical assembly in living cells remains challenging. We have now developed an efficient and general platform to precisely control the formation of assemblies in living cells. We introduced an O-[bis(dimethylamino)phosphono]tyrosine protection strategy in the self-assembly motif as the Trojan horse, whereby the programmed precursors resist hydrolysis by phosphatases on and inside cells because the unmasking of the enzymatic cleavage site occurs selectively in the acidic environment of lysosomes. After demonstrating the multistage self-assembly processes in vitro by liquid chromatography/mass spectrometry (LC-MS), cryogenic electron microscopy (Cryo-EM), and circular dichroism (CD), we investigated the formation of site-specific self-assembly in living cells using confocal laser scanning microscopy (CLSM), LC-MS, and biological electron microscopy (Bio-EM). Controlling chemical assembly in living systems spatiotemporally may have applications in supramolecular chemistry, materials science, synthetic biology, and chemical biology.

[Secondary male hypogonadism induced by sellar space-occupying lesion: Clinical analysis of 22 cases].

OBJECTIVE: To analyze the clinical characteristics of secondary male hypogonadism induced by sellar space-occupying lesion, explore its pathogenesis, and improve its diagnosis and treatment. METHODS: We retrospectively analyzed the clinical data about 22 cases of secondary male hypogonadism induced by sellar space-occupying lesion, reviewed related literature, and investigated the clinical manifestation, etiological factors, and treatment methods of the disease. Hypogonadism developed in 10 of the patients before surgery and radiotherapy (group A) and in the other 12 after it (group B). The patients received endocrine therapy with Andriol (n=7) or hCG (n=15). RESULTS: The average diameter of the sellar space-occupying lesions was significantly longer in group A than in B (ï¼»2.35±0.71ï¼½ vs ï¼»1.83±0.36ï¼½ cm, P<0.05) and the incidence rate of prolactinomas was markedly higher in the former than in the latter group (60% vs 0, P<0.01). The levels of lutein hormone (LH), follicle stimulating hormone (FSH) and testosterone (T) were remarkably decreased in group B after surgery and radiotherapy (P<0.01). Compared with the parameters obtained before endocrine therapy, all the patients showed significant increases after intervention with Andriol or hCG in the T level (ï¼»0.78±0.40ï¼½ vs ï¼»2.71±0.70ï¼½ ng/ml with Andriol; ï¼»0.93±0.44ï¼½ vs ï¼»3.07±0.67ï¼½ ng/ml with hCG) and IIEF-5 score (5.00±2.61 vs 14.50±3.62 with Andriol; 5.36±1.82 vs 15.07±3.27 with hCG) (all P<0.01). The testis volume increased and pubic hair began to grow in those with hypoevolutism. The patients treated with hCG showed a significantly increased testis volume (P<0.01) and sperm was detected in 7 of them, whose baseline testis volume was markedly larger than those that failed to produce sperm (ï¼»11.5±2.3ï¼½ vs ï¼»7.5±2.3ï¼½ ml, P<0.01). Those treated with Andriol exhibited no significant difference in the testis volume before and after intervention and produced no sperm, either. CONCLUSIONS: Hypothyroidism might be attributed to surgery- or radiotherapy-induced damage to the pituitary tissue, space-occupying effect of sellar lesion, and hyperprolactinemia. Both Andriol and hCG can improve the T level and erectile function, but the former does not help spermatogenesis.

An eye- tracking technology and MLP-based color matching design method.

Images are a significant source of inspiration for designers to carry out the color design. However, the absence of animated images in the product color design can create confusion for designers. To translate the colours of the animated images into product colours, this work used eye-tracking technology to aid colour extraction and the multilayer perceptron neural network (MLP) algorithm to train a product colour decision model to filter the best product colour schemes. Firstly, eye tracking technology is used to collect the distribution of hotspots of the subject while viewing the animated images. Based on the distribution of eye-tracking hotspots, the most interesting animated colours were extracted. Then, the MLP is applied to train a colour decision model for children's shopping cart products, and the colour decision model is used to filter the optimal solution for the product colour, and finally the colour design is completed from the animated colour to the three-colour children's shopping cart product. Experimental results show that the color extraction based on the eye-tracking technology and the color scheme screening based on the intelligent algorithm can realize the effective conversion from animated image colors to product colors. This work proposes a color scheme design method from animations to products, which further expands the image color sources in product color design and can accurately find the color scheme that matches the animated image and the product.

Cu+-Mediated CO Coordination for Promoting C-C Coupling for CO2 and CO Electroreduction.

Selective electrochemical upgrading of CO2 to multicarbon (C2+) products requires a C-C coupling process, yet the underlying promoting mechanism of widely involved Cu oxidation states remains largely unclear, hindering the subtle design of efficient catalysts. Herein, we unveil the critical role of Cu+ in promoting C-C coupling via coordination with a CO intermediate during electrochemical CO2 reduction. We find that, relative to other halogen anions, iodide (I-) in HCO3- electrolytes accelerates the generation of strongly oxidative hydroxyl radicals that accounts for the formation of Cu+, which can be dynamically stabilized by I- via the formation of CuI. The in situ generated CO intermediate strongly binds to CuI sites, forming nonclassical Cu(CO)n+ complexes, leading to an approximately 3.0-fold increase of C2+ Faradaic efficiency at -0.9 VRHE relative to that of I--free Cu surfaces. Accordingly, a deliberate introduction of CuI into I--containing HCO3- electrolytes for direct CO electroreduction brings about a 4.3-fold higher C2+ selectivity. This work provides insights into the role of Cu+ in C-C coupling and the enhanced C2+ selectivity for CO2 and CO electrochemical reduction.

Triggered Self-Sorting of Peptides to Form Higher-Order Assemblies in a Living System.

Biological components (protein, DNA, lipid rafts, etc.) self-sort to form higher-order structures with elegant modulation by endogenous stimuli for maintaining cellular functions in living cells. However, the challenge of producing self-sorted higher-order assemblies of peptides in living systems (cells and tissues) spatiotemporally has yet to be achieved. This work reports the using of a biocompatible strategy to construct self-sorted assemblies of peptides in living cells and tumor-bearing mice. The results show that the designed peptides self-sort to form distinct nanostructures in living cancer cells using an endogenous trigger, as evidenced by confocal laser scanning microscopy and Bio-EM. Wound-healing experiments indicate that the in situ generation of self-sorted nanostructures exhibits a synergistic effect that significantly decreases the migration of cancer cells. In vivo experiments demonstrate that the designed peptides could self-sort in tumor-bearing mice and improve the tumor penetrating ability of the impenetrable component in tumor tissue. We can further program the formation of self-sorted materials through orthogonal triggers by introducing an exogenous trigger (light) and an endogenous trigger independently. Thus, this work provides a strategy to control multiple self-assembling processes in the context of the living system and provides a general strategy to construct self-sorted structures for the emergent properties of materials science.

Hydroxyl radicals dominate reoxidation of oxide-derived Cu in electrochemical CO2 reduction.

Cuδ+ sites on the surface of oxide-derived copper (OD-Cu) are of vital importance in electrochemical CO2 reduction reaction (CO2RR). However, the underlying reason for the dynamically existing Cuδ+ species, although thermodynamically unstable under reductive CO2RR conditions, remains uncovered. Here, by using electron paramagnetic resonance, we identify the highly oxidative hydroxyl radicals (OH•) formed at room temperature in HCO3- solutions. In combination with in situ Raman spectroscopy, secondary ion mass spectrometry, and isotope-labelling, we demonstrate a dynamic reduction/reoxidation behavior at the surface of OD-Cu and reveal that the fast oxygen exchange between HCO3- and H2O provides oxygen sources for the formation of OH• radicals. In addition, their continuous generations can cause spontaneous oxidation of Cu electrodes and produce surface CuOx species. Significantly, this work suggests that there is a "seesaw-effect" between the cathodic reduction and the OH•-induced reoxidation, determining the chemical state and content of Cuδ+ species in CO2RR. This insight is supposed to thrust an understanding of the crucial role of electrolytes in CO2RR.

In Situ Construction of Functional Assemblies in Living Cells for Cancer Therapy.

Peptide-based materials hold great promise for various biomedical applications and have drawn increasing attention over the past five years. Despite the progress in fabrication and handling peptide materials in vitro, manipulating assemblies of peptides in living cells (or animals) is still in its infancy. In this contributing review, recent work is summarized using endogenous triggers to construct functional assemblies of peptides in vivo. After introducing the triggers for inducing peptide assemblies, the recent progress is highlighted of the in situ construction of assemblies for biomedical applications with emphasis on cancer therapy. Finally, a brief perspective is provided to discuss the future promises and challenges of this emerging area of supramolecular chemistry.

Molecular-Scale Insights into Electrochemical Reduction of CO2 on Hydrophobically Modified Cu Surfaces.

Depressing the competitive hydrogen evolution reaction (HER) to promote current efficiency toward carbon-based chemicals in the electrocatalytic CO2 reduction reaction (CO2RR) is desirable. A strategy is to apply the hydrophobically molecular-modified electrodes. However, the molecular-scale catalytic process remains poorly understood. Using alkanethiol-modified hydrophobic Cu as an electrode and CO2-saturated KHCO3 as an electrolyte, we reveal that H2O, rather than HCO3-, is the major H+ source for the HER, determined by differential electrochemical mass spectrometry with isotopic labeling. As a result, using in situ Raman, we find that the hydrophobic molecules screen the cathodic electric field effect on the reorientation of interfacial H2O to a "H-down" configuration toward Cu surfaces that corresponds to the decreased content of H-bonding-free water, leading to unfavorable H2O dissociation and thus decreased H+ source for the HER. Further, density functional theory calculations suggest that the absorbed alkanethiol molecules alter the electronic structure of Cu sites, thus decreasing the formation energy barrier of CO2RR intermediates, which consequently increases the CO2RR selectivity. This work provides a molecular-level understanding of improved CO2RR on hydrophobically molecule-modified catalysts and presents general references for catalytic systems having H2O-involved competitive HER.

Dynamically loading IFC models on a web browser based on spatial semantic partitioning.

Industry foundation classes (IFC) is an open and neutral data format specification for building information modeling (BIM) that plays a crucial role in facilitating interoperability. With increases in web-based BIM applications, there is an urgent need for fast loading large IFC models on a web browser. However, the task of fully loading large IFC models typically consumes a large amount of memory of a web browser or even crashes the browser, and this significantly limits further BIM applications. In order to address the issue, a method is proposed for dynamically loading IFC models based on spatial semantic partitioning (SSP). First, the spatial semantic structure of an input IFC model is partitioned via the extraction of story information and establishing a component space index table on the server. Subsequently, based on user interaction, only the model data that a user is interested in is transmitted, loaded, and displayed on the client. The presented method is implemented via Web Graphics Library, and this enables large IFC models to be fast loaded on the web browser without requiring any plug-ins. When compared with conventional methods that load all IFC model data for display purposes, the proposed method significantly reduces memory consumption in a web browser, thereby allowing the loading of large IFC models. When compared with the existing method of spatial partitioning for 3D data, the proposed SSP entirely uses semantic information in the IFC file itself, and thereby provides a better interactive experience for users.

3D2SeqViews: Aggregating Sequential Views for 3D Global Feature Learning by CNN With Hierarchical Attention Aggregation.

Learning 3D global features by aggregating multiple views is important. Pooling is widely used to aggregate views in deep learning models. However, pooling disregards a lot of content information within views and the spatial relationship among the views, which limits the discriminability of learned features. To resolve this issue, 3D to Sequential Views (3D2SeqViews) is proposed to more effectively aggregate the sequential views using convolutional neural networks with a novel hierarchical attention aggregation. Specifically, the content information within each view is first encoded. Then, the encoded view content information and the sequential spatiality among the views are simultaneously aggregated by the hierarchical attention aggregation, where view-level attention and class-level attention are proposed to hierarchically weight sequential views and shape classes. View-level attention is learned to indicate how much attention is paid to each view by each shape class, which subsequently weights sequential views through a novel recursive view integration. Recursive view integration learns the semantic meaning of view sequence, which is robust to the first view position. Furthermore, class-level attention is introduced to describe how much attention is paid to each shape class, which innovatively employs the discriminative ability of the fine-tuned network. 3D2SeqViews learns more discriminative features than the state-of-the-art, which leads to the outperforming results in shape classification and retrieval under three large-scale benchmarks.