Construction Of Scaffolds Research Articles

Switchable Reactivity of Cyclopropane Diesters toward (3 + 3) and (3 + 2) Cycloadditions with Benzoquinone Esters.

Herein, we describe an unprecedented (3 + 3) cycloaddition reaction of the donor-acceptor cyclopropanes with quinone esters toward the construction of chroman scaffolds in moderate to good yields. Interestingly, the strategy is also adjustable toward a (3 + 2) cycloaddition by just switching the Lewis acid to furnish benzofuran scaffolds. Based on the choice of Lewis acid used, the same set of precursors has been used to deliver the benzopyran and benzofuran derivatives.

De Novo Construction of Chiral Aminoindolines by Cu-Catalyzed Asymmetric Cyclization and Subsequent Discovery of an Unexpected Sulfonyl Migration.

Searching for efficient strategies to access structurally novel aminoindolines is of great significance for drug discovery. However, catalytic asymmetric de novo construction of aminoindoline scaffolds with functionality primed for diversification still remains elusive. Here, we report a Cu-catalyzed asymmetric cyclization of ethynyl benzoxazinones with amines, producing chiral 3-aminoindolines in good yield and with high enantioselectivity (up to 97% yield and 98:2 er). Moreover, a radical-mediated sulfonyl migration of these products was unexpectedly found, further affording new chiral 3-aminoindolines bearing alkenyl sulfonyl groups with retained enantiopurity (up to 84% yield and 98:2 er). Bioactivity evaluations indicate that these 3-aminoindolines show notable antitumor activities and chirality is proven to have a significant impact on their antitumor activity.

Construction of functional magnetic scaffold with temperature control switch for long-distance vascular injury

Fusion of endothelial monolayer for rapid reendothelialization is the key to vascular transplantation, which is crucial for remodeling long-distance (≥10 mm) vascular injury (LDVJ) and reducing the long-term repair period. Although silk fibroin (SF) has been widely prepared as a scaffold to repair vascular injuries, it is still challenging to remodel LDVJs. The design and manufacture of functional scaffolds with a rapid reendothelialization enhancement effect are helpful to solve this problem. Here, we developed a well-designed functional magnetic scaffold (MDP) with a temperature-controlled switch, intelligently regulating the release of magnetic nanoparticles (MNPs) to induce macrophages migration and M2 polarization. The results show that the radial support force of MDP is appropriately five times higher than that of pure silk fibroin scaffold (SFC), and the degradation of MDP is delayed, which is beneficial to maintaining the integrity of the scaffold. MDP induces the migration of macrophages, upregulates the expression of repair cytokines such as TGF-β, IL-10 and VEGF, and promotes the proliferation of mouse aortic vascular smooth muscle (MOVAS) cells. More importantly, the enhanced migration of macrophages at the phase transition temperature is more conducive to the proliferation and accumulation of vascular repair-related cells, which is conducive to rapid reendothelialization. In addition, MDP also significantly regulates the polarization of macrophages to M2 type, which is conducive to the secretion of repair cytokines to further promote vascular recovery. The evaluation of endothelial cells' adhesion and function also proved that MDP could increase the expression of vascular endothelial cadherin (VE-Cad) and collagen IV (COL IV) and has the potential for rapid reendothelialization. The replacement model in vivo animal experiments further proved that MDP exhibited a better repair effect than SFC, providing a new option for the repair of LDVJ in the future.

An Access to Highly Functionalized Dihydrobenzofuran Spirooxindole Scaffolds.

We have developed an efficient protocol for the construction of polycyclic dihydrobenzofuran spirooxindole scaffolds via base promoted cascade annulation of Morita-Baylis-Hillman (MBH) carbonates of isatins with ortho-hydroxychalcones or ortho-hydroxy-β-nitrostyrenes. The complex polycyclic compounds were conveniently synthesized in satisfactory yields and with high diastereoselectivity. This protocol provides a swift and convenient approach for the assembly of diverse highly functionalized dihydrobenzofuran spirooxindoles and also features broad substrate scope, high molecular convergence, and excellent atomic economy.

Mechanism Study of the Effect of Selective Laser Melting Energy Density on the Microstructure and Properties of Formed Renewable Porous Bone Scaffolds

To investigate the effect of selective laser melting (SLM) energy densities on the performance of porous 316L stainless steel bone scaffolds, the porous bone scaffolds with a face-centered cubic (FCC) structure were prepared using SLM technology, and a comprehensive study combining finite element analysis (FEA) and experiments was conducted on the SLM-formed 316L porous bone scaffolds. The mechanism of how various energy densities affect bone scaffolds were identified, and the effects of different energy densities on the primary dendrite spacing, grain orientation, residual stress, and transient melt pool variation in the scaffolds were discussed and summarized. It was found that the change in the energy densities had a more serious effect on the primary dendrite spacing, with the primary dendrite spacing increasing from 320 to 501 nm when the energy densities were increased from 41.7 to 111.1 J/mm3. In addition, analysis of the residual stress in the formed scaffolds showed that when an energy density of 41.7 J/mm3 was chosen for construction, the internal residual stress in the scaffolds reached a minimum value of 195.78 MPa, a reduction of approximately 36.6% compared to that of 111.1 J/mm3 for the porous scaffold. For the other properties of the scaffolds, the choice of low energy densities for the construction of FCC-structured porous bone scaffolds allowed for a maximum 10% reduction in the controlled deformation and a maximum 17% increase in the compressive properties. At the same time, it was found that the analysis results of the SLM-forming process by the FEA method were consistent with the experimental results. The main innovation of this paper is the proposal of the best construction parameters for porous bone scaffolds with an FCC structure formed by SLM and verification of the rationality of the best parameters through macro and micro experimental analysis, which guides the construction of porous bone scaffolds with an FCC structure formed by additive manufacturing. In addition, this study used finite element simulation to analyze the SLM process. This provides early prediction, optimization, and improvement for SLM-forming FCC porous bone scaffolds. The most important thing is that FEA can be used to more rapidly and economically analyze SLM. In the future, FEA can be used to provide a reference for porous bone scaffolds with different structures, different construction energy densities, different materials, and additive manufacturing in other industries.

Applications of N-Halo Reagents in Multicomponent Reactions: A Still Underrated Approach for the Construction of Heterocyclic Scaffolds

Abstract:Heterocyclic scaffolds are important from both academic and industrial points of view. Due to their biological and pharmacological activities, they are useful intermediates in organic synthesis and have great interest in medicinal and natural products chemistry. N-halo compounds bearing an electron-withdrawing group on nitrogen (e.g., carbonyl, sulfonyl) present the unique chemical properties of the N-X bond that give them broad synthetic utility for diverse organic transformation. In the past years, significant progress has been achieved in the synthesis of heterocyclic compounds with the intermediacy of N-halo compounds. Numerous strategies (e.g., electrophilic cyclizations, asymmetric halocyclizations, oxidative cyclizations, radical processes) were implemented featuring high atom- and step-economy, and more efficient procedures are continually being developed. An interesting approach consists of using Nhalo compounds to promote multicomponent reactions (MCRs), which rapidly became an emerging field in heterocyclic construction. MCRs are recognized for their mild conditions, high convergence, and efficiency. Thus, the present review will focus attention on the main topics and utilization of N-halo compounds (N-halosuccinimides, trihaloisocyanuric acids, N-halosulfonamides, etc.) as green and convenient reagents in heterocyclic construction via MCRs. Examples of the preparation of azoles, pyridines, 1,4-dihydropyridines, chromenes, and xanthenes, among other scaffolds are presented and discussed.

BMSC exosome-enriched acellular fish scale scaffolds promote bone regeneration

Tissue engineering scaffolds are essential for repairing bone defects. The use of biomimetic scaffolds for bone tissue engineering has been investigated for decades. To date, the trend in this area has been moved toward the construction of biomimetic acellular scaffolds with effective modification to enhance the osteogenic differentiation efficiency of bone marrow mesenchymal stem cells (BMSCs). The exosomes derived from BMSCs have been shown as a potential therapeutic tool for repairing bone defects. In this study, we demonstrated the pro-osteogenic effects of exosomes derived form osteogenic differentiated BMSCs (OBMSC) and presented a novel exosmes-functionalized decellularized fish scale (DE-FS) scaffold for promoting bone regeneration in vivo. The DE-FS scaffolds were obtained through decellularization and decalcification processes, which exhibited high biocompatibility and low immunological rejection. The intrinsic anisotropic structures of DE-FS could enhance the adhesion and proliferation ability of BMSCs in vitro. In addition, we demonstrated that the porous structure of DE-FS endowed them with the capacity to load and release exosomes to BMSCs, resulting in the enhanced osteogenic differentiation of BMSCs. Concerning these pro-osteogenic effects, it was further proved that OBMSC exosome-modified DE-FS scaffolds could effectively promote bone regeneration in the mouse calvarial defect models. In conclusion, our work provided a new insight to design exosome-riched biomimetic scaffolds for bone tissue engineering and clinical applications.

Construction of Non-Biaryl Atropisomeric Amide Scaffolds Bearing a C-N Axis via Enantioselective Catalysis.

The significant scaffold offered by atropisomeric amides with a C–N chiral axis has been extensively utilized for pharmaceuticals, agricultural science, and organic syntheses. As a result, the field of atropisomer synthesis has attracted considerable interest within chemistry communities. To date, a range of catalytic atroposelective approaches has been reported for the efficient construction of these challenging scaffolds. However, greatly concise and highly useful methodologies for the synthesis of these atropisomeric compounds, focusing on transition-metal, chiral amine, and phosphoric acid catalysis reactions, etc., are still desirable. Hence, it is indispensable to succinctly and systematically present all such reports by means of disclosing the mechanistic analysis and application, as well as the challenges and issues associated with the establishment of these atropisomers. In this review, we summarize the development of catalytic asymmetric synthetic strategies to access non-biaryl atropisomers rotating around a C–N chiral axis, including the reaction methods, mechanism, late-stage transformations, and applications.

Bioinspired stretchable helical nanofiber yarn scaffold for locomotive tissue dynamic regeneration

<h2>Summary</h2> Simulating the microstructure and mechanical properties of natural tissues to achieve rapid tissue regeneration and protect cells under strain during body movement is a giant challenge in locomotive tissue engineering. Here, we built a hierarchical helical scaffold with high stretchability, which not only structurally resembles natural tissues but also matches their non-affine deformation mechanical properties. The cells on this scaffold can maintain high viability under cyclic strains, because the non-planar motion of coil structures mitigates the local maximum strain during stretching. Moreover, the <i>in vivo</i> experiments demonstrated that the scaffold affords a stable structural and mechanical microenvironment for cell growth and tissue morphogenesis. This helical scaffold breaks the inherent mindset of fixation repairing and makes it possible for reconstruction of the defective tissue even in moderate motion. The study proposes a new thinking about construction of stretchable scaffolds with superior mechanical properties for repairing locomotive tissue injuries.

Cross-Section Dimension Measurement of Construction Steel Pipe Based on Machine Vision

Currently, the on-site measuring of the size of a steel pipe cross-section for scaffold construction relies on manual measurement tools, which is a time-consuming process with poor accuracy. Therefore, this paper proposes a new method for steel pipe size measurements that is based on edge extraction and image processing. Our primary aim is to solve the problems of poor accuracy and waste of labor in practical applications of construction steel pipe inspection. Therefore, the developed method utilizes a convolutional neural network and image processing technology to find an optimum solution. Our experiment revealed that the edge image that is proposed in the existing convolutional neural network technology is relatively rough and is unable to calculate the steel pipe’s cross-sectional size. Thus, the suggested network model optimizes the current technology and combines it with image processing technology. The results demonstrate that compared with the richer convolutional features (RCF) network, the optimal dataset scale (ODS) is improved by 3%, and the optimal image scale (OIS) is improved by 2.2%. At the same time, the error value of the Hough transform can be effectively reduced after improving the Hough algorithm.

Construction of enzyme-laden vascular scaffolds based on hyaluronic acid oligosaccharides-modified collagen nanofibers for antithrombosis and in-situ endothelialization of tissue-engineered blood vessels

The current use of synthetic grafts often yields low patency in the reconstruction of small-diameter blood vessels owing to the deposition of thrombi and imperfect coverage of the endothelium on the graft lumen. Therefore, the design of vascular scaffolds with antithrombotic performance and endothelialization is greatly required. Herein, we developed an enzyme-laden scaffold based on hyaluronic acid oligosaccharides-modified collagen nanofibers (labeled HA-COL) to improve the anti-platelet capacity and endothelialization of vascular grafts. In this study, HA-COL nanofibers not only encouraged the endothelialization of vascular scaffolds, but acted as an antiplatelet enzyme-laden platform. Apyrase (Apy) and 5’-nucleotidase (5’-NT) were covalently grafted onto the nanofibers, which in turn converted the platelet-sensitive substance: adenosine diphosphate (ADP) into adenosine monophosphate (AMP) and adenosine, thereby, improving the antithrombotic performance of the scaffolds. Notably, the catalytic end-product: adenosine would work in coordination with HA-COL to synergistically enhance the endothelialization of the vascular scaffolds. The results demonstrated that the enzyme-laden scaffolds maintained catalytic performance, reduced platelet adhesion and aggregation, and guaranteed higher patency after 1-month in situ transplantation. Moreover, these scaffolds showed optimal cytocompatibility, tissue compatibility, scaffold biodegradability and tissue regenerative capability during in vivo implantation. Overall, these engineered vascular scaffolds demonstrated their capacity for endothelialization and antithrombotic performance, suggesting their potential for small-diameter vascular tissue engineering applications. Statement of significanceConsidering the critical problems in small-diameter vascular reconstruction, the enzyme-laden vascular scaffolds were prepared for improving in-situ endothelialization and antithrombotic performances of artificial blood vessels. The electrospun HA-COL nanofibers were used as the main matrix materials, which provided favorable structural templates for the regeneration of vasculature and functioned as a platform for the loading of enzymes. The enzyme-laden scaffolds with the biomimetic cascading reaction would convert ADP into adenosine, thereby, decreasing the sensitivity of platelets and improving the antithrombotic performance of tissue-engineered blood vessels (TEBVs). The nanofibrous scaffolds exhibited optimal cytocompatibility, tissue compatibility and regenerative capability, working together with catalytic products of dual-enzyme reaction that would synergistically contribute to TEBVs endothelialization. This study provides a new method for the improvement of in-situ endothelialization of small-diameter TEBVs while qualified with antithrombotic performance.

Isocyanide-Based Multicomponent Reactions in Water: Advanced Green Tools for the Synthesis of Heterocyclic Compounds.

Reaction rate acceleration using green methods is an intriguing area of research for chemists. In this regard, water as a "green solvent" plays a crucial role in the acceleration of some organic transformations and reveals exclusive selectivity and reactivity in comparison with conventional organic solvents. In particular, multicomponent reactions (MCRs) as sustainable tools lead to the rapid generation of small-molecule libraries in water and aqueous media due to the prominent role of the hydrophobic effect. MCRs, as diversity-oriented synthesis (DOS) methods, have great efficiency with simple operations, atom, pot, and step economy synthesis, and mechanistic beauty. Among diverse classes of MCRs, isocyanide-based multicomponent reactions (I-MCRs), as sustainable and versatile reactions, have gained considerable attention in the synthesis of diverse heterocycle rings, especially in drug design because of the peculiar nature of isocyanide as a particular active reactant. I-MCRs that are performed in water are mild, environmentally friendly, and easily controlled, and have a reduced number of workup, purification, and extraction steps, which fit well with the advantages of "green" chemistry. Performing these powerful organic transformations in water and aqueous media is accompanied by acceleration owing to negative activation volumes, which originate from connecting several reactants together to generate a single product. It should be noted that the combination of MCR strategy and aqueous phase reaction is of growing interest for the development of sustainable synthetic techniques in organic conversions. However, an exclusive account focusing on the recent progress in eco-friendly I-MCRs for the construction of heterocycles in water and aqueous media is particularly lacking. This review highlights the progress of various kinds of I-MCRs in water and aqueous media as benign methods for the efficient construction of vital heterocyclic scaffolds, with a critical discussion of the subject in the period 2000-2021. We hope that this themed collection will be of interest and beneficial for organic and pharmaceutical chemists and will inspire more reaction development in this fascinating field.

Calculation of stresses on 3D scaffolds fabricated using extrusion-based bioprinting using a semi-analytical approach

The scaffold is essential to tissue engineering. In particular, the mechanical property of scaffolds has a significant impact on the success rate of regeneration. While numerous techniques exist for measuring mechanical properties, Compression test, three-point bending test, and nano-indentation test are the most common. Nevertheless, the mechanical property of porous structures cannot be accurately measured by previous testing methods. Combining superposition principles with the Flamant solution, this study developed semi-analytical solutions. Through compression testing and FEM simulation, the semi-analytical solution was fully validated. The solution can calculate not only the maximum stress of layer-by-layer construction of complex 3D scaffolds, but also the maximum load-bearing capacity if the mechanical property of the material is known.

A Multifunctional 3D Bioprinting System for Construction of Complex Tissue Structure Scaffolds: Design and Application.

Three-dimensional (3D) bioprinting offers a potentially powerful new approach to reverse engineering human pathophysiology to address the problem of developing more biomimetic experimental systems. Human tissues and organs are multiscale and multi-material structures. The greatest challenge for organ printing is the complexity of the structural elements, from the shape of the macroscopic structure to the details of the nanostructure. A highly bionic tissue-organ model requires the use of multiple printing processes. Some printers with multiple nozzles and multiple processes are currently reported. However, the bulk volume, which is inconvenient to move, and the high cost of these printing systems limits the expansion of their applications. Scientists urgently need a multifunctional miniaturized 3D bioprinter. In this study, a portable multifunctional 3D bioprinting system was built based on a modular design and a custom written operating application. Using this platform, constructs with detailed surface structures, hollow structures, and multiscale complex tissue analogs were successfully printed using commercial polymers and a series of hydrogel-based inks. With further development, this portable, modular, low-cost, and easy-to-use Bluetooth-enabled 3D printer promises exciting opportunities for resource-constrained application scenarios, not only in biomedical engineering but also in the education field, and may be used in space experiments.

Dual gradients of bioactive components on electrospun fibers for cell migration and controlled stem cell differentiation

The construction of gradient scaffolds to mimic the in vivo microenvironment for promoting tissue regeneration is attractive, especially by incorporating biochemical cues with physical guidance to manipulate cell behavior. Here, we report a general method to generate dual concentration-gradient of two types of bioactive components on scaffolds composed of uniaxially aligned electrospun nanofibers through layer-by-layer self-assembly. Different layers of collagen (COL) and chondroitin sulfate (CS) are sequentially coated onto the specific positions of uniaxially aligned electrospun polycaprolactone (PCL) nanofibers upon electrostatic attraction. In this case, dual stepwise gradients of COL and CS are generated along the fiber alignment. In demonstrating the potential application, the dual gradients can effectively promote the migration and proliferation of bone marrow stem cells (BMSCs) and spatially control their osteogenic differentiation. This simple strategy for generating dual gradients can be easily extended to different types of gradient scaffolds for bone regeneration and related applications involving cell migration, stem cell differentiation, and tissue interface.

Self-Searching Writing of Human-Organ-Scale Three-Dimensional Topographic Scaffolds with Shape Memory by Silkworm-like Electrospun Autopilot Jet.

Bioengineered scaffolds satisfying both the physiological and anatomical considerations could potentially repair partially damaged tissues to whole organs. Although three-dimensional (3D) printing has become a popular approach in making 3D topographic scaffolds, electrospinning stands out from all other techniques for fabricating extracellular matrix mimicking fibrous scaffolds. However, its complex charge-influenced jet–field interactions and the associated random motion were hardly overcome for almost a century, thus preventing it from being a viable technique for 3D topographic scaffold construction. Herein, we constructed, for the first time, geometrically challenging 3D fibrous scaffolds using biodegradable poly(ε-caprolactone), mimicking human-organ-scale face, female breast, nipple, and vascular graft, with exceptional shape memory and free-standing features by a novel field self-searching process of autopilot polymer jet, essentially resembling the silkworm-like cocoon spinning. With a simple electrospinning setup and innovative writing strategies supported by simulation, we successfully overcame the intricate jet–field interactions while preserving high-fidelity template topographies, via excellent target recognition, with pattern features ranging from 100’s μm to 10’s cm. A 3D cell culture study ensured the anatomical compatibility of the so-made 3D scaffolds. Our approach brings the century-old electrospinning to the new list of viable 3D scaffold constructing techniques, which goes beyond applications in tissue engineering.

Integrated construction of silkworm cocoon-inspired 3D scaffold for improving cell manufacture and cryopreservation

Although cellular therapy holds enormous promise in treating intractable diseases, its application potential has been significantly hampered due to the scarcity of reliable and consistent cell sources. Therefore, a high-efficiency strategy that improves cell production and storage is desperately needed. Herein, we develop a versatile 3D bioinspired scaffold (Cryosilk) for improving scalable cell manufacture and cryopreservation. A bottom-up fabrication technique integrating electrospinning, in situ surface functionalization and freeze-shaping was explored to construct Cryosilk with biomimetic features and functions of silkworm cocoons. Cryosilk is composed of a core-shell heterostructure with silk fibroin/poly alanine fiber core and silk sericin shell, generating a 3D cocoon-mimicking fibrous structure. Importantly, Cryosilk possesses improved thermal conductivity and ice crystal resistance capability, thus enabling to cryopreserve biological samples with minimal cryodamage. Furthermore, Cryosilk not only promotes cell adhesion and growth, but achieves rapid and uniform rewarming process, which provides high cryopreservation efficacy for immune cells and stem cells. Particularly, Cryosilk can maintain cell viability and biofunctions of stem cell-scaffold constructs after freeze-thawing, which can be directly implanted to promote wound healing. Thus, Cryosilk offers unprecedented efficacy in cell manufacture and cryopreservation, which provides sufficient and high-quality precious cells and tissue engineered scaffolds for cellular therapy.

A smart magnetic hydrogel containing exosome promotes osteogenic commitment of human adipose-derived mesenchymal stem cells.

Objective(s):Exosomes, as nano-sized extracellular vehicles acting as cell-to-cell communicators, are novel promising therapeutics in the area of bone tissue engineering. Moreover, magnetic nanoparticles, whose integration with other appropriate components is viewed as an intriguing approach to strengthen bone tissue engineering efficacy. We investigated the effect of magnetic enriched with exosomes on osteogenic differentiation.Materials and Methods:Exosomes were isolated from human adipose-derived mesenchymal stem cells by Exo-spin™ kit (MSC-EX). Alginate (Alg) scaffold containing 1% (w/w) cobalt ferrite nanoparticles (CoFe2O4) was produced. MSC-EX were gently loaded onto Alg and Alg-cobalt ferrite (Alg-CF) scaffolds yielding Alg-EX and Alg-CF-EX scaffolds. The effects of MSC-Ex and magnetic hydrogel composite under an external static magnetic field (SMF) on proliferation and differentiation of MSCs were evaluated by alkaline phosphatase (ALP) activity measurement, alizarin red staining, and energy dispersive X-ray (EDX) analysis.Results:Our results showed that Alg and Alg-CF scaffolds were not only cytotoxic but also supported AdMSCs proliferation. MSC-EX loading of the scaffolds enhanced AdMSCs proliferation significantly. According to the results, Alg-CF-EX scaffolds under magnetic stimulation exhibited the most potent effect on osteogenic differentiation of cultured AdMSCs as evidenced by higher ALP activity and mineralization.Conclusion:We provided evidence that the combination of Alg hydrogel, CFNPs, and MSC-EX resulted in the construction of a bone tissue-engineering scaffold that highly supports the osteogenic commitment of MSCs.

Three-dimensional flexible and stretchable gold foam scaffold for real-time electrochemical sensing in cells and in vivo

Compared with typical two-dimensional electrodes, the three-dimensional (3D) cell culture platform can simulate the real cell survival environment for cell growth to accurately reproduce cell functions. Moreover, considering that living cells are exposed to various of mechanical force in the microenvironment, the construction of 3D electrodes with excellent flexible, stretchable, and biocompatibility is of great significance to real-time monitor mechanically evoked biomolecule release from cells. Herein, we demonstrated a straightforward and effective three-step approach to fabricate three-dimensional flexible and stretchable gold foam scaffold (3D Au foam scaffold) for construction of 3D cell culture integrated electrochemical sensing platform. The excellent biological and electrical properties of Au nanostructures and porous networks of the 3D scaffold endow the platform with desirable biocompatibility and sensitive electrochemical sensing performance. As a proof of concept, the 3D Au foam scaffold functionalized with cobalt based nanocubes (Co NCs/Au foam scaffold) was validated to provide 3D culture for human umbilical vein endothelial cells (HUVECs), and synchronously real-time monitor superoxide anion (O2•-) released by HUVECs under mechanical stretching. Furthermore, 3-mercaptopropionic acid (3-MPA) modified 3D Au foam (3-MPA/Au foam scaffold) was successfully used for real-time monitoring of catecholamines in rat brain. The results demonstrate the great potential of this 3D Au foam scaffold for real-time electrochemical monitoring biomolecules in vitro and in vivo, providing convenience for future research on mechanotransduction relevant processes.

Stereoselective construction of azepine-containing bridged scaffolds via organocata-lytic bicyclization of yne-allenone esters with nitrones

A new organocatalytic double annulation cascade involving scission/recombination of N-O bonds of nitrones is reported for the first time, and used to produce a range of hitherto unprecedented tricyclic bridged-fused benzo[d]azepines bearing three stereogenic centers with moderate to good yields and complete diastereoselectivity. A quinine-catalyzed reaction of yne‑allenone esters with nitrones worked well and provided a convergent and regioselective pathway to access these three-dimensional scaffolds from the planar conjugated system. Density functional theory (DFT) calculations have been applied to understand the key process for forming diradical intermediates.