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Injectable granular gels consisting of densely packed microgels serving as scaffolding biomaterial have recently shown great potential for applications in tissue regeneration, which allow administration via minimally invasive surgery, on-target cargo delivery, and high efficiency in nutrient/waste exchange. However, limitations such as insufficient mechanical strength, structural integrity, and uncontrollable differentiation of the encapsulated cells in the scaffolds hamper their further applications in the biomedical field. Herein, we developed a new class of granular gels via bottom-up assembly of cell-laden microgels via photo-triggered imine-crosslinking (PIC) chemistry based on the microfluidic technique. The particulate nature of the granular gels rendered them with shear-thinning and self-healing behavior, thereby functioning as an injectable and adaptable cellularized scaffold for bone tissue regeneration. Specifically, single cell-laden, monodisperse microgels composed of methacrylate- and o-nitrobenzene-functionalized hyaluronic acid and gelatin were prepared using a high-throughput microfluidic technique with a production rate up to 3.7 × 108 microgels/hr, wherein the PIC chemistry alleviated the oxygen inhibition on free-radical polymerization and facilitated enhanced fabrication accuracy, accelerated gelation rate, and improved network strength. Further in vitro and in vivo studies demonstrated that the microgels can serve as carriers to support the activity of the encapsulated mesenchymal stem cells; these cell-laden microgels can also be used as cellularized bone fillers to induce the regeneration of bone tissues as evidenced by the in vivo experiment using the rat femoral condyle defect model. In general, these results represent a significant step toward the precise fabrication of engineered tissue mimics with single-cell resolution and high cell-density and can potentially offer a powerful tool for the design and applications of a next generation of tissue engineering strategy. Statement of significance: Using microfluidic droplet-based technology, we hereby developed a new class of injectable and moldable granular gels via bottom-up assembly of cell-laden microgels as a versatile platform for tissue regeneration. Phototriggered imine-crosslinking chemistry was introduced for microgel cross-linkage, which allowed for the fabrication of microgels with improved matrix homogeneity, accelerated gelation process, and enhanced mechanical strength. We demonstrated that the microgel building blocks within the granular gels facilitated the proliferation and differentiation of the encapsulated mesenchymal stem cells, which can further serve as a cellularized scaffold for the treatment of bone defects.

A rigid-axle-based molecular rotaxane was designed to mediate efficient K+/Cl− channel co-transport by simultaneously introducing heteroditopic receptors, which presents a new model for designing synthetic channels for salt co-transport.

Based on photoinduced S-nitrosylation and Schiff base reaction, a novel hydrogel fabrication strategy has been established to rapidly construct reinforced, biocompatible hydrogels for 3D printing and for related biomedical applications.

Coumarin-based PPGs that feature electron-rich thiophene-derived substitutions at the C3-position of a coumarin scaffold have demonstrated a high uncaging quantum yield (Φu) as well as an efficient photolysis rate.

A light-activated crosslinking strategy was proposed to prepare a polymer with high robustness and serum stability for cytosol protein delivery. It can deliver proteins into cytosols with maintained bioactivities even in 50% FBS-containing medium.

Substrate photopatterning has provided versatile applications in biomedical fields. Herein, an universal and efficient photoligation reaction has been used to prepare a patterned capture substrate for a sandwich SERS immunoassay. Photoirradiation induces mild and efficient immobilization of antibodies at the desired region of a gold surface, and the antibody-antigen interaction helps the substrate to capture the antigens in solution specifically. After exposing to SERS probes, i.e., the gold nanoparticles labelled with both antibodies and intrinsically strong Raman reporters, multiple quantitative SERS determination of antigens can be achieved with high sensitivity and specificity. The limit of detection can be as low as 10−12 mol/L for four kinds of cancer biomarkers, which provides a promising method for the construction of highly sensitive and high-throughput SERS detection chip and the application of in vitro diagnosis.

Photoisomerization chemistry was used to simulate light signal transduction, in which the light-controlled reciprocating translocation of molecules in lipids activates or deactivates the hydrolysis reaction for an encapsulated substrate.

Pepper fluorescent RNAs are a recently reported bright, stable and multicolor fluorogenic aptamer tag that enable imaging of diverse RNAs in live cells. To investigate the molecular basis of the superior properties of Pepper, we determined the structures of complexes of Pepper aptamer bound with its cognate HBC or HBC-like fluorophores at high resolution by X-ray crystallography. The Pepper aptamer folds in a monomeric non-G-quadruplex tuning-fork-like architecture composed of a helix and one protruded junction region. The near-planar fluorophore molecule intercalates in the middle of the structure and is sandwiched between one non-G-quadruplex base quadruple and one noncanonical G·U wobble helical base pair. In addition, structure-based mutational analysis is evaluated by in vitro and live-cell fluorogenic detection. Taken together, our research provides a structural basis for demystifying the fluorescence activation mechanism of Pepper aptamer and for further improvement of its future application in RNA visualization. Structural analysis of the Pepper aptamer in complex with its cognate HBC or HBC-like color variants reveals that it binds fluorophore molecules via one non-G-quadruplex base quadruple and one noncanonical G·U base pair.

Peptide-based supramolecular hydrogels have attracted great attention due to their good biocompatibility and biodegradability and have become promising candidates for biomedical applications. The bottom-up self-assembly endows the peptides with a highly ordered secondary structure, which has proven to be an effective strategy to improve the mechanical properties of hydrogels through strong physical interactions and energy dissipation. Inspired by the excellent mechanical properties of spider-silk, which can be attributed to the rich β-sheet crystal formation by the hydrophobic peptide fragment, a hydrophobic peptide (HP) that can form a β-sheet assembly was designed and introduced into a poly(vinyl alcohol) (PVA) scaffold to improve mechanical properties of hydrogels by the cooperative intermolecular physical interactions. Compared with hydrogels without peptide grafting (P-HP0), the strong β-sheet self-assembly domain endows the hybrid hydrogels (P-HP20, P-HP29, and P-HP37) with high strength and toughness. The fracture tensile strength increased from 0.3 to 2.1 MPa (7 times), the toughness increased from 0.4 to 21.6 MJ m-3 (54 times), and the compressive strength increased from 0.33 to 10.43 MPa (31 times) at 75% strain. Moreover, the hybrid hydrogels are enzymatically degradable due to the dominant contribution of the β-sheet assembly for network cross-linking. Combining the good biocompatibility and sustained drug release of the constructed hydrogels, this hydrophobic β-sheet peptide represents a promising candidate for the rational design of hydrogels for biomedical applications.

Inspired by the nontrivial and controlled movements of molecular machines, we report an azobenzene-based molecular shuttle PR2 , which can perform light-gated ion transport across lipid membranes. The amphiphilicity and membrane-spanned molecular length enable PR2 to insert into the bilayer membrane and efficiently ferry K + (EC 50 = 4.1 µM) through the thermally driven stochastic shuttle motion of the crown ether ring along the axle. The significant difference in shuttling rate between trans - PR2 and cis - PR2 induced by molecular isomerization enables the light-gated ion transport, i.e., ON/OFF in situ regulation of transport activity and single-channel current. This work represents an example of using a photoswitchable molecular machine to realize the gated ion transport, which truly reflects the value of molecular machines functioning in biomembranes.

Effective healing of skin wounds is essential for our survival. Although skin has strong regenerative potential, dysfunctional and disfiguring scars can result from aberrant wound repair. Skin scarring involves excessive deposition and misalignment of ECM (extracellular matrix), increased cellularity, and chronic inflammation. Transforming growth factor-β (TGFβ) signaling exerts pleiotropic effects on wound healing by regulating cell proliferation, migration, ECM production, and the immune response. Although blocking TGFβ signaling can reduce tissue fibrosis and scarring, systemic inhibition of TGFβ can lead to significant side effects and inhibit wound re-epithelization. In this study, we develop a wound dressing material based on an integrated photo-crosslinking strategy and a microcapsule platform with pulsatile release of TGF-β inhibitor to achieve spatiotemporal specificity for skin wounds. The material enhances skin wound closure while effectively suppressing scar formation in murine skin wounds and large animal preclinical models. Our study presents a strategy for scarless wound repair., Dysfunctional and disfiguring scars can result from aberrant wound repair. Here, the authors develop a wound dressing material based on an integrated photo-crosslinking strategy and a microcapsule platform with pulsatile release of TGF-β inhibitor to achieve spatiotemporal specificity for scarless wound repair.

Here, we report a strategy to deliver drug nanoparticles into cells with nucleus-targeting ability under a spatiotemporal control. The nanoparticles were constructed through self-assembly of photoresponsive prodrugs and free drugs. By incorporating a nucleus localization sequence in the system, drug nanoparticles could be delivered into nuclei upon visible light irradiation. The drug nanoparticles showed high drug loading capacity and specific nucleus-targeting ability, which efficiently killed cancer cells. This self-assembly strategy could be applied to other hydrophobic drugs and targeting ligands for photo-controlled organelle-targeted drug delivery.

Nature or synthetic systems that can self-assemble into biomimetic membranes and form compartments in aqueous solution have received extensive attention. However, these systems often have the problems of requiring complex processes or lacking of control in simulating lipid synthesis and membrane formation of cells. This paper demonstrates a conceptually new strategy that uses a photoligation chemistry to convert nonmembrane molecules to yield liposomes. Lysosphingomyelin (Lyso) and 2-nitrobenzyl alcohol derivatives (NBs) are used as precursors and the amphiphilic character of Lyso promotes the formation of mixed aggregates with NBs, bringing the lipid precursors into close proximity. Light irradiation triggers the conversion of NBs into reactive aldehyde intermediates, and the preassembly facilitates the efficient and specific ligation between aldehyde and Lyso amine over other biomolecules, thereby accelerating the synthesis of phospholipids and forming membrane compartments similar to natural lipids. The light-controllable transformation represents the use of an external energy stimulus to form a biomimetic phospholipid membrane, which has a wide range of applications in medicinal chemistry, synthetic biological and abiogenesis., A photoligation chemistry was used to drive the formation of biomimetic membranes in situ. The preassembly of precursors promotes the synthesis of lipid, which is an important feature as a candidate for simulating natural membrane functions.

In situ forming redox responsive nanoparticles have been developed based on amphiphilic copolymers-phototriggered disulfide-cross-link macromolecules (PDCM). Upon 405 nm light irradiation, the macrocyclic thiol caged coumarin phototrigger in PDCM can release free thiols, and these free thiols subsequently realize in situ disulfide cross-link via reacting with a pyridyl disulfide group inside the PDCM assembled nanoparticles. The phototriggered disulfide-cross-link strategy can be conducted rapidly, conveniently, and cleanly without adding any cross-linkers or catalysts. Via changing irradiation condition, nanoparticles with different cross-link densities can be formed. These nanoparticles can encapsulate hydrophobic guest molecules with good stability and achieve redox-triggered release under GSH reduction. Intracellular experiments show that these nanoparticles can be used as promising drug carriers.

Regulating cell-surface interactions plays a key role for biomaterials and their applications in cell-based therapies. In this paper, we demonstrated a dual-responsive hydrogel platform to achieve phototriggered protein immobilization and reduction-induced protein release. By

The construction of a biomaterial matrix with biological properties is of great importance to developing functional materials for clinical use. However, the site-specific immobilization of growth factors to endow materials with bioactivities has been a challenge to date. Considering the wide existence of glycosylation in mammalian proteins or recombinant proteins, we establish a bioaffinity-based protein immobilization strategy (bioanchoring method) utilizing the native sugar-lectin interaction between concanavalin A (Con A) and the oligosaccharide chain on glycosylated bone morphogenetic protein-2 (GBMP-2). The interaction realizes the site-specific immobilization of GBMP-2 to a substrate modified with Con A while preserving its bioactivity in a sustained and highly efficient way, as evidenced by its enhanced ability to induce osteodifferentiation compared with that of the soluble GBMP-2. Moreover, the surface with Con A-bioanchored GBMP-2 can be reused to stimulate multiple batches of C2C12 cells to differentiate almost to the same degree. Even after 4 month storage at 4 °C in phosphate-buffered saline (PBS), the Con A-bioanchored GBMP-2 still maintains the bioactivity to stimulate the differentiation of C2C12 cells. Furthermore, the ectopic ossification test proves the in vivo bioactivity of bioanchored GBMP-2. Overall, our results demonstrate that the tag-free and site (i.e., sugar chain)-specific protein immobilization strategy represents a simple and generic alternative, which is promising to apply for other glycoprotein immobilization and application. It should be noted that although the lectin we utilized can only bind to d-mannose/d-glucose, the diversity of the lectin family assures that a specific lectin could be offered for other sugar types, thus expanding the applicable scope further.

Despite its central importance in cellular metabolism, many details remain to be determined regarding subcellular lactate metabolism and its regulation in physiology and disease, as there is sensitive spatiotemporal resolution of lactate distribution, and dynamics remains a technical challenge. Here, we develop and characterize an ultrasensitive, highly responsive, ratiometric lactate sensor, named FiLa, enabling the monitoring of subtle lactate fluctuations in living cells and animals. Utilizing FiLa, we demonstrate that lactate is highly enriched in mammalian mitochondria and compile an atlas of subcellular lactate metabolism that reveals lactate as a key hub sensing various metabolic activities. In addition, FiLa sensors also enable direct imaging of elevated lactate levels in diabetic mice and facilitate the establishment of a simple, rapid, and sensitive lactate assay for point-of-care clinical screening. Thus, FiLa sensors provide powerful, broadly applicable tools for defining the spatiotemporal landscape of lactate metabolism in health and disease.

Light signal transduction pathways are the central components of mechanisms that regulate plant development, in which photoreceptors receive light and participate in light signal transduction. Chemical systems can be designed to mimic these biological processes that have potential applications in smart sensing, drug delivery and synthetic biology. Here, we synthesized a series of simple photoresponsive molecules for use as photoreceptors in artificial light signal transduction. The hydrophobic structures of these molecules facilitate their insertion into vesicular lipid bilayers, and reversible photoisomerization initiates the reciprocating translocation of molecules in the membrane, thus activating or deactivating the hydrolysis reaction of a precatalyst in the transducer for an encapsulated substrate, resulting in a light controllable output signal. This study represents the first example of using simplified synthetic molecules to simulate light signal transduction performed by complex biomolecules.

Here we demonstrate that a precise macroscopic supramolecular assembly (MSA) can be achieved using a surface photopatterning strategy. The electrostatic interaction of the photopatterned polyelectrolytes drives hydrogel cuboids to form a stable MSA on a millimeter scale and the spatial controllability of light enables the hydrogels to be assembled into complex supramolecular architectures.

Fluorescent RNAs (FRs), aptamers that bind and activate fluorescent dyes, have been used to image abundant cellular RNA species. However, limitations such as low brightness and limited availability of dye/aptamer combinations with different spectral characteristics have limited use of these tools in live mammalian cells and in vivo. Here, we develop Peppers, a series of monomeric, bright and stable FRs with a broad range of emission maxima spanning from cyan to red. Peppers allow simple and robust imaging of diverse RNA species in live cells with minimal perturbation of the target RNA's transcription, localization and translation. Quantification of the levels of proteins and their messenger RNAs in single cells suggests that translation is governed by normal enzyme kinetics but with marked heterogeneity. We further show that Peppers can be used for imaging genomic loci with CRISPR display, for real-time tracking of protein-RNA tethering, and for super-resolution imaging. We believe these FRs will be useful tools for live imaging of cellular RNAs.

On the basis of the complexity of the extracellular matrix, it is very important to control the three-dimensional (3D) biochemical and physical properties of hydrogels at the microscale level. In t...

The development of a moldable and removable gel technique for wound dressing is becoming highly desirable. Herein, we describe a facile method to generate an adaptable and dissolvable network of PEG-thiols and aldehyde groups in oxidized dextran. The dynamic covalent chemistry of the thiol-aldehyde addition reaction provides hydrogels with typical rheological behavior and thus endows the hydrogels with an excellent adaptability for the initial operation of wound coverage. Upon addition of free thiol compounds, the dynamic covalent cross-linked hydrogels will dissolve via thiol-hemithioacetal exchange reaction. The successful application as a temporary dressing for scalded wounds indicated the hydrogels had both adaptability and dissolvability based on the thiol-aldehyde addition reaction, which is significant for biomedical areas.

We exploit the thiol-aldehyde addition (TAA) reaction to build a dynamic covalent cross-linking (DCC) hydrogel in the physiological-pH environment. Due to the rapid and reversible TAA reaction, the resulting hydrogels are readily adapted for convenient manipulation, for example, free molding, easy injection, and self-healing. Meanwhile, the labile hemithioacetal bonds within the DCC hydrogel can convert to thermodynamically stable bonds via spontaneous thiol transfer reactions, thereby realizing poststabilization as needed. The successful application as a long-term scaffold for repair of barely self-healed bone defect indicated the hydrogels with both adaptability and mechanical stability based on thiol-aldehyde addition reaction is significant for biomedical areas.

Inspired by the natural phospholipid structures for cell membrane, a synthetic phospholipid LC with an ion recognition group benzo-18-crown-6 (B18C6) moiety was prepared which has been demonstrated to be able to transport ions across the lipid bilayers. Fluorescent vesicle assay shows that LC has an excellent transport activity, and the EC50 value for K+ is 11.2 μM. The voltage clamp measurement exhibits regular square-like current signals with considerably long opening times, which indicates that LC achieves efficient ion transport through a channel mechanism and its single channel conductivity is 17 pS. Both of the vesicle assay and patch clamp tests indicate that LC has selectivity for Rb+, whose ionic radius is larger than the cavity of crown ether. It suggests that the sandwich interaction may play a key role in the ion transport across lipid bilayers. All these results help us to speculate that LC transports ions via a channel mechanism with a tetrameric aggregate as the active structure. In addition, LC had obvious toxicity to HeLa cells, and the IC50 was 100.0 μM after coculture for 36 h. We hope that this simple synthetic phospholipid will offer novel perspectives in the development of more efficient and selective ion transporters.

Pulsing cellular dynamics in genetic circuits have been shown to provide critical capabilities to cells in stress response, signaling and development. Despite the fascinating discoveries made in the past few years, the mechanisms and functional capabilities of most pulsing systems remain unclear, and one of the critical challenges is the lack of a technology that allows pulsatile regulation of transgene expression both in vitro and in vivo. Here, we describe the development of a synthetic BRET-based transgene expression (LuminON) system based on a luminescent transcription factor, termed luminGAVPO, by fusing NanoLuc luciferase to the light-switchable transcription factor GAVPO. luminGAVPO allows pulsatile and quantitative activation of transgene expression via both chemogenetic and optogenetic approaches in mammalian cells and mice. Both the pulse amplitude and duration of transgene expression are highly tunable via adjustment of the amount of furimazine. We further demonstrated LuminON-mediated blood-glucose homeostasis in type 1 diabetic mice. We believe that the BRET-based LuminON system with the pulsatile dynamics of transgene expression provides a highly sensitive tool for precise manipulation in biological systems that has strong potential for application in diverse basic biological studies and gene- and cell-based precision therapies in the future., Pulsing cellular dynamics in genetic circuits have been shown to provide critical capabilities to cells in diverse cellular activities. Here the authors show a synthetic BRET-based transgene expression system that allows pulsatile and quantitative activation of gene expression both in live cells and in vivo.

“AND” logic responsive polyetherimide (PEI)-based polymers PENS were constituted by attaching the photoresponsive o-nitrobenzyl phototrigger and reductive responsive disulfide linker to the polymer PEI. This dual-responsive system maintained micelle-like assembly upon single photo or reductive stimuli. The disassembly only occurred when photo and reductive signals were input at the same time. This smart system was therefore applied as a carrier for the controlled release of the anti-cancer drug doxorubicin (DOX), which exhibited effective release only when UV irradiation and GSH reduction were applied simultaneously.

A novel in situ phototriggered-imine-crosslink (PIC) three-component biomimetic composite hydrogel, which was composed of hyaluronic acid (HA), gelatin, and hydroxyapatite nanoparticles (n-HAps), was successfully prepared in this study. o-Nitrobenzyl derivative NB was grafted to HA (HA-NB). Upon 365 nm light irradiation, o-nitrosobenzaldehydes were photo-generated and subsequently reacted with amino-bearing gelatin to build a hydrogel via imine ligation (HA-NB/gelatin/n-HAp). SEM showed that n-HAps could uniformly disperse in the HA-NB/gelatin hydrogel structure. Rheological analysis revealed that the composite hydrogel exhibited good light-sensitivity. The hydrogel was also biocompatible and demonstrated the ability to stimulate the osteogenesis of encapsulated hBMSCs attributed to n-HAps. Moreover, the osteogenic capacity was evaluated by means of applying the composite hydrogel in a critical-sized calvarial defect model of rats for 8 weeks. As indicated by micro-CT, sequential fluorescent labeling and histological analyses, newly formed bone was significantly enhanced in the composite hydrogel group. These data indicated that the phototriggered-imine-crosslink HA-NB/gelatin/n-HAp hydrogel can be used as a promising strategy for bone defect repair applications.

RNA-binding proteins (RBPs) play an essential role in regulating the function of RNAs in a cellular context, but our ability to control RBP activity in time and space is limited. Here, we describe the engineering of LicV, a photoswitchable RBP that binds to a specific RNA sequence in response to blue light irradiation. When fused to various RNA effectors, LicV allows for optogenetic control of RNA localization, splicing, translation and stability in cell culture. Furthermore, LicV-assisted CRISPR-Cas systems allow for efficient and tunable photoswitchable regulation of transcription and genomic locus labeling. These data demonstrate that the photoswitchable RBP LicV can serve as a programmable scaffold for the spatiotemporal control of synthetic RNA effectors.

Here we report the use of 2-nitrobenzyl alcohol (NB) as a photoreactive group with amine selectivity and explore its applications for photoaffinity labeling and crosslinking of biomolecules. This work confirms that NB is an efficient photoreactive group and has great potential in drug discovery, chemical biology and protein engineering.

In this study, we developed an injectable antibacterial hydrogel based on hyaluronic acid (HA) and chlorhexidine (CHX) for cardiovascular implantable electronic device (CIED) infection treatment. To balance stability and moldability, the HA scaffold was pre-crosslinked by 1,4-butanediol diglycidyl ether (BDDE) and then ground to form an HA microgel (CHA). Then, the antibacterial agent CHX was further crosslinked in the CHA microgel through electrostatic interactions between CHA and CHX to obtain hybrid crosslinked hydrogels (CHA/CHX). These hydrogels exhibited shear-thinning/self-recovery behavior, allowing easy injection into the CIED pocket and good matching with the pocket shape without extra space requirements, which represents an improvement on previously reported methods. In vitro and in vivo antibacterial tests showed that the CHA/CHX hydrogels had both good biocompatibility and very effective antibacterial action. The above results indicated that the CHA/CHX hydrogels would be an excellent candidate for CIED pocket infection treatment.

Unlike the traditional block amphiphilic polymersomes, we herein report a lipid-like amphiphilic polymer that self-assembles into photo-responsive polymersomes for drug delivery. The introduction of a quaternary ammonium moiety not only provides a hydrophilic segment of the polymersomes, but also enables electrostatic adsorption with folic acid, thus achieving the targeting of cancer cells with overexpression of folate receptor. Upon light irradiation, the photocleavage reaction of the o-nitrobenzyl moiety disintegrates polymersomes by changing the polymer structure from cationic amphiphilic state to zwitterionic hydrophilic state, thus realizing photo-triggered drug release. The data showed that anticancer drugs (doxorubicin hydrochloride, DOX·HCl) can be loaded into the hydrophilic cavity of polymersomes and controllably released by photo-induced disintegration of polymersomes. Cellular assay showed that the active targeting of folic acid and photo-triggered release endowed the DOX-loaded polymersomes with a higher cytotoxicity to HeLa cells. Such cationic polymersomes provide a novel strategy for designing effective and intelligent drug carriers, and have potential application as a novel integrated platform for targeted drug delivery.

Hydrogels have long been used for encapsulating stem cell-derived conditioned mediums to achieve skin regeneration after wounding. However, inappropriate mechanical strength, low adhesion and low elasticity limit their clinical application. To address these challenges, we engineered a hyaluronic acid-based hydrogel grafted with methacrylic anhydride and N-(2-aminoethyl)-4-[4-(hydroxymethyl)-2-methoxy-5-nitrophenoxy]-butanamide (NB) groups to encapsulate a lyophilized amnion-derived conditioned medium (AM-CM). This hydrogel can photopolymerize in situ within 3 s by photo-initiated free-radical crosslinking between methacrylate moieties. Meanwhile, the formed o-nitrosobenzaldehyde groups by photo-irradiation could covalently bond with the amino groups of tissue surface, which allowed strong tissue adhesion. Furthermore, the hydrogel possessed excellent mechanical properties, high elasticity, favorable biocompatibility and prolonged AM-CM release. Our further vitro and in vivo studies showed that the hydrogel significantly accelerated diabetic wound healing by regulating macrophage polarization and promoting angiogenesis. The engineered hydrogel with AM-CM release has high potential to treat chronic wounds in clinics.

Inspired by natural biomolecular machines, synthetic molecular-level machines have been proven to perform well-defined mechanical tasks and measurable work. To mimic the function of channel proteins, we herein report the development of a synthetic molecular shuttle, [2]rotaxane 3, as a unimolecular vehicle that can be inserted into lipid bilayers to perform passive ion transport through its stochastic shuttling motion. The [2]rotaxane molecular shuttle is composed of an amphiphilic molecular thread with three binding stations, which is interlocked in a macrocycle wheel component that tethers a K+ carrier. The structural characteristics enable the rotaxane to transport ions across the lipid bilayers, similar to a cable car, transporting K+ with an EC50 value of 1.0 μM (3.0 mol % relative to lipid). We expect that this simple molecular machine will provide new opportunities for developing more effective and selective ion transporters.

A new class of coumarin photocaging groups modified with an electron-rich styryl moiety at the 3-position was constructed. The large π-conjugated structure and stabilization of the carbocation intermediates by electron donors endowed the new photocaging groups with excellent long-wavelength absorption, large two-photon absorption cross-sections, and high uncaging quantum yields. Moreover, the new photocaging groups displayed unique photobleaching properties after photocleavage as a result of the intramolecular cyclization rearrangement of a carbocation intermediate to form five-membered ring byproducts and block the styryl conjugation at the 3-position. These superior properties of the new photocaging groups are extremely beneficial for high-concentration samples and thick specimens, thus extending the application of photocaging groups in many fields.

This work proposes a new method of transition metal and nonmetal partial cosubstitution for improving the dehydrogenation properties of magnesium borohydride that has a high hydrogen capacity of 14...