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Intrinsically stretchable bioelectronic devices based on soft and conducting organic materials have been regarded as the ideal interface for seamless and biocompatible integration with the human body. A remaining challenge is to combine high mechanical robustness with good electrical conduction, especially when patterned at small feature sizes. We develop a molecular engineering strategy based on a topological supramolecular network, which allows for the decoupling of competing effects from multiple molecular building blocks to meet complex requirements. We obtained simultaneously high conductivity and crack-onset strain in a physiological environment, with direct photopatternability down to the cellular scale. We further collected stable electromyography signals on soft and malleable octopus and performed localized neuromodulation down to single-nucleus precision for controlling organ-specific activities through the delicate brainstem.

Multicellular biological systems, most notably living neural networks, exhibit highly complex physical organization properties that pose challenges for building cell-specific and biocompatible interfaces. We developed a novel approach to genetically program cells to chemically assemble artificial structures that modify the electrical properties of neuronsin situ, opening up the possibility of minimally-invasive cell-specific interfaces with neural circuits in living animals. However, the efficiency and biocompatibility of this approach were challenged by limited membrane targeting of the constructed material. Here, we report a method with significantly improved molecular construct properties, which expresses highly localized enzymes targeted to the plasma membrane of primary neurons with minimal intracellular retention. Polymers synthesizedin situby this approach form dense clusters on the targeted cell membrane, and neurons remain viable after polymerization. This platform can be readily extended to incorporate a broad range of materials onto the surface membranes of specific cells within complex tissues, using chemistry that may further enable the next generation of interfaces with living biological systems.

Intrinsically stretchable bioelectronic devices based on soft and conducting organic materials have been regarded as the ideal interface for seamless and biocompatible integration with the human body. However, the grand challenge remains for the conducting polymer to possess both high mechanical ductility and good electrical conduction at cellular level feature sizes. This longstanding material limitation in organic bioelectronics has impeded the full exploitation of its unique benefits. Here, we introduce a new molecular engineering strategy based on rationally designed topological supramolecular networks, which allows effective decoupling of competing effects from multiple molecular building blocks to meet complex requirements. We achieve two orders of magnitude improvement in the conductivity under 100% strain in physiological environment, along with the capability for direct photopatterning down to 2 μm. These unprecedented capabilities allow us to realize previously inaccessible bioelectronic applications including high-resolution monitoring of ‘soft and malleable’ creatures, e.g., octopus, and localized neuromodulation down to single nucleus precision for controlling organ-specific activities through delicate tissues, e.g., brainstem.

Exercise confers protection against obesity, type 2 diabetes and other cardiometabolic diseases1-5. However, the molecular and cellular mechanisms that mediate the metabolic benefits of physical activity remain unclear6. Here we show that exercise stimulates the production of N-lactoyl-phenylalanine (Lac-Phe), a blood-borne signalling metabolite that suppresses feeding and obesity. The biosynthesis of Lac-Phe from lactate and phenylalanineoccurs in CNDP2+ cells, including macrophages,monocytes and otherimmune and epithelial cells localized to diverse organs. In diet-induced obese mice, pharmacological-mediated increases in Lac-Phe reduces food intake without affecting movement or energy expenditure. Chronic administration of Lac-Phe decreases adiposity and body weight and improves glucose homeostasis. Conversely, genetic ablation of Lac-Phe biosynthesis in mice increases food intake and obesity following exercise training. Last, large activity-inducible increases in circulating Lac-Phe are alsoobserved in humans and racehorses, establishing this metabolite as a molecular effector associated with physical activity across multiple activity modalities and mammalian species. These data define a conserved exercise-inducible metabolite that controls food intake and influences systemic energy balance.

The 4-quinolones and their analogs are a heterogeneous group of biologically active compounds that have evolved in modern days to provide utilities at the forefront of antibiotic research. They have been used to combat Gram-negative or Gram-positive bacteria, suppress tumor growth, and treat many serious infections. These antimicrobial agents have also been used to promote apoptosis and DNA repair for the treatment of cancer. This review summarizes the experimental progress made in the synthetic development of various catalytic routes to preparing 4-quinolones and their analogs; discusses our current understanding of the reaction mechanisms involving biocatalytic synthesis, general catalytic synthesis, and asymmetric synthesis; and finally presents the future prospects of the emerging field.

Nanocomposites are emerging complex nanoscale materials composed of different phases that have received considerable attention as a result of their widespread impact on a myriad of fields. Having said this, it is important to recognize that poor colloidal stabilities in physiological media and non-specific interactions with biology are key limitations prohibiting their successful translation into the development of practical technologies with real impact. Herein, PAA coated Au/Fe

Spatial and temporal distributions of metal ions in vitro and in vivo are crucial in our understanding of the roles of metal ions in biological systems, and yet there is a very limited number of methods to probe metal ions with high space and time resolution, especially in vivo. To overcome this limitation, we report a Zn(2+)-specific near infrared (NIR) DNAzyme nanoprobe for real-time metal ion tracking with spatiotemporal control in early embryos and larvae of zebrafish. By conjugating photocaged DNAzymes onto lanthanide-doped upconversion nanoparticles (UCNPs), we have achieved upconversion of a deep tissue penetrating NIR 980 nm light into 365 nm emission. The UV photon then efficiently photo-decages a substrate strand containing a nitrobenzyl group at the 2’-OH of adenosine ribonucleotide, allowing enzymatic cleavage by a complementary DNA strand containing a Zn(2+)-selective DNAzyme. The product containing a visible FAM fluorophore that is initially quenched by BHQ1 and Dabcyl quenchers, is released after cleavage, resulting in higher fluorescent signals. The DNAzyme-UCNP probe enables Zn(2+) sensing by exciting in the NIR biological imaging window in both living cells and zebrafish embryos, and detecting in the visible region. This report introduces a platform that can be used to understand the Zn(2+) distribution with spatiotemporal control, thereby giving insights into the dynamical Zn(2+) ion distribution in intracellular and in vivo models.

The on-site and real-time detection of metal ions is important for environmental monitoring and for understanding the impact of metal ions on human health. However, developing sensors selective for a wide range of metal ions that can work in the complex matrices of untreated samples and cells presents significant challenges. To meet these challenges, DNAzymes, an emerging class of metal ion-dependent enzymes selective for almost any metal ion, have been functionalized with fluorophores, nanoparticles and other imaging agents and incorporated into sensors for the detection of metal ions in environmental samples and for imaging the metal ions in living cells. Herein, we highlight the recent developments of DNAzyme-based fluorescent, colorimetric, SERS, electrochemical and electrochemiluminscent sensors for metal ions for these applications.

DNA-modified particles are used extensively for applications in sensing, material science, and molecular biology. The performance of such DNA-modified particles is greatly dependent on the degree of surface coverage, but existing methods for quantitation can only be employed for certain particle compositions and/or conjugation chemistries. We have developed a simple and broadly applicable exonuclease III (Exo III) digestion assay based on the cleavage of phosphodiester bonds—a universal feature of DNA-modified particles—to accurately quantify DNA probe surface coverage on diverse, commonly used particles of different compositions, conjugation chemistries, and sizes. Our assay utilizes particle-conjugated, fluorophore-labeled probes that incorporate two abasic sites; these probes are hybridized to a complementary DNA (cDNA) strand, and quantitation is achieved via cleavage and digestion of surface-bound probe DNA via Exo III’s apurinic endonucleolytic and exonucleolytic activities. The presence of the two abasic sites in the probe greatly speeds up the enzymatic reaction without altering the packing density of the probes on the particles. Probe digestion releases a signal-generating fluorophore and liberates the intact cDNA strand to start a new cycle of hybridization and digestion, until all fluorophore tags have been released. Since the molar ratio of fluorophore to immobilized DNA is 1:1, DNA surface coverage can be determined accurately based on the complete release of fluorophores. Our method delivers accurate, rapid, and reproducible quantitation of thiolated DNA on the surface of gold nanoparticles, and also performs equally well with other conjugation chemistries, substrates, and particle sizes, and thus offers a broadly useful assay for quantitation of DNA surface coverage.

Nanocomposites are emerging complex nanoscale materials composed of different phases that have received considerable attention as a result of their widespread impact on a myriad of fields. Having said this, it is important to recognize that poor colloidal stabilities in physiological media and non-specific interactions with biology are key limitations prohibiting their successful translation into the development of practical technologies with real impact. Herein, PAA coated Au/Fe3O4 composite magnetic nanoparticles (NPs) with monodispersity and high biostability were engineered for the development of a highly sensitive C-reactive protein (CRP) chemiluminescence immunoassay (CLIA), based on the horseradish peroxidase (HRP)–luminol–H2O2 system. In addition, zwitterionic glycerophosphoryl choline (GPC) was employed as a co-blocking agent to reduce the nonspecific adsorption. This assay reports a limit of detection (LOD) of 2.5 pM with high reproducibility verified clinically and demonstrating improved progress towards translation into clinics.

Next-generation SERS-active dealloyed particles with intra-nanogaps might empower and drive the translation of SERS techniques into the clinics.

The discovery and elucidation of genetic codes has profoundly changed not only biology but also many fields of science and engineering. The fundamental building blocks of life comprises of four simple deoxyribonucleotides and yet their combinations serve as the carrier of genetic information that encodes for proteins that can carry out many biological functions due to their unique functionalities. Inspired by nature, the functionalities of DNA molecules have been used as a capping ligand for controlling morphology of nanomaterials, and such a control is sequence dependent, which translates into distinct physical and chemical properties of resulting nanoparticles. Herein, an overview on the use of DNA as engineered codes for controlling the morphology of metal nanoparticles, such as gold, silver, and Pd-Au bimetallic nanoparticles is provided. Fundamental insights into rules governing DNA controlled growth mechanisms are also summarized, based on understanding of the affinity of the DNA nucleobases to various metals, the effect of combination of nucleobases, functional modification of DNA, the secondary structures of DNA, and the properties of the seed employed. The resulting physical and chemical properties of these DNA encoded nanomaterials are also reviewed, while perspectives into the future directions of DNA-mediated nanoparticle synthesis are provided.

Lanthanide-doped upconversion nanoparticles enable anti-Stokes emission via nonlinear processes, where low-energy excitation photons in the near-infrared window can be upconverted into high-energy emission ones in the visible or ultraviolet regions. The past decade has seen great success in the high-quality synthesis of upconversion nanoparticles with controlled structure, crystalline phase, size, and shape. The unique capacity of upconversion nanocrystals to undertake near-infrared excitation, amalgamated with their excellent luminescent characteristics, such as massive anti-Stokes spectral shift, sharp emission band, multicolor emission, and long luminescence lifetime, makes these nanomaterials prime candidates for a plethora of applications. Herein, we review the field of upconversion nanoparticles from the perspectives of fundamental luminescence mechanisms, new synthetic routes, and current practical approaches to tuning emission color and enhancing upconversion efficiency. In particular, we highlight the recent advances in utilizing upconversion nanocrystals for bioimaging, therapy, biosensing, neuroscience, super-resolution imaging, photoswitching, and lasing applications. We also discuss the key challenges and issues that are critical for the further implementation of upconversion nanoparticles in diverse settings.