M1 macrophage accumulation and excessive inflammation are commonly encountered issues in diabetic wounds and can fail in the healing process. Hence, hydrogel dressings with immunoregulatory capacity have great promise in the clinical practice of diabetic wound healing. However, current immunoregulatory hydrogels are always needed for complex interventions and high‐cost treatments, such as cytokines and cell therapies. In this study, a novel glycyrrhizic acid (GA)‐based hybrid hydrogel dressing with intrinsic immunoregulatory properties is developed to promote rapid diabetic wound healing. This hybrid hydrogel consists of interpenetrating polymer networks composed of inorganic Zn2+‐induced self‐assembled GA and photo‐crosslinked methyl acrylated silk fibroin (SF), realizing both excellent injectability and mechanical strength. Notably, the SF/GA/Zn hybrid hydrogel can regulate macrophage responses in the inflammatory microenvironment, circumventing the use of any additives. The immunomodulatory properties of the hydrogel can be harnessed for safe and efficient therapeutics that accelerate the three phases of wound repair and serve as a promising dressing for the management of diabetic wounds.

Immunoregulation in Diabetic Wound Repair with a Photoenhanced Glycyrrhizic Acid Hydrogel Scaffold

Polyamines in cancer: integrating organismal metabolism and antitumour immunity

Near-infrared (NIR) fluorescence imaging has improved imaging depth relative to conventional fluorescence imaging in the visible region, demonstrating great potential in both fundamental biomedical research and clinical practice. To improve the detection specificity, NIR fluorescence imaging probes have been under extensive development. This review summarizes the particular application of optical imaging probes with the NIR-I window (700–900 nm) or the NIR-II window (1000–1700 nm) emission for diagnosis of nephron-urological diseases. These molecular probes have enabled contrast-enhanced imaging of anatomical structures and physiological function as well as molecular imaging and early diagnosis of acute kidney injury, iatrogenic ureteral injury and bladder cancer. The design strategies of molecular probes are specifically elaborated along with representative imaging applications. The potential challenges and perspectives in this field are also discussed.

/pdf/near-infrared-fluorescent-molecular-probes-for-imaging-and-rf3ml8q0a5.pdf

Near-infrared fluorescent molecular probes for imaging and diagnosis of nephro-urological diseases

Live cell discrimination is the first and essential step to understand complex biosystems. Conventional cell discrimination involving various antibodies relies on selective surface biomarkers. Compared to antibodies, the fluorescent probe strategy allows the utilisation of intracellular biomarkers, providing broader options with unique chemical principles to achieve the live cell distinction. In general, fluorescent probes can be retained in cells by interacting with biomolecules, accumulating via transporters, and participating in metabolism. Based on the target difference, fluorescent probe strategy can be divided into several categories: protein-oriented live cell distinction (POLD), carbohydrate-oriented live cell distinction (COLD), DNA-oriented live cell distinction (DOLD), gating-oriented live cell distinction (GOLD), metabolism-oriented live cell distinction (MOLD) and lipid-oriented live cell distinction (LOLD). In this review, we will outline the concepts and mechanisms of different strategies, introduce their applications in cell-type discrimination, and discuss their advantages and challenges in this area. We expect this tutorial will provide a new perspective on the mechanisms of fluorescent probe strategy and facilitate the development of cell-type-specific probes.

Fluorescent probe strategy for live cell distinction.

Spatially resolved in vivo imaging of inflammation-associated mRNA via enzymatic fluorescence amplification in a molecular beacon

Activated macrophages have the potential to be ideal targets for imaging inflammation. However, probe selectivity over non-activated macrophages and probe delivery to target tissue have been challenging. Here, we report a small molecule probe specific for activated macrophages, called CDg16, and demonstrate its application to visualizing inflammatory atherosclerotic plaques in vivo. Through a systematic transporter screen using a CRISPR activation library, we identify the orphan transporter Slc18b1/SLC18B1 as the gating target of CDg16.

/pdf/imaging-inflammation-using-an-activated-macrophage-probe-41lp3n0uhu.pdf

Imaging inflammation using an activated macrophage probe with Slc18b1 as the activation-selective gating target.

Microglia, the brain-resident macrophage, are involved in brain development and contribute to the progression of neural disorders. Despite the importance of microglia, imaging of live microglia at a cellular resolution has been limited to transgenic mice. Efforts have therefore been dedicated to developing new methods for microglia detection and imaging. Using a thorough structure-activity relationships study, we developed CDr20, a high-performance fluorogenic chemical probe that enables the visualization of microglia both in vitro and in vivo. Using a genome-scale CRISPR-Cas9 knockout screen, the UDP-glucuronosyltransferase Ugt1a7c was identified as the target of CDr20. The glucuronidation of CDr20 by Ugt1a7c in microglia produces fluorescence.

Visualizing Microglia with a Fluorescence Turn-On Ugt1a7c Substrate.

Self-Cleaving Protein Linkers with Modulated Ph-Responsiveness: A New Platform for Selective Control of Protein Drug Function

Virus-templated redox nanowire network for enzyme electrode.

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Imaging inflammation using an activated macrophage probe with Slc18b1 as the activation-selective gating target.

Visualizing Microglia with a Fluorescence Turn-On Ugt1a7c Substrate.

Self-Cleaving Protein Linkers with Modulated Ph-Responsiveness: A New Platform for Selective Control of Protein Drug Function

Virus-templated redox nanowire network for enzyme electrode.