Development of Diselenide-Containing Poly(β-amino ester)s for Potent mRNA Delivery to the Spleen.

Polymer-based nanocarriers hold promise for nucleic acid delivery, yet the clinical translation of mRNA polymeric carriers remains hindered by insufficient delivery efficiency and cytotoxicity. Here, we synthesized 180 diselenide-containing poly(β-amino ester)s (PBAEs) via Michael addition. In vitro screening identified PBAEs with superior mRNA delivery efficiency, showing that hydrophobic amine backbones with ionizable cationic amine end-capping are critical.

Enhanced mRNA delivery via incorporating hydrophobic amines into lipid nanoparticles.

Lipid nanoparticles (LNPs) have shown promising performance in mRNA delivery. Nevertheless, a thorough understanding of the relationship between mRNA delivery efficacy and the structure of LNPs remains imperative. In this study, we systematically investigated the effects of additional hydrophobic amines on the physicochemical properties of mRNA LNPs and their delivery efficacy.

Enhanced Pulmonary and Splenic mRNA Delivery Using DOTAP-Incorporated Poly(β-Amino Ester)-Lipid Nanoparticles.

mRNA-based therapies hold tremendous promise for treating various diseases, yet their clinical success is hindered by delivery challenges. This study developed a library of 140 lipocationic Poly(β-amino ester)s (PBAEs) and formulated lipid-polymer hybrid nanoparticles (LPHs) with four helper lipids, including 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), to enhance mRNA delivery. Initial screening of four representative PBAEs identified the D/P4-1 formulation (DOTAP/PBAE molar ratio of 4:1) as the most effective.

Alkaline Phosphatase-Instructed Peptide Assemblies for Imaging and Therapeutic Applications.

Self-assembly, a powerful strategy for constructing highly stable and well-ordered supramolecular structures, widely exists in nature and in living systems. Peptides are frequently used as building blocks in the self-assembly process due to their advantageous characteristics, such as ease of synthesis, tunable mechanical stability, good biosafety, and biodegradability. Among the initiators for peptide self-assembly, enzymes are excellent candidates for guiding this process under mild reaction conditions.

Peptide-based supramolecular hydrogels and their biotherapeutic applications.

In recent years, supramolecular hydrogels have made groundbreaking research progress in biomedical fields such as drug delivery, biosensing, imaging analysis, and tissue engineering. Peptides, with their unique characteristics of facile preparation, low immunogenicity and easy biodegradability, are commonly used as building blocks of supramolecular hydrogels. Peptide-based supramolecular hydrogels loaded with drugs, prepared physical means or covalent crosslinking, exhibit unique three-dimensional network structures and strong water retention capacities.

A bibliometric analysis of transcranial alternating current stimulation.

Background: Transcranial alternating current stimulation (tACS) can apply currents of varying intensity to the scalp, modulating cortical excitability and brain activity. tACS is a relatively new neuromodulation intervention that is now widely used in clinical practice. Many papers related to tACS have been published in various journals.

Bibliometric Analysis of Brain Stimulation Technologies in Sleep Disorders.

BACKGROUND Sleep disorders are a common disease faced by people today and can lead to fatigue, lack of concentration, impaired memory, and even death. In recent years, the development of brain stimulation techniques has provided a new perspective for the treatment of sleep disorders. However, there is a lack of bibliometric analyses related to sleep disorders and brain stimulation techniques.

Branched hydrophobic tails in lipid nanoparticles enhance mRNA delivery for cancer immunotherapy.

Efficient and safe delivery of vulnerable mRNA is a long-standing challenge for the broad application of the emerging mRNA-based therapeutics. Herein, a combinatorial library containing 119 novel lipids was constructed via sequential aza-Michael addition reactions of arylates and varying amines to tackle the ongoing challenge in mRNA delivery. Through in vitro screening of the lipid library on IGROV 1 cells, we identified several synthetic lipids with superior mRNA delivery efficacy.

Weak acid-initiated slow release of Dexamethasone from hydrogel to treat orbital inflammation.

Orbital inflammation is a prevalent and prolonged ocular disease that poses a significant challenge to clinicians. Glucocorticoid Dexamethasone sodium phosphate (Dex) has demonstrated efficacy in the clinical treatment of nonspecific orbital inflammation. However, frequent administration is required due to the short half-life of Dex, which may lead to drug waste and adverse side effects.

Intracellular Construction of Cathepsin B-Guided Gadolinium Nanoparticles for Enhanced T -Weighted MR Tumor Imaging.

Magnetic resonance imaging (MRI) is a superior and noninvasive imaging technique with unlimited tissue penetration depth and superb spatiotemporal resolution, however, using intracellular self-assembly of Gd-containing nanoparticles to enhance the T -weighted MR contrast of cancer cells in vivo for precise tumor MRI is rarely reported. The lysosomal cysteine protease cathepsin B (CTSB) is regarded as an attractive biomarker for the early diagnosis of cancers and metastasis. Herein, taking advantage of a biocompatible condensation reaction, a "smart" Gd-based CTSB-responsive small molecular contrast agent VC-Gd-CBT is developed, which can self-assemble into large intracellular Gd-containing nanoparticles by glutathione reduction and CTSB cleavage to enhance the T -weighted MR contrast of CTSB-overexpressing MDA-MB-231 cells at 9.

Quality of clinical practice guidelines relevant to rehabilitation of knee osteoarthritis: A systematic review.

Objective: This systematic review summarized the rehabilitation recommendations for treating and managing knee osteoarthritis (OA) in practice guidelines and evaluated their applicability and quality using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument.

Data Sources: PubMed, the Cochrane Library, EMBASE, CINAHL, PEDro, Guideline central, Guideline International Network and Agency for Healthcare Research and Quality (AHRQ) were used to search for relevant studies published between 1 January 2008 and 31 May 2022.

Methods: AGREE II was used to evaluate the included guidelines quality, SPSS 25.

V1-Cal hydrogelation enhances its effects on ventricular remodeling reduction and cardiac function improvement post myocardial infarction.

Myocardial infarction (MI) is a major cause of disability and mortality worldwide. A cell permeable peptide V1-Cal has shown remarkable therapeutic effects on ML However, using V1-Cal to improve long-term cardiac function after MI is presently limited by its short half-life. Herein, we co-assembled V1-Cal with a well-known hydrogelator Nap-Phe-Phe-Tyr (NapFFY) to obtain a new supramolecular hydrogel V1-Cal/NapFFY.

Structural Exploration of Polycationic Nanoparticles for siRNA Delivery.

RNA interference (RNAi) is a promising approach to the treatment of genetic diseases by the specific knockdown of target genes. Functional polymers are potential vehicles for the effective delivery of vulnerable small interfering RNA (siRNA), which is required for the broad application of RNAi-based therapeutics. The development of methods for the facile modulation of chemical structures of polymeric carriers and an elucidation of detailed delivery mechanisms remain important areas of research.

Functional Muscle Network in Post-stroke Patients during Quiet Standing.

The overall muscle activation of post-stroke patients during standing has not been well understood. Functional muscle network provides a tool to quantify the functional synchronization across a large number of muscles. In order to investigating the functional muscle network of stroke survivors during quiet standing, we recruited 8 post-stroke hemiplegic patients and required them to stand still for 30 s with eyes open and closed.

Lysosome-Targeted and Fluorescence-Turned "On" Cytotoxicity Induced by Alkaline Phosphatase-Triggered Self-Assembly.

Selectively inducing lysosomal membrane permeabilization (LMP) is a promising strategy for cancer therapy. But integrating alkaline phosphatase (ALP)-instructed self-assembly and lysosome-targeting to induce LMP for selective killing of cancer cells was not reported. Herein, a pyrene-peptide conjugate Py-Phe-Phe-Glu-Tyr(H PO )-Gly-lyso (Py-Yp-Lyso) is rationally designed and demonstrated for its lysosome-targeting cytotoxicity on cancer cells, together with its pyrene (Py) excimer fluorescence turning "on" at 480 nm.

Alkaline phosphatase-triggered self-assembly of near-infrared nanoparticles for the enhanced photoacoustic imaging of tumors.

In this chapter, we discuss the need for the development of enzyme-activatable probes in the field of tumor-targeted photoacoustic (PA) imaging, then we give a brief description of the innovation of designing alkaline phosphatase (ALP)-activatable probes for PA imaging. After that, we provide detailed protocols for the syntheses and characterizations of a near-infrared photoacoustic imaging probe, 1P, developed in our research group. With this tool, 1P could form nanoparticles 1-NPs under the catalysis of ALP and thus could be used to enhance PA imaging both in vitro and in vivo.

Bioluminescence Imaging of Urokinase-Type Plasminogen Activator Activity and in Tumors.

Urokinase-type plasminogen activator (uPA) is a cell-secreted serine protease and plays a significant role in numerous biological processes. Overexpression of uPA has been proved to be relevant to some malignant tumors as well as poor prognosis. However, bioluminescence (BL) probes for selectively sensing uPA activity have not been reported up to now.

A Golgi-Targeting and Dual-Color "Turn-On" Probe for Spatially Precise Imaging of Furin.

Development of fluorescence probes for highly accurate detection of cancer-related enzyme activity is important in early cancer diagnosis. Herein, we report a Golgi-targeting and dual-color "Turn-On" probe for imaging furin with high spatial precision. By integrating the principles of Förster resonance energy transfer and intramolecular charge transfer, the probe was designed to be non-fluorescent.

Sustained Release of Two Bioactive Factors from Supramolecular Hydrogel Promotes Periodontal Bone Regeneration.

Intact and stable bone reconstruction is ideal for the treatment of periodontal bone destruction but remains challenging. In research, biomaterials are used to encapsulate stem cells or bioactive factors for periodontal bone regeneration, but, to the best of our knowledge, using a supramolecular hydrogel to encapsulate bioactive factors for their sustained release in bone defect areas to promote periodontal bone regeneration has not been reported. Herein, we used a well-studied hydrogelator, NapFFY, to coassemble with SDF-1 and BMP-2 to prepare a supramolecular hydrogel, SDF-1/BMP-2/NapFFY.

Facile syntheses of conjugated polymers for photothermal tumour therapy.

Development of photothermal materials which are able to harness sunlight and convert it to thermal energy seems attractive. Besides carbon-based nanomaterials, conjugated polymers are emerging promising photothermal materials but their facile syntheses remain challenging. In this work, by modification of a CBT-Cys click condensation reaction and rational design of the starting materials, we facilely synthesize conjugated polymers poly-2-phenyl-benzobisthiazole (PPBBT) and its dihexyl derivative with good photothermal properties.

Alkaline Phosphatase-Triggered Self-Assembly of Near-Infrared Nanoparticles for the Enhanced Photoacoustic Imaging of Tumors.

Photoacoustic (PA) imaging is advantageous for the diagnosis of superficial cancer with high spatial resolution. However, to the best of our knowledge, using an alkaline phosphatase (ALP)-activatable probe for the enhanced PA imaging of tumors has not been reported. In this work, we rationally designed a NIR probe IR775-Phe-Phe-Tyr(HPO)-OH (1P) for PA imaging ALP activity in vitro and in tumor.

Tandem Enzymatic Self-Assembly and Slow Release of Dexamethasone Enhances Its Antihepatic Fibrosis Effect.

Many chronic liver diseases will advance to hepatic fibrosis and, if without timely intervention, liver cirrhosis or even hepatocellular carcinoma. Anti-inflammation could be a standard therapeutic strategy for hepatic fibrosis treatment, but a "smart" strategy of hepatic fibrosis-targeted, either self-assembly or slow release of an anti-inflammation drug ( e.g.

Fluorine substitution enhances the self-assembling ability of hydrogelators.

When supramolecular hydrogels are applied as tissue culture scaffolds, their mechanical strength and biocompatibility are the two most important factors that must be considered. However, systematic studies on the structure-mechanical property (or structure-cytotoxicity) relationship of hydrogels are rare. Herein, we rationally designed three hydrogelators and their corresponding phosphate precursors, and systematically studied their self-assembling ability and cytotoxicity.

Intracellular synthesis of d-aminoluciferin for bioluminescence generation.

d-Luciferin is the most widely used substrate for bioluminescence (BL) applications but its low chemical stability always affects its performance. Herein, we rationally designed two chemically stable precursor molecules CBT-d-cystine-CBT (d-1) and CBT-l-cystine-CBT (l-1), and subjected them to reduction-controlled condensation to form 1-oligomer and subsequent proteolysis to yield d-aminoluciferin for BL generation in cells and in vivo. We envision that our precursor molecules might serve as d-luciferin alternatives for a wide range of BL applications in the near future.