Conductive, stretchable, environmentally‐friendly, and strain‐sensitive elastomers are attracting immense research interest because of their potential applications in various areas, such as ...human–machine interfaces, healthcare monitoring, and soft robots. Herein, a binary networked elastomer is reported based on a composite hydrogel of polyvinyl alcohol (PVA) and polyethyleneimine (PEI), which is demonstrated to be ultrastretchable, mechanically robust, biosafe, and antibacterial. The mechanical stretchability and toughness of the hydrogels are optimized by tuning the constituent ratio and water content. The optimal hydrogel (PVA2PEI1‐75) displays an impressive tensile strain as high as 500% with a corresponding tensile stress of 0.6 MPa. Furthermore, the hydrogel elastomer is utilized to fabricate piezoresistive sensors. The as‐made strain sensor displays seductive capability to monitor and distinguish multifarious human motions with high accuracy and sensitivity, like facial expressions and vocal signals. Therefore, the elastomer reported in this study holds great potential for sensing applications in the era of the Internet of Things (IoTs).
A binary networked elastomer based on polyvinyl alcohol (PVA) and polyethyleneimine (PEI) exhibits ultrastretchable, mechanically robust, biosafety, and antibacterial properties. Through optimizing the constituent ratio and water content, the composite hydrogel displays seductive elasticity and is further used to monitor and distinguish multifarious human motions with high accuracy and sensitivity, like facial expressions and vocal signals.
The chemogenetic technology designer receptors exclusively activated by designer drugs (DREADDs) afford remotely reversible control of cellular signaling, neuronal activity and behavior. Although the ...combination of muscarinic-based DREADDs with clozapine-N-oxide (CNO) has been widely used, sluggish kinetics, metabolic liabilities and potential off-target effects of CNO represent areas for improvement. Here, we provide a new high-affinity and selective agonist deschloroclozapine (DCZ) for muscarinic-based DREADDs. Positron emission tomography revealed that DCZ selectively bound to and occupied DREADDs in both mice and monkeys. Systemic delivery of low doses of DCZ (1 or 3 μg per kg) enhanced neuronal activity via hM3Dq within minutes in mice and monkeys. Intramuscular injections of DCZ (100 μg per kg) reversibly induced spatial working memory deficits in monkeys expressing hM4Di in the prefrontal cortex. DCZ represents a potent, selective, metabolically stable and fast-acting DREADD agonist with utility in both mice and nonhuman primates for a variety of applications.
Abstract
The use of photothermal agents (PTAs) in cancer photothermal therapy (PTT) has shown promising results in clinical studies. The rapid degradation of PTAs may address safety concerns but ...usually limits the photothermal stability required for efficacious treatment. Conversely, PTAs with high photothermal stability usually degrade slowly. The solutions that address the balance between the high photothermal stability and rapid degradation of PTAs are rare. Here, we report that the inherent Cu
2+
-capturing ability of black phosphorus (BP) can accelerate the degradation of BP, while also enhancing photothermal stability. The incorporation of Cu
2+
into BP@Cu nanostructures further enables chemodynamic therapy (CDT)-enhanced PTT. Moreover, by employing
64
Cu
2+
, positron emission tomography (PET) imaging can be achieved for in vivo real-time and quantitative tracking. Therefore, our study not only introduces an “ideal” PTA that bypasses the limitations of PTAs, but also provides the proof-of-concept application of BP-based materials in PET-guided, CDT-enhanced combination cancer therapy.
Peptide-based materials that have diverse structures and functionalities are an important type of biomaterials. In former times, peptide-based nanomaterials with excellent stability were constructed ...through self-assembly. Compared with individual peptides, peptide-based self-assembly nanomaterials that form well-ordered superstructures possess many advantages such as good thermo- and mechanical stability, semiconductivity, piezoelectricity and optical properties. Moreover, due to their excellent biocompatibility and biological activity, peptide-based self-assembly nanomaterials have been vastly used in different fields. In this review, we provide the advances of peptide-based self-assembly nanostructures, focusing on the driving forces that dominate peptide self-assembly and assembly mechanisms of peptides. After that, we outline the synthesis and properties of peptide-based nanomaterials, followed by the applications of functional peptide nanomaterials. Finally, we provide perspectives on the challenges and future of peptide-based nanomaterials.
Peptide-based self-assembly nanomaterials possess many advantages. Based on their ability to self-assemble, peptide nanomaterials provide huge potential applications in biomedical and material technologies. The widespread applications of peptide nanomaterials can significantly affect our daily life in the future. Display omitted
•This review summarizes the advances of peptide-based nanomaterials, focusing on the mechanisms, properties, and applications.•Outlining the synthesis and properties of peptide nanomaterials is helpful for the relevant research fields.•The peptide-based nanomaterials show potential applications in many fields.
Antibacterial coating is rapidly emerging as a pivotal strategy for mitigating spread of bacterial pathogens. However, many challenges still need to be overcome in order to develop a smart coating ...that can achieve on‐demand antibacterial effects. In this study, a Staphylococcus aureus (S. aureus) sensitive peptide sequence is designed, and an antibiotic is then conjugated with this tailor‐made peptide. The antibiotic‐peptide conjugate is then linked to the surface of a titanium implant, where the peptide can be recognized and cleaved by an enzyme secreted by S. aureus. This allows for the release of antibiotics in the presence of S. aureus, thus achieving delivery of an antibacterial specifically when an infection occurs.
Tailor‐made peptide–vancomycin conjugate is linked to the surface of a titanium implant, where the peptide can be recognized and cleaved by an enzyme secreted by Staphylococcus aureus. This allows for the release of antibiotics in the presence of S. aureus, thus achieving delivery of an antibacterial specifically when an infection occurs.
•BNCT has more potential to effectively target multicentric deposits of tumors.•This review focuses on tumor-targeting boron delivery agents developed recently.•This review provides a summary and ...critical perspective of boron delivery agents.
Boron neutron capture therapy (BNCT) is a potential cancer radiotherapeutic modality, which takes advantage of the neutron capture response that occurs when boron (10B) is struck by low-energy thermal neutrons, triggering a nuclear fission reaction that ultimately causes cell death. Because the fatal radiation is restricted to approximately a single cell diameter, only cells with significant boron accumulation that are in the neutron field will be destroyed. Tumor-targeted 10B delivery agents are an essential component of BNCT. Currently, two low molecular weight boron-containing compounds, sodium mercaptoundecahydro-closo-dodecaborate (BSH) and borylphenylalanine (BPA), are mainly used in BNCT. Although both have suboptimal tumor selectivity, they have shown some therapeutic effect in patients with high-grade gliomas and several other kinds of tumors. In order to improve the efficacy of BNCT, significant effort has been devoted to developing new boron delivery agents that possess better uptake and favorable pharmacokinetic characteristics for clinical use. This review focuses on various boron delivery agents that have been developed over the past 40 years, including boron-containing amino acids, boron-containing compound conjugated-nucleosides, porphyrin derivatives, peptides, monoclonal antibodies, and different types of nanomaterials for 10B delivery. The principles underlying BNCT and the clinical trials with BNCT are briefly introduced in the first part of this review. In the second part, we provide a detailed overview of various boron delivery agents and discuss their merits and limitations. Additionally, the preclinical outcomes of these agents are included in this review and the most promising delivery agents are highlighted and compared. In summary, this article provides an overview of boron delivery agents, and critically analyzes their clinical prospects, from the view of medicinal chemists and nuclear medicine physicians.
The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is predominately localized to the outer mitochondrial membrane in steroidogenic cells. Brain TSPO ...expression is relatively low under physiological conditions, but is upregulated in response to glial cell activation. As the primary index of neuroinflammation, TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), major depressive disorder (MDD) and obsessive compulsive disorder (OCD). In this context, numerous TSPO-targeted positron emission tomography (PET) tracers have been developed. Among them, several radioligands have advanced to clinical research studies. In this review, we will overview the recent development of TSPO PET tracers, focusing on the radioligand design, radioisotope labeling, pharmacokinetics, and PET imaging evaluation. Additionally, we will consider current limitations, as well as translational potential for future application of TSPO radiopharmaceuticals. This review aims to not only present the challenges in current TSPO PET imaging, but to also provide a new perspective on TSPO targeted PET tracer discovery efforts. Addressing these challenges will facilitate the translation of TSPO in clinical studies of neuroinflammation associated with central nervous system diseases.
The 18 kDa translocator protein (TSPO) expression in the central nervous system is upregulated in response to glial cell activation. There is a great potential for the future application of TSPO radioligands as diagnostic and prognostic tools, as well as for assessing therapeutic interventions for neurologic diseases. Display omitted
The endocannabinoid system (ECS) is involved in a wide range of biological functions and comprises cannabinoid receptors and enzymes responsible for endocannabinoid synthesis and degradation. Over ...the past 2 decades, significant advances toward developing drugs and positron emission tomography (PET) tracers targeting different components of the ECS have been made. Herein, we summarized the recent development of PET tracers for imaging cannabinoid receptors 1 (CB1R) and 2 (CB2R) as well as the key enzymes monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), particularly focusing on PET neuroimaging applications. State-of-the-art PET tracers for the ECS will be reviewed including their chemical design, pharmacological properties, radiolabeling, as well as preclinical and human PET imaging. In addition, this review addresses the current challenges for ECS PET biomarker development and highlights the important role of PET ligands to study disease pathophysiology as well as to facilitate drug discovery.
Synaptic dysfunction provoking dysregulated cortical neural circuits is currently hypothesized as a key pathophysiological process underlying clinical manifestations in Alzheimer's disease and ...related neurodegenerative tauopathies. Here, we conducted PET along with postmortem assays to investigate time course changes of excitatory and inhibitory synaptic constituents in an rTg4510 mouse model of tauopathy, which develops tau pathologies leading to noticeable brain atrophy at 5-6 months of age. Both male and female mice were analyzed in this study. We observed that radiosignals derived from
Cflumazenil, a tracer for benzodiazepine receptor, in rTg4510 mice were significantly lower than the levels in nontransgenic littermates at 2-3 months of age. In contrast, retentions of (E)-
CABP688, a tracer for mGluR5, were unaltered relative to controls at 2 months of age but then gradually declined with aging in parallel with progressive brain atrophy. Biochemical and immunohistochemical assessment of postmortem brain tissues demonstrated that inhibitory, but not excitatory, synaptic constituents selectively diminished without overt loss of somas of GABAergic interneurons in the neocortex and hippocampus of rTg4510 mice at 2 months of age, which was concurrent with enhanced immunoreactivity of cFos, a well-characterized immediate early gene, suggesting that impaired inhibitory neurotransmission may cause hyperexcitability of cortical circuits. Our findings indicate that tau-induced disruption of the inhibitory synapse may be a critical trigger of progressive neurodegeneration, resulting in massive neuronal loss, and PET assessments of inhibitory versus excitatory synapses potentially offer
indices for hyperexcitability and excitotoxicity early in the etiologic pathway of neurodegenerative tauopathies.
In this study, we examined the in vivo status of excitatory and inhibitory synapses in the brain of the rTg4510 tauopathy mouse model by PET imaging with (E)-
CABP688 and
Cflumazenil, respectively. We identified inhibitory synapse as being significantly dysregulated before brain atrophy at 2 months of age, while excitatory synapse stayed relatively intact at this stage. In line with this observation, postmortem assessment of brain tissues demonstrated selective attenuation of inhibitory synaptic constituents accompanied by the upregulation of cFos before the formation of tau pathology in the forebrain at young ages. Our findings indicate that selective degeneration of inhibitory synapse with hyperexcitability in the cortical circuit constitutes the critical early pathophysiology of tauopathy.
Objective
Although astrocytic pathology is a pathological hallmark of progressive supranuclear palsy (PSP), its pathophysiological role remains unclear. This study aimed to assess astrocyte ...reactivity in vivo in patients with PSP. Furthermore, we investigated alterations in brain lactate levels and their relationship with astrocyte reactivity.
Methods
We included 30 patients with PSP‐Richardson syndrome and 30 healthy controls; in patients, tau deposition was confirmed through 18F‐florzolotau positron emission tomography. Myo‐inositol, an astroglial marker, and lactate were quantified in the anterior cingulate cortex through magnetic resonance spectroscopy. We measured plasma biomarkers, including glial fibrillary acidic protein as another astrocytic marker. The anterior cingulate cortex was histologically assessed in postmortem samples of another 3 patients with PSP with comparable disease durations.
Results
The levels of myo‐inositol and plasma glial fibrillary acidic protein were significantly higher in patients than those in healthy controls (p < 0.05); these increases were significantly associated with PSP rating scale and cognitive function scores (p < 0.05). The lactate level was high in patients, and correlated significantly with high myo‐inositol levels. Histological analysis of the anterior cingulate cortex in patients revealed reactive astrocytes, despite mild tau deposition, and no marked synaptic loss.
Interpretation
We discovered high levels of astrocyte biomarkers in patients with PSP, suggesting astrocyte reactivity. The association between myo‐inositol and lactate levels suggests a link between reactive astrocytes and brain energy metabolism changes. Our results indicate that astrocyte reactivity in the anterior cingulate cortex precedes pronounced tau pathology and neurodegenerative processes in that region, and affects brain function in PSP. ANN NEUROL 2024;96:247–261
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