Covalent organic frameworks (COFs) as drug-delivery carriers have been mostly evaluated in vitro due to the lack of COFs nanocarriers that are suitable for in vivo studies. Here we develop a series ...of water-dispersible polymer-COF nanocomposites through the assembly of polyethylene-glycol-modified monofunctional curcumin derivatives (PEG-CCM) and amine-functionalized COFs (APTES-COF-1) for in vitro and in vivo drug delivery. The real-time fluorescence response shows efficient tracking of the COF-based materials upon cellular uptake and anticancer drug (doxorubicin (DOX)) release. Notably, in vitro and in vivo studies demonstrate that PEG-CCM@APTES-COF-1 is a smart carrier for drug delivery with superior stability, intrinsic biodegradability, high DOX loading capacity, strong and stable fluorescence, prolonged circulation time and improved drug accumulation in tumors. More intriguingly, PEG
-CCM@APTES-COF-1 presents an effective targeting strategy for brain research. We envisage that PEG-CCM@APTES-COF-1 nanocomposites represent a great promise toward the development of a multifunctional platform for cancer-targeted in vivo drug delivery.
The poor prognosis of esophageal squamous cell carcinoma (ESCC) highlights the need for novel strategies against this disease. Our previous study suggested the involvement of CCL2 and tumor ...associated macrophages (TAMs) in esophageal carcinogenesis. Despite the recognition of TAMs as a promising target for cancer treatment, mechanisms underlying its infiltration, activation and tumor-promotive function in ESCC remain unknown.
Human esophageal tissue array and TCGA database were used to evaluate the clinical relevance of CCL2 and TAMs in ESCC. F344 rats and C57BL/6 mice were treated with N-nitrosomethylbenzylamine (NMBA) to establish orthotopic models of esophageal carcinogenesis. CCL2/CCR2 gene knockout mice and macrophage-specific PPARG gene knockout mice were respectively used to investigate the role of infiltration and polarization of TAMs in ESCC. CCL2-mediated monocyte chemotaxis was estimated in malignantly transformed Het-1A cells. THP-1 cells were used to simulate TAMs polarization in vitro. RNA-sequencing was performed to uncover the mechanism.
Increasing expression of CCL2 correlated with TAMs accumulation in esophageal carcinogenesis, and they both predicts poor prognosis in ESCC cohort. Animal studies show blockade of CCL2-CCR2 axis strongly reduces tumor incidence by hindering TAMs recruitment and thereby potentiates the antitumor efficacy of CD8
T cells in the tumor microenvironment. More importantly, M2 polarization increases PD-L2 expression in TAMs, resulting in immune evasion and tumor promotion through PD-1 signaling pathway.
This study highlights the role of CCL2-CCR2 axis in esophageal carcinogenesis. Our findings provide new insight into the mechanism of immune evasion mediated by TAMs in ESCC, suggesting the potential of TAMs-targeted strategies for ESCC prevention and immunotherapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite the growing research interest in highly bio-compatible carbon quantum dots (CQDs) for bioimaging, the synthesis of red-emitting CQDs with high photoluminescence efficiency and a sharp ...emission spectrum remains a formidable challenge in this field. Herein, we established a rational strategy for the synthesis of highly efficient ultra-narrow red-emitting CQDs by adopting a conjugated aromatic amine precursor (tris(4-aminophenyl)amine, TAPA) and introducing oxidative radical reagents. The resultant CQDs, T-CQDs featured red PL (615 ± 2 nm) with a high photoluminescence quantum yield (84 ± 5%) and a narrow emission linewidth (FWHM = 27 ± 1 nm), which together represented one of the highest levels in the field of CQDs so far. The T-CQDs were then further analyzed from the spectral and structural aspects, and the repeatability and universality of this strategy have also been discussed. Finally, the T-CQDs were successfully applied for both one-photon imaging and two-photon imaging with various bio-samples, both
in vitro
and
in vivo
.
Ultra-narrow red-emitting carbon quantum dots with a high PLQY are rationally synthesized for NIR-II triggered two-photon bioimaging.
The long application life and stable performance of stretchable electronics have been putting forward requirements for both higher mechanical properties and better self‐healing ability of polymeric ...substrates. However, for self‐healing materials, simultaneously improving stretchability and robustness is still challenging. Here, by incorporating sliding crosslinker (polyrotaxanes) and hydrogen bonds into a polymer, a highly stretchable and self‐healable elastomer with good mechanical strength is achieved. The elastomer exhibits very high stretchability, such that it can be stretched to 2800% with a fracture strength of 1.05 MPa. Moreover, the elastomer can achieve nearly complete self‐healing (93%) at 55 °C. Next, tensile tests under different temperatures, step extension experiments, and in situ small angle X‐ray scattering confirm that the excellent stretchability is attributed to the combined effects of sliding cyclodextrins along guest chains and hydrogen bonds. Furthermore, a strain sensor by coating the single‐wall carbon nanotubes onto the surface of the elastic substrate is fabricated.
A new strategy, by incorporating sliding crosslinks and hydrogen bonds into a polymer to achieve a highly stretchable and self‐healable elastomer with good mechanical strength, is reported in this work.
Early stage exposure of foodborne substances, such as brightening agent titanium dioxide nanoparticles (TiO2 NPs), can cause long-term effects in adulthood. We aimed to explore the potential adverse ...effect of long-term dietary intake of TiO2 NPs. After feeding for 2–3 months from weaning, TiO2 NPs-exposed mice showed lower body weight and induced intestinal inflammation. However, this phenomenon was not observed in gut microbiota-removed mice. TiO2 NPs exposure rarely affected the diversity of microbial communities, but significantly decreased the abundance of several probiotic taxa including Bifidobacterium and Lactobacillus. Additionally, TiO2 NPs aggravated DSS-induced chronic colitis and immune response in vivo, and reduced the population of CD4+T cells, regulatory T cells, and macrophages in mesenteric lymph nodes. Therefore, dietary TiO2 NPs could interfere with the balance of immune system and dynamic of gut microbiome, which may result in low-grade intestinal inflammation and aggravated immunological response to external stimulus, thus introducing potential health risk.
Stretchable electrodes are playing important roles in the measurement of bio‐electrical signals especially in wearable electronic devices. These electrodes usually adopt commercial elastomers such as ...polydimethylsiloxane or polystyrene‐ethylene‐butylene‐styrene as substrates, which result in poor stability and reliability due to weak interfacial adhesion between electrodes and human skin. Here, dopamine is introduced into the hydrogen bonding based elastomer as pendent groups. The elastomer shows both mechanical strength and adhesion strength at the same time. It exhibits high stress at break (1.9 MPa) and high fracture strain (5100%). Significantly, it exhibits a high adhesive strength (≈62 kPa) and underwater adhesive strength (≈16 kPa) with epithelial tissue. Thus, a stretchable bio‐interfacial electrode is fabricated by spray‐coating silver nanowires on the elastic substrate, which is stretchable, self‐healable, and highly adhesive and suitable for electromyogram measurement.
Dopamine and hydrogen bonding are introduced into a polymer to realize a highly adhesive and self‐healing elastomer. Based on the elastomer, a bio‐interfacial electrode is fabricated for electromyography tests.
In this paper, we reported for the first time that Au(III) decorated carbon dot cluster (Au(III)/CDC) was synthesized to detect glutathione through fluorescence "off-on" approach. The "off" process ...was realized by the introduction of Au(III) on luminescent carbon dots (CDs), which formed the complex of Au(III)/CDC and quenched the fluorescence of CDs efficiently. This "off" process was used to detect Au(III) with the selectivity among 21 metal ions and the limitation was 0.48 μM (S/N=3). Au(III) could be removed from the complex by biothiol in the solution, which restored the fluorescence of CDC to achieve the "on" process. This process was selective for biothiols (especially for glutathione) among saccharides, dopamine and amino acids and the limit of detection was 2.02 μM (S/N=3). Due to the dependence of the fluorescence restoration on the concentration of glutathione, Au(III)/CDC was applied as the fluorescence sensor for detection of glutathione in the solution and cellular cytosol. By referring to the fluorescence change in the solution, the intracellular glutathione with/without oxygen stress was evaluated. As compared with the commercial assay, our Au(III)/CDC based assay was simple, facile and low cost, which would be useful to measure intracellular glutathione at different cellular states.
Adopting self‐healing, robust, and stretchable materials is a promising method to enable next‐generation wearable electronic devices, touch screens, and soft robotics. Both elasticity and ...self‐healing are important qualities for substrate materials as they comprise the majority of device components. However, most autonomous self‐healing materials reported to date have poor elastic properties, i.e., they possess only modest mechanical strength and recoverability. Here, a substrate material designed is reported based on a combination of dynamic metal‐coordinated bonds (β‐diketone–europium interaction) and hydrogen bonds together in a multiphase separated network. Importantly, this material is able to undergo self‐healing and exhibits excellent elasticity. The polymer network forms a microphase‐separated structure and exhibits a high stress at break (≈1.8 MPa) and high fracture strain (≈900%). Additionally, it is observed that the substrate can achieve up to 98% self‐healing efficiency after 48 h at 25 °C, without the need of any external stimuli. A stretchable and self‐healable dielectric layer is fabricated with a dual‐dynamic bonding polymer system and self‐healable conductive layers are created using polymer as a matrix for a silver composite. These materials are employed to prepare capacitive sensors to demonstrate a stretchable and self‐healable touch pad.
Dynamic metal‐coordinated bonds (β‐diketone–europium interaction) and hydrogen bonds, are combined in a multiphase separated network, in a new strategy to enable a robust and elastic capacitive sensor with autonomous self‐healing properties.
Macrophage polarization is mainly steered by metabolic reprogramming in the tissue microenvironment, thus leading to distinct outcomes of various diseases. However, the role of lipid metabolism in ...the regulation of macrophage alternative activation is incompletely understood. Using human THP-1 and mouse bone marrow derived macrophage polarization models, we revealed a pivotal role for arachidonic acid metabolism in determining the phenotype of M2 macrophages. We demonstrated that macrophage M2 polarization was inhibited by arachidonic acid, but inversely facilitated by its derived metabolite prostaglandin E2 (PGE2). Furthermore, PPARγ bridges these two seemingly unrelated processes
via
modulating oxidative phosphorylation (OXPHOS). Through inhibiting PPARγ, PGE2 enhanced OXPHOS, resulting in the alternative activation of macrophages, which was counterweighted by the activation of PPARγ. This connection between PGE2 biosynthesis and macrophage M2 polarization also existed in human and mouse esophageal squamous cell carcinoma. Our results highlight the critical role of arachidonic acid and metabolic PGE2 as immune regulators in modulating tissue homeostasis and pathological process.
Atomically dispersed Co-N-C materials represent the promising alternatives to precious metal-based catalysts for oxygen reduction reactions (ORR), due to the abundance and low cost of their ...constituent elements with maximized atom utilization. However, boosting their performances by modulating the active site structure still remains a challenge. Herein we have reported a pyrolysis-free synthetic method to prepare a new ORR catalyst with Co-N5 active sites by using nitrogen-functionalized reduced graphene oxide to anchor Co-Porphyrin molecules and provide the axial ligand for the cobalt center. The ORR half-wave potential of the obtained catalyst reached 0.908 V, and the maximum power density was significantly increased by 1.63 times compared with the catalyst with traditional Co-N4 active sites in alkaline polymer electrolyte fuel cells (APEFCs). Combined with density functional theory (DFT) calculations and electrochemical analysis, the results show that the electronic and geometric structure are remarkably changed after the Co 3d orbitals are rehybridized with the axially coordinated ligand orbitals, which greatly increases the rate of ORR. Importantly, in-situ Raman spectroscopy can dynamically track the conversion of Co-OH and Co-O species, further revealing that Co-N5 is the active site and electron localization strategy induced by axial Co-N coordination can enhance the O2 adsorption and activation, thus boosting ORR performance. Therefore, our research provides an atomic-level insight into the relationship between the electronic structure of the active center and the ORR performance and guidance for the rational design of high-efficiency electrocatalysts.
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•Axial coordinated CoN5 structures were prepared via a pyrolysis-free synthetic method.•Power density using CoN5 MEA exhibits a 1.63 times increment compared with the traditional CoN4 MEA.•In-situ Raman spectroscopy can dynamically track the conversion of Co-OH and Co-O species, further revealing that Co-N5 were the active sites.
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