Background and Purpose
Increasing evidence suggests systemic inflammation‐caused skeletal muscle atrophy as a major clinical feature of cachexia. Triptolide obtained from Tripterygium wilfordii Hook ...F possesses potent anti‐inflammatory and immunosuppressive effects. The present study aims to evaluate the protective effects and molecular mechanisms of triptolide on inflammation‐induced skeletal muscle atrophy.
Experimental Approach
The effects of triptolide on skeletal muscle atrophy were investigated in LPS‐treated C2C12 myotubes and C57BL/6 mice. Protein expressions and mRNA levels were analysed by western blot and qPCR, respectively. Skeletal muscle mass, volume and strength were measured by histological analysis, micro‐CT and grip strength, respectively. Locomotor activity was measured using the open field test.
KEY RESULTS
Triptolide (10–100 fM) up‐regulated protein synthesis signals (IGF‐1/p‐IGF‐1R/IRS‐1/p‐Akt/p‐mTOR) and down‐regulated protein degradation signal atrogin‐1 in C2C12 myotubes. In LPS (100 ng·ml−1)‐treated C2C12 myotubes, triptolide up‐regulated MyHC, IGF‐1, p‐IGF‐1R, IRS‐1 and p‐Akt. Triptolide also down‐regulated ubiquitin‐proteasome molecules (n‐FoxO3a/atrogin‐1/MuRF1), proteasome activity, autophagy‐lysosomal molecules (LC3‐II/LC3‐I and Bnip3) and inflammatory mediators (NF‐κB, Cox‐2, NLRP3, IL‐1β and TNF‐α). However, AG1024, an IGF‐1R inhibitor, suppressed triptolide‐mediated effects on MyHC, myotube diameter, MuRF1 and p62 in LPS‐treated C2C12 myotubes. In LPS (1 mg·kg−1, i.p.)‐challenged mice, triptolide (5 and 20 μg·kg−1·day−1, i.p.) decreased plasma TNF‐α levels and it increased skeletal muscle volume, cross‐sectional area of myofibers, weights of the gastrocnemius and tibialis anterior muscles, forelimb grip strength and locomotion.
Conclusions and Implications
These findings reveal that triptolide prevented LPS‐induced inflammation and skeletal muscle atrophy and have implications for the discovery of novel agents for preventing muscle wasting.
We propose all‐dielectric metasurfaces that can be actively re‐configured using the phase‐change material Ge2Sb2Te5 (GST) alloy. With selectively controlled phase transitions on the composing GST ...elements, metasurfaces can be tailored to exhibit varied functionalities. Using phase‐change GST rod as the basic building block, we have modelled metamolecules with tunable optical response when phase change occurs on select constituent GST rods. Tunable gradient metasurfaces can be realized with variable supercell period consisting of different patterns of the GST rods in their amorphous and crystalline states. Simulation results indicate a range of functions can be delivered, including multilevel signal modulating, near‐field coupling of GST rods, and anomalous reflection angle controlling. This work opens up a new space in exploring active meta‐devices with broader applications that cannot be achieved in their passive counterparts with permanent properties once fabricated.
The all‐dielectric reconfigurable metasurfaces based on switchable phase‐change material Ge2Sb2Te5 with functional diversity for light modulation are shown. The tunability of EIT resonance on phase‐change metamolecule and the steering of gradient metasurface are demonstrated by selectively modifying the phase of selected constituent Ge2Sb2Te5 rods.
Photoluminescent gold nanodots (Au NDs) are prepared via etching and codeposition of hybridized ligands, an antimicrobial peptide (surfactin; SFT), and 1‐dodecanethiol (DT), on gold nanoparticles ...(≈3.2 nm). As‐prepared ultrasmall SFT/DT–Au NDs (size ≈2.5 nm) are a highly efficient antimicrobial agent. The photoluminescence properties and stability as well as the antimicrobial activity of SFT/DT–Au NDs are highly dependent on the density of SFT on Au NDs. Relative to SFT, SFT/DT–Au NDs exhibit greater antimicrobial activity, not only to nonmultidrug‐resistant bacteria but also to the multidrug‐resistant bacteria. The minimal inhibitory concentration values of SFT/DT–Au NDs are much lower (>80‐fold) than that of SFT. The antimicrobial activity of SFT/DT–Au NDs is mainly due to the synergistic effect of SFT and DT–Au NDs on the disruption of the bacterial membrane. In vitro cytotoxicity and hemolysis analyses have revealed superior biocompatibility of SFT/DT–Au NDs than that of SFT. Moreover, in vivo methicillin‐resistant S. aureus–infected wound healing studies in rats show faster healing, better epithelialization, and are more efficient in the production of collagen fibers when SFT/DT–Au NDs are used as a dressing material. This study suggests that the SFT/DT–Au NDs are a promising antimicrobial candidate for preclinical applications in treating wounds and skin infections.
Surfactin, an antimicrobial lipopeptide, when self‐assembled on photoluminescent gold nanodots (Au NDs) exhibits an >80‐fold improvement in its antimicrobial activity against multidrug‐resistant bacteria. Antibacterial wound‐healing assays further reveal that the surfactin–Au ND hybrid material is superior to that of surfactin alone on a bacteria‐infected flesh wound in rats.
MicroRNAs (miRNAs) are small non-coding RNA molecules capable of negatively regulating gene expression to control many cellular mechanisms. The miRTarBase database ...(http://mirtarbase.mbc.nctu.edu.tw/) provides the most current and comprehensive information of experimentally validated miRNA-target interactions. The database was launched in 2010 with data sources for >100 published studies in the identification of miRNA targets, molecular networks of miRNA targets and systems biology, and the current release (2013, version 4) includes significant expansions and enhancements over the initial release (2010, version 1). This article reports the current status of and recent improvements to the database, including (i) a 14-fold increase to miRNA-target interaction entries, (ii) a miRNA-target network, (iii) expression profile of miRNA and its target gene, (iv) miRNA target-associated diseases and (v) additional utilities including an upgrade reminder and an error reporting/user feedback system.
In this study, we investigated the antibacterial activity of silver-coated gold nanoparticles (Au-Ag NPs) immobilized on cellulose paper. Ag NPs are known to have strong antibacterial properties, ...while Au NPs are biocompatible and relatively simple to prepare. We made the Au-Ag NPs using a facile process called Ag enhancement, in which Au NPs serve as the nuclei for precipitation of a Ag coating, the thickness of which can be easily controlled by varying the ratio of the reactants. After synthesis, electron microscopy showed that the Au-Ag NPs displayed a core-shell structure, and that they could be successfully immobilized onto a cellulose membrane by heat treatment. We then investigated the antibacterial properties of this NP-coated cellulose paper against E. coli JM109. The inhibition rate, growth curve, and AATCC 100 activity test showed that cellulose paper coated with 15 nm Au-Ag NPs possessed excellent antibacterial activity against E. coli JM109. These results suggest that Au-Ag NPs immobilized on cellulose paper could be a valuable antibacterial technology for applications such as food packaging, clothing, wound dressings, and other personal care products.
Photocatalytic hydrogen evolution from natural seawater faces the severe challenges of abundant salts, which adsorb on the active sites and result in undesirable side reactions and photocatalyst ...poisoning. Herein, a series of main‐chain‐engineered discontinuously conjugated polymer (DCP) photocatalysts is presented with bifunctional crown ether (CE) structures for hydrogen evolution from seawater. The hydrophilic CE can significantly inhibit the aggregation of DCPs induced by salts. Meanwhile, cyclic CE can effectively adsorb cations to uncover the active sites to increase their interaction with protons, which can increase the hydrogen evolution rates and significantly reduce the efficiency roll‐off in natural seawater. Through atomistic studies, the formation of hydrogen bonds with bifunctional CE is elucidated and further analysis of the microscale mechanisms is also conducted using molecular dynamics and ab initio techniques. This work suggests that CE‐based polymer has the potential to enhance its ability to produce hydrogen through photocatalysis using seawater.
The first example of incorporating crown ether structure into polymer photocatalysts is demonstrated via a main‐chain‐engineering strategy. The innovative approach significantly reduces ion adsorption on the active sites, resulting in less hydrogen evolution reaction (HER) roll‐off in natural seawater. P‐8CE, in particaular, shows remarkable results with 200% and 258% higher HER than the model photocatalyst, PCzDBTO, in pure water and natural seawater, respectively.
Conjugated polymers (CPs) have recently gained increasing attention as photocatalysts for sunlight-driven hydrogen evolution. However, they suffer from insufficient electron output sites and poor ...solubility in organic solvents, severely limiting their photocatalytic performance and applicability. Herein, solution-processable all-acceptor (A
-A
)-type CPs based on sulfide-oxidized ladder-type heteroarene are synthesized. A
-A
-type CPs showed upsurging efficiency improvements by two to three orders of magnitude, compared to their donor-acceptor -type CP counterparts. Furthermore, by seawater splitting, PBDTTTSOS exhibited an apparent quantum yield of 18.9% to 14.8% at 500 to 550 nm. More importantly, PBDTTTSOS achieved an excellent hydrogen evolution rate of 35.7 mmol h
g
and 150.7 mmol h
m
in the thin-film state, which is among the highest efficiencies in thin film polymer photocatalysts to date. This work provides a novel strategy for designing polymer photocatalysts with high efficiency and broad applicability.
MXenes with interesting optical and electrical properties have been attractive in biomedical applications such as antibacterial and anticancer agents, but their low photogeneration efficiency of ...reactive oxygen species (ROS) and poor stability are major concerns against microbial resistance. Water-dispersible single layer Ti.sub.3C.sub.2T.sub.x-based MXene through etching tightly stacked MAX phase precursor using a minimally intensive layer delamination method. After addition of Cu(II) ions, the adsorbed Cu(II) ions underwent self-redox reactions with the surface oxygenated moieties of MXene, leading to in situ formation of Cu.sub.2O species to yield Cu.sub.2O/Ti.sub.3C.sub.2T.sub.x nanosheets (heterostructures). Under NIR irradiation, the Cu.sub.2O enhanced generation of electron-hole pairs, which boosted the photocatalytic production of superoxide and subsequent transformation into hydrogen peroxide. Broad-spectrum antimicrobial performance of Cu.sub.2O/Ti.sub.3C.sub.2T.sub.x nanosheets with sharp edges is attributed to the direct contact-induced membrane disruption, localized photothermal therapy, and in situ generated cytotoxic free radicals. The minimum inhibitory concentration of Cu.sub.2O/Ti.sub.3C.sub.2T.sub.x nanosheets reduced at least tenfold upon NIR laser irradiation compared to pristine Cu.sub.2O/Ti.sub.3C.sub.2T.sub.x nanosheets. The Cu.sub.2O/Ti.sub.3C.sub.2T.sub.x nanosheets were topically administrated on the methicillin-resistant Staphylococcus aureus (MRSA) infected wounds on diabetic mice. Upon NIR illumination, Cu.sub.2O/Ti.sub.3C.sub.2T.sub.x nanosheets eradicated MRSA and their associated biofilm to promote wound healing. The Cu.sub.2O/Ti.sub.3C.sub.2T.sub.x nanosheets with superior catalytic and photothermal properties have a great scope as an effective antimicrobial modality for the treatment of infected wounds.
Stromal barriers, such as the abundant desmoplastic stroma that is characteristic of pancreatic ductal adenocarcinoma (PDAC), can block the delivery and decrease the tumour-penetrating ability of ...therapeutics such as tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), which can selectively induce cancer cell apoptosis. This study aimed to develop a TRAIL-based nanotherapy that not only eliminated the extracellular matrix barrier to increase TRAIL delivery into tumours but also blocked antiapoptotic mechanisms to overcome TRAIL resistance in PDAC.
Nitric oxide (NO) plays a role in preventing tissue desmoplasia and could thus be delivered to disrupt the stromal barrier and improve TRAIL delivery in PDAC. We applied an
combinatorial phage display technique to identify novel peptide ligands to target the desmoplastic stroma in both murine and human orthotopic PDAC. We then constructed a stroma-targeted nanogel modified with phage display-identified tumour stroma-targeting peptides to co-deliver NO and TRAIL to PDAC and examined the anticancer effect in three-dimensional spheroid cultures
and in orthotopic PDAC models
.
The delivery of NO to the PDAC tumour stroma resulted in reprogramming of activated pancreatic stellate cells, alleviation of tumour desmoplasia and downregulation of antiapoptotic BCL-2 protein expression, thereby facilitating tumour penetration by TRAIL and substantially enhancing the antitumour efficacy of TRAIL therapy.
The co-delivery of TRAIL and NO by a stroma-targeted nanogel that remodels the fibrotic tumour microenvironment and suppresses tumour growth has the potential to be translated into a safe and promising treatment for PDAC.
Continued efforts are made for the utilization of CO2 as a C1 feedstock for regeneration of valuable chemicals and fuels. Mechanistic study of molecular (electro‐/photo‐)catalysts disclosed that ...initial step for CO2 activation involves either nucleophilic insertion or direct reduction of CO2. In this study, nucleophilic activation of CO2 by complex (NO)2Fe(μ‐MePyr)2Fe(NO)22− (2, MePyr=3‐methylpyrazolate) results in the formation of CO2‐captured complex (NO)2Fe(MePyrCO2)− (2‐CO2, MePyrCO2=3‐methyl‐pyrazole‐1‐carboxylate). Single‐crystal structure, spectroscopic, reactivity, and computational study unravels 2‐CO2 as a unique intermediate for reductive transformation of CO2 promoted by Ca2+. Moreover, sequential reaction of 2 with CO2, Ca(OTf)2, and KC8 established a synthetic cycle, 2 → 2‐CO2 → (NO)2Fe(μ‐MePyr)2Fe(NO)2 (1) → 2, for selective conversion of CO2 into oxalate. Presumably, characterization of the unprecedented intermediate 2‐CO2 may open an avenue for systematic evaluation of the effects of alternative Lewis acids on reduction of CO2.
In anionic 2, a nucleophilic pyrazolate ligand, the neutral {Fe(NO)2}10 unit, and the K‐18‐crown‐6‐ether+ countercation work in concert to promote the capture and nucleophilic activation of CO2 through the assembly of stable 2‐CO2. Relying on the one‐electron reduction power of the {Fe(NO)2}10 core in the anionic complex (NO)2Fe(MePyrCO2)−, addition of dicationic Ca2+ further initiates the C−C coupling of activated/reduced CO2 and yields precipitated calcium oxalate.
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