Purpose
This work was to identify the function and mechanism of miR‐219a‐5p in regulating knee osteoarthritis (KOA).
Methods
Rat fibroblast‐like synoviocytes (FLSs) were isolated to construct KOA ...cell model by lipopolysaccharide and adenosine triphosphate treatment. miR‐219a‐5p and FBXO3 expression in FLSs was modulated by transfection. Flow cytometry was executed to research FLSs apoptosis. Caspase‐1 and IL‐1β expression in FLSs was researched by immunofluorescence. The binding between miR‐219a‐5p and FBXO3 was identified by dual luciferase reporter gene assay. KOA rat model and miR‐219a‐5p up‐modulation KOA rat model were constructed. Step size of rats was analyzed. Knee joints of rats were experienced Safranin O‐fast green staining to evaluate the knee joint injury. FBXO3, pyroptosis‐associated proteins, and IL‐1β and IL‐18 expression in FLSs and articular cartilage tissues of rats were assessed by Western blot, qRT‐PCR and Enzyme‐linked immunosorbent assay.
Results
KOA cell model had higher apoptosis percentage, expression of pyroptosis‐associated proteins, and IL‐1β and IL‐18 level. miR‐219a‐5p up‐modulation decreased the above indicators, whereas miR‐219a‐5p down‐modulation increased the above indicators. FBXO3 expression was directly repressed by miR‐219a‐5p. Loss of FBXO3 suppressed the above indicators. FBXO3 counteracted the suppression of miR‐219a‐5p on the above indicators. miR‐219a‐5p agomir attenuated knee joint injury, increased step size of KOA rats, and reduced FBXO3, pyroptosis‐associated proteins and level of IL‐1β and IL‐18 in the articular cartilage tissues of KOA rats.
Conclusion
miR‐219a‐5p suppressed the pyroptosis in KOA by inactivating the NLRP3 signaling via targeting FBXO3, which might be a promising target for ameliorating KOA in the clinic.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Rhizospheric degradation is a green and in situ strategy to accelerate dissipation of organic pollutants in soils. However, the mechanism on microbial degradation of phthalic acid esters (PAEs) in ...rhizosphere is still unclear. Here, the bacterial community and function genes in bulk and rhizospheric soils of maize (Zea mays L.) exposed to gradient concentrations of di-(2-ethylhexyl) phthalate (DEHP) were analyzed with 16 S rRNA, metagenomic sequencing and quantitative PCR (qPCR). Maize rhizosphere significantly increased the dissipation of DEHP by 4.02–11.5% in comparison with bulk soils. Bacterial community in rhizosphere exhibited more intensive response and shaped its beneficial structure and functions to DEHP stress than that in bulk soils. Both rhizospheric and pollution effects enriched more PAE-degrading bacteria (e.g., Bacillus and Rhizobium) and function genes in rhizosphere than in bulk soil, which played important roles in degradation of PAEs in rhizosphere. The PAE-degrading bacteria (including genera Sphingomonas, Sphingopyxis and Lysobacter) identified as keystone species participated in DEHP biodegradation. Identification of PAE intermediates and metagenomic reconstruction of PAE degradation pathways demonstrated that PAE-degrading bacteria degraded PAEs through cooperation with PAE-degrading and non-PAE-degrading bacteria. This study provides a comprehensive knowledge for the microbial mechanism on the superior dissipation of PAEs in rhizosphere.
Display omitted
•Rhizosphere and pollution enriched PAE-degrading bacteria and genes.•Enriched PAE-degrading bacteria and genes enhanced rhizosphere degradation.•Keystone species of bacterial community participated in PAE biodegradation.•Metagenome reveals the microbial mechanism of PAE rhizosphere degradation.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A series of phenanthroline‐based ligands have been synthesised and their influence as bidentate nitrogen ligands in heteroleptic Cu(P^P)(N^N)+ photosensitisers in light‐driven water reduction has ...been studied. In this noble‐metal‐free Cu–Fe‐based photocatalytic water reduction system, the structural effects of the nitrogen ligands have been explored, including the steric and electronic effects of substituents at the 2,9‐ and 4,7‐positions of phenanthroline. Ligands were prepared that led to increased hydrogen generation, with turnover numbers (TONCu) of up to 1388 being observed. All the new complexes were electrochemically and photophysically characterised. We demonstrate for the first time that the presence of fluorine in nitrogen ligands increases the efficacy of copper complexes in photocatalytic hydrogen production.
Hydrogen production: A series of phenanthroline‐based ligands have been synthesised and the photosensitising ability of their heteroleptic Cu(P^P)(N^N)+ complexes in light‐driven Cu–Fe‐based water reduction has been studied (see scheme). In this noble‐metal‐free system, the steric and electronic effects of the substituents at the 2,9‐ and 4,7‐positions of phenanthroline have been explored. It is shown for the first time that the presence of fluorine in nitrogen ligands increases the efficacy of copper complexes in photocatalytic hydrogen production.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
An efficient chiral 4-aryl-pyridine-N-oxide (ArPNO) nucleophilic organocatalyst was rationally designed, synthesized, and applied to the acylative dynamic kinetic resolution of azoles, aldehydes, and ...anhydride. The restriction of the pyridine’s C-4 position, where the dialkylamino group should be always present when using chiral pyridine-N-oxide as an acyl transfer catalyst, was overcome, thereby allowing structural diversity at this position. In the presence of 5 mol % 3,5-dimethylphenyl-derived ArPNO catalyst, the corresponding 2,5-disubstituted tetrazole hemiaminal esters were obtained in up to 93% yields, >20:1 rr, and 99% ee. Other N-heteroaromatics, including substituted pyrazole, imidazole, purine, benzimidazole, and benzotriazole, were also suitable substrates. Mechanistic studies by control experiments and density functional theory calculations indicated that an acyloxypyridinium cation was formed, and the nucleophilic substitution of azole hemiaminal with the acyloxypyridinium cation was the rate-determining step. Furthermore, the nucleophilic ability of oxygen in pyridine-N-oxide was higher than that of nitrogen in pyridine. This work provides an effective method for the utilization of the C-4 position of the pyridine ring, allowing the development of more varied chiral 4-substituted pyridine-N-oxides as efficient nucleophilic organocatalysts.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
Autophagy is an endogenous protective process; the loss of autophagy could destabilize proteostasis and elevate intracellular oxidative stress, which is critically involved in the development of ...cardiac hypertrophy and heart failure. Oridonin, a natural tetracycline diterpenoid from the Chinese herb Rabdosia, has autophagy activation properties. In this study, we tested whether oridonin protects against cardiac hypertrophy in mice and cardiomyocytes. We implemented aortic banding to induce a cardiac hypertrophy mouse model, and oridonin was given by gavage for 4 weeks. Neonatal rat cardiomyocytes were stimulated with angiotensin II to simulate neurohumoural stress. Both in vivo and in vitro studies suggested that oridonin treatment mitigated pressure overload-induced cardiac hypertrophy and fibrosis, and also preserved heart function. Mice that received oridonin exhibited increased antioxidase activities and suppressed oxidative injury compared with the aortic banding group. Moreover, oridonin enhanced myocardial autophagy in pressure-overloaded hearts and angiotensin II-stimulated cardiomyocytes. Mechanistically, we discovered that oridonin administration regulated myocardial P21, and cytoplasmic P21 activated autophagy via regulating Akt and AMPK phosphorylation. These findings were further corroborated in a P21 knockout mouse model. Collectively, pressure overload-induced autophagy dysfunction causes intracellular protein accumulation, resulting in ROS injury while aggravating cardiac hypertrophy. Thus, our data show that oridonin promoted P21-related autophagic lysosomal degradation, hence attenuating oxidative injury and cardiac hypertrophy.
Developing flexible electrodes with high active materials loading and excellent mechanical stability is of importance to flexible electronics, yet remains challenging. Herein, robust flexible ...electrodes with an encapsulated core‐multishell structure are developed via a spraying‐hydrothermal process. The multilayer electrode possesses an architecture of substrate/reduced graphene oxide (rGO)/bimetallic complex/rGO/bimetallic complex/rGO from the inside to the outside, where the cellulosic fibers serve as the substrate, namely, the core; and the multiple layers of rGO and bimetallic complex, are used as active materials, namely, the shells. The inner two rGO interlayers function as the cement that chemically bind to two adjacent layers, while the two outer rGO layers encapsulate the inside structure effectively protecting the electrode from materials detachment or electrolyte corrosion. The electrodes with a unique core‐multishell structure exhibit excellent cycle stability and exceptional temperature tolerance (−25 to 40 °C) for lithium and sodium storage. A combination of experimental and theoretical investigations are carried out to gain insights into the synergetic effects of cobalt‐molybdenum‐sulfide (CMS) materials (the bimetallic complex), which will provide guidance for future exploration of bimetallic sulfides. This strategy is further demonstrated in other substrates, showing general applicability and great potential in the development of flexible energy storage devices.
The encapsulated core–multishell structure with an architecture of substrate/reduced graphene oxide (rGO)/bimetallic complex/rGO/bimetallic complex/rGO is used to fabricate robust and high energy density electrodes for lithium/sodium storage, with a high proportion of active material (20 wt%) and mechanical strength. The underlying synergistic effect of bimetal ions is revealed via experimental investigations and theoretical calculations.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
NIR-II fluorescence imaging is one powerful tool of molecular imaging, which shows a promising future in cancer early diagnosis and image-guided therapy. The advancements of molecular imaging probes ...would be conducive to the enhancement in the contrast and fidelity of cancer imaging. Epidermal growth factor receptor (EGFR) is a biomarker widely used for cancer theranostics, and we herein developed a novel EGFR-targeting NIR-II fluorescent probe CH1055-PEG1k-GE11 utilizing CH1055 as a core to couple with EGFR-targeting peptides GE11
via
a mild crosslinking strategy. The results suggested that CH1055-PEG1k-GE11 possessed enhanced EGFR-targeting capability
in vitro
and achieved high contrast imaging of EGFR-highly expressing tumors
in vivo
. During the 24 h imaging after intravenous injection, CH1055-PEG1k-GE11 enabled a tumor-to-background ratio substantially surpassing the Rose criterion of 5 since 1 h postinjection (p.i.) and reached the highest value of 12.89 at 2 h p.i. Moreover, this probe was partially renal-clearable and exhibited favorable biocompatibility based on the results of cell viability and hematoxylin and eosin assays. Based on the above facts, CH1055-PEG1k-GE11 may have promising application prospects in the imaging of tumors with a high EGFR-expression.
A novel NIR-II fluorescent probe CH1055-PEG1k-GE11 enabled high contrast imaging of tumor with a high EGFR-expression
in vivo
.
ObjectiveMany studies have already suggested the role of long non-coding RNAs (lncRNAs) in Alzheimer’s disease (AD), but the functions of lncRNA Taurine Upregulated Gene 1 (TUG1) in AD have been ...scarcely discussed. This study aims to verify how TUG1 affects hippocampal neurons in AD through modulation of microRNA-15a (miR-15a)/Rho-associated protein kinase 1 (ROCK1).MethodAD mice was modeled through injection of β-amyloid 25-35 (Aβ25-35) into the lateral ventricle. After modeling, the mice were injected with altered TUG1 and/or miR-15a agomir lentiviruses. The spatial learning ability and memory ability of mice were detected through Morris water maze test. Hippocampal neuronal apoptosis and oxidative stress indicators in AD mice were then detected. The hippocampal neuron AD model was induced by Aβ25-35. Next, the neurons were, respectively, transfected with altered TUG1 vector and/or miR-15a mimics to determine the proliferation inhibition and apoptosis of hippocampal neurons. The interactions between TUG1 and miR-15a, and between miR-15a and ROCK1 were assessed using bioinformatic prediction, dual luciferase reporter gene assay and RNA-pull-down assay.ResultsIn the animal models, Aβ25-35-induced mice exhibited decreased spatial learning and memory ability, obvious pathological injury, promoted hippocampal neuronal apoptosis and decreased antioxidant ability. TUG1 silencing and miR-15a elevation improved spatial learning ability and memory ability, ameliorated pathological injury, depressed neuronal apoptosis, and strengthened antioxidant ability of hippocampal neurons in AD mice. In cellular models, Aβ25-35-treated hippocampal neurons presented inhibited neuronal viability and promoted neuronal apoptosis. TUG1 silencing and miR-15a elevation increased viability and limited apoptosis of Aβ25-35-treated hippocampal neurons. TUG1 specifically bound to miR-15a, and miR-15a targeted ROCK1.ConclusionCollectively, this study reveals that TUG1 knockdown restricts apoptosis of hippocampal neurons in AD by elevating miR-15a and suppressing ROCK1 expression, and provides a new therapeutic target for AD treatment.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•Physical NW-EP and chemical Cl2 were compared to remove culturable and viable cells.•NW-EP had ∼3–5 times lower energy consumption for culturable cell removal than Cl2.•NW-EP inhibited the formation ...of VBNC cells via destroying cell wall and membrane.•Osmotic pressure caused gradual inactivation of VBNC cells with cell wall damage.•NW-EP showed excellent adaptability to control VBNC cells in DI, tap and lake waters.
The induction of viable but nonculturable (VBNC) bacteria with cellular integrity and low metabolic activity by chemical disinfection causes a significant underestimation of potential microbiological risks in drinking water. Herein, a physical Co3O4 nanowire-assisted electroporation (NW-EP) was developed to induce cell damage via the locally enhanced electric field over nanowire tips, potentially achieving effective inhibition of VBNC cells as compared with chemical chlorination (Cl2). NW-EP enabled over 5-log removal of culturable cell for various G+/G- bacteria under voltage of 1.0 V and hydraulic retention time of 180 s, and with ∼3–6 times lower energy consumption than Cl2. NW-EP also achieved much higher removals (∼84.6 % and 89.5 %) of viable Bacillus cereus (G+) and Acinetobacter schindleri (G-) via generating unrecoverable pores on cell wall and reversible/irreversible pores on cell membrane than Cl2 (∼28.6 % and 41.1 %) with insignificant cell damage. The residual VBNC bacteria with cell wall damage and membrane pore resealing exhibited gradual inactivation by osmotic stress, leading to ∼99.8 % cell inactivation after 24 h storage (∼59.4 % for Cl2). Characterizations of cell membrane integrity and cell morphology revealed that osmotic stress promoted cell membrane damage for the gradual inactivation of VBNC cells during storage. The excellent adaptability of NW-EP for controlling VBNC cells in DI, tap and lake waters suggested its promising application potentials for drinking water, such as design of an external device on household taps.
Display omitted
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cardiac remodeling predisposes to heart failure if the burden is unresolved, and heart failure is an important cause of mortality in humans. The aim of the present study was to identify the key genes ...involved in cardiac pathological remodeling induced by pressure overload. Gene expression profiles of the GSE5500, GSE18224, GSE36074 and GSE56348 datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs), defined as |log2FC|>1 (FC, fold change) and an adjusted P‑value of <0.05, were screened using the R software with the limma package. Gene ontology enrichment analysis was performed and a protein‑protein interaction (PPI) network of the DEGs was constructed. A cardiac remodeling model induced by transverse aortic constriction (TAC) was established. Furthermore, consistent DEGs were further validated using reverse transcription‑quantitative polymerase chain reaction (RT‑PCR) analysis, western blotting and immunohistochemistry in the ventricular tissue samples after TAC or sham operation. A total of 24 common DEGs were identified (23 significantly upregulated and 1 downregulated), of which 9 genes had been previously confirmed to be directly involved in cardiac remodeling. Hence, the level of expression of the other 15 genes was detected in subsequent studies via RT‑PCR. Based on the results of the PPI network analysis and RT‑PCR, we further detected the protein levels of Itgbl1 and Asporin, which were consistent with the results of bioinformatics analysis and RT‑PCR. The expression of Itgbl1, Aspn, Fstl1, Mfap5, Col8a1, Ltbp2, Mfap4, Pamr1, Cnksr1, Aqp8, Meox1, Gdf15 and Srpx was found to be upregulated in a mouse model of cardiac remodeling, while that of Retnla was downregulated. Therefore, the present study identified the key genes implicated in cardiac remodeling, aiming to provide new insight into the underlying mechanism.
PDF
