Studies on the relationship between osteoporosis and intervertebral disc degeneration (IVDD) are inconsistent. Therefore, we assessed whether IVDD is affected by vertebral osteoporosis in ...ovariectomized mice and investigated the underlying pathogenesis of IVDD related to osteoporosis.
Thirty healthy female C57BL/6 J mice aged 8 weeks were randomly divided into two groups: a control group (sham operation, n = 15) and an ovariectomy group (OVX; bilateral ovariectomy, n = 15). At 12 weeks after surgery, the bone quantity and microstructure in the lumbar vertebra and endplate as well as the volume of the L4/5 disc space were evaluated by microcomputed tomography (micro-CT). The occurrence and characteristic alterations of IVDD were identified via histopathological staining. The osteoclasts were detected using tartrate-resistant acid phosphatase (TRAP) staining. Type II collagen (Col II), osterix (OSX), osteopontin (OPN), and vascular endothelial growth factor (VEGF) expression in the intervertebral disc were detected by immunohistochemical analysis.
OVX significantly increased the body weight and decreased the uterus weight. Micro-CT analysis showed that osteoporosis of the vertebra and osteochondral remodeling of the endplate were accompanied by an increase in the endplate porosity and a decrease in the disc volume in the OVX group. Likewise, histological evaluation revealed that IVDD occurred at 12 weeks after ovariectomy, with features of endochondral ossification of the endplate, loose and broken annulus fibrosus, and degeneration of nucleus pulposus. TRAP staining showed that numerous active osteoclasts appeared in the subchondral bone and cartilaginous endplate of OVX mice, whereas osteoclasts were rarely detected in control mice. Immunohistochemical analysis demonstrated that the expression of osterix was significantly increased, notably in the endplate of OVX mice. In addition, Col II was decreased in the ossification endplate and the degenerative annulus fibrosus, where OPN and VEGF expressions were elevated in OVX mice.
OVX induced vertebral osteoporosis and osteochondral remodeling of the cartilaginous endplate contributing to the angiogenesis and an increase in porosity of the bone-cartilage surface, and also affected the matrix metabolism which consequently had detrimental effects on the intervertebral disc. Our study suggests that preserving the structural integrity and the function of the adjacent structures, including the vertebrae and endplates, may protect the disc against degeneration.
Finding highly efficient hydrogen evolution reaction (HER) catalysts is pertinent to the ultimate goal of transformation into a net-zero carbon emission society. The design principles for such HER ...catalysts lie in the well-known structure-property relationship, which guides the synthesis procedure that creates catalyst with target properties such as catalytic activity. Here we report a general strategy to synthesize 10 kinds of single-atom-doped CoSe
-DETA (DETA = diethylenetriamine) nanobelts. By systematically analyzing these products, we demonstrate a volcano-shape correlation between HER activity and Co atomic configuration (ratio of Co-N bonds to Co-Se bonds). Specifically, Pb-CoSe
-DETA catalyst reaches current density of 10 mA cm
at 74 mV in acidic electrolyte (0.5 M H
SO
, pH ~0.35). This striking catalytic performance can be attributed to its optimized Co atomic configuration induced by single-atom doping.
The bacterial infection has a significant impact on the human health. With the widespread use of antibiotics, the bacterial resistance has increased significantly, which necessitates the urgent ...identification of novel antibacterial materials. In this study, a hydrogel with an inherent antibacterial ability, self-assembled from a heterochiral peptide C
16
-
D
L
4
L
R
4
, has been reported. The hydrogel demonstrated optimal rheological and injectable properties. It revealed a time-dependent antibacterial activity against Gram-positive
Staphylococcus aureus
and
Bacillus subtilis
as well as Gram-negative
Escherichia coli
and
Shigella sonnei
. After 5 h treatment with the hydrogel, the survival rate of
S. aureus
,
B. subtilis, E. coli
and
Sh. sonnei
bacteria was decreased to 5.9%, 0%, 5.3% and 11.09%, respectively. The chiral nanofibers with a diameter of 15–20 nm in the hydrogel were observed to be conducive to the aggregation of bacteria and destruction of the cell membrane to achieve the antibacterial effect. In addition, the in vitro analysis on the mouse embryonic fibroblasts confirmed the superior biocompatibility of the hydrogel. The results obtained in this study provide the basis for the development of the functional antibacterial hydrogels by the self-assembly of the heterochiral peptides.
Graphical abstract
Polypeptide N‐acetylgalactosaminyltransferases (GalNAc‐Ts), a group of isoenzymes that initiate mucin‐type O‐glycosylation, have been shown to mediate tumor growth and metastasis in various cancer ...types. However, data on the clinical significance and features of GalNAc‐Ts remain scant. Here, we used Oncomine and The Cancer Genome Atlas (TCGA) databases to analyze the transcription and survival effect of GALNTs (N‐acetylgalactosaminyltransferase genes) in pan‐cancer. The data showed that the GALNTs were aberrantly expressed in various human cancers and significantly associated with patients’ clinical outcomes. The expression of 13 GALNTs were correlated with prognosis in brain low grade glioma (LGG) patients. In addition, based on the expression profiles of GALNT family genes in TCGA‐LGG dataset, we identified 2 molecular subtypes (cluster1/2) by consensus clustering and analyzed tumor heterogeneity. Our results demonstrated that cluster 2 group was associated with poor prognosis, CD8+ T cells, macrophages and DCs infiltration, up‐regulated expression of immune checkpoints, and higher tumor immune dysfunction and exclusion score, indicating that GalNAc‐Ts might contribute to tumor immune escape. Furthermore, we employed LASSO regression and time‐dependent ROC analysis to construct a GALNTs‐related prognostic signature with the TCGA‐LGG dataset, and then validated the signature using 2 external cohorts. Taken together, our study successfully developed a novel prognostic biomarker for LGG and provides a basis for personalized immunotherapy in brain cancer.
Summary sentence
This study successfully developed a novel prognostic biomarker for LGG and provides a basis for personalized immunotherapy in brain cancer.
Graphical
Development of a novel prognostic biomarker for LGG that may support evauation of immunotherapy strategies in brain cancer.
Background and Purpose
Sirtuin1 (SIRT1), the founding member of mammalian class III histone deacetylases, is reported to be a drug target involved in fibrotic diseases. However, whether it is an ...effective drug target in hypertrophic scar treatment is still not known.
Experimental Approach
In the present study, we observed that SIRT1 localized to both the epidermis and the dermis of skin tissues by immunohistochemistry. After knock‐down of SIRT1 by shRNA or up‐regulating SIRT1 by resveratrol, the expression of α‐SMA, Col1 and Col3 in fibroblasts were detected by western blots. A mouse excision wound healing model was used to observe the changes in collagen fibre associated with the different expression levels of SIRT1.
Key Results
SIRT1 expression was inhibited in hypertrophic scar tissue. The down‐regulation of SIRT1 resulted in an increased expression of α‐SMA, Col1 and Col3 in hypertrophic scar‐derived fibroblasts. In contrast, the up‐regulation of SIRT1 not only inhibited the expression of α‐SMA, Col1 and Col3 in hypertrophic scar‐derived fibroblasts but also blocked the activation of TGFβ1‐induced normal skin‐derived fibroblasts. In the mouse model of wound healing, the deletion of SIRT1 resulted in denser collagen fibres and a more disordered structure, whereas resveratrol treatment led to a more organized and thinner collagen fibre, which was similar to that observed during normal wound healing.
Conclusions and Implications
The results revealed that SIRT1 negatively regulates TGFβ1‐induced fibroblast activation and inhibits excessive scar formation and is, therefore, a promising drug target for hypertrophic scar formation.
Summary
Aims
Neural stem cells (NSCs) in the adult mammalian spinal cord are activated in response to spinal cord injury (SCI); however, mechanisms modulating this process are not clear. Here, we ...noticed SCI elevated expression of vascular endothelial growth factor (VEGF) and we aimed to validate the roles of VEGF in NSCs activation after SCI and investigated the related signals during the process.
Methods
In vitro we detected whether VEGF promoted spinal cord NSCs proliferation and investigated the involved signals; In vivo, we injected VEGF into rat spinal cord to check the NSCs activation.
Results
In vitro, VEGF triggered spinal cord NSCs proliferation and maintained self‐renewal. Further investigations demonstrated VEGF transactivated epidermal growth factor receptor (EGFR) through VEGF receptor 2 (VEGFR2) to promote spinal cord NSCs proliferation. In vivo, we injected VEGF into spinal cord by laminectomy to confirm the roles of VEGF‐VEGFR2‐EGFR signals in NSCs activation. VEGF significantly elevated the number of activated NSCs and increased EGFR phosphorylation. In contrast, intraspinal injection of specific inhibitors targeting EGFR and VEGFR2 decreased NSCs activation after SCI. Our results demonstrate that VEGF‐VEGFR2‐EGFR axis is important for NSCs activation after SCI, providing new insights into the mechanisms of spinal cord NSCs activation postinjury.
Defects can introduce atomic structural modulation and tailor performance of materials. Herein, it demonstrates that semiconductor WO
with inert electrocatalytic behavior can be activated through ...defect-induced tensile strains. Structural characterizations reveal that when simply treated in Ar/H
atmosphere, oxygen vacancies will generate in WO
and cause defective structures. Stacking faults are found in defects, thus modulating electronic structure and transforming electrocatalytic-inert WO
into highly active electrocatalysts. Density functional theory (DFT) calculations are performed to calculate
H adsorption energies on various WO
surfaces, revealing the oxygen vacancy composition and strain predicted to optimize the catalytic activity of hydrogen evolution reaction (HER). Such defective tungsten oxides can be integrated into commercial proton exchange membrane (PEM) electrolyser with comparable performance toward Pt-based PEM. This work demonstrates defective metal oxides as promising non-noble metal catalysts for commercial PEM green-hydrogen generation.
Purpose
Ischemic penumbra is the main therapeutic target for acute ischemic stroke. The aim in this study is to investigate the potential serum biomarkers of penumbra that could fulfill a ...complementary role in the acute stroke clinical decision‐making process.
Experimental Design
An established focal cerebral ischemia model is applied in rats. Using isobaric tags for relative and absolute quantitation combined with liquid chromatography‐tandem mass spectrometry, the global expression profiles of proteins in ischemic penumbra tissue and serum from rats subjected to different ischemic times are identified and quantified. Candidate biomarkers are screened out with bioinformatics analysis and further validated by western blotting.
Results
Herein, a total of 4568 proteins in the penumbra and 1915 proteins in the serum are identified. Two proteins related to the penumbra, RHOA, and CDC42, are screened out through an integrative analysis. The expression levels of RHOA and CDC42 in the penumbra and serum gradually increase synchronously with the prolonged ischemia time.
Conclusions and Clinical Relevance
The study provides the results of a proteomic analysis to identify serum biomarkers of the penumbra. Upregulation of RHOA and CDC42 may be useful for the early assessment of ischemic penumbra and could serve as potential serum biomarkers.
The reliability redundancy allocation problem (RRAP) is a well-known tool in system design, development, and management. The RRAP is always modeled as a nonlinear mixed-integer non-deterministic ...polynomial-time hardness (NP-hard) problem. To maximize the system reliability, the integer (component active redundancy level) and real variables (component reliability) must be determined to ensure that the cost limit and some nonlinear constraints are satisfied. In this study, a bi-objective RRAP is formulated by changing the cost constraint as a new goal, because it is necessary to balance the reliability and cost impact for the entire system in practical applications. To solve the proposed problem, a new simplified swarm optimization (SSO) with a penalty function, a real one-type solution structure, a number-based self-adaptive new update mechanism, a constrained nondominated-solution selection, and a new pBest replacement policy is developed in terms of these structures selected from full-factorial design to find the Pareto solutions efficiently and effectively. The proposed SSO outperforms several metaheuristic state-of-the-art algorithms, e.g., nondominated sorting genetic algorithm II (NSGA-II) and multi-objective particle swarm optimization (MOPSO), according to experimental results for four benchmark problems involving the bi-objective active RRAP.
•An bi-objection active reliability redundancy allocation problem (RRAP) to reduce the cost and enhance the reliability is considered.•For MOSSO, full-factorial design is implemented to determine the best combinations with different replacement policies, update strategies, and roles of pBest.•For four RRAP benchmark problems, proposed multi-objective SSO (MOSSO) outperforms nondominated sorting genetic algorithm II (NSGA-II) and multi-objective particle swarm optimization (MOPSO) with regard to the Pareto plots and spacing (SP) values.
As a novel imaging marker, pericoronary fat attenuation index (FAI) reflects the local coronary inflammation which is one of the major mechanisms for in-stent restenosis (ISR). We aimed to validate ...the ability of pericoronary FAI to predict ISR in patients undergoing percutaneous coronary intervention (PCI).
Patients who underwent coronary CT angiography (CCTA) before PCI within 1 week between January 2017 and December 2019 at our hospital and had follow-up invasive coronary angiography (ICA) or CCTA were enrolled. Pericoronary FAI was measured at the site where stents would be placed. ISR was defined as ≥ 50% diameter stenosis at follow-up ICA or CCTA in the in-stent area. Multivariable analysis using mixed effects logistic regression models was performed to test the association between pericoronary FAI and ISR at lesion level.
A total of 126 patients with 180 target lesions were included in the study. During 22.5 months of mean interval time from index PCI to follow-up ICA or CCTA, ISR occurred in 40 (22.2%, 40/180) stents. Pericoronary FAI was associated with a higher risk of ISR (adjusted OR = 1.12, p = 0.028). The optimum cutoff was - 69.6 HU. Integrating the dichotomous pericoronary FAI into current state of the art prediction model for ISR improved the prediction ability of the model significantly (△area under the curve = + 0.064; p = 0.001).
Pericoronary FAI around lesions with subsequent stent placement is independently associated with ISR and could improve the ability of current prediction model for ISR.
Pericoronary fat attenuation index can be used to identify the lesions with high risk for in-stent restenosis. These lesions may benefit from extra anti-inflammation treatment to avoid in-stent restenosis.
• Pericoronary fat attenuation index reflects the local coronary inflammation. • Pericoronary fat attenuation index around lesions with subsequent stents placement can predict in-stent restenosis. • Pericoronary fat attenuation index can be used as a marker for future in-stent restenosis.
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