Previous studies have demonstrated that nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX)-mediated oxidative stress plays a key role in brain injury following cerebral ...ischemia/reperfusion (I/R) and myosin regulatory light chain kinase (MLCK) has been reported to be involved in NOX activation in lung endothelium. This study was performed to explore the correlation between MLCK and NOX following cerebral I/R and the underlying mechanisms. Sprague–Dawley (SD) rats were subjected to 2 h middle cerebral artery occlusion and 24 h reperfusion to establish a model of focal cerebral I/R injury. At the end of experiments, neurological function, infarct volume, cellular apoptosis, activities of MLCK and NOX, messenger RNA (mRNA) and protein expression of NOX (NOX1–NOX4), phosphorylation level of myosin regulatory light chain (MLC
20
) and hydrogen peroxide (H
2
O
2
) level were determined. The results showed that I/R treatment led to increase in neurological deficit score, infarct volume and cellular apoptosis, accompanied by the elevated activities of MLCK and NOX, expressions of NOX2 and NOX4, levels of phosphorylation MLC
20
and H
2
O
2
, these effects were attenuated by MLCK specific inhibitor (ML-7). NOX inhibitors (diphenylene iodonium (DPI) or apocynin) were able to achieve similar results to that of ML-7 except no effect on MLCK activity and MLC
20
phosphorylation. These results suggest that activation of MLCK contributes to cerebral I/R oxidative injury through upregulation of NOX2 and NOX4 expression, which is involved in phosphorylation of MLC
20
.
Based on the correlation between inflammation and reactive oxygen species and viscosity, a fluorescent probe (
SWJT-19
) was designed for a relay detection of hypochlorite ions and viscosity. The ...synthesized probe could quickly and selectively detect hypochlorite ions, as well as viscosity of the system effectively. Moreover, the probe had been successfully applied to sequentially detect hypochlorite ions and viscosity in organisms, as well as imaging in mouse inflammation.
A new fluorescent probe has been developed for relay detection of hypochlorite ions and viscosity.
Modeling high‐dimensional dynamic processes is a challenging task. In this regard, probabilistic slow feature analysis (PSFA) is revealed to be advantageous for dynamic soft sensor modeling, which ...can extract slowly varying intrinsic features from high‐dimensional data. However, nonlinearities prevalent in industrial processes are not considered, which could lead to unsatisfactory prediction performance. In this paper, a weighted PSFA (WPSFA)‐based soft sensor model is proposed for nonlinear dynamic chemical process. In WPSFA, a weighted log‐likelihood function of complete data is constructed to linearize the nonlinear state emission equation. Then, the expectation maximization algorithm is applied to estimate the model parameters and a locally weighted regression model is established for quality prediction. Finally, the feasibility and effectiveness of the proposed approach are well illustrated through a numerical example and a real industrial process.
A data‐driven soft sensor based on weighted probabilistic slow feature analysis is proposed for nonlinear dynamic processes. A nonlinear model structure is designed, in which a weighted log‐likelihood function of complete data is constructed to linearize the nonlinear state emission equation. The feasibility and effectiveness of the proposed approach are illustrated through a numerical example and a real industrial process.
Renal fibrosis is the common pathological process of various chronic kidney diseases (CKD). Recent studies indicate that mitochondrial fragmentation is closely associated with renal fibrosis in CKD. ...However, the molecular mechanisms leading to mitochondrial fragmentation remain to be elucidated. The present study investigated the role of regulators of calcineurin 1 (RCAN1) in mitochondrial fission and renal interstitial fibrosis using conditional knockout mice in which RCAN1 was genetically deleted in tubular epithelial cells (TECs). TEC‐specific deletion of RCAN1 attenuated tubulointerstitial fibrosis and epithelial to mesenchymal transition (EMT)‐like phenotype change after unilateral ureteral obstruction (UUO) and ischemia reperfusion injury (IRI) through suppressing TGF‐β1/Smad3 signaling pathway. TEC‐specific deletion of RCAN1 also reduced the tubular apoptosis after UUO by inhibiting cytochrome c/caspase‐9 pathway. Ultrastructure analysis revealed a marked decrease in mitochondrial fragmentation in TECs of RCAN1‐deficient mice in experimental CKD models. The expression of mitochondrial profission proteins dynamin‐related protein 1 (Drp1) and mitochondrial fission factor (Mff) was also downregulated in obstructed kidney of TEC‐specific RCAN1‐deficient mice. Furthermore, TEC‐specific deletion of RCAN1 attenuated the dysfunctional tubular autophagy by regulating PINK1/Parkin‐induced mitophagy in CKD. RCAN1 knockdown and knockout similarly improved the mitochondrial quality control in HK‐2 cells and primary cultured mouse tubular cells stimulated by TGF‐β1. Put together, our data indicated that RCAN1 plays an important role in the progression of tubulointerstitial fibrosis through regulating the mitochondrial quality. Therefore, targeting RCAN1 may provide a potential therapeutic approach in CKD.
Renal tubular damage plays a key role in the pathogenesis of diabetic kidney disease (DKD), and one of the main pathological process associated with DKD in diabetic mice is the ferroptosis, a novel ...form of cell death caused by iron-dependent lipid peroxidation. Several researches suggested that empagliflozin may treat renal injury, but its effects on diabetic-related ferroptosis and underlying mechanisms were not fully elucidated. In this study, the influence of empagliflozin on renal injury was evaluated in vivo and in vitro in a mouse model and in high-glucose (HG) or Erastin-stimulated renal HK-2 cell line, respectively. Ferroptosis-related markers were assessed, including GSH, labile iron levels, and ferroptosis regulators by Western blot, qRT-PCR, immunohistochemistry, and immunofluorescence. The level of malondialdehyde (MDA) and the fluorescence intensity of BODIPY probe indicated the level of lipid peroxidation. It was demonstrated that solute carrier family 7, member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) were less expressed in renal biopsy samples from patients affected by DKD than in those from non-diabetic renal disease patients (NDRD), proving the ferroptosis of tubular epithelial cells in case of DKD. Furthermore, empagliflozin markedly decreased the ferroptosis impairment in DKD mice, as well as in HG model of HK-2 cells. Our investigations showed the ability of empagliflozin to suppress ferroptosis was partially countered by AMP-activated protein kinase (AMPK) inhibitor, which led to a reduction of the nuclear translocation of the antioxidant transcription factor NFE2-related factor 2 (NRF2) and downregulation of target genes such as GPX4, ferritin heavy chain 1 (FTH1), and SLC7A11, while AMPK agonists were responsible for the enhancement of the protective effects of empagliflozin. Taken together, our findings showed that empagliflozin may prevent the development of ferroptosis by promoting the AMPK-mediated NRF2 activation pathway, providing important insights for possible novel treatment approaches for DKD.
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•Ferroptosis was involved in the pathogenesis of DKD.•Empagliflozin alleviated the occurrence of renal tubular cell ferroptosis in DKD.•Empagliflozin inhibited HG-mediated renal tubular ferroptosis dependent on AMPK/NRF2 axis.
Doping of a cluster has often been used to stabilize and modify the structure and properties of the resulting doped cluster. In the current work, we reported the structures, stabilities and ...electronic properties of 3d transition metal (V, Cr, Mn, Fe, Co, Ni) atoms doped B16− clusters using CALYPSO searching method and density functional theory. The drum-shaped MB16− are favored for M = V, Cr, Mn, Fe and Co with high symmetry of C2v, C4v, C4v, D8d and D8d symmetry respectively, while M = Ni with Cs symmetry exhibits an open bowl-shaped structure. The infrared spectra, Raman spectra and photoelectron spectra are predicted and can be used to identify the structures of these isomers from experiments. The stabilities are discussed by analyzing the binding energy, substitution reaction, HOMO–LUMO gaps and chemical hardness. In addition, electronic properties are analyzed by calculating the charge transfer, magnetic properties and chemical bonding. Finally, with the assembly of FeB16− and CoB16− drum-shaped clusters, two different Fe2B24− and Co2B24− clusters, which are structurally characterized as tubular forms whose triple rings are composed of three eight-membered boron rings, are identified in a high symmetry C4v, respectively. Subsequently, the magnetic properties are investigated. The present results open a door for the discovery of more drum-shaped assemblies.
Abstract
Skeletal muscle atrophy is prevalent and remarkably increases the risk of cardiovascular (CV) events and mortality in hemodialysis (HD) patients. However, whether diaphragm dysfunction ...predicts clinical outcomes in HD patients is unknown. This was a prospective cohort study of 103 HD patients. After assessment of diaphragm function by ultrasonography and collection of other baseline data, a 36-month follow-up was then initiated. Participants were divided into diaphragm dysfunction (DD+) group and normal diaphragm function (DD−) group, according to cutoff value of thickening ratio (i.e. the change ratio of diaphragm thickness) at force respiration. The primary endpoint was the first nonfatal CV event or all-cause mortality. A secondary endpoint was less serious CV events (LSCEs, a composite of heart failure readmission, cardiac arrhythmia or myocardial ischemia needed pharmacological intervention in hospital). 98 patients were eligible to analysis and 57 (58.16%) were men. 28 of 44 patients(63.64%) in DD+ group and 23 of 54 patients (42.59%) in DD− group had at least one nonfatal CV event or death (
p
= 0.038). Compared to DD− group, DD+ group had significantly higher incidence of LSCEs (21
vs.
14,
p
= 0.025) and shorter survival time (22.02 ± 12.98 months
vs.
26.74 ± 12.59 months,
p
= 0.046). Kaplan–Meier analysis revealed significantly higher risks of primary endpoint (
p
= 0.039), and LSCEs (
p
= 0.040) in DD+ group. Multivariate hazard analysis showed that DD+ group had significantly higher risk of primary endpoint hazard ratio (HR) 1.59; 95% confident interval (CI) 1.54–1.63, and LSCEs (HR 1.47; 95%CI 1.40–1.55). Ultrasound-assessed diaphragm dysfunction predicts clinical outcomes in HD patients.
Trial registration: This study was registered with Chinese Clinical Trials Registry (
www.chictr.org.cn
) as ChiCTR1800016500 on Jun 05, 2018.
National key protected wild plants (NKPWPs) are species with important conservation value based on genetics, ecology, culture, and/or scientific research, which are also confronted with serious ...threats. However, their geographical distribution patterns and conservation status remain unclear. In this study, we compiled 1032 species of NKPWPs. We measured the diversity to identify hotspots of NKPWPs based on species richness, weighted range size rarity and a complementarity‐based analysis. Comparing the distribution and hotspots of NKPWPs with the coverage of Chinese nature reserves (NRs), we assessed conservation effectiveness and identified conservation gaps. The results identified 13 diversity hotspots; only 9.5% of them were covered by NRs with >30% of the grid cell area, and even 19.5% were not covered at all by NRs. Overall, 44.7% of NKPWPs were effectively protected by national NRs. Despite this success, 571 species in Yunnan, Guizhou, Sichuan, Chongqing, Guangxi, Guangdong, southern Hainan, Taiwan, and northern Xinjiang remain unprotected by NRs. The protected proportion of plants with first‐level protection was lower than that of plants with second‐level protection. The low overall proportion of protected hotspots indicates that the conservation outlook for NKPWPs is not optimistic. This study identifies priority conservation areas and conservation gaps and provides a scientific reference for the conservation of wild plants in China.
This study identified hotspots for priority conservation and conservation gaps of national key protected wild plants (NKPWPs) based on species richness, weighted range size rarity and a complementarity‐based analysis. The protected proportion of plants with first‐level protection is lower than that with second‐level protection, and the low proportion of protected hotspots indicates that the conservation status of NKPWPs is not optimistic.
Abstract
Background
The Oral Health-related Quality of Life (OHRQoL) is a multi-dimensional concept commonly used to examine the impact of health status on quality of life, and the Oral Health Impact ...Profile-14 (OHIP-14) questionnaire is a good self-assessment tool. This study was designed to investigate the factor structure of the OHIP-14 scale Chinese version, measurement invariance and latent mean differences across genders among college students.
Methods
The online survey was completed by 919 college students. This study used confirmatory factor analysis (CFA) to check the structural models of the OHIP-14 scale, The correlation of each item with the scale total score could test homogeneity, and Cronbach’s alpha (Cronbach’s α) could evaluate internal consistency. Multi-group CFA was used to explore whether the Chinese version of the OHIP-14 scale was used in male and female populations for measurement consistency. T-test compared scores between men and women. Regression analyses were used to evaluate the relationship between age, gender, education, subject, and the score on the OHIP-14 scale.
Results
We found that the 7-factor structure had the best fit index in the sample. According to Cronbach’s α, the overall score of OHIP was 0.958, and Cronbach’s α for 7 factors was: functional limitation was 0.800, physical pain was 0.854, psychological discomfort was 0.902, physical disability was 0.850, psychological disability was 0.768, social disability was 0.862, social handicap was 0.819 and the test–retest reliability interval was 0.723. Multi-group confirmatory factor analysis supported residual measurement invariance across gender. T-test for scores showed that females scored higher significantly than men as did the overall score, in terms of physical pain (
p
<0.001), physical disability (
p
<0.001), and psychological disability (
p
<0.001).
Conclusions
This study found the OHIP-14 Chinese version to be a good tool for assessing the college students' OHRQoL in China, allowing people to conduct self-assessments.
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•The additive MgO to Ni/SiO2 catalyst could enhance CO2 activation and dissociation.•Nien-0.4 %MgO catalyst possessed high activity and strong coke resistance.•The providing electron ...capacity of additive MgO became stronger as the Ni particle size was smaller.•The smaller Ni particle size and higher Ni electron density promoted CO2 activation and dissociation.
Design and preparation of coke resistant nickel-based (Ni-based) catalyst is the key point for the industrial application of carbon dioxide reforming of methane. In this work, MgO-promoted Ni/SiO2 catalysts with tunable particle size were prepared by the multiple-impregnation method and were employed to catalyze carbon dioxide reforming of methane. Results showed that the additive MgO was an electron donor, and its providing electron capacity to Ni became stronger as the Ni particle size was smaller. Catalytic activity evaluation presented that the Nien-0.4 %MgO catalyst possessed superior catalytic activity (CH4 and CO2 conversions maintained at 83.6 % and 89.9 %) at 750 °C. Its carbon deposition amount was only 0.16 wt.% after 100 h runs. The higher activity and the stronger coke resistance of the Nien-0.4 %MgO catalyst were due to the smaller Ni particle size (8.4 nm) and higher Ni electron density, which could promote CO2 activation and dissociation, and finally balance the formation rates of C species and O species over the MgO-promoted Ni/SiO2 catalysts.