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Atherosclerosis (AS) with iron and lipid overload and systemic inflammation is a risk factor for Alzheimer’s disease. M1 macrophage/microglia participate in neuronal pyroptosis and recently have been reported to be the ferroptosis-resistant phenotype. Quercetin plays a prominent role in preventing and treating neuroinflammation, but the protective mechanism against neurodegeneration caused by iron deposition is poorly understood. ApoE–/–mice were fed a high-fat diet with or without quercetin treatment. The Morris water maze and novel object recognition tests were conducted to assess spatial learning and memory, and nonspatial recognition memory, respectively. Prussian blue and immunofluorescence staining were performed to assess the iron levels in the whole brain and in microglia, microglia polarization, and the degree of microglia/neuron ferroptosis. In vitro, we further explored the molecular biological alterations associated with microglial polarization, neuronal pyroptosis, and ferroptosis via Western blot, flow cytometry, CCK8, LDH, propidium iodide, and coculture system. We found that quercetin improved brain lesions and spatial learning and memory in AS mice. Iron deposition in the whole brain or microglia was reversed by the quercetin treatment. In the AS group, the colocalization of iNOS with Iba1 was increased, which was reversed by quercetin. However, the colocalization of iNOS with PTGS2/TfR was not increased in the AS group, suggesting a character resisting ferroptosis. Quercetin induced the expression of Arg-1 and decreased the colocalizations of Arg-1 with PTGS2/TfR. In vitro, ox-LDL combined with ferric ammonium citrate treatment (OF) significantly shifted the microglial M1/M2 phenotype balance and increased the levels of free iron, ROS, and lipid peroxides, which was reversed by quercetin. M1 phenotype induced by OF caused neuronal pyroptosis and was promoted to ferroptosis by L-NIL treatment, which contributed to neuronal ferroptosis as well. However, quercetin induced the M1 to M2 phenotype and inhibited M2 macrophages/microglia and neuron pyroptosis or ferroptosis. In summary, quercetin alleviated neuroinflammation by inducing the M1 to M2 phenotype to inhibit neuronal pyroptosis and protected neurons from ferroptosis, which may provide a new idea for neuroinflammation prevention and treatment.

Purpose: In order to extend the application of the original octagonal Goodman–Smith fatigue limit diagram, which is commonly used for the evaluation of structure fatigue stress in engineering, a modification of it is proposed for the structure made of S355 steel (commonly used in high-speed electric multiple units (EMUs) bogie frame). Design/methodology/approach: The modification is made based on Deutscher Verband für Schweißen und verwandte Verfahren e. V. (DVS) 1612 standard and the γ-P-S-N curve, with consideration of the fatigue evaluation requirements of different survival rates and confidence levels. The verification of the modification is performed for three welded joints and for the comparison with the experimental data. Findings: The results indicate that the design survival rate, the design safety margin and the fatigue stress evaluation of welded joint types are all improved by using the modified diagram. Originality/value: There are relatively few studies on modifying octagonal Goodman–Smith fatigue limit diagram. In this paper, a modified diagram is proposed and applied in order to ensure the safety and durability of key welded structures of rail vehicles.

2-Hydroxyglutarate (2-HG) is an unconventional oncometabolite of α-ketoglutarate. Isocitrate dehydrogenase mutation is generally acknowledged to be the main cause of 2-HG accumulation. In isocitrate dehydrogenase mutant tumors, 2-HG accumulation inhibits α-ketoglutarate/Fe(II)-dependent dioxygenases, resulting in epigenetic alterations. Recently, the increase of 2-HG has also been observed in the cases of mitochondrial dysfunction and hypoxia. In these cases, 2-HG not only inhibits α-ketoglutarate/Fe(II)-dependent dioxygenases to regulate epigenetics but also affects other cellular pathways, such as regulating hypoxia-inducible transcription factors and glycolysis. These provide a new perspective for the study of 2-HG.

BackgroundThe aetiology of diabetes is complex with limited treatment strategies. Growing animal studies have shown that targeted antiageing can improve the outcomes of diabetes. However, population evidence is limited. This study aims to evaluate the associations of biological ageing with all-cause and cause-specific mortality among people with diabetes.MethodsA total of 5278 people with diabetes from the National Health and Nutrition Examination Survey 1999–2014 were included. Biological ageing was measured from different perspectives, including phenotypic age, biological age, telomere length and klotho concentration. Phenotypic/biological age acceleration was the residual resulting from a linear model when regressing phenotypic/biological age on chronological age. Cox proportional hazards models were used to examine the relationships between ageing and all-cause, cardiovascular disease (CVD), and cancer mortality.ResultsOver median follow-up for 7.3 years, 1355 diabetics died. There was a positive and linear association of mortality with phenotypic age acceleration (HRall-cause1.04; HRCVD1.04; HRcancer1.04, p<0.001) and biological age acceleration (HRall-cause1.03; HRCVD1.04; HRcancer1.03, p<0.001). Telomere length was inversely associated with all-cause mortality (tertile (T)3 vs T1: HR 0.67, p<0.05). The concentration of klotho had a U-shaped relationship with mortality (T2 vs T1: HRall-cause0.62; HRCVD0.48; HRcancer0.47, p<0.05). Further, stratified analysis by age and sex found that the associations of ageing-related markers with mortality were more significant in the aged and female subgroup.ConclusionsBiological ageing was positively associated with mortality among people with diabetes, indicating therapies targeting antiageing could be encouraged to halt the progression of diabetes.

Emerging evidence suggests that higher circulating long-chain n-3 polyunsaturated fatty acids (n-3PUFA) levels were intimately associated with lower prevalence of obesity and insulin resistance. However, the understanding of bioactivity and potential mechanism of α-linolenic acid-rich flaxseed oil (ALA-FO) against insulin resistance was still limited. This study evaluated the effect of FO on high-fat diet (HFD)-induced insulin resistance in C57BL/6J mice focused on adipose tissue lipolysis. Mice after HFD feeding for 16 weeks (60% fat-derived calories) exhibited systemic insulin resistance, which was greatly attenuated by medium dose of FO (M-FO), paralleling with differential accumulation of ALA and its n-3 derivatives across serum lipid fractions. Moreover, M-FO was sufficient to effectively block the metabolic activation of adipose tissue macrophages (ATMs), thereby improving adipose tissue insulin signaling. Importantly, suppression of hypoxia-inducible factors HIF-1α and HIF-2α were involved in FO-mediated modulation of adipose tissue lipolysis, accompanied by specific reconstitution of n-3PUFA within adipose tissue lipid fractions.

Graphene oxide (GO) is considered to be an emerging environmental pollutant with its inevitable release into the environment. Thus, its potential environmental risks and biosafety are receiving increased attention. In this study, Paeonia ostiiwas exposed to GO under drought stress. The results demonstrated that GO prevented soil water from evaporating due to its hydrophilic oxygen-containing functional groups and did not change the soil pH. Moreover, GO treatment resulted in lower increases in reactive oxygen species, relative electrical conductivity and free proline content, and greater increases in the antioxidant enzyme activities of P. ostiiunder drought stress compared with those in the control. And under drought stress, higher photosynthesis, more intact mesophyll cells and organelles and open stomata were found in P. ostiiunder GO treatment. Furthermore, GO treatment induced greater changes in the expression patterns of genes required for lignin biosynthesis, photosynthesis-antenna proteins, carbon fixation in photosynthetic organisms, and glyoxylate and dicarboxylate metabolism. Additionally, GO did not accumulate in P. ostiidue to the soil environment and the electrostatic repulsion between GO and the roots. GO did not have toxic effects on P. ostiiand was an effective soil water retention agent; therefore, it could be economically beneficial for the production of plants under drought stress.

ABSTRACTOil bodies (OBs) are organelles of lipid storage in plants. In order to clarify the properties of OBs development in herbaceous peony (Paeonia lactifloraPall.) seeds, this research had studied anatomical structures, particle size, zeta potential, the stability of OBs and characteristics of oleosin gene (OLE). It showed that OB particle size increased gradually during seed development, OBs accumulated in the endosperm cells, and their zeta potential firstly decreased and then increased. Temperature had not affected the stability of OBs, they could be maintained stably under the conditions of neutral and alkaline pH and less than 50 mM NaCl. Subsequently, P. lactiflora OLEwas isolated, it had 824 bp in full-length and a 435-bp open reading frame encoding 144 amino acids with isoelectric point 9.40, which had three transmembrane domain and did not has a signal peptide, and belonged to the stable protein. Alpha helix was the main part of the secondary structure, no glycosylation site and 14 potential phosphorylation sites were found. Additionally, the express level of OLEinitially increased and then decreased, and reached the highest on 60 days after flowering. These results could contribute to understand the properties of OBs development and characteristics of OLEin P. lactifloraseeds.

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Increasing evidence has demonstrated the benefits of α-linolenic acid-rich flaxseed oil (ALA-FO) against lipid metabolism abnormality in both rodent models and humans. However, the metabolic response of FO to insulin resistance and type 2 diabetes is still inconsistent. This study aimed to explore the effect of FO on chronic high fat diet (HFD)-induced hepatic steatosis, insulin resistance, and inflammation, mainly focusing on hepatic n-3 fatty acid remodeling and endoplasmic reticulum (ER) unfolded protein response. The results showed that lard-based HFD feeding for 16 weeks (60% fat-derived calories) induced whole-body insulin resistance, lipid profile abnormality, and inflammation in mice, which was alleviated by FO in a dose-dependent manner. Moreover, FO effectively improved hepatic steatosis and insulin resistance in mice by modulating the specific location of ALA and its long-chain n-3 fatty acids across hepatic lipid fractions and enhancing insulin-stimulated phosphorylation of hepatic insulin receptor subtract-1 (IRS-1) tyrosine 632 and protein kinase B (AKT) (p< 0.05). Importantly, the differential depositions of ALA and its long-chain n-3 fatty acids in plasma and ER membranes were observed, concomitant with the rescued ER unfolded protein response and Jun N-terminal kinase (JNK) signaling in mice liver.

Daminozide is a plant growth retardant that inhibits 2-oxoglutarate-dependent dioxygenase activity in the gibberellin biosynthesis pathway, but few studies have focused on its effect on the flavonoid biosynthesis pathway involved in flower color. In the present study, the effect of daminozide on the regulation of flower color was investigated. An herbaceous peony (Paeonia lactifloraPall.) cultivar ‘Fenzhu Pan’ was used as the material and treated with daminozide. Color parameters of petals were measured; flavonoid composition and content as well as flavonoid biosynthetic gene expression were monitored. The results showed that daminozide treatment caused less red coloration in herbaceous peony. The content of total anthocyanins was decreased by 23%, and the content of total anthoxanthins was increased by 8%; thus, it appeared that less red coloration in daminozide-treated flowers was associated with restricted anthocyanin accumulation. Furthermore, the gene expression patterns of flavonoid 3′-hydroxylase, dihydroflavonol 4-reductase and anthocyanidin synthase were lower after daminozide treatment, which could decrease anthocyanin accumulation and lead to less red coloration in flowers. These findings would improve our understanding of daminozide regulation of flower color in herbaceous peony.

A sensitivity-enhanced hot-wire anemometer based on a cladding-etched optical fiber Bragg grating (FBG) coated with a layer of silver film and optically heated by using a 1480 nm laser diode is demonstrated. The silver film absorbs the laser power to heat the FBG to a certain high temperature and the airflow cools down the FBG hot-wire with the cooling effect and hence the Bragg wavelength of the FBG is determined by the airflow velocity. Experimental measurement results show that the heating efficiency of the FBG hot wire is improved by 3.8 times in magnitude by etching the fiber cladding from 125 µm down to 73.4 µm, and the achieved airflow velocity sensitivities, under a laser power of 200 mW, are −3 180 pm/(m/s), −889 pm/(m/s), −268 pm/(m/s), and −8.7 pm/(m/s) at different airflow velocities of 0.1 m/s, 0.5 m/s, 1.5 m/s, and 17 m/s, respectively. In comparison, the sensitivities are only −2193 pm/(m/s), −567 pm/(m/s), −161 pm/(m/s), and −4.9 pm/(m/s) for the reference anemometer without cladding etching even at a much higher heating laser power of 530 mW. These results prove that the method by using a cladding-etched FBG to improve sensitivity of FBG-based hot-wire anemometers works and the sensitivity is improved significantly.

Herbaceous peony (Paeonia lactifloraPall.) is one of the color-leaved ornamental spring plants, with graceful appearance and splendid color. However, the underlying mechanism of this coloration variation from purple to green has not been studied in P. lactiflora. In th study, the leaves in purple, purple–green, and green stages were compared in terms of anatomical, physiological, and molecular. We found that the variation of leaf color from purple to green was mainly determined by the change in pigments distributed in the leaf surface. Physiological experiments showed a significant increase in chlorophyll contents and a notable reduction in anthocyanin contents in leaves from the purple to green stages. We further found that the anthocyanin biosynthesis-related dihydroflavonol 4-reductase (DFR) gene and anthocyanin synthase (ANS) gene as well as chlorophyll biosynthesis-related glutamyl-tRNA reductase (HEMA) gene showed a decreased trend in leaves from purple to green stages, whereas the chlorophyll degradation-related chlorophyll breductase (NYC) gene showed a rising trend. Alteration of DFRand ANSgene expression might reduce anthocyanin accumulation, whereas increased HEMAgene expression would enhance chlorophyll biosynthesis and reduced NYCgene expression would inhibit chlorophyll degradation. Consequently, reduction in anthocyanins and enhanced deposition of chlorophylls resulted in leaf coloration variation from purple to green in P. lactiflora, which could improve our understanding of its mechanism for further studies.

The mechanical strength of inflorescence stems is an important trait in cut flowers. Calcium ions (Ca2+) play a pivotal role in maintaining stem strength, but little is known about the underlying molecular mechanisms. In this study, we treated herbaceous peony (Paeonia lactifloraPall.) with ethyl glycol tetraacetic acid (EGTA), an effective Ca2+chelator, and used morphology indicators, spectroscopic analysis, histochemical staining, electron microscopy, and proteomic techniques to investigate the role of Ca2+in inflorescence stem mechanical strength. The EGTA treatment reduced the mechanical strength of inflorescence stems, triggered the loss of Ca2+from cell walls, and reduced lignin in thickened secondary walls in xylem cells as determined by spectroscopic analysis and histochemical staining. Electron microscopy showed that the EGTA treatment also resulted in significantly fewer xylem cell layers with thickened secondary walls as well as in reducing the thickness of these secondary walls. The proteomic analysis showed 1065 differentially expressed proteins (DEPs) at the full-flowering stage (S4). By overlapping the Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) analysis results, we identified 43 DEPs involved in signal transduction, transport, energy metabolism, carbohydrate metabolism, and secondary metabolite biosynthesis. Using quantitative real-time polymerase chain reaction (qRT-PCR) analysis, we showed that EGTA treatment inhibited Ca2+sensors and secondary wall biosynthesis-related genes. Our findings revealed that EGTA treatment reduced the inflorescence stem mechanical strength by reducing lignin deposition in xylem cells through altering the expression of genes involved in Ca2+binding and secondary wall biosynthesis.