| 1. |
|
|
| 2. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
|
|
| 3. |
- Beal, Jacob, et al.
(författare)
-
Robust estimation of bacterial cell count from optical density
- 2020
-
Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
|
|
| 4. |
-
- 2019
-
Tidskriftsartikel (refereegranskat)
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Li, Jie, et al.
(författare)
-
Heat stress alters G-protein coupled receptor-mediated function and endothelium-dependent relaxation in rat mesenteric artery
- 2008
-
Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 588:2-3, s. 280-285
-
Tidskriftsartikel (refereegranskat)abstract
- Heat stress has been demonstrated to have strong cardiovascular effects. However, the underlying mechanism-mediated cardiovascular effects are still not fully understood. The present study was designed to examine if heat stress alters vascular G-protein coupled receptor-mediated vasomotion and endothelium function in rat mesenteric artery. Rats were divided into two groups, heat stress rats and control. The G-protein coupled receptors of endothelin type B (ETB) receptor-, endothelin type A (ETA) receptor-, 5-hydroxytryptamine (5-HT) receptor-, calcitonin gene-related peptide (CGRP) receptor-, alpha-adrenoceptor-mediated vosoactivity and endothelium-dependent relaxation on rat mesenteric artery ring segments were monitored by a myograph system. The plasma level of CGRP was determined by radioimmunological assay. Compared with control arterial segments, the contractile response curves of sarafotoxin 6c, a selective ETB receptor agonist and 5-HT in the arterial segments from heat stress rats were shifted towards left. An increased maximum contraction (E-max) induced by sarafotoxin 6c, but not 5-HT, was seen in the arterial segments from heat stress rats. CGRP-incluced relaxation in endothelium-denuded arterial segments from heat stress rats was enhanced. The relaxation in endothelium-intact arterial segments induced by acetylcholine was significantly decreased in heat stress rats. In addition, the plasma concentration of CGRP was increased in heat stress rats. The endothelium-dependent relaxation was characterized and shown there was a decrease in nitric oxide and endothelium-derived hyperpolarising factor-mediated relaxation in the arterial segments from heat stress rats. In conclusion, heat stress induces an enhanced vascular endothelin ETB-, 5-HT-receptors-mediated contraction, an enhanced CGRP-receptor-induced relaxation and damage to endothelium-dependent relaxation.
|
|
| 9. |
|
|
| 10. |
- Cao, Lei, et al.
(författare)
-
Cigarette smoke upregulates rat coronary artery endothelin receptors in vivo.
- 2012
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:3
-
Tidskriftsartikel (refereegranskat)abstract
- Cigarette smoking is a strong cardiovascular risk factor and endothelin (ET) receptors are related to coronary artery diseases. The present study established an in vivo secondhand smoke (SHS) exposure model and investigated the hypothesis that cigarette smoke induces ET receptor upregulation in rat coronary arteries and its possible underlying mechanisms.
|
|
| 11. |
- Cao, Lei, et al.
(författare)
-
Secondhand cigarette smoke induces increased expression of contractile endothelin receptors in rat coronary arteries via a MEK1/2 sensitive mechanism
- 2021
-
Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 55:1, s. 50-55
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Cigarette smoke, a strong risk factor for cardiovascular diseases, upregulates contractile endothelin (ET) receptors in coronary arteries. The present study examined the effects of second hand cigarette smoke exposure on the contractile endothelin receptors and the role of the MEK1/2 pathway in rat coronary arteries. Design: Rats were exposed to secondhand smoke (SHS) for 8 weeks followed by intraperitoneal injection of a MEK1/2 inhibitor, U0126 daily for another 4 weeks. Contractile responses of isolated coronary arteries were recorded by a sensitive wire myograph. The receptor protein expression levels were examined by Western blotting. Results: The results showed that SHS in vivo caused increased expression of ET receptors ETA and ETB, and that the MEK1/2 blocker U0126 significantly reversed SHS exposure-increased ETA-mediated contractile responses and protein levels. Similar alterations were observed in ETB receptors. U0126 showed dose-dependent effects on SHS-induced response on contractile property and protein levels of the ETB receptor. However, only the higher dose U0126 (15 mg/kg) had inhibitory effects on the ETA receptor. Conclusions: Taken together, our data show that SHS increases contractile ET receptors and MEK1/2 pathway inhibitor offsets SHS exposure-induced ETA and ETB receptor upregulation in rat coronary arteries.
|
|
| 12. |
|
|
| 13. |
- Cao, Lei, et al.
(författare)
-
Secondhand smoke exposure induces Raf/ERK/MAPK-mediated upregulation of cerebrovascular endothelin ETA receptors.
- 2011
-
Ingår i: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cigarette smoking enhances the risk of stroke. However, the underlying molecular mechanisms are largely unknown. The present study established an in vivo rat secondhand cigarette smoking (SHS) model and examined the hypothesis that SHS upregulates endothelin receptors with increased cerebrovascular contraction via the Raf/extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinases (MAPK) pathway. RESULTS: Rats were exposed to SHS for up to 8 weeks. The cerebral artery vasoconstriction was recorded by a sensitive myograph. The mRNA and protein expressions for endothelin receptors in cerebral arteries were studied by real-time PCR and Western blot. Compared to fresh air exposed rats, cerebral arteries from SHS rats exhibited stronger contractile responses (P < 0.05) mediated by endothelin type A (ETA) receptors. The expressions of mRNA and protein for ETA receptors in the cerebral arteries from SHS rats were higher (P < 0.05) than that in control. SHS did not affect endothelin type B (ETB) receptor-mediated contractions, mRNA or protein levels. The results suggest that SHS upregulates ETA, but not ETB receptors in vivo. After SHS exposure, the mRNA levels of Raf-1 and ERK1/2, the protein expression of phosphorylated (p)-Raf-1 and p-ERK1/2 were increased (P < 0.05). Raf-1 inhibitor, GW5074 suppressed the enhanced ETA receptor-mediated contraction, mRNA and protein levels induced by SHS. In addition, GW5074 inhibited the SHS-caused increased mRNA and phosphorylated protein levels of Raf-1 and ERK1/2, suggesting that SHS induces activation of the Raf/ERK/MAPK pathway. CONCLUSIONS: SHS upregulates cerebrovascular ETA receptors via the Raf/ERK/MAPK pathway, which provides novel understanding of mechanisms involved in SHS-associated stroke.
|
|
| 14. |
- Cao, Lei, et al.
(författare)
-
The effects of MEK1/2 inhibition on cigarette smoke exposure-induced ET receptor upregulation in rat cerebral arteries
- 2016
-
Ingår i: Toxicology and Applied Pharmacology. - : Elsevier BV. - 0041-008X. ; 304, s. 70-78
-
Tidskriftsartikel (refereegranskat)abstract
- Cigarette smoking, a major stroke risk factor, upregulates endothelin receptors in cerebral arteries. The present study examined the effects of MEK1/2 pathway inhibition on cigarette smoke exposure-induced ET receptor upregulation. Rats were exposed to the secondhand smoke (SHS) for 8 weeks followed by intraperitoneal injection of MEK1/2 inhibitor, U0126 for another 4 weeks. The urine cotinine levels were assessed with high-performance liquid chromatography. Contractile responses of isolated cerebral arteries were recorded by a sensitive wire myograph. The mRNA and protein expression levels of receptor and MEK/ERK1/2 pathway molecules were examined by real-time PCR and Western blotting, respectively. Cerebral artery receptor localization was determined with immunohistochemistry. The results showed the urine cotinine levels from SHS exposure group were significantly higher than those from the fresh group. In addition, the MEK1/2 inhibitor, U0126 significantly reduced SHS exposure-increased ETA receptor mRNA and protein levels as well as contractile responses mediated by ETA receptors. The immunoreactivity of increased ETA receptor expression was primarily cytoplasmic in smooth muscle cells. In contrast, ETB receptor was noted in endothelial cells. However, the SHS-induced decrease in endothelium-dependent relaxation was unchanged after U0126 treatment. Furthermore, SHS increased the phosphorylation of MEK1/2 and ERK1/2 protein in cerebral arteries. By using U0126 could inhibit the phosphorylated ERK1/2 protein but not MEK1/2. Taken together, our data show that treatment with MEK1/2 pathway inhibitor offsets SHS exposure-induced ETA receptor upregulation in rat cerebral arteries.
|
|
| 15. |
- Cao, Zhi-Guo, et al.
(författare)
-
Particle size : A missing factor in risk assessment of human exposure to toxic chemicals in settled indoor dust
- 2012
-
Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 49, s. 24-30
-
Tidskriftsartikel (refereegranskat)abstract
- For researches on toxic chemicals in settled indoor dust, selection of dust fraction is a critical influencing factor to the accuracy of human exposure risk assessment results. However, analysis of the selection of dust fraction in recent studies revealed that there is no consensus. This study classified and presented researches on distribution of toxic chemicals according to dust particle size and on relationship between dust particle size and human exposure possibility. According to the literature, beyond the fact that there were no consistent conclusions on particle size distribution of adherent fraction, dust with particle size less than 100 mu m should be paid more attention and that larger than 250 mu m is neither adherent nor proper for human exposure risk assessment. Calculation results based on literature data show that with different selections of dust fractions, analytical results of toxic chemicals would vary up to 10-fold, which means that selecting dust fractions arbitrarily will lead to large errors in risk assessment of human exposure to toxic chemicals in settled dust. Taking into account the influence of dust particle size on risk assessment of human exposure to toxic chemicals, a new methodology for risk assessment of human exposure to toxic chemicals in settled indoor dust is proposed and human exposure parameter systems to settled indoor dust are advised to be established at national and regional scales all over the world.
|
|
| 16. |
- Li, Jie, et al.
(författare)
-
Minimally modified LDL upregulates endothelin type B receptors in rat basilar artery
- 2012
-
Ingår i: Microvascular Research. - : Elsevier BV. - 1095-9319 .- 0026-2862. ; 83:2, s. 178-184
-
Tidskriftsartikel (refereegranskat)abstract
- Minimally modified low density lipoprotein (mmLDL) is a well-known risk factor for cerebral vascular diseases and upregulation of endothelin type B (ETB) receptors plays key roles in the pathogenesis. The present study was designed to examine if mmLDL upregulated endothelin ETB receptors in basilar artery and its possible intracellular signaling molecular mechanisms. Rat basilar arteries were cultured for 24 h in the presence of mmLDL with specific inhibitors. The artery contractile responses and receptor expressions of mRNA and protein were investigated using myograph system, real-time PCR and Western blot techniques, respectively. Results showed that ETB receptor agonist, sarafotoxin 6c induced a weak contraction in fresh basilar artery segments. After organ culture the contraction curve mediated by ETB receptor was shifted towards the left with an increased E-max of 88 +/- 6%. The mmLDL 10 mu g/mL further shifted the concentration contractile curves towards the left with an increased E-max of 116 +/- 12%. The organ culture significantly increased ETB receptor mRNA and protein levels from fresh arteries, which was further enhanced by mmLDL The staurosporine (PKC inhibitor), both SB386023 and U0126 (extracellular signal related kinases 1 and 2 inhibitor), and wedelolactone (NF-kappa B inhibitor) almost totally abolished organ culture-increased and mmLDL-increased contraction and expressions of endothelin ETB receptor. SP600125 (C-jun terminal kinase inhibitor) and SB203580 (p38 inhibitor) attenuated both organ cultured-induced and mmLDL-induced upregulation of endothelin ETB receptors. In conclusion, mmLDL upregulates ETB receptors of cerebral basilar artery via the PKC. MAPK and NF-kappa B signal pathways. (C) 2011 Elsevier Inc. All rights reserved.
|
|
| 17. |
- Li, Jie, et al.
(författare)
-
Regional variations of vasomotion to G-protein coupled receptor agonists following heat stress in rats
- 2010
-
Ingår i: Journal of Pharmacy and Pharmacology. - 0022-3573. ; 62:3, s. 315-322
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives This study was designed to compare vascular contractile and relaxing responses to G-protein coupled receptor agonists among the different regions of arteries following heat stress in rats. Methods Heat exposure was performed by increasing the internal temperature of the rats to 42 degrees C for 15 min. After heat stress for 48 h, a rnyograph system was used to monitor the contractile responses in rat renal, femoral and mesenteric arteries to agonists of endothelin type B (ETB) receptor, endothelin type A (ETA) receptor, serotonin receptor and alpha-adrenoceptor, respectively. In addition, calcitonin gene-related peptide (CGRP)-induced vasodilation was studied. Key findings The results showed that heat stress induced decreased contractions mediated by alpha-adrenoceptors and serotonin receptors (at lower concentration), while it increased contraction mediated by endothelin ETB receptors and enhanced relaxation mediated by CGRP receptors in the renal artery. Heat stress increased contractions mediated by endothelin ETB receptors, endothelin ETA receptors and alpha-adrenoceptors in the femoral artery. In the mesenteric artery, heat stress increased contractions mediated by endothelin ETB and serotonin receptors and relaxation mediated by CGRP receptors. Conclusions The vasomotor responses to the G-protein coupled receptor agonists with altered vascular contractions and relaxations were different in rat renal, femoral and mesenteric arteries after heat stress. This might have contributed to the redistribution of blood flow and aids understanding of the preconditioning phenomenon.
|
|
| 18. |
|
|
| 19. |
- Wang, Zhaoming, et al.
(författare)
-
Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
|
|
| 20. |
- Xie, Yuan, et al.
(författare)
-
Key molecular alterations in endothelial cells in human glioblastoma uncovered through single-cell RNA sequencing
- 2021
-
Ingår i: JCI Insight. - : American Society For Clinical Investigation. - 2379-3708. ; 6:15
-
Tidskriftsartikel (refereegranskat)abstract
- Passage of systemically delivered pharmacological agents into the brain is largely blocked by the blood-brain-barrier (BBB), an organotypic specialization of brain endothelial cells (ECs). Tumor vessels in glioblastoma (GBM), the most common malignant brain tumor in humans, are abnormally permeable, but this phenotype is heterogeneous and may differ between the tumor's center and invasive front. Here, through single-cell RNA sequencing (scRNA-seq) of freshly isolated ECs from human glioblastoma and paired tumor peripheral tissues, we have constructed a molecular atlas of human brain ECs providing unprecedented molecular insight into the heterogeneity of the human BBB and its molecular alteration in glioblastoma. We identified 5 distinct EC phenotypes representing different states of EC activation and BBB impairment, and associated with different anatomical locations within and around the tumor. This unique data resource provides key information for designing rational therapeutic regimens and optimizing drug delivery.
|
|
| 21. |
- Zhang, Jin-Yan, et al.
(författare)
-
Dimethylsulfoxide-soluble Smoking Particles and Nicotine Affect Vascular Contractibility
- 2009
-
Ingår i: Archives of Pharmacal Research. - : Springer Science and Business Media LLC. - 1976-3786 .- 0253-6269. ; 32:10, s. 1475-1481
-
Tidskriftsartikel (refereegranskat)abstract
- The aim is to study the effect of dimethylsulfoxide-soluble smoking particles (DSP) and nicotine on the contractility of rat mesenteric artery. The superior mesenteric artery segments were cultured with DSP or nicotine for 24 h. The vascular contractibility was recorded with myograph system. DSP 0.4 mL/L and nicotine 0.48 and 0.96 mg/L shifted the concentration-contractile curves induced by sarafotoxin 6c, a selective agonist for ETB receptor toward the left with increased E-max. DSP 0.4 mL/L and nicotine 0.96 mg/L shifted ETA receptor-mediated the concentration-contractile curves toward the left with increased E-max. However, nicotine 0.06 mg/L which is the equivalent concentration of nicotine in DSP 0.4 mL/L did not affect the curves and the E-max mediated with ETA receptor and ETB receptor. DSP 0.2 and 0.4 mL/L shifted the concentration-contractile curves induced by noradrenaline toward the right with decreased E-max. Neither did nicotine 0.06 and 0.96 mg/L. Both DSP and nicotine shifted the concentration-contractile curves induced by 5-hydroxytryptamine (5-HT) toward the right parallely. DSP changed the phenotypes towards an increased efficacy of ETA receptor and ETB receptor, and a reduced efficacy of 5-HT receptor and alpha-adrenocceptor. The effects of DSP on ETB receptor, ETA receptor and alpha-adrenocceptor were independent of nicotine. The effect on 5-HT receptor was responsible to nicotine.
|
|
| 22. |
- Abbafati, Cristiana, et al.
(författare)
-
- 2020
-
Tidskriftsartikel (refereegranskat)
|
|
| 23. |
- Beier, Sebastian, et al.
(författare)
-
Construction of a map-based reference genome sequence for barley, Hordeum vulgare L.
- 2017
-
Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
-
Tidskriftsartikel (refereegranskat)abstract
- Barley (Hordeum vulgare L.) is a cereal grass mainly used as animal fodder and raw material for the malting industry. The map-based reference genome sequence of barley cv. â € Morex' was constructed by the International Barley Genome Sequencing Consortium (IBSC) using hierarchical shotgun sequencing. Here, we report the experimental and computational procedures to (i) sequence and assemble more than 80,000 bacterial artificial chromosome (BAC) clones along the minimum tiling path of a genome-wide physical map, (ii) find and validate overlaps between adjacent BACs, (iii) construct 4,265 non-redundant sequence scaffolds representing clusters of overlapping BACs, and (iv) order and orient these BAC clusters along the seven barley chromosomes using positional information provided by dense genetic maps, an optical map and chromosome conformation capture sequencing (Hi-C). Integrative access to these sequence and mapping resources is provided by the barley genome explorer (BARLEX).
|
|
| 24. |
- Birney, Ewan, et al.
(författare)
-
Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
-
Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
|
|
| 25. |
- Cai, Yan, et al.
(författare)
-
Infliximab alleviates inflammation and ex vivo airway hyperreactivity in asthmatic E3 rats
- 2011
-
Ingår i: International Immunology. - : Oxford University Press (OUP). - 1460-2377 .- 0953-8178. ; 23:7, s. 443-451
-
Tidskriftsartikel (refereegranskat)abstract
- Tumor necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of asthma, and neutralization of TNF-alpha is an effective therapy for inflammatory diseases. The present study tested the idea that a TNF-alpha antibody, infliximab, may be useful in the management of asthma. E3 rats were immunized with ovalbumin (OVA)/alum and received infliximab intra-peritoneally. Two weeks later, OVA-PBS was instilled intranasally daily for 7 days. Bronchoalveolar lavage fluids (BALFs), serum and lung homogenates were collected for analysis of cells and inflammatory mediators. Contractile responses of lobar-bronchus segments to agonists were functionally tested. Pulmonary tissues were investigated using histological examination. The results showed that the sensitized 'model E3 rats' exhibited an increase in the total amount of inflammatory cells, primarily eosinophils, in BALF and pulmonary tissue, as well as epithelial damage. Serum levels of IgE increased and so did the levels of nitric oxide, inducible nitric oxide synthase, TNF-alpha and IL-4, IL-5 and IL-13 in lung homogenate and serum. Furthermore, the contractile responses in bronchi induced by endothelin-1, sarafotoxin 6c and bradykinin increased and isoprenaline-induced relaxations decreased. All these changes induced by the sensitization procedure were reduced by the infliximab treatment. The results suggest that infliximab prevents the development of local airway inflammation and antagonizes changes of the bronchial smooth muscle receptor phenotype, thereby blocking the development of airway smooth muscle hyperreactivity of asthmatic rats.
|
|
| 26. |
- Cao, Da-fu, et al.
(författare)
-
Evaluation of prestress losses in prestressed concrete specimens subjected to freeze–thaw cycles
- 2016
-
Ingår i: Structure and Infrastructure Engineering. - Abington, UK : Taylor & Francis. - 1573-2479 .- 1744-8980. ; 12:2, s. 159-170
-
Tidskriftsartikel (refereegranskat)abstract
- Prestressed concrete structures are considered to be reliable and durable. However, their long-term performance when subjected to frost attack is still unclear. In this work, experiments were carried out to evaluate the prestress losses in post-tensioned prestressed concrete specimens subjected to freeze–thaw cycles (FTCs). Two cases were considered: in one case, a series of specimens were prepared and tested in a freeze–thaw chamber; in the second case, the same series of specimens were tested in an indoor environment (outside the chamber). The difference between the prestress losses of the specimens inside the freeze–thaw chamber and those outside the chamber equalled the prestress losses due to FTCs. When using mathematical models to predict the prestress losses due to the FTCs, it was found that they were relatively small when the concrete was slightly damaged. However, they increased rapidly when the FTCs were repeated. The eccentricity of the prestress wires led to larger prestress losses when subjected to FTCs. Moreover, the same cross section and eccentricity resulted in similar prestress losses due to the FTCs, and the relatively high-strength concrete could withstand more FTCs.
|
|
| 27. |
- Cao, Huiming, et al.
(författare)
-
Effect of Enterohepatic Circulation on the Accumulation of Per- and Polyfluoroalkyl Substances : Evidence from Experimental and Computational Studies
- 2022
-
Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 56:5, s. 3214-3224
-
Tidskriftsartikel (refereegranskat)abstract
- The pharmacokinetic characteristics of per- and polyfluoroalkyl substances (PFAS) affect their distribution and bioaccumulation in biological systems. The enterohepatic circulation leads to reabsorption of certain chemicals from bile back into blood and the liver and thus influences their elimination, yet its influence on PFAS bioaccumulation remains unclear. We explored the role of enterohepatic circulation in PFAS bioaccumulation by examining tissue distribution of various PFAS in wild fish and a rat model. Computational models were used to determine the reabsorbed fractions of PFAS by calculating binding affinities of PFAS for key transporter proteins of enterohepatic circulation. The results indicated that higher concentrations were observed in blood, the liver, and bile compared to other tissues for some PFAS in fish. Furthermore, exposure to a PFAS mixture on the rat model showed that the reabsorption phenomenon appeared during 8-12 h for most long-chain PFAS. Molecular docking calculations suggest that PFAS can bind to key transporter proteins via electrostatic and hydrophobic interactions. Further regression analysis adds support to the hypothesis that binding affinity of the apical sodium-dependent bile acid transporter is the most important variable to predict the human half-lives of PFAS. This study demonstrated the critical role of enterohepatic circulation in reabsorption, distribution, and accumulation of PFAS.
|
|
| 28. |
- Cao, Huiming, et al.
(författare)
-
Screening of Potential PFOS Alternatives To Decrease Liver Bioaccumulation : Experimental and Computational Approaches
- 2019
-
Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 53:5, s. 2811-2819
-
Tidskriftsartikel (refereegranskat)abstract
- Perfluorooctanesulfonate (PFOS) is a persistent organic pollutant with significant bioaccumulation potential in liver tissues. Exposure to PFOS could cause increase of liver weight, induce adenomas of the liver, and cause hepatomegaly. Alternatives of PFOS might be designed and synthesized that have significantly lower liver bioaccumulation. In this study, we conducted animal exposure experiments to investigate tissue accumulations of 14 per- and polyfluoroalkyl substances. Correlation analysis demonstrated that accumulation of the compounds in rat liver had strong correlations with their binding affinities of liver fatty acid binding protein (LFABP). Thus, we combined a quantitative structure-activity relationship model with molecular dynamics (MD) simulations to develop computational models to predict the LFABP binding affinities of two newly synthesized alternatives, perfluorodecalin-2-sulfonic acid and N-diperfluorobutanoic acid. The binding characteristics of the PFOS alternatives for LFABP were elaborated to explore how the different structural modifications of molecules influenced the underlying binding mechanisms. Subsequent animal experiments demonstrated that the binding free energy calculations based on the MD simulations provided a good indicator to reflect the relative degree of liver accumulation of the PFOS alternatives in the same exposure doses and durations. Our findings from the combination of experimental exposure and computational model can provide helpful information to design potential alternatives of PFOS with weak LFABP binding capability and low liver accumulation.
|
|
| 29. |
|
|
| 30. |
- Cao, Yong-Xiao, et al.
(författare)
-
Ligustilide induces vasodilatation via inhibiting voltage dependent calcium channel and receptor-mediated Ca(2+) influx and release.
- 2006
-
Ingår i: Vascular Pharmacology. - : Elsevier BV. - 1537-1891. ; 45:3, s. 171-176
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present study was to investigate the effect of ligustilide on vasodilatation in rat mesenteric artery and the mechanisms responsible for it. Isometric tension of rat mesenteric artery rings was recorded by a sensitive myograph system in vitro. The results showed that ligustilide at concentrations more than 10 mu M relaxed potassium chloride (KCl)-preconstricted rat mesenteric artery in a con centration-dependent manner. The vasodilatation effect of ligustilide was not dependent on endothelium. Ligustilide rightwards shifted concentration-response curves induced by KCl, calcium chloride (CaCl2), noradrenaline (NA) or 5-hydroxytryptamine (5-HT) in a non-parallel manner. This suggests that the vasodilatation effects were most likely via voltage-dependent calcium channel (VDCC) and receptor-operated calcium channel (ROCC). Propranolol, glibenclamide, tetraethylammonium and barium chloride did not affect the vasodilation induced by ligustilide, showing that beta-adrenoceptor, ATP sensitive potassium channel, calcium-activated potassium channel and inwardly rectifying potassium channel were not involved in the vasodilatation. Ligustilide concentration-dependently inhibited the vasoconstriction induced by NA or CaCl2 in Ca2+-free medium, indicating that the vasodilatation relates to inhibition of extracellular Ca2+ influx through VDCC and ROCC, and intracellular Ca2+ release from Ca2+ store. Since caffeine-induced contraction was inhibited by ligustilide, inhibition of intracellular Ca2+ released by ligustilide occurred via the ryanodine receptors. Our results suggest that ligustilide induces vasodilatation in rat mesenteric artery by inhibiting the VDCC and ROCC, and receptor-mediated Ca2+ influx and release. (c) 2006 Elsevier Inc. All rights reserved.
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
- Ding, Xue Bing, et al.
(författare)
-
Impaired meningeal lymphatic drainage in patients with idiopathic Parkinson’s disease
- 2021
-
Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:3, s. 411-418
-
Tidskriftsartikel (refereegranskat)abstract
- Animal studies implicate meningeal lymphatic dysfunction in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease (PD). However, there is no direct evidence in humans to support this role1–5. In this study, we used dynamic contrast-enhanced magnetic resonance imaging to assess meningeal lymphatic flow in cognitively normal controls and patients with idiopathic PD (iPD) or atypical Parkinsonian (AP) disorders. We found that patients with iPD exhibited significantly reduced flow through the meningeal lymphatic vessels (mLVs) along the superior sagittal sinus and sigmoid sinus, as well as a notable delay in deep cervical lymph node perfusion, compared to patients with AP. There was no significant difference in the size (cross-sectional area) of mLVs in patients with iPD or AP versus controls. In mice injected with α-synuclein (α-syn) preformed fibrils, we showed that the emergence of α-syn pathology was followed by delayed meningeal lymphatic drainage, loss of tight junctions among meningeal lymphatic endothelial cells and increased inflammation of the meninges. Finally, blocking flow through the mLVs in mice treated with α-syn preformed fibrils increased α-syn pathology and exacerbated motor and memory deficits. These results suggest that meningeal lymphatic drainage dysfunction aggravates α-syn pathology and contributes to the progression of PD.
|
|
| 34. |
- Fu, Jiahong, et al.
(författare)
-
Effect of an impinging jet on the flow characteristics and thermal performance of mainstream in battery cooling of hybrid electric vehicles
- 2022
-
Ingår i: International Journal of Heat and Mass Transfer. - : Elsevier BV. - 0017-9310. ; 183
-
Tidskriftsartikel (refereegranskat)abstract
- The novel concept of impinging jet cooling, i.e., an active-passive air cooling strategy, was proposed to achieve improved battery thermal management in hybrid vehicles, and this method is supported by excess high pressure discharged air. To comprehensively realize the active-passive combined cooling behavior, a rectangular channel with a jet impingement hole was utilized to experimentally and numerically study the flow characteristics and thermal performance of the joint cooling mechanism. The numerical results were confirmed by the experimental data in this work, the maximum deviations of the offset and Nusselt numbers are 18.8% and 7.5%, respectively. The thermal transport performs much better under the interaction between the mainstream and impinging jet, i.e., the average Nusselt number and maximum Nusselt number can be increased by 0.43-16.55, 5.73-34.42, respectively, at inlet pressures of the impinging jet in the range of 1–6 bar. The values of Nu/Nu0/(f/f0) 1/3 are improved by 1.52–3.33. The jet fluid was deflected under the influence of the mainstream and a vortex can be induced, which is beneficial for the heat transfer performance. The jet fluid closely reached the heated plane at a relatively large volume flow rate and the heat transfer performance was excellent once the jet fluid touched the heated plane. The thermal boundary layer becomes thinned under the impact of the impinging jet but the magnitude of the reduction is relatively slight.
|
|
| 35. |
- Fu, Jiahong, et al.
(författare)
-
EXPERIMENTAL STUDY ON HEAT TRANSFER ENHANCEMENT OF AIR JET IMPINGEMENT FOR ELECTRONICS THERMAL MANAGEMENT
- 2022
-
Ingår i: Journal of Enhanced Heat Transfer. - 1065-5131. ; 29:4, s. 63-80
-
Tidskriftsartikel (refereegranskat)abstract
- Jet impingement cooling was investigated on a flat heating surface placed in a flow channel, including single jet cooling, in-line double jet cooling, and combined crossflow and jet cooling; cross-flow cooling was a baseline for comparison. In addition, the in-line double jet cooling was explored with various jet distances. Local Nusselt number distribution was experimentally achieved by the liquid crystal method, and the measurements were carried out under various jet pressures ranging from 1 bar to 4 bar. It was found that heat transfer depends on the jet distance because one jet may produce a crossflow effect on the other jet, affecting the formation of longitudinal vortices which could enhance heat transfer. It was seen that in comparison to the crossflow cooling, the average Nusselt number is enhanced by 110%, 150%, and 380%by the single jet cooling, the in-line double jet cooling, and the combined cooling, respectively, and correspondingly the maximum Nusselt number is enhanced by 160%, 240%, and 540%, respectively. In the combined cooling, there is a deflection distance ranging from 0 mm to 10 mm depending on the jet pressure.
|
|
| 36. |
- Gao, Yan, et al.
(författare)
-
Differential accumulation and elimination behavior of perfluoroalkyl acid isomers in occupational workers in a manufactory in China
- 2015
-
Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 49:11, s. 6953-6962
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, serum and urine samples were collected from 36 occupational workers in a fluorochemical manufacturing plant in China from 2008 to 2012 to evaluate the body burden and possible elimination of linear and branched perfluoroalkyl acids (PFAAs). Indoor dust, total suspended particles (TSP), diet, and drinking water samples were also collected to trace the occupational exposure pathway to PFAA isomers. The geometric mean concentrations of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexanesulfonate (PFHxS) isomers in the serum were 1386, 371, and 863 ng mL(-1), respectively. The linear isomer of PFOS, PFOA, and PFHxS was the most predominant PFAA in the serum, with mean proportions of 63.3, 91.1, and 92.7% respectively, which were higher than the proportions in urine. The most important exposure routes to PFAA isomers in the occupational workers were considered to be the intake of indoor dust and TSP. A renal clearance estimation indicated that branched PFAA isomers had a higher renal clearance rate than did the corresponding linear isomers. Molecular docking modeling implied that linear PFOS (n-PFOS) had a stronger interaction with human serum albumin (HSA) than branched isomers did, which could decrease the proportion of n-PFOS in the blood of humans via the transport of HSA.
|
|
| 37. |
- Jia, Yanhua, et al.
(författare)
-
Wearable Thermoelectric Materials and Devices for Self-Powered Electronic Systems
- 2021
-
Ingår i: Advanced Materials. - : WILEY-V C H VERLAG GMBH. - 0935-9648 .- 1521-4095. ; 33:42
-
Forskningsöversikt (refereegranskat)abstract
- The emergence of artificial intelligence and the Internet of Things has led to a growing demand for wearable and maintenance-free power sources. The continual push toward lower operating voltages and power consumption in modern integrated circuits has made the development of devices powered by body heat finally feasible. In this context, thermoelectric (TE) materials have emerged as promising candidates for the effective conversion of body heat into electricity to power wearable devices without being limited by environmental conditions. Driven by rapid advances in processing technology and the performance of TE materials over the past two decades, wearable thermoelectric generators (WTEGs) have gradually become more flexible and stretchable so that they can be used on complex and dynamic surfaces. In this review, the functional materials, processing techniques, and strategies for the device design of different types of WTEGs are comprehensively covered. Wearable self-powered systems based on WTEGs are summarized, including multi-function TE modules, hybrid energy harvesting, and all-in-one energy devices. Challenges in organic TE materials, interfacial engineering, and assessments of device performance are discussed, and suggestions for future developments in the area are provided. This review will promote the rapid implementation of wearable TE materials and devices in self-powered electronic systems.
|
|
| 38. |
- Jiang, Haiying, et al.
(författare)
-
A Highly Crystalline Wide-Band-Gap Conjugated Polymer toward High-Performance As-Cast Nonfullerene Polymer Solar Cells
- 2017
-
Ingår i: ACS Applied Materials and Interfaces. - : AMER CHEMICAL SOC. - 1944-8244 .- 1944-8252. ; 9:41, s. 36061-36069
-
Tidskriftsartikel (refereegranskat)abstract
- A new wide-band-gap conjugated polymer PBODT was successfully synthesized that showed high crystallinity and was utilized as, the active material in nonfullerene bulk-heterojunction, polymer solar cells (PSCs). The photovoltaic devices based on the as-cast blend films of PBODT with ITIC and IDIC acceptors showed notable power conversion efficiencies (PCEs) of 7.06% and 9:09%, with high open-circuit voltages of 1.00 and 0.93 V that correspond to low energy losses of 0.59 and 0.69 eV, respectively. In the case of PBODT:ITIC, lower exciton quenching efficiency and monomolecular recombination are found for devices with small driving force. On the other hand, the relatively higher driving force and suppressed monomolecular recombination for PBODT:IDIC devices are identified to be the reason for their higher short-circuit current density (J(sc)) and higher PCEs. In addition, when processed with the nonchlorinated solvent 1,2,4-trimethylbenzene, a good, PCE of 8.19% was still, achieved for the IDIC-based device. Our work shows that such wide-band-gap polymers have great potential for the environmentally friendly fabrication of highly efficient PSCs.
|
|
| 39. |
- Jiang, Qinglin, et al.
(författare)
-
High Thermoelectric Performance in n-Type Perylene Bisimide Induced by the Soret Effect
- 2020
-
Ingår i: Advanced Materials. - : WILEY-V C H VERLAG GMBH. - 0935-9648 .- 1521-4095. ; 32:45
-
Tidskriftsartikel (refereegranskat)abstract
- Low-cost, non-toxic, abundant organic thermoelectric materials are currently under investigation for use as potential alternatives for the production of electricity from waste heat. While organic conductors reach electrical conductivities as high as their inorganic counterparts, they suffer from an overall low thermoelectric figure of merit (ZT) due to their small Seebeck coefficient. Moreover, the lack of efficient n-type organic materials still represents a major challenge when trying to fabricate efficient organic thermoelectric modules. Here, a novel strategy is proposed both to increase the Seebeck coefficient and achieve the highest thermoelectric efficiency for n-type organic thermoelectrics to date. An organic mixed ion-electron n-type conductor based on highly crystalline and reduced perylene bisimide is developed. Quasi-frozen ionic carriers yield a large ionic Seebeck coefficient of -3021 mu V K-1, while the electronic carriers dominate the electrical conductivity which is as high as 0.18 S cm(-1)at 60% relative humidity. The overall power factor is remarkably high (165 mu W m(-1)K(-2)), with aZT= 0.23 at room temperature. The resulting single leg thermoelectric generators display a high quasi-constant power output. This work paves the way for the design and development of efficient organic thermoelectrics by the rational control of the mobility of the electronic and ionic carriers.
|
|
| 40. |
- Lei, Ying, et al.
(författare)
-
The Raf-1 inhibitor GW5074 and dexamethasone suppress sidestream smoke-induced airway hyperresponsiveness in mice
- 2008
-
Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Sidestream smoke is closely associated with airway inflammation and hyperreactivity. The present study was designed to investigate if the Raf-1 inhibitor GW5074 and the anti-inflammatory drug dexamethasone suppress airway hyperreactivity in a mouse model of sidestream smoke exposure. Methods: Mice were repeatedly exposed to smoke from four cigarettes each day for four weeks. After the first week of the smoke exposure, the mice received either dexamethasone intraperitoneally every other day or GW5074 intraperitoneally every day for three weeks. The tone of the tracheal ring segments was recorded with a myograph system and concentration-response curves were obtained by cumulative administration of agonists. Histopathology was examined by light microscopy. Results: Four weeks of exposure to cigarette smoke significantly increased the mouse airway contractile response to carbachol, endothelin-1 and potassium. Intraperitoneal administration of GW5074 or dexamethasone significantly suppressed the enhanced airway contractile responses, while airway epithelium-dependent relaxation was not affected. In addition, the smoke-induced infiltration of inflammatory cells and mucous gland hypertrophy were attenuated by the administration of GW5074 or dexamethasone. Conclusion: Sidestream smoke induces airway contractile hyperresponsiveness. Inhibition of Raf-1 activity and airway inflammation suppresses smoking-associated airway hyperresponsiveness.
|
|
| 41. |
- Li, Faji, et al.
(författare)
-
Genetic architecture of grain yield in bread wheat based on genome-wide association studies
- 2019
-
Ingår i: BMC Plant Biology. - : BioMed Central. - 1471-2229. ; 19
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundIdentification of loci for grain yield (GY) and related traits, and dissection of the genetic architecture are important for yield improvement through marker-assisted selection (MAS). Two genome-wide association study (GWAS) methods were used on a diverse panel of 166 elite wheat varieties from the Yellow and Huai River Valleys Wheat Zone (YHRVWD) of China to detect stable loci and analyze relationships among GY and related traits.ResultsA total of 326,570 single nucleotide polymorphism (SNP) markers from the wheat 90K and 660K SNP arrays were chosen for GWAS of GY and related traits, generating a physical distance of 14,064.8Mb. One hundred and twenty common loci were detected using SNP-GWAS and Haplotype-GWAS, among which two were potentially functional genes underpinning kernel weight and plant height (PH), eight were at similar locations to the quantitative trait loci (QTL) identified in recombinant inbred line (RIL) populations in a previous study, and 78 were potentially new. Twelve pleiotropic loci were detected on eight chromosomes; among these the interval 714.4-725.8Mb on chromosome 3A was significantly associated with GY, kernel number per spike (KNS), kernel width (KW), spike dry weight (SDW), PH, uppermost internode length (UIL), and flag leaf length (FLL). GY shared five loci with thousand kernel weight (TKW) and PH, indicating significantly affected by two traits. Compared with the total number of loci for each trait in the diverse panel, the average number of alleles for increasing phenotypic values of GY, TKW, kernel length (KL), KW, and flag leaf width (FLW) were higher, whereas the numbers for PH, UIL and FLL were lower. There were significant additive effects for each trait when favorable alleles were combined. UIL and FLL can be directly used for selecting high-yielding varieties, whereas FLW can be used to select spike number per unit area (SN) and KNS.ConclusionsThe loci and significant SNP markers identified in the present study can be used for pyramiding favorable alleles in developing high-yielding varieties. Our study proved that both GWAS methods and high-density genetic markers are reliable means of identifying loci for GY and related traits, and provided new insight to the genetic architecture of GY.
|
|
| 42. |
- Li, He, et al.
(författare)
-
Enhanced G-protein coupled receptors-mediated contraction and reduced endothelium-dependent relaxation in hypertension
- 2007
-
Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 557:2-3, s. 186-194
-
Tidskriftsartikel (refereegranskat)abstract
- The present study was designed to demonstrate a hypothesis that some G-protein coupled receptors are up-regulated and a dysfunction of endothelium occurs in hypertension. The arteries from hypertensive patients and spontaneously hypertensive rats (SHR) were tested. An in vitro myograph system was used to obtain concentration-contraction curves mediated by endothelin ETA, endothelin ETB, 5-hydroxytryptamine 2A (5HT(2A))-receptors and alpha(1)-adrenoceptors in the arterial segments. In hypertensive patients, the maximum contractions (E-max) induced by endothelin ETB, endothelin ETA and 5-HT receptors were significantly increased with elevated pEC(50) values, while a significantly leftward shift of alpha(1)-adrenoceptor-mediated contraction was seen. Similar results were obtained in SHR. Specific antagonists for 5-HT2A receptors or alpha(1)-adrenoceptors rightward shifted the concentration-contractile curves induced by 5-HT or noradrenalin, while the Emax were not significantly altered, suggesting that the contractions were mediated by 5-HT2A receptors and ocl-adrenoceptors, respectively. Endothelium-dependent maximum relaxation (R-max) in the arterial segments induced by acetylcholine was significantly decreased in both hypertensive patients and SHR. In addition, nitric oxide- and endothelium-derived hyperpolarizing factor-mediated dilatations were decreased significantly and the arterial enclothelial cells were in part lost in SHR. In conclusion, endotheliD ETB, endothelin ETA, 5-HT2A receptor- and alpha-adrenoceptor-mediated contractions were increased in hypertension, while the endotheliurn and its ftinctions were damaged. (c) 2006 Elsevier B.V All rights reserved.
|
|
| 43. |
- Li, Jie, et al.
(författare)
-
Minimally modified LDL upregulates endothelin type B receptors in rat coronary artery via ERK1/2 MAPK and NF-kappa B pathways
- 2012
-
Ingår i: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. - : Elsevier BV. - 1388-1981. ; 1821:4, s. 582-589
-
Tidskriftsartikel (refereegranskat)abstract
- Minimally modified low density lipoprotein (mmLDL) is a well-known risk factor for coronary artery disease. Upregulation of vascular endothelin type B (ETB) receptors on the vascular smooth muscle cells is predicted to be the molecular mechanism that leads to cardiovascular pathogenesis. The objective of the present study was to examine the hypothesis that mmLDL upregulates ETB receptors in rat coronary artery. The contractile responses to sarafotoxin 6c (ETB receptor agonist) were studied using a sensitive myograph. ETB receptor mRNA and protein expression was determined using real-time PCR and Western blot analysis. The results showed that organ culture increased the contractile responses induced by sarafotoxin 6c and the levels of ETB receptor mRNA and protein. This increase was further enhanced by the addition of mmLDL (10 mu g/mL). Specific ERK1/2 inhibitors (SB386023 and U0126) and an NF-kappa B inhibitor (wedelolactone) attenuated the mmLDL-increased ETB receptor-mediated contraction and ETB receptor mRNA and protein levels. Wedelolactone significantly attenuated the mmLDL-decreased I kappa B-alpha protein expression. Consistent with this result, I kappa B-alpha protein expression was significantly decreased by culture with mmLDL compared to the level of expression in the organ culture group. However, the JNK inhibitor, SP600125 or p38 pathway inhibitor, SB203580 did not inhibit mmLDL-enhanced effects. The PKC inhibitor, staurosporine attenuated only culture-alone-increased effects. In conclusion, mmLDL upregulates the ETB receptors in rat coronary arterial smooth muscle cells, mainly via activation of the ERK1/2 MAPK and the downstream transcriptional factor NF-kappa B. (C) 2011 Elsevier B.V. All rights reserved.
|
|
| 44. |
- Li, Shuijie, et al.
(författare)
-
Impaired oxygen-sensitive regulation of mitochondrial biogenesis within the von Hippel–Lindau syndrome
- 2022
-
Ingår i: Nature Metabolism. - : Nature Publishing Group. - 2522-5812. ; 4:6, s. 739-758
-
Tidskriftsartikel (refereegranskat)abstract
- Mitochondria are the main consumers of oxygen within the cell. How mitochondria sense oxygen levels remains unknown. Here we show an oxygen-sensitive regulation of TFAM, an activator of mitochondrial transcription and replication, whose alteration is linked to tumours arising in the von Hippel–Lindau syndrome. TFAM is hydroxylated by EGLN3 and subsequently bound by the von Hippel–Lindau tumour-suppressor protein, which stabilizes TFAM by preventing mitochondrial proteolysis. Cells lacking wild-type VHL or in which EGLN3 is inactivated have reduced mitochondrial mass. Tumorigenic VHL variants leading to different clinical manifestations fail to bind hydroxylated TFAM. In contrast, cells harbouring the Chuvash polycythaemia VHLR200W mutation, involved in hypoxia-sensing disorders without tumour development, are capable of binding hydroxylated TFAM. Accordingly, VHL-related tumours, such as pheochromocytoma and renal cell carcinoma cells, display low mitochondrial content, suggesting that impaired mitochondrial biogenesis is linked to VHL tumorigenesis. Finally, inhibiting proteolysis by targeting LONP1 increases mitochondrial content in VHL-deficient cells and sensitizes therapy-resistant tumours to sorafenib treatment. Our results offer pharmacological avenues to sensitize therapy-resistant VHL tumours by focusing on the mitochondria.
|
|
| 45. |
- Li, Tao, et al.
(författare)
-
AIF Overexpression Aggravates Oxidative Stress in Neonatal Male Mice After Hypoxia-Ischemia Injury
- 2022
-
Ingår i: Molecular Neurobiology. - : Springer Science and Business Media LLC. - 0893-7648 .- 1559-1182. ; 59:11, s. 6613-6631
-
Tidskriftsartikel (refereegranskat)abstract
- There are sex differences in the severity, mechanisms, and outcomes of neonatal hypoxia-ischemia (HI) brain injury, and apoptosis-inducing factor (AIF) may play a critical role in this discrepancy. Based on previous findings that AIF over-expression aggravates neonatal HI brain injury, we further investigated potential sex differences in the severity and molecular mechanisms underlying the injury using mice that overexpress AIF from homozygous transgenes. We found that the male sex significantly aggravated AIF-driven brain damage, as indicated by the injury volume in the gray matter (2.25 times greater in males) and by the lost volume of subcortical white matter (1.71 greater in males) after HI. As compared to females, male mice exhibited more severe brain injury, correlating with reduced antioxidant capacities, more pronounced protein carbonylation and nitration, and increased neuronal cell death. Under physiological conditions (without HI), the doublecortin-positive area in the dentate gyrus of females was 1.15 times larger than in males, indicating that AIF upregulation effectively promoted neurogenesis in females in the long term. We also found that AIF stimulated carbohydrate metabolism in young males. Altogether, these findings corroborate earlier studies and further demonstrate that AIF is involved in oxidative stress, which contributes to the sex-specific differences observed in neonatal HI brain injury.
|
|
| 46. |
- Li, Xiaoqing, et al.
(författare)
-
Antihyperuricemic Effect of Green Alga Ulva lactuca Ulvan through Regulating Urate Transporters
- 2021
-
Ingår i: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 69:38, s. 11225-11235
-
Tidskriftsartikel (refereegranskat)abstract
- A novel polysaccharide from Ulva lactuca (ULP) was purified using a Sepharose CL-4B column. Fourier transform infrared spectroscopy, high-performance liquid chromatography, and nuclear magnetic resonance spectroscopy were employed to analyze the structure of ULP. It consisted of rhamnose (Rha), glucuronic acid (GluA), galactose (Gal), and xylose (Xyl) at a molar ratio of 32.75:22.83:1.07:6.46 with the molecular weight of 2.24 x 10(5) Da. The four major glycosidic residues found in ULP were -> 2,3)-alpha-L-Rhap-(1 ->, -> 4)-beta-D-GlcpA-(1 ->, -> 2,6)-beta-D-Galp-(1 ->, and -> 4)-beta-D-Xylp-(1 ->. The antihyperuricemic activity of ULP was exhibited by detecting related biochemical indexes, urate transporter gene expressions, renal histopathology, and intestinal microbiota shifts. ULP obviously decreased the levels of serum uric acid (UA), blood urea nitrogen, and creatinine, while inhibited serum and hepatic xanthine oxidase activities as well as improved renal injury in hyperuricemic mice. Furthermore, the upregulation of UA excretion genes ABCG2/OAT1 and downregulation of UA resorption genes URAT1 and GLUT9 were detected. In addition, ULP exerted its antihyperuricemic effect through regulating the intestinal microbiome, characterized by elevating the helpful microbial abundance, meanwhile declining the harmful bacterial abundance and restoring the gut microbiome homeostasis. This study demonstrates the antihyperuricemic activity of ULP and its potential effect for the treatment of hyperuricemia-related diseases.
|
|
| 47. |
- Li, Yong, et al.
(författare)
-
Buoyancy and Thermal Acceleration of Supercritical n-Decane in a Rectangular Channel
- 2022
-
Ingår i: Journal of Thermophysics and Heat Transfer. - 0887-8722. ; 36:2, s. 419-430
-
Tidskriftsartikel (refereegranskat)abstract
- In this work, supercritical n-decane flowing in ducts with different orientations is thoroughly investigated in terms of secondary flow, wall shear stress, and thermal acceleration. It is known that the secondary flow strength hardly plays a role in cases of flowing upward, flowing downward, or flowing horizontally at a small heat flux/mass flux. Still, an attachment point can be found at the center for cases of flowing upward and flowing downward, and this enhances the heat transfer. For a large heat flux/mass flux, thermal transport depends not only on the secondary flow strength but also on the secondary flow structure. Besides, a separation point is found at the center for flowing up/downward cases, and the more adjacent the attachment point is to the heated wall, the more serious is the thermal transport. The wall shear stress is beneficial to heat transfer but also relies on the distribution profile. Thermal acceleration can really diminish or even restrain the HTD phenomenon, but it is not the reason to cause the difference of heat transfer behavior for channels with different orientations.
|
|
| 48. |
- Li, Yong, et al.
(författare)
-
竖直矩形通道内超临界正癸烷振荡特性的大涡模拟
- 2022
-
Ingår i: Nanjing Hangkong Hangtian Daxue Xuebao/Journal of Nanjing University of Aeronautics and Astronautics. - 1005-2615. ; 54:2, s. 281-289
-
Tidskriftsartikel (refereegranskat)abstract
- Active generative cooling based on supercritical hydrocarbon fuel is regarded as one of the most promising methods for scramjet thermal management. A large eddy simulation method is used to explore the transient change law of the initial flow, and heat transfer behaviors of supercritical hydrocarbon fuel is in rectangular channels. An oscillation effect can be proved in the convective heat transfer process, i.e., the temperature and velocity distributions fluctuate strongly. By monitoring the velocity variation rule of 10-4 s time scale, the approximate trigonometric frequency and amplitude are present in this oscillation. At the initial heating condition, the high-temperature fluid, which is close to the heated wall, flows into the low-temperature region under the effect of buoyancy force. As the fluid temperature gradually reaches the pseudo-critical value, its thermo-physical properties change dramatically. The friction factor oscillates as well as the fluid kinetic energy. Correspondingly, the enhanced vortex is induced away from the heated wall. Over time, the enhanced vortex begins to move to the heated wall and the low-temperature fluid impinges on the wall. Consequently, the thermal transport is enhanced.
|
|
| 49. |
- Liu, Hao, et al.
(författare)
-
Graphene oxide for nonvolatile memory application by using electrophoretic technique
- 2020
-
Ingår i: Materials Today Communications. - : Elsevier BV. - 2352-4928. ; 25
-
Tidskriftsartikel (refereegranskat)abstract
- The experimental work presented here, for the first time using electrophoretic technique to fabricate graphene oxide (GO)-based resistive random access memory (RRAM). By using electrophoretic technique, nonvolatile RRAM devices with Aluminum (Al)/GO/Indium tin oxide (ITO) cross-bar sandwich-like structure were fabricated. The fabricated devices show typical bipolar resistant switching behavior with ON/OFF ratio more than 10, retention time more than 102 s, and transition voltage less than 1.7 V. The switching mechanism for the devices is ascribed to the formation and rupture of the conducting filament induced by the diffusion of oxygen ions. The results show that the electrophoretic technique holds great potential for film manufacturing for RRAM.
|
|
| 50. |
|
|
