| 1. |
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| 2. |
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| 3. |
- Kumar, Sonal, et al.
(författare)
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A Bi-based artificial interphase to achieve ultra-long cycling life of Al-metal anode in non-aqueous electrolyte
- 2024
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Ingår i: Energy Storage Materials. - 2405-8297. ; 65
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Tidskriftsartikel (refereegranskat)abstract
- Rechargeable aluminum-ion batteries (RAB) with Al-metal anode are regarded as cost-effective and environmentally sustainable energy storage systems. However, tapping the high volumetric capacity of the Al-anode has been a challenge because of the spontaneous and irreversible formation of the oxide layer on its surface that renders it electrochemically inactive. Though recently reported AlCl3-based electrolytes overcome this problem by breaking down this oxide layer, their highly corrosive nature hampers commercialization. Here, we investigate a novel approach to protect the Al-anode from severe oxidation by engineering an artificial protective interphase. A unique and less corrosive combination of Al(CF3SO3)3 salt and BiCl3 additive reacts with the Al-anode intrinsically to form an inorganic-rich protective bilayer. This layer is electronically insulating and significantly reduces the charge transfer resistance and surface activation energy at the anode, enabling plating/stripping at extremely low overpotential of <0.1 V that can be sustained for record-long cycling times of >4000 h.
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| 4. |
- Zhou, Bin, et al.
(författare)
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Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4.4 million participants
- 2016
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Ingår i: The Lancet. - : Elsevier B.V.. - 0140-6736 .- 1474-547X. ; 387:10027, s. 1513-1530
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Tidskriftsartikel (refereegranskat)abstract
- Background: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are aff ecting the number of adults with diabetes.Methods: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue.Findings: We used data from 751 studies including 4372000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-17.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target.Interpretation: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults aff ected, has increased faster in low-income and middle-income countries than in high-income countries.
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| 5. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 6. |
- Daré, Elisabetta, et al.
(författare)
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Methylmercury and H2O2 provoke lysosomal damage in human astrocytoma D384 cells followed by apoptosis
- 2001
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Ingår i: Free Radical Biology & Medicine. - Linköping : Elsevier. - 0891-5849 .- 1873-4596. ; 30:12, s. 1347-1356
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Tidskriftsartikel (refereegranskat)abstract
- Methylmercury (MeHg) is a neurotoxic agent acting via diverse mechanisms, including oxidative stress. MeHg also induces astrocytic dysfunction, which can contribute to neuronal damage. The cellular effects of MeHg were investigated in human astrocytoma D384 cells, with special reference to the induction of oxidative-stress-related events. Lysosomal rupture was detected after short MeHg-exposure (1 μM, 1 h) in cells maintaining plasma membrane integrity. Disruption of lysosomes was also observed after hydrogen peroxide (H2O2) exposure (100 μM, 1 h), supporting the hypothesis that lysosomal membranes represent a possible target of agents causing oxidative stress. The lysosomal alterations induced by MeHg and H2O2 preceded a decrease of the mitochondrial potential. At later time points, both toxic agents caused the appearance of cells with apoptotic morphology, chromatin condensation, and regular DNA fragmentation. However, MeHg and H2O2 stimulated divergent pathways, with caspases being activated only by H2O2. The caspase inhibitor z-VAD-fmk did not prevent DNA fragmentation induced by H2O2, suggesting that the formation of high-molecular-weight DNA fragments was caspase independent with both MeHg and H2O2. The data point to the possibility that lysosomal hydrolytic enzymes act as executor factors in D384 cell death induced by oxidative stress.
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| 7. |
- Garner, B, et al.
(författare)
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On the cytoprotective role of ferritin in macrophages and its ability to enhance lysosomal stability.
- 1997
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Ingår i: Free radical research. - : Taylor & Francis. - 1071-5762 .- 1029-2470. ; 27, s. 487-500
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Macrophages have a great capacity to take up (e.g. by endocytosis and phagocytosis) exogenous sources of iron which could potentially become cytotoxic, particularly following the intralysosomal formation of low-molecular weight, redox active iron, and under conditions of oxidative stress. Following autophagocytosis of endogenous ferritin/apoferritin, these compounds may serve as chelators of such lysosomal iron and counteract the occurrence of iron-mediated intralysosomal oxidative reactions. Such redox-reactions have been shown to lead to destabilisation of lysosomal membranes and result in leakage of damaging lysosomal contents to the cytosol. In this study we have shown: (i) human monocyte-derived macrophages to accumulate ferritin in response to iron exposure; (ii) iron to destabilise macrophage secondary lysosomes when the cells are exposed to H2O2; and (iii) endocytosed apoferritin to act as a stabiliser of the acidic vacuolar compartment of iron-loaded macrophages. While the endogenous ferritin accumulation which was induced by iron exposure was not sufficient to protect cells from the damaging effects of H2O2, exogenously added apoferritin, as well as the potent iron chelator desferrioxamine, afforded significant protection. It is suggested that intralysosomal formation of haemosiderin, from partially degraded ferritin, is a protective strategy to suppress intralysosomal iron-catalysed redox reactions. However, under conditions of severe macrophage lysosomal iron-overload, induction of ferritin synthesis is not enough to completely prevent the enhanced cytotoxic effects of H2O2.
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| 8. |
- Guo, Jin, et al.
(författare)
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Decoupling economic and energy growth : aspiration or reality?
- 2021
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Ingår i: Environmental Research Letters. - : Institute of Physics Publishing (IOPP). - 1748-9326. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- Energy has long been a driving force of economic growth; however, it comes with environmental costs and security challenges. This study analyzes the energy-economy nexus and explores their decoupling possibilities by using cross-country data over the years 1971-2014. The results indicate that, while energy use and economic growth exhibit a typical inverted U-shaped decoupling relationship for the industrialized countries, they have been rising in tandem for the developing economies. Among factors, it is the economic scale, population size, and energy intensity that are the decisive factors. Among countries, it is the U.S., China, and India, which mainly dominate the global economy-energy trend. Overall, we conclude that any global economy-energy decoupling may confront challenges and uncertainty. To better decouple economic growth from energy use, we propose policies for more structural reforms, a clean energy system, improved energy efficiency, and efficient energy demand-side management.
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| 9. |
- Jiang, Wei, et al.
(författare)
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Cerebrospinal fluid and plasma lipopolysaccharide (LPS) levels in HIV-1 infection and associations with inflammation, blood-brain barrier permeability and neuronal injury.
- 2021
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 223:9, s. 1612-1620
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Tidskriftsartikel (refereegranskat)abstract
- HIV infection is associated with increased systemic microbial translocation, neuro-inflammation and occasionally neuronal injury. Whether systemic LPS penetrates into the brain and contributes to neuro-inflammation remain unknown in HIV. Here, we measured plasma and cerebrospinal fluid (CSF) LPS levels along with biomarkers of neuro-inflammation (white blood cell counts and 40 soluble markers) and neurofilament light chain (NfL). Notably, CSF LPS was undetectable in all samples, including three HIV-infected individuals with dementia. Increased plasma LPS, neuro-inflammation, and blood-brain barrier (BBB) dysfunction were found in untreated HIV-infected individuals, but not in healthy or treated HIV-infected individuals. Plasma LPS levels were directly correlated with various markers of inflammation in both plasma and CSF, as well as with degree of BBB permeability but not with CSF NfL in HIV-infected subjects. These results suggest that the magnitude of microbial translocation associates with neuro-inflammation and BBB permeability in HIV without direct penetration into the central nervous system (CNS).
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| 10. |
- Larsson, David A, et al.
(författare)
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Oxysterol mixtures, in atheroma-relevant proportions, display synergistic and proapoptotic effects
- 2006
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Ingår i: Free Radical Biology & Medicine. - : Elsevier BV. - 0891-5849 .- 1873-4596. ; 41:6, s. 902-910
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Tidskriftsartikel (refereegranskat)abstract
- Apoptotic cells in atheroma lesions may contribute to plaque development and instability. Oxysterols constitute the major toxic component in oxLDL and are present in mixed forms in human atheroma lesions. However, the cellular effects of oxysterols have been mostly studied individually. In the present study, we investigated the cytotoxic effects of 7β-hydroxycholesterol (7βOH), 7-ketocholesterol (7keto), 25-hydroxycholesterol (25OH), and 27-hydroxycholesterol (27OH) on U937 monocytic cells, both individually and in atheroma-relevant mixtures mimicking the oxysterol composition reported in human atheroma lesions. Apoptosis and necrosis were studied by examining cell morphology, phosphatidylserine exposure, caspase activation, and the terminal dUTP nick end-labeling technique. Cellular reactive oxygen species and total amount of reduced thiols were measured by using fluorescence probes and 5,5′-dithiobis-(2-nitrobenzoic acid), respectively. We found that 7βOH and 7keto induced caspase activation, ROS production, cellular thiol depletion, permeabilization of lysosomal and mitochondrial membranes, and cell death. 25OH and 27OH did not cause any of the above alterations, whereas 7βOH and 7keto exerted synergistic toxic effects. Although single 25OH or 27OH exhibited quenching effects on both 7βOH- and 7keto-induced cell death, the combination of all four oxysterols in atheroma-relevant proportions was proapoptotic. Our findings indicate that the major oxysterols accumulated in human atheroma are proapoptotic and may contribute to atherosclerotic lesion development. © 2006 Elsevier Inc. All rights reserved.
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| 11. |
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| 12. |
- Li, Wei, 1962-, et al.
(författare)
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Alpha-tocopherol and astaxanthin decrease macrophage infiltration, apoptosis and vulnerability in atheroma of hyperlipidaemic rabbits
- 2004
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Ingår i: Journal of Molecular and Cellular Cardiology. - : Elsevier BV. - 0022-2828 .- 1095-8584. ; 37:5, s. 969-978
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Tidskriftsartikel (refereegranskat)abstract
- The composition of atherosclerotic plaques, not just macroscopical lesion size, has been implicated in their susceptibility to rupture and the risk of thrombus formation. By focusing on the quality of lipids, macrophages, apoptosis, collagen, metalloproteinase expression and plaque integrity, we evaluated the possible anti-atherosclerotic effect of the antioxidants α-tocopherol and astaxanthin in Watanabe heritable hyperlipidemic (WHHL) rabbits. Thirty-one WHHL rabbits were divided into three groups and were fed a standard diet, as controls (N =10), or a standard diet with the addition of 500 mg α-tocopherol per kg feed (N =11) or 100 mg astaxanthin per kg feed (N =10) for 24 weeks. We found that both antioxidants, particularly astaxanthin, significantly decreased macrophage infiltration in the plaques although they did not affect lipid accumulation. All lesions in the astaxanthin-treated rabbits were classified as early plaques according to the distribution of collagen and smooth muscle cells. Both antioxidants also improved plaque stability and significantly diminished apoptosis, which mainly occurred in macrophages, matrix metalloproteinase three expressions and plaque ruptures. Although neither antioxidant altered the positive correlations between the lesion size and lipid accumulation, the lesion size and apoptosis were only positively correlated in the control group. Astaxanthin and α-tocopherol may improve plaque stability by decreasing macrophage infiltration and apoptosis in this atherosclerotic setting. Apoptosis reduction by α-tocopherol and astaxanthin may be a new anti-atherogenic property of these antioxidants. © 2004 Elsevier Ltd. All rights reserved.
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| 13. |
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| 14. |
- Li, Wei, 1962-, et al.
(författare)
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Apoptotic Death of Inflammatory Cells in Human Atheroma
- 2001
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : Ovid Technologies (Wolters Kluwer Health). - 1079-5642 .- 1524-4636. ; 21:7, s. 1124-1130
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Tidskriftsartikel (refereegranskat)abstract
- Although the accumulation of cholesterol and other lipidic material is unquestionably important in atherogenesis, the reasons why this material progressively accumulates, rather than being effectively cleared by phagocytic cells such as macrophages, are not completely understood. We hypothesize that atheromatous lesions may represent "death zones" that contain toxic materials such as oxysterols and in which monocytes/macrophages become dysfunctional and apoptotic. Indeed, cathepsins B and L, normally confined to the lysosomal compartment, are present in the cytoplasm and nuclei of apoptotic (caspase-3-positive) macrophages within human atheroma. The possible involvement of oxysterols is suggested by experiments in which cultured U937 and THP-1 cells exposed to 7-oxysterols similarly undergo marked lysosomal destabilization, caspase-3 activation, and apoptosis. Like macrophages within atheroma, intralysosomal cathepsins B and L are normally present in the cytoplasm and nuclei of these oxysterol-exposed cells. Lysosomal destabilization, cathepsin release, and apoptosis may be causally related, because inhibitors of cathepsins B and L suppress oxysterol-induced apoptosis. Thus, toxic materials such as 7-oxysterols in atheroma may impair the clearance of cholesterol and other lipidic material by fostering the apoptotic death of phagocytic cells, thereby contributing to further development of atherosclerotic lesions.
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| 15. |
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| 16. |
- Li, Wei, 1962-, et al.
(författare)
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Foam cell death induced by 7β-hydroxycholesterol is mediated by labile iron-driven oxidative injury : Mechanisms underlying induction of ferritin in human atheroma
- 2005
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Ingår i: Free Radical Biology & Medicine. - : Elsevier BV. - 0891-5849 .- 1873-4596. ; 39:7, s. 864-875
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Tidskriftsartikel (refereegranskat)abstract
- Human atherosclerotic lesions typically contain large amounts of ferritin associated with apoptotic macrophages and foam cells, although the reasons are unknown. In the present investigation, we studied the relationship between ferritin induction and occurrence of apoptosis in 7β-hydroxycholesterol (7β-OH)-treated monocytic cells and macrophages. We found that 7β-OH enlarges the intracellular labile iron pool, increases formation of reactive oxygen species (ROS), and induces ferritin and cytosolic accumulation of lipid droplets, lysosomal destabilization, and apoptototic macrophage death. Since ferritin is a phase II-type protective protein, our findings suggest that ferritin upregulation here worked as an inefficient defense mechanism. Addition to the culture medium of both a membrane-permeable iron chelator 10-phenanthroline and the non-membrane-permeable iron chelators apoferritin and desferrioxamine afforded significant protection against the 7β-OH-induced effects. Consequently, endocytosed iron compounds dramatically augmented 7β-OH-induced cytotoxicity. We conclude that oxidized lipid 7β-OH causes not only foam cell formation but also oxidative damage with abnormal metabolism of cellular iron. The findings suggest that modulation of iron metabolism in human atheroma may be a potential therapeutic strategy against atherosclerosis. © 2005 Elsevier Inc. All rights reserved.
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| 17. |
- Li, Wei, 1962-, et al.
(författare)
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Induction of cell death by the lysosomotropic detergent MSDH
- 2000
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Ingår i: FEBS Letters. - 0014-5793 .- 1873-3468. ; 470:1, s. 35-39
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Tidskriftsartikel (refereegranskat)abstract
- Controlled lysosomal rupture was initiated in lysosome-rich, macrophage-like cells by the synthetic lysosomotropic detergent, O-methyl-serine dodecylamide hydrochloride (MSDH). When MSDH was applied at low concentrations, resulting in partial lysosomal rupture, activation of pro-caspase-3-like proteases and apoptosis followed after some hours. Early during apoptosis, but clearly secondary to lysosomal destabilization, the mitochondrial transmembrane potential declined. At high concentrations, MSDH caused extensive lysosomal rupture and necrosis. It is suggested that lysosomal proteases, if released to the cytosol, may cause apoptosis directly by pro-caspase activation and/or indirectly by mitochondrial attack with ensuing discharge of pro-apoptotic factors.
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| 18. |
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| 19. |
- Li, Wei, 1962-
(författare)
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Oxidative stress, macrophages, iron, and atherosclerosis
- 1997
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Macrophages have a great capacity to take up exogenous material, such as oxidatively modified low density lipoproteins (oxLDL) and different sources of iron containing structures. OxLDL is taken up into macrophage lysosomes by receptor-mediated endocytosis, but poorly degraded, resulting in foam-cell formation. The foam cell formation and the cytotoxicity of oxLDL to several arterial wall cells might contribute to atherogenesis. The iron sequestrated by macrophages could potentially become cytotoxic, particularly following intralysosomal accumulation of low-molecular weight iron in a redox-active form, and under conditions of oxidative stress. Following autophagocytosis, endogenous ferritin/apoferritin may serve as chelators of such lysosomal iron and counteract the occurrence of iron-mediated intra-lysosomal oxidative reactions.In the present study, we estimated the influence of oxLDL on lysosomal enzyme activity, lysosomal membrane stability, and the modulation of these cellular characteristics by high density lipoprotein (HDL) and vitamin E (vit-E). We also examined iron-stimulated ferritin synthesis, and the effects of exogenously added apoferritin on cells and lysosomal membrane stability following oxidative stress. Human monocyte-derived macrophages and J-774 cells were used in the study. The activities of the lysosomal enzymes, cathepsin-L and N-acetyl-ß-glucosarninidase (NAßGase), were biochemically assayed on cellular fractions. The lysosomal integrity was estimated by an acridine orange (AO) vital staining test as well as by immunocytochemical cathepsin-D demonstration. Cellular ferritin was assayed by ELISA, and lysosomal iron was demonstrated by autometallography and transmission electron microscopy.We found that the total activities of NAßGase and cathepsin-L were significantly decreased, whereas their relative cytosolic activities were enhanced after oxLDL-exposure. Labilization of the lysosomal membranes was further proven by a decreased lysosomal AO-uptake and a relocation to the cytosol of cathepsin-D. as estimated by light- and electron microscopic immunocytochemistry. HDL and vit-E diminished the cytotoxicity of oxLDL by decreasing the lysosomal damage. The synthesis and accumulation of ferritin in HMDM are responses to the iron-exposure, but ferritin is not efficient enough to protect the lysosomes from oxidative stress. Endocytosed apoferritin acts as a stabilizer of the acidic vacuolar compartment of iron-loaded macrophages.
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| 20. |
- Li, Wei, 1962-
(författare)
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Oxidized Lipids and Lysosomal Pathology in Atherogenesis
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Macrophages take up large amount of exogenous materials such as oxidatively modified low-density lipoproteins (oxLDL) and lysosomotropic agents. OxLDL is taken up into macrophage lysosomes through receptor-mediated endocytosis, but poorly degraded, resulting in foam cell formation. Cholesterol oxidation products, major toxic components of oxLDL, are involved in foam cell formation and the initiation of atherosclerosis. The production of ROS/RNS, cytokines, and matrix proteases by macrophages and the apoptosis of arterial cells may contribute to atherosclerotic plaque development and destabilization.We had four objectives in this study, first we study the influence of oxLDL on lysosomal membrane stability, location and activity of lysosomal enzymes, macrophage cell death, and the modulation of these cellular characteristics by high-density lipoprotein (HDL), vitantin E (vit E), and the iron chelator desferrioximine (DFO) or iron complex. Second, we examined the role of lysosomal enzymes in macrophage apoptosis induced by oxysterols, the major cytotoxic components of oxLDL. Third, we analyzed the expression of cysteine protease cathepsins B and L and studied their relationship to macrophage apoptosis in human atherosclerotic lesions. And fourth, we investigated whether lysosomal rupture and release of lysosomal enzymes could initiate apoptosis using the lysosomotropic detergent MSDH.The results suggest that oxLDL causes lysosomal destabilization and relocation of lysos'omal enzymes as indicated by increased cytosolic NABGase, cathepsin-L, and cathepsin D, and decreased lysosomal acridine orange (AO)-induced red fluorescence. AcLDL had no cytotoxic effects on the cells and their lysosomes. HDL, vit E, and the iron chelator DFO diminished the cytotoxicity of oxLDL by decreasing lysosomal damage, while the iron complex enhanced oxLDL cytotoxicity. Macrophage apoptosis induced by ChOx and 7-oxysterols (7B-OH and 7- keto) is associated with lysosomal rupture and release of lysosomal enzymes to the cytosol. The lysosomal punctuated immune-granularity of cathepsins B and L was decreased in 7 -oxysteroltreated cells compared to control cells. Moreover, there is enhancement and dispersion of cathepsins B and L immunoreactivity throughout 7-oxysterols-treated cells and an extensive immunoreaction in the nuclei and around nuclear areas of apoptotic cells. Using MSDH, a lysosomotropic detergent, we further demonstrated that lysosomal rupture and release of lytic enzymes indeed play an initial role in macrophage apoptosis.There is a lesion dependent eo-expression of cathepsins B and Land caspase-3 in early and advanced human atherosclerotic lesions, which is associated with macrophage apoptosis.We conclude that macrophage cell death including apoptosis induced by oxLDL and oxysterols is associated with lysosomal rupture and relocation of lysosomal hydrolytic enzymes to the cytosol. The released enzymes may initiate ceU death by activating the caspase cascade, attacking mitochondria, or directly attacking the nuclear of the cells. The high eo-expression of cathepsins B and L with caspase-3 in apoptotic macrophages in human atheroma lesions suggests that macrophage apoptosis and related hydrolytic enzymes may play an important role in lesion development and plaque instability.
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| 21. |
- Lind, Lars, et al.
(författare)
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Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
- 2021
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Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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| 22. |
- Nilsson, Sigrid, 1997-
(författare)
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Vasomotor Symptoms, Cardiovascular Risk and the Role of Physical Activity in Midlife Women
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The menopausal transition is, for most women, accompanied by hot flushes and night sweats (i.e., vasomotor symptoms, VMS). VMS has been associated with a worsened cardiovascular risk profile, but whether VMS constitutes an independent risk marker for developing subclinical atherosclerotic cardiovascular disease (ASCVD) is still uncertain. Visceral adipose tissue (VAT) contributes more to systemic low-grade inflammation than abdominal subcutaneous adipose tissue (ASAT), enhancing atherosclerosis development. Physical activity is an effective behavioral strategy to maintain and improve cardiovascular health. Whether a resistance training intervention (RTI) could reduce low-grade inflammation and VAT volume in postmenopausal women with VMS remains unclear, and whether the RTI-associated effects could be maintained over time requires further investigation.Material and Methods: This thesis is based on three studies. Study 1 was conducted on a subset of participants from the cross-sectional population-based Swedish CArdioPulmonary BioImage Study (SCAPIS), including women 50-64 years of age. The women underwent comprehensive cardiovascular assessments and completed an extensive female-specific questionnaire. VMS was assessed on a 4-point scale. Subclinical ASCVD was detected via coronary computed tomography angiography (CCTA), computed tomography (CT), and carotid ultrasound. Study 2 is a sub-study of 65 postmenopausal women with VMS and low physical activity, randomized to either three days/week of an RTI or unchanged physical activity for 15 weeks. Women underwent anthropometric measurements, magnetic resonance imaging (MRI), and blood sampling at baseline and after 15 weeks. During the last followup contact in Study 2 after two years, 35 women agreed to attend an additional clinic visit to reevaluate cardiovascular risk markers, marking the inception of Study 3.Results: Of 2995 women included in Study 1, 14.2% reported severe VMS (n = 425), 18.1% moderate VMS (n = 543), and 67.7% no or mild VMS (n = 2027). Current or previous severe VMS, but not moderate VMS, was significantly associated with CCTA-detected coronary atherosclerosis, with odds ratio (OR) before and after multivariable adjustment 1.36, 95% confidence interval (CI) 1.08 – 1.72 and 1.33, 95% CI 1.02 – 1.72, respectively. This association was only present for >5 years durations of severe VMS or when the onset of severe VMS occurred before menopause. Adjustment for menopausal hormone therapy strengthened the association for women with severe VMS >5 years (OR 1.67, 95% CI 1.16 – 2.40). Women compliant with an RTI had compared to a control group (CG), decreased adiponectin (p < 0.01), ASAT (p < 0.01), VAT (p < 0.01), total abdominal adipose tissue (TAAT) (p < 0.01) and fat ratio (p <0.001). Furthermore, an RTI reduced moderate to severe VMS frequency to six months post-intervention compared to a CG, but did neither contribute to preserved cardiovascular health markers nor improved health-related quality of life (HRQoL) after two years compared to a CG.Conclusions: There is a need for extra vigilance regarding cardiovascular risk factors in the group of women suffering from severe VMS. Implementing a 15-week RTI in these women could counteract the VAT redistribution and alter the frequency of moderate to severe VMS with maintained effects up to six months.
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| 23. |
- Shao, Jingchen, 1989, et al.
(författare)
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p27(KIP1) and PTEN cooperate in myeloproliferative neoplasm tumor suppression in mice
- 2016
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Ingår i: Experimental Hematolgy & Oncology. - : Springer Science and Business Media LLC. - 2162-3619. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- PTEN acts as a phosphatase for PIP3 and negatively regulates the PI3K/AKT pathway, and p27(KIP1) is a cyclin-dependent kinase inhibitor that regulates the G1 to S-phase transition by binding to and regulating the activity of cyclin-dependent kinases. Genetic alterations of PTEN or CDKN1B (p27(KIP1)) are common in hematological malignancies. To better understand how mutations in these two genes might cooperate in leukemogenesis, we inactivated both genes in the hematological compartment in mice. Here, we show that the combined inactivation of Pten and Cdkn1b results in a more severe myeloproliferative neoplasm phenotype associated with lower hemoglobin, enlarged spleen and liver, and shorter lifespan compared to inactivation of Pten alone. More severe anemia and increased myeloid infiltration and destruction of the spleen contributed to the earlier death of these mice, and elevated p-AKT, cyclin D1, and cyclin D3 might contribute to the development of this phenotype. In conclusion, PTEN and p27(KIP1) cooperate in tumor suppression in the hematological compartment.
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| 24. |
- Wang, Linqin, et al.
(författare)
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A crosslinked polymer as dopant-free hole-transport material for efficient n-i-p type perovskite solar cells
- 2021
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Ingår i: Journal of Energy Chemistry. - : Elsevier BV. - 2095-4956 .- 2096-885X. ; 55, s. 211-218
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Tidskriftsartikel (refereegranskat)abstract
- A new crosslinked polymer, called P65, with appropriate photo-electrochemical, opto-electronic, and thermal properties, has been designed and synthesized as an efficient, dopant-free, hole-transport material (HTM) for n-i-p type planar perovskite solar cells (PSCs). P65 is obtained from a low-cost and easily synthesized spiro[fluorene-9,9′-xanthene]-3′,6′-diol (SFX-OH)-based monomer X65 through a free-radical polymerization reaction. The combination of a three-dimensional (3D) SFX core unit, hole-transport methoxydiphenylamine group, and crosslinked polyvinyl network provides P65 with good solubility and excellent film-forming properties. By employing P65 as a dopant-free hole-transport layer in conventional n-i-p type PSCs, a power conversion efficiency (PCE) of up to 17.7% is achieved. To the best of our knowledge, this is the first time a 3D, crosslinked, polymeric dopant-free HTM has been reported for use in conventional n-i-p type PSCs. This study provides a new strategy for the future development of a 3D crosslinked polymeric dopant-free HTM with a simple synthetic route and low-cost for commercial, large-scale applications in future PSCs.
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| 25. |
- Wang, Linqin, et al.
(författare)
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Impact of Linking Topology on the Properties of Carbazole-Based Hole-Transport Materials and their Application in Solid-State Mesoscopic Solar Cells
- 2019
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Ingår i: Solar RRL. - : Wiley-VCH Verlagsgesellschaft. - 2367-198X. ; 3:9
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Tidskriftsartikel (refereegranskat)abstract
- Carbazole is a promising core for the molecular design of hole-transport materials (HTMs) for solid-state mesoscopic solar cells (ssMSCs), such as solid-state dye-sensitized solar cells (ssDSSCs) and perovskite solar cells (PSCs) due to its low cost and excellent optoelectronic properties of its derivatives. Although carbazole-based HTMs are intensely investigated in ssMSCs and promising device performance is demonstrated, the fundamental understanding of the impact of linking topology on the properties of carbazole-based HTMs is lacking. Herein, the effect of the linking topology on the optical and electronic properties of a series of carbazole-based HTMs with 2,7-substitution and 3,6-substitution is systematically investigated. The results demonstrate that the 2,7-substituted carbazole-based HTMs display higher hole mobility and conductivity among this series of analogous molecules, thereby exhibiting better device performance. In addition, the conductivity of the HTMs is improved after light treatment, which explains the commonly observed light-soaking phenomenon of ssMSCs in general. All these carbazole-based HTMs are successfully applied in ssMSCs and one of the HTMs X50-based devices yield a promising efficiency of 6.8% and 19.2% in ssDSSCs and PSCs, respectively. This study provides guidance for the molecular design of effective carbazole-based HTMs for high-performance ssMSCs and related electronic devices.
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| 26. |
- Ward, Liam, et al.
(författare)
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Proteomics and multivariate modelling reveal sex-specific alterations in distinct regions of human carotid atheroma
- 2018
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Ingår i: Biology of Sex Differences. - : BMC. - 2042-6410. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAtherosclerotic lesions are comprised of distinct regions with different proteomic profiles. Men and women develop differences in lesion phenotype, with lesions from women generally being more stable and less prone to rupture. We aimed to investigate the differences in proteomic profiles between sexes, including distinct lesion regions, to identify altered proteins that contribute to these differences observed clinically.MethodsCarotid endarterectomy samples (ten men/ten women) were obtained, and intraplaque biopsies from three distinct regions (internal control, fatty streak and plaque) were analysed by tandem-mass spectrometry. Multivariate statistical modelling, using orthogonal partial least square-discriminant analysis, was used to discriminate the proteomes between men and women.ResultsMultivariate discriminant modelling revealed proteins from 16 functional groups that displayed sex-specific associations. Additional statistics revealed ten proteins that display region-specific alterations when comparing sexes, including proteins related to inflammatory response, response to reactive oxygen species, complement activation, transport and blood coagulation. Transport protein afamin and blood coagulation proteins antithrombin-III and coagulation factor XII were significantly increased in plaque region from women. Inflammatory response proteins lysozyme C and phospholipase A2 membrane-associated were significantly increased in plaque region from men. Limitations with this study are the small sample size, limited patient information and lack of complementary histology to control for cell type differences between sexes.ConclusionsThis pilot study, for the first time, utilises a multivariate proteomic approach to investigate sexual dimorphism in human atherosclerotic tissue, and provides an essential proteomic platform for further investigations to help understand sexual dimorphism and plaque vulnerability in atherosclerosis.
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| 27. |
- Ward, Liam, 1989-
(författare)
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Sex differences in atherosclerosis and exercise effects
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cardiovascular disease (CVD) is the leading cause of death globally, with atherosclerosis being the main cause of cardiovascular diseases. Atherosclerosis is an inflammatory disease of the blood vessel wall, which over time will cause thickening and hardening of the vessel wall. Atherosclerosis can result in catastrophic vascular events, such as myocardial infarction and stroke. There are distinct sex differences in CVD mortality at different ages, before menopause women have a lower mortality of CVD in comparison to men, which equalises after menopause. In addition to sex differences in the incidence of CVD, there are also distinct sex differences in the phenotype of atherosclerotic plaques, with men generally developing more severe and vulnerable plaques that are at risk of rupture.This thesis aimed to investigate the sex differences in atherosclerosis, in particular how the proteome and pathophysiology differs. In addition, we sought to investigate the potential benefit of an exercise programme, in reducing CVD risks, using a randomised controlled trial including postmenopausal women.Sex differences in atherosclerosis were first investigated via proteomic analysis of human carotid endarterectomy samples. Initially, five intraplaque biopsies were taken from distinct atheroma regions, including; internal control, fatty streak, plaque shoulder, plaque centre, and fibrous cap. Protein extracts from these biopsies were subjected to analysis by mass spectrometry. The novel sampling method was successful in reducing the effect of plaque heterogeneity, a limitation in previous proteomic studies of atherosclerosis, and a number of previously unreported proteins were identified in human carotid atheroma. In addition to this, with the inclusion of multivariate statistical modelling, it was found that 43 proteins significantly discriminated the carotid atheroma between men and women. These proteins were grouped by function, and it was found that atheroma from men was associated with the increased abundance of inflammatory response proteins, including phospholipase-A2 membrane associated and lysozyme C, and atheroma from women was associated with increased abundance of blood coagulation, complement activation, and transport proteins, notably including; antithrombin-III, coagulation factor XII, and afamin. In addition, differences were also ii observed in the abundance of iron metabolism related proteins. These sex differences were further expanded upon from a pathophysiological perspective. Immunohistochemistry stainings of ferritin and transferrin receptor 1 were found significantly increased in the atheroma from men. Moreover, the levels of plasma haemoglobin were also significantly increased in men and were associated with the development of more vulnerable and severe plaque types. The more vulnerable and severe plaque types were also associated with significantly greater macrophage infiltration. In summary, these results are indicative of men developing atheroma with greater inflammation that are more vulnerable, due to increased iron and inflammatory proteins and macrophage infiltration, whereas atheroma from women develop with less inflammation and a more stable phenotype.The randomised controlled clinical trial aimed at investigating the effects of resistance training (RT), over a 15-week period, in postmenopausal women. Plasma samples were obtained at week-0 and week-15 of the study period, and analyses were performed primarily using a series of immunoassays. Results showed that women participating in RT, with good compliance, were associated with significant decreases in plasma levels of ferritin, lipids, and inflammatory adipokines. These results suggest that the use of regular RT may be a beneficial intervention in reducing the levels of body iron, lipids, and inflammation, all of which are risk factors for the development of CVD. However, validation studies are required in a larger cohort of postmenopausal women, in addition to the inclusion or complementary studies in middle-aged men.In summary, the works included in this thesis further expand on the current knowledge of sex differences in atherosclerosis, and also provides information on the potential of an exercise intervention to beneficially reduces the effects of known risk factors of CVD.
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| 28. |
- Wei, Chu, et al.
(författare)
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CO2 allocation and equity issues under China's carbon neutrality targets : Recent advances and a review
- 2024
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Ingår i: China economic review. - : Elsevier. - 1043-951X .- 1873-7781. ; 83
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- This editorial establishes the context for our special issue, devoted to exploring CO2 allocation and equity considerations within the framework of China's ambitions for carbon neutrality. As the world's largest greenhouse gas emitter, China has made a pivotal development in mitigating climate change efforts with its commitment to achieving carbon neutrality by 2060. This collection of 16 diverse papers delves into recent advancements, challenges, and thematic explorations related to carbon dioxide emissions, providing a holistic analysis of the allocation mechanisms and the critical balance between equity and efficiency. The contributions, which span a wide range of disciplines, collectively reveal the nuances of integrating economic growth, social justice, and environmental stewardship in China's transition to a sustainable, low -carbon future. The editorial not only synthesizes the key insights from the included papers but also frames the overarching narrative, highlighting the significance of collaborative and equitable approaches in achieving China's carbon neutrality targets.
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| 29. |
- Wei, Chu, et al.
(författare)
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Digital technology and energy sustainability : Impacts and policy needs
- 2021
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Ingår i: Resources, Conservation and Recycling. - : Elsevier. - 0921-3449 .- 1879-0658. ; 170
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Tidskriftsartikel (refereegranskat)abstract
- This special issue aims to focus on the impact of the emerging digital technologies on the sustainability of energy systems, and consequently the needs for policy measures to provide an appropriate regulatory framework and confront associated unintended challenges. Different and innovative methodological approaches are encouraged. The content of this special issue is not limited to a certain country. The editors welcome any case studies from developed and developing countries with clear relevance for global digital technology development. Topics of specific interest include, but are not limited to, the following: Impacts of digital technology and digitalization practice on energy systems, climate and, the environment. Possible changes resulting from digitalization in electricity generation, mobility, housing, etc. and consequences of energy digitalization for energy market reforms. Impacts of digital technology and digitalization on economic growth, social inequality, sustainability, and quality of life. Impacts of digital technology on access to affordable modern energy services, especially in rural areas. Policy responses to deal with the high energy consumption of new digital infrastructure in energy systems. The role of digital technology in supporting energy security. Emerging questions about energy sustainability during the growth of digital technology.
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| 30. |
- Wei, Chu, et al.
(författare)
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Digital technology and energy sustainability : Recent advances, challenges, and opportunities
- 2023
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Ingår i: Resources, Conservation and Recycling. - : Elsevier. - 0921-3449 .- 1879-0658. ; 190
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Digitalization and sustainability represent two global mainstreams, which affect many dimensions of economic activity and daily life. However, their interaction remains still underexploited with different synergies and tradeoffs between these goals. This Virtual Special Issue (VSI) entitled "Digital technology and energy sustainability: impacts and policy needs" presents recent research on the nexus between digital technology and energy sustainability. This editorial introduces seven recent studies on a variety of topics, presenting core materials and guidance in the related domains. The findings indicate that scope, topic, measurement, method, and data might be in contrast or even in contradiction to previous studies. Although the black box of the complex nexus between digital technology and energy sustainability is still not fully uncovered, the findings indicate that the spatial factor and technology-induced rebound effect are most likely the underlying mechanisms. Additional future research directions for exploring the digitalization-sustainability interaction are discussed in this VSI.
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| 31. |
- Wei, Chu, et al.
(författare)
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Recent advances in China's sustainable transition studies
- 2022
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Ingår i: Letters in spatial and resource sciences. - : Springer Nature. - 1864-4031 .- 1864-404X. ; 15:3, s. 279-286
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Tidskriftsartikel (refereegranskat)abstract
- The world is confronted with increasing uncertainty and divisive threats to a sustainable global transition. Deglobalization is driving economic decoupling, and the pandemic is further preventing social exchange. The outcome of the 26th UN Climate Change Conference is a rare source of positive news. This special issue, entitled "Space Reconstruction in China's Sustainable Transition: Land, Energy and Carbon Emission", makes a timely academic contribution in response to these problems by presenting some recent research concerns and advances. This introductory article presents the latest policy debate and summarizes the major findings from six articles covered in the special issue. We show that academic society is worried about the negative effect of divisive trends on sustainable transition. Moreover, China's great spatial heterogeneity calls for an equitable and stable strategy to direct the transition process.
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| 32. |
- Wu, Shimei, et al.
(författare)
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Electricity consumption as a new indicator of inequality
- 2022
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Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 90
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Tidskriftsartikel (refereegranskat)abstract
- Inequality is a growing public concern and economic threat. The degree of which, however, varies greatly depending on the choice of indicators for measurement. In this paper, we compare the strength and weaknesses of the existing indicators such as income and wealth and propose a new measure of inequality based on household electricity consumption. We believe that our measure has the advantage of capturing both service flows and stock values of durables, embodying both the outcome and opportunity inequality, and confronting fewer measurement issues. The new inequality measure based on electricity consumption may complement the existing ones by providing a relatively complete and well-balanced picture of the overall welfare inequality.
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| 33. |
- Wu, Shimei, et al.
(författare)
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Quantifying Energy Consumption in Household Surveys : An Alternative Device-based Accounting Approach
- 2020
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Ingår i: Field Methods. - : SAGE Publications. - 1525-822X .- 1552-3969. ; 32:2, s. 213-232
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Tidskriftsartikel (refereegranskat)abstract
- The exercise of quantifying the energy consumption data assembled through household surveys, either by the recall-based approach or the meter-based approach, remains a challenging task, especially in rural areas of developing countries. In this article, we propose a device-based bottom-up accounting method for estimating household energy consumption. This method provides microlevel disaggregated estimates at the intensive margin and documents other difficult-to-measure energy consumption such as biomass at the extensive margin. Even though measurement errors of the household survey might still exist, the structured questionnaire of daily routine behavior questions should greatly alleviate the problem. The new method supplements the existing household energy statistical system, improves its flexibility, and is particularly applicable in developing countries and/or rural areas. We apply the method to a Chinese rural household survey and discuss its differences and similarities with the conventional methods.
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| 34. |
- Yu, Zhengquan, 1965-, et al.
(författare)
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3-Aminopropanal is a lysosomotropic aldehyde that causes oxidative stress and apoptosis by rupturing lysosomes
- 2003
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley-Blackwell. - 0903-4641 .- 1600-0463. ; 111:6, s. 643-652
-
Tidskriftsartikel (refereegranskat)abstract
- During cerebral ischemia and following trauma, potent cytotoxic polyamine-derived aminoaldehydes form, diffuse, and damage adjacent tissues not directly subjected to the initial insult. One such aldehyde is 3-aminopropanal (3-AP). The mechanisms by which such a small aldehydic compound is excessively cytotoxic have been unclear until recently when we showed that 3-AP, having the structure of a weak lysosomotropic base, concentrates within the acidic vacuolar compartment and causes lysosomal rupture that, in turn, induces caspase activation and apoptotic cell death. Here, using cultured J774 cells and 3-AP as a way to selectively burst lysosomes, we show that moderate lysosomal rupture induces a transient wave of oxidative stress. The start of this oxidative stress period is concomitant with a short period of enhanced mitochondrial membrane potential that later fades and is replaced by a decreased potential before the oxidative stress diminishes. The result of the study suggests that oxidative stress, which has often been described during apoptosis induced by agonists other than oxidative stress per se, may be a consequence of lysosomal rupture with direct and/or indirect effects on mitochondrial respiration and electron transport causing a period of passing enhanced formation of reactive oxygen species.
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| 35. |
- Yuan, Ximing, 1959-, et al.
(författare)
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Carotid Atheroma From Men Has Significantly Higher Levels of Inflammation and Iron Metabolism Enabled by Macrophages
- 2018
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Ingår i: Stroke. - : LIPPINCOTT WILLIAMS & WILKINS. - 0039-2499 .- 1524-4628. ; 49:2, s. 419-425
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-Men differ from women in the manifestation of atherosclerosis and iron metabolism. Intraplaque hemorrhage and hemoglobin (Hb) catabolism by macrophages are associated with atherosclerotic lesion instability. The study aims were to investigate sex differences in (1) lesion severity in relation to blood Hb, (2) iron homeostasis in human carotid plaques, and (3) macrophage polarization within atheroma. Methods-The carotid artery samples from 39 men and 23 women were immunostained with cell markers for macrophages, smooth muscle cells, ferritin, and TfR1 (transferrin receptor 1), which were further analyzed according to sex in relation to iron, Hb, and lipids in circulation. Additionally, samples of predefined regions from human carotid atherosclerotic lesions, including internal controls, were used for proteomic analysis by mass spectrometry. Results-Male patients, compared with women, had larger necrotic cores and more plaque rupture, which were associated with higher levels of Hb. Atheroma of male patients had significantly higher levels of Hb in circulation and CD68 macrophages, ferritin, and TfR1 in lesions. CD68 macrophages were significantly correlated with ferritin and TfR1. Plaques from male patients comparatively possessed higher levels of inflammatory macrophage subsets, CD86 (M1) and CD163 (M2), but lower levels of STF (serotransferrin) and HPX (hemopexin). Conclusions-Male patients with carotid atheroma had more advanced and ruptured lesions associated with significantly higher levels of inflammatory macrophage infiltration and high iron stores in the blood and in their plaques. These findings help to understand sex differences and iron metabolism in atherosclerosis and factors related to atheroma progression.
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| 36. |
- Yuan, Xi Ming, 1959-, et al.
(författare)
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Lysosomal destabilization during macrophage damage induced by cholesterol oxidation products
- 2000
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Ingår i: Free Radical Biology & Medicine. - 0891-5849 .- 1873-4596. ; 28:2, s. 208-218
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that oxidized low-density lipoprotein (LDL) induces damage to the macrophage lysosomal membranes, with ensuing leakage of lysosomal contents and macrophage cell death. Cholesterol oxidation products (ChOx) have been reported to be the major cytotoxic components of oxidized LDL/LDL− and also to stimulate cholesterol accumulation in vascular cells. In the present study, we characterized the initial events during macrophage damage induced by cholesterol oxidation products (ChOx). Within 24 h of exposure, ChOx caused lysosomal destabilization, release to the cytosol of the lysosomal marker-enzyme cathepsin D, apoptosis, and postapoptotic necrosis. Enhanced autophagocytosis and chromatin margination was found 12 h after the exposure to ChOx, whereas apoptosis and postapoptotic necrosis was pronounced 24 and 48 h after the exposure. Some lysosomal vacuoles were then filled with degraded cellular organelles, indicating phagocytosis of apoptotic bodies by surviving cells. Because caspase-3 activation was detected in the ChOx-exposed cells, lysosomal destabilization may associate with the leakage of lysosomal enzymes, and activation of the caspase cascade. MnSOD mRNA levels were markedly increased after 24 h of exposure to ChOx, suggesting associated induction of mitochondrial protection repair or turnover. We conclude that ChOx-induced damage to lysosomes and mitochondria are sequelae to the cascade of oxysterol cytotoxic events. The early disruption of lysosomes induced by ChOx, with resultant autophagocytosis may be a critical event in apoptosis and/or necrosis of macrophages/foam cells during the development of atherosclerotic lesions.
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| 37. |
- Yuan, Xi Ming, 1959-, et al.
(författare)
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Secretion of ferritin by iron-laden macrophages and influence of lipoproteins
- 2004
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Ingår i: Free radical research. - : Informa UK Limited. - 1071-5762 .- 1029-2470. ; 38:10, s. 1133-1142
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence supports a role of cellular iron in the initiation and development of atherosclerosis. We and others reported earlier that iron-laden macrophages are associated with LDL oxidation, angiogenesis, nitric oxide production and apoptosis in atherosclerotic processes. Here we have further studied perturbed iron metabolism in macrophages, their interaction with lipoproteins and the origin of iron accumulation in human atheroma. In both early and advanced human atheroma lesions, hemoglobin and ferritin accumulation correlated with the macrophage-rich areas. Iron uptake into macrophages, via transferrin receptors or scavenger receptor-mediated erythrophagocytosis, increased cellular iron and accelerated ferritin synthesis at both mRNA and protein levels. The binding activity of iron regulatory proteins was enhanced by desferrioxamine (DFO) and decreased by hemin and iron compounds. Iron-laden macrophages exocytosed both iron and ferritin into the culture medium. Exposure to oxidized low-density lipoprotein (oxLDL, ≥50 μg/ml,) resulted in <20% apoptosis of iron-laden human macrophages, but cells remained impermeable after a 24 h period and an increased excretion of ferritin could be observed by immunostaining techniques. Exposure to high-density lipoprotein (HDL) significantly decreased ferritin excretion from these cells. We conclude: (i) erythrophagocytosis and hemoglobin catabolism by macrophages contribute to ferritin accumulation in human atherosclerotic lesions and, (ii) iron uptake into macrophages leads to increased synthesis and secretion of ferritin, (iii) oxidized LDL and HDL have different effects on these processes.
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| 38. |
- Zhang, Cheng, et al.
(författare)
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Discovery of therapeutic agents targeting PKLR for NAFLD using drug repositioning
- 2022
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Ingår i: eBioMedicine. - : Elsevier BV. - 2352-3964. ; 83
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Tidskriftsartikel (refereegranskat)abstract
- Background Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of liver pathologies. However, no medical treatment has been approved for the treatment of NAFLD. In our previous study, we found that PKLR could be a potential target for treatment of NALFD. Here, we investigated the effect of PKLR in in vivo model and performed drug repositioning to identify a drug candidate for treatment of NAFLD. Methods Tissue samples from liver, muscle, white adipose and heart were obtained from control and PKLR knock-out mice fed with chow and high sucrose diets. Lipidomics as well as transcriptomics analyses were conducted using these tissue samples. In addition, a computational drug repositioning analysis was performed and drug candidates were identified. The drug candidates were both tested in in vitro and in vivo models to evaluate their toxicity and efficacy. Findings The Pklr KO reversed the increased hepatic triglyceride level in mice fed with high sucrose diet and partly recovered the transcriptomic changes in the liver as well as in other three tissues. Both liver and white adipose tissues exhibited dysregulated circadian transcriptomic profiles, and these dysregulations were reversed by hepatic knockout of Pklr. In addition, 10 small molecule drug candidates were identified as potential inhibitor of PKLR using our drug repositioning pipeline, and two of them significantly inhibited both the PKLR expression and triglyceride level in in vitro model. Finally, the two selected small molecule drugs were evaluated in in vivo rat models and we found that these drugs attenuate the hepatic steatosis without side effect on other tissues. Interpretation In conclusion, our study provided biological insights about the critical role of PKLR in NAFLD progression and proposed a treatment strategy for NAFLD patients, which has been validated in preclinical studies. Copyright (C) 2022 The Authors. Published by Elsevier B.V.
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| 39. |
- Zhang, Jinbao, et al.
(författare)
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The Importance of Pendant Groups on Triphenylamine-Based Hole Transport Materials for Obtaining Perovskite Solar Cells with over 20% Efficiency
- 2018
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Ingår i: Advanced Energy Materials. - : Wiley. - 1614-6832 .- 1614-6840. ; 18:2
-
Tidskriftsartikel (refereegranskat)abstract
- Tremendous progress has recently been achieved in the field of perovskite solar cells (PSCs) as evidenced by impressive power conversion efficiencies (PCEs); but the high PCEs of >20% in PSCs has so far been mostly achieved by using the hole transport material (HTM) spiro-OMeTAD; however, the relatively low conductivity and high cost of spiro-OMeTAD significantly limit its potential use in large-scale applications. In this work, two new organic molecules with spiro[fluorene-9,9-xanthene] (SFX)-based pendant groups, X26 and X36, have been developed as HTMs. Both X26 and X36 present facile syntheses with high yields. It is found that the introduced SFX pendant groups in triphenylamine-based molecules show significant influence on the conductivity, energy levels, and thin-film surface morphology. The use of X26 as HTM in PSCs yields a remarkable PCE of 20.2%. In addition, the X26-based devices show impressive stability maintaining a high PCE of 18.8% after 5 months of aging in controlled (20%) humidity in the dark. We believe that X26 with high device PCEs of >20% and simple synthesis show a great promise for future application in PSCs, and that it represents a useful design platform for designing new charge transport materials for optoelectronic applications.
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| 40. |
- Zhang, Wei, et al.
(författare)
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Organic Salts as p-Type Dopants for Efficient LiTFSI-Free Perovskite Solar Cells
- 2020
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 12:30, s. 33751-33758
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Tidskriftsartikel (refereegranskat)abstract
- Despite the ubiquity and importance of organic hole-transport materials in photovoltaic devices, their intrinsic low conductivity remains a drawback. Thus, chemical doping is an indispensable solution to this drawback and is essentially always required. The most widely used p-type dopant, FK209, is a cobalt coordination complex. By reducing Co(III) to Co(II), Spiro-OMeTAD becomes partially oxidized, and the film conductivity is initially increased. In order to further increase the conductivity, the hygroscopic co-dopant LiTFSI is typically needed. However, lithium salts are normally quite hygroscopic, and thus, water absorption has been suggested as a significant reason for perovskite degradation and therefore limited device stability. In this work, we report a LiTFSI-free doping process by applying organic salts in relatively high amounts. The film conductivity and morphology have been studied at different doping amounts. The resulting solar cell devices show comparable power conversion efficiencies to those based on conventional LiTFSI-doped Spiro-OMeTAD but show considerably better long-term device stability in an ambient atmosphere.
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| 41. |
- Zhang, Wei, 1989-, et al.
(författare)
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Single crystal structure and opto-electronic properties of oxidized Spiro-OMeTAD
- 2020
-
Ingår i: Chemical Communications. - : Royal Society of Chemistry. - 1359-7345 .- 1364-548X. ; 56:10, s. 1589-1592
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Tidskriftsartikel (refereegranskat)abstract
- Single crystals of Spiro(TFSI)2 were grown, the optical and electronic properties were characterized and compared with neutral Spiro-OMeTAD. Density-functional theory was used to get insights into binding and band structure properties. The flat valence bands indicate a rather limited orbital overlap in Spiro(TFSI)2.
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| 42. |
- Zhang, Wei, et al.
(författare)
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The Central Role of Ligand Conjugation for Properties of Coordination Complexes as Hole-Transport Materials in Perovskite Solar Cells
- 2019
-
Ingår i: ACS Applied Energy Materials. - : AMER CHEMICAL SOC. - 2574-0962. ; 2:9, s. 6768-6779
-
Tidskriftsartikel (refereegranskat)abstract
- Two zinc-based coordination complexes Y3 and Y4 have been synthesized and characterized, and their performance as hole-transport materials (HTMs) for perovskite solar cells (PSCs) has been investigated. The complex Y3 contains two separate ligands, and the molecular structure can be seen as a disconnected porphyrin ring. On the other hand, Y4 consists of a porphyrin core and therefore is a more extended conjugated system as compared to Y3. The optical and redox properties of the two different molecular complexes are comparable. However, the hole mobility and conductivity of Y4 as macroscopic material are remarkably higher than that of Y3. Furthermore, when employed as hole-transport materials in perovskite solar cells, cells containing Y4 show a power conversion efficiency (PCE) of 16.05%, comparable to the Spiro-OMeTAD-based solar cells with an efficiency around 17.08%. In contrast, solar cells based on Y3 show a negligible efficiency of about 0.01%. The difference in performance of Y3 and Y4 is analyzed and can be attributed to the difference in packing of the nonplanar and planar building blocks in the corresponding materials.
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| 43. |
- Zhengquan, Yu, 1965-, et al.
(författare)
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Human neuroblastoma (SH-SY5Y) cells are highly sensitive to the lysosomotropic aldehyde 3-aminopropanal
- 2004
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 1016:2, s. 163-169
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Tidskriftsartikel (refereegranskat)abstract
- 3-Aminopropanal (3-AP), a degradation product of polyamines such as spermine, spermidine and putrescine, is a lysosomotropic small aldehyde that causes apoptosis or necrosis of most cells in culture, apparently by inducing moderate or extensive lysosomal rupture, respectively, and secondary mitochondrial changes. Here, using the human neuroblastoma SH-SY5Y cell line, we found simultaneous occurrence of apoptotic and necrotic cell death when cultures were exposed to 3-AP in concentrations that usually are either nontoxic, or only cause apoptosis. At 30 mM, but not at 10 mM, the lysosomotropic base and proton acceptor NH3 completely blocked the toxic effect of 3-AP, proving that 3-AP is lysosomotropic and suggesting that the lysosomal membrane proton pump of neuroblastoma cells is highly effective, creating a lower than normal lysosomal pH and, thus, extensive intralysosomal accumulation of lysosomotropic drugs. A wave of internal oxidative stress, secondary to changes in mitochondrial membrane potential, followed and gave rise to further lysosomal rupture. The preincubation of cells for 24 h with a chain-breaking free radical-scavenger, α-tocopherol, before exposure to 3-AP, significantly delayed both the wave of oxidative stress and the secondary lysosomal rupture, while it did not interfere with the early 3-AP-mediated phase of lysosomal break. Obviously, the reported oxidative stress and apoptosis/necrosis are consequences of lysosomal rupture with ensuing release of lysosomal enzymes resulting in direct/indirect effects on mitochondrial permeability, membrane potential, and electron transport. The induced oxidative stress seems to act as an amplifying loop causing further lysosomal break that can be partially prevented by α-tocopherol. Perhaps secondary brain damage during a critical post injury period can be prevented by the use of drugs that temporarily raise lysosomal pH, inactivate intralysosomal 3-AP, or stabilize lysosomal membranes against oxidative stress.
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