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| 3. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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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.
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- Xie, Sisi, et al.
(författare)
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Dietary ketone body-escalated histone acetylation in megakaryocytes alleviates chemotherapy-induced thrombocytopenia
- 2022
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Ingår i: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 14:673
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Tidskriftsartikel (refereegranskat)abstract
- Chemotherapy-induced thrombocytopenia (CIT) is a severe complication in patients with cancer that can lead to impaired therapeutic outcome and survival. Clinically, therapeutic options for CIT are limited by severe adverse effects and high economic burdens. Here, we demonstrate that ketogenic diets alleviate CIT in both animals and humans without causing thrombocytosis. Mechanistically, ketogenic diet-induced circulating beta-hydroxybutyrate (beta-OHB) increased histone H3 acetylation in bone marrow megakaryocytes. Gain- and loss-of-function experiments revealed a distinct role of 3-beta-hydroxybutyrate dehydrogenase (BDH)-mediated ketone body metabolism in promoting histone acetylation, which promoted the transcription of platelet biogenesis genes and induced thrombocytopoiesis. Genetic depletion of the megakaryocyte-specific ketone body transporter monocarboxylate transporter 1 (MCT1) or pharmacological targeting of MCT1 blocked beta-OHB-induced thrombocytopoiesis in mice. A ketogenesis-promoting diet alleviated CIT in mouse models. Moreover, a ketogenic diet modestly increased platelet counts without causing thrombocytosis in healthy volunteers, and a ketogenic lifestyle inversely correlated with CIT in patients with cancer. Together, we provide mechanistic insights into a ketone body-MCT1-BDH-histone acetylation-platelet biogenesis axis in megakaryocytes and propose a non-toxic, low-cost dietary intervention for combating CIT.
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- Abd Nikooie Pour, Mina, et al.
(författare)
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Results of the Ontology Alignment Evaluation Initiative 2022
- 2022
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Ingår i: CEUR Workshop Proceedings. - : CEUR-WS. ; , s. 84-128, s. 84-128
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Konferensbidrag (refereegranskat)abstract
- The Ontology Alignment Evaluation Initiative (OAEI) aims at comparing ontology matching systems on precisely defined test cases. These test cases can be based on ontologies of different levels of complexity and use different evaluation modalities. The OAEI 2022 campaign offered 14 tracks and was attended by 18 participants. This paper is an overall presentation of that campaign. © 2022 Copyright for this paper by its authors.
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| 6. |
- Abd Nikooie Pour, Mina, et al.
(författare)
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Results of the Ontology Alignment Evaluation Initiative 2023
- 2023
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Ingår i: Proceedings of the 18th International Workshop on Ontology Matching co-located with the 22nd International Semantic Web Conference (ISWC 2023), Athens, Greece, November 7, 2023.. - : CEUR Workshop Proceedings. ; , s. 97-139
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Konferensbidrag (refereegranskat)
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- Chen, Ke-Ling, et al.
(författare)
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Effects of Tocilizumab on Experimental Severe Acute Pancreatitis and Associated Acute Lung Injury
- 2016
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Ingår i: Critical Care Medicine. - : LIPPINCOTT WILLIAMS & WILKINS. - 0090-3493 .- 1530-0293. ; 44:8, s. E664-E677
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the therapeutic effects of tocilizumab, an antibody against interleukin-6 receptor, on experimental severe acute pancreatitis and associated acute lung injury. The optimal dose of tocilizumab and the activation of interleukin-6 inflammatory signaling were also investigated. Design: Randomized experiment. Setting: Research laboratory at a university hospital. Subject: Experimental severe acute pancreatitis in rats. Interventions: Severe acute pancreatitis was induced by retrograde injection of sodium taurocholate (50 mg/kg) into the biliopancreatic duct. In dose-study, rats were administered with different doses of tocilizumab (1, 2, 4, 8, and 16 mg/kg) through the tail vein after severe acute pancreatitis induction. In safety-study, rats without severe acute pancreatitis induction were treated with high doses of tocilizumab (8, 16, 32, and 64 mg/kg). Serum and tissue samples of rats in time-study were collected for biomolecular and histologic evaluations at different time points (2, 6, 12, 18, and 24 hr). Measurements and Main Results: 1) Under the administration of tocilizumab, histopathological scores of pancreas and lung were decreased, and severity parameters related to severe acute pancreatitis and associated lung injury, including serum amylase, C-reactive protein, lung surfactant protein level, and myeloperoxidase activity, were all significant alleviated in rat models. 2) Dose-study demonstrated that 2 mg/kg tocilizumab was the optimal treatment dose. 3) Basing on multi-organ pathologic evaluation, physiological and biochemical data, no adverse effect and toxicity of tocilizumab were observed in safety-study. 4) Pancreatic nuclear factor-kappa B and signal transducer and activator of transcription 3 were deactivated, and the serum chemokine (C-X-C motif) ligand 1 was down-regulated after tocilizumab administration. Conclusions: Our study demonstrated tocilizumab, as a marketed drug commonly used for immune-mediated diseases, was safe and effective for the treatment of experimental severe acute pancreatitis and associated acute lung injury. Our findings provide experimental evidences for potential clinical application of tocilizumab in severe acute pancreatitis and associated complications.
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| 8. |
- Chen, Yi-Jing, et al.
(författare)
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Molecular Engineering of Perylene Diimide Polymers with a Robust Built-in Electric Field for Enhanced Solar-Driven Water Splitting
- 2023
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Ingår i: Angewandte Chemie International Edition. - : WILEY-V C H VERLAG GMBH. - 1433-7851 .- 1521-3773.
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Tidskriftsartikel (refereegranskat)abstract
- The built-in electric field of the polymer semiconductors could be regulated by the dipole moment of its building blocks, thereby promoting the separation of photogenerated carriers and achieving efficient solar-driven water splitting. Herein, three perylene diimide (PDI) polymers, namely oPDI, mPDI and pPDI, are synthesized with different phenylenediamine linkers. Notably, the energy level structure, light-harvesting efficiency, and photogenerated carrier separation and migration of polymers are regulated by the orientation of PDI unit. Among them, oPDI enables a large dipole moment and robust built-in electric field, resulting in enhanced solar-driven water splitting performance. Under simulated sunlight irradiation, oPDI exhibits the highest photocurrent of 115.1 mu A cm-2 for photoelectrochemical oxygen evolution, which is 11.5 times that of mPDI, 26.8 times that of pPDI and 104.6 times that of its counterparts PDI monomer at the same conditions. This work provides a strategy for designing polymers by regulating the orientation of structural units to construct efficient solar energy conversion systems. Three perylene diimide (PDI) polymers were designed and synthesized such that the molecular orientation of the PDI units was regulated to create and modulate their built-in electric fields. Due to the large dipole moment and interfacial electric field, oPDI enables an extraordinary photocurrent density of 115.1 mu A & sdot; cm-2, which is 11.5 and 26.8 times that of mPDI and pPDI, respectively.image
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| 9. |
- Gao, Yun, et al.
(författare)
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Microsecond-response perovskite light-emitting diodes for active-matrix displays
- 2024
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Ingår i: NATURE ELECTRONICS. - : NATURE PORTFOLIO. - 2520-1131. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Perovskite light-emitting diodes (PeLEDs) could be of use in the development of active-matrix displays. However, due to ion migration in crystal structure, PeLEDs have electroluminescence rise times over milliseconds, which is problematic for the development of high-refresh-rate displays. Here, we show that the electroluminescence rise time of PeLEDs can be reduced to microseconds using an individual-particle passivation strategy. The approach is based on BF4 - ions that can passivate every nanocrystal in a perovskite emissive layer during film deposition. It leads to a defect-free film with discrete nanostructure and excellent crystallinity, which inhibits ion migration. Our strategy can be applied in perovskite nanocrystal films with different colours: red (635 nm), green (520 nm) and blue (475 nm). These PeLEDs all demonstrate response times within microseconds and high external quantum efficiencies of 22.7%, 26.2% and 18.1%, respectively. This allows us to create microsecond-response active-matrix PeLEDs that exhibit external quantum efficiencies above 20% at a display brightness of 500-3,000 cd m-2 for green devices with a resolution of 30 pixels per inch. We also develop microsecond-response red, green and blue active-matrix displays with 90 pixels per inch. An individual-particle passivation strategy that reduces ion migration in perovskite nanocrystal film can be used to make high-refresh-rate active-matrix displays with microsecond response times reduced by three orders of magnitude compared with typical perovskite light-emitting diodes.
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| 10. |
- Huang, Chih-Yang, et al.
(författare)
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Heteroepitaxially grown homojunction gallium oxide PN diodes using ion implantation technologies
- 2024
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Ingår i: Materials Today Advances. - : ELSEVIER. - 2590-0498. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Although advancements in n- and p-doping of gallium oxide (Ga2O3) are underway, the realization of functional pn diodes remains elusive. Here, we present the successful fabrication of a Ga2O3 pn diode utilizing ion implantation technology. The Ga2O3 epilayers were grown on c-plane sapphire substrates by metalorganic chemical vapor deposition (MOCVD). P-type conductivity Ga2O3 epilayer, confirmed by Hall effect analysis, was achieved by phosphorus (P) ion implantation followed with a rapid thermal annealing (RTA) process. This p-Ga2O3 epilayer reveals a significant reduction in resistivity (<10(6)) compared to undoped Ga2O3, demonstrating the successful inclusion and activation of P within the crystal lattice. X-ray diffraction analysis shows that the Ga2O3 epilayers were grown in high crystal quality. Although the crystallinity of Ga2O3 was slightly degraded after P ion implantation, the structure was recovered to high-quality crystal after RTA treatment. For the device structure, p-type Ga2O3 was formed first, followed n-type Ga2O3 regrowth to create a pn junction diode. The obtained results demonstrate a built-in voltage of 4.8 V, 4.2 V, and 4.308 V from simulation, fabricated pn diodes measured by I-V and C-V, respectively. A high breakdown voltage of 900 V was also obtained for the lateral pn diode grown on sapphire substrate. As concerning temperature stability, I-V curves of Ga2O3 pn diode were measured from 25 degrees C to 150 degrees C in steps of 25 degrees C. At elevated temperatures, for both forward and reverse biases, consecutive increasing currents were measured. These could be resulted from dominant diffusion and drift currents over recombination current at a given bias. In addition, the reverse current saturated (@V > 3kT/q) and remained very low at 2x10(-8) A, as the diode operated at 150 degrees C. The behavior could be due to Ga2O3 being a wide bandgap material.
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