Flavones exhibit a variety of beneficial effects and are well known for their medicinal importance in several diseases, including cardiovascular, neurodegenerative and cancer. The inclusion of the ...piperazine ring to the flavone backbone is an important strategy in drug discovery but only a few studies have synthesized piperazinyl flavone compounds to test their biological activity. While there is a major focus on the antioxidant properties of drugs in therapy of several diseases of inflammatory origin, we synthesized a series of the novel piperazinyl flavone analogues bearing the phenyl ring with different substituents. The analogues were evaluated for in vitro antioxidant activity against superoxide anion radical, hydroxyl radical, 2,2‐diphenyl‐1‐picrylhydrazyl radical, and hydrogen peroxide scavenging properties. The total antioxidant status based on the absorbance of the 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulphonic acid) radical cation (ABTS+•) and total antioxidant capacity using the Fe(III)‐ferrozine complex were also monitored. The results of the above studies showed that the compounds synthesized were found possessed moderate radical scavenging potential, and that their interaction with reactive oxygen species is complex and depends on their structural conformation and the type of substituent R in the piperazine ring being attached. Best antiradical activity were found for the compounds with methoxy groups on the phenyl ring of substituent R, whereas the presence of methoxy or trifluoromethyl groups in substituent R resulted in higher ABTS+• and ion Fe(III) reduction. These compounds are promising molecules to be used for their antioxidant properties and may be regarded, after improvement of the antioxidant potential, to control diseases of free radical etiology.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
492.
Commissioning and preliminary performance of the MEG II drift chamber Chiappini, M.; Chiarello, G.; Baldini, A.M. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
10/2022, Volume:
1041
Journal Article
Peer reviewed
In the quest for Lepton Flavor Violation (LFV) the MEG experiment at the Paul Scherrer Institut (PSI) represents the state of the art in the search for the charged LFV decay μ+→e+γ, setting the most ...stringent upper limit on the BR(μ+→e+γ)≤4.2×10−13 (90% C.L.). An upgrade of MEG, MEG II, was designed and it recently started the physics data taking, with the aim to reach a sensitivity level of 6×10−14. The Cylindrical Drift CHamber (CDCH) is a key detector in order to improve the e+ angular and momentum resolutions at the 6.5 mrad and 100 keV/c level. The CDCH is a low-mass single volume detector with high granularity: 9 layers of 192 drift cells each, few mm wide, defined by 12000 wires in a stereo configuration for longitudinal hit localization. After the assembly, the CDCH was transported to PSI for the commissioning phase and it has been integrated into the MEG II experimental apparatus since 2018. The operational stability was reached in 2020 and the complete readout electronics was tested for the first time in 2021. A preliminary analysis of 2020–2021 data is presented.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Surface morphology changes and deuterium (D) retention in Toughened, Fine-Grained Recrystallized Tungsten (TFGR W) with TaC dispersoids (W-TaC) and pure tungsten exposed to D plasmas to a fluence of ...1026D/m2s were studied as a function of the D ion flux (1022–1024D/m2s). As the flux increased from 1022D/m2s to 1024D/m2s, the numbers of blisters increased for both materials. However, smaller blisters were observed on W-TaC compared to pure W. In W-TaC, cracks beneath the surface along grain boundaries were observed, which were comparable to the blister sizes. The reason for the smaller blister sizes may arise from smaller grain sizes of W-TaC. In addition, reduction of the D retention in W-TaC was observed for higher flux exposures. D depth profiles indicate this reduction arises due to decrease in trapping in the bulk.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Mesenchymal stromal cells (MSCs) in bone marrow are important for bone homeostasis. Although platelet‐derived growth factor (PDGF) has been reported to be involved in osteogenic differentiation of ...MSCs, the role remains controversial and the network of PDGF signaling for MSCs has not been clarified. To clarify the underlying regulatory mechanism of MSC functions mediated by PDGF, we deleted the PDGF receptor (PDGFR)β gene by Cre‐loxP strategy and examined the role of PDGF in osteogenic differentiation of MSCs and fracture repair. In cultured MSCs, the mRNA expression of PDGF‐A, ‐B, ‐C, and ‐D as well as PDGFRα and β was detected. Depletion of PDGFRβ in MSCs decreased the mitogenic and migratory responses and enhanced osteogenic differentiation as evaluated by increased alkaline phosphatase (ALP) activity and mRNA levels of ALP, osteocalcin (OCN), bone morphogenetic protein (BMP) 2, Runx2, and osterix in quantitative RT‐PCR. PDGF‐BB, but not PDGF‐AA, inhibited osteogenic differentiation accompanied by decreased ALP activity and mRNA levels, except for BMP2. These effects of PDGF‐BB were eliminated by depletion of PDGFRβ in MSCs except that PDGF‐BB still suppressed osterix expression in PDGFRβ‐depleted MSCs. Depletion of PDGFRβ significantly increased the ratio of woven bone to callus after fracture. From the combined analyses of PDGF stimulation and specific PDGFRβ gene deletion, we showed that PDGFRβ signaling distinctively induces proliferative and migratory responses but strongly inhibits osteogenic differentiation of MSCs. The effects of PDGFRα on the osteogenic differentiation were very subtle. PDGFRβ could represent an important target for guided tissue regeneration or tissue engineering of bone.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This study aimed to evaluate the effects of doxorubicin (Dox) on bone microstructure and metabolism in a mouse model of soft tissue sarcoma.
CCRF S-180II cells (2-4×10
cells/0.2 ml) were injected ...subcutaneously into the back of mice. The mice were divided into four groups according to tumor and treatment status and were reared and sacrificed after 2 or 4 weeks. Micro-computed tomography (CT) was performed to calculate the architecture of the femoral bone. The proximal tibia was double stained with tartrate-resistant acid phosphatase (TRACP) and alkaline phosphatase (ALP), and bone morphometry was performed.
Trabecular bone mass was significantly reduced in the Sarcoma and Sarcoma+Dox groups. Cortical bone thickness was reduced in the DOX group, with a stronger effect observed in the Sarcoma+Dox group. In bone morphometry, osteoclast number at the bone surface (Oc.N/BS) was significantly lower in the Dox, Sarcoma, and Sarcoma+Dox groups than in the Control group at 2 weeks. The osteoblast surface at the bone surface (Ob.S/BS) was significantly lower in the Dox and Sarcoma groups than in the Control group at 2 weeks. At 4 weeks, the differences were smaller for both Oc.N/BS and Ob.S/BS.
The use of doxorubicin alone worsened the cortical bone structure; however, the presence of both soft-tissue sarcoma and doxorubicin use worsened both cortical and trabecular bone structures from an early stage.
Deuterium retention in Toughened, Fine-Grained Recrystallized W (TFGR W-1.1wt%TiC) was studied, compared to pure W. D implantation was performed to a fluence of 1×1024m−2 at temperatures of 473–873K, ...followed by TDS. It was found that D retention in TFGR W is higher than in pure W at all irradiation temperatures. Namely, at 673K, D retention in TFGR W is six times higher than pure W. TDS spectrum of TFGR W irradiated at 573K has a large peak around ∼700K with small shoulder up to ∼1100K. In the case of D+He simultaneous irradiation, D retention is about 30% lower than for pure D. In addition, plasma exposure experiment was also conducted in TEXTOR, followed by NRA. Higher retention in TFGR W-1.1wt%TiC could be attributed to high grain boundary diffusion (then trapping deeper into the bulk) and formation of TiD2.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK