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  • 2025

    Background/Objectives: Overexpressed in various solid tumors, the gastrin-releasing peptide receptor (GRPR) is a promising target for cancer diagnosis and therapy. However, the high pancreas uptake of the current clinically evaluated GRPR-targeted radiopharmaceuticals limits their applications. In this study, we replaced the Pro14 residue in our previously reported GRPR-targeted LW02056 and ProBOMB5 with 4,4-difluoroproline (diF-Pro) to obtain an agonist LW02060 (DOTA-Pip-[D-Phe6,Tle10,NMe-His12,diF-Pro14]Bombesin(6–14)) and an antagonist LW02080 (DOTA-Pip-[D-Phe6,NMe-Gly11,Leu13(ψ)diF-Pro14]Bombesin(6–14)), respectively. Methods/Results: The binding affinities (Ki) of Ga-LW02060, Ga-LW02080, Lu-LW02060, and Lu-LW02080 were measured by in vitro competition binding assays using PC-3 cells and were found to be 5.57 ± 2.47, 21.7 ± 6.69, 8.00 ± 2.61, and 32.1 ± 8.14 nM, respectively. The 68Ga- and 177Lu-labeled ligands were obtained in 36–75% decay-corrected radiochemical yields with >95% radiochemical purity. PET imaging, SPECT imaging, and ex vivo biodistribution studies were conducted in PC-3 tumor-bearing mice. Both [68Ga]Ga-LW02060 and [68Ga]Ga-LW02080 enabled clear tumor visualization in PET images at 1 h post-injection (pi). Tumor uptake values of [68Ga]Ga-LW02060 and [68Ga]Ga-LW02080 at 1 h pi were 16.8 ± 2.70 and 7.36 ± 1.33 %ID/g, respectively, while their pancreas uptake values were 3.12 ± 0.89 and 0.38 ± 0.04 %ID/g, respectively. Compared to [177Lu]Lu-LW02080, [177Lu]Lu-LW02060 showed higher tumor uptake at all time points (1, 4, 24, 72, and 120 h pi). However, fast tumor clearance was observed for both [177Lu]Lu-LW02060 and [177Lu]Lu-LW02080. Conclusions: Our data demonstrate that [68Ga]Ga-LW02060 is promising for clinical translation for the detection of GRPR-expressing tumor lesions. However, further optimizations are needed for [177Lu]Lu-LW02060 and [177Lu]Lu-LW02080 to prolong tumor retention for therapeutic applications.
    • Book : 18(2)
    • Pub. Date : 2025
    • Page : pp.234-234
    • Keyword :
  • 2025

    본 논문은 일본 고도성장기(1955~1972)에 제작된 특수촬영 영화 <고질라> 시리즈를 중심으로 괴수를 다루는 영화적 상상력과 전후 일본의 집단적 기억과 정체성 변용과의 관계를 고찰하고 있다. 1954년에 개봉된 영화 《고질라》는 핵실험으로 깨어난 ‘수폭괴수’ 고질라를 통해 전쟁과 피폭의 기억, 그리고 냉전 시대의 폭력적 위협을 알레고리적으로 담아냈다. 이 영화에서 고질라는 일본의 도시를 유린하는 무시무시한 존재로 그려졌으며, 고질라를 물리치며 스스로 목숨을 버린 과학자 세리자와의 자기희생적 결단은 폭력의 연쇄를 거부하는 메시지를 전달하고 있다. 즉, 이 영화는 냉전 시기 미소의 핵 무기 경쟁과 전쟁 위협에 대한 일본인의 불안을 반영하며, 그것에 대한 대안적 담론으로 ‘평화주의’를 강조하고 있다. 그러나 1960년대 이후 <고질라> 영화는 괴수 간의 대결을 중심으로 한 서바이벌 장르로 변화했다. 이 시기의 고질라는 일본을 침략하는 외부 괴수들로부터 도시를 보호하는 수호자 역할을 부여받았으며, 점차 친근하고 귀여운 이미지로 재구성되었다. 이러한 변화는 대중 소비사회의 발전과 관객층의 저연령화에 부응한 상업적 전략의 결과였다. 동시에 이것은 전쟁에 대한 불안이 약해지고 그 결과 평화주의에 대한 강력한 지지가 대세를 형성하는 시대적 분위기 속에서 폭력의 표현에 대한 더 큰 자유를 원하는 심정이 낳은 결과이기도 했다. 특히 고질라는 수폭괴수의 아이덴티티에서 벗어나고 피폭의 기억에서 점차 분리됨으로써 현실적 대응물과 연결되지 않은 소위 시뮬라크르로 변모했다. 본 논문은 이러한 고질라의 변화가 단순히 영화적 트렌드의 변화를 넘어, 전후 일본사회의 기억 재구성과 문화적 정체성의 변화를 상징적으로 보여주는 사건이라고 주장한다. 1950년대 고질라가냉전기 폭력과 전쟁의 기억을 알레고리적으로 드러냈다면, 1960년대 이후의 고질라는 폭력의 유희화를 통해 관객의 흥미를 유도하며 현실과는 분리된 쾌락의 대상이자 유희의 상징이 되었다. 그리고 이런 변용은 냉전의 위협이 편재했던 1950년대를 ‘전후 속 전시’로 타자화하고, 이에 대해 1960년대를 ‘전후 속 전후’로 의미화하는 방식으로 전후라는 시간을 재편하려 했던 당대의 집합적 의지를 배경으로 하고 있었다.
    • Pub. Date : 2025
    • Page : pp.210-243
    • Keyword :
  • 2025

    Two extensions of the variational method with explicit energy functionals (EEFs) with respect to the spin-orbit force were performed. In this method, the energy per nucleon of nuclear matter is explicitly expressed as a functional of various two-body distribution functions, starting from realistic nuclear forces. The energy was then minimized by solving the Euler–Lagrange equation for the distribution functions derived from the EEF. In the first extension, an EEF of symmetric nuclear matter at zero temperature was constructed using the two-body central, tensor, and spin-orbit nuclear forces. The energy per nucleon calculated using the Argonne v8’ two-body nuclear potential was found to be lower than those calculated using other many-body methods, implying that the energy contribution caused by the spin-orbit correlation, whose relative orbital angular momentum operator acts on other correlations, is necessary. In a subsequent extension, the EEF of neutron matter at zero temperature, including the spin-orbit force, was extended to neutron matter at finite temperatures using the method by Schmidt and Pandharipande. The thermodynamic quantities of neutron matter calculated using the Argonne v8’ nuclear potential were found to be reasonable and self-consistent.
    • Book : 8(1)
    • Pub. Date : 2025
    • Page : pp.11-11
    • Keyword :
  • 2025

    Dynamical decoupling multipulse sequences can be applied to solid-state spins for sensing weak oscillating fields from nearby single nuclear spins. By periodically reversing the probing system's evolution, other noises are counteracted and filtered out over the total evolution. However, the technique is subject to intricate interactions resulting in additional resonant responses, which can be misinterpreted with the actual signal intended to be measured. We experimentally characterize three of these effects present in single nitrogen-vacancy centers in diamond, where we also develop a numerical simulation model without rotating-wave approximation, showing robust correlation to the experimental data. Regarding centers with the N15 nitrogen isotope, we observe that a small misalignment in the bias magnetic field causes the precession of the nitrogen nuclear spin to be sensed by the electronic spin of the center. Another studied case of ambiguous resonances comes from the coupling with lattice C13 nuclei, where we use the echo modulation frequencies to obtain the interaction Hamiltonian and then utilize the latter to simulate multipulse sequences. Finally, we also measure and simulate the effects from the free evolution of the quantum system during finite pulse durations. Due to the large data volume and the strong dependence of these ambiguous resonances with specific experimental parameters, we provide a simulations data set with a user-friendly graphical interface, where users can compare simulations with their own experimental data for spectral disambiguation. Although focused on nitrogen-vacancy centers and dynamical decoupling sequences, these results and the developed model can potentially be applied to other solid-state spins and quantum sensing techniques. Published by the American Physical Society 2025
    • Book : 111(2)
    • Pub. Date : 2025
    • Page :
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  • 2025

    The discovery of effective cysteine protease inhibitors with crude protein kiwi extracts (CPKEs) has created novel challenges and prospects for pharmaceutical development. Despite extensive research on CPKEs, limited research has been conducted on treating atopic dermatitis (AD). Therefore, the objective of this work was to investigate the anti-inflammatory effects of CPKEs on TNF-α activation in a HaCaT cell model and in a DNCB (1-chloro-2, 4-dinitrochlorobenzene)-induced atopic dermatitis animal model. The molecular weight of the CPKE was determined using SDS-PAGE under non-reducing (17 kDa and 22 kDa) and reducing conditions (25 kDa, 22 kDa, and 15 kDa), whereas gelatin zymography was performed to examine the CPKE’s inhibitory impact on cysteine protease (actinidin and papain) activity. Moreover, the CPKE remains stable at 60 °C, with pH levels varying from 4 to 11, as determined by the azocasein assay. CPKE treatment decreased the phosphorylation of mitogen-activated protein kinase (MAPK) and Akt, along with the activation of nuclear factor-kappa B (NF-κB)-p65 in tumor necrosis factor-α (TNF-α)-stimulated HaCaT cells. Five-week-old BALB/c mice were treated with DNCB to act as an AD-like animal model. The topical application of CPKE to DNCB-treated mice for three weeks substantially decreased clinical dermatitis severity and epidermal thickness and reduced eosinophil infiltration and mast cells into ear and skin tissues. These findings imply that CPKE derived from kiwifruit might be a promising therapy option for inflammatory skin diseases such as AD.
    • Book : 26(4)
    • Pub. Date : 2025
    • Page : pp.1534-1534
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  • 2025

    Using (2712±14)×106 ψ(2S) events collected with the BESIII detector at the BEPCII collider, we search for the decays ηc(2S)ωω and ηc(2S)ωϕ via the process ψ(2S)γηc(2S). No statistically significant signals are observed. The upper limits of their product branching fractions at the 90% confidence level are determined to be B(ψ(2S)γηc(2S),ηc(2S)ωω)<1.04×106 and B(ψ(2S)γηc(2S),ηc(2S)ωϕ)<1.85×107, respectively. We also update the branching fractions of χcJωω and χcJωϕ via the ψ(2S)γχcJ transition. Their branching fractions are determined to be B(χc0ωω)=(10.66±0.11±0.57)×104, B(χc1ωω)=(6.43±0.07±0.31)×104, B(χc2ωω)=(8.75±0.08±0.42)×104, B(χc0ωϕ)=(1.18±0.03±0.07)×104, B(χc1ωϕ)=(2.04±0.15±0.11)×105, and B(χc2ωϕ)=(9.58±1.07±0.76)×106, where the first uncertainties are statistical and the second are systematic. Published by the American Physical Society 2025
    • Book : 111(3)
    • Pub. Date : 2025
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  • 2025

    AbstractMast cells (MCs) have a well-established detrimental role in allergic conditions, but they can also impact on diverse malignant conditions, including melanoma. To study the latter, previous studies have mainly evaluated how MCs can influence melanomas/melanoma cells. However, the inverse scenario, i.e., whether melanoma/melanoma cells might impact on MCs has received less attention. Here we investigated this issue and show that melanoma cell-conditioned medium had a strong growth-inhibitory impact on MCs, which was attributed to inhibition of MC proliferation combined with induction of apoptosis. Further, our data indicate that such effects were attributable to melanin present in the melanoma cell-conditioned medium, as similar anti-proliferative effects were seen in response to both free melanin and to melanocores enriched from melanoma-conditioned medium. Melanin did not reduce the expression of MC markers, but was shown to impair MC activation. We also demonstrate that melanin is taken up by MCs, both in cultured MCs andin vivoin melanoma tumors, and it was observed that melanin, after uptake, can be found in the MC nucleus. Further, we show that melanin had marked effects on the nuclear morphology in MCs accompanied by clipping of core histone 3, and it is demonstrated that these events were dependent on translocation of tryptase, a granule-localized protease, into the MC nucleus. Tryptase was also shown to affect the mechanism of melanin-induced cell death. Altogether, the present study outlines a novel mechanism by which melanoma cells can suppress MC function, potentially representing an immunosuppressive mechanism that may influence tumor growth.
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