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Syngeneic natural killer cell therapy activates dendritic and T cells in metastatic lungs and effectively treats low-burden metastases
No full text[[abstract]]Natural killer (NK) cells can control metastasis through cytotoxicity and IFN-γ production independently of T cells in experimental metastasis mouse models. The inverse correlation between NK activity and metastasis incidence supports a critical role for NK cells in human metastatic surveillance. However, autologous NK cell therapy has shown limited benefit in treating patients with metastatic solid tumors. Using a spontaneous metastasis mouse model of MHC-I(+) breast cancer, we found that transfer of IL-15/IL-12-conditioned syngeneic NK cells after primary tumor resection promoted long-term survival of mice with low metastatic burden and induced a tumor-specific protective T cell response that is essential for the therapeutic effect. Furthermore, NK cell transfer augments activation of conventional dendritic cells (cDCs), Foxp3(-)CD4(+) T cells and stem cell-like CD8(+) T cells in metastatic lungs, to which IFN-γ of the transferred NK cells contributes significantly. These results imply direct interactions between transferred NK cells and endogenous cDCs to enhance T cell activation. We conducted an investigator-initiated clinical trial of autologous NK cell therapy in six patients with advanced cancer and observed that the NK cell therapy was safe and showed signs of effectiveness. These findings indicate that autologous NK cell therapy is effective in treating established low burden metastases of MHC-I(+) tumor cells by activating the cDC-T cell axis at metastatic sites
Ultrafast magneto-inductive synthesis of carbon dots from plant-based precursors using deep eutectic solvents: A comparative study with traditional hydrothermal methods
No full text[[abstract]]The batch hydrothermal synthesis of carbon dots (CDs) has limitations in terms of yields and production capacity. This work aimed to develop an efficient and rapid technique to synthesize CDs through magneto-induction from natural plant-based precursors. Firstly, the influence of temperature and duration in a batch hydrothermal method was studied, using lignin, palm empty fruit bunch (EFB), glucose, sucrose, and xylose as the precursors. Green and sustainable deep eutectic solvents (DESs), specifically choline chloride (ChCl)/lactic acid (ChLa), ChCl/urea (ChUr), ChCl/1,3 butanediol (ChBu), and ChCl/oxalic acid (ChOx), were utilized in the batch hydrothermal synthesis of CDs. This study demonstrated that the CDs derived from ChLa and ChOx showed a high quantum yield (%QY) when lignin was the precursor. In contrast, the CDs from ChLa and ChBu demonstrated a high %QY for biomass EFB precursor, and the CDs from ChUr and ChBu achieved a high %QY for glucose, sucrose, and xylose precursors, respectively. ChBu demonstrated a well-balanced %QY and promising CD characteristics alongside a notably higher mass yield across all precursors, making it the ideal choice for the magneto-inductive synthesis study. Magnetic hyperthermia (MHT) stands out by producing superior CDs with an impressive QY of 23.44 % and a remarkable mass yield of 28.85 %. The MHT method generated the highest CD productivity of 62.72 mg CDs/g Lig/h from lignin in ChBu solvent at 25 wt% Fe3O4 in only 180 sec (ChBuLig25wtFe180s). This was 11.18 times higher than the conventional hydrothermal method, which required an exogenous heat source at 220 °C for 10 h. The MHT method cut production costs by 13.41 times compared to traditional hydrothermal methods. This significant cost-saving stems primarily from its ability to dramatically shorten processing times, enhance heat transfer efficiency to the carbon nanostructures, and reduce overall expenses. These advantages culminate in a more efficient, streamlined, and practical production process, delivering superior CD productivity
Outdoor activity during class recess prevents myopia onset and shift in premyopic children: Subgroup analysis in the recess outside classroom study
No full text[[abstract]]Purpose: To investigate whether premyopia is a risk factor for myopia onset and whether outdoor activities can protect against myopia development in premyopic children in the Recess Outside Classroom (ROC) study. Methods: Nonmyopic schoolchildren aged 7–11 years were recruited from two schools in Taiwan. One school implemented the ROC program, which encouraged children to go outdoors during recess. The control school maintained its usual schedule. A cycloplegic autorefraction was performed. Premyopia was defined as spherical equivalent refraction ≤ +0.75 diopters (D) and > –0.50 D. Results: After one year of follow-up, multivariate logistic analysis revealed that the ROC program reduced the risk of myopia onset by 61 % (odds ratio [OR] = 0.39, 95 % confidence interval [CI]: 0.21–0.70, P = 0.002). However, premyopia status increased the risk of myopia onset by 14 times compared to hyperopic status (OR = 14.0, 95 % CI: 1.86–105.3, P = 0.010). In the subgroup analysis of premyopic children, the myopic shift was also significantly lower in the ROC group than in the control group (–0.20 ± 0.60 D/year vs. –0.40 ± 0.66 D/year, P = 0.017). Myopia incidence in premyopic children was significantly lower in the ROC group than in the control group (19.6 % vs. 37.8 %, P = 0.001). Multivariate regression analysis showed that participation in the ROC program was significantly associated with a lower myopic shift in premyopic children (–0.22 D/year, 95 % CI: –0.39 to –0.06, P = 0.008) Conclusions: Premyopia is a risk factor for myopia onset. A school policy that includes more outdoor time can effectively prevent myopia onset and shift in premyopic children
[[alternative]]Heterocyclic compounds as kinase inhibitors for therapeutic uses
No full text[[abstract]]本揭露提供一種如下式I所示的雜環化合物及含有此類化合物中之一者的醫藥組合物：還揭示以雜環化合物中之一者治療由集落刺激因子-1受體調節的病症之方法
ベンズイミダゾール化合物,及びアルツハイマー病又はハンチントン病の治療のためのその使用
No full text[[abstract]]Benzimidazole compounds of formula (I), shown below, are disclosed. The compounds are potent human glutaminyl cyclase inhibitors. Also disclosed is a pharmaceutical composition containing one of these compounds and a pharmaceutical acceptable carrier, as well as a method of treating Alzheimer's disease or Huntington's disease by administering to a subject in need thereof an effective amount of such a compound
苯并咪唑化合物及其在製備治療阿茲海默症或亨丁頓氏症的藥物中的用途
No full text[[abstract]]本發明提供了一種如式(I)所示的苯并咪唑化合物，該化合物是有效的人類麩酸胺環化酶抑制劑。本發明還提供了一種含有該等化合物中之一化合物及醫藥上可接受載體的醫藥組合物以及一種藉由對需要治療阿茲海默症或亨丁頓氏症的個體投予有效量的該化合物來治療阿茲海默症或亨丁頓氏症的方法
Proline derivatives
No full text[[abstract]]Compounds of formula (I) shown in the specification. Also disclosed is a method for treating hepatitis C virus infection with these compounds
Poly heterocyclic conjugates and their pharmaceutical uses
No full text[[abstract]]Compounds of Formula (I) shown below and a pharmaceutical composition containing one of the compounds. Each of the variables is defined herein. Also disclosed is a method of treating a condition associated with uncontrolled cell growth with a compound of Formula (I)
PTGR2 inhibitors and their use
No full text[[abstract]]Disclosed are compounds of formula (I) as follows:in which each of R1, R2, R3, R4, R5, L1, W, and Het is defined herein. Also provides are a method of inhibiting prostaglandin reductase 2 (“PTGR2”) using such a compound and a pharmaceutical composition containing same
[[alternative]]Heterocyclic compounds and use thereof
No full text[[abstract]]本案揭露一種式(I)之化合物或其藥學上可接受之鹽類：其中，每個變數R1-R6、L、m以及n在本文中定義。本案也揭露一種以式(I)之化合物治療鴉片受體相關病症之方法，以及包含其之醫藥組成物