A major challenge in photodynamic cancer therapy (PDT) is avoiding PDT-induced hypoxia, which can lead to cancer recurrence and progression through activation of various angiogenic factors and ...significantly reduce treatment outcomes. Reported here is an acetazolamide (AZ)-conjugated BODIPY photosensitizer (AZ-BPS) designed to mitigate the effects of PDT-based hypoxia by combining the benefits of anti-angiogenesis therapy with PDT. AZ-BPS showed specific affinity to aggressive cancer cells (MDA-MB-231 cells) that overexpress carbonic anhydrase IX (CAIX). It displayed enhanced photocytotoxicity compared to a reference compound, BPS, which is an analogous PDT agent that lacks an acetazolamide unit. AZ-BPS also displayed an enhanced in vivo efficacy in a xenograft mouse tumor regrowth model relative to BPS, an effect attributed to inhibition of tumor angiogenesis by both PDT-induced ROS generation and CAIX knockdown. AZ-BPS was evaluated successfully in clinical samples collected from breast cancer patients. We thus believe that the combined approach described here represents an attractive therapeutic approach to targeting CAIX-overexpressing tumors.
Objectives
This study was conducted in order to assess the performance of the Liver Imaging Reporting and Data System (LI-RADS) treatment response (TR) (LR-TR) categorization on gadoxetic ...acid-enhanced MRI (Gd-EOB-MRI) for detecting viable tumors in hepatocellular carcinoma (HCC) treated with locoregional treatment (LRT) and to investigate the added value of ancillary features (AFs) to conventional enhancement-based criteria.
Methods
This retrospective study included 183 patients with Gd-EOB-MRI after LRT for HCC and appropriate reference standards for tumor viability (84 viable and 99 nonviable). Two independent radiologists assigned per-lesion mRECIST and TR categories (TR-nonviable, TR-equivocal, or TR-viable) according to the LR-TR algorithm and modified LR-TR algorithms including mLR-TR(TP) allowing transitional phase (TP) washout and mLR-TR(AF) allowing category adjustment by applying AFs. Diagnostic performances of imaging criteria were compared using the Cochran’s
Q
test with post hoc analysis.
Results
For detecting viable tumors, LR-TR-viable resulted in sensitivities of 64.5%/39.3% and specificities of 98.0%/98.0% in reviewers 1/2. In comparison to LR-TR-viable, mRECIST-viable, mLR-TR(TP)-viable, and mLR-TR(AF)-viable showed significantly higher sensitivities (92.9%/94.0%, 77.4%/56.6%, and 86.9%/83.3% in reviewers 1/2) (
p
s < 0.001). The specificity of mRECIST-viable (73.7%/62.6%) was significantly lower than that of LR-TR-viable (
p
s < 0.001), while those of mLR-TR(TP)-viable and mLR-TR(AF)-viable were greater than 95% (98.0%/96.0% and 97.0%/96.0%), statistically equivalent to LR-TR-viable (
p
s > 0.05). TR-equivocal was least assigned on mLR-TR(AF) (1.1%/7.7%) than LR-TR (15.8%/32.2%) or mLR-TR(TP) (6.6%/23.5%) in both reviewers.
Conclusion
The LR-TR algorithm on Gd-EOB-MRI provides a specific diagnosis of viable tumor but with limited sensitivity. By applying AFs in the category adjustment, more sensitive and confident diagnosis can be achieved without significant loss of specificity.
Key Points
• The LI-RADS treatment response (LR-TR) algorithm on Gd-EOB-MRI provides a highly specific diagnosis of viable HCC but with limited sensitivity.
• The inferior sensitivity of LR-TR-viable category to that of mRECIST can be improved by applying ancillary features in the category adjustment.
Pathway-targeted cancer drugs can produce dramatic responses that are invariably limited by the emergence of drug-resistant cells. We found that many drug-treated “oncogene-addicted” cancer cells ...engage a positive feedback loop leading to Stat3 activation, consequently promoting cell survival and limiting overall drug response. This was observed in cancer cells driven by diverse activated kinases, including EGFR, HER2, ALK, and MET, as well as mutant KRAS. Specifically, MEK inhibition led to autocrine activation of Stat3 via the FGF receptor and JAK kinases, and pharmacological inhibition of MEK together with JAK and FGFR enhanced tumor regression. These findings suggest that inhibition of a Stat3 feedback loop may augment the response to a broad spectrum of drugs that target pathways of oncogene addiction.
•Many oncogene-addicted cancer cells initially respond well to pathway-targeted drugs•Multiple resistance mechanisms limit the overall efficacy of most cancer drugs•A Stat3-mediated feedback loop engaged by drug treatment contributes to resistance•Disrupting Stat3 feedback enhances drug efficacy in many oncogene-addicted cells
Lee et al. identify a specific autocrine feedback activation loop of Stat3 signaling following receptor tyrosine kinase or MEK inhibition in oncogene-addicted cells that promotes drug resistance, suggesting that disrupting this loop could enhance the efficacy of drugs targeting these oncogenic pathways.
Over the past number of years, the power conversion efficiency of perovskite solar cells has remained at 25.5%, reflecting a respectable result for the general incorporation of organometallic ...trihalide perovskite solar cells. However, perovskite solar cells still suffer from long-term stability issues. Perovskite decomposes upon exposure to moisture, thermal, and UV-A light. Studies related to this context have remained ongoing. Recently, research was mainly conducted on the stability of perovskite against non-radiative recombination. This study improved a critical instability in perovskite solar cells arising from non-radiative recombination and UV-A light using a passivation layer. The passivation layer comprised a polyaniline (PANI) polymer as an interfacial modifier inserted between the active layer and the electron transport layer. Accordingly, the UV-A light did not reach the active layer and confined the Pb
ions at PANI passivation layer. This study optimized the perovskite solar cells by controlling the concentration, thickness and drying conditions of the PANI passivation layer. As a result, the efficiency of the perovskite solar cell was achieved 15.1% and showed over 84% maintain in efficiency in the ambient air for one month using the 65 nm PANI passivation layer.
The methanation of CO2 has been actively pursued as a practical approach to mitigating global climate change. However, the complexity of the catalyst development process has hindered the development ...of new catalysts for CO2 methanation; as a result, few catalysts are commercially available. Herein, a multifunctional self‐catalytic reactor (SCR) is prepared via metal 3D printing and selective electrochemical dissolution as a method to not only simplify the catalyst development process but also fabricate active catalysts for CO2 methanation. The combination of metal 3D printing and selective electrochemical dissolution is demonstrated as a feasible method to prepare active catalysts for the methanation of CO2 in a short time. In addition, the use of an electrochemical method enables the formation of galvanic cells on the SCR; these cells continuously generate active sites via self‐dissolution during a simple refresh process, resulting in high reusability of the SCR. The proposed method represents a new facile technique to fabricate highly reusable catalysts that exhibit superior performance for CO2 methanation, and the results provide a guideline for preparing metal 3D‐printed catalysts that will satisfy industrial demand.
Metal 3D printing is revolutionizing the industry by enabling rapid and cost‐effective production of complex metal 3D products with intricate geometries, attracting significant attention in recent ...years. Particularly, metal 3D‐printed catalysts have emerged as a cutting‐edge fusion technology that serves as both catalysts and reactors, referred to as self‐catalytic reactors (SCRs). Therefore, this concept article aims to introduce the recent advancements in metal 3D printing technology in the catalyst and reactor field, and illustrate the various aspects for the rational design of self‐catalytic reactors.
Metal 3D printing has attracted recent attention as a cutting‐edge fusion technology in the catalyst field due to advantages such as design flexibility, variety of material selection, and ease of mass production. Additionally, catalytic efficiency can be enhanced by adjusting surface functionalization and geometric structural design. Metal 3D‐printed catalysts are expected to provide a new direction for catalysis research by integrating existing individual catalyst and reactor research, thereby shortening the realization of a carbon‐neutral society.
Background and purpose - We aimed to evaluate the ability of artificial intelligence (a deep learning algorithm) to detect and classify proximal humerus fractures using plain anteroposterior shoulder ...radiographs.
Patients and methods - 1,891 images (1 image per person) of normal shoulders (n = 515) and 4 proximal humerus fracture types (greater tuberosity, 346; surgical neck, 514; 3-part, 269; 4-part, 247) classified by 3 specialists were evaluated. We trained a deep convolutional neural network (CNN) after augmentation of a training dataset. The ability of the CNN, as measured by top-1 accuracy, area under receiver operating characteristics curve (AUC), sensitivity/specificity, and Youden index, in comparison with humans (28 general physicians, 11 general orthopedists, and 19 orthopedists specialized in the shoulder) to detect and classify proximal humerus fractures was evaluated.
Results - The CNN showed a high performance of 96% top-1 accuracy, 1.00 AUC, 0.99/0.97 sensitivity/specificity, and 0.97 Youden index for distinguishing normal shoulders from proximal humerus fractures. In addition, the CNN showed promising results with 65-86% top-1 accuracy, 0.90-0.98 AUC, 0.88/0.83-0.97/0.94 sensitivity/specificity, and 0.71-0.90 Youden index for classifying fracture type. When compared with the human groups, the CNN showed superior performance to that of general physicians and orthopedists, similar performance to orthopedists specialized in the shoulder, and the superior performance of the CNN was more marked in complex 3- and 4-part fractures.
Interpretation - The use of artificial intelligence can accurately detect and classify proximal humerus fractures on plain shoulder AP radiographs. Further studies are necessary to determine the feasibility of applying artificial intelligence in the clinic and whether its use could improve care and outcomes compared with current orthopedic assessments.
Celotno besedilo
Dostopno za:
DOBA, FSPLJ, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Outbreak of African swine fever in South Korea, 2019 Kim, Hyun‐Joo; Cho, Ki‐Hyun; Lee, Soo‐Kyoung ...
Transboundary and emerging diseases,
March 2020, 2020-Mar, 2020-03-00, 20200301, Letnik:
67, Številka:
2
Journal Article
Recenzirano
Odprti dostop
African swine fever, a fatal haemorrhagic disease of swine, was confirmed in domestic pigs for the first time in South Korea in September 2019. The causative virus belonged to the p72 genotype II and ...had an additional tandem repeat sequence in the intergenic region (IGR) between the I73R and I329L.
Under endoplasmic reticulum (ER)‐stress conditions, the unfolded protein response (UPR) generates a defense mechanism in mammalian cells. The regulation of UPR signaling is important in oocyte ...maturation, embryo development, and female reproduction of pigs. Recent studies have shown that melatonin plays an important role as an antioxidant to improve pig oocyte maturation. However, there is no report on the role of melatonin in the regulation of UPR signaling and ER‐stress during in vitro maturation (IVM) of porcine oocytes. Therefore, the objective of this study was to investigate the antioxidative effects of melatonin on porcine oocyte maturation through the regulation of ER‐stress and UPR signaling. We investigated the changes in the mRNA/protein expression levels of three UPR signal genes (Bip/Grp78, ATF4, P90/50ATF6, sXbp1, and CHOP) on oocytes, cumulus cells, and cumulus‐oocyte complexes (COCs) during IVM (metaphase I; 22 hours and metaphase II; 44 hours) by Western blot and reverse transcription‐polymerase chain reaction analysis. Treatment with the ER‐stress inducer, tunicamycin (Tm), significantly increased expression of UPR markers. Additionally, cumulus cell expansion and meiotic maturation of oocytes were reduced in COCs of Tm‐treated groups (1, 5, and 10 μg/mL). We confirmed the reducing effects of melatonin (0.1 μmol/L) on ER‐stress after pretreatment with Tm (5 μg/mL; 22 hours) in maturing COCs. Addition of melatonin (0.1 μmol/L) to Tm‐pretreated COCs recovered meiotic maturation rates and expression of most UPR markers. In conclusion, we confirmed a role for melatonin in the modulation of UPR signal pathways and reducing ER‐stress during IVM of porcine oocytes.
Cesium‐based perovskite nanocrystals (NCs) have outstanding photophysical properties improving the performances of lighting devices. Fundamental studies on excitonic properties and hot‐carrier ...dynamics in perovskite NCs further suggest that these materials show higher efficiencies compared to the bulk form of perovskites. However, the relaxation rates and pathways of hot‐carriers are still being elucidated. By using ultrafast transient spectroscopy and calculating electronic band structures, we investigated the dependence of halide in Cs‐based perovskite (CsPbX3 with X=Br, I, or their mixtures) NCs on the hot‐carrier relaxation processes. All samples exhibit ultrafast (<0.6 ps) hot‐carrier relaxation dynamics with following order: CsPbBr3 (310 fs)>CsPbBr1.5I1.5 (380 fs)>CsPbI3 NC (580 fs). These result accounts for a reduced light emission efficiency of CsPbI3 NC compared to CsPbBr3 NC.
Significant dependence of the hot‐carrier relaxation rate on the halide (Br, I, or their mixture) is mainly attributable to the density of states for holes in the valence band of CsPbX3 nanocrystals. The hot‐carrier relaxation rate is observed to decrease from CsPbBr3 to CsPbI3 NC. VB=valence band, CB=conduction band.
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