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Although organic solar cells (OSCs) have received increasing attention because of their high device efficiencies, the fundamental mechanism governing their photostability remains elusive. Herein, the effect of the luminescence stability of the acceptor components on the burn‐in voltage loss of binary and ternary OSCs is demonstrated. A systematic characterization reveals that the acceptor component experiences an abnormal decrease in luminescence under photoaging—specifically, photoinduced luminescence quenching—because of a photoinduced conformational change. This phenomenon increases nonradiative recombination in blends and thus causes a substantial nonradiative voltage loss of OSCs. Moreover, an introduction of a third component with high luminescence stability can effectively reduce the burn‐in voltage loss of OSCs. A composition‐dependent photostability study of the resultant ternary OSCs reveals that the reduction in the burn‐in voltage loss of OSCs is mainly driven by the third component distributed in the mixed phase; high luminescence stability of this component effectively prevents the increase in nonradiative voltage loss by photoaging. The results suggest that improving the luminescence stability of the acceptor components can be an effective method for highly stable photovoltaics with greatly reduced burn‐in voltage loss. [ABSTRACT FROM AUTHOR]

Since written reference works on ancient design techniques are still extant, it is possible to gain an understanding of the development of these designs. In particular, we are able to investigate dimensional standards used for wood members using the Kiwari (木割: a method of determining the dimensions of all wood members using a proportion determined based on the diameter of the columns) in Kiwari-sho (木割書: a manual of dimensional standards for wood members). The objective of this study was to confirm whether the design techniques that have been collected under the term "dimensional standards for building (木割術: Kiwari-jutsu)" were actually utilized in the construction of buildings and whether they are a sustainable technology. This study will provide an understanding of the correlation between the techniques used and the dimensions of the remains of structures putatively built using such techniques. Furthermore, based on this analysis, this study will be useful in both quantifying the influence that dimensional standards techniques had on buildings at the time of their construction and as reference material that can be used when restoring the remains of cultural properties. [ABSTRACT FROM AUTHOR]

It is considered that it is difficult to build a well-constructed building without proportional or dimensional relationships of precise parts, so it is estimated that Korea has some sort of numerical determination method now. Also, in China there is "Ying Zao Fa Shi: 営造法式" of technical books and it is doubtful that there is no similar technology in Korea with the same architectural flow, given that there are ways to decide "Kiwarisho: 木割書" in Japan. Therefore, focus on this point and aim to clarify the dimension determination method of Miruk-jõn Hall Kumsan-sa Temple using analysis method of each proportional method in Japan. [ABSTRACT FROM AUTHOR]

We identified treatment-naïve diabetic macular edema (DME) patients with or without subretinal fluid (SRF). We compared their baseline characteristics: aqueous concentrations of interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, and IL-17, as well as tumor necrosis factor-α, vascular endothelial growth factor (VEGF), and placental growth factor (PlGF). We also compared fundus and optical coherence tomography (OCT) findings, and responsiveness to anti-VEGF treatments. Of 67 DME patients, 18 (26.87%) had SRF. Compared to the no SRF group, the SRF group had significantly higher levels of IL-6, IL-8, VEGF, and PlGF in aqueous humor. After grouping according to diabetic retinopathy stage, non-proliferative diabetic retinopathy (NPDR) patients with SRF had higher aqueous levels of IL-6 and IL-8, compared to NPDR patients without SRF. Moreover, proliferative diabetic retinopathy (PDR) patients with SRF had higher aqueous levels of VEGF and PlGF, compared to PDR patients without SRF. Fundus and OCT analyses revealed that the SRF group had a greater proportion of patients with succinate or patch-shaped hard exudates involving the macula, and greater central subfield thickness (CST) at baseline. After 6 months of anti-VEGF treatments, the SRF group showed better responsiveness in terms of CST; however, visual acuity was not correlated with responsiveness. Considering higher aqueous levels of VEGFs and pro-inflammatory cytokines, SRF could be a biomarker related to diabetic retinopathy activity. DME patients with SRF showed better anatomical responsiveness to anti-VEGF treatments, but did not show better functional improvement on short-term evaluation compared to those of DME patients without SRF. [ABSTRACT FROM AUTHOR]

Histone H3 lysine 27 (H3K27M) mutations represent the canonical oncohistone, occurring frequently in midline gliomas but also identified in haematopoietic malignancies and carcinomas. H3K27M functions, at least in part, through widespread changes in H3K27 trimethylation but its role in tumour initiation remains obscure. To address this, we created a transgenic mouse expressing H3.3K27M in diverse progenitor cell populations. H3.3K27M expression drives tumorigenesis in multiple tissues, which is further enhanced by Trp53 deletion. We find that H3.3K27M epigenetically activates a transcriptome, enriched for PRC2 and SOX10 targets, that overrides developmental and tissue specificity and is conserved between H3.3K27M-mutant mouse and human tumours. A key feature of the H3K27M transcriptome is activation of a RAS/MYC axis, which we find can be targeted therapeutically in isogenic and primary DIPG cell lines with H3.3K27M mutations, providing an explanation for the common co-occurrence of alterations in these pathways in human H3.3K27M-driven cancer. Taken together, these results show how H3.3K27M-driven transcriptome remodelling promotes tumorigenesis and will be critical for targeting cancers with these mutations. Histone H3 at lysine 27 (H3K27M) is often mutated in cancer but its role in tumour initiation is unclear. Here, the authors generated a transgenic model expressing H3.3K27M from the Fabp7 gene promoter, demonstrating that H3.3K27M can initiate diverse tumorigesis on its own, acting through a RAS/MYC transcriptomic programme. [ABSTRACT FROM AUTHOR]

Cancer predisposition syndromes are associated with an increased risk of developing primary malignancies. Here we discuss those which are associated with an increased risk of tumors of the central nervous system (CNS) and gastrointestinal (GI) tract. These can be grouped into those in which the CNS tumors predominate versus those in which the GI cancers predominate. The former include constitutional mismatch repair deficiency (CMMRD) syndrome, Li–Fraumeni syndrome (LFS), and Cowden syndrome (CS) while the latter include familial adenomatosis polyposis 1 (FAP1), Lynch syndrome and polymerase proofreading-associated polyposis syndrome (PPAP). Tumor specificity does exist as medulloblastoma occur in FAP, LFS and CMMRD while glioma are most commonly seen in all replication repair-deficient genes and LFS. Choroid plexus carcinoma is strictly observed in LFS while Cowden syndrome patients develop Lhermitte Duclos disease or meningioma. In each syndrome, specific types of low-grade and high-grade gastrointestinal cancers can occur, but these will be discussed elsewhere. Underlying cancer predisposition syndromes are important to consider when faced with brain tumors, particularly in the pediatric and young adult age groups, as identification of an underlying germ line mutation may change the upfront management of the patient and has implications for future cancer surveillance for both the patient and potentially affected family members. Considerations of family history, presence of skin lesions and consanguinity provide valuable information in identifying patients at potential increased risk. [ABSTRACT FROM AUTHOR]

The expression of total and phosphorylated IGF1R and Src was determined by Western blot analysis. f A549 cells were treated with linsitinib (1 M) or dasatinib (100 nM) for 1 day. The immunoprecipitants were further subjected to Western blot analysis using anti-pTyr, anti-IGF1R, and anti-IR antibodies. e R- cells were treated with LL28 (0.1 and 1 M) for 8 h. The expression of total and phosphorylated IGF1R and Src was evaluated by Western blot analysis. g A549, H1299, and H460 cells were treated with LL28 (0.1 M) for 1, 3, and 5 days. [Extracted from the article]

Rational design and synthetic feasibility are critical factors for the photoaffinity labelling (PAL) approach, which can identify protein targets of bioactive small molecules under native cellular conditions. In this study, we developed photoaffinity labelling probes derived from 1,3,4‐oxadiazin‐5(6H)‐ones (OPALs) for LL‐2003, a previously reported potential anticancer agent against IGF‐1R and Src. Our photoaffinity labelling strategy enabled successful photo‐crosslinking of the probes (OPAL‐6 and OPAL‐8) with the target proteins in both mammalian cell lysates and live MCF7, A549, HepG2 and HeLa cells in situ. In vitro and in situ labelling demonstrated different patterns and expression levels of the proteome, and the strongest band for Src appeared in the A549 cell line. An in‐gel fluorescence scan combined with MS/MS analysis of the IGF‐1R overexpressed insect proteome labelled by OPAL‐6 and OPAL‐8 identified the binding location of the synthesized probes. [ABSTRACT FROM AUTHOR]

Understanding how Munc18 proteins govern exocytosis is crucial because mutations of this protein cause severe secretion deficits in neuronal and immune cells. Munc18-2 has indispensable roles in the degranulation of mast cell, partly by binding and chaperoning a subset of syntaxin isoforms. However, the key syntaxin that, crucially, participates in the degranulation -- whose levels and intracellular localization are regulated by Munc18-2 -- remains unknown. Here, we demonstrate that double knockdown of Munc18-1 and Munc-2 in mast cells results in greatly reduced degranulation accompanied with strikingly compromised expression levels and localization of syntaxin-3. This phenotype is fully rescued by wild-type Munc18 proteins but not by the K46E, E59K and K46E/E59K mutants of Munc-18 domain 1, each of which exhibits completely abolished binding to 'closed' syntaxin-3. Furthermore, knockdown of syntaxin-3 strongly impairs degranulation. Collectively, our data argue that residues Lys46 and Glu59 of Munc18 proteins are indispensable for mediating the interaction between Munc18 and closed syntaxin-3, which is essential for degranulation by chaperoning syntaxin-3. Our results also indicate that the functional contribution of these residues differs between immune cell degranulation and neuronal secretion. [ABSTRACT FROM AUTHOR]

Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-021-00442-z, published online 25 October 2021 The original version of this Article contained an error in the Acknowledgments section. "This work has supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 52020A015400343)." now reads: "This work has supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2020R1G1A1007646).". [Extracted from the article]

Infant gliomas have paradoxical clinical behavior compared to those in children and adults: low-grade tumors have a higher mortality rate, while high-grade tumors have a better outcome. However, we have little understanding of their biology and therefore cannot explain this behavior nor what constitutes optimal clinical management. Here we report a comprehensive genetic analysis of an international cohort of clinically annotated infant gliomas, revealing 3 clinical subgroups. Group 1 tumors arise in the cerebral hemispheres and harbor alterations in the receptor tyrosine kinases ALK, ROS1, NTRK and MET. These are typically single-events and confer an intermediate outcome. Groups 2 and 3 gliomas harbor RAS/MAPK pathway mutations and arise in the hemispheres and midline, respectively. Group 2 tumors have excellent long-term survival, while group 3 tumors progress rapidly and do not respond well to chemoradiation. We conclude that infant gliomas comprise 3 subgroups, justifying the need for specialized therapeutic strategies. Infant gliomas behave differently to their childhood or adult counterparts. Here, the authors perform a large-scale genetic analysis of these tumours, revealing genetic alterations which may offer therapeutic opportunities. [ABSTRACT FROM AUTHOR]

Keywords: target identification; photoaffinity labelling; fluorescence probes; proteomics; proteins The labelling strategy enabled successful photo-crosslinking with target proteins in both insect cell lysates and mammalian live cells, demonstrating the efficient and selective labelling of Src. Target identification, photoaffinity labelling, fluorescence probes, proteomics, proteins. [Extracted from the article]

Background: Both the type I insulin-like growth factor receptor (IGF1R) and Src pathways are associated with the development and progression of numerous types of human cancer, and Src activation confers resistance to anti-IGF1R therapies. Hence, targeting both IGF1R and Src concurrently is one of the main challenges in combating resistance to the currently available anti-IGF1R-based anticancer therapies. However, the enhanced toxicity from this combinatorial treatment could be one of the main hurdles for this strategy, suggesting the necessity of developing a novel strategy for co-targeting IGF1R and Src to meet an urgent clinical need. Methods: We synthesized a series of 4-aminopyrazolo[3,4-d]pyrimidine-based dual IGF1R/Src inhibitors, selected LL28 as an active compound and evaluated its potential antitumor effects in vitro and in vivo using the MTT assay, colony formation assays, flow cytometric analysis, a tumor xenograft model, and the KrasG12D/+-driven spontaneous lung tumorigenesis model. Results: LL28 markedly suppressed the activation of IGF1R and Src and significantly inhibited the viability of several NSCLC cell lines in vitro by inducing apoptosis. Administration of mice with LL28 significantly suppressed the growth of H1299 NSCLC xenograft tumors without overt toxicity and substantially reduced the multiplicity, volume, and load of lung tumors in the KrasG12D/+-driven lung tumorigenesis model. Conclusions: The present results suggest the potential of LL28 as a novel anticancer drug candidate targeting both IGF1R and Src, providing a new avenue to efficient anticancer therapies. Further investigation is warranted in advanced preclinical and clinical settings. [ABSTRACT FROM AUTHOR]