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Overexpressed pro-survival B-cell lymphoma-2 (BCL-2) family proteins BCL-2 and BCL-XL can render tumor cells malignant. Leukemia drug venetoclax is currently the only approved selective BCL-2 inhibitor. However, its application has led to an emergence of resistant mutations, calling for drugs with an innovative mechanism of action. Herein we present cyclic peptides (CPs) with nanomolar-level binding affinities to BCL-2 or BCL-XL, and further reveal the structural and functional mechanisms of how these CPs target two proteins in a fashion that is remarkably different from traditional small-molecule inhibitors. In addition, these CPs can bind to the venetoclax-resistant clinical BCL-2 mutants with similar affinities as to the wild-type protein. Furthermore, we identify a single-residue discrepancy between BCL-2 D111 and BCL-XL A104 as a molecular "switch" that can differently engage CPs. Our study suggests that CPs may inhibit BCL-2 or BCL-XL by delicately modulating protein-protein interactions, potentially benefiting the development of next-generation therapeutics. Pro-survival B-cell lymphoma-2 (BCL-2) family proteins BCL-2 and BCL-XL are the targets of anti-tumour drugs, but resistance is emerging. The authors present cyclic peptides against BCL-2 and BCL-XL, with a distinct mechanism of targeting characterised. [ABSTRACT FROM AUTHOR]

Nephroblastoma, an overexpressed gene (NOV) protein, plays an important role in proliferation, differentiation, angiogenesis, adhesion, invasion and tumorigenesis, but the function of amino-truncated NOV is different. This study is to investigate the role of amino-truncated NOV in the progression of bladder cancer. Using immunohistochemistry and Western blot analysis, we detected the amino-truncated NOV in bladder cancer, and statistical analysis was performed to estimate the association between the expression of amino-truncated NOV and the patient's prognosis by SPSS 19.0. With transduction of amino-truncated NOV, we evaluated alteration for proliferation, migration, invasion and chemoresistance in bladder cancer cells, as well as some proteins related to Wnt/β-catenin pathway and epithelial–mesenchymal transition. The truncated variant of the NOV protein was located in a nucleus other than the cytoplasm and highly expressed in bladder cancer, which was also linked to higher pathological grade and positive lymph node metastasis as well as recurrence. The exact sequence of this truncated protein was confirmed, and it was a 26-kDa splicing. The truncated NOV protein found in bladder cancer was cut at the 187th amino acid of the full-length protein. It was also involved in bladder cancer progression and chemoresistance through a mechanism involving epithelial–mesenchymal transition (EMT) and the Wnt/β-catenin signaling pathway. Our findings provide experimental evidence that the nuclear NOV protein expression is a potential biomarker in the prognostic evaluation of bladder cancer and enhanced amino-truncated NOV expression is potentially important for bladder cancer cell invasion, metastasis and chemoresistance during progression. [ABSTRACT FROM AUTHOR]

Global energy consumption is growing rapidly, with the frequency and intensity of extreme events constantly increasing, posing a long-term threat to power supply and consumption. Therefore, analyzing the spatiotemporal characteristics of electricity consumption and quantitatively assessing the impact of extreme events on electricity consumption are of great significance. Based on fine-grained electricity consumption data from Europe for the years 2019–2022, this paper employs a data mining perspective and four methods including Z-score, Isolation Forest, Local Outlier Factor, and Autoencoder to detect abnormal electricity consumption during extreme events. Additionally, it combines indicators such as elastic loss, vulnerability, and duration to measure the impact of extreme events on electricity consumption. It is found that low temperatures could lead to abrupt changes in electricity consumption, with Northern Europe being more significantly affected by low temperatures. The COVID-19 pandemic had the most significant impact on electricity consumption in Europe, with the middle part of Europe being the hardest hit during the first wave of the pandemic. Electricity anomalies during the pandemic period were related to national pandemic control policies and exhibited some lag. High temperatures persisted for a longer duration in the middle part of Europe. [ABSTRACT FROM AUTHOR]

High-performance near-ultraviolet organic light-emitting diodes (NUV OLEDs) are very limited due to the scarcity of short-wavelength emitters. Herein, three weak-conjugation donor–acceptor molecules are designed using carbazole and phenanthroimidazole as the donor and the acceptor, respectively. These molecules exhibit excellent thermal and morphological stability and efficient NUV photoluminescence. Using these dyes as dopants, the devices at 10 wt% doping concentration exhibit efficient UV emission with small full width at half maximum (FWHM) values of 38, 38, 56 nm and small Commission Internationale de L'Eclairage coordinate y values (CIEy) of 0.028, 0.028, 0.045, respectively. The doped device showed a maximum external quantum efficiency of 7.97% and high exciton utility efficiency in the range of 62–93%. Using an ortho-position molecule as an emitter, the nondoped device exhibited small efficiency roll-offs (2% at 100 cd m−2 and 18% at 1000 cd m−2) and excellent color purity (a FWHM of 36 nm and a CIEy coordinate of 0.037) with the peak wavelength at 404 nm. This research provides a method for designing efficient NUV emitters for OLEDs with good color purity and small efficiency roll-off by weak-conjugation link between a donor and an acceptor. [ABSTRACT FROM AUTHOR]

The first dual nickel/photoredox-catalyzed enantioselective reductive cross-coupling of racemic α-chloro thioesters with aryl iodides has been developed. This strategy avoids the need for organometallic reagents or stoichiometric metal reductants. This reaction could tolerate a wide range of substrate scope with excellent reactivity and high enantioselectivities (up to 91% ee) to access a variety of chiral α-aryl thioesters. The synthetic utility of the corresponding α-aryl thioesters is demonstrated. Furthermore, we explored the mechanism of such an enantioselective radical cross-coupling process. [ABSTRACT FROM AUTHOR]