Abnormal metabolism of tumour cells is closely related to the occurrence and development of breast cancer, during which the expression of NF‐E2‐related factor 2 (Nrf2) is of great significance. ...Metastatic breast cancer is one of the most common causes of cancer death worldwide; however, the molecular mechanism underlying breast cancer metastasis remains unknown. In this study, we found that the overexpression of Nrf2 promoted proliferation and migration of breast cancers cells. Inhibition of Nrf2 and overexpression of Kelch‐like ECH‐associated protein 1 (Keap1) reduced the expression of glucose‐6‐phosphate dehydrogenase (G6PD) and transketolase of pentose phosphate pathway, and overexpression of Nrf2 and knockdown of Keap1 had opposite effects. Our results further showed that the overexpression of Nrf2 promoted the expression of G6PD and Hypoxia‐inducing factor 1α (HIF‐1α) in MCF‐7 and MDA‐MB‐231 cells. Overexpression of Nrf2 up‐regulated the expression of Notch1 via G6PD/HIF‐1α pathway. Notch signalling pathway affected the proliferation of breast cancer by affecting its downstream gene HES‐1, and regulated the migration of breast cancer cells by affecting the expression of EMT pathway. The results suggest that Nrf2 is a potential molecular target for the treatment of breast cancer and targeting Notch1 signalling pathway may provide a promising strategy for the treatment of Nrf2‐driven breast cancer metastasis.
Organic donor–acceptor systems have attracted much attention due to their various potential applications. However, the rational construction and modulation of highly ordered donor–acceptor systems ...could be a challenge due to the complicated self‐assembly process of donor and acceptor species. Considering the well‐defined arrangement of species at the molecule level, a crystalline host–guest system could be an ideal platform for the rational construction of donor–acceptor systems. Herein, it is shown how the rational construction of highly tunable donor–acceptor materials can be achieved based on a crystalline host–guest platform. Within the well‐established metal–organic framework NKU‐111 as the crystalline host enabled by the relatively stable coordination‐directed assembly, the introduction and arrangement of guest molecules in the crystals allow the rational construction of the NKU‐111⊃guest donor–acceptor system. The donor–acceptor interaction in the systems can be readily modulated with different guest molecules, which can be justified by the well‐demonstrated guest‐dependent characteristics. Accordingly, the NKU‐111⊃guest reveals highly tunable donor–acceptor properties such as charge‐transfer‐based emissions and electrical conductivity. This work indicates the potential of crystalline host–guest systems as an ideal platform for systematic investigations of donor–acceptor materials.
A donor–acceptor material based on a host–guest crystalline material platform is raised. As a proof of concept, a metal–organic framework (NKU‐111) is utilized as a host acceptor for the accommodation of aromatic donor guests. The resulting donor–acceptor system features highly tunable charge‐transfer‐based emissions and conductivity, indicating the rationality and efficiency of this strategy.
Photonic materials use photons as information carriers and offer the potential for unprecedented applications in optical and optoelectronic devices. In this study, we introduce a new strategy for ...photonic materials using metal–organic frameworks (MOFs) as the host for the rational construction of donor–acceptor (D–A) heterostructure crystals. We have engineered a rich library of heterostructure crystals using the MOF NKU‐111 as a host. NKU‐111 is based upon an electron‐deficient tridentate ligand (acceptor) that can bind to various electron‐rich guests (donors). The resulting heterocrystals exhibit spatially segregated multi‐color emission resulting from the guest‐dependent charge‐transfer (CT) emission. Spatially effective mono‐directional energy transfer results from tuning the energy gradient between adjacent domains through the selection of donor guest molecules, which suggests potential applications in integrated optical circuit devices, for example, photonic diodes, on‐chip signal processing, optical logic gates.
MOF logic: A crystalline metal–organic framework (MOF) host–guest platform is used for the construction of a rich library of donor–acceptor (D–A) heterostructure crystals. The approach could facilitate the construction of heterocrystal devices for optical logic computation applications.
Microbial fuel cells (MFCs) can directly convert the chemical energy stored in organic matter to electricity and are of considerable interest for power generation and wastewater treatment. However, ...the current MFCs typically exhibit unsatisfactorily low power densities that are largely limited by the sluggish transmembrane and extracellular electron-transfer processes. Here, we report a rational strategy to boost the charge-extraction efficiency in
MFCs substantially by introducing transmembrane and outer-membrane silver nanoparticles. The resulting
-silver MFCs deliver a maximum current density of 3.85 milliamperes per square centimeter, power density of 0.66 milliwatts per square centimeter, and single-cell turnover frequency of 8.6 × 10
per second, which are all considerably higher than those of the best MFCs reported to date. Additionally, the hybrid MFCs feature an excellent fuel-utilization efficiency, with a coulombic efficiency of 81%.
To study the mechanisms of relapse in acute lymphoblastic leukemia (ALL), we performed whole-genome sequencing of 103 diagnosis-relapse-germline trios and ultra-deep sequencing of 208 serial samples ...in 16 patients. Relapse-specific somatic alterations were enriched in 12 genes (NR3C1, NR3C2, TP53, NT5C2, FPGS, CREBBP, MSH2, MSH6, PMS2, WHSC1, PRPS1, and PRPS2) involved in drug response. Their prevalence was 17% in very early relapse (<9 months from diagnosis), 65% in early relapse (9-36 months), and 32% in late relapse (>36 months) groups. Convergent evolution, in which multiple subclones harbor mutations in the same drug resistance gene, was observed in 6 relapses and confirmed by single-cell sequencing in 1 case. Mathematical modeling and mutational signature analysis indicated that early relapse resistance acquisition was frequently a 2-step process in which a persistent clone survived initial therapy and later acquired bona fide resistance mutations during therapy. In contrast, very early relapses arose from preexisting resistant clone(s). Two novel relapse-specific mutational signatures, one of which was caused by thiopurine treatment based on in vitro drug exposure experiments, were identified in early and late relapses but were absent from 2540 pan-cancer diagnosis samples and 129 non-ALL relapses. The novel signatures were detected in 27% of relapsed ALLs and were responsible for 46% of acquired resistance mutations in NT5C2, PRPS1, NR3C1, and TP53. These results suggest that chemotherapy-induced drug resistance mutations facilitate a subset of pediatric ALL relapses.
•Chemotherapy-induced mutagenesis may cause drug resistance mutations in ALL, leading to relapse.
•Thiopurines in particular likely cause drug resistance mutations in NT5C2, NR3C1, and TP53.
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Bloodborne infections with Candida albicans are an increasingly recognized complication of modern medicine. Here, we present a mouse model of low-grade candidemia to determine the effect of ...disseminated infection on cerebral function and relevant immune determinants. We show that intravenous injection of 25,000 C. albicans cells causes a highly localized cerebritis marked by the accumulation of activated microglial and astroglial cells around yeast aggregates, forming fungal-induced glial granulomas. Amyloid precursor protein accumulates within the periphery of these granulomas, while cleaved amyloid beta (Aβ) peptides accumulate around the yeast cells. CNS-localized C. albicans further activate the transcription factor NF-κB and induce production of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor (TNF), and Aβ peptides enhance both phagocytic and antifungal activity from BV-2 cells. Mice infected with C. albicans display mild memory impairment that resolves with fungal clearance. Our results warrant additional studies to understand the effect of chronic cerebritis on cognitive and immune function.
Metformin was proposed to be a candidate for host-directed therapy for COVID-19. However, its efficacy remains to be validated. In this study, we compared the outcome of metformin users and nonusers ...in hospitalized COVID-19 patients with diabetes. Hospitalized diabetic patients with confirmed COVID-19 in the Tongji Hospital of Wuhan, China, from January 27, 2020 to March 24, 2020, were grouped into metformin and no-metformin groups according to the diabetic medications used. The demographics, characteristics, laboratory parameters, treatments, and clinical outcome in these patients were retrospectively assessed. A total of 283 patients (104 in the metformin and 179 in the no-metformin group) were included in this study. There were no significant differences between the two groups in gender, age, underlying diseases, clinical severity, and oxygen-support category at admission. The fasting blood glucose level of the metformin group was higher than that of the no-metformin group at admission and was under effective control in both groups after admission. Other laboratory parameters at admission and treatments after admission were not different between the two groups. The length of hospital stay did not differ between the two groups (21.0 days for metformin versus 19.5 days for no metformin,
= 0.74). However, in-hospital mortality was significantly lower in the metformin group (3/104 (2.9%) versus 22/179 (12.3%),
= 0.01). Antidiabetic treatment with metformin was associated with decreased mortality compared with diabetics not receiving metformin. This retrospective analysis suggests that metformin may offer benefits in patients with COVID-19 and that further study is indicated.
A ternary polymer memory device based on a single polymer with on‐chain Ir(III) complexes is fabricated by combining multiple memory mechanisms into one system. Excellent ternary memory ...performances—low reading, writing, and erasing voltages and good stability for all three states—are achieved.
Molecular materials possessing photo‐tunable polarization switching is promising for optical switches, smart sensors, and data storage devices. However, it is challenging to devise a molecular ...material featuring simultaneous switchable magnetic and dielectric properties with regard to non‐invasive and convenient light stimulus. Herein, we report a new Hofmann‐type metal–organic framework (MOF) {Fe(bpt)Pt(CN)4} ⋅ 0.5anth (1, bpt=2,5‐bis(4‐pyridyl)thiophen; anth=anthracene), which displays thermo‐ and photo‐switchable magnetic and dielectric properties. Photo‐monitored structural analyses revealed that it was the photo‐induced deformation of FeII coordination sphere and relative movement of guest anthracene that resulted in the variation of the local electric dipoles. These findings provide a new strategy to realize polarization switching through the light‐induced spin crossover, and would be of fundamental significance for future photo‐switchable and multifunctional materials.
A new 3D Hofmann‐type metal–organic framework (MOF) {Fe(bpt)Pt(CN)4} ⋅ 0.5anth (1, bpt=2,5‐bis(4‐pyridyl)thiophen; anth=anthracene) is prepared. It displays thermo‐ and photo‐switchable magnetic and dielectric properties accompanied by structural phase transitions between different space groups.
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