The ten–eleven translocation (TET) family of methylcytosine dioxygenases initiates demethylation of DNA and is associated with tumorigenesis in many cancers; however, the mechanism is mostly unknown. ...Here we identify upstream activators and downstream effectors of TET1 in breast cancer using human breast cancer cells and a genetically engineered mouse model. We show that depleting the architectural transcription factor high mobility group AT-hook 2 (HMGA2) induces TET1 . TET1 binds and demethylates its own promoter and the promoter of homeobox A (HOXA) genes, enhancing its own expression and stimulating expression of HOXA genes including HOXA7 and HOXA9 . Both TET1 and HOXA9 suppress breast tumor growth and metastasis in mouse xenografts. The genes comprising the HMGA2–TET1–HOXA9 pathway are coordinately regulated in breast cancer and together encompass a prognostic signature for patient survival. These results implicate the HMGA2–TET1–HOX signaling pathway in the epigenetic regulation of human breast cancer and highlight the importance of targeting methylation in specific subpopulations as a potential therapeutic strategy.
The combustion has long been applied for industrial synthesis of carbon materials such as fullerenes as well as carbon particles (known as carbon black), but the components and structures of the ...carbon soot are far from being clarified. Herein, we retrieve an unprecedented hydrofullerene C66H4 from a soot of a low-pressure combustion of benzene–acetylene–oxygen. Unambiguously characterized by single-crystal X-ray diffraction, the C66H4 renders a nonclassical geometry incorporating two heptagons and two pairs of fused pentagons in a C 2v symmetry. The common vertexes of the fused pentagons are bonded with four hydrogen atoms to convert the hydrogen-linking carbon atoms from sp2 to sp3 hybridization, which together with the adjacent heptagons essentially releases the sp2-bond strains on the abutting-pentagon sites of the diheptagonal fused pentagon C66 (dihept-C66). DFT computations suggest the possibility for an in situ hydrogenation process leading to stabilization of the dihept-C66. In addition, the experiments have been carried out to study heptagon-dependent properties of dihept-C66H4, indicating the key responsibility of the heptagon for changing hydrocarbon activity and electronic properties. The present work with the unprecedented double-heptagon-containing hydrofullerene successfully isolated and identified as one of the low-pressure combustion products shows that the heptagon is a new building block for constructing fullerene products in addition to pentagons and hexagons in low-pressure combustion systems.
Homogeneous and heterogeneous reactions wherein the resulting products remain dissolved in solvents generally require complicated separation and purification process, despite the advantage of ...heterogeneous systems allowing retrieval of catalysts. Herein, we have developed an efficient approach for the one‐pot tandem synthesis of quinazolines, quinazolinones and benzothiadiazine 1,1‐dioxides from alcohols and amines utilizing a bifunctional bipyridinium photocatalyst with redox and Lewis acid sites using air as an oxidant. Through solvent‐modulation strategy, the photocatalytic system exhibits high performance and enables most products to separate spontaneously. Consequently, the homogeneous catalyst can be reused by direct centrifugation isolation of the products. Notably, the method is also applicable to the less active substrates, such as heterocyclic alcohols and aliphatic alcohols, and thus provides an efficient and environmentally friendly photocatalytic route with spontaneous separation of N‐heterocycles to reduce production costs and meet the needs of atomic economy and green chemistry.
The first reusable homogeneous system with spontaneous product separation for transforming alcohols and amines into N‐heterocycles through solvent‐modulated one‐pot tandem reactions has been developed by utilizing the bifunctional small‐molecule photocatalyst with redox and Lewis acid sites, which demonstrates excellent substrate compatibility and holds significant promise for industrial‐scale production.
Supramolecular nanomedicines based on self‐assembly of D‐peptides have been of great interest as potential candidates for cancer therapy. Neuropilin‐1 (NRP1) and mouse double minute 2 (MDM2) have ...been considered as the anticancer targets because of their overexpression in cancers. However, NRP1/MDM2‐targeted D‐peptide supramolecular nanomedicines remain unreported. Here, a potent anticancer D‐peptide supramolecular nanomedicine targeting NRP1 and MDM2, termed as NMTP‐5, is identified by using structure‐based virtual screening techniques. NMTP‐5 exhibits good biostability and strong cellular uptake performance. Moreover, NMTP‐5 displays strong anticancer activity to SK‐Hep‐1 cells in vitro and in vivo, with no apparent host toxicity. This work demonstrates that NMTP‐5 can be used as a potential chemotherapeutic agent for the treatment of liver cancer.
Here, a potent anticancer supramolecular nanomedicine targeting neuropilin‐1 (NRP1) and mouse double minute 2 (MDM2), termed as NMTP‐5, is reported. After entering the cytosol of cancer cell by targeting NRP1, NMTP‐5 up‐regulates the level of p53 by interfering MDM2‐p53 interaction and induces cell death. Therefore, NMTP‐5 can be used as a potential chemotherapeutic agent for liver cancer therapy.
The citric acid cycle is central to the regulation of energy homeostasis and cell metabolism. Mutations in enzymes that catalyse steps in the citric acid cycle result in human diseases with various ...clinical presentations. The intermediates of the citric acid cycle are present at micromolar concentration in blood and are regulated by respiration, metabolism and renal reabsorption/extrusion. Here we show that GPR91 (ref. 3), a previously orphan G-protein-coupled receptor (GPCR), functions as a receptor for the citric acid cycle intermediate succinate. We also report that GPR99 (ref. 4), a close relative of GPR91, responds to α-ketoglutarate, another intermediate in the citric acid cycle. Thus by acting as ligands for GPCRs, succinate and α-ketoglutarate are found to have unexpected signalling functions beyond their traditional roles. Furthermore, we show that succinate increases blood pressure in animals. The succinate-induced hypertensive effect involves the renin-angiotensin system and is abolished in GPR91-deficient mice. Our results indicate a possible role for GPR91 in renovascular hypertension, a disease closely linked to atherosclerosis, diabetes and renal failure.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this paper, an effective wavelength detection approach based on long short-term memory (LSTM) network is proposed for fiber Bragg grating (FBG) sensor networks. The FBG sensor network utilizes a ...model-sharing mechanism, where the whole spectral wavelength is divided into several shareable regions and spectral overlap is allowed in each region. LSTM, a representative recurrent neural network in deep learning, is applied to learn the features directly from the spectra of FBGs and build the wavelength detection model. By feeding the spectra sequentially into the well-trained model, the Bragg wavelengths of FBGs can be quickly determined under overlap. The obtained LSTM model can be repeatedly used without re-training to improve the multiplexing capability. The results demonstrate that the LSTM-based method can realize high-accuracy and high-speed wavelength detection in the spectral overlapping situations. The proposed approach offers a flexible tool to enhance the sensing capacity of FBG sensor networks.
Formation subsidence is inevitable during marine hydrate decomposition, and the consequent casing deformation seriously threatens the security of sustainable hydrate production. Owing to insufficient ...observed data of formation subsidence in field, displacement boundary condition of casing is undetermined. Thus the conventional static methods are inapplicable for the calculation of casing deformation in hydrate production well. The present work aims at proposing an approach to investigate dynamic deformation of the casing during hydrate production. In the proposed methodology, based on the movement theory of hydrate decomposition front, hydrate decomposition process can be simulated, in which hydrate reservoir strength formation subsidence showed time-dependent characteristics. By considering the actual interactions among casing, cement and formation, three models of hydrate production well are developed to reveal the static and dynamic deformation mechanisms of the casing. The application of the proposed methodology is demonstrated through a case study. Results show that buckling deformation and bending deformation of casing reduce the passing ability of downhole tools in deformed casing by 4.2% and 7.5%, respectively. With the progress of hydrate production, buckling deformation will increase obviously, while a little increase of bending deformation will occur, as the formation slippage induced by formation inclination is much larger than that caused by hydrate decomposition. The proposed approach can provide theoretical reference for improving casing integrity of marine hydrate production.
infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for ...population-wide and family-based
infection control and management to reduce the related disease burden.
Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements.
Experts discussed and modified the original 23 statements on family-based
infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1)
infection and transmission among family members, (2) prevention and management of
infection in children and elderly people within households, and (3) strategies for prevention and management of
infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based
infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases.
is transmissible from person to person, and among family members. A family-based
prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.
Spinel materials are attractive to photocatalytic degradation of contaminants. In this study, strontium (Sr) doped spinel cobalt chromite (CoCr2O4) was synthesized by solution combustion method and ...characterized using techniques such as X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), electron paramagnetic resonance (EPR), and electrochemical impedance spectroscopy (EIS). 30 -50 nm-cubic CoCr2O4 nanocrystals were obtained, and phase transitions of CoO6→CoO4 and CrO4→CrO6 occurred as the Sr doping content increased until 0.6 % Sr doped sample displayed an inverse spinel phase. The modifications in composition and structure induced the co-existence of multivalent states for Co and Cr, which in turn changed the optical, complex impedance, and magnetic spin state of CoCr2O4. The 0.6 % Sr-doped sample showed the highest photocatalytic efficiency of 93 % due to enhanced optical absorption, reduced energy band gap, oxygen vacancies formation, and a high spin state of Co. The XRD structure and photocatalytic activity remained stable even after five cycles without any leakage of metal elements. The degradation pathway and Mott-Schottky curves were employed to elucidate the mechanism behind this enhancement. The strategy employed in this study proved effective, and the synthesized materials show promise for the photocatalytic degradation of contaminants.
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