The existence of breast cancer stem cells (BCSCs) is a major reason underlying cancer metastasis and recurrence after chemotherapy and radiotherapy. Targeting BCSCs may ameliorate breast cancer ...relapse and therapy resistance. Here we report that expression of the pseudokinase Tribble 3 (TRIB3) positively associates with breast cancer stemness and progression. Elevated TRIB3 expression supports BCSCs by interacting with AKT to interfere with the FOXO1-AKT interaction and suppress FOXO1 phosphorylation, ubiquitination, and degradation by E3 ligases SKP2 and NEDD4L. The accumulated FOXO1 promotes transcriptional expression of SOX2, a transcriptional factor for cancer stemness, which in turn, activates FOXO1 transcription and forms a positive regulatory loop. Disturbing the TRIB3-AKT interaction suppresses BCSCs by accelerating FOXO1 degradation and reducing SOX2 expression in mouse models of breast cancer. Our study provides insights into breast cancer development and confers a potential therapeutic strategy against TRIB3-overexpressed breast cancer.
Development of practical deuteration reactions is highly valuable for organic synthesis, analytic chemistry and pharmaceutic chemistry. Deuterodehalogenation of organic chlorides tends to be an ...attractive strategy but remains a challenging task. We here develop a photocatalytic system consisting of an aryl-amine photocatalyst and a disulfide co-catalyst in the presence of sodium formate as an electron and hydrogen donor. Accordingly, many aryl chlorides, alkyl chlorides, and other halides are converted to deuterated products at room temperature in air (>90 examples, up to 99% D-incorporation). The mechanistic studies reveal that the aryl amine serves as reducing photoredox catalyst to initiate cleavage of the C-Cl bond, at the same time as energy transfer catalyst to induce homolysis of the disulfide for consequent deuterium transfer process. This economic and environmentally-friendly method can be used for site-selective D-labeling of a number of bioactive molecules and direct H/D exchange of some drug molecules.
Due to the highest theoretical specific capacity of 4200 mA h g−1 for Li4.4Si, silicon(Si)-based materials could fulfill the increasing demands of high-energy lithium-ion batteries (LIBs). However, ...the intrinsic huge volume expansion during the lithiation/delithiation process results in rapid capacity decay and short cycle life and restricts the satisfactory electrical performance of Si-based anodes. Binder plays an important role of maintaining the contact integrity between active material, conductive additive and the current collector, thereby reducing the pulverization of the Si particles during charge/discharge. Here, the review systematically summarizes the synthesis methods, design principles and working mechanisms, including chemical composition, superstructure, and various interactions between different functional moieties of synthetic binders and natural biomass binders, to reveal the structure-composition-performance relationship, offer practical solutions to challenging problems associated with defects of Si-based electrode materials in LIBs and aim at exploiting new family of binders that could be used in industrial level as well as providing design principles for other electrode binders in rechargeable batteries.
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•Working mechanisms and design principles of Si-based anodes binders are presented.•Synergistic strategy of combining binders with anode structure design is discussed.•Synthesis methods, applied anodes, ICE and cycling performance are listed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Benzene hydrogenation is an important industrial process. The reaction is incomplete, resulting in a mixture of benzene, cyclohexane, and/or cyclohexene that have to be separated before any further ...reactions. The currently used extractive and azeotropic distillations are operationally complex and energy intensive. Adsorptive separation provides an alternative energy‐efficient method. However, the separation of the ternary mixture by adsorptive separation has not yet been reported. In the present research, we report two macrocyclic hosts with hydrogen‐bonding sites in their cavities that are able to separate the ternary mixture of benzene, cyclohexene, and cyclohexane. N−H⋅⋅⋅π interactions were found to play a key role in the selective separation. In addition, fast adsorption, high loading ratios, and easy recycling are achieved with the present system, which is promising for practical applications.
Mixtures of benzene, cyclohexene, and cyclohexane can be separated through solid‐vapor adsorption by using the activated solids of amide naphthotubes. N−H⋅⋅⋅π interactions are found to play a key role in the adsorption selectivity among the three structurally similar molecules.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Mitochondrial dysfunction and impaired Ca
handling are involved in the development of diabetic cardiomyopathy (DCM). Dynamic relative protein 1 (Drp1) regulates mitochondrial fission by changing its ...level of phosphorylation, and the Orai1 (Ca
release-activated calcium channel protein 1) calcium channel is important for the increase in Ca
entry into cardiomyocytes. We aimed to explore the mechanism of Drp1 and Orai1 in cardiomyocyte hypertrophy caused by high glucose (HG). We found that Zucker diabetic fat rats induced by administration of a high-fat diet develop cardiac hypertrophy and impaired cardiac function, accompanied by the activation of mitochondrial dynamics and calcium handling pathway-related proteins. Moreover, HG induces cardiomyocyte hypertrophy, accompanied by abnormal mitochondrial morphology and function, and increased Orai1-mediated Ca
influx. Mechanistically, the Drp1 inhibitor mitochondrial division inhibitor 1 (Mdivi-1) prevents cardiomyocyte hypertrophy induced by HG by reducing phosphorylation of Drp1 at serine 616 (S616) and increasing phosphorylation at S637. Inhibition of Orai1 with single guide RNA (sgOrai1) or an inhibitor (BTP2) not only suppressed Drp1 activity and calmodulin-binding catalytic subunit A (CnA) and phosphorylated-extracellular signal-regulated kinase (p-ERK1/2) expression but also alleviated mitochondrial dysfunction and cardiomyocyte hypertrophy caused by HG. In addition, the CnA inhibitor cyclosporin A and p-ERK1/2 inhibitor U0126 improved HG-induced cardiomyocyte hypertrophy by promoting and inhibiting phosphorylation of Drp1 at S637 and S616, respectively. In summary, we identified Drp1 as a downstream target of Orai1-mediated Ca
entry, via activation by p-ERK1/2-mediated phosphorylation at S616 or CnA-mediated dephosphorylation at S637 in DCM. Thus, the Orai1-Drp1 axis is a novel target for treating DCM.
The aim of this study is to assess the prevalence of small intestinal bacterial overgrowth (SIBO) by hydrogen breath test in patients with autism spectrum disorders (ASD) with respect to a consistent ...control group. From 2011 to 2013, 310 children with ASD and 1240 sex- and age-matched typical children were enrolled in this study to undergo glucose breath test. The study participants were considered to exhibit SIBO when an increase in H
2
of ≥20 ppm or CH
4
of ≥10 ppm with respect to the fasting value was observed up to 60 min after the ingestion of glucose. Ninety-six children with autism suffered from SIBO, giving a prevalence rate of SIBO was 31.0% (95% CI 25.8–36.1%). In contrast, 9.3% of the typical children acknowledged SIBO. The difference between groups was statistically significant (
P
< 0.0001). The median Autism Treatment Evaluation Checklist (ATEC) score in the children with autism and with SIBO was significantly high when compared with the children without autism and without SIBO 98 (IQR, 45–120) vs. 63 (32–94),
P
< 0.001. For the autism group, the 6-GI Severity Index (6-GSI) score was found to be strongly and significantly correlated with the total ATEC score (
r
= 0.639,
P
< 0.0001). SIBO was significantly associated with worse symptoms of autism, demonstrating that children with SIBO may significantly contribute to symptoms of autism.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, ODKLJ, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Myeloid-derived suppressor cells (MDSCs) are pathologically activated and relatively immature myeloid cells that have been implicated in the immunological regulation of many pathologic conditions. ...Phenotypically and morphologically, MDSCs are similar to neutrophils (PMN-MDSCs) and monocytes (M-MDSCs). However, they have potent suppressive activity and distinct gene expression profiles and biochemical characteristics. No or very few MDSCs are observed in steady-state physiological conditions. Therefore, until recently, accumulation of MDSCs was considered a consequence of pathological processes or pregnancy. Here, we report that MDSCs with a potent ability to suppress T cells are present during the first weeks of life in mice and humans. MDSC suppressive activity was triggered by lactoferrin and mediated by nitric oxide, PGE2, and S100A9 and S100A8 proteins. MDSCs from newborns had a transcriptome similar to that of tumor MDSCs, but with strong upregulation of an antimicrobial gene network, and had potent antibacterial activity. MDSCs played a critical role in control of experimental necrotizing enterocolitis (NEC) in newborn mice. MDSCs in infants with very low weight, who are prone to NEC, had lower MDSC levels and suppressive activity than did infants with normal weight. Thus, the transitory presence of MDSCs may be critical for regulation of inflammation in newborns.
Ischemic stroke leads to neuronal damage induced by excitotoxicity, inflammation, and oxidative stress. Astrocytes play diverse roles in stroke and ischemia‐induced inflammation, and autophagy is ...critical for maintaining astrocytic functions. Our previous studies showed that the activation of G protein‐coupled receptor 30 (GPR30), an estrogen membrane receptor, protected neurons from excitotoxicity. However, the role of astrocytic GPR30 in maintaining autophagy and neuroprotection remained unclear. In this study, we found that the neuroprotection induced by G1 (GPR30 agonist) in wild‐type mice after a middle cerebral artery occlusion was completely blocked in GPR30 conventional knockout (KO) mice but partially attenuated in astrocytic or neuronal GPR30 KO mice. In cultured primary astrocytes, glutamate exposure induced astrocyte proliferation and decreased astrocyte autophagy by activating mammalian target of rapamycin (mTOR) and c‐Jun N‐terminal kinase (JNK) and inhibiting p38 mitogen‐activated protein kinase (MAPK) pathway. G1 treatment restored autophagy to its basal level by regulating the p38 pathway but not the mTOR and JNK signaling pathways. Our findings revealed a key role of GPR30 in neuroprotection via the regulation of astrocyte autophagy and support astrocytic GPR30 as a potential drug target against ischemic brain damage.
Main Points
Astrocytic GPR30 was involved in the neuroprotection.
Autophagic deficiency of astrocytes induced by glutamate promoted inflammatory cytokine release.
GPR30 activation restored autophagy balance in astrocytes by regulating the p38 MAPK pathway.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Metal clusters have been very attractive due to their aesthetic structures and fascinating properties. Different from nanoparticles, each cluster of a macroscopic sample has a well-defined structure ...with identical composition, size, and shape. As the disadvantages of polydispersity are ruled out, informative structure–property relationships of metal clusters can be established. The formation of a high-nuclearity metal cluster involves the organization of metal ions into a complex entity in an ordered way. To achieve controllable preparation of metal clusters, it is helpful to introduce a directing agent in the formation process of a cluster. To this end, anion templates have been used to direct the formation of high nuclearity clusters. In this Account, the role of anions played in the formation of a variety of silver clusters has been reviewed. Silver ions are positively charged, so anionic species could be utilized to control the formation of silver clusters on the basis of electrostatic interactions, and the size and shape of the resulted clusters can be dictated by the templating anions. In addition, since the anion is an integral component in the silver clusters described, the physical properties of the clusters can be modulated by functional anions. The templating effects of simple inorganic anions and polyoxometales are shown in silver alkynyl clusters and silver thiolate clusters. Intercluster compounds are also described regarding the importance of anions in determining the packing of the ion pairs and making contribution to electron communications between the positive and negative counterparts. The role of the anions is threefold: (a) an anion is advantageous in stabilizing a cluster via balancing local positive charges of the metal cations; (b) an anion template could help control the size and shape of a cluster product; (c) an anion can be a key factor in influencing the function of a cluster through bringing in its intrinsic properties. Properties including electron communication, luminescent thermochromism, single-molecule magnet, and intercluster charge transfer associated with anion-directed silver clusters have been discussed. We intend to attract chemists’ attention to the role that anions could play in determining the structures and properties of metal complexes, especially clusters. We hope that this Account will stimulate more efforts in exploiting new role of anions in various metal cluster systems. Anions can do much more than counterions for charge balance, and they should be considered in the design and synthesis of cluster-based functional materials.
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IJS, KILJ, NUK, PNG, UL, UM
Developing effective and safe catalysts operated in the in-depth removal of iodinated X-ray contrast media is important for overcoming slow removal efficiency-induced highly toxic iodine-replaced ...disinfection byproducts (I-DBPs). In this study, a novel oxygen vacancies enriched heterogeneous biochar catalyst (Mo-Co-ECM) from the invasive plant was synthesized by a facile one-step hydrothermal carbonization method and used for the in-depth removal of iohexol (IOH) by the activation of peroxymonosulfate (PMS). The results indicated that after adding PMS for 3 min, the removal efficiency of IOH in Mo-Co-ECM/PMS system reached 100% and exhibited a superior degradation efficiency compared to Co-ECM/PMS and ECM/PMS system. Only nine I-DBPs were found during the degradation, which were dominated by small molecules compounds (MW<400). The in-depth degradation suppresses the formation of the toxic intermediates. The density functional theory and electron spin resonance showed that due to the existence of Mo and oxygen vacancies, the electron transfer ability was improved, which accelerated the cycle of Co3+/Co2+, so as to enhance the catalytic activity of Mo-Co-ECM/PMS system. This study is expected to provide a general way for decreasing the production of toxic intermediates during the advanced oxidation of contaminants, meanwhile recovering resources.
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•The oxygen vacancies enriched bimetal biochar was facilely developed for PMS activation.•In-depth degradation of IOH can be achieved after adding PMS for 3 min.•Significant role of oxygen vacancies in improved the electron transfer ability of Co was revealed.•The formation of toxic intermediates is suppressed due to the in-depth degradation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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