Purification of the C8 alkylaromatics o-xylene, m-xylene, p-xylene, and ethylbenzene remains among the most challenging industrial separations, due to the similar shapes, boiling points, and ...polarities of these molecules. Herein, we report the evaluation of the metal–organic frameworks Co2(dobdc) (dobdc4– = 2,5-dioxido-1,4-benzenedicarboxylate) and Co2(m-dobdc) (m-dobdc4– = 4,6-dioxido-1,3-benzenedicarboxylate) for the separation of xylene isomers using single-component adsorption isotherms and multicomponent breakthrough measurements. Remarkably, Co2(dobdc) distinguishes among all four molecules, with binding affinities that follow the trend o-xylene > ethylbenzene > m-xylene > p-xylene. Multicomponent liquid-phase adsorption measurements further demonstrate that Co2(dobdc) maintains this selectivity over a wide range of concentrations. Structural characterization by single-crystal X-ray diffraction reveals that both frameworks facilitate the separation through the extent of interaction between each C8 guest molecule with two adjacent cobalt(II) centers, as well as the ability of each isomer to pack within the framework pores. Moreover, counter to the presumed rigidity of the M2(dobdc) structure, Co2(dobdc) exhibits an unexpected structural distortion in the presence of either o-xylene or ethylbenzene that enables the accommodation of additional guest molecules.
Abstract Parkinson disease (PD) is a systemic disease with variegated non-motor deficits and neurological symptoms, including impaired olfaction, autonomic failure, cognitive impairment and ...psychiatric symptoms, in addition to the classical motor symptoms. Many non-motor symptoms appear before or in parallel with motor deficits and then worsen with disease progression. Although there is a relationship, albeit not causal, between motor symptoms and the presence of Lewy bodies (LBs) and neurites filled with abnormal α-synuclein, other neurological alterations are independent of the amount of α-synuclein inclusions in neurons and neurites, thereby indicating that different mechanisms probably converge in the degenerative process. This may apply to complex alterations interfering with olfactory and autonomic nervous system functions, emotions, sleep regulation, and behavioral, cognitive and mental performance. Involvement of the cerebral cortex leading to impaired behavior and cognition is related to several convergent altered factors including: a. dopaminergic, noradrenergic, serotoninergic and cholinergic cortical innervation; b. synapses; c. cortical metabolism; d. mitochondrial function and energy production; e. oxidative damage; f. transcription; g. protein expression; h. lipid composition; and i. ubiquitin–proteasome system and autophagy, among others. This complex situation indicates that multiple subcellular failure in selected cell populations is difficult to reconcile with a reductionistic scenario of a single causative cascade of events leading to non-motor symptoms in PD. Furthermore, these alterations may appear at early stages of the disease and may precede the appearance of substantial irreversible cell loss by years. These observations have important implications in the design of therapeutic approaches geared to prevention and treatment of PD.
Transcription factor 7-like 2 (TCF7L2) polymorphisms are strongly associated with type 2 diabetes, but controversially with plasma lipids and cardiovascular disease. Interactions of the Mediterranean ...diet (MedDiet) on these associations are unknown. We investigated whether the TCF7L2-rs7903146 (C>T) polymorphism associations with type 2 diabetes, glucose, lipids, and cardiovascular disease incidence were modulated by MedDiet.
A randomized trial (two MedDiet intervention groups and a control group) with 7,018 participants in the PREvención con DIetaMEDiterránea study was undertaken and major cardiovascular events assessed. Data were analyzed at baseline and after a median follow-up of 4.8 years. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) for cardiovascular events.
The TCF7L2-rs7903146 polymorphism was associated with type 2 diabetes (odds ratio 1.87 95% CI 1.62-2.17 for TT compared with CC). MedDiet interacted significantly with rs7903146 on fasting glucose at baseline (P interaction = 0.004). When adherence to the MedDiet was low, TT had higher fasting glucose concentrations (132.3 ± 3.5 mg/dL) than CC+CT (127.3 ± 3.2 mg/dL) individuals (P = 0.001). Nevertheless, when adherence was high, this increase was not observed (P = 0.605). This modulation was also detected for total cholesterol, LDL cholesterol, and triglycerides (P interaction < 0.05 for all). Likewise, in the randomized trial, TT subjects had a higher stroke incidence in the control group (adjusted HR 2.91 95% CI 1.36-6.19; P = 0.006 compared with CC), whereas dietary intervention with MedDiet reduced stroke incidence in TT homozygotes (adjusted HR 0.96 95% CI 0.49-1.87; P = 0.892 for TT compared with CC).
Our novel results suggest that MedDiet may not only reduce increased fasting glucose and lipids in TT individuals, but also stroke incidence.
Triple-negative breast cancer (TNBC) is a collection of biologically diverse cancers characterized by distinct transcriptional patterns, biology, and immune composition. TNBCs subtypes include two ...basal-like (BL1, BL2), a mesenchymal (M) and a luminal androgen receptor (LAR) subtype. Through a comprehensive analysis of mutation, copy number, transcriptomic, epigenetic, proteomic, and phospho-proteomic patterns we describe the genomic landscape of TNBC subtypes. Mesenchymal subtype tumors display high mutation loads, genomic instability, absence of immune cells, low PD-L1 expression, decreased global DNA methylation, and transcriptional repression of antigen presentation genes. We demonstrate that major histocompatibility complex I (MHC-I) is transcriptionally suppressed by H3K27me3 modifications by the polycomb repressor complex 2 (PRC2). Pharmacological inhibition of PRC2 subunits EZH2 or EED restores MHC-I expression and enhances chemotherapy efficacy in murine tumor models, providing a rationale for using PRC2 inhibitors in PD-L1 negative mesenchymal tumors. Subtype-specific differences in immune cell composition and differential genetic/pharmacological vulnerabilities suggest additional treatment strategies for TNBC.
The widespread deployment of carbon capture and sequestration as a climate change mitigation strategy could be facilitated by the development of more energy-efficient adsorbents. Diamine-appended ...metal–organic frameworks of the type diamine–M2(dobpdc) (M = Mg, Mn, Fe, Co, Ni, Zn; dobpdc4– = 4,4′-dioxidobiphenyl-3,3′-dicarboxylate) have shown promise for carbon-capture applications, although questions remain regarding the molecular mechanisms of CO2 uptake in these materials. Here we leverage the crystallinity and tunability of this class of frameworks to perform a comprehensive study of CO2 chemisorption. Using multinuclear nuclear magnetic resonance (NMR) spectroscopy experiments and van-der-Waals-corrected density functional theory (DFT) calculations for 13 diamine–M2(dobpdc) variants, we demonstrate that the canonical CO2 chemisorption products, ammonium carbamate chains and carbamic acid pairs, can be readily distinguished and that ammonium carbamate chain formation dominates for diamine–Mg2(dobpdc) materials. In addition, we elucidate a new chemisorption mechanism in the material dmpn–Mg2(dobpdc) (dmpn = 2,2-dimethyl-1,3-diaminopropane), which involves the formation of a 1:1 mixture of ammonium carbamate and carbamic acid and accounts for the unusual adsorption properties of this material. Finally, we show that the presence of water plays an important role in directing the mechanisms for CO2 uptake in diamine–M2(dobpdc) materials. Overall, our combined NMR and DFT approach enables a thorough depiction and understanding of CO2 adsorption within diamine–M2(dobpdc) compounds, which may aid similar studies in other amine-functionalized adsorbents in the future.
Metal–organic frameworks featuring ligands with open chelating groups are versatile platforms for the preparation of a diverse set of heterogeneous catalysts through postsynthetic metalation. The ...crystalline nature of these materials allows them to be characterized via X-ray diffraction, which provides valuable insight into the structure of the metal sites that facilitate catalysis. A highly porous and thermally robust zirconium-based metal–organic framework, Zr6O4(OH)4(bpydc)6 (bpydc2– = 2,2′-bipyridne-5,5′-dicarboxylate), bears open bipyridine sites that readily react with a variety of solution- and gas-phase metal sources to form the corresponding metalated frameworks. Remarkably, Zr6O4(OH)4(bpydc)6 undergoes a single-crystal-to-single-crystal transformation upon metalation that involves a change in space group from Fm3̅m to Pa3̅. This structural transformation leads to an ordering of the metalated linkers within the framework, allowing structural characterization of the resulting metal complexes. Furthermore, Zr6O4(OH)4(bpydc)6 yields an active heterogeneous catalyst for arene C–H borylation when metalated with Ir(COD)2BF4 (COD = 1,5-cyclooctadiene). These results highlight the unique potential of metal–organic frameworks as a class of heterogeneous catalysts that allow unparalleled structural characterization and control over their active sites.
With a current estimate of ~1,000 million tons, mesopelagic fishes likely dominate the world total fishes biomass. However, recent acoustic observations show that mesopelagic fishes biomass could be ...significantly larger than the current estimate. Here we combine modelling and a sensitivity analysis of the acoustic observations from the Malaspina 2010 Circumnavigation Expedition to show that the previous estimate needs to be revised to at least one order of magnitude higher. We show that there is a close relationship between the open ocean fishes biomass and primary production, and that the energy transfer efficiency from phytoplankton to mesopelagic fishes in the open ocean is higher than what is typically assumed. Our results indicate that the role of mesopelagic fishes in oceanic ecosystems and global ocean biogeochemical cycles needs to be revised as they may be respiring ~10% of the primary production in deep waters.
The mechanical characterization of plain foamed concrete (PFC) and fiber-reinforced foamed concrete (FRFC) with a density of 700 kg/m3 was performed with compression and tension tests. FRFC was ...reinforced with the natural fiber henequen (untreated or alkaline-treated) at volume fractions of 0.5%, 1% and 1.5%. Polypropylene fiber reinforcement was also used as a reference. For all FRFCs, the inclusion of the fibers enhanced the compressive and tensile strengths and plastic behavior, which was attributed to the increase of specimen integrity. Under compressive loading, after the peak strength, there was no considerable loss in strength and a plateau-like regime was observed. Under tensile loading, the fibers significantly increased the tensile strength of the FRFCs and prevented a sudden failure of the specimens, which was in contrast to the brittle behavior of the PFC. The tensile behavior enhancement was higher when treated henequen fibers were used, which was attributed to the increase in the fiber–matrix bond produced by the alkaline treatment. The microscopic characterization showed that the inclusion of fibers did not modify the air-void size and its distribution. Higher energy absorption was observed for FRFCs when compared to the PFC, which was attributed to the enhanced toughness and ductility by the fibers. The results presented herein warrant further research of FRFC with natural henequen fibers for engineering applications.
Potentiating anti-tumor immunity by inducing tumor inflammation and T cell-mediated responses are a promising area of cancer therapy. Immunomodulatory agents that promote these effects function via a ...wide variety of mechanisms, including upregulation of antigen presentation pathways. Here, we show that major histocompatibility class-I (MHC-I) genes are methylated in human breast cancers, suppressing their expression. Treatment of breast cancer cell lines with a next-generation hypomethylating agent, guadecitabine, upregulates MHC-I expression in response to interferon-γ. In murine tumor models of breast cancer, guadecitabine upregulates MHC-I in tumor cells promoting recruitment of CD8+ T cells to the microenvironment. Finally, we show that MHC-I genes are upregulated in breast cancer patients treated with hypomethylating agents. Thus, the immunomodulatory effects of hypomethylating agents likely involve upregulation of class-I antigen presentation to potentiate CD8+ T cell responses. These strategies may be useful to potentiate anti-tumor immunity and responses to checkpoint inhibition in immune-refractory breast cancers.
Metal–organic frameworks that flex to undergo structural phase changes upon gas adsorption are promising materials for gas storage and separations, and achieving synthetic control over the pressure ...at which these changes occur is crucial to the design of such materials for specific applications. To this end, a new family of materials based on the flexible metal–organic framework Co(bdp) (bdp2– = 1,4-benzenedipyrazolate) has been prepared via the introduction of fluorine, deuterium, and methyl functional groups on the bdp2– ligand, namely, Co(F-bdp), Co(p-F2-bdp), Co(o-F2-bdp), Co(D4-bdp), and Co(p-Me2-bdp). These frameworks are isoreticular to the parent framework and exhibit similar structural flexibility, transitioning from a low-porosity, collapsed phase to high-porosity, expanded phases with increasing gas pressure. Powder X-ray diffraction studies reveal that fluorination of the aryl ring disrupts edge-to-face π–π interactions, which work to stabilize the collapsed phase at low gas pressures, while deuteration preserves these interactions and methylation strengthens them. In agreement with these observations, high-pressure CH4 adsorption isotherms show that the pressure of the CH4-induced framework expansion can be systematically controlled by ligand functionalization, as materials without edge-to-face interactions in the collapsed phase expand at lower CH4 pressures, while frameworks with strengthened edge-to-face interactions expand at higher pressures. Importantly, this work puts forth a general design strategy relevant to many other families of flexible metal–organic frameworks, which will be a powerful tool in optimizing these phase-change materials for industrial applications.
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