A metal–organic gel (metallogel) based on the new tetracarboxyl ligand N 1,N 4-(diterephthalic acid)terephthalamide in combination with chromium(III) has been converted into its xero- and aerogel ...and demonstrated to have excellent specific sorption properties for dyes in its metallogel state, where fuchsine is adsorbed faster than the two other dyes, calcein and disulfine blue, and for water, sulfur dioxide and carbon dioxide in its xero- and aerogel state. The metallogel showed very good shape retention and could be extruded from molds in designed shapes. In a rheology experiment, the storage modulus was determined to be 1440 Pa, and the metallogel is elastic up to 3 Hz, breaking at strains higher than 0.3%. Additional metallogels utilizing the same ligand with a wide range of metal ions (Al(III), Fe(III), Co(III), In(III), and Hg(II)) have also been synthesized, and the aluminum and mixed aluminum–chromium derivative were also converted into its aerogel. The highly porous Cr, Al, and AlCr metal–organic aerogels proved stable against water vapor in a physisorption experiment and were used to model breakthrough curves for SO2/CO2 gas mixtures with the idealized adsorbed solution theory from their physisorption isotherms. The breakthrough simulation utilized SO2/CO2 equivalencies from a real world application and showed effective retention of SO2 from the gas mixture. Furthermore, the materials in this work exhibit the highest SO2 uptake values for metal–organic aerogels so far (up to 116.8 cm3 g–1, or 23.4 wt %).
The circadian clockwork evolved as an adaptation to daily environmental changes and allows temporal alignment of functions between cells and organs on a systemic level in complex multicellular ...organisms. These clock functions are particularly important in the skin, which is directly exposed to the external environment. Recent studies have revealed the important impact of circadian rhythmicity on stem cell (SC) homeostasis and regeneration in both young and old skin. This review discusses how the circadian clock regulates tissue function in skin-resident SCs and their niche and how altered daily rhythms in aged SCs negatively affect skin regeneration.
The enantiopure Schiff bases (R or S)-N-1-(X-C6H4)ethyl-2-hydroxy-1-naphthaldimine {X = H (R or S)-HL1, p-CH3O (R or S)-HL2, and p-Br (R- or S)-HL3} react with cobalt(II) acetate to give bis(R or ...S)-N-1-(X-C6H4)ethyl-2-oxo-1-naphthaldiminato-κ2 N,O-Λ/Δ-cobalt(II) {X = H Λ/Δ-Co-(R or S)-L1, p-CH3O Λ/Δ-Co-(R or S)-L2, and p-Br Λ/Δ-Co-(R or S)-L3} (1–3), respectively. Induced Λ and Δ chirality originates at the metal center of the C 2-symmetric molecule in pseudotetrahedral geometry. Differential scanning calorimetry analyses explored the thermal stability of the complexes, which undergo reversible phase transformation from crystalline solid to isotropic liquid phase for 1 and 3 but irreversible phase transformation for 2. Like other cobalt(II) complexes, compounds 1–3 exhibit a continuous ensemble of absorption and circular dichroism bands, which span from the UV to IR region and can be collected into a superspectrum. Infrared vibrational circular dichroism (IR-VCD) spectra witness the coupling between Co2+-centered low-lying electronic states and ligand-centered vibrations. The coupling produces enhanced and almost monosignate VCD spectra, with both effects being mode-dependent in terms of the A or B symmetry (in the C 2 point group) and distance from the Co2+ core.
The circadian clock temporally organizes cellular physiology throughout the day, allowing daily environmental changes to be anticipated and potentially harmful physiologic processes to be temporally ...separated. By synchronizing all cells at the tissue level, the circadian clock ensures coherent temporal organismal physiology. Recent advances in our understanding of adult stem cell physiology suggest that aging and perturbations in circadian rhythmicity in stem cells are tightly intertwined. Here we discuss how circadian rhythms regulate and synchronize adult stem cell functions and how alterations in clock function during aging modulate the extrinsic and intrinsic mechanisms that determine adult stem cell homeostasis.
A mixed‐valent, one‐dimensional Cu(I/II) coordination polymer with the formula CuII{CuI3(Hmpba)(mpba)2}DMF ⋅ ∼3DMF was obtained with the bifunctional ligand 4‐(3,5‐dimethyl‐1H‐pyrazol‐4‐yl)benzoic ...acid (H2mpba) in N,N‐dimethylformamide (DMF) via solvothermal reaction. The compound exhibits a trinuclear {CuI3(Hmpba)(mpba)2}2− metallo‐linker with the softer Cu(I) linearly‐coordinated by the softer pyrazolate nitrogen donor atom. This metallo‐linker connects the harder Cu(II) ions through its harder carboxylate groups into a chain structure. Two Cu(II) ions form a paddlewheel unit and are, thus, surrounded by four carboxylate groups. Cu(II) is five‐coordinated with a terminal DMF ligand. Parallel chains are connected into supramolecular layers through the common R22(8) hydrogen‐bond motif of the singly‐deprotonated carboxyl groups of the Hmpba ligand. These layers are further organized by Cu(I)−Cu(I) interactions into a 3D supramolecular array.
The mammalian circadian clockwork has evolved as a timing system that allows the daily environmental changes to be anticipated so that behavior and tissue physiology can be adjusted accordingly. The ...circadian clock synchronizes the function of all cells within tissues in order to temporally separate preclusive and potentially harmful physiologic processes and to establish a coherent temporal organismal physiology. Thus, the proper functioning of the circadian clockwork is essential for maintaining cellular and tissue homeostasis. Importantly, aging reduces the robustness of the circadian clock, resulting in disturbed sleep–wake cycles, a lowered capacity to synchronize circadian rhythms in peripheral tissues, and reprogramming of the circadian clock output at the molecular function levels. These circadian clock–dependent behavioral and molecular changes in turn further accelerate the process of aging. Here we review the current knowledge about how aging affects the circadian clock, how the functional decline of the circadian clock affects aging, and how the circadian clock machinery and the molecular processes that underlie aging are intertwined.
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•The circadian clock organizes tissue physiology and maintains tissue homeostasis.•Aging reduces the robustness of the circadian clock.•Reprogramming of the circadian transcriptome occurs in aged stem cells and tissues.•The clock affects aging-related processes and is intertwined with aging-related pathways.•Circadian clock components are essential for a normal lifespan in mice.
Significance Cell death by regulated necrosis causes tremendous tissue damage in a wide variety of diseases, including myocardial infarction, stroke, sepsis, and ischemia–reperfusion injury upon ...solid organ transplantation. Here, we demonstrate that an iron-dependent form of regulated necrosis, referred to as ferroptosis, mediates regulated necrosis and synchronized death of functional units in diverse organs upon ischemia and other stimuli, thereby triggering a detrimental immune response. We developed a novel third-generation inhibitor of ferroptosis that is the first compound in this class that is stable in plasma and liver microsomes and that demonstrates high efficacy when supplied alone or in combination therapy.
Receptor-interacting protein kinase 3 (RIPK3)-mediated necroptosis is thought to be the pathophysiologically predominant pathway that leads to regulated necrosis of parenchymal cells in ischemia–reperfusion injury (IRI), and loss of either Fas-associated protein with death domain (FADD) or caspase-8 is known to sensitize tissues to undergo spontaneous necroptosis. Here, we demonstrate that renal tubules do not undergo sensitization to necroptosis upon genetic ablation of either FADD or caspase-8 and that the RIPK1 inhibitor necrostatin-1 (Nec-1) does not protect freshly isolated tubules from hypoxic injury. In contrast, iron-dependent ferroptosis directly causes synchronized necrosis of renal tubules, as demonstrated by intravital microscopy in models of IRI and oxalate crystal-induced acute kidney injury. To suppress ferroptosis in vivo, we generated a novel third-generation ferrostatin (termed 16-86), which we demonstrate to be more stable, to metabolism and plasma, and more potent, compared with the first-in-class compound ferrostatin-1 (Fer-1). Even in conditions with extraordinarily severe IRI, 16-86 exerts strong protection to an extent which has not previously allowed survival in any murine setting. In addition, 16-86 further potentiates the strong protective effect on IRI mediated by combination therapy with necrostatins and compounds that inhibit mitochondrial permeability transition. Renal tubules thus represent a tissue that is not sensitized to necroptosis by loss of FADD or caspase-8. Finally, ferroptosis mediates postischemic and toxic renal necrosis, which may be therapeutically targeted by ferrostatins and by combination therapy.
Shaping of metal-organic frameworks (MOFs) and tuning of their sorption properties is a very important and challenging aspect for the usage of MOFs for many applications. Both shaping and tuning can ...be addressed by composite preparation as an effective method. Herein, we present the shaping of the hydrothermally stable MOFs aluminum fumarate, MIL-160(Al) and MIL-101(Cr) using the freeze-casting method with the hydrophilic polymer binders polyacrylic acid (PAA), sodium polyacrylate (PAANa), polyethylene glycol (PEG), polyethylene imine (PEI), polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP). Furthermore, the effect of in-situ cross-linking below the freezing point (cryopolymerization) on the textural properties of monoliths was also investigated using MIL-101(Cr) and aluminum fumarate with the polymer PVA. The selected MOFs were chosen due to their outstanding stability, sorption properties and differing hydrophilicities. In the obtained mechanically stable monoliths, each MOF showed a different compatibility with the used polymers. From 21 different MOF@polymer composites with 80 wt% loading of MOF, 12 of them exhibited negligible pore blocking effects and very high nitrogen sorption properties in correspondence with the MOF mass fraction. On the other hand, water uptake is especially in cases of MOF@PVA and MOF@PVP in good agreement with the MOF fraction and can be enhanced by the contribution of the hydrophilic polymer to the composite. In particular, most MIL-101(Cr) composites showed a hydrophilic shift to lower relative pressure p·p0−1 compared to the rather hydrophobic neat MIL-101(Cr). IR spectroscopy indicated a clear interaction of PEI with the Al-MOFs aluminum fumarate and MIL-160(Al) resulting in MOF pore blocking. The molecular weight of the polymer is not significant for the freeze-casting method but plays an important role in the cryopolymerization.
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•Optimization of freeze-casting method for MOF@polymer monolith preparation.•21 different MOF@polymer monoliths with up to 80 wt% Alfum, MIL-160 und MIL-101(Cr) studied.•Retention of the textural (porosity) properties of the MOFs in the MOF@polymer monoliths.•Hydrophilic shift of the water uptake to lower relative pressure p·p0−1 in the MOF@polymer monoliths.
Mammals rely on a network of circadian clocks to control daily systemic metabolism and physiology. The central pacemaker in the suprachiasmatic nucleus (SCN) is considered hierarchically dominant ...over peripheral clocks, whose degree of independence, or tissue-level autonomy, has never been ascertained in vivo. Using arrhythmic Bmal1-null mice, we generated animals with reconstituted circadian expression of BMAL1 exclusively in the liver (Liver-RE). High-throughput transcriptomics and metabolomics show that the liver has independent circadian functions specific for metabolic processes such as the NAD+ salvage pathway and glycogen turnover. However, although BMAL1 occupies chromatin at most genomic targets in Liver-RE mice, circadian expression is restricted to ∼10% of normally rhythmic transcripts. Finally, rhythmic clock gene expression is lost in Liver-RE mice under constant darkness. Hence, full circadian function in the liver depends on signals emanating from other clocks, and light contributes to tissue-autonomous clock function.
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•The liver clock oscillates in the absence of all other clocks in vivo•Only ∼20% of hepatic rhythms are autonomous despite recruitment of BMAL1 to chromatin•The liver clock is sufficient for oscillation of glycogen and NAD+ salvage metabolism•These autonomous oscillations depend on the light-dark cycle
A autonomous branch of the liver circadian clock is independent from all other clocks yet still dependent on the light-dark cycle.
The gut microbiota modulates host susceptibility to intestinal inflammation, but the cell types and the signalling pathways orchestrating this bacterial regulation of intestinal homeostasis remain ...poorly understood. Here, we investigated the function of intestinal epithelial toll-like receptor (TLR) responses in the dextran sodium sulfate (DSS)-induced mouse model of colitis.
We applied an in vivo genetic approach allowing intestinal epithelial cell (IEC)-specific deletion of the critical TLR signalling adaptors, MyD88 and/or TIR-domain-containing adapter-inducing interferon-β (TRIF), as well as the downstream ubiquitin ligase TRAF6 in order to reveal the IEC-intrinsic function of these TLR signalling molecules during DSS colitis.
Mice lacking TRAF6 in IECs showed exacerbated DSS-induced inflammatory responses that ensued in the development of chronic colon inflammation. Antibiotic pretreatment abolished the increased DSS susceptibility of these mice, showing that epithelial TRAF6 signalling pathways prevent the gut microbiota from driving excessive colitis. However, in contrast to epithelial TRAF6 deletion, blocking epithelial TLR signalling by simultaneous deletion of MyD88 and TRIF specifically in IECs did not affect DSS-induced colitis severity. This in vivo functional comparison between TRAF6 and MyD88/TRIF deletion in IECs shows that the colitis-protecting effects of epithelial TRAF6 signalling are not triggered by TLRs.
Intestinal epithelial TRAF6-dependent but MyD88/TRIF-independent and, thus, TLR-independent signalling pathways are critical for preventing propagation of DSS-induced colon inflammation by the gut microbiota. Moreover, our experiments using mice with dual MyD88/TRIF deletion in IECs unequivocally show that the gut microbiota trigger non-epithelial TLRs rather than epithelial TLRs to restrict DSS colitis severity.
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