Monosodium urate crystals alter the circadian clock in macrophages leading to loss of NLRP3 inflammasome repression: Implications for timing of the gout flare.

Gout is caused by monosodium urate (MSU) crystal deposition within joints. This leads to acute episodes of inflammation ("gout flares") driven by NLRP3 inflammasome activation in macrophages. Gout flares are frequently present during late night/early morning. The reason for this timing is unclear. Recent evidence suggests the NLRP3 inflammasome is under circadian control. The purpose of this study was to determine whether MSU crystals cause changes in the circadian clock in macrophages leading to time-of-day differences in NLRP3 inflammasome activation. Levels of circadian clock components were measured in undifferentiated "monocytic" and PMA-differentiated "macrophagic" THP-1 cells cultured with/without MSU crystals. Caspase-1 activity was measured to assess NLRP3 inflammasome activity. MSU crystal exposure resulted in minimal effects on clock genes in THP-1 monocytes but BMAL1, CRY1, PER2, and REV-ERBα showed altered expression with reduced protein levels of BMAL1 and REV-ERBα in THP-1 macrophages. REV-ERBα activation or BMAL1 over-expression resulted in reduced MSU crystal-induced caspase-1 activity. BMAL1 knockdown resulted in a further increase in MSU crystal-induced caspase-1 activity, but only at times of day when BMAL1 levels were naturally high. MSU crystal-induced NLRP3 inflammasome activation was greatest at the time of day when BMAL1 levels were naturally low. MSU crystals alter the expression of circadian clock components in THP-1 macrophages leading to loss of BMAL1 and REV-ERBα-mediated repression of NLRP3 inflammasome activity and time-of-day differences in susceptibility to inflammasome activation. Our findings suggest that the nocturnal risk of gout flare is at least partially a consequence of altered circadian control of immune cell function.

Experimental demonstration of necessary conditions for X-ray induced synthesis of cesium superoxide.

Absorption of sufficiently energetic X-ray photons by a molecular system results in a cascade of ultrafast electronic relaxation processes which leads to a distortion and dissociation of its molecular structure. Here, we demonstrate that only decomposition of powdered cesium oxalate monohydrate induced by monochromatic X-ray irradiation under high pressure leads to the formation of cesium superoxide. Whereas, for an unhydrated form of cesium oxalate subjected to the same extreme conditions, only degradation of the electron density distribution is observed. Moreover, the corresponding model of X-ray induced electronic relaxation cascades with an emphasis on water molecules' critical role is proposed. Our experimental results suggest that the presence of water molecules in initially solid-state systems (i.e. additional electronic relaxation channels) together with applied high pressure (reduced interatomic/intermolecular distance) could potentially be a universal criteria for chemical and structural synthesis of novel compounds via X-ray induced photochemistry.

Electron Density Changes across the Pressure-Induced Iron Spin Transition.

High-pressure single-crystal x-ray diffraction is used to experimentally map the electron-density distribution changes in (Fe,Mg)O as ferrous iron undergoes a pressure-induced transition from high- to low-spin states. As the bulk density and elasticity of magnesiowüstite-one of the dominant mineral phases of Earth's mantle-are affected by this electronic transition, our results have applications to geophysics as well as to validating first-principles calculations. The observed changes in diffraction intensities indicate a spin-transition-induced change in orbital occupancies of the Fe ion in general accord with crystal-field theory, illustrating the use of electron density measurements for characterizing high-pressure d-block chemistry and motivating further studies characterizing chemical bonding under pressure.

Discrimination of Staphylococcus aureus Strains from Coagulase-Negative Staphylococci and Other Pathogens by Fourier Transform Infrared Spectroscopy.

Staphylococcus aureus is an extremely infectious and malignant pathogen among many bacteria species. The aim of this work is to provide a robust classification model that would be able to identify S. aureus independent of the culture growth stage and the variations in bacteria concentration in suspension and also one that would be able to identify the pathogen among both taxonomically close species of the same genus and taxonomically distant species of different genera, using Fourier transform infrared spectroscopy (FTIR). In total, the spectra of 141 isolates of 17 bacteria have been used. Based on a combination of principal component analysis (PCA) and linear discriminant analysis (LDA), an identification model providing 100% sensitivity and 98% specificity was built. Inherent reliability and flexibility of the model have been shown. The proposed method of analysis allows us to get closer to the diagnostic requirements in the field of clinical microbiology, and it can be utilized for typing of other pathogenic bacteria species.

Stability of Ar(H2)2 to 358 GPa.

"Chemical precompression" through introducing impurity atoms into hydrogen has been proposed as a method to facilitate metallization of hydrogen under external pressure. Here we selected Ar(H2)2, a hydrogen-rich compound with molecular hydrogen, to explore the effect of "doping" on the intermolecular interaction of H2 molecules and metallization at ultrahigh pressure. Ar(H2)2 was studied experimentally by synchrotron X-ray diffraction to 265 GPa, by Raman and optical absorption spectroscopy to 358 GPa, and theoretically using the density-functional theory. Our measurements of the optical bandgap and the vibron frequency show that Ar(H2)2 retains 2-eV bandgap and H2 molecular units up to 358 GPa. This is attributed to reduced intermolecular interactions between H2 molecules in Ar(H2)2 compared with that in solid H2 A splitting of the molecular vibron mode above 216 GPa suggests an orientational ordering transition, which is not accompanied by a change in lattice symmetry. The experimental and theoretical equations of state of Ar(H2)2 provide direct insight into the structure and bonding of this hydrogen-rich system, suggesting a negative chemical pressure on H2 molecules brought about by doping of Ar.

Vanadium Diboride (VB2) Synthesized at High Pressure: Elastic, Mechanical, Electronic, and Magnetic Properties and Thermal Stability.

Vanadium diboride (VB2) with an AlB2-type structure has been synthesized at 8 GPa and 1700 K in a D-DIA-type multianvil apparatus. The obtained bulk modulus is B0 = 262(2) GPa with fixed B' = 4.0 for VB2 via high-pressure X-ray diffraction measurements. Meanwhile, VB2 has also been demonstrated to possess a high Vickers hardness of 27.2 ± 1.5 GPa, a high thermal stability of 1410 K in air, among the highest for transition-metal borides, and an extremely low resistivity value (41 µΩ cm) at room temperature. Results from first-principles calculations regarding the mechanical and electronic properties of VB2 are largely consistent with the experimental observations and further suggest that VB2 possesses simultaneously the properties of a hard and refractory ceramic and those of an excellent electric conductor.

Chemistry through cocrystals: pressure-induced polymerization of C2H2·C6H6 to an extended crystalline hydrocarbon.

The 1 : 1 acetylene-benzene cocrystal, C2H2·C6H6, was synthesized under pressure in a diamond anvil cell (DAC) and its evolution under pressure was studied with single-crystal X-ray diffraction and Raman spectroscopy. C2H2·C6H6 is stable up to 30 GPa, nearly 10× the observed polymerization pressure for molecular acetylene to polyacetylene. Upon mild heating at 30 GPa, the cocrystal was observed to undergo an irreversible transition to a mixture of amorphous hydrocarbon and a crystalline phase with similar diffraction to i-carbon, a nanodiamond polymorph currently lacking a definitive structure. Characterization of this i-carbon-like phase suggests that it remains hydrogenated and may help explain previous observations of nanodiamond polymorphs. Potential reaction pathways in C2H2·C6H6 are discussed and compared with other theoretical extended hydrocarbons that may be obtained through crystal engineering. The cocrystallization of benzene with other more inert gases may provide a novel pathway to selectively control the rich chemistry of these materials.

Physical interface dynamics alter how robotic exosuits augment human movement: implications for optimizing wearable assistive devices.

BACKGROUND: Wearable assistive devices have demonstrated the potential to improve mobility outcomes for individuals with disabilities, and to augment healthy human performance; however, these benefits depend on how effectively power is transmitted from the device to the human user. Quantifying and understanding this power transmission is challenging due to complex human-device interface dynamics that occur as biological tissues and physical interface materials deform and displace under load, absorbing and returning power. METHODS: Here we introduce a new methodology for quickly estimating interface power dynamics during movement tasks using common motion capture and force measurements, and then apply this method to quantify how a soft robotic ankle exosuit interacts with and transfers power to the human body during walking. We partition exosuit end-effector power (i.e., power output from the device) into power that augments ankle plantarflexion (termed augmentation power) vs. power that goes into deformation and motion of interface materials and underlying soft tissues (termed interface power). RESULTS: We provide empirical evidence of how human-exosuit interfaces absorb and return energy, reshaping exosuit-to-human power flow and resulting in three key consequences: (i) During exosuit loading (as applied forces increased), about 55% of exosuit end-effector power was absorbed into the interfaces. (ii) However, during subsequent exosuit unloading (as applied forces decreased) most of the absorbed interface power was returned viscoelastically. Consequently, the majority (about 75%) of exosuit end-effector work over each stride contributed to augmenting ankle plantarflexion. (iii) Ankle augmentation power (and work) was delayed relative to exosuit end-effector power, due to these interface energy absorption and return dynamics. CONCLUSIONS: Our findings elucidate the complexities of human-exosuit interface dynamics during transmission of power from assistive devices to the human body, and provide insight into improving the design and control of wearable robots. We conclude that in order to optimize the performance of wearable assistive devices it is important, throughout design and evaluation phases, to account for human-device interface dynamics that affect power transmission and thus human augmentation benefits.

A pilot study of selective lipopolysaccharide adsorption and coupled plasma filtration and adsorption in adult patients with severe sepsis.

AIM: To evaluate the safety and effectiveness of combined extracorporeal therapy in patients with severe sepsis after cardiac surgery. MATERIALS AND METHODS: Twenty patients received combined extracorporeal therapy (LPS-adsorption with Toraymyxin columns + CPFA). The inclusion criteria were clinical signs of severe sepsis, EAA = 0.6, and PCT >2 ng/ml. 20 comparable patients in the control group received only standard therapy. RESULTS: Each patient in the study group received 2 daily treatments of combined extracorporeal therapy. In contrast to controls, we noted an increase in the values of MAP from 73 to 82 mm Hg, (p < 0.001) and the mean oxygenation index (from 180 to 246, p < 0.001), decrease of EAA from 0.77 to 0.55, p < 0.001, and PCT (from 6.23 to 2.83 ng/ml, p < 0.001). The 28-day survival rate was 65 and 35% in the study and control groups respectively, p = 0.11. CONCLUSION: The combined use of LPS-adsorption and CPFA in a single circuit with standard therapy is a safe and possibly effective adjunctive method for treating severe sepsis.

A role for subducting clays in the water transportation into the Earth's lower mantle.

Subducting sedimentary layer typically contains water and hydrated clay minerals. The stability of clay minerals under such hydrous subduction environment would therefore constraint the lithology and physical properties of the subducting slab interface. Here we show that pyrophyllite (Al2Si4O10(OH)2), one of the representative clay minerals in the alumina-silica-water (Al2O3-SiO2-H2O, ASH) system, breakdowns to contain further hydrated minerals, gibbsite (Al(OH)3) and diaspore (AlO(OH)), when subducts along a water-saturated cold subduction geotherm. Such a hydration breakdown occurs at a depth of ~135 km to uptake water by ~1.8 wt%. Subsequently, dehydration breakdown occurs at ~185 km depth to release back the same amount of water, after which the net crystalline water content is preserved down to ~660 km depth, delivering a net amount of ~5.0 wt% H2O in a phase assemblage containing δ-AlOOH and phase Egg (AlSiO3(OH)). Our results thus demonstrate the importance of subducting clays to account the delivery of ~22% of water down to the lower mantle.

Hydrophilization and Functionalization of Fullerene C60 with Maleic Acid Copolymers by Forming a Non-Covalent Complex.

In this study, we report an easy approach for the production of aqueous dispersions of C60 fullerene with good stability. Maleic acid copolymers, poly(styrene-alt-maleic acid) (SM), poly(N-vinyl-2-pyrrolidone-alt-maleic acid) (VM) and poly(ethylene-alt-maleic acid) (EM) were used to stabilize C60 fullerene molecules in an aqueous environment by forming non-covalent complexes. Polymer conjugates were prepared by mixing a solution of fullerene in N-methylpyrrolidone (NMP) with an aqueous solution of the copolymer, followed by exhaustive dialysis against water. The molar ratios of maleic acid residues in the copolymer and C60 were 5/1 for SM and VM and 10/1 for EM. The volume ratio of NMP and water used was 1:1.2-1.6. Water-soluble complexes (composites) dried lyophilically retained solubility in NMP and water but were practically insoluble in non-polar solvents. The optical and physical properties of the preparations were characterized by UV-Vis spectroscopy, FTIR, DLS, TGA and XPS. The average diameter of the composites in water was 120-200 nm, and the ξ-potential ranged from -16 to -20 mV. The bactericidal properties of the obtained nanostructures were studied. Toxic reagents and time-consuming procedures were not used in the preparation of water-soluble C60 nanocomposites stabilized by the proposed copolymers.

White Laue and powder diffraction studies to reveal mechanisms of HCP-to-BCC phase transformation in single crystals of Mg under high pressure.

Mechanisms of hexagonal close-packed (HCP) to body-centered cubic (BCC) phase transformation in Mg single crystals are observed using a combination of polychromatic beam Laue diffraction and monochromatic beam powder diffraction techniques under quasi-hydrostatic pressures of up to 58 ± 2 GPa at ambient temperature. Although experiments were performed with both He and Ne pressure media, crystals inevitably undergo plastic deformation upon loading to 40-44 GPa. The plasticity is accommodated by dislocation glide causing local misorientations of up to 1°-2°. The selected crystals are tracked by mapping Laue diffraction spots up to the onset of the HCP to BCC transformation, which is determined to be at a pressure of 56.6 ± 2 GPa. Intensity of the Laue reflections from HCP crystals rapidly decrease but no reflections from crystalline BCC phase are observed with a further increase of pressure. Nevertheless, the powder diffraction shows the formation of 110 BCC peak at 56.6 GPa. The peak intensity increases at 59.7 GPa. Upon the full transformation, a powder-like BCC aggregate is formed revealing the destructive nature of the HCP to BCC transformation in single crystals of Mg.

Phase Transitions of Cu and Fe at Multiscales in an Additively Manufactured Cu-Fe Alloy under High-Pressure.

A state of the art, custom-built direct-metal deposition (DMD)-based additive manufacturing (AM) system at the University of Michigan was used to manufacture 50Cu-50Fe alloy with tailored properties for use in high strain/deformation environments. Subsequently, we performed preliminary high-pressure compression experiments to investigate the structural stability and deformation of this material. Our work shows that the alpha (BCC) phase of Fe is stable up to ~16 GPa before reversibly transforming to HCP, which is at least a few GPa higher than pure bulk Fe material. Furthermore, we observed evidence of a transition of Cu nano-precipitates in Fe from the well-known FCC structure to a metastable BCC phase, which has only been predicted via density functional calculations. Finally, the metastable FCC Fe nano-precipitates within the Cu grains show a modulated nano-twinned structure induced by high-pressure deformation. The results from this work demonstrate the opportunity in AM application for tailored functional materials and extreme stress/deformation applications.

Nontrivial nanostructure, stress relaxation mechanisms, and crystallography for pressure-induced Si-I → Si-II phase transformation.

Crystallographic theory based on energy minimization suggests austenite-twinned martensite interfaces with specific orientation, which are confirmed experimentally for various materials. Pressure-induced phase transformation (PT) from semiconducting Si-I to metallic Si-II, due to very large and anisotropic transformation strain, may challenge this theory. Here, unexpected nanostructure evolution during Si-I → Si-II PT is revealed by combining molecular dynamics (MD), crystallographic theory, generalized for strained crystals, and in situ real-time Laue X-ray diffraction (XRD). Twinned Si-II, consisting of two martensitic variants, and unexpected nanobands, consisting of alternating strongly deformed and rotated residual Si-I and third variant of Si-II, form [Formula: see text] interface with Si-I and produce almost self-accommodated nanostructure despite the large transformation volumetric strain of [Formula: see text]. The interfacial bands arrest the [Formula: see text] interfaces, leading to repeating nucleation-growth-arrest process and to growth by propagating [Formula: see text] interface, which (as well as [Formula: see text] interface) do not appear in traditional crystallographic theory.

Mid-regional pro-adrenomedullin as a predictor of in-hospital mortality in adult patients with COVID-19: a single-centre prospective study.

BACKGROUND: To determine the predictive value of mid-regional pro-adrenomedullin (MR-proADM) compared to routine clinical and laboratory parameters in patients with COVID-19. METHODS: A total of 135 adult patients hospitalized with COVID-19 were included in a prospective single-centre study. In addition to routine parameters, the levels of MR-proADM in blood plasma were measured on the day of hospitalization. The patients were divided into 2 groups: those who survived and were discharged (n = 115, 85%) and those who did not survive (n = 20, 15%). Data are presented as median and interquartile range. RESULTS: The non-survivors had a statistically significantly greater age (73.4 [63.5-84.8] vs. 62.2 [50.3-71.4] years, P = 0.001), a lower level of haemoglobin oxygen saturation (91 [87-92] vs. 92 [92-93]%, P < 0.001), lower lymphocyte level (13 [7-30] vs. 21 [15-27]%, P = 0.03), higher lactate dehydrogenase (338 [273-480] vs. 280 [233-383] EU L-1, P = 0.04) and aspartate aminotransferase levels (49 [28-72] vs. 33 [23-47] EU L-1, P = 0.03), a higher National Early Warning (NEWS) score (7 [7- 8] vs. 6 [5-7] points, P < 0.001), and higher procalcitonin (0.16 [0.11-0.32] vs. 0.1 [0.07-0.18] ng mL-1, P = 0.006) and MR-proADM levels (1.288 [0.886-1.847] vs. 0.769 [0.6-0.955] nmol L-1, P < 0.001). MR-proADM had the highest predictive value for death during hospital stay (cut-off: 0.895 nmol L-1, AUC ROC 0.78 [95% CI: 0.66-0.90], sensitivity 75%, specificity 69%, OR 6.58 [95% CI: 2.22-19.51]). CONCLUSIONS: Compared with other indicators, MR-proADM has the highest predictive value for in-hospital mortality in patients with COVID-19.

Overview of HPCAT and capabilities for studying minerals and various other materials at high-pressure conditions.

High-Pressure Collaborative Access Team (HPCAT) is a synchrotron-based facility located at the Advanced Photon Source (APS). With four online experimental stations and various offline capabilities, HPCAT is focused on providing synchrotron x-ray capabilities for high pressure and temperature research and supporting a broad user community. Overall, the array of online/offline capabilities is described, including some of the recent developments for remote user support and the concomitant impact of the current pandemic. General overview of work done at HPCAT and with a focus on some of the minerals relevant work and supporting capabilities is also discussed. With the impending APS-Upgrade (APS-U), there is a considerable effort within HPCAT to improve and add capabilities. These are summarized briefly for each of the end-stations.

How linker's modification controls swelling properties of highly flexible iron(III) dicarboxylates MIL-88.

A series of organically modified iron(III) terephthalate MIL-88B and iron(III) 4,4'-biphenyl dicarboxylate MIL-88D flexible solids have been synthesized and characterized through a combination of X-ray diffraction, IR spectroscopy, and thermal analysis (MIL stands for Material from Institut Lavoisier). The swelling amplitude of the highly flexible MOFs tuned by introducing functional groups onto the phenyl rings shows a clear dependence on the steric hindrance and on the number of groups per aromatic ring. For instance, while the introduction of four methyl groups per spacer in dried MIL-88B results in a large permanent porosity, introducing two or four methyl groups in MIL-88D allows an easier pore opening in the presence of liquids without drastically decreasing the swelling magnitude. The influence of the degree of saturation of the metal center and the nature of the solvent on the swelling is also discussed. Finally, a computationally assisted structure determination has led to a proposal of plausible structures for the closed (dried) and open forms of modified MIL-88B and MIL-88D and to evaluation of their framework energies subject to the nature of the functional groups.

The stability of subducted glaucophane with the Earth's secular cooling.

The blueschist to eclogite transition is one of the major geochemical-metamorphic processes typifying the subduction zone, which releases fluids triggering earthquakes and arc volcanism. Although glaucophane is an index hydrous mineral for the blueschist facies, its stability at mantle depths in diverse subduction regimes of contemporary and early Earth has not been experimentally determined. Here, we show that the maximum depth of glaucophane stability increases with decreasing thermal gradients of the subduction system. Along cold subduction geotherm, glaucophane remains stable down ca. 240 km depth, whereas it dehydrates and breaks down at as shallow as ca. 40 km depth under warm subduction geotherm or the Proterozoic tectonic setting. Our results imply that secular cooling of the Earth has extended the stability of glaucophane and consequently enabled the transportation of water into deeper interior of the Earth, suppressing arc magmatism, volcanism, and seismic activities along subduction zones.

Software for Bioprinting.

The bioprinting of heterogeneous organs is a crucial issue. To reach the complexity of such organs, there is a need for highly specialized software that will meet all requirements such as accuracy, complexity, and others. The primary objective of this review is to consider various software tools that are used in bioprinting and to reveal their capabilities. The sub-objective was to consider different approaches for the model creation using these software tools. Related articles on this topic were analyzed. Software tools are classified based on control tools, general computer-aided design (CAD) tools, tools to convert medical data to CAD formats, and a few highly specialized research-project tools. Different geometry representations are considered, and their advantages and disadvantages are considered applicable to heterogeneous volume modeling and bioprinting. The primary factor for the analysis is suitability of the software for heterogeneous volume modeling and bioprinting or multimaterial three-dimensional printing due to the commonality of these technologies. A shortage of specialized suitable software tools is revealed. There is a need to develop a new application area such as computer science for bioprinting which can contribute significantly in future research work.

Co-production of MCR-1 and NDM-1 by Escherichia coli sequence type 31 isolated from a newborn in Moscow, Russia.

An Escherichia coli sequence type 31 isolate co-harbouring mcr-1 and blaNDM-1 genes on the plasmids of Incl2 and IncC groups, respectively, was recovered from a newborn with ventilator-associated pneumonia in Moscow, Russia. The convergence of polymyxin and carbapenem resistance and its expansion beyond Southeast Asia is a serious threat to human health.