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Atopic dermatitis (AD) is a common, chronic relapsing, and remitting inflammatory skin disease that is characterized by erythematous, scaly, and pruritic lesions often located over the flexural surfaces. Treatment goals of AD include the reduction of itching and burning, as well as the reduction of skin changes. Treatment of AD includes emollients and skin care, topical therapies including topical corticosteroids and steroid-sparing therapies, systemic therapies, and phototherapy.

Hybrid organic–inorganic perovskite (HOIP) crystals are promising optoelectronic materials, but little is known about either the thermodynamic and kinetic controls on crystal growth or the underlying growth mechanism(s). Herein, we use fluid-cell atomic force microscopy (AFM) and solution nuclear magnetic resonance (NMR) spectroscopy to investigate the growth of the model HOIP crystal CH3NH3PbBr3(MAPbBr3) and to determine how formic acid (HCOOH) modulates the thermodynamics and kinetics of growth. The results show that growth of MAPbBr3in dimethylformamide (DMF) proceeds through the classical pathway by the spreading of molecular crystal steps generated at screw dislocations on the {100} surface. Temperature-dependent step velocity measurements demonstrate that with increasing concentration, HCOOH decreases the solubility of MAPbBr3. From the AFM data, we also determine the apparent kinetic coefficient (β) of step movement as a function of HCOOH concentration. 1H NMR measurements indicate that HCOOH increases the lifetime of the methylammonium (MA+) ions and promotes the association of MAPbBr3, thus tuning the solubility of the perovskite. We further propose that HCOOH alters the molecular tumbling motion and bulk diffusion of the MA+ions, possibly via H-bonding. Our findings establish a direct correlation between the mesoscale crystal growth kinetics and the molecular-scale interactions between organic additives and constituent ions, providing unprecedented insights for developing predictive syntheses of HOIP crystals with defined size, crystal habit and shape, and defect distribution.

Multivalent battery chemistries have been explored in response to the increasing demand for high-energy rechargeable batteries utilizing sustainable resources. Solvation structures of working cations have been recognized as a key component in the design of electrolytes; however, most structure–property correlations of metal ions in organic electrolytes usually build upon favorable static solvation structures, often overlooking solvent exchange dynamics. We here report the ion solvation structures and solvent exchange rates of magnesium electrolytes in various solvents by using multimodal nuclear magnetic resonance (NMR) analysis and molecular dynamics/density functional theory (MD/DFT) calculations. These magnesium solvation structures and solvent exchange dynamics are correlated to the combined effects of several physicochemical properties of the solvents. Moreover, Mg2+transport and interfacial charge transfer efficiency are found to be closely correlated to the solvent exchange rate in the binary electrolytes where the solvent exchange is tunable by the fraction of diluent solvents. Our primary findings are (1) most battery-related solvents undergo ultraslow solvent exchange coordinating to Mg2+(with time scales ranging from 0.5 μs to 5 ms), (2) the cation transport mechanism is a mixture of vehicular and structural diffusion even at the ultraslow exchange limit (with faster solvent exchange leading to faster cation transport), and (3) an interfacial model wherein organic-rich regions facilitate desolvation and inorganic regions promote Mg2+transport is consistent with our NMR, electrochemistry, and cryogenic X-ray photoelectron spectroscopy (cryo-XPS) results. This observed ultraslow solvent exchange and its importance for ion transport and interfacial properties necessitate the judicious selection of solvents and informed design of electrolyte blends for multivalent electrolytes.

Supplemental Digital Content is Available in the Text.PRIVENT study report No. 3—Prescreening data—Objective tyndallometry (laser flare photometry) is independently influenced by age, sex, lens status, and the presence and the extent of rhegmatogenous retinal detachment.

Metal carbonates, which are ubiquitous in the near-surface mineral record, are a major product of biomineralizing organisms and serve as important targets for capturing anthropogenic CO2emissions. However, pathways of carbonate mineralization typically diverge from classical predictions due to the involvement of disordered precursors, such as the dense liquid phase (DLP), yet little is known about DLP formation or solidification processes. Using in situ methods we report that a highly hydrated bicarbonate DLP forms via liquid–liquid phase separation and transforms into hollow hydrated amorphous CaCO3particles. Acidic proteins and polymers extend DLP lifetimes while leaving the pathway and chemistry unchanged. Molecular simulations suggest that the DLP forms via direct condensation of solvated Ca²+⋅(HCO3−)2complexes that react due to proximity effects in the confined DLP droplets. Our findings provide insight into CaCO3nucleation that is mediated by liquid–liquid phase separation, advancing the ability to direct carbonate mineralization and elucidating an often-proposed complex pathway of biomineralization.

The subpectoral diverticulum (SPD) is an extension of the respiratory system in birds that is located between the primary muscles responsible for flapping the wing1,2. Here we survey the pulmonary apparatus in 68 avian species, and show that the SPD was present in virtually all of the soaring taxa investigated but absent in non-soarers. We find that this structure evolved independently with soaring flight at least seven times, which indicates that the diverticulum might have a functional and adaptive relationship with this flight style. Using the soaring hawks Buteo jamaicensisand Buteo swainsonias models, we show that the SPD is not integral for ventilation, that an inflated SPD can increase the moment arm of cranial parts of the pectoralis, and that pectoralis muscle fascicles are significantly shorter in soaring hawks than in non-soaring birds. This coupling of an SPD-mediated increase in pectoralis leverage with force-specialized muscle architecture produces a pneumatic system that is adapted for the isometric contractile conditions expected in soaring flight. The discovery of a mechanical role for the respiratory system in avian locomotion underscores the functional complexity and heterogeneity of this organ system, and suggests that pulmonary diverticula are likely to have other undiscovered secondary functions. These data provide a mechanistic explanation for the repeated appearance of the SPD in soaring lineages and show that the respiratory system can be co-opted to provide biomechanical solutions to the challenges of flight and thereby influence the evolution of avian volancy.

The power of quantum chemistry to predict the ground and excited state properties of complex chemical systems has driven the development of computational quantum chemistry software, integrating advances in theory, applied mathematics, and computer science. The emergence of new computational paradigms associated with exascale technologies also poses significant challenges that require a flexible forward strategy to take full advantage of existing and forthcoming computational resources. In this context, the sustainability and interoperability of computational chemistry software development are among the most pressing issues. In this perspective, we discuss software infrastructure needs and investments with an eye to fully utilize exascale resources and provide unique computational tools for next-generation science problems and scientific discoveries.

Predictive understanding of the molecular interaction of electrolyte ions and solvent molecules and their chemical reactivity on electrodes has been a major challenge but is essential for addressing instabilities and surface passivation that occur at the electrode–electrolyte interface of multivalent magnesium batteries. In this work, the isolated intrinsic reactivities of prominent chemical species present in magnesium bis(trifluoromethanesulfonimide) (Mg(TFSI)2) in diglyme (G2) electrolytes, including ionic (TFSI–, [Mg(TFSI)]+, [Mg(TFSI):G2]+, and [Mg(TFSI):2G2]+) as well as neutral molecules (G2) on a well-defined magnesium vanadate cathode (MgV2O4) surface, have been studied using a combination of first-principles calculations and multimodal spectroscopy analysis. Our calculations show that nonsolvated [Mg(TFSI)]+is the strongest adsorbing species on the MgV2O4surface compared with all other ions while partially solvated [Mg(TFSI):G2]+is the most reactive species. The cleavage of C–S bonds in TFSI–to form CF3–is predicted to be the most desired pathway for all ionic species, which is followed by the cleavage of C–O bonds of G2 to yield CH3+or OCH3–species. The strong stabilization and electron transfer between ionic electrolyte species and MgV2O4is found to significantly favor these decomposition reactions on the surface compared with intrinsic gas-phase dissociation. Experimentally, we used state-of-the-art ion soft landing to selectively deposit mass-selected TFSI–, [Mg(TFSI):G2]+, and [Mg(TFSI):2G2]+on a MgV2O4thin film to form a well-defined electrolyte–MgV2O4interface. Analysis of the soft-landed interface using X-ray photoelectron, X-ray absorption near-edge structure, electron energy-loss spectroscopies, as well as transmission electron microscopy confirmed the presence of decomposition species (e.g., MgFx, carbonates) and the higher amount of MgFxwith [Mg(TFSI):G2]+formed in the interfacial region, which corroborates the theoretical observation. Overall, these results indicate that Mg2+desolvation results in electrolyte decomposition facilitated by surface adsorption, charge transfer, and the formation of passivating fluorides on the MgV2O4cathode surface. This work provides the first evidence of the primary mechanisms leading to electrolyte decomposition at high-voltage oxide surfaces in multivalent batteries and suggests that the design of new, anodically stable electrolytes must target systems that facilitate cation desolvation.

Liquid–liquid phase separation (LLPS) is a common phenomenon, but LLPS of electrolytes prepared in miscible organic solvents is rarely documented. In this study, we report four new cases of LLPS that occur in MgTFSI2or ZnTFSI2electrolytes in mixed organic solvents, and we use multimodal NMR methods to investigate the speciation differences between the upper and lower phases of these electrolytes. The conditions for the formation of this LLPS share four common features: cations with high charge density; anions with low charge density; a strongly coordinating solvent (indicated by its Gutmann donor number) with high compressibility; and a relatively weak coordinating solvent with low relative permittivity and high mobility. With these conditions, the cations tend to draw the strongly coordinating solvents together to form a densely packed, energetically favorable ion solvation region, while the cosolvents with low relative permittivity tend to form an ion-depleted dilute phase. Therefore, the driving force for LLPS with miscible solvents is the preferred interaction between cations and the strongly coordinating solvents that overcomes entropy loss due to phase separation. Furthermore, contact ion pairs and large ion aggregates are clearly evidenced in the dilute upper layer due to the incomplete screening of electrostatic interactions by the weaker cosolvent. This LLPS driven by cation solvation may be more common in multivalent electrolytes and is a design consideration that should not be overlooked in this context.

Atopic dermatitis (AD) is a common, chronic relapsing, and remitting inflammatory skin disease that is characterized by erythematous, scaly, and pruritic lesions often located over the flexural surfaces. Treatment goals of AD include the reduction of itching and burning, as well as the reduction of skin changes. Treatment of AD includes emollients and skin care, topical therapies including topical corticosteroids and steroid-sparing therapies, systemic therapies, and phototherapy.

Our current understanding of human gait is mostly based on studies using hard, level surfaces in a laboratory environment. However, humans navigate a wide range of different substrates every day, which incur varied demands on stability and efficiency. Several studies have shown that when walking on natural compliant substrates there is an increase in energy expenditure. However, these studies report variable changes to other aspects of gait such as muscle activity. Discrepancies between studies exist even within substrate types (e.g. sand), which suggests that relatively ‘fine-scale’ differences in substrate properties exert quantifiable influences on gait mechanics. In this study, we compared human walking mechanics on a range of sand substrates that vary in overall foot sinking depth. We demonstrated that variation in the overall sinking depth in sand was associated with statistically significant changes in joint angles and spatiotemporal variables in human walking but exerted relatively little influence on pendular energy recovery and muscle activations. Significant correlated changes between gait metrics were frequently recovered, suggesting a degree of coupled or mechanistic interaction in their variation within and across substrates. However, only walking speed (and its associated spatiotemporal variables) correlated frequently with absolute foot sinkage depth within individual sand substrates, but not across them. This suggests that a causative relationship between walking speed and foot sinkage depth within individual sand substates is not coupled with systematic changes in joint kinematics and muscle activity in the same way as is observed across sand substrates.

Muscle spindle abundance is highly variable in vertebrates, but the functional determinants of this variation are unclear. Recent work has shown that human leg muscles with the lowest abundance of muscle spindles primarily function to lengthen and absorb energy, while muscles with a greater spindle abundance perform active-stretch–shorten cycles with no net work, suggesting that muscle spindle abundance may be underpinned by muscle function. Compared with other mammalian muscles, the digastric muscle contains the lowest abundance of muscle spindles and, therefore, might be expected to generate substantial negative work. However, it is widely hypothesised that as a jaw-opener (anatomically) the digastric muscle would primarily function to depress the jaw, and consequently do positive work. Through a combination of X-ray reconstruction of moving morphology (XROMM), electromyography and fluoromicrometry, we characterised the 3D kinematics of the jaw and digastric muscle during feeding in rabbits. Subsequently, the work loop technique was used to simulate in vivo muscle behaviour in situ, enabling muscle force to be quantified in relation to muscle strain and hence determine the muscle's function during mastication. When functioning on either the working or balancing side, the digastric muscle generates a large amount of positive work during jaw opening, and a large amount of negative work during jaw closing, on average producing a relatively small amount of net negative work. Our data therefore further support the hypothesis that muscle spindle abundance is linked to muscle function; specifically, muscles that absorb a relatively large amount of negative work have a low spindle abundance.

The design of cathode materials that remain chemically and structurally stable during repetitive ion insertion and extraction poses a significant challenge in developing multivalent batteries. The cycling stability of traditional metal oxide-based cathode is challenged by sluggish diffusion of multivalent cations and parasitic reactivity at interfacial regimes, including the cathode electrolyte interphase layer (CEI). Understanding the reactions at the cathode-electrolyte interface, particularly those induced by non-stoichiometric surface layers, is a crucial design parameter for both cathode materials and electrolytes. In this study, we employed multimodal analysis, including in situand ex situX-ray photoelectron spectroscopy (XPS), high resolution transmission electron microscopy (TEM) and electrochemical impedance spectroscopy (EIS) to examine the surface reactions and subsequent structural and chemical evolutions of the CEI on high voltage magnesium vanadium oxide (MgV2O4) spinel cathode during the Mg2+insertion/extraction processes. The results revealed that the presence of non-stoichiometric surface layers in the magnesium vanadium oxide cathode drive the decomposition of bis(trifluoromethanesulfonyl)imide (TFSI-) anion, leading to the formation of the CEI layer. The CEI layer could inhibit the Mg2+ion transfer processes. Accompanying this reactivity-driven degradation, the magnesium vanadium oxide cathode undergoes pulverization, forming clusters of nanosized particles. This process likely improves cycling ability by creating new intercalation sites and shortening the diffusion pathway for the Mg2+cations. This study demonstrates that controlling surface stoichiometry and engineering morphological properties are critical design parameters for high performance cathodes for multivalent batteries.

Heart‐on‐a‐Chip The cover depicts the merging of new cell types in heart‐on‐a‐chip systems using the analogy of cells meeting over dinner. The main concept of the paper – the incorporation of a novel cell type into miniature cardiac tissues – is illustrated by the two cells meeting in an artificial setting (under camera and lights), and casting a shadow of a heart, conveying that engineered cardiac constructs mimic real cardiac tissue. More details can be found in article 2302642by Milica Radisic and co‐workers. Cover illustration by SciFig (https://sci‐fig.com/).

Epicardial cells (EPIs) form the outer layer of the heart and play an important role in development and disease. Current heart‐on‐a‐chip platforms still do not fully mimic the native cardiac environment due to the absence of relevant cell types, such as EPIs. Here, using the Biowire II platform, engineered cardiac tissues with an epicardial outer layer and inner myocardial structure are constructed, and an image analysis approach is developed to track the EPI cell migration in a beating myocardial environment. Functional properties of EPI cardiac tissues improve over two weeks in culture. In conditions mimicking ischemia reperfusion injury (IRI), the EPI cardiac tissues experience less cell death and a lower impact on functional properties. EPI cell coverage is significantly reduced and more diffuse under normoxic conditions compared to the post‐IRI conditions. Upon IRI, migration of EPI cells into the cardiac tissue interior is observed, with contributions to alpha smooth muscle actin positive cell population. Altogether, a novel heart‐on‐a‐chip model is designed to incorporate EPIs through a formation process that mimics cardiac development, and this work demonstrates that EPI cardiac tissues respond to injury differently than epicardium‐free controls, highlighting the importance of including EPIs in heart‐on‐a‐chip constructs that aim to accurately mimic the cardiac environment. This work presents a novel heart‐on‐a‐chip model that incorporates epicardial cells (EPI) in tissue constructs with myocardial/epicardial localization. EPI cardiac tissues form through a process mimicking cardiac development and respond to injury differently than epicardium‐free controls. These findings highlight the importance of including EPIs in heart‐on‐a‐chip constructs to accurately mimic the cardiac environment for studies of development and disease.

The intricate anatomical structure and high cellular density of the myocardium complicate the bioengineering of perfusable vascular networks within cardiac tissues. In vivoneonatal studies highlight the key role of resident cardiac macrophages in post-injury regeneration and angiogenesis. Here, we integrate human pluripotent stem-cell-derived primitive yolk-sac-like macrophages within vascularized heart-on-chip platforms. Macrophage incorporation profoundly impacted the functionality and perfusability of microvascularized cardiac tissues up to 2 weeks of culture. Macrophages mitigated tissue cytotoxicity and the release of cell-free mitochondrial DNA (mtDNA), while upregulating the secretion of pro-angiogenic, matrix remodeling, and cardioprotective cytokines. Bulk RNA sequencing (RNA-seq) revealed an upregulation of cardiac maturation and angiogenesis genes. Further, single-nuclei RNA sequencing (snRNA-seq) and secretome data suggest that macrophages may prime stromal cells for vascular development by inducing insulin like growth factor binding protein 7 (IGFBP7) and hepatocyte growth factor (HGF) expression. Our results underscore the vital role of primitive macrophages in the long-term vascularization of cardiac tissues, offering insights for therapy and advancing heart-on-a-chip technologies.

Efforts to expand the technological capability of batteries have generated increased interest in divalent cationic systems. Electrolytes used for these electrochemical applications often incorporate cyclic ethers as electrolyte solvents; however, the detailed solvation environments within such systems are not well-understood. To foster insights into the solvation structures of such electrolytes, Ca(TFSI)2and Zn(TFSI)2dissolved in tetrahydrofuran (THF) and 2-methyl-tetrahydrofuran were investigated through multi-nuclear magnetic resonance spectroscopy (17O, 43Ca, and 67Zn NMR) combined with quantum chemistry modeling of NMR chemical shifts. NMR provides spectroscopic fingerprints that readily couple with quantum chemistry to identify a set of most probable solvation structures based on the best agreement between the theoretically predicted and experimentally measured values of chemical shifts. The multi-nuclear approach significantly enhances confidence that the correct solvation structures are identified due to the required simultaneous agreement between theory and experiment for multiple nuclear spins. Furthermore, quantum chemistry modeling provides a comparison of the solvation cluster formation energetics, allowing further refinement of the preferred solvation structures. It is shown that a range of solvation structures coexist in most of these electrolytes, with significant molecular motion and dynamic exchange among the structures. This level of solvation diversity correlates with the solubility of the electrolyte, with Zn(TFSI)2/THF exhibiting the lowest degree of each. Comparisons of analogous Ca2+and Zn2+solvation structures reveal a significant cation size effect that is manifested in significantly reduced cation–solvent bond lengths and thus stronger solvent bonding for Zn2+relative to Ca2+. The strength of this bonding is further reduced by methylation of the cyclic ether ring. Solvation shells containing anions are energetically preferred in all the studied electrolytes, leading to significant quantities of contact ion pairs and consequently neutrally charged clusters. It is likely that the transport and interfacial de-solvation/re-solvation properties of these electrolytes are directed by these anion interactions. These insights into the detailed solvation structures, cation size, and solvent effects, including the molecular dynamics, are fundamentally important for the rational design of electrolytes in multivalent battery electrolyte systems.

Aqueous rechargeable Zn metal batteries (RZMBs) are promising candidates for coupling with intermittent renewable energy sources to realize a carbon-neutral energy transition. However, irreversible issues of Zn metal anodes and a poor understanding of the interphasial chemistry severely limit the viability of RZMBs. Here, we demonstrate that the addition of an asymmetric alkylammonium cation, trimethylethyl ammonium-bis(trifluoromethylsulfonyl)imide (Me3EtN-TFSI), as a supporting salt into a traditional aqueous electrolyte results in improved Zn anode reversibility. Performance improvements are attributed to the formation of interphasial chemistries including ZnF2, ZnCO3, and fluoro-polymeric species, especially when combined with CO2.By tailoring the Zn interphase, this electrolyte exhibited excellent stability in Na2V6O16· 1.63H2O (HNVO)/Zn full cells, with a high specific capacity sustained (>100 mAh g−1) over 1,000 cycles at 300 mA g−1. A combination of experiments and modeling showed the importance of tuning interphases to further improve Zn reversibility and RZMBs.

ABSTRACTBackground: DNA methylation markers have been associated with lung cancer risk and may identify aetiologically relevant genomic regions, or alternatively, be markers of disease risk factors or biological processes associated with disease development.Methods: In a nested case–control study, we measured blood leukocyte DNA methylation levels in pre-diagnostic samples collected from 430 participants (208 cases; 222 controls) in the 1989 CLUE II cohort. We compared DNA methylation levels with case/control status to identify novel genomic regions, both single CpG sites and differentially methylated regions (DMRs), while controlling for known DNA methylation changes associated with smoking using a previously described pack-years-based smoking methylation score. Stratification analyses were conducted over time from blood draw to diagnosis, histology, and smoking status.Results: We identified 16 single CpG sites and 40 DMRs significantly associated with lung cancer risk (q < 0.05). The identified genomic regions were associated with genes including H19, HOXA3/HOXA4, RUNX3, BRICD5, PLXNB2, and RP13. For the single CpG sites, the strongest association was noted for cg09736286 in the DIABLO gene (OR [for 1 SD] = 2.99, 95% CI: 1.95–4.59, P-value = 4.81 × 10–7). We found that CpG sites in the HOXA3/HOXA4 region were hypermethylated in cases compared to controls.Conclusion: The single CpG sites and DMRs that we identified represented significant measurable differences in lung cancer risk, providing potential biomarkers for lung cancer risk stratification. Future studies will need to examine whether these regions are causally related to lung cancer.

ABSTRACTThe mammalian kidney has extensive repair capacity; however, identifying adult renal stem cells has proven elusive. We applied an epigenetic marker of foetal cell origin (FCO) in diverse human tissues as a probe for developmental cell persistence, finding a 5.4-fold greater FCO proportion in kidney. Normal kidney FCO proportions averaged 49% with extensive interindividual variation. FCO proportions were significantly negatively correlated with immune-related gene expression and positively correlated with genes expressed in the renal medulla, including those involved in renal organogenesis (e.g., FGF2, PAX8, and HOXB7). FCO associated genes also mapped to medullary nephron segments in mouse and rat, suggesting evolutionary conservation of this cellular compartment. Renal cancer patients whose tumours contained non-zero FCO scores survived longer. The kidney appears unique in possessing substantial foetal epigenetic features. Further study of FCO-related gene methylation may elucidate regenerative regulatory programmes in tissues without apparent discrete stem cell compartments.

Clinicians in the primary care setting will encounter various different skin conditions requiring procedural intervention. There are many different procedural approaches to treatment. Knowing which modalities are available and best suited to handle a particular skin lesion allows for flexibility for patient and clinician. Although some treatment modalities may be used more than others, it is helpful to be at least familiar with basic in office skin procedures such as removal of foreign bodies, cryotherapy, electrosurgery, and treatment of keloids, as these procedures are helpful in addressing the wide variety of the most commonly encountered skin issues in primary care.